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Sample records for oxidized low-density lipoprotein-induced

  1. Protective effect of oleanolic acid on oxidized-low density lipoprotein induced endothelial cell apoptosis.

    PubMed

    Cao, Jianhua; Li, Guanghui; Wang, Meizhi; Li, Hui; Han, Zhiwu

    2015-10-01

    Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a naturally-occurring triterpenoid with various promising pharmacological properties. The present study was conducted to determine the protective effects of OA against oxidized low-density lipoprotein (ox-LDL) induced endothelial cell apoptosis and the possible underlying mechanisms. Our results showed that ox-LDL significantly decreased cell viability and induced apoptosis in human umbilical vein endothelial cells (HUVECs). OA in the co-treatment showed a protective effect against ox-LDL induced loss in cell viability and an increase in apoptosis, which was associated with the modulating effect of OA on ox-LDL induced hypoxia-inducible factor 1α(HIF-1α) expression. Moreover, our results showed that the modulating effect of OA against ox-LDL induced HIF-1α expression was obtained via inhibition of lipoprotein receptor 1 (LOX-1)/reactive oxygen species (ROS) signaling. Collectively, we suggested that the protective effect of OA against ox-LDL induced HUVEC apoptosis might, at least in part, be obtained via inhibition of the LOX-1/ROS/HIF-1α signaling pathway. PMID:26559024

  2. [Oxidized low density lipoprotein induces macrophage endoplasmic reticulum stress via CD36.].

    PubMed

    Yao, Shu-Tong; Sang, Hui; Yang, Na-Na; Kang, Li; Tian, Hua; Zhang, Ying; Song, Guo-Hua; Qin, Shu-Cun

    2010-10-25

    The purpose of the present study is to explore the effect of oxidized low density lipoprotein (ox-LDL) on the induction of endoplasmic reticulum stress (ERS) and the underlying mechanisms in ox-LDL-induced macrophage foam-forming process. RAW264.7 macrophages were cultured in DMEM medium containing 10% fetal bovine serum, and then treated with ox-LDL (25, 50 and 100 mg/L), anti-CD36 monoclonal antibody+ox-LDL and tunicamycin (TM), respectively. After incubation for 24 h, the cells were collected. The cellular lipid accumulation was showed by oil red O staining and the content of cellular total cholesterol was quantified by enzymatic colorimetry. The expression of glucose-regulated protein 94 (GRP94), a molecular marker of ERS, was determined by immunocytochemistry assay. The levels of GRP94 protein, phosphorylated inositol-requiring enzyme 1 (p-IRE1) and X box binding protein 1 (XBP1) in RAW264.7 cells were detected by Western blotting. The results indicated that after incubation with ox-LDL (25, 50 and 100 mg/L) for 24 h, a large amount of lipid droplets were found in the cytoplasm, and the contents of cellular total cholesterol were increased by 2.1, 2.8 and 3.1 folds compared with the control, respectively. Anti-CD36 antibody decreased markedly the cellular lipid accumulation induced by ox-LDL at 100 mg/L. Both ox-LDL and TM, a specific ERS inducer, could up-regulate the protein expression of GRP94 in a dose-dependent manner. Furthermore, p-IRE1 and XBP1, two key components of the unfolded protein response, were also significantly induced by the treatment with ox-LDL. The up-regulations of the three proteins induced by ox-LDL were inhibited significantly when the macrophages were pre-incubated with anti-CD36 antibody. These results suggest that ox-LDL may induce ERS in a dose-dependent way and subsequently activate the unfolded protein response signaling pathway in RAW264.7 macrophages, which is potentially mediated by scavenger receptor CD36. PMID:20945046

  3. Capsaicin protects endothelial cells and macrophage against oxidized low-density lipoprotein-induced injury by direct antioxidant action.

    PubMed

    Chen, Kuo-Shuen; Chen, Pei-Ni; Hsieh, Yih-Shou; Lin, Chin-Yin; Lee, Yi-Hsun; Chu, Shu-Chen

    2015-02-25

    Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation. PMID:25603234

  4. Oxidized Low Density Lipoprotein Induces Differentiation and Adhesion of Human Monocytes and the Monocytic Cell Line U937

    NASA Astrophysics Data System (ADS)

    Frostegard, Johan; Nilsson, Jan; Haegerstrand, Anders; Hamsten, Anders; Wigzell, Hans; Gidlund, Magnus

    1990-02-01

    Hypercholesterolemia is a major risk factor for development of atherosclerosis. In experimental animals fed a high-cholesterol diet, monocytes adhere to the arterial endothelium and penetrate into the intima where they differentiate into macrophages and ingest lipids thus giving rise to fatty streaks, the earliest type of atherosclerotic plaque. Macrophages express few receptors for normal low density lipo-protein (LDL) but can take up oxidized LDL by way of a scavenger receptor. The present study was designed to investigate the possible role of oxidized LDL in recruitment of resident intimal macrophages. We found that oxidized LDL induced enhanced expression of major histocompatibility complex class II molecules on human monocytes and U937 cells, a well-established system for studies of monocytic differentiation. Oxidized LDL also induced enhanced expression of the surface antigen LEuM3 but caused decreased expression of CD4 antigen, a pattern compatible with expression of a more differentiated macrophage-like phenotype. Oxidized LDL also initiated aggregation of monocytes and U937 cells and stimulated adhesion of U937 cells to cultured endothelial cells. The results indicate that oxidized LDL may contribute to development of atherosclerosis by inducing adhesion of monocytes to the arterial intima and by stimulating intimal monocytes to differentiate into resident macrophages.

  5. Adiponectin inhibits oxidized low density lipoprotein-induced increase in matrix metalloproteinase 9 expression in vascular smooth muscle cells

    PubMed Central

    Saneipour, Maryam; Ghatreh-Samani, Keihan; Heydarian, Esfandiar; Farrokhi, Effat; Abdian, Narges

    2015-01-01

    BACKGROUND High expression of matrix metalloproteinase 9 (MMP9) during vascular injury and inflammation plays an important role in atherosclerotic plaque formation and rupture. In the process of atherosclerosis, oxidized low-density lipoprotein (oxLDL) upregulates MMP9 in human aortic vascular smooth muscle cells (HA/VSMCs). Adiponectin is an adipose tissue-derived hormone that has been shown to exert anti-atherogenic and anti-inflammatory effects. The aim of this study was to investigate the effect of adiponectin on MMP9 expression under pathogenic condition created by oxLDL in HA/VSMCs. METHODS In this experimental study, HA/VSMC were stimulated with oxLDL alone and in the presence of adiponectin for 24 and 48 h. The expression of MMP9 gene was determined by real-time polymerase chain reaction method. The protein level of this gene was investigated by western blotting technique. RESULTS An oxLDL increased MMP9 expression 2.16 ± 0.24- and 3.32 ± 0.25-fold after 24 and 48 h, respectively and adiponectin decreased oxLDL-induced MMP9 expression in a time-dependent manner. CONCLUSION These results show that adiponectin changes extracellular matrix by reducing MMP9 mRNA and protein, therefore, may stabilize lesions and reduce atheroma rupture. PMID:26405452

  6. Resistance of mitochondrial DNA-depleted cells against oxidized low-density lipoprotein-induced macrophage pyroptosis.

    PubMed

    Yan, Hai; Li, Yunyun; Peng, Xue; Huang, Dake; Gui, Li; Huang, Baojun

    2016-05-01

    Oxidized low-density lipoprotein (Ox-LDL)-induced macrophage pyroptosis is critical in atherosclerosis inflammation and plaque instability. It has been reported that mitochondrial (mt)DNA-depleted (rho0) cells demonstrate resistance to apoptosis. However, little is known about the susceptibility of rho0 cells to Ox-LDL-induced macrophage pyroptosis. Pyroptosis, a caspase-1-dependent programmed cell death, which compromises membrane integrity, cleaves pro-interleukin (IL)‑1β and pro‑IL‑18 into IL‑1β and IL‑18, respectively and releases damage‑associated molecular pattern molecules, is triggered by a variety of stimuli, including Ox‑LDL. In the present study, the expression levels of cleaved caspase‑1 and IL‑1β in Ox‑LDL‑treated J774A.1 rho0 cells were observed to be significantly decreased when compared with Ox‑LDL‑treated J774A.1 normal cells. Furthermore, J774A.1 rho0 cells exhibited a significant reduction in the ratios of dead cells and lactate dehydrogenase release following Ox‑LDL stimulation compared with the J774A.1 normal cells. In addition, the loss of mtDNA did not influence Ox‑LDL‑induced cholesterol accumulation in J774A.1 rho0 cells, which was observed by Oil Red O staining and CHOD‑PAP assay. Finally, J774A.1 rho0 cells exhibited reduced reactive oxygen species (ROS) production and were capable of maintaining the mitochondrial membrane potential following Ox‑LDL treatment. Thus, the results indicate that the loss of mtDNA potentially rendered murine macrophage J774A.1 resistant to Ox‑LDL‑induced pyroptosis by mitigating NACHT, LRR and PYD domains-containing protein 3 inflammasome activation through reducing ROS production. In addition, mtDNA depletion did not interrupt Ox-LDL-induced intracellular lipid accumulation and continued to maintain the mitochondrial membrane potential. PMID:27035880

  7. Ethanol extract of propolis protects endothelial cells from oxidized low density lipoprotein-induced injury by inhibiting lectin-like oxidized low density lipoprotein receptor-1-mediated oxidative stress.

    PubMed

    Fang, Yongqi; Li, Jinguo; Ding, Mingde; Xu, Xiaoyan; Zhang, Jiajun; Jiao, Peng; Han, Ping; Wang, Jiafu; Yao, Shutong

    2014-12-01

    Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), as the primary oxidized low-density lipoprotein (ox-LDL) receptor on endothelial cells, plays a crucial role in endothelial injury, which is a driving force in the initiation and development of atherosclerosis. Our previous studies have shown that ethanol extract of propolis (EEP) promotes reverse cholesterol transport and inhibits atherosclerotic lesion development. However, the protective effects of EEP against ox-LDL-induced injury in endothelial cells and the underlying mechanisms are still unknown. This study was designed to test the hypothesis that EEP attenuates ox-LDL-induced endothelial oxidative injury via modulation of LOX-1-mediated oxidative stress. Our results showed that exposure of human umbilical vein endothelial cells (HUVECs) to ox-LDL (100 mg/L) led to the decrease in cell viability and increase in lactate dehydrogenase (LDH) release, caspase-3 activation, and apoptosis, whereas pretreatment with EEP (7.5, 15 and 30 mg/L) protected against such damages in a dose-dependent manner. In addition, EEP mitigated ox-LDL uptake by HUVECs and attenuated ox-LDL-upregulated LOX-1 expression both at the mRNA and protein levels. Moreover, EEP suppressed the ox-LDL-induced oxidative stress as assessed by decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, reactive oxygen species (ROS), and malondialdehyde (MDA) generation as well as increased antioxidant enzyme activities. Similar results were observed in the anti-LOX-1 antibody or diphenyleneiodonium (DPI)-pretreated HUVECs. These data indicate that EEP may protect HUVECs from ox-LDL-induced injury and that the mechanism at least partially involves its ability to inhibit endothelial LOX-1 upregulation and subsequent oxidative stress. PMID:24962173

  8. Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

    SciTech Connect

    Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong Tang Jian

    2007-11-16

    Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE{sup -/-} mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.

  9. Delphinidin-3-Glucoside Protects against Oxidized Low-Density Lipoprotein-Induced Mitochondrial Dysfunction in Vascular Endothelial Cells via the Sodium-Dependent Glucose Transporter SGLT1

    PubMed Central

    Chen, Ming-liang; Chen, Chun-ye; Chang, Hui; Zhang, Ting; Wang, Li; Zhu, Jun-dong; Zhang, Qian-yong; Mi, Man-tian

    2013-01-01

    Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis. PMID:23874689

  10. Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

    SciTech Connect

    Ou, Hsiu-Chung; Lee, Wen-Jane; Lee, Shin-Da; Huang, Chih-Yang; Chiu, Tsan-Hung; Tsai, Kun-Ling; Hsu, Wen-Cheng; Sheu, Wayne Huey-Herng

    2010-10-15

    Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20 {mu}M) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-{kappa}B and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.

  11. Chlamydia pneumoniae Augments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

    PubMed Central

    Yaraei, Kambiz; Campbell, Lee Ann; Zhu, Xiaodong; Liles, W. Conrad; Kuo, Cho-chou; Rosenfeld, Michael E.

    2005-01-01

    Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 μg/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2. PMID:15972525

  12. Oxidized low-density lipoprotein induces calpain-dependent cell death and ubiquitination of caspase 3 in HMEC-1 endothelial cells.

    PubMed Central

    Pörn-Ares, M Isabella; Saido, Takaomi C; Andersson, Tommy; Ares, Mikko P S

    2003-01-01

    Oxidized low-density lipoprotein (oxLDL) is known to induce apoptosis in endothelial cells, and this is believed to contribute to the progression of atherosclerosis. In the present study we made the novel observation that oxLDL-induced death of HMEC-1 cells is accompanied by activation of calpain. The mu-calpain inhibitor PD 151746 decreased oxLDL-induced cytotoxicity, whereas the general caspase inhibitor BAF (t-butoxycarbonyl-Asp-methoxyfluoromethylketone) had no effect. Also, oxLDL provoked calpain-dependent proteolysis of cytoskeletal alpha-fodrin in the HMEC-1 cells. Our observation of an autoproteolytic cleavage of the 80 kDa subunit of mu-calpain provided further evidence for an oxLDL-induced stimulation of calpain activity. The Bcl-2 protein Bid was also cleaved during oxLDL-elicited cell death, and this was prevented by calpain inhibitors, but not by inhibitors of cathepsin B and caspases. Treating the HMEC-1 cells with oxLDL did not result in detectable activation of procaspase 3 or cleavage of PARP [poly(ADP-ribose) polymerase], but it did cause polyubiquitination of caspase 3, indicating inactivation and possible degradation of this protease. Despite the lack of caspase 3 activation, oxLDL treatment led to the formation of nucleosomal DNA fragments characteristic of apoptosis. These novel results show that oxLDL initiates a calpain-mediated death-signalling pathway in endothelial cells. PMID:12775216

  13. Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-κB Pathway

    PubMed Central

    Wang, Xiantao; Sun, Yuhan; Yang, Huafeng; Lu, Yuanxi; Li, Lang

    2016-01-01

    This study was designed to investigate the apoptosis induced by oxidized low-density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor κB (NF-κB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions significantly. Decrease of Bcl-2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL-induced cardiomyocyte apoptosis, TLR4 and NF-κB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-κB signaling pathway. PMID:27279424

  14. ORMDL3 contributes to the risk of atherosclerosis in Chinese Han population and mediates oxidized low-density lipoprotein-induced autophagy in endothelial cells.

    PubMed

    Ma, Xiaochun; Qiu, Rongfang; Dang, Jie; Li, Jiangxia; Hu, Qin; Shan, Shan; Xin, Qian; Pan, Wenying; Bian, Xianli; Yuan, Qianqian; Long, Feng; Liu, Na; Li, Yan; Gao, Fei; Zou, Chengwei; Gong, Yaoqin; Liu, Qiji

    2015-01-01

    ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population. Following the detection of its statistical correlation with AS, we further explored the functional relevance of ORMDL3 and hypothesized a potential role mediating autophagy as autophagy is activated upon modified lipid, inflammation and ER stress. Our results demonstrated that in endothelial cells oxidized low-density lipoprotein (ox-LDL) up-regulated ORMDL3 expression and knockdown of ORMDL3 alleviated not only ox-LDL-induced but also basal autophagy. BECN1 is essential for autophagy initiation and silencing of ORMDL3 suppressed ox-LDL-induced as well as basal BECN1 expression. In addition, deletion of ORMDL3 resulted in greater sensitivity to ox-LDL-induced cell death. Taken together, ORMDL3 might represent a causal gene mediating autophagy in endothelial cells in the pathogenesis of AS. PMID:26603569

  15. Notoginsenoside R1 inhibits oxidized low-density lipoprotein induced inflammatory cytokines production in human endothelial EA.hy926 cells.

    PubMed

    Su, Ping; Du, Shijing; Li, Hang; Li, Zhi; Xin, Wenfeng; Zhang, Wensheng

    2016-01-01

    Notoginsenoside R1 (NG-R1), a unique and main active ingredient of Panax notoginseng, has been described to exhibit anti-inflammatory activity. However, its protective effects against oxidized low-density lipoprotein (oxLDL)-induced inflammatory injury in vascular endothelial cells have not been clarified. In the present study, we have evaluated the anti-inflammatory effects of NG-R1 on oxLDL-induced endothelial cells and its possible molecular mechanism of action. Our results showed that NG-R1 treatment significantly attenuated oxLDL-induced expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. These effects were accompanied with suppression of oxLDL-induced activation of NF-κB and Mitogen-activated protein kinases (MAPK). Moreover, NG-R1 also increased in Peroxisome proliferator-activated receptor γ (PPARγ) protein expression and transcription levels, and attenuated oxLDL-induced suppression of PPARγ expression. The inhibition of NG-R1 on oxLDL-induced TNF-α and IL-1β productions can be reversed by PPARγ antagonist GW9662. In conclusion, these data suggested that NG-R1 could suppress oxLDL-induced inflammatory cytokines production via activating PPARγ, which subsequently inhibiting oxLDL-induced NF-κB and MAPK activation. PMID:26607460

  16. ORMDL3 contributes to the risk of atherosclerosis in Chinese Han population and mediates oxidized low-density lipoprotein-induced autophagy in endothelial cells

    PubMed Central

    Ma, Xiaochun; Qiu, Rongfang; Dang, Jie; Li, Jiangxia; Hu, Qin; Shan, Shan; Xin, Qian; Pan, Wenying; Bian, Xianli; Yuan, Qianqian; Long, Feng; Liu, Na; Li, Yan; Gao, Fei; Zou, Chengwei; Gong, Yaoqin; Liu, Qiji

    2015-01-01

    ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population. Following the detection of its statistical correlation with AS, we further explored the functional relevance of ORMDL3 and hypothesized a potential role mediating autophagy as autophagy is activated upon modified lipid, inflammation and ER stress. Our results demonstrated that in endothelial cells oxidized low-density lipoprotein (ox-LDL) up-regulated ORMDL3 expression and knockdown of ORMDL3 alleviated not only ox-LDL-induced but also basal autophagy. BECN1 is essential for autophagy initiation and silencing of ORMDL3 suppressed ox-LDL-induced as well as basal BECN1 expression. In addition, deletion of ORMDL3 resulted in greater sensitivity to ox-LDL-induced cell death. Taken together, ORMDL3 might represent a causal gene mediating autophagy in endothelial cells in the pathogenesis of AS. PMID:26603569

  17. Oxidized low density lipoprotein induces bone morphogenetic protein-2 in coronary artery endothelial cells via Toll-like receptors 2 and 4.

    PubMed

    Su, Xin; Ao, Lihua; Shi, Yi; Johnson, Thomas R; Fullerton, David A; Meng, Xianzhong

    2011-04-01

    Vascular calcification is a common complication in atherosclerosis. Bone morphogenetic protein-2 (BMP-2) plays an important role in atherosclerotic vascular calcification. The aim of this study was to determine the effect of oxidized low density lipoprotein (oxLDL) on BMP-2 protein expression in human coronary artery endothelial cells (CAECs), the roles of Toll-like receptor (TLR) 2 and TLR4 in oxLDL-induced BMP-2 expression, and the signaling pathways involved. Human CAECs were stimulated with oxLDL. The roles of TLR2 and TLR4 in oxLDL-induced BMP-2 expression were determined by pretreatment with neutralizing antibody, siRNA, and overexpression. Stimulation with oxLDL increased cellular BMP-2 protein levels in a dose-dependent manner (40-160 μg/ml). Pretreatment with neutralizing antibodies against TLR2 and TLR4 or silencing of these two receptors reduced oxLDL-induced BMP-2 expression. Overexpression of TLR2 and TLR4 enhanced the cellular BMP-2 response to oxLDL. Furthermore, oxLDL was co-localized with TLR2 and TLR4. BMP-2 expression was associated with activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK)1/2. Inhibition of NF-κB and ERK1/2 reduced BMP-2 expression whereas inhibition of p38 MAPK had no effect. In conclusion, oxLDL induces BMP-2 expression through TLR2 and TLR4 in human CAECs. The NF-κB and ERK1/2 pathways are involved in the signaling mechanism. These findings underscore an important role for TLR2 and TLR4 in mediating the BMP-2 response to oxLDL in human CAECs and indicate that these two immunoreceptors contribute to the mechanisms underlying atherosclerotic vascular calcification. PMID:21325271

  18. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway

    SciTech Connect

    Chen, T.-G.; Chen, T.-L.; Chang, H.-C.; Tai, Y.-T.; Cherng, Y.-G.; Chang, Y.-T.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2007-02-15

    Cerebral endothelial cells (CECs) are crucial components of the blood-brain barrier. Oxidized low-density lipoprotein (oxLDL) can induce cell injuries. In this study, we attempted to evaluate the effects of oxLDL on mouse CECs and its possible mechanisms. Mouse CECs were isolated from brain tissues and identified by immunocytochemical staining of vimentin and Factor VIII. oxLDL was prepared from LDL oxidation by copper sulfate. Exposure of mouse CECs to oxLDL decreased cell viability in concentration- and time-dependent manners. oxLDL time-dependently caused shrinkage of cell morphologies. Administration of oxLDL to CECs induced DNA fragmentation in concentration- and time-dependent manners. Analysis of the cell cycle revealed that oxLDL concentration- and time-dependently increased the proportion of CECs which underwent apoptosis. Analysis of confocal microscopy and immunoblot revealed that oxLDL significantly increased cellular and mitochondrial Bax levels as well as the translocation of this proapoptotic protein from the cytoplasm to mitochondria. In parallel with the increase in the levels and translocation of Bax, oxLDL time-dependently decreased the mitochondrial membrane potential. Exposure of mouse CECs to oxLDL decreased the amounts of mitochondrial cytochrome c, but enhanced cytosolic cytochrome c levels. The amounts of intracellular reactive oxygen species were significantly augmented after oxLDL administration. Sequentially, oxLDL increased activities of caspase-9, -3, and -6 in time-dependent manners. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, significantly decreased caspase-6 activity and the oxLDL-induced DNA fragmentation and cell apoptosis. This study showed that oxLDL induces apoptotic insults to CECs via signal-transducing events, including enhancing Bax translocation, mitochondrial dysfunction, cytochrome c release, increases in intracellular reactive oxygen species, and cascade activation of caspase-9, -3, and -6. Therefore, ox

  19. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway.

    PubMed

    Chen, Tyng-Guey; Chen, Ta-Liang; Chang, Huai-Chia; Tai, Yu-Ting; Cherng, Yih-Giun; Chang, Ya-Ting; Chen, Ruei-Ming

    2007-02-15

    Cerebral endothelial cells (CECs) are crucial components of the blood-brain barrier. Oxidized low-density lipoprotein (oxLDL) can induce cell injuries. In this study, we attempted to evaluate the effects of oxLDL on mouse CECs and its possible mechanisms. Mouse CECs were isolated from brain tissues and identified by immunocytochemical staining of vimentin and Factor VIII. oxLDL was prepared from LDL oxidation by copper sulfate. Exposure of mouse CECs to oxLDL decreased cell viability in concentration- and time-dependent manners. oxLDL time-dependently caused shrinkage of cell morphologies. Administration of oxLDL to CECs induced DNA fragmentation in concentration- and time-dependent manners. Analysis of the cell cycle revealed that oxLDL concentration- and time-dependently increased the proportion of CECs which underwent apoptosis. Analysis of confocal microscopy and immunoblot revealed that oxLDL significantly increased cellular and mitochondrial Bax levels as well as the translocation of this proapoptotic protein from the cytoplasm to mitochondria. In parallel with the increase in the levels and translocation of Bax, oxLDL time-dependently decreased the mitochondrial membrane potential. Exposure of mouse CECs to oxLDL decreased the amounts of mitochondrial cytochrome c, but enhanced cytosolic cytochrome c levels. The amounts of intracellular reactive oxygen species were significantly augmented after oxLDL administration. Sequentially, oxLDL increased activities of caspase-9, -3, and -6 in time-dependent manners. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, significantly decreased caspase-6 activity and the oxLDL-induced DNA fragmentation and cell apoptosis. This study showed that oxLDL induces apoptotic insults to CECs via signal-transducing events, including enhancing Bax translocation, mitochondrial dysfunction, cytochrome c release, increases in intracellular reactive oxygen species, and cascade activation of caspase-9, -3, and -6. Therefore, ox

  20. Enhancement in efferocytosis of oxidized low-density lipoprotein-induced apoptotic RAW264.7 cells through Sirt1-mediated autophagy.

    PubMed

    Liu, Baoxin; Zhang, Buchun; Guo, Rong; Li, Shuang; Xu, Yawei

    2014-03-01

    Macrophages play a key role in atherosclerotic plaque formation and rupture. These phagocytic cells are important in the scavenging of modified lipoproteins, unwanted or dead cells and cellular debris through efferocytosis. Sirtuin1 (Sirt1), a member of the conserved sirtuin family and a key regulator in the progression of atherosclerosis exerts protective effects by regulating autophagy, a well-known survival mechanism. Inhibition of autophagy may also result in defective efferocytosis. This study aimed to investigate the effect of Sirt1 on the efferocytosis of oxidized low-density lipoprotein (ox-LDL)-induced apoptotic RAW264.7 cells through upregulation of autophagy. The apoptotic cells were incubated with high and low concentrations of Sirt1 activator resveratrol (RSV) and Sirt1 inhibitor nicotinamide (NAM) as well as autophagy inhibitor 3-methyl-adenine (3-MA) + low concentration RSV. Apoptosis was determined by flow cytometry (FCM) of annexin-V/propidium iodide (AV/PI) dual staining. Total proteins were extracted and protein levels were detected through western blot analysis. The ox-LDL uptake and efferocytosis of apoptotic RAW264.7 cells were detected by oil red O staining and calculation of the phagocytic index of apoptotic RAW264.7 cells. The expression of Sirt1 and autophagy marker proteins was simultaneously increased with the stimulation of low concentration RSV (all P<0.05) and decreased in low and high NAM groups (all P<0.05), compared with the control group. Efferocytosis was highest in the low concentration RSV group (P<0.001) and relatively lower in the low and high concentration NAM groups (both P<0.05) compared with the control group, which was similar to the change in the expression of Sirt1 and autophagy marker proteins. The results showed that the efferocytosis of apoptotic RAW264.7 cells was significantly improved with the upregulation of Sirt1‑mediated autophagy. Therefore, Sirt1 may serve as a novel therapeutic target for the treatment of

  1. Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells.

    PubMed

    Hao, Shuangying; Ji, Jiajie; Zhao, Hongting; Shang, Longcheng; Wu, Jing; Li, Huihui; Qiao, Tong; Li, Kuanyu

    2015-01-01

    Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis. PMID:26633327

  2. XJP-1 protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by inhibiting NADPH oxidase subunit expression and modulating the PI3K/Akt/eNOS pathway.

    PubMed

    Fu, Rong; Wang, Qiujuan; Guo, Qinglong; Xu, Jinyi; Wu, Xiaoming

    2013-01-01

    Endothelial apoptosis triggered by oxidized low-density lipoprotein (ox-LDL) can accelerate the progression of endothelial dysfunction in atherosclerosis. (±)7,8-Dihydroxy-3-methyl-isochromanone-4 (XJP-1) is a natural phenolic compound derived from banana peel. In the present study, we investigated the anti-apoptotic effect of XJP-1 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL and explored underlying mechanisms. Our results showed that in the presence of ox-LDL, XJP-1 significantly attenuated ox-LDL-mediated cytotoxicity, apoptosis, caspase-3 activation, reactive oxygen species (ROS) generation, and NADPH oxidase subunit (p22phox and p47phox) expression in HUVECs. In addition, the anticytotoxic and anti-apoptotic effect of XJP-1 was partially inhibited by a PI3K inhibitor (LY294002), an Akt inhibitor (SH-6), a specific eNOS inhibitor (l-NAME) and a NADPH oxidase inhibitor (DPI). In exploring the underlying mechanisms of XJP-1 action, we found that XJP-1 eliminated ox-LDL-induced dephosphorylation of Akt and eNOS in a dose-dependent manner. However, XJP-1 alone upregulation of Akt and eNOS phosphorylation were blocked by LY294002 and SH-6. Moreover, XJP-1 increased NO production, but this effect was abolished by LY294002, SH-6 and l-NAME. The inhibition of ox-LDL-induced endothelial dysfunction by XJP-1 is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. PMID:22980246

  3. Oxidized low-density lipoprotein-induced periodontal inflammation is associated with the up-regulation of cyclooxygenase-2 and microsomal prostaglandin synthase 1 in human gingival epithelial cells

    SciTech Connect

    Nagahama, Yu; Obama, Takashi; Usui, Michihiko; Kanazawa, Yukari; Iwamoto, Sanju; Suzuki, Kazushige; Miyazaki, Akira; Yamaguchi, Tomohiro; Yamamoto, Matsuo; Itabe, Hiroyuki

    2011-10-07

    Highlights: {yields} OxLDL-induced responses in human gingival epithelial cells were studied. {yields} OxLDL enhanced the production of IL-8, IL-1{beta} and PGE{sub 2} in Ca9-22 cells. {yields} An NF-{kappa}B inhibitor suppressed the expression of COX-2 and mPGES1 induced by oxLDL. {yields} Unlike the case in macrophages, oxLDL did not increase the CD36 level. -- Abstract: Periodontitis is characterized by chronic gingival tissue inflammation, and inflammatory mediators such as IL-8 and prostaglandin E{sub 2} (PGE{sub 2}) are associated with disease progression. Previously we showed that oxidatively modified low-density lipoprotein (oxLDL) was present in gingival crevicular fluid. In this study, the role of oxLDL in the gingival epithelial cell inflammatory response was further investigated using Ca9-22 cells and primary human oral keratinocytes (HOK). Treatment of Ca9-22 cells and HOK with oxLDL induced an up-regulation of IL-8 and the PGE{sub 2}-producing enzymes, cyclooxygenase-2 and microsomal PGE{sub 2} synthase-1. These responses induced by oxLDL were significantly suppressed by a nuclear factor-kappa B (NF-{kappa}B) inhibitor. However, unlike the result in macrophages, oxLDL did not lead to an increase in CD36 expression in these two cells. These results suggest that oxLDL elicits gingival epithelial cell inflammatory responses through an activation of the NF-{kappa}B pathway. These data suggest a mechanistic link between periodontal disease and lipid metabolism-related disorders, including atherosclerosis.

  4. L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

    PubMed Central

    Xie, Xiang-Zhu; Huang, Xin; Zhao, Shui-Ping; Yu, Bi-Lian; Zhong, Qiao-Qing; Cao, Jian

    2016-01-01

    Background: Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein-1 (MCP-1). Oxidized low-density lipoprotein (oxLDL) participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinflammatory function of oxLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. Methods: Fully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentration of L-4F (0–50 μg/ml) with oxLDL (50 μg/ml) stimulated, with/without protein kinase A (PKA) inhibitor H-89 (10 μmol/L) preincubated. The concentrations of MCP-1 in the supernatant, the mRNA expression of MCP-1, the levels of CCAAT/enhancer binding protein α (C/EBPα), and CCAAT/enhancer binding protein β (C/EBPβ) were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. Results: OxLDL stimulation induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F (50 μg/ml) (P > 0.05). OxLDL stimulation showed no significant effect on C/EBPα protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPβ protein level in oxLDL-induced 3T3-L1 adipocytes. Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP

  5. Hypertriglyceridemic very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages.

    PubMed

    Gianturco, S H; Bradley, W A; Gotto, A M; Morrisett, J D; Peavy, D L

    1982-07-01

    Triglyceride-rich lipoproteins may be responsible for the lipid accumulation in macrophages that can occur in hypertriglyceridemia. Chylomicrons and very low density lipoproteins (VLDL, total and with flotation constant [S(f)] 100-400) from fasting hypertriglyceridemic subjects induced a massive accumulation of oil red O-positive inclusions in unstimulated peritoneal macrophages. Cell viability was not affected. The predominant lipid that accumulated in cells exposed to hypertriglyceridemic VLDL was triglyceride. Hypertriglyceridemic VLDL stimulated the incorporation of [(14)C]oleate into cellular triglyceride up to ninefold in 16 h, but not into cholesteryl esters. Mass increase in cellular triglyceride was 38-fold. The stimulation of cellular triglyceride formation was dependent on time, temperature, and concentration of hypertriglyceridemic VLDL. By contrast, VLDL, low density, and high density lipoproteins from fasting normolipemic subjects had no significant effect on oleate incorporation into neutral lipids or on visible lipid accumulation.(125)I-Hypertriglyceridemic VLDL (S(f) 100-400) were degraded by macrophages in a dose-dependent manner, with 50 and 100% saturation observed at 3 and 24 mug protein/ml (2.5 and 20 nM), respectively. Hypertriglyceridemic VLDL inhibited the internalization and degradation of (125)I-hypertriglyceridemic VLDL (4 nM) by 50% at 3 nM. Cholesteryl ester-rich VLDL from cholesterol-fed rabbits gave 50% inhibition at 5 nM. Low density lipoproteins (LDL) inhibited by 10% at 5 nM and 40% at 47 nM. Acetyl LDL at 130 nM had no effect. We conclude that the massive triglyceride accumulation produced in macrophages by hypertriglyceridemic VLDL is a direct consequence of uptake via specific receptors that also recognize cholesteryl ester-rich VLDL and LDL but are distinct from the acetyl LDL receptor. Uptake of these triglyceride-rich lipoproteins by monocyte-macrophages in vivo may play a significant role in the pathophysiology of

  6. Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits low density lipoprotein-induced signaling in platelets.

    PubMed

    Relou, Ingrid A M; Gorter, Gertie; Ferreira, Irlando Andrade; van Rijn, Herman J M; Akkerman, Jan-Willem N

    2003-08-29

    At physiological concentrations, low density lipoprotein (LDL) increases the sensitivity of platelets to aggregation- and secretion-inducing agents without acting as an independent activator of platelet functions. LDL sensitizes platelets by inducing a transient activation of p38MAPK, a Ser/Thr kinase that is activated by the simultaneous phosphorylation of Thr180 and Tyr182 and is an upstream regulator of cytosolic phospholipase A2 (cPLA2). A similar transient phosphorylation of p38MAPK is induced by a peptide mimicking amino acids 3359-3369 in apoB100 called the B-site. Here we report that the transient nature of p38MAPK activation is caused by platelet endothelial cell adhesion molecule 1 (PECAM-1), a receptor with an immunoreceptor tyrosine-based inhibitory motif. PECAM-1 activation by cross-linking induces tyrosine phosphorylation of PECAM-1 and a fall in phosphorylated p38MAPK and cPLA2. Interestingly, LDL and the B-site peptide also induce tyrosine phosphorylation of PECAM-1, and studies with immunoprecipitates indicate the involvement of c-Src. Inhibition of the Ser/Thr phosphatases PP1/PP2A (okadaic acid) makes the transient p38MAPK activation by LDL and the B-site peptide persistent. Inhibition of Tyr-phosphatases (vanadate) increases Tyr-phosphorylated PECAM-1 and blocks the activation of p38MAPK. Together, these findings suggest that, following a first phase in which LDL, through its B-site, phosphorylates and thereby activates p38MAPK, a second phase is initiated in which LDL activates PECAM-1 and induces dephosphorylation of p38MAPK via activation of the Ser/Thr phosphatases PP1/PP2A. PMID:12775720

  7. Minimally modified low-density lipoprotein induces macrophage endoplasmic reticulum stress via toll-like receptor 4.

    PubMed

    Yao, Shutong; Yang, Nana; Song, Guohua; Sang, Hui; Tian, Hua; Miao, Cheng; Zhang, Ying; Qin, Shucun

    2012-07-01

    Minimally modified low-density lipoprotein (mm-LDL) induces intimal foam cell formation, which is promoted by endoplasmic reticulum stress (ERS), a cross-point to link cellular processes with multiple risk factors that exist in all stages of atherosclerosis. However, it remains unclear whether mm-LDL-induced lipid accumulation in macrophages involves ERS and its underlying mechanisms. We showed that mm-LDL induced the accumulation of lipid droplets in RAW264.7 macrophages with increased free cholesterol in the endoplasmic reticulum, which was markedly attenuated by pretreatment with an antibody against toll-like receptor 4 (TLR4). Additionally, mm-LDL stimulated the transport of Cy3-labeled activating transcription factor 6 (ATF6), a key sensor to the unfolded protein response (UPR), from cytoplasm into nucleus. The expression of phosphorylated inositol-requiring enzyme 1 (p-IRE1), another sensor to the UPR, and its two downstream molecules, X box binding protein 1 and glucose-regulated protein 78 (GRP78), were significantly upregulated by mm-LDL. The alterations induced by mm-LDL were all significantly inhibited by antibodies against TLR4 or CD36. In addition, the upregulation of p-IRE1 and GRP78 and the nuclear translocation of ATF6 induced by mm-LDL were significantly attenuated by TLR4 siRNA. These results suggest that mm-LDL may induce free cholesterol accumulation in the endoplasmic reticulum and subsequently stimulate ERS and activate the UPR signaling pathway mediated by ATF6 and IRE1 in macrophages, a process that is potentially mediated by TLR4. PMID:22480542

  8. NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells

    PubMed Central

    Park, Il Hwan; Hwang, Hye Mi; Jeon, Byeong Hwa; Kwon, Hyung-Joo; Hoe, Kwang Lae; Kim, Young Myeong; Ryoo, Sungwoo

    2015-01-01

    Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-θ (PKCθ) and protein kinase C-β (PKCβ) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCθ and PKCβ stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox−/− mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated h

  9. Oxidized low-density lipoprotein-induced foam cell formation is mediated by formyl peptide receptor 2.

    PubMed

    Lee, Ha Young; Oh, Eunseo; Kim, Sang Doo; Seo, Jeong Kon; Bae, Yoe-Sik

    2014-01-17

    The increased level of LDL and its modification into oxLDL has been regarded as an important risk factor for the development of cardiovascular diseases such as atherosclerosis. Although some scavenger receptors including CD36 and RAGE have been considered as target receptors for oxLDL, involvement of other receptors should be investigated for oxLDL-induced pathological responses. In this study, we found that oxLDL-induced foam cell formation was inhibited by formyl peptide receptor 2 (FPR2) antagonist WRW(4). oxLDL also stimulated calcium signaling and chemotactic migration in FPR2-expressing RBL-2H3 cells but not in vector-expressing RBL-2H3 cells. Moreover, oxLDL stimulated TNF-α production, which was also almost completely inhibited by FPR2 antagonist. Our findings therefore suggest that oxLDL stimulates macrophages, resulting in chemotactic migration, TNF-α production, and foam cell formation via FPR2 signaling, and thus likely contributes to atherogenesis. PMID:24361884

  10. Protective Effect of Irisin on Atherosclerosis via Suppressing Oxidized Low Density Lipoprotein Induced Vascular Inflammation and Endothelial Dysfunction

    PubMed Central

    Zhang, Yuzhu; Mu, Qian; Zhou, Zheng; Song, Haibo; Zhang, Yuan; Wu, Fei; Jiang, Miao; Wang, Fang; Zhang, Wen; Li, Liang; Shao, Lei; Wang, Xingli; Li, Shiwu; Yang, Lijun; Wu, Qi; Zhang, Mingxiang; Tang, Dongqi

    2016-01-01

    Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases. PMID:27355581

  11. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation.

    PubMed

    Sundaram, V; Hanna, A N; Koneru, L; Newman, H A; Falko, J M

    1997-10-01

    Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that L-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean +/- SEM hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 +/- 0.0.65 and 14 +/- 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 +/- 0.55 h, and that during the euthyroid phase was 12 +/- 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism. PMID:9329379

  12. Diffusion of nitric oxide into low density lipoprotein.

    PubMed

    Denicola, Ana; Batthyány, Carlos; Lissi, Eduardo; Freeman, Bruce A; Rubbo, Homero; Radi, Rafael

    2002-01-11

    A key early event in the development of atherosclerosis is the oxidation of low density lipoprotein (LDL) via different mechanisms including free radical reactions with both protein and lipid components. Nitric oxide (( small middle dot)NO) is capable of inhibiting LDL oxidation by scavenging radical species involved in oxidative chain propagation reactions. Herein, the diffusion of ( small middle dot)NO into LDL is studied by fluorescence quenching of pyrene derivatives. Selected probes 1-(pyrenyl)methyltrimethylammonium (PMTMA) and 1-(pyrenyl)-methyl-3-(9-octadecenoyloxy)-22,23-bisnor-5-cholenate (PMChO) were chosen so that they could be incorporated at different depths of the LDL particle. Indeed, PMTMA and PMChO were located in the surface and core of LDL, respectively, as indicated by changes in fluorescence spectra, fluorescence quenching studies with water-soluble quenchers and the lifetime values (tau(o)) of the excited probes. The apparent second order rate quenching constants of ( small middle dot)NO (k(NO)) for both probes were 2.6-3.8 x 10(10) m(-1) s(-1) and 1.2 x 10(10) m(-1) s(-1) in solution and native LDL, respectively, indicating that there is no significant barrier to the diffusion of ( small middle dot)NO to the surface and core of LDL. Nitric oxide was also capable of diffusing through oxidized LDL. Considering the preferential partitioning of ( small middle dot)NO in apolar milieu (6-8 for n-octanol:water) and therefore a larger ( small middle dot)NO concentration in LDL with respect to the aqueous phase, a corrected k(NO) value of approximately 0.2 x 10(10) m(-1) s(-1) can be determined, which still is sufficiently large and consistent with a facile diffusion of ( small middle dot)NO through LDL. Applying the Einstein-Smoluchowsky treatment, the apparent diffusion coefficient (D(')NO) of ( small middle dot)NO in native LDL is on average 2 x 10(-5) cm(2) s(-1), six times larger than that previously reported for erythrocyte plasma membrane

  13. Intact human ceruloplasmin oxidatively modifies low density lipoprotein.

    PubMed Central

    Ehrenwald, E; Chisolm, G M; Fox, P L

    1994-01-01

    Ceruloplasmin is a plasma protein that carries most of the copper found in the blood. Although its elevation after inflammation and trauma has led to its classification as an acute phase protein, its physiological role is uncertain. A frequently reported activity of ceruloplasmin is its ability to suppress oxidation of lipids. In light of the intense recent interest in the oxidation of plasma LDL, we investigated the effects of ceruloplasmin on the oxidation of this lipoprotein. In contrast to our expectations, highly purified, undegraded human ceruloplasmin enhanced rather than suppressed copper ion-mediated oxidation of LDL. Ceruloplasmin increased the oxidative modification of LDL as measured by thiobarbituric acid-reacting substances by at least 25-fold in 20 h, and increased electrophoretic mobility, conjugated dienes, and total lipid peroxides. In contrast, ceruloplasmin that was degraded to a complex containing 115- and 19-kD fragments inhibited cupric ion oxidation of LDL, as did commercial preparations, which were also degraded. However, the antioxidant capability of degraded ceruloplasmin in this system was similar to that of other proteins, including albumin. The copper in ceruloplasmin responsible for oxidant activity was not removed by ultrafiltration, indicating a tight association. Treatment of ceruloplasmin with Chelex-100 removed one of seven copper atoms per molecule and completely blocked oxidant activity. Restoration of the copper to ceruloplasmin also restored oxidant activity. These data indicate that ceruloplasmin, depending on the integrity of its structure and its bound copper, can exert a potent oxidant rather than antioxidant action on LDL. Our results invite speculation that ceruloplasmin may be in part responsible for oxidation of LDL in blood or in the arterial wall and may thus have a physiological role that is quite distinct from what is commonly believed. Images PMID:8163654

  14. Role of oxidized low-density lipoprotein in the atherosclerosis of uremia.

    PubMed

    Drüeke, T B; Nguyen Khoa, T; Massy, Z A; Witko-Sarsat, V; Lacour, B; Descamps-Latscha, B

    2001-02-01

    Lipoprotein oxidation is involved in the genesis of atherosclerosis. In chronic renal failure (CRF), oxidative stress is enhanced because of an imbalance between pro-oxidant and antioxidant systems. Oxidative modifications of low-density lipoproteins (LDLs) occur not only at the level of lipid moiety, but also of protein moiety. We have shown that oxidation of LDL by hypochlorous acid (HOCl) in vitro, reflecting increased myeloperoxidase activity in vivo, leads to modifications of apoliproteins such that the latter in turn are capable of triggering macrophage nicotinamide adenine dinucleotide phosphate-oxidase activation. These oxidative changes of LDL protein moiety, if shown to occur to a significant extent in uremic patients in vivo, may represent an important alternative pathway in the pathogenesis of atheromatous lesions. PMID:11168995

  15. Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid.

    PubMed

    Malle, Ernst; Marsche, Gunther; Arnhold, Jürgen; Davies, Michael J

    2006-04-01

    Substantial evidence supports the notion that oxidative processes contribute to the pathogenesis of atherosclerosis and coronary heart disease. The nature of the oxidants that give rise to the elevated levels of oxidised lipids and proteins, and decreased levels of antioxidants, detected in human atherosclerotic lesions are, however, unclear, with multiple species having been invoked. Over the last few years, considerable data have been obtained in support of the hypothesis that oxidants generated by the heme enzyme myeloperoxidase play a key role in oxidation reactions in the artery wall. In this article, the evidence for a role of myeloperoxidase, and oxidants generated therefrom, in the modification of low-density lipoprotein, the major source of lipids in atherosclerotic lesions, is reviewed. Particular emphasis is placed on the reactions of the reactive species generated by this enzyme, the mechanisms and sites of damage, the role of modification of the different components of low-density lipoprotein, and the biological consequences of such oxidation on cell types present in the artery wall and in the circulation, respectively. PMID:16698314

  16. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    SciTech Connect

    Frei, B. )

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  17. Oxidized low density lipoprotein (LDL) and platelet intracellular calcium: interaction with nitric oxide.

    PubMed

    Zuliani, V; Tommasol, R; Gaino, S; Degan, M; Cominacini, L; Davoli, A; Lechi, C; Lechi, A; Minuz, P

    1998-01-01

    The present study tested the effects of ox-low density lipoprotein (LDL) on nitric oxide (NO)-dependent decrease in agonist-stimulated [Ca2+]i. The effects of ox-LDL on platelet aggregation were also evaluated. Platelets loaded with FURA 2 AM (2 micromol/litre) were incubated with NO-donors for 2-10 min to obtain a 40-50% reduction in \\[Ca2+]i and with NO-donors plus ox-LDL (100 microg of protein/ml). Thrombin (0.03 U/ml) was used as an agonist. In some experiments 8-Br-cGMP (0.5-1 mmol/l) was used to investigate the NO-dependent intraplatelet signalling system. Slightly oxidized LDL was obtained by leaving native LDL in the light at room temperature for at least 7 days. Ox-LDL did not cause any increase in thrombin-induced [Ca2+] (control: 215.4 +/- 44.3 nmol/l, ox-LDL 223.4 +/- 35.3 nmol/l, M +/- SEM; n = 8) and platelet aggregation (control: 78.7 +/- 4.9% , ox-LDL: 78.9 +/- 4.2% , n = 12). Ox-LDL antagonized the effects of NO-donors on platelet [Ca2+]i (NO-donor: 137.4 +/- 22.1 nmol/l, NO + ox-LDL: 177.3 +/- 27.6 nmol/l, n = 11; P < 0.001) and platelet aggregation (NO-donor: 15.4 +/- 3.4% , NO + ox-LDL: 28.9 +/- 3.8%, n = 24; P < 0.001). Ox-LDL did not affect the inhibitory activities of 8-Br-cGMP on platelet aggregation (8-Br-cGMP: 22.0 +/- 8.5%, 8-Br-cGMP + ox-LDL: 19.3 +/- 7.8%, n = 5) and platelet [Ca2+]i . In conclusion, slightly oxidized LDL does not directly activate platelets and does not i affect the intracellular NO-dependent signalling system. The present results suggest that LDL reduces the antiplatelet activity of NO mainly by preventing its biological effects. PMID:16793716

  18. Stimulated arachidonate metabolism during foam cell transformation of mouse peritoneal macrophages with oxidized low density lipoprotein.

    PubMed Central

    Yokode, M; Kita, T; Kikawa, Y; Ogorochi, T; Narumiya, S; Kawai, C

    1988-01-01

    Changes in arachidonate metabolism were examined in mouse peritoneal macrophages incubated with various types of lipoproteins. Oxidized low density lipoprotein (LDL) was incorporated by macrophages and stimulated macrophage prostaglandin E2 (PGE2) and leukotriene C4 syntheses, respectively, 10.8- and 10.7-fold higher than by the control. Production of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin, was also stimulated. No stimulation was found with native LDL, which was minimally incorporated by the cells. Acetylated LDL and beta-migrating very low density lipoprotein (beta-VLDL), though incorporated more efficiently than oxidized LDL, also had no stimulatory effect. When oxidized LDL was separated into the lipoprotein-lipid peroxide complex and free lipid peroxides, most of the stimulatory activity was found in the former fraction, indicating that stimulation of arachidonate metabolism in the cell is associated with uptake of the lipoprotein-lipid peroxide complex. These results suggest that peroxidative modification of LDL could contribute to the progression of atheroma by stimulating arachidonate metabolism during incorporation into macrophages. Images PMID:3125226

  19. The Effect of Acetaminophen on Oxidative Modification of Low-Density Lipoproteins in Hypercholesterolemic Rabbits

    PubMed Central

    Özsoy, Meral Baş; Pabuçcuoğlu, Aysun

    2007-01-01

    Oxidative modification of low-density lipoproteins (LDL) contributes to the pathology of atherosclerosis. Antioxidants may protect LDL against oxidative modification. Acetaminophen, a widely used analgesic and antipyretic agent, has significant antioxidant properties. However, there is little evidence to suggest that acetaminophen acts as an antioxidant for LDL oxidation in vivo. In this study, we investigated the in vivo effect of acetaminophen on LDL oxidation in hypercholesterolemic rabbits. The oxidative modification of LDL was identified by conjugated dienes and thiobarbituric acid-reactive substances (TBARS). In the cholesterol group which rabbits were fed a diet contained 1% g cholesterol for 8 weeks, TBARS contents and conjugated diene levels in the plasma and isolated LDL samples significantly increased compared with the control rabbits (p<0.05). However, in the cholesterol + acetaminophen group, the TBARS contents and conjugated diene levels were significantly lower than that of the cholesterol group (p<0.05). The results from in vitro studies also demonstrated that the LDL isolated from serum was oxidized by Cu++ ions and this oxidation reduced in the presence of acetaminophen. The reduced oxidative modification of LDL by acetaminophen may be of therapeutic value in preventing the development and progression of atherosclerosis. PMID:18392104

  20. Lectin-like oxidized low-density lipoprotein receptor (LOX-1) in sickle cell disease vasculopathy.

    PubMed

    Chen, Mingyi; Qiu, Hong; Lin, Xin; Nam, David; Ogbu-Nwobodo, Lucy; Archibald, Hannah; Joslin, Amelia; Wun, Ted; Sawamura, Tatsuya; Green, Ralph

    2016-09-01

    Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL. Increased expression of LOX-1 has been demonstrated in atherosclerotic lesions and diabetic vasculopathy. In this study, we investigate the expression of LOX-1 receptor in sickle cell disease (SCD) vasculopathy. Expression of LOX-1 in brain vascular endothelium is markedly increased and LOX-1 gene expression is upregulated in cultured human brain microvascular endothelial cells by incubation with SCD erythrocytes. Also, the level of circulating soluble LOX-1 concentration is elevated in the plasma of SCD patients. Increased LOX-1 expression in endothelial cells is potentially involved in the pathogenesis of SCD vasculopathy. Soluble LOX-1 concentration in SCD may provide a novel biomarker for risk stratification of sickle cell vascular complications. PMID:27519944

  1. Vitamin C protects low-density lipoprotein from homocysteine-mediated oxidation.

    PubMed

    Alul, Rushdi H; Wood, Michael; Longo, Joseph; Marcotte, Anthony L; Campione, Allan L; Moore, Michael K; Lynch, Sean M

    2003-04-01

    Homocysteine, an atherogenic amino acid, promotes iron-dependent oxidation of low-density lipoprotein (LDL). We investigated whether vitamin C, a physiological antioxidant, could protect LDL from homocysteine-mediated oxidation. LDL (0.2 mg of protein/ml) was incubated at 37 degrees C with homocysteine (1000 microM) and ferric iron (10-100 microM) in either the absence (control) or presence of vitamin C (5-250 microM). Under these conditions, vitamin C protected LDL from oxidation as evidenced by an increased lag time preceding lipid diene formation (> or = 5 vs. 2.5 h for control), decreased thiobarbituric acid-reactive substances accumulation (< or = 19 +/- 1 nmol/mg when vitamin C > or = 10 microM vs. 32 +/- 3 nmol/mg for control, p <.01), and decreased lipoprotein anodic electrophoretic mobility. Near-maximal protection was observed at vitamin C concentrations similar to those in human blood (50-100 microM); also, some protection was observed even at low concentrations (5-10 microM). This effect resulted neither from altered iron redox chemistry nor enhanced recycling of vitamin E in LDL. Instead, similar to previous reports for copper-dependent LDL oxidation, we found that vitamin C protected LDL from homocysteine-mediated oxidation through covalent lipoprotein modification involving dehydroascorbic acid. Protection of LDL from homocysteine-mediated oxidation by vitamin C may have implications for the prevention of cardiovascular disease. PMID:12654477

  2. In vitro oxidative footprinting provides insight into apolipoprotein B-100 structure in low density lipoprotein

    PubMed Central

    Chakraborty, Sourav; Cai, Yang; Tarr, Matthew A.

    2015-01-01

    Low density lipoprotein (LDL) is a major cholesterol carrier in human blood. Oxidations of apolipoprotein B-100 (apo B-100, LDL protein) could be pro-atherogenic and play critical roles in early stages of plaque formation in the arterial wall. The structure of apo B-100 is still poorly understood, partially due to its size (550 KDa, 4563 amino acids). To gain an insight into LDL structure, we mapped the regions of apo B-100 in human LDL which were prone to oxidation using peroxynitrite and hypochlorite as probes. In this study, LDL was incubated with various concentrations of peroxynitrite and sodium hypochlorite in bicarbonate buffer. The LDL protein apo B-100 was delipidated, denatured, alkylated and subjected to tryptic digestion. Tryptic peptides were analyzed employing liquid chromatography – tandem mass spectrometry (LC-MS/MS). Database search was performed against the apo B-100 database (P04114) using “SEQUEST” algorithm to identify peroxynitrite and hypochlorite mediated oxidations markers nitrotyrosine, nitrotryptophan, hydroxy-tryptophan and 3-chlorotyrosine. Several site specific oxidations were identified in apo B-100 after treatment of intact LDL particles with the oxidants. We hypothesize that these regions could be accessible to oxidant and critical for early events in atherosclerotic plaque deposition. PMID:25176030

  3. Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole.

    PubMed Central

    Iuliano, L.; Colavita, A. R.; Camastra, C.; Bello, V.; Quintarelli, C.; Alessandroni, M.; Piovella, F.; Violi, F.

    1996-01-01

    1. The oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Natural and synthetic antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Synthetic antioxidants are currently being tested, by they are not necessarily safe for human use. 2. We have previously reported that dipyridamole, currently used in clinical practice, is a potent scavenger of free radicals. Thus, we tested whether dipyridamole could affect LDL oxidation at chemical and cellular level. 3. Chemically induced LDL oxidation was made by Cu(II), Cu(II) plus hydrogen peroxide or peroxyl radicals generated by thermolysis of 2,2'-azo-bis(2-amidino propane). Dipyridamole, (1-10 microM), inhibited LDL oxidation as monitored by diene formation, evolution of hydroperoxides and thiobarbituric acid reactive substances, apoprotein modification and by the fluorescence of cis-parinaric acid. 4. The physiological relevance of the antioxidant activity was validated by experiments at the cellular level where dipyridamole inhibited endothelial cell-mediated LDL oxidation, their degradation by monocytes, and cytotoxicity. 5. In comparison with ascorbic acid, alpha-tocopherol and probucol, dipyridamole was the more efficient antioxidant with the following order of activity: dipyridamole > probucol > ascorbic acid > alpha-tocopherol. The present study shows that dipyridamole inhibits oxidation of LDL at pharmacologically relevant concentrations. The inhibition of LDL oxidation is unequivocally confirmed by use of three different methods of chemical oxidation, by several methods of oxidation monitoring, and the pharmacological relevance is demonstrated by the superiority of dipyridamole over the naturally occurring antioxidants, ascorbic acid and alpha-tocopherol and the synthetic antioxidant probucol. Images Figure 6 PMID:8968553

  4. Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation.

    PubMed

    Lin, Hsin-Hung; Charles, Albert Linton; Hsieh, Chang-Wei; Lee, Ya-Chi; Ciou, Jhih-Ying

    2015-01-01

    The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling-time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; gān jú huā), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; shān zhā), and Roselle (Hibiscus sabdariffa Linn.; luò shén) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis. PMID:26151009

  5. Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation

    PubMed Central

    Lin, Hsin-Hung; Charles, Albert Linton; Hsieh, Chang-Wei; Lee, Ya-Chi; Ciou, Jhih-Ying

    2014-01-01

    The relationship between the antioxidant activities and inhibitory effect of 14 Chinese medicinal herbs against oxidized low-density lipoprotein (LDL) formation was evaluated. Prolongation of the lag phase of LDL oxidation depended on the concentration of the herbs. The concentration of each herb that was able to prolong the lag time by about two-fold was calculated and expressed as doubling-time concentration. The lower the doubling-time concentration, the stronger the inhibitory effect exhibited toward LDL oxidation. Among them, Chrysanthemi Flos (Chrysanthemum morifolium ramat; 甘菊花 gān jú huā), Crataegi Fructus (Crataegus pinnatifida Bge. var. major N.E.Br.; 山楂 shān zhā), and Roselle (Hibiscus sabdariffa Linn.; 洛神 luò shén) showed significant inhibitory effects. Correlation coefficients between doubling-time concentration and radical-scavenging activities were high; the total phenolic content was also high. In conclusion, phenolic compounds contributed not only to antioxidant activities, but also to the inhibitory effect against LDL oxidation. Chrysanthemi Flos, Crataegi Fructus, and H. sabdariffa, with lower doubling-time concentrations, could be potent phytochemical agents to reduce LDL oxidation and prevent the progression of atherosclerosis. PMID:26151009

  6. N-acetylcysteine inhibits in vivo oxidation of native low-density lipoprotein

    PubMed Central

    Cui, Yuqi; Narasimhulu, Chandrakala A.; Liu, Lingjuan; Zhang, Qingbin; Liu, Patrick Z.; Li, Xin; Xiao, Yuan; Zhang, Jia; Hao, Hong; Xie, Xiaoyun; He, Guanglong; Cui, Lianqun; Parthasarathy, Sampath; Liu, Zhenguo

    2015-01-01

    Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR−/−) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR−/− mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia. PMID:26536834

  7. Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro

    PubMed Central

    Tanaka, Miori; Kishimoto, Yoshimi; Saita, Emi; Suzuki-Sugihara, Norie; Kamiya, Tomoyasu; Taguchi, Chie; Iida, Kaoruko; Kondo, Kazuo

    2016-01-01

    The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 μg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression. PMID:27314393

  8. Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro.

    PubMed

    Tanaka, Miori; Kishimoto, Yoshimi; Saita, Emi; Suzuki-Sugihara, Norie; Kamiya, Tomoyasu; Taguchi, Chie; Iida, Kaoruko; Kondo, Kazuo

    2016-01-01

    The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 μg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression. PMID:27314393

  9. Overexpression of LOXIN Protects Endothelial Progenitor Cells From Apoptosis Induced by Oxidized Low Density Lipoprotein.

    PubMed

    Veas, Carlos; Jara, Casandra; Willis, Naomi D; Pérez-Contreras, Karen; Gutierrez, Nicolas; Toledo, Jorge; Fernandez, Paulina; Radojkovic, Claudia; Zuñiga, Felipe A; Escudero, Carlos; Aguayo, Claudio

    2016-04-01

    Human endothelial progenitor cells (hEPC) are adult stem cells located in the bone marrow and peripheral blood. Studies have indicated that hEPC play an important role in the recovery and repair of injured endothelium, however, their quantity and functional capacity is reduced in several diseases including hypercholesterolemia. Recently, it has been demonstrated that hEPC express lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its activation by oxidized low-density lipoprotein (ox-LDL) induces cellular dysfunction and apoptosis. This study aimed to investigate whether overexpression of LOXIN, a truncated isoform of LOX-1 that acts as a dominant negative, plays a protective role against ox-LDL-induced apoptosis in hEPC. Human endothelial progenitor cells exposed to ox-LDL showed a significant increase in LOX-1 expression, and apoptosis began at ox-LDL concentrations above 50 μg/mL. All hEPC apoptosed at 200 μg/mL ox-LDL. High LOXIN expression was generated using adenoviral systems in hEPC and SiHa cells transduced with 100 colony-forming units per cell. Transduced LOXIN localized to the plasma membrane and blocked ox-LDL uptake mediated by LOX-1. Overexpression of LOXIN protected hEPC from ox-LDL-induced apoptosis, and therefore maybe a novel way of improving hEPC function and quantity. These results suggest that adenoviral vectors of LOXIN may provide a possible treatment for diseases related to ox-LDL and vascular endothelium dysfunction, including atherosclerosis. PMID:26771151

  10. Oxidation-labile subfraction of human plasma low density lipoprotein isolated by ion-exchange chromatography.

    PubMed

    Shimano, H; Yamada, N; Ishibashi, S; Mokuno, H; Mori, N; Gotoda, T; Harada, K; Akanuma, Y; Murase, T; Yazaki, Y

    1991-05-01

    We isolated subfractions of human plasma low density lipoprotein (LDL) using ion-exchange chromatography. Plasma LDL from normolipidemic subjects were applied to a DEAE Sepharose 6B column. After elution of the bulk of LDL at 150 mM NaCl (the major fraction), the residual LDL was eluted at 500 mM NaCl and designated as the minor fraction. The minor fraction, only less than 1% of total LDL, tended to be somewhat similar in certain properties to oxidized LDL, e.g., an increased negative charge, higher protein/cholesterol ratio, and a higher flotation density than native LDL. These results were consistent with data reported by Avogaro et al. (1988. Arteriosclerosis. 8: 79-87). However, assays of 125I-labeled LDL binding activity for LDL receptors equal to that of the major fraction. Incorporation of [14C]oleate into cholesteryl ester [acyl-CoA:cholesterol acyltransferase (ACAT) activity] in mouse peritoneal macrophages incubated with the minor fraction was only slightly greater than that with the major fraction. Incubation of the minor fraction with 0.5 microM Cu2+ caused a remarkable stimulation of ACAT activity, while stimulation by the major fraction required incubation with 5 microM Cu2+, suggesting that the minor fraction was relatively labile to oxidation. The minor but definite presence of a plasma LDL subfraction more negative and susceptible to oxidation implicates the possibility of its association with atherogenesis. PMID:2072039

  11. Anti-oxidized low-density lipoprotein antibodies in myeloperoxidase–positive vasculitis patients preferentially recognize hypochlorite-modified low density lipoproteins

    PubMed Central

    Slot, M C; Theunissen, R; van Paassen, P; Damoiseaux, J G M C; Cohen Tervaert, J W

    2007-01-01

    Many patients surviving vasculitis are prone to accelerated atherosclerosis and often have enhanced levels of antibodies to oxidized low-density lipoprotein (oxLDL). To measure anti-oxLDL antibodies, oxidation of LDL is achieved with copper (Cu) or malondialdehyde (MDA). Because, in vivo, LDL may be oxidized with myeloperoxidase (MPO) or its product hypochlorite, we measured anti-hypochlorite LDL antibodies in patients with vasculitis, haemodialysis patients and healthy controls. A newly developed enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to oxLDL as modified by hypochlorite. Results are compared with data obtained by standard LDL oxidation using MDA–LDL or Cu–LDL as substrate. Results were compared between anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients (n = 93), haemodialysis (HD) patients (n = 59) and healthy controls (HC; n = 43). Furthermore, patients with MPO–ANCA-associated vasculitis (n = 47) were compared with patients with proteinase 3 (PR3)–ANCA associated vasculitis (n = 46). Optimal cut-off points were determined by receiver operator characteristic (ROC) curve analysis. Anti-oxLDL antibodies are enhanced in AAV patients (MDA–LDL and hypochlorite–LDL) and in HD patients (hypochlorite–LDL), when compared to HC. Furthermore, patients with MPO–ANCA-associated vasculitis had higher levels of antibodies to hypochlorite–LDL than patients with PR3–ANCA-associated vasculitis. Our newly developed assay, in which hypochlorite–LDL is used as substrate, seems a more sensitive assay than traditional assays to measure oxLDL antibodies. Furthermore, our results suggest that enhanced MPO-mediated LDL oxidation occurs in patients with MPO–ANCA. PMID:17521320

  12. Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein.

    PubMed

    Schroder, Helmut; Marrugat, Jaume; Fíto, Montserrat; Weinbrenner, Tanja; Covas, Maria-Isabel

    2006-04-15

    Findings on the association of alcohol consumption and oxidation of low-density lipoprotein (LDL), which is thought to play a crucial role in the generation of atherosclerotic lesion, are inconsistent. The aim of the present study was to investigate the association of total alcohol consumption and type of alcoholic beverage with circulating plasma LDL oxidation. This cross-sectional study included data of circulating oxidized LDL (ox-LDL) from a subpopulation of 587 men and women enrolled in a population-based survey conducted in 2000 in Girona (Spain). Multivariate analysis was performed to describe the independent association of alcohol consumption and ox-LDL. Increasing alcohol consumption was associated with high in vivo ox-LDL levels in the present population. The consumption of 10 g of alcohol was associated with an increase of 2.40 U/L of ox-LDL (p = 0.002). Adjustment for dietary variables, leisure-time physical activity, educational level, smoking, LDL-cholesterol, high-density lipoprotein-cholesterol, glycemia, triglycerides, diabetes, body mass index, waist circumference, and systolic and diastolic blood pressures only slightly modified this association (p = 0.003). In this full adjusted model the consumption of 10 g of alcohol per day was associated with an increase of 2.11 U/L of ox-LDL. Consumption of wine (ml/day) was associated with increasing ox-LDL levels (p = 0.029), however, attenuated after controlling for alcohol. No significant relationship of ox-LDL with alcohol-independent consumption of wine, beer, and spirits was observed. Alcohol consumption was independently and directly associated with circulating ox-LDL in the present population. PMID:16631537

  13. CD36 Binds Oxidized Low Density Lipoprotein (LDL) in a Mechanism Dependent upon Fatty Acid Binding*

    PubMed Central

    Jay, Anthony G.; Chen, Alexander N.; Paz, Miguel A.; Hung, Justin P.; Hamilton, James A.

    2015-01-01

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes. PMID:25555908

  14. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein.

    PubMed

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L; Varughese, Kottayil I

    2015-01-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential. PMID:26578342

  15. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein

    PubMed Central

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L.; Varughese, Kottayil I.

    2015-01-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential. PMID:26578342

  16. Upregulation of Sestrin2 Expression Protects Against Macrophage Apoptosis Induced by Oxidized Low-Density Lipoprotein

    PubMed Central

    Hu, Hong-Juan; Shi, Ze-Ya; Lin, Xiao-Lin; Chen, San-Mei; Wang, Qing-Yan

    2015-01-01

    Sestrin2 is involved in a different cellular response to stress conditions. However, the function of Sestrin2 in the cardiovascular system remains unknown. In the present study, we tested whether Sestrin2 has a beneficial effect on macrophage cell apoptosis induced by oxidized low-density lipoprotein (oxLDL). We found that oxLDL induces expression of Sestrin2 in RAW264.7 cells in a time-dependent and dose-dependent manner. We also found that knockdown of Sestrin2 using small RNA interference promotes cell apoptosis and reactive oxygen species production induced by oxLDL. In addition, our results show that the c-Jun NH(2)-terminal kinase (JNK)/c-Jun pathway is activated by oxLDL. Inhibiting the activity of the JNK pathway abolishes the increase of Sestrin2 induced by oxLDL. These findings suggest that the inductive effect of Sestrin2 is mediated by the JNK/c-Jun pathway. Our results indicate that the induction of Sestrin2 acts as a compensatory response to oxLDL for survival, implying that stimulating expression of Sestrin2 might be an effective pharmacological target for the treatment of lipid-related cardiovascular diseases. PMID:25692450

  17. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein

    NASA Astrophysics Data System (ADS)

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L.; Varughese, Kottayil I.

    2015-11-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.

  18. l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein

    PubMed Central

    Zhu, Mingzhu; Du, Junbao; Chen, Siyao; Liu, Angie Dong; Holmberg, Lukas; Chen, Yonghong; Zhang, Chunyu; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation. PMID:25514411

  19. Effect of Albizia julibrissin water extracts on low-density lipoprotein oxidization.

    PubMed

    Vaughn, Katherine; McClain, Colt; Carrier, Danielle Julie; Wallace, Sunny; King, Jerry; Nagarajan, Shanmugam; Clausen, Edgar

    2007-06-13

    High-value phytochemicals could be extracted from biomass prior to the current cellulosic pretreatment technologies (i.e., lime, ammonia, dilute acid, or pressurized hot water treatments) provided that the extraction is performed with a solvent that is compatible with the pretreatment. This work reports on the extraction of flavonoids from Albizia julibrissin biomass. While extracting A. julibrissin foliage with 50 degrees C water, 2.227 mg/g of hyperoside and 8.134 mg/g quercitrin were obtained, which is in the realm of what was obtained with 60% methanol. A. julibrissin foliage, flower, and whole plant extracts were tested in terms of their potential to inhibit low-density lipoprotein (LDL) oxidization. The highest inhibition was obtained with foliage water extracts, which were standardized at 2.5 microM of flavonoids. Also, the 2.5 microM foliage water extract resulted in a reduction from 43% to only 1% of the observed monocyte adherence. To have commercial application, A. julibrissin water extracts should be devoid of toxicity. The A. julibrissin foliage, flower, and whole plant water extracts were not toxic to Vero 76 cells. In summary, A. julibrissin biomass can be extracted with 50 degrees C water to yield an antioxidant stream, showing that it may be possible to couple extraction of valuable phytochemicals to the cellulosic pretreatment step. PMID:17497875

  20. Proteome analysis of human monocytic THP-1 cells primed with oxidized low-density lipoproteins.

    PubMed

    Kang, Jeong Han; Kim, Hyun Tae; Choi, Myung-Sook; Lee, Won Ha; Huh, Tae-Lin; Park, Yong Bok; Moon, Byung Jo; Kwon, Oh-Shin

    2006-02-01

    Native low-density lipoprotein (LDL) and oxidized LDL (oxLDL) possess a wide variety of biological properties, and play a central role in atherogenesis. In this study, we used a proteomic analysis of human monocyte THP-1 cells induced with oxLDL or with LDL, to identify proteins potentially involved in atherosclerotic processes. Of the 2500 proteins detected, 93 were differentially expressed as a result of priming with LDL or oxLDL. The proteins were unambiguously identified by comparing the masses of their tryptic peptides with those of all known proteins using MALDI-TOF MS and the NCBI database. The largest differences in expression were observed for vimentin (94-fold increase), meningioma-expressed antigen 6 (48-fold increase), serine/threonine protein phosphatase 2A (40-fold increase), and beta-1,3-galactosyltransferase (15-fold increase). In contrast, the abundance of an unnamed protein product and phosphogluconate dehydrogenase decreased 30-fold and 25-fold, respectively. The expression of some selected proteins was confirmed by Western blot and RT-PCR analyses. The proteins identified in this study are attractive candidates for further biomarker research. This description of the altered protein profiles induced by oxLDL in human monocytes will support functional studies of the macrophage-derived foam cells involved in the pathogenesis of atherosclerosis. PMID:16402358

  1. Rutaecarpine Reverses the Altered Connexin Expression Pattern Induced by Oxidized Low-density Lipoprotein in Monocytes.

    PubMed

    Liu, Yong; Fu, Yan-Qi; Peng, Wei-Jie; Yu, Yan-Rong; Wu, Yu-Si; Yan, Hang; Huang, Qi-Ren; He, Ming; Luo, Dan

    2016-06-01

    Adhesion of monocytes to the vascular endothelium is crucial in atherosclerosis development. Connexins (Cxs) which form hemichannels or gap junctions, modulate monocyte-endothelium interaction. We previously found that rutaecarpine, an active ingredient of the Chinese herbal medicine Evodia, reversed the altered Cx expression induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells, and consequently decreases the adhesive properties of endothelial cells to monocytes. This study further investigated the effect of rutaecarpine on Cx expression in monocytes exposed to ox-LDL. In cultured human monocytic cell line THP-1, ox-LDL rapidly reduced the level of atheroprotective Cx37 but enhanced that of atherogenic Cx43, thereby inhibiting adenosine triphosphate release through hemichannels. Pretreatment with rutaecarpine recovered the expression of Cx37 but inhibited the upregulation of Cx43 induced by ox-LDL, thereby improving adenosine triphosphate-dependent hemichannel activity and preventing monocyte adhesion. These effects of rutaecarpine were attenuated by capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. The antiadhesive effects of rutaecarpine were also attenuated by hemichannel blocker 18α-GA. This study provides additional evidence that rutaecarpine can modulate Cx expression through transient receptor potential vanilloid subtype 1 activation in monocytes, which contributes to the antiadhesive properties of rutaecarpine. PMID:26859198

  2. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  3. Abdominal adiposity, insulin resistance, and oxidized low-density lipoproteins in Latino adolescents.

    PubMed

    Ryder, Justin R; Vega-López, Sonia; Djedjos, Constantine S; Shaibi, Gabriel Q

    2013-01-01

    Abdominal obesity and insulin resistance (IR) place youth at higher risk for premature cardiovascular disease (CVD), but the underlying mechanisms are not clear. In adults, abdominal obesity and IR contribute to the oxidation of low-density lipoprotein (LDL). Whether similar mechanisms are operational in Latino adolescents is unknown. Therefore, we determined whether IR and abdominal adiposity are associated with higher oxLDL concentrations in Latino adolescents. Data from 123 Latino adolescents (16.3 ± 2.5 years; female = 74) were used for the present analysis. Participants were assessed for waist circumference, fasting serum oxLDL, and insulin sensitivity by the whole body insulin sensitivity index. In separate linear regression models adjusting for age and sex, both waist circumference and insulin sensitivity were significant predictors of oxLDL (β = 1.9; p = 0.002; R2 = 0.13, β = -1.7; p = 0.006; R2 = 0.11, respectively). When insulin sensitivity and waist circumference were included in the same model, both remained independent predictors of oxLDL (β = 1.7; p = 0.016 and, β = -1.5; p = 0.055, respectively; R2 = 0.16). These results suggest that insulin resistance and abdominal adiposity are associated with higher levels of LDL oxidation which may be a mechanism contributing to increased CVD risk in Latino adolescents. PMID:24238302

  4. Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function.

    PubMed

    Löhrke, B; Viergutz, T; Krüger, B

    2005-12-01

    The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5-11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3beta-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17beta-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation

  5. Chitin-glucan fiber effects on oxidized low-density lipoprotein: a randomized controlled trial

    PubMed Central

    Bays, H E; Evans, J L; Maki, K C; Evans, M; Maquet, V; Cooper, R; Anderson, J W

    2013-01-01

    Background/objectives: Elevated oxidized low-density lipoprotein (OxLDL) may promote inflammation, and is associated with increased risk of atherosclerotic coronary heart disease and worsening complications of diabetes mellitus. The primary objective of this study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels. Subjects/methods: This 6-week, randomized, double-blind, placebo-controlled study of a novel, insoluble fiber derived from the Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37–4.92 mmol/l and glucose ⩽6.94 mmol/l. Participants were randomly assigned to receive CG (4.5 g/day; n=33), CG (1.5 g/day; n=32), CG (1.5 g/day) plus OO extract (135 mg/day; n=30), or matching placebo (n=35). Results: Administration of 4.5 g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5 g/day group (P=0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels. Adverse events did not substantively differ between treatments and placebo. Conclusions: In this 6-week study, CG (4.5 g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis. PMID:22948945

  6. Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins

    PubMed Central

    Brunner, Monika; Gruber, Miriam; Schmid, Diethart; Baran, Halina; Moeslinger, Thomas

    2015-01-01

    Oxidized low-density lipoprotein (ox-LDL) is assumed to be a major causal agent in hypercholesteraemia-induced atherosclerosis. Because the proliferation of lipid-loaden macrophages within atherosclerotic lesions has been described, we investigated the dependence of macrophage proliferation on the inhibition of inducible nitric oxide synthase (iNOS) by hypochlorite oxidized LDL. Ox-LDL induces a dose dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-interferon stimulated mouse macrophages (J774.A1) with concomitant macrophage proliferation as assayed by cell counting, tritiated-thymidine incorporation and measurement of cell protein. Native LDL did not influence macrophage proliferation and inducible nitric oxide synthesis. iNOS protein and mRNA was reduced by HOCl-oxidized LDL (0-40 µg/ml) as revealed by immunoblotting and competitive semiquantitative PCR. Macrophage proliferation was increased by the addition of the iNOS inhibitor L-NAME. The addition of ox-LDL to L-NAME containing incubations induced no further statistically significant increase in cell number. Nitric oxide donors decreased ox-LDL induced macrophage proliferation and nitric oxide scavengers restored macrophage proliferation to the initial values achieved by ox-LDL. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with ox-LDL demonstrates that the proliferative actions of ox-LDL are associated with a decrease of NO-induced apoptosis. Our data show that inhibition of iNOS dependent nitric oxide production caused by hypochlorite oxidized LDL enhances macrophage proliferation. This might be a key event in the pathogenesis of atherosclerotic lesions. PMID:26600745

  7. Oxidized low density lipoprotein suppresses lipopolysaccharide-induced inflammatory responses in microglia: Oxidative stress acts through control of inflammation

    SciTech Connect

    Kim, Ohn Soon; Lee, Chang Seok; Joe, Eun-hye; Jou, Ilo . E-mail: jouilo@ajou.ac.kr

    2006-03-31

    Low density lipoprotein (LDL) is readily oxidized under certain conditions, resulting in the formation of oxidized LDL (oxLDL). Despite numerous in vitro reports that reveal the pathogenic role of oxidative stress, anti-oxidative strategies have underperformed in the clinic. In this study, we examine the role of oxLDL in brain inflammatory responses using cultured rat brain microglia. We demonstrate that oxLDL inhibits lipopolysaccharide (LPS)-induced inflammatory responses in these cells. It also decreases LPS-induced expression of inducible nitric oxide synthase and production of nitric oxide, and reduces LPS-induced secretion of tumor necrosis factor-{alpha} and monocyte chemoattractant protein-1. Oxysterols, known components of oxLDL and endogenous agonists of liver X receptor, can simulate the inhibitory effects of oxLDL in LPS-activated microglia. In addition, their inhibitory effects were mimicked by liver X receptor (LXR) agonists and potentiated by a retinoid X receptor agonist, suggesting these molecules heterodimerize to function as oxysterol receptors. Taken together, our results demonstrate that oxLDL inhibits LPS-induced inflammatory responses in brain microglia and that these inhibitory effects are mediated by oxysterols and, at least in part, by the nuclear receptor LXR. Our results suggest an additional mechanism of action for oxidative stress that acts indirectly via modulation of inflammatory responses. Although further studies are needed, these results answer in part the question of why anti-oxidative strategies have not been successful in clinical situations. Moreover, as brain inflammation participates in the initiation and progression of several neurodegenerative disorders, the present data provide information that should prove a useful guide for designing therapeutic strategies to combat oxidative brain diseases.

  8. Relationship between oxidized low-density lipoprotein antibodies and obesity in different glycemic situations

    PubMed Central

    Babakr, Abdullatif Taha; Elsheikh, Osman Mohamed; Almarzouki, Abdullah A; Assiri, Adel Mohamed; Abdalla, Badr Eldin Elsonni; Zaki, Hani Yousif; Fatani, Samir H; NourEldin, EssamEldin Mohamed

    2014-01-01

    Background Autoantibodies to oxidized low-density lipoprotein (oxLDL) are a heterogeneous group of antibodies that are controversially discussed to be either pathogenic or protective. Biochemical and anthropometric measurements correlated with increased levels of these antibodies are also controversial, especially in conditions of impaired glucose tolerance and type 2 diabetes mellitus. The present study was conducted to evaluate levels of oxLDL antibodies and their correlation with obesity in different glycemic situations. Methods Two hundred and seventy-four adult males were classified into three subgroups: group 1 (n=125), comprising a control group of nondiabetic subjects; group 2 (n=77), comprising subjects with impaired glucose tolerance; and group 3 (n=72), comprising patients with type 2 diabetes mellitus. Body mass index was calculated, and measurement of oxLDL and oxLDL antibodies was performed. Results Higher mean concentrations of oxLDL were found in the type 2 diabetes mellitus and impaired glucose tolerance groups (143.5±21.9 U/L and 108.7±23.7 U/L, respectively). The mean value for the control group was 73.5±27.5 U/L (P<0.001). Higher mean concentrations of anti-oxLDL antibodies were observed in the type 2 diabetes mellitus and impaired glucose tolerance groups (55.7±17.8 U/L and 40.4±17.6 U/L, respectively). The mean value for the control group was 20.4±10 U/L (P<0.001). Levels of anti-oxLDL antibodies were found to be positively and significantly correlated with body mass index in the control group (r=0.46), impaired glucose tolerance (r=0.51), type 2 diabetes mellitus group (r=0.46), and in the whole study population (r=0.44; P<0.001). Conclusion Anti-oxLDL antibody levels were increased in subjects with type 2 diabetes mellitus and impaired glucose tolerance and were positively correlated with obesity and body mass index. PMID:25368528

  9. Gold nanoparticle-conjugated anti-oxidized low-density lipoprotein antibodies for targeted lipidomics of oxidative stress biomarkers.

    PubMed

    Hinterwirth, Helmut; Stübiger, Gerald; Lindner, Wolfgang; Lämmerhofer, Michael

    2013-09-01

    Oxidized low-density lipoproteins (OxLDLs), in particular, oxidized phosphatidylcholines (OxPCs), are known to be involved in pathophysiological processes such as cardiovascular diseases and are described as potential biomarkers, for example, for atherosclerosis. In our study, we used the specific affinity of anti-OxLDL antibodies (Abs) conjugated to gold nanoparticles (GNPs) for extraction and enrichment of OxPCs via selective trapping of OxLDLs from plasma combined with the sensitive detection by liquid chromatography/tandem-mass spectrometry (LC-MS/MS). Successful bioconjugation chemistry of Abs via a bifunctional polyethylene glycol (PEG) spacer and protein G linkage, respectively, was controlled by measuring the surface plasmon resonance (SPR) spectra, size, and zeta potentials. Furthermore, the amount of Ab immobilized onto GNP via the PEG linker was determined. With the optimized immobilization chemistry, the ability and potential of the GNP-based extraction procedure was used for the determination of the dissociation constant, K(d), of the OxLDL binding to the GNP-Ab conjugate. Moreover, apparent K(d)'s were determined for individual PCs and their oxidation products using the compound-specific selected reaction monitoring mode, which allows the characterization of the Ab affinity and, thus, assessment of the potential antigenicity of (Ox)PCs bound to OxLDLs. In summary, the application of GNP-based bioanalysis for selective targeting of OxLDLs and the fast and sensitive detection by LC-MS/MS offers new possibilities for targeted lipidomics in lipoproteins as well as for oxidative stress lipid biomarker screening. PMID:23895666

  10. Pathways for oxidation of low density lipoprotein by myeloperoxidase: tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine.

    PubMed

    Heinecke, J W

    1997-01-01

    Many lines of evidence implicate oxidation of low density lipoprotein (LDL) in the pathogenesis of atherosclerosis, a chronic inflammatory disease. The physiologically relevant mechanisms have not been identified, but phagocytic white cells may play an important role because macrophage-rich lesions characterize the disorder. Recent studies have shown that myeloperoxidase, a heme enzyme secreted only by phagocytes, is present in human atherosclerotic tissue. The enzyme is a potent catalyst of LDL oxidation in vitro, it co-localizes with macrophages in lesions, and it generates products that are detectable in atherosclerotic plaque. These findings suggest that myeloperoxidase may promote LDL oxidation in the artery wall. This article reviews the enzyme's ability to generate a range of oxidants, including tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine. These products have the potential to damage host molecules as well as microbes, suggesting a mechanism that may contribute to atherosclerotic vascular disease. PMID:9259996

  11. Mechanisms of oxidative damage of low density lipoprotein in human atherosclerosis.

    PubMed

    Heinecke, J W

    1997-10-01

    Oxidatively damaged LDL may play a critical role in the pathogenesis of atherosclerotic vascular disease. Several pathways promote LDL oxidation in vitro but the physiologically relevant mechanisms have proven difficult to identify. Detection of stable compounds that result from specific reaction pathways has provided the first insights into the mechanism of oxidative damage in the human artery wall. Mass spectrometric analysis of protein oxidation products isolated from atherosclerotic tissue implicate tyrosyl radical, reactive nitrogen intermediates and hypochlorous acid in LDL oxidation and lesion formation in vivo. Hypochlorous acid is only generated by the phagocytic enzyme myeloperoxidase, which can also generate tyrosyl radical and reactive nitrogen intermediates. Chiral phase high-pressure liquid chromatography analysis of lipid oxidation products suggests that cellular lipoxygenases may also play a role at certain stages. In contrast, LDL isolated from atherosclerotic tissue is not enriched in protein oxidation products characteristic of free metal ions, which are the most widely studied in vitro model of LDL oxidation. These observations provide the first direct chemical evidence for reaction pathways that promote LDL oxidation in human atherosclerosis. PMID:9335950

  12. Endothelial NOS-dependent activation of c-Jun NH(2)- terminal kinase by oxidized low-density lipoprotein

    NASA Technical Reports Server (NTRS)

    Go, Y. M.; Levonen, A. L.; Moellering, D.; Ramachandran, A.; Patel, R. P.; Jo, H.; Darley-Usmar, V. M.

    2001-01-01

    Oxidized low-density lipoprotein (oxLDL) is known to activate a number of signal transduction pathways in endothelial cells. Among these are the c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase, and extracellular signal-regulated kinase (ERK). These mitogen-activated protein kinases (MAP kinase) determine cell survival in response to environmental stress. Interestingly, JNK signaling involves redox-sensitive mechanisms and is activated by reactive oxygen and nitrogen species derived from both NADPH oxidases, nitric oxide synthases (NOS), peroxides, and oxidized low-density lipoprotein (oxLDL). The role of endothelial NOS (eNOS) in the activation of JNK in response to oxLDL has not been examined. Herein, we show that on exposure of endothelial cells to oxLDL, both ERK and JNK are activated through independent signal transduction pathways. A key role of eNOS activation through a phosphatidylinositol-3-kinase-dependent mechanism leading to phosphorylation of eNOS is demonstrated for oxLDL-dependent activation of JNK. Moreover, we show that activation of ERK by oxLDL is critical in protection against the cytotoxicity of oxLDL.

  13. The inhibiting activity of areca inflorescence extracts on human low density lipoprotein oxidation induced by cupric ion.

    PubMed

    Chen, Weijun; Zhang, Chunmei; Huang, Yulin; Cheng, Fangfang; Shen, Yan; Wang, Rencai; Tang, Minmin; Zheng, Yajun; Zhao, Songlin

    2012-03-01

    The oxidative modification of human low density lipoprotein (LDL) plays a significant role in atherosclerosis. In this study, the inhibiting activity of areca inflorescence extracts (AIEs) on LDL oxidation was investigated by an in vitro study with Trolox as the standard antioxidant. The kinetics of LDL oxidation, thiobarbituric acid reactive substances assay, ferric-reducing antioxidant power assay and copper chelation assay were also evaluated to assess the antioxidant activities of AIEs, and the results revealed that AIEs could delay the lag time and inhibit the formation of malondialdehyde in the process of LDL peroxidation induced by Cu(2+). The boiled water extract displayed the highest antioxidant activity compared with the ambient water extract and ethanol extract. The total phenolic contents and phenolic components of AIEs were also measured by high performance liquid chromatography method. Epicatechin, gallic acid and coumalic acid were the primary phenolic acids in AIEs. PMID:21942744

  14. Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, C. K.; Ehrenwald, E.; Fox, P. L.

    1996-01-01

    Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.

  15. The oxidized low-density lipoprotein receptor mediates vascular effects of inhaled vehicle emissions

    EPA Science Inventory

    Rationale: To determine vascular signaling pathways involved in air pollution (vehicular engine emission) exposure -induced exacerbation of atherosclerosis, associated with onset of clinical cardiovascular events. Objective: To elucidate the role of oxidized LDL (oxLDL) and its ...

  16. Oxidation of Plasmalogen, Low-Density Lipoprotein, and RAW 264.7 Cells by Photoactivatable Atomic Oxygen Precursors

    PubMed Central

    Bourdillon, Max T.; Ford, Benjamin A.; Knulty, Ashley T.; Gray, Colleen N.; Zhang, Miao; Ford, David A.; McCulla, Ryan D.

    2016-01-01

    The oxidation of lipids by endogenous or environmental reactive oxygen species (ROS) generates a myriad of different lipid oxidation products that have important roles in disease pathology. The lipid oxidation products obtained in these reactions is dependent upon the identity of the reacting ROS. The photoinduced deoxygenation of various aromatic heterocyclic oxides has been suggested to generate ground state atomic oxygen (O(3P)) as an oxidant; however, very little is known about reactions between lipids and O(3P). To identify lipid oxidation products arising from the reaction of lipids with O(3P), photoactivatable precursors of O(3P) were irradiated in the presence of lysoplasmenylcholine, low-density lipoprotein, and RAW 264.7 cells under aerobic and anaerobic conditions. Four different aldehyde products consistent with the oxidation of plasmalogens were observed. The four aldehydes were: tetradecanal, pentadecanal, 2-hexadecenal, and hexadecanal. Depending upon the conditions, either pentadecanal or 2-hexadecenal was the major product. Increased amounts of the aldehyde products were observed in aerobic conditions. PMID:27096146

  17. Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein.

    PubMed

    Seo, Jin-Won; Yang, Eun-Jeong; Yoo, Kyung-Hwa; Choi, In-Hong

    2015-01-01

    LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-α and IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis. PMID:26294848

  18. Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation

    SciTech Connect

    Lee, Ha Young; Kim, Sang Doo; Baek, Suk-Hwan; Choi, Joon Hyuk; Cho, Kyung-Hyun; Zabel, Brian A.; Bae, Yoe-Sik

    2013-03-29

    Highlights: ► SAA induced macrophage foam cell formation. ► SAA stimulated upregulation of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1). ► SAA-induced LOX1 expression and foam cell formation is mediated by JNK/NF-κB signaling. ► HDL-conjugated SAA also stimulates foam cell formation via LOX1 upregulation. ► The finding reveals a novel mechanism of action of SAA in the pathogenesis of atherosclerosis. -- Abstract: Elevated levels of serum amyloid A (SAA) is a risk factor for cardiovascular diseases, however, the role of SAA in the pathophysiology of atherosclerosis remains unclear. Here we show that SAA induced macrophage foam cell formation. SAA-stimulated foam cell formation was mediated by c-jun N-terminal kinase (JNK) signaling. Moreover, both SAA and SAA-conjugated high density lipoprotein stimulated the expression of the important scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) via nuclear factor-κB (NF-κB). A LOX1 antagonist carrageenan significantly blocked SAA-induced foam cell formation, indicating that SAA promotes foam cell formation via LOX1 expression. Our findings therefore suggest that SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis.

  19. Effects of flow on LOX-1 and oxidized low-density lipoprotein interactions in brain endothelial cell cultures.

    PubMed

    Mao, Xiaoou; Xie, Lin; Greenberg, David A

    2015-12-01

    Fluid shear stress and uptake of oxidized low-density lipoprotein (ox-LDL) into the vessel wall both contribute to atherosclerosis, but the relationship between shear stress and ox-LDL uptake is unclear. We examined the effects of flow, induced by orbital rotation of bEnd.3 brain endothelial cell cultures for 1 wk, on ox-LDL receptor (LOX-1) protein expression, ox-LDL uptake and ox-LDL toxicity. Orbitally rotated cultures showed no changes in LOX-1 protein expression, ox-LDL uptake or ox-LDL toxicity, compared to stationary cultures. Flow alone does not modify ox-LDL/LOX-1 signaling in bEnd.3 brain endothelial cells in vitro, suggesting that susceptibility of atheroprone vascular sites to lipid accumulation is not due solely to effects of altered flow on endothelium. PMID:26462413

  20. Cholesteryl-ester transfer protein enhances the ability of high-density lipoprotein to inhibit low-density lipoprotein oxidation.

    PubMed

    Hine, David; Mackness, Bharti; Mackness, Mike

    2011-09-01

    Therapeutic strategies to increase high-density lipoprotein (HDL) to treat or prevent vascular disease include the use of cholesteryl-ester transfer protein (CETP) inhibitors. Here, we show, to the best of our knowledge for the first time, that addition of CETP to HDL enhances the ability of HDL to inhibit low-density lipoprotein oxidation by ∼ 30% for total HDL and HDL(2) (both P < 0.05) and 75% for HDL(3) (P < 0.01). Therefore, CETP inhibition may be detrimental to the antiatherosclerotic properties of HDL, and these findings may partly explain the failure of the CETP inhibitor, torcetrapib, treatment to retard vascular disease despite large increases in HDL, in addition to its "off target" toxicity, a property which appears not to be shared by other members of this class of CETP inhibitor currently under clinical trial. Further, detailed studies are urgently required. PMID:21815241

  1. Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice

    PubMed Central

    Napoli, Claudio; Ackah, Eric; de Nigris, Filomena; Del Soldato, Piero; D'Armiento, Francesco P.; Crimi, Ettore; Condorelli, Mario; Sessa, William C.

    2002-01-01

    The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n = 10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 ± 12.3% compared with that of the placebo (P < 0.001). Regular aspirin did not reduce significantly aortic lesions (−5.1 ± 2.3%) compared with the placebo [P = 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P < 0.001) as well as by the prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX-4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P < 0.01), and macrophages–derived foam cells (F4/80 monoclonal antibody, P < 0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice. PMID:12209007

  2. The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells.

    PubMed

    Lin, Feng-Yen; Tsao, Nai-Wen; Shih, Chun-Ming; Lin, Yi-Wen; Yeh, Jong-Shiua; Chen, Jaw-Wen; Nakagami, Hironori; Morishita, Ryuichi; Sawamura, Tatsuya; Huang, Chun-Yao

    2015-01-01

    Late-outgrowth endothelial progenitor cells (EPCs) are stress-resistant and responsible for reparative functions in the cardiovascular system. Oxidized-LDL (oxLDL) plays a critical role in cardiovascular disease pathogenesis. However, it is largely unknown what the impacts of oxLDL are on late-outgrowth EPCs. This study aimed to investigate the concentration-related effects of oxLDL on EPC functions and related angiogenesis, in vitro and in vivo. In this study, early and late-outgrowth EPCs were generated from circulating human mononuclear cells. oxLDL may regulate EPC vasculogenic function via the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Lower concentrations (5 μg/mL) of oxLDL can potentiate EPC tube formation in vitro and in vivo by activating eNOS mechanisms, which are mediated by p38 MAPK- and SAPK/JNK-related pathways. Higher concentrations of oxLDL (10-50 μg/mL) impaired EPC function via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathways and consequent inhibition of eNOS activity, which could be reversed by anti-oxidants (diphenylene iodonium and apocynin) and gp91phox siRNA. In conclusion, oxLDL has concentration-dependent biphasic effects on human late-outgrowth EPC tube formation in vitro and in vivo. PMID:26017136

  3. Oxidized Low-Density Lipoprotein Is Present in Astrocytes Surrounding Cerebral Infarcts and Stimulates Astrocyte Interleukin-6 Secretion

    PubMed Central

    Shie, Feng-Shiun; Neely, M. Diana; Maezawa, Izumi; Wu, Hope; Olson, Sandy J.; Jürgens, Günther; Montine, Kathleen S.; Montine, Thomas J.

    2004-01-01

    Ischemic injury to brain is associated with both disruption of the blood-brain barrier and increased oxidative stress. Given the neurotoxicity associated with exposure to oxidized low-density lipoprotein (oxLDL) in vitro, we tested the hypothesis that oxLDL may be present in parenchymal cells of cerebrum after infarction and that oxLDL may influence the pathophysiology of cerebral infarction. Our results showed that the subacute phase of cerebral infarction in patients was characterized by the appearance of oxLDL epitopes in astrocytes, but not neurons or microglia, in the perinecrotic zone. We further demonstrated that minimally oxLDL was most effectively internalized by primary cultures of rat astrocytes, and that exposure to minimal oxLDL stimulated astrocyte interleukin-6 secretion but did not alter nitric oxide production. These results demonstrate for the first time that oxLDL is present in brain parenchyma of patients with ischemic infarction and suggest a potential mechanism by which oxLDL may activate innate immunity and thereby indirectly influence neuronal survival. PMID:15039206

  4. The Biphasic Effects of Oxidized-Low Density Lipoprotein on the Vasculogenic Function of Endothelial Progenitor Cells

    PubMed Central

    Lin, Feng-Yen; Tsao, Nai-Wen; Shih, Chun-Ming; Lin, Yi-Wen; Yeh, Jong-Shiua; Chen, Jaw-Wen; Nakagami, Hironori; Morishita, Ryuichi; Sawamura, Tatsuya; Huang, Chun-Yao

    2015-01-01

    Late-outgrowth endothelial progenitor cells (EPCs) are stress-resistant and responsible for reparative functions in the cardiovascular system. Oxidized-LDL (oxLDL) plays a critical role in cardiovascular disease pathogenesis. However, it is largely unknown what the impacts of oxLDL are on late-outgrowth EPCs. This study aimed to investigate the concentration-related effects of oxLDL on EPC functions and related angiogenesis, in vitro and in vivo. In this study, early and late-outgrowth EPCs were generated from circulating human mononuclear cells. oxLDL may regulate EPC vasculogenic function via the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Lower concentrations (5 μg/mL) of oxLDL can potentiate EPC tube formation in vitro and in vivo by activating eNOS mechanisms, which are mediated by p38 MAPK- and SAPK/JNK-related pathways. Higher concentrations of oxLDL (10-50 μg/mL) impaired EPC function via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathways and consequent inhibition of eNOS activity, which could be reversed by anti-oxidants (diphenylene iodonium and apocynin) and gp91phox siRNA. In conclusion, oxLDL has concentration-dependent biphasic effects on human late-outgrowth EPC tube formation in vitro and in vivo. PMID:26017136

  5. Effect of garlic supplementation on oxidized low density lipoproteins and lipid peroxidation in patients of essential hypertension.

    PubMed

    Dhawan, Veena; Jain, Sanjay

    2004-11-01

    Reactive oxygen species (ROS) has been implicated in the pathogenesis of many diseases including hypertension. Therefore, certain compounds with antioxidative capacity are believed to be protective against such diseases. Some components of garlic are known to possess antioxidative properties. Therefore, in the present study we investigated the effect of short-term garlic supplementation in essential hypertensive patients (EH) on indices of oxidative stress. Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls were enrolled for the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were obtained at start of the study, i.e. 0 day, and thereafter, 2 months (follow-up). Lipids and lipoprotein subfractions, plasma-oxidized low-density lipoproteins (ox-LDL), plasma and urinary concentration of 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha) as a biomarker of oxidative stress in vivo, and the total antioxidant status (TOS) of these individuals were determined. We observed a moderate hypercholesterolemia and a significantly raised blood pressure in hypertensive patients as compared to the controls. The indices of oxidative stress, i.e. plasma ox-LDL and plasma and urinary concentration of 8-iso-PGF2alpha were significantly increased in EH group. Further, hypertensive patients had a significantly low TOS as compared to the control group. With in 2 months of GP supplementation, there was a significant decline in both systolic (SBP) and diastolic blood pressures (DBP) and a significant reduction in ox-LDL and 8-iso-PGF2alpha levels in Group I patients. Further, a moderate increase in the TOS was also observed in this group as compared to their control counterparts. These findings suggest that dietary supplementation of garlic may be beneficial in reducing blood pressure and oxidative stress in hypertensive individuals. PMID:15646031

  6. Circulating oxidized low-density lipoproteins and arterial elasticity: comparison between men with metabolic syndrome and physically active counterparts

    PubMed Central

    2010-01-01

    Background Accumulation of oxidized low-density lipoproteins in the intimae of arteries and endothelial dysfunction are key events in the development of atherosclerosis. Patients with metabolic syndrome are at high risk for cardiovascular diseases but the linkage between metabolic syndrome and atherosclerosis is incompletely understood. We studied whether the levels of oxidized LDL and arterial elasticity differ between metabolic syndrome patients and physically active controls. Methods 40 men with metabolic syndrome and 40 physically active controls participated in this cross-sectional study. None of the study subjects had been diagnosed with cardiovascular disease. Levels of oxidized LDL were assessed by a two-site ELISA immunoassay. Arterial elasticity was assessed non-invasively by the HDI/PulseWave™ CR-2000 arterial tonometer. Results Levels of oxidized LDL were 89.6 ± 33.1 U/L for metabolic syndrome subjects and 68.5 ± 23.6 U/L for controls (p = 0.007). The difference remained significant after adjustment for LDL cholesterol. Large artery elasticity index (C1) was 16.2 ± 4.1 mL/mmHgx10 for metabolic syndrome subjects and 19.4 ± 3.7 mL/mmHgx10 for controls (p = 0.001), small artery indices (C2) were 7.0 ± 3.2 mL/mmHgx100 and 6.5 ± 2.9 mL/mmHgx100 (NS), respectively. Conclusions Subjects with metabolic syndrome had elevated levels of oxidized LDL and reduced large arterial elasticity compared to controls. This finding may partly explain the increased risk for cardiovascular diseases among metabolic syndrome patients. Trial registration ClinicalTrials.gov NCT01114763 PMID:20727144

  7. Oxidized Low-Density Lipoprotein Contributes to Atherogenesis via Co-activation of Macrophages and Mast Cells

    PubMed Central

    Chen, Chong; Khismatullin, Damir B.

    2015-01-01

    Oxidized low-density lipoprotein (OxLDL) is a risk factor for atherosclerosis, due to its role in endothelial dysfunction and foam cell formation. Tissue-resident cells such as macrophages and mast cells release inflammatory mediators upon activation that in turn cause endothelial activation and monocyte adhesion. Two of these mediators are tumor necrosis factor (TNF)-α, produced by macrophages, and histamine, produced by mast cells. Static and microfluidic flow experiments were conducted to determine the number of adherent monocytes on vascular endothelium activated by supernatants of oxLDL-treated macrophages and mast cells or directly by oxLDL. The expression of adhesion molecules on activated endothelial cells and the concentration of TNF-α and histamine in the supernatants were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. A low dose of oxLDL (8 μg/ml), below the threshold for the clinical presentation of coronary artery disease, was sufficient to activate both macrophages and mast cells and synergistically increase monocyte-endothelium adhesion via released TNF-α and histamine. The direct exposure of endothelial cells to a much higher dose of oxLDL (80 μg/ml) had less effect on monocyte adhesion than the indirect activation via oxLDL-treated macrophages and mast cells. The results of this work indicate that the co-activation of macrophages and mast cells by oxLDL is an important mechanism for the endothelial dysfunction and atherogenesis. The observed synergistic effect suggests that both macrophages and mast cells play a significant role in early stages of atherosclerosis. Allergic patients with a lipid-rich diet may be at high risk for cardiovascular events due to high concentration of low-density lipoprotein and histamine in arterial vessel walls. PMID:25811595

  8. Oxidised low density lipoprotein causes human macrophage cell death through oxidant generation and inhibition of key catabolic enzymes.

    PubMed

    Katouah, Hanadi; Chen, Alpha; Othman, Izani; Gieseg, Steven P

    2015-10-01

    Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death. PMID:26255116

  9. Z-Scan Analysis: a New Method to Determine the Oxidative State of Low-Density Lipoprotein and Its Association with Multiple Cardiometabolic Biomarkers

    NASA Astrophysics Data System (ADS)

    de Freitas, Maria Camila Pruper; Figueiredo Neto, Antonio Martins; Giampaoli, Viviane; da Conceição Quintaneiro Aubin, Elisete; de Araújo Lima Barbosa, Milena Maria; Damasceno, Nágila Raquel Teixeira

    2016-04-01

    The great atherogenic potential of oxidized low-density lipoprotein has been widely described in the literature. The objective of this study was to investigate whether the state of oxidized low-density lipoprotein in human plasma measured by the Z-scan technique has an association with different cardiometabolic biomarkers. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I and apolipoprotein B, paraoxonase-1, and glucose were analyzed using standard commercial kits, and low-density lipoprotein cholesterol was estimated using the Friedewald equation. A sandwich enzyme-linked immunosorbent assay was used to detect electronegative low-density lipoprotein. Low-density lipoprotein and high-density lipoprotein sizes were determined by Lipoprint® system. The Z-scan technique was used to measure the non-linear optical response of low-density lipoprotein solution. Principal component analysis and correlations were used respectively to resize the data from the sample and test association between the θ parameter, measured with the Z-scan technique, and the principal component. A total of 63 individuals, from both sexes, with mean age 52 years (±11), being overweight and having high levels of total cholesterol and low levels of high-density lipoprotein cholesterol, were enrolled in this study. A positive correlation between the θ parameter and more anti-atherogenic pattern for cardiometabolic biomarkers together with a negative correlation for an atherogenic pattern was found. Regarding the parameters related with an atherogenic low-density lipoprotein profile, the θ parameter was negatively correlated with a more atherogenic pattern. By using Z-scan measurements, we were able to find an association between oxidized low-density lipoprotein state and multiple cardiometabolic biomarkers in samples from individuals with different cardiovascular risk factors.

  10. A phagocytosis assay for oxidized low-density lipoprotein versus immunoglobulin G-coated microbeads in human U937 macrophages.

    PubMed

    Vance, David T; Dufresne, Jaimie; Florentinus-Mefailoski, Angelique; Tucholska, Monika; Trimble, William; Grinstein, Sergio; Marshall, John G

    2016-05-01

    The human monocyte cell line U937 was differentiated into an adherent macrophage phenotype using phorbol 12-myristate 13-acetate (PMA) to assay the phagocytosis of oxidized low-density lipoprotein (oxLDL) that may play a role in atherosclerosis. Microbeads were coated with the inflammatory ligand oxLDL to create a novel phagocytosis assay that models the binding of macrophages to oxLDL in the solid phase such as found in the fatty streaks of the arteries. The oxLDL was prepared with LDL from human ethylenediaminetetraacetic acid (EDTA) plasma oxidized with an excess (5 mM) of the strong oxidizing agent CuSO4 and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blot. The binding of the oxLDL to the beads was confirmed by DilC18-oxLDL staining and confocal microscopy in addition to trypsin digestion of the microbeads for liquid chromatography, electrospray ionization, and tandem mass spectrometry. Phagocytosis of the oxLDL versus human bulk immunoglobulin G1 (IgG1)-coated microbeads was assayed over time, in the presence and absence of serum factors, by pulse chase and with enzyme inhibitor treatments. The ligand beads were then stained with specific antibodies to oxLDL versus human IgG to differentially stain external versus engulfed ligand microbeads. The phagocytosis of oxLDL and IgG ligand microbeads was abolished by the actin polymerization inhibitors cytochalasin D and latrunculin. Pharmacological inhibitors of the receptor enzymes JAK, SRC, and PLC prevented both IgG and oxLDL receptor function. In contrast, the function of the oxLDL phagocytic receptor complex was more sensitive to inhibition of PTK2, PKC, and SYK activity. PMID:26800863

  11. Oxidized low-density lipoprotein accelerates the destabilization of extracellular-superoxide dismutase mRNA during foam cell formation.

    PubMed

    Makino, Junya; Nii, Miyuki; Kamiya, Tetsuro; Hara, Hirokazu; Adachi, Tetsuo

    2015-06-01

    Extracellular-superoxide dismutase (EC-SOD) is one of the main anti-oxidative enzymes that protect cells against the damaging effects of superoxide. In the present study, we investigated the regulation of EC-SOD expression during the oxidized low density lipoprotein (oxLDL)-induced foam cell formation of THP-1-derived macrophages. The uptake of oxLDL into THP-1-derived macrophages was increased and EC-SOD expression was decreased in a time-dependent manner by oxLDL. Furthermore, EC-SOD suppression by oxLDL was mediated by the binding to scavenger receptors, especially CD36, from the results with siRNA experience. EC-SOD expression is known to be regulated by histone acetylation and binding of the transcription factor Sp1/3 to the EC-SOD promoter region in human cell lines. However, oxLDL did not affect these processes. On the other hand, the stability of EC-SOD mRNA was decreased by oxLDL. Moreover, oxLDL promoted destabilization of ectopically expressed mRNA from EC-SOD or chimeric Cu,Zn-SOD gene with the sequence corresponding to 3'UTR of EC-SOD mRNA, whereas oxLDL had no effect on ectopic mRNA produced from EC-SOD gene lacking the sequence. These results suggested that oxLDL decreased the expression of EC-SOD, which, in turn, accelerated the destabilization of EC-SOD mRNA, leading to weaker protection against oxidative stress and atherosclerosis. PMID:25906743

  12. Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H(2)O(2) from DNA damage.

    PubMed

    Tselepis, A; Doulias, P; Lourida, E; Glantzounis, G; Tsimoyiannis, E; Galaris, D

    2001-06-15

    Trimetazidine is a well-established anti-ischemic drug, which has been used for long time in the treatment of pathological conditions related with the generation of reactive oxygen species. However, although extensively studied, its molecular mode of action remains largely unknown. In the present study, the ability of trimetazidine to protect low-density lipoproteins (LDL) from oxidation and cultured cells from H(2)O(2)-induced DNA damage was investigated. Trimetazidine, tested at concentrations 0.02 to 2.20 mM, was shown to offer significant protection to LDL exposed to three different oxidizing systems, namely copper, Fe/ascorbate, and met-myoglobin/H(2)O(2). The oxidizability of LDL was estimated by measuring, (i) the lag period, (ii) the maximal rate of conjugated diene formation, (iii) the total amount of conjugated dienes formed, (iv) the electrophoretic migration of LDL protein in agarose gels (REM), and (v) the inactivation of the enzyme PAF-acetylhydrolase present in LDL. In addition, the presence of trimetazidine decreased considerably the DNA damage in H(2)O(2)-exposed Jurkat cells in culture. H(2)O(2) was continuously generated by the action of glucose oxidase at a rate of 11.8 +/- 1.5 microM per min (60 ng enzyme per 100 microl), and DNA damage was assessed by the single cell gel electrophoresis assay (also called comet assay). The protection offered by trimetazidine in this system (about 30% at best) was transient, indicating modification of this agent during its action. These results indicate that trimetazidine can modulate the action of oxidizing agents in different systems. Although its mode of action is not clarified, the possibility that it acts as a lipid barrier permeable transition metal chelator is considered. PMID:11390180

  13. Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine

    PubMed Central

    Viora, Marina; Quaranta, Maria Giovanna; Straface, Elisabetta; Vari′, Rosaria; Masella, Roberta; Malorni, Walter

    2001-01-01

    This study investigates the in vitro effects of oxidized low-density lipoproteins (ox-LDL), ‘physiological’ pro-oxidants, N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, and their combination on human peripheral blood mononuclear cell functions. We found that treatment with ox-LDL induced a significant down-regulation of proliferative response to mitogens, antigens and interleukin-2. Lipid extracts from ox-LDL were able to reproduce the same effect as the lipoprotein. On the other hand, NAC exposure induced a significant up-regulation of proliferative responses to all the stimuli used. Moreover, we showed that natural killer (NK) cell-mediated cytotoxic activity was significantly down-regulated by ox-LDL while treatment with NAC induced a significant up-regulation of NK-cell activity. Finally, we found that ox-LDL and NAC exerted opposite effects on the cytokine network, interfering both at the protein secretion level and the messenger RNA synthesis level. More importantly, when NAC was used in combination with ox-LDL the proliferative responses, NK-cell-mediated cytotoxic activity and cytokine production were restored to values comparable to controls. These data indicate that ox-LDL and NAC modulate immune functions, exerting opposite effects reflecting their pro-oxidant and antioxidant behaviours. Our results add new insights to the key role played by redox imbalance as a modulator of immune system homeostasis and suggest that an antioxidant drug such as NAC could be useful against pathologies associated with an increase in lipid peroxidation. PMID:11899429

  14. Protective effect of rosuvastatin treatment by regulating oxidized low-density lipoprotein expression in a rat model of liver fibrosis

    PubMed Central

    Yu, Shuiping; Zhou, Xueling; Hou, Bingzong; Tang, Bo; Li, Jian; Zhang, Baimeng

    2016-01-01

    The present study aimed to evaluate the protective effect of rosuvastatin treatment on the mechanism of oxidized low-density lipoprotein (Ox-LDL) in rats with liver fibrosis. In total, 72 male Sprague-Dawley rats were divided into 3 groups: 24 in the control group (A), 24 in the obstructive jaundice models group (B) and 24 in the rosuvastatin group (C). Each group was further divided into four subgroups for assessment at different time-points. The obstructive jaundice models were established and rosuvastatin was administered by gavage. Liver fibrosis indicators, Ox-LDL, malonaldehyde (MDA) and superoxide dismutase (SOD), were measured and liver pathological changes were observed at weeks 1, 2, 3 and 4 after model induction. In groups B and C, the rat models were successfully established, and there were significant changes in the expression of Ox-LDL and the three liver fibrosis indicators when compared to group A (P<0.01). However, the expression of Ox-LDL and the three liver fibrosis indicators in group C were decreased compared with group B (P<0.05), while SOD increased (P<0.05) and MDA decreased (P<0.05). The three liver fibrosis indicators were different in comparison to group B (P<0.05). Thus, there appeared to be an association between the expression of Ox-LDL and liver fibrosis. Treatment with rosuvastatin could regulate the expression of Ox-LDL and improve liver fibrosis in rat models with obstructive jaundice. PMID:27588174

  15. Olmesartan Attenuates the Impairment of Endothelial Cells Induced by Oxidized Low Density Lipoprotein through Downregulating Expression of LOX-1

    PubMed Central

    Zhang, Hua; Ma, Genshan; Yao, Yuyu; Qian, Huidong; Li, Weizhang; Chen, Xinjun; Jiang, Wenlong; Zheng, Ruolong

    2012-01-01

    Oxidized low density lipoprotein (ox-LDL) and its receptor, lectin-Like ox-LDL receptor-1 (LOX-1), play important roles in the development of endothelial injuries. Olmesartan can protect endothelial cells from the impairment caused by various pathological stimulations. In the present study we investigated whether olmesartan decreased the impairment of endothelial cells induced by ox-LDL by exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in mice for 3 weeks led to the remarkable impairment of endothelial cells, including increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK) and expression of apoptotic genes such as B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3. Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly reduced. All these effects, however, were significantly suppressed by the treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1 expression either in cultured endothelial cells or in the aortas of mice, which was reversed with the administration of olmesartan. Our data indicated that olmesartan may attenuate the impairment of endothelial cell via down-regulation of the increased LOX-1 expression induced by ox-LDL. PMID:22408405

  16. The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line

    PubMed Central

    2011-01-01

    Background The purpose of this study was to identify the affect on the proliferation Eca-109 cells treated with oxidized low-density lipoprotein (ox-LDL) combined with adriamycin (ADM). Methods Eca-109 cell were cultured in the presence of oxLDL/ADM, and cell proliferation tested by MTT and cell apoptosis was monitored by the proportion of apoptosis and cell cycle by flow cytomester. We simultaneously evaluated the level of associated- apoptosis Bcl-2, Bax, and Caspase-3 gene mRNA and protein. Results OxLDL were cytotoxic and activate apoptosis. OxLDL combined with ADM significant enhanced the proportion rate of apoptosis on a time and dose dependency. The expressions of the inhibiting apoptosis Bcl-2 gene mRNA and protein were down regulated, whereas, the expressions of the promoting apoptosis Bax, and Caspase-3 genes mRNA and protein were up regulation. Conclusion These results suggested that oxLDL have cytotoxicity and activate apoptosis on the Eca-109 cells. OxLDL combined with ADM have a synergistic effect on the apoptosis induced Eca-109 cells. Furthermore, oxLDL may contribute to the improvement of clinical chemotherapy of cancer need to make further investigation. PMID:21711568

  17. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    PubMed Central

    Georgoulidou, Anastasia; Roumeliotis, Athanasios; Roumeliotis, Stefanos; Giannakopoulou, Efstathia; Papanas, Nikolaos; Passadakis, Ploumis; Manolopoulos, Vangelis G.; Vargemezis, Vassilis

    2015-01-01

    Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = −5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought. PMID:26064982

  18. The effect of adiponectin on osteonectin gene expression by oxidized low density lipoprotein-treated vascular smooth muscle cells.

    PubMed

    Niknam, Sara; Ghatreh-Samani, Keihan; Farrokhi, Effat

    2015-01-01

    Osteonectin is a bone- associated protein involved in vascular calcification. Adiponectin may protect against cardiovascular disease but possible effects on vascular calcification have been poorly studied. The aim of this study was to investigate the modulatory effect of adiponectin on oxidized low density lipoprotein (oxLDL)- induced expression of osteonectin in human aorta vascular smooth muscle cells (HA/VSMCs). HA/VSMCs were cultured in F12K media and then treated with oxLDL (100 µg/mL) in the presence or absence of adoponectin (5 µg/mL) for 24 and 48 hours. mRNA expression and protein level of osteonectin were determined by quantitative real-time PCR and western blot analysis, respectively. After exposure to oxLDL, osteonectin expression increased 1.62 ± 0.23- and 6.62 ± 0.48-fold after 24 and 48 hours respectively compared to the control. Adiponectin increased oxLDL- induced osteonectin expression in a time-dependent manner after 24 and 48 hours (3.24 ± 0.39- and 24.93 ± 2.15-fold, respectively). Western blotting confirmed that osteonectin protein was upregulated by adiponectin.Our data suggest that OxLDL might cause the increase of osteonectin expression both at mRNA and protein level. This upregulation is intensified by adiponectin. PMID:25815284

  19. Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein.

    PubMed

    Yang, Ke; Zhang, Xiao Jie; Cao, Li Juan; Liu, Xin He; Liu, Zhu Hui; Wang, Xiao Qun; Chen, Qiu Jin; Lu, Lin; Shen, Wei Feng; Liu, Yan

    2014-01-01

    Oxidized low-density lipoprotein (oxLDL)-regulated secretion of inflammatory cytokines in smooth muscle cells (SMCs) is regarded as an important step in the progression of atherosclerosis; however, its underlying mechanism remains unclear. This study investigated the role of toll-like receptor 4 (TLR4) in oxLDL-induced expression of inflammatory cytokines in SMCs both in vivo and in vitro. We found that the levels of TLR4, interleukin 1-β (IL1-β), tumor necrosis factor-α (TNFα), monocyte chemoattractant protein 1 (MCP-1) and matrix metalloproteinase-2 (MMP-2) expression were increased in the SMCs of atherosclerotic plaques in patients with femoral artery stenosis. In cultured primary arterial SMCs from wild type mice, oxLDL caused dose- and time-dependent increase in the expression levels of TLR4 and cytokines. These effects were significantly weakened in arterial SMCs derived from TLR4 knockout mice (TLR4-/-). Moreover, the secretion of inflammatory cytokines was blocked by TLR4-specific antibodies in primary SMCs. Ox-LDL induced activation of p38 and NFκB was also inhibited in TLR4-/- primary SMCs or when treated with TLR4-specific antibodies. These results demonstrated that TLR4 is a crucial mediator in oxLDL-induced inflammatory cytokine expression and secretion, and p38 and NFκB activation. PMID:24755612

  20. The Effect of Adiponectin on Osteonectin Gene Expression by Oxidized Low Density Lipoprotein-Treated Vascular Smooth Muscle Cells

    PubMed Central

    Niknam, Sara; Ghatreh-Samani, Keihan; Farrokhi, Effat

    2015-01-01

    Osteonectin is a bone- associated protein involved in vascular calcification. Adiponectin may protect against cardiovascular disease but possible effects on vascular calcification have been poorly studied. The aim of this study was to investigate the modulatory effect of adiponectin on oxidized low density lipoprotein (oxLDL)- induced expression of osteonectin in human aorta vascular smooth muscle cells (HA/VSMCs). HA/VSMCs were cultured in F12K media and then treated with oxLDL (100 µg/mL) in the presence or absence of adoponectin (5 µg/mL) for 24 and 48 hours. mRNA expression and protein level of osteonectin were determined by quantitative real-time PCR and western blot analysis, respectively. After exposure to oxLDL, osteonectin expression increased 1.62 ± 0.23- and 6.62 ± 0.48-fold after 24 and 48 hours respectively compared to the control. Adiponectin increased oxLDL- induced osteonectin expression in a time-dependent manner after 24 and 48 hours (3.24 ± 0.39- and 24.93 ± 2.15-fold, respectively). Western blotting confirmed that osteonectin protein was upregulated by adiponectin.Our data suggest that OxLDL might cause the increase of osteonectin expression both at mRNA and protein level. This upregulation is intensified by adiponectin. PMID:25815284

  1. Normal human IgG prevents endothelial cell activation induced by TNFα and oxidized low-density lipoprotein atherogenic stimuli

    PubMed Central

    RONDA, N; BERNINI, F; GIACOSA, R; GATTI, R; BALDINI, N; BUZIO, C; ORLANDINI, G

    2003-01-01

    Normal human immunoglobulin G (IgG) has anti-inflammatory and immuno-regulatory properties, which are exploited in the therapy of selected diseases. A putative mechanisms of action is the direct regulation of endothelial cell function by natural antiendothelial cell antibodies. Endothelium activation is a critical event in atherosclerosis. We have verified the ability of normal human IgG to modulate endothelial responses to the atherogenic stimuli tumour necrosis factor-α (TNFα) and oxidized low-density lipoproteins (oxLDL) in vitro. Confocal microscopy was used to visualize vascular cell adhesion molecule-1 (CD106) expression on endothelial cells, cytoplasmic free calcium ([Ca++]i) modifications and fluorescein-coupled oxLDL internalization. Cytokine secretion was measured by ELISA on cell supernatants. IgG prevented TNFα induced CD106 membrane expression and an increase in [Ca++]i, and inhibited the secretion of interleukin-6 (IL-6) and macrophage-colony-stimulating factor (M-CSF). IgG also inhibited CD106 expression induced by oxLDL and one pathway of their internalization, but were ineffective on oxLDL induced [Ca++]i rise and apoptosis. F(ab)′2 fragments from IgG, but not monoclonal IgG, reproduce IgG effects. These findings point to a regulatory role for specific antibodies included in circulating normal IgG towards proinflammatory responses of endothelial cells in atherogenesis and suggest possible development of new therapeutic strategies. PMID:12869027

  2. Tartaric Acid-based Amphiphilic Macromolecules with Ether Linkages Exhibit Enhanced Repression of Oxidized Low Density Lipoprotein Uptake

    PubMed Central

    Abdelhamid, Dalia; Zhang, Yingue; Lewis, Daniel R.; Moghe, Prabhas V.; Welsh, William J.; Uhrich, Kathryn E.

    2015-01-01

    Cardiovascular disease initiates with the atherogenic cascade of scavenger receptor- (SR-) mediated oxidized low-density lipoprotein (oxLDL) uptake. Resulting foam cell formation leads to lipid-rich lesions within arteries. We designed amphiphilic macromolecules (AMs) to inhibit these processes by competitively blocking oxLDL uptake via SRs, potentially arresting atherosclerotic development. In this study, we investigated the impact of replacing ester linkages with ether linkages in the AM hydrophobic domain. We hypothesized that ether linkages would impart flexibility for orientation to improve binding to SR binding pockets, enhancing anti-atherogenic activity. A series of tartaric acid-based AMs with varying hydrophobic chain lengths and conjugation chemistries were synthesized, characterized, and evaluated for bioactivity. 3-D conformations of AMs in aqueous conditions may have significant effects on anti-atherogenic potency and were simulated by molecular modeling. Notably, ether-linked AMs exhibited significantly higher levels of inhibition of oxLDL uptake than their corresponding ester analogues, indicating a dominant effect of linkage flexibility on pharmacological activity. The degradation stability was also enhanced for ether-linked AMs. These studies further suggested that alkyl chain length (i.e., relative hydrophobicity), conformation (i.e., orientation), and chemical stability play a critical role in modulating oxLDL uptake, and guide the design of innovative cardiovascular therapies. PMID:25890704

  3. Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters.

    PubMed Central

    Lehr, H A; Hübner, C; Finckh, B; Angermüller, S; Nolte, D; Beisiegel, U; Kohlschütter, A; Messmer, K

    1991-01-01

    In vitro studies indicate that oxidatively modified low density lipoprotein (oxLDL) promotes leukocyte adhesion to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters, we studied whether (a) oxLDL elicits leukocyte/endothelium interaction in vivo, and whether (b) leukotrienes play a mediator role in this event. Leukocyte/endothelium interaction was assessed in the time course after intravenous injection of native human LDL (4 mg/kg body wt) and of oxLDL (7.5 microM Cu++, 6 h, 37 degrees C) into control hamsters and into hamsters, pretreated with the selective leukotriene biosynthesis inhibitor MK-886 (20 mumol/kg, i.v.). While no effect was seen after injection of native LDL, oxLDL elicited an immediate induction of leukocyte adhesion to the endothelium of arterioles and postcapillary venules. Total and differential leukocyte counts suggest that all leukocyte subsets were likewise affected by oxLDL with no specific preference for monocytes. Stimulation of leukocyte adhesion was entirely prevented in inhibitor-treated animals, suggesting the important mediator role of leukotrienes in oxLDL-induced leukocyte/endothelium interaction. Images PMID:2056134

  4. Effect of Oxidized Low Density Lipoprotein on the Expression of Runx2 and SPARC Genes in Vascular Smooth Muscle Cells

    PubMed Central

    Farrokhi, Effat; Ghatreh Samani, Keihan; Hashemzadeh, Morteza; Tabatabaiefar, Mohammad Amin

    2015-01-01

    Background: Vascular calcification is an important stage in atherosclerosis. During this stage, vascular smooth muscle cells (VSMC) synthesize many osteogenic factors such as osteonectin (encoded by SPARC). Oxidative stress plays a critical role in atherosclerosis progression, and its accumulation in the vascular wall stimulates the development of atherosclerosis and vascular calcification. The osteonectin overexpression has been observed in the arterial wall during the course of atherosclerosis. However, the regulatory mechanism of oxidized low density lipoprotein (oxLDL)-mediated vascular calcification remains to be clarified. The aim of this study was to investigate the effect of oxLDL on the osteonectin gene expression through the Runx2 transcription factor. Methods: In this experimental study, VSMC were cultured in F-12K media and then treated with oxLDL. The expression of Runx2 and osteonectin genes was determined by real-time PCR method. Protein levels were investigated by the western blotting technique. The Runx2 gene was knocked down using siRNA in order to determine whether Runx2 regulates the osteonectin expression in VSMC induced by oxLDL. Then transfected cells were treated with oxLDL, and the expression levels of Runx2 and osteonectin were determined again. Results: oxLDL was found to increase Runx2 and osteonectin gene expression (4.8 ± 0.47- and 9.2 ± 1.96-fold, respectively) after 48 h. Western blotting analysis confirmed the induced levels of Runx2 and osteonectin proteins. However, oxLDL-induced osteonectin expression was not observed to be blocked by Runx2 knockdown. Conclusion: The up-regulation of osteonectin by oxLDL is independent of Runx2, and it may be mediated by other transcription factors. PMID:26025968

  5. Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved.

    PubMed

    Chen, Chao-Hung; Ke, Liang-Yin; Chan, Hua-Chen; Lee, An-Sheng; Lin, Kun-Der; Chu, Chih-Sheng; Lee, Mei-Yueh; Hsiao, Pi-Jung; Hsu, Chin; Chen, Chu-Huang; Shin, Shyi-Jang

    2016-08-01

    Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1(-/-) mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease. PMID:27256691

  6. Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S

    PubMed Central

    Chen, Chao-Hung; Ke, Liang-Yin; Chan, Hua-Chen; Lee, An-Sheng; Lin, Kun-Der; Chu, Chih-Sheng; Lee, Mei-Yueh; Hsiao, Pi-Jung; Hsu, Chin; Chen, Chu-Huang; Shin, Shyi-Jang

    2016-01-01

    Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. “Stimulated by retinoic acid 6” (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1−/− mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease. PMID:27256691

  7. Effect of lycopene on the copper-induced oxidation of low-density lipoprotein in broiler chickens.

    PubMed

    Lee, Kyung-Woo; Choo, Won-Don; Kang, Chang-Won; An, Byoung-Ki

    2016-01-01

    The present study was undertaken to investigate whether dietary lycopene (LP) could prevent the copper-mediated oxidation of low density lipoprotein (LDL), and affect growth performance, relative organ weights, plasma and meat lipid profiles, and LP contents in plasma and tissues in broiler chickens. A total of 160 day-old male broiler chicks were randomly allotted into 16 pens with rice husk as a bedding material. Each experiment had 4 replicates, 10 chicks per replicate (n = 4 per treatment). A corn-soybean meal base diet was used as a control diet (CONT). To formulate the experimental diets, the base diet was added with LP at the levels of 10 (LP10) or 20 mg/kg (LP20), or 17 g/kg of tomato paste (TP17) which was equivalent to 5 ppm of LP. The experiment lasted 4 weeks. Growth performance and relative organ weights were not affected (p > 0.05) by any of dietary treatments. Dietary LP significantly lowered (p < 0.05) triglyceride and LDL cholesterol at 2 weeks of age, but did not affect them at 4 weeks of age. Total cholesterol in thigh meats was not altered by dietary treatments. LP was not detected in leg meats in all chicks, nor in liver or plasma of the CONT group. LP was found in liver and plasma, being the former greater in the concentration, of the chicks fed diets containing LP10, LP20, or TP17. At 2 and 4 weeks, the copper-mediated oxidation of LDL was delayed (p < 0.05) in either LP- or TP-fed chickens compared with the CONT group. In conclusion, LP lowers triglyceride and LDL cholesterol, is deposited into serum and liver, and prevents the LDL oxidation in broiler chickens, confirming the role of LP in the lipid-lowering and antioxidant properties in broiler chickens. PMID:27047715

  8. Losartan attenuated lipopolysaccharide-induced lung injury by suppression of lectin-like oxidized low-density lipoprotein receptor-1

    PubMed Central

    Deng, Wang; Deng, Yue; Deng, Jia; Wang, Dao-Xin; Zhang, Ting

    2015-01-01

    Introduction: Recent study has shown that renin-angiotensin system plays an important role in the development of acute lung injury (ALI) with high level of angiotensin II (AngII) generated form AngI catalyzed by angiotensin-converting enzyme. AngII plays a major effect mainly through AT1 receptor. Therefore, we speculate inhibition of AT1 receptor may possibly attenuate the lung injury. Losartan, an antagonist of AT1 receptor for angiotensin II, attenuated lung injury by alleviation of the inflammation response in ALI, but the mechanism of losartan in ALI still remains unclear. Methods: Thirty male Sprague-Dawley rats were randomly divided into Control group, ALI group (LPS), and Losartan group (LPS + Losartan). Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis. The expressions of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), intercellular adhesion molecule-1 (ICAM-1) and caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. Results: In ALI group, TNF-α and protein level in BALF, MPO activity in lung tissue, pulmonary edema and lung injury were significantly increased. Losartan significantly reduced LPS-induced increase in TNF-α and protein level in BALF, MPO activity, pulmonary edema and lung injury in LPS-induced lung injury. The mRNA and protein expression levels of LOX-1 were significantly decreased with the administration of losartan in LPS-induced lung injury. Also, losartan blocked the protein levels of caspase-3 and ICAM-1 mediated by LOX-1 in LPS-induced lung injury. Conclusions: Losartan attenuated lung injury by alleviation of the inflammation and cell apoptosis by inhibition of LOX-1 in LPS-induced lung injury. PMID:26884836

  9. Association between soluble lectin-like oxidized low-density lipoprotein receptor 1 levels and coronary slow flow phenomenon

    PubMed Central

    Caglar, Ilker Murat; Ozde, Cem; Caglar, Fatma Nihan Turhan; Akturk, Ibrahim Faruk; Ugurlucan, Murat; Karakaya, Osman

    2016-01-01

    Introduction The coronary slow flow phenomenon (CSFP) has been associated with myocardial ischemia, myocardial infarction, life-threatening arrhythmias, sudden cardiac death and increased cardiovascular mortality similar to coronary artery disease (CAD). Possible underlying mechanisms of CSFP are endothelial dysfunction, chronic inflammation, microvascular dysfunction and diffuse atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) seems to play an important role in the pathogenesis of atherosclerosis. We hypothesized that sLOX-1 might be associated with CSFP, and aimed to research the relationship between sLOX-1 and CSFP. Material and methods Forty patients with angiographically proven CSFP and 43 patients with a normal coronary flow pattern (NCFP) were included in this study. Coronary blood flow was measured according to the Thrombolysis In Myocardial Infarction (TIMI) frame count method. sLOX-1 levels were measured in all study subjects. Results Serum levels of sLOX-1 were significantly higher in the CSFP group than the NCFP group (1061.80 ±422.20 ng/ml vs. 500.043 ±282.97 ng/ml, p < 0.001, respectively). Multivariate logistic regression analysis including sLOX-1, MPV, GGT and uric acid levels revealed a significant association between sLOX-1 levels and CSFP (Exp (B)/OR: 1.006, 95% CI: 1.002–1.010, p = 0.001). Conclusions The present study demonstrated that serum sLOX-1 levels were significantly higher in patients with CSFP and there was a strong association between high sLOX-1 levels and CSFP. High serum sLOX-1 levels may have an important role in the pathogenesis of CSFP. Future studies are needed to confirm these results. PMID:26925116

  10. Screening, expression, and characterization of an anti-human oxidized low-density lipoprotein single-chain variable fragment.

    PubMed

    Kumano-Kuramochi, Miyuki; Fujimura, Takashi; Komba, Shiro; Maeda-Yamamoto, Mari; Machida, Sachiko

    2016-09-01

    Increased levels of oxidized low-density lipoprotein (OxLDL) in the blood circulation are correlated with atherosclerosis. Monoclonal antibody-based detection systems have been reported for OxLDL. We identified novel single-chain variable fragments (scFvs) having affinity for human OxLDL and related ligands. We constructed an scFv library from nonimmunized human spleen mRNA. Two types (γ+κ and μ+λ) of scFv phage libraries were enriched by biopanning, and five scFv clones with affinity for OxLDL were identified. The γκ5 scFv, which showed the highest affinity for OxLDL, was cloned into pET-22b(+) and expressed in Escherichia coli BL21(DE3). γκ5, expressed as an inclusion body in BL21(DE3), was refolded and purified. The specificity and sensitivity of γκ5 were analyzed using enzyme-linked immunosorbent assays (ELISAs). The γκ5 scFv showed affinity for OxLDL and acetylated LDL. The sensitivity of γκ5 to low concentrations (1-2 μg/mL) of OxLDL was higher than that to AcLDL and LDL. Finally, we developed a sandwich ELISA using γκ5 and CTLD14 (a lectin-like OxLDL receptor-1 ligand recognition region), which allowed specific detection of OxLDL at a level below 0.1 μg/mL. Our results indicated that the γκ5 scFv was a promising molecule for the detection of modified LDL at very low concentrations. PMID:27038672

  11. Scavenging of reactive oxygen species and inhibition of the oxidation of low density lipoprotein by the aqueous extraction of Anoectochilus formosanus.

    PubMed

    Shih, Chun-Ching; Wu, Yueh-Wern; Lin, Wen-Chuan

    2003-01-01

    The ability of Anoectochilus formosanus extract (AFE) to react with relevant biological oxidants was evaluated in this study. In addition, its effect on oxidation of low density lipoprotein (LDL) was investigated in vitro and in vivo. AFE could scavenge reactive oxygen species, such as superoxide anion and hydroxyl radical. The study of human LDL oxidation showed that AFE delayed oxidation in a concentration-dependent manner. In vivo studies also showed that oral administration of AFE delayed the oxidation of LDL from hyperlipidemic hamsters. The ability of AFE to scavenge free radicals suggests that it may be a promising anti-atherogenic agent. PMID:12723752

  12. Lectin-like Oxidized Low-Density Lipoprotein (LDL) Receptor (LOX-1): A Chameleon Receptor for Oxidized LDL.

    PubMed

    Zeya, Bushra; Arjuman, Albina; Chandra, Nimai Chand

    2016-08-16

    LOX-1, one of the main receptors for oxLDL, is found mainly on the surface of endothelial cells. It is a multifacet 52 kDa type II transmembrane protein that structurally belongs to the C-type lectin family. It exists with short intracellular N-terminal and long extracellular C-terminal hydrophilic domains separated by a hydrophobic domain of 26 amino acids. LOX-1 acts like a bifunctional receptor either showing pro-atherogenicity by activating the NFκB-mediated down signaling cascade for gene activation of pro-inflammatory molecules or playing an atheroprotective agent by receptor-mediated uptake of oxLDL in the presence of an anti-inflammatory molecule like IL-10. Mildly, moderately, and highly oxidized LDL show their characteristic features upon LOX-1 activation and its ligand binding indenture. The polymorphic LOX-1 genes are intensively associated with increased susceptibility to myocardial diseases. The splicing variant LOX IN dimerizes with the native form of LOX-1 and protects cells from damage by oxidized LDL. In the developing field of regenerating medicine, LOX-1 is a potential target for therapeutic intervention. PMID:27419271

  13. Reduction of Cu(II) by lipid hydroperoxides: implications for the copper-dependent oxidation of low-density lipoprotein.

    PubMed Central

    Patel, R P; Svistunenko, D; Wilson, M T; Darley-Usmar, V M

    1997-01-01

    The Cu(II)-promoted oxidation of lipids is a lipid hydroperoxide (LOOH)-dependent process that has been used routinely to assess the oxidizability of low-density lipoprotein (LDL) in human subjects. Metal-dependent redox reactions, including those mediated by copper, have been implicated in the pathogenesis ofatherosclerosis. Despite its widespread use and possible biological significance, key elements of the mechanism are not clear. For example, although it is evident that copper acts as a catalyst, which implies a redox cycle between the Cu(II) and Cu(I) redox states, the reductants remain uncertain. In LDL these could include alpha-tocopherol, amino acid residues on the protein and LOOH. However, both alpha-tocopherol and amino acid residues are probably consumed before the most rapid phase of lipid peroxidation occurs, suggesting that another reductant must be donating electrons to Cu(II), the most likely candidate being LOOH. This role has been disputed, since LDLs nominally devoid of LOOH are still capable of reducing Cu(II) to Cu(I) and thermodynamic calculations for this reaction are not favourable. Direct investigation of the role of LOOH as reductant has not been reported and in the present study, using simple lipid systems and LDL, we have re-examined this issue using the Cu(I) chelator bathocuproine. We have shown that Cu(II) may promote lipid peroxidation in liposomes, which do not contain either protein or alpha-tocopherol, and that this is associated with reduction to Cu(I). The data also indicate that an equilibrium between free Cu(II) and LOOH exists, which only in the presence of an oxidizable substrate, i.e. unsaturated fatty acids, is shifted towards formation of Cu(I) and lipid-derived peroxyl radicals. We propose that reduction of Cu(II) by LOOH is a necessary component in sustaining the propagation of lipid peroxidation and that the formation of peroxyl radicals and their products in a lipid environment is sufficient to overcome thermodynamic

  14. Pericoronary Adipose Tissue as Storage and Supply Site for Oxidized Low-Density Lipoprotein in Human Coronary Plaques

    PubMed Central

    Uchida, Yasumi; Uchida, Yasuto; Shimoyama, Ei; Hiruta, Nobuyuki; Kishimoto, Toshihiko; Watanabe, Soichiro

    2016-01-01

    Objectives It is generally believed that low-density lipoprotein enters the vascular wall from its lumen and oxidized (oxLDL), after which it plays an important role in atherosclerosis. Because voluminous epicardial adipose tissue is a risk factor for coronary events, there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue, acts as a risk factor by supplying oxLDL to the coronary arterial wall. The present study was performed whether PCAT stores and supplies oxLDL to the coronary wall. Methods Localization of oxLDL in PCAT and its relation to plaque morphology were examined by immunohistochemical techniques in 27 epicardial coronary arteries excised from 9 human autopsy cases. Results OxLDL deposited in all PCAT of the studied cases. The percent (%) incidence of oxLDL in the intima of 25 normal segment, 19 white plaques, 15 yellow plaques without necrotic core (NC) and 10 yellow plaques with NC, was 32, 84, 93 (p<0.05 vs normal segments and yellow plaques with NC), and 30, respectively. OxLDL deposited either in dotted or diffuse pattern. Double immunohistochemical staining revealed that the dotted oxLDL was that contained in CD68(+)-macrophages. The oxLDL-containing macrophages were observed in the interstitial space but not inside of the vasa vasorum, and they traversed PCAT, adventitia, external and internal elastic laminae, suggesting their migration towards the intima. Diffuse oxLDL deposits were observed in 17 preparations, the majority of which were co-localized with the vasa vasorum in outer or in both inner and outer halves of intima, and rarely in the inner half alone. Conclusions The results suggested that PCAT is a supply source of oxLDL to coronary intima and acts as a risk factor for coronary events, that oxLDL increasingly deposits in the intima with plaque growth and decreases after plaque maturation, and therefore molecular therapies targeting the PCAT before plaque growth could be effective

  15. The activation energy of oxidative thermal degradation of radiation- and peroxide-crosslinked low-density polyethylene

    SciTech Connect

    Matusevich, Yu.I.; Butovskaya, G.V.; Krul, L.P.

    1994-11-01

    The parameters of thermal degradation (kinetic order of the reaction, preexponential factor logA, and activation energy E{sub d}) of low-density polyethylene crosslinked by radiation or by dicumyl peroxide were determined from thermogravimetric data processed using the complementarity-based method of {open_quotes}supercorrelations.{close_quotes} The degradation of the polymer was found to obey a first-order rate equation. At mass losses of 10-20%, the parameters logA and E{sub d} were shown to decrease with an increasing degree of crosslinking because of the evolution of low-molecular radiolysis products and the low probability of chain radical processes. In the region of more intense destruction, E{sub d} (as well as logA) increases because the degradation of crosslinked polymer macromolecules requires greater energy consumption.

  16. Effects of lactic acid bacteria on low-density lipoprotein susceptibility to oxidation and aortic fatty lesion formation in hyperlipidemic hamsters.

    PubMed

    Ito, M; Oishi, K; Yoshida, Y; Okumura, T; Sato, T; Naito, E; Yokoi, W; Sawada, H

    2015-01-01

    We investigated the effects of Streptococcus thermophilus YIT 2001, a strain of lactic acid bacteria, on the susceptibility of low-density lipoprotein (LDL) to oxidation and the formation of aortic fatty lesions in hyperlipidemic hamsters. S. thermophilus YIT 2001 had the highest in vitro antioxidative activity against LDL oxidation among the 79 strains of lactic acid bacteria and bifidobacteria tested, which was about twice that of S. thermophilus YIT 2084. The lag time of LDL oxidation in the YIT 2001 feeding group was significantly longer than in controls, but was unchanged in the YIT 2084 group. After the feeding of YIT 2001, lag times were prolonged and areas of aortic fatty lesions were dose-dependently attenuated, although there were no effects on plasma lipid levels. These results suggest that YIT 2001 has the potential to prevent the formation of aortic fatty lesions by inhibiting LDL oxidation. PMID:25380799

  17. The influence of medium components on Cu(2+)-dependent oxidation of low-density lipoproteins and its sensitivity to superoxide dismutase.

    PubMed

    Thomas, C E

    1992-09-22

    The extent of in vitro Cu(2+)-dependent oxidation of low-density lipoproteins (LDL) has been reported to vary widely depending upon reaction conditions. In this study, the effect of proteins and amino acids on Cu(2+)-induced LDL oxidation was examined. Treatment of LDL with 5 microM CuSO4 for 18 h in either phosphate-buffered saline (PBS) or Ham's F-10 medium resulted in extensive oxidation as determined by the content of thiobarbituric acid reactive substances (TBARS) and by increased lipoprotein electronegativity. In PBS, oxidation was entirely blocked by histidine and the tripeptide, gly-his-lys (GHK). Oxidation was also prevented by bovine serum albumin, but superoxide dismutase (SOD) provided only 20% protection. Both proteins bound similar amounts of Cu2+, but albumin appeared to be a more effective peroxyl radical trap as evidenced by its ability to prevent LDL oxidation induced by 2,2'-azo-bis(2-amidinopropane hydrochloride). In F-10 medium, SOD had marked inhibitory effects, in contrast to PBS. The addition of disulfides to PBS markedly enhanced the ability of SOD to inhibit oxidation. These results indicate that medium components which affect Cu2+ availability influence LDL oxidation and suggest that albumin is ideally suited as a plasma antioxidant to prevent oxidative modification of LDL. Furthermore, in certain instances, the inhibitory effects of SOD may be attributable to effects such as Cu2+ binding rather than dismutation of superoxide. PMID:1390878

  18. Effects of a 12-week healthy-life exercise program on oxidized low-density lipoprotein cholesterol and carotid intima-media thickness in obese elderly women

    PubMed Central

    Park, Jong-Hwan; Park, Hyuntae; Lim, Seung-Taek; Park, Jin-Kee

    2015-01-01

    [Purpose] This study examined the effects of a 12-week exercise program on plasma level of oxidized low-density lipoprotein cholesterol in obese elderly women, who are at increased risk of heart disease morbidity. [Subjects and Methods] Twenty participants were assigned into either a control (n = 10) or a supervised exercise program (n = 10) group. The 12-week exercise intervention was performed 3 days per week and involved combined aerobic exercise, resistance exercise, and traditional Korean dance. [Results] Two-factor analysis of variance revealed significant group × time interactions for body mass, diastolic blood pressure, appendicular muscle mass. For high-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and the ratio of oxidized low-/high-density lipoprotein cholesterol, two-factor analysis of variance revealed significant interactions (group × time), indicating responses differed significantly between the control and exercise groups after 12 weeks. [Conclusion] A 12-week low- to moderate-intensity exercise program appears to be beneficial for obese elderly women by improving risk factors for cardiovascular disease. PMID:26157235

  19. Effects of a 12-week healthy-life exercise program on oxidized low-density lipoprotein cholesterol and carotid intima-media thickness in obese elderly women.

    PubMed

    Park, Jong-Hwan; Park, Hyuntae; Lim, Seung-Taek; Park, Jin-Kee

    2015-05-01

    [Purpose] This study examined the effects of a 12-week exercise program on plasma level of oxidized low-density lipoprotein cholesterol in obese elderly women, who are at increased risk of heart disease morbidity. [Subjects and Methods] Twenty participants were assigned into either a control (n = 10) or a supervised exercise program (n = 10) group. The 12-week exercise intervention was performed 3 days per week and involved combined aerobic exercise, resistance exercise, and traditional Korean dance. [Results] Two-factor analysis of variance revealed significant group × time interactions for body mass, diastolic blood pressure, appendicular muscle mass. For high-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and the ratio of oxidized low-/high-density lipoprotein cholesterol, two-factor analysis of variance revealed significant interactions (group × time), indicating responses differed significantly between the control and exercise groups after 12 weeks. [Conclusion] A 12-week low- to moderate-intensity exercise program appears to be beneficial for obese elderly women by improving risk factors for cardiovascular disease. PMID:26157235

  20. Protective Effect of Antioxidant Extracts from Grey Oyster Mushroom, Pleurotus pulmonarius (Agaricomycetes), Against Human Low-Density Lipoprotein Oxidation and Aortic Endothelial Cell Damage.

    PubMed

    Abidin, Mohamad Hamdi Zainal; Abdullah, Noorlidah; Abidin, Nurhayati Zainal

    2016-01-01

    This study evaluated the in vitro antioxidant capacities of extracts from Pleurotus pulmonarius via Folin-Ciocalteu, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, metal chelating, cupric ion reducing antioxidant capacity, and lipid peroxidation inhibition assays. Extract compositions were determined by phenol-sulfuric acid; Coomassie Plus (Bradford) protein; Spectroquant zinc, copper, and manganese test assays; and liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-mass spectrometry (GC/MS). Methanol-dichloromethane extract, water fraction, hot water, aqueous extract and hexane fraction exhibited the most potent extracts in the antioxidant activities. LC/MS/MS and GC/MS showed that the extracts contained ergothioneine, ergosterol, flavonoid, and phenolic compounds. The selected potent extracts were evaluated for their inhibitory effect against oxidation of human low-density lipoproteins and protective effects against hydrogen peroxide-induced cytotoxic injury in human aortic endothelial cells. The crude aqueous extract was deemed most potent for the prevention of human low-density lipoprotein oxidation and endothelial membrane damage. Ergothioneine might be the compound responsible for the activities, as supported by previous reports. Thus, P. pulmonarius may be a valuable antioxidant ingredient in functional foods or nutraceuticals. PMID:27279533

  1. Purification, crystallization and preliminary X-ray analysis of the ligand-binding domain of human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1)

    SciTech Connect

    Ishigaki, Tomoko; Ohki, Izuru; Oyama, Takuji; Machida, Sachiko; Morikawa, Kousuke; Tate, Shin-ichi

    2005-05-01

    Two different fragments of the ligand-binding domain of LOX-1, the major receptor for oxidized low-density lipoprotein (LDL) on endothelial cells, have been crystallized in different forms. Two different fragments of the ligand-binding domain of LOX-1, the major receptor for oxidized low-density lipoprotein (LDL) on endothelial cells, have been crystallized in different forms. One crystal form contains the disulfide-linked dimer, which is the form of the molecule present on the cell surface; the other contains a monomeric form of the receptor that lacks the cysteine residue necessary to form disulfide-linked homodimers. The crystal of the monomeric ligand-binding domain belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 56.79, b = 67.57, c = 79.02 Å. The crystal of the dimeric form belongs to space group C2, with unit-cell parameters a = 70.86, b = 49.56, c = 76.73 Å, β = 98.59°. Data for the dimeric form of the LOX-1 ligand-binding domain have been collected to 2.4 Å. For the monomeric form of the ligand-binding domain, native, heavy-atom derivative and SeMet-derivative crystals have been obtained; their diffraction data have been measured to 3.0, 2.4 and 1.8 Å resolution, respectively.

  2. Oxidized Low-Density Lipoprotein-β2-Glycoprotein I Complex But Not Free Oxidized LDL Is Associated With the Presence and Severity of Coronary Artery Disease.

    PubMed

    Bliden, Kevin P; Chaudhary, Rahul; Lopez, Luis R; Damrongwatanasuk, Rongras; Guyer, Kirk; Gesheff, Martin G; Franzese, Christopher J; Kaza, Himabindu; Tantry, Udaya S; Gurbel, Paul A

    2016-09-01

    Oxidized low-density lipoprotein (oxLDL) and β2-glycoprotein I (β2GPI) have been identified in human atherosclerotic lesions and when complexed have been implicated as a pro-atherothrombotic antigen. We examined the association of free oxLDL and oxLDL-β2GPI complex in patients with coronary artery disease who underwent elective cardiac catheterization. Serum was collected from patients with suspected coronary artery disease immediately before elective cardiac catheterization who were either treated (n = 385) or not treated (n = 150) with statins and from healthy volunteers (n = 134). OxLDL and oxLDL-β2GPI complex levels were determined by enzyme-linked immunosorbent assay. Disease severity was defined angiographically as none-minimal (<20%), moderate (20% to 75%), and severe (>75%) luminal diameter obstruction of any major coronary vessel. Both oxLDL and oxLDL-β2GPI complex were lower in patients on statins (p <0.001). In statin-naive patients, oxLDL-β2GPI complex, but not free oxLDL, was associated with severe coronary artery disease (p = 0.036). However, no association was observed in patients on statins. LDL4 and triglycerides increased with oxLDL-β2GPI complex quartiles (p = 0.001). OxLDL-β2GPI complex (>0.32 U/ml) was predictive of severe atherosclerosis by receiver-operating characteristic curve analysis in statin-naive patients (area under the curve 0.66, p = 0.002). In conclusion, oxLDL-β2GPI appears more predictive of coronary artery disease severity than oxLDL alone in statin-naive patients. PMID:27401271

  3. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein.

    PubMed Central

    Watson, A D; Berliner, J A; Hama, S Y; La Du, B N; Faull, K F; Fogelman, A M; Navab, M

    1995-01-01

    Our group has previously demonstrated that oxidized phospholipids in mildly oxidized LDL (MM-LDL) produced by oxidation with lipoxygenase, iron, or cocultures of artery wall cells increase monocyte-endothelial interactions and this sequence of events is blocked by HDL. To obtain further insight into the mechanism by which HDL abolishes the activity of MM-LDL we investigated the effect of the HDL-associated ester hydrolase paraoxonase (PON). Treatment of MM-LDL with purified PON significantly reduced the ability of MM-LDL to induce monocyte-endothelial interactions. Inactivation of PON by pretreating HDL with heat or EDTA reduced the ability of HDL to inhibit LDL modification. HPLC analysis of phospholipids isolated from MM-LDL before and after treatment with purified PON showed that the 270 nm absorbance of phospholipids was decreased, while no effect was observed on 235 nm absorbance. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and specific fractions of Ox-PAPC isolated by HPLC induced the same monocyte-endothelial interactions as did MM-LDL. Biologically active and inactive HPLC fractions of Ox-PAPC were compared by fast atom bombardment-mass spectrometry which revealed that active fractions possessed ions with a mass to charge [correction of change] ratio greater than native PAPC by multiples of 16 D suggesting the addition of 3 and 4 oxygen atoms to PAPC. Comparison of Ox-PAPC by fast atom bombardment-mass spectrometry before and after PON treatment showed that PON destroyed these multi-oxygenated molecules found in biologically active fractions of Ox-PAPC. These results suggest that PON in HDL may protect against the induction of inflammatory responses in artery wall cells by destroying biologically active lipids in mildly oxidized LDL. Images PMID:8675659

  4. Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages.

    PubMed

    Hazell, L J; Stocker, R

    1993-02-15

    Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4 degrees C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL-associated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37 degrees C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary

  5. Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis.

    PubMed

    Ismael, Fahd O; Proudfoot, Julie M; Brown, Bronwyn E; van Reyk, David M; Croft, Kevin D; Davies, Michael J; Hawkins, Clare L

    2015-05-01

    Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F2-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis. PMID:25795019

  6. [Low density lipoprotein apheresis].

    PubMed

    Zaliūnas, Remigijus; Slapikas, Rimvydas; Gustiene, Olivija; Siurkus, Jonas; Vaitkus, Eduardas

    2003-01-01

    Increased blood cholesterol concentration is one of the main factors in ischemic heart disease, development of which is determined by atherosclerotic changes in coronary vessels. Diet and treatment with 3-hydroxi-3-metilglutaril coenzyme A (HMG-CoA) reductase inhibitors helps to reduce low density lipoprotein cholesterol (LDL-Ch) blood concentration up to recommended level of 3.0 mmol/l in most patients but in some patients particularly with familial dyslipidemias cholesterol concentration remains increased even after treatment with maximal doses of lipid-regulating agents or their combinations. The most frequently used mechanical methods of cholesterol removal from blood include the procedures of extracorporeal apheresis. Low density lipoprotein (LDL) apheresis not only significantly reduces the blood concentrations of total cholesterol (TCh), and LDL-Ch, lipoprotein (a) (Lp(a) and fibrinogen but also stops the progression of atherosclerosis in coronary vessels. PMID:14704503

  7. Oxidized wax as compatibilizer in linear low-density polyethylene-clay nanocomposites: x-ray diffraction and dynamic mechanical analysis.

    PubMed

    Geethamma, V G; Luyt, Adriaan S

    2008-04-01

    Oxidized paraffin wax was used as a compatibilizer in composites of linear low-density polyethylene and layered nano silicate clays. X-ray diffraction analyses were carried out to investigate the crystalline morphology of five types of clays, oxidized wax, and their composites with LLDPE. The composites exhibited different X-ray diffraction and dynamic mechanical behaviour in the presence of different clays. Generally, the composites retained the partially crystalline behaviour of LLDPE, and no exfoliation was observed. Increased amount of wax did not change the morphology in most cases. The incorporation of clay resulted in an observable increase in the storage modulus of LLDPE. These values also increased with the addition of oxidized wax for most of the composites. The loss modulus increased with the amount of clay, irrespective of its nature. In most cases these values also increased with the incorporation of wax. The composites with 10% clay and 10% oxidized wax showed the highest storage and loss moduli, irrespective of the nature of the clay. The tan delta values did not change considerably with the addition of clay or wax. PMID:18572590

  8. Antioxidative Effects and Inhibition of Human Low Density Lipoprotein Oxidation In Vitro of Polyphenolic Compounds in Flammulina velutipes (Golden Needle Mushroom).

    PubMed

    Rahman, Mohammad Azizur; Abdullah, Noorlidah; Aminudin, Norhaniza

    2015-01-01

    Dietary polyphenolic compounds mediate polynomial actions in guarding against multiple diseases. Atherosclerosis is an oxidative stress driven pathophysiological complication where free radical induced oxidative modification of low density lipoprotein (LDL) plays the ground breaking role. Mushrooms have been highly regarded for possessing an antioxidant arsenal. Polyphenolic compounds present in dietary mushrooms seem pertinent in withstanding LDL oxidation en route to controlling atherosclerosis. In this study, the antioxidative effect of five solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ) of Flammulina velutipes was evaluated. M : DCM fraction showed the most potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging effect with IC50 of 0.86 mg/mL and total phenolic content of 56.36 gallic acid equivalent/g fraction. In LDL oxidation inhibitory tests, M : DCM fraction at 1 µg/mL concentration mostly lengthened the lag time (125 mins) of conjugated diene formation and inhibited the formation of thiobarbituric acid reactive substances (48.71%, at 1 mg/mL concentration). LC-MS/MS analyses of M : DCM fraction identified the presence of polyphenolic substances protocatechuic acid, p-coumaric, and ellagic acid. These chain-breaking polyphenolics might impart the antioxidative effects of F. velutipes. Thus, mushroom-based dietary polyphenolic compounds might be implicated in slowing down the progression of atherosclerosis. PMID:26180589

  9. Antioxidative Effects and Inhibition of Human Low Density Lipoprotein Oxidation In Vitro of Polyphenolic Compounds in Flammulina velutipes (Golden Needle Mushroom)

    PubMed Central

    Rahman, Mohammad Azizur; Abdullah, Noorlidah; Aminudin, Norhaniza

    2015-01-01

    Dietary polyphenolic compounds mediate polynomial actions in guarding against multiple diseases. Atherosclerosis is an oxidative stress driven pathophysiological complication where free radical induced oxidative modification of low density lipoprotein (LDL) plays the ground breaking role. Mushrooms have been highly regarded for possessing an antioxidant arsenal. Polyphenolic compounds present in dietary mushrooms seem pertinent in withstanding LDL oxidation en route to controlling atherosclerosis. In this study, the antioxidative effect of five solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ) of Flammulina velutipes was evaluated. M : DCM fraction showed the most potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging effect with IC50 of 0.86 mg/mL and total phenolic content of 56.36 gallic acid equivalent/g fraction. In LDL oxidation inhibitory tests, M : DCM fraction at 1 µg/mL concentration mostly lengthened the lag time (125 mins) of conjugated diene formation and inhibited the formation of thiobarbituric acid reactive substances (48.71%, at 1 mg/mL concentration). LC-MS/MS analyses of M : DCM fraction identified the presence of polyphenolic substances protocatechuic acid, p-coumaric, and ellagic acid. These chain-breaking polyphenolics might impart the antioxidative effects of F. velutipes. Thus, mushroom-based dietary polyphenolic compounds might be implicated in slowing down the progression of atherosclerosis. PMID:26180589

  10. Feeding the nitric oxide synthase inhibitor L-N(omega)nitroarginine elevates serum very low density lipoprotein and hepatic triglyceride synthesis in rats.

    PubMed

    Goto, T; Ohnomi, S; Khedara, A; Kato, N; Ogawa, H; Yanagita, T

    1999-05-01

    This study was conducted to study the influence of dietary L-N(omega)nitroarginine (L-NNA), a nitric oxide (NO) synthase inhibitor, on serum lipids and lipoproteins and on the activities of enzymes related to lipid metabolism in rats. Feeding rats a diet containing 0.2 g/kg L-NNA for 5 weeks elevated serum concentrations of triglyceride, cholesterol, phospholipid, and free fatty acid and reduced serum nitrate (an oxidation product of NO). The elevation in serum triglyceride was mainly due to the elevation in very low density lipoprotein (VLDL) triglyceride. Contents of cholesterol and phospholipid in the VLDL fraction also were elevated by L-NNA. L-NNA treatment caused significantly higher activity of hepatic microsomal phosphatidate phosphohydrolase (the rate-limiting enzyme in triglyceride synthesis) and lower activity of hepatic carnitine palmitoyltransferase (the rate-limiting enzyme in fatty acid oxidation). Activities of hepatic enzymes responsible for fatty acid synthesis such as glucose-6-phosphate dehydrogenase, malic enzyme, and fatty acid synthase were unaffected by L-NNA. The activity of hepatic microsomal phosphocholine cytidyltransferase (the rate-limiting enzyme in phosphatidylcholine synthesis) was reduced significantly by L-NNA. Our results suggest that lower NO production caused the elevations in hepatic triglyceride synthesis by higher esterification of fatty acid and lower fatty acid oxidation, leading to an enrichment of VLDL triglyceride. PMID:15539300

  11. Inhibition of low-density lipoprotein oxidation by oral herbal mixtures Maharishi Amrit Kalash-4 and Maharishi Amrit Kalash-5 in hyperlipidemic patients.

    PubMed

    Sundaram, V; Hanna, A N; Lubow, G P; Koneru, L; Falko, J M; Sharma, H M

    1997-11-01

    Low-density lipoprotein (LDL) oxidation is central to the pathogenesis of atherosclerosis. We have shown previously that the herbal mixtures Maharishi Amrit Kalash-4 (MAK-4) and Maharishi Amrit Kalash-5 (MAK-5) inhibit LDL oxidation induced by cupric ions (Cu+2) and endothelial cells in vitro and that MAK-4 reduces atherosclerosis in Watanabe heritable hyperlipidemic rabbits that were fed this herbal mixture. This study evaluates the antioxidant activity of MAK-4 and MAK-5 in vivo. Ten hyperlipidemic patients prescribed stable hypolipidemic therapy were treated with MAK-4 and MAK-5 for 18 weeks. Plasma lipoprotein, plasma lipid peroxide, and LDL oxidation studies were performed every 6 weeks. Apolipoprotein A, apolipoprotein B, and lipoprotein (a) levels were measured at baseline and 18 weeks. After 12 weeks of treatment with MAK-4 and MAK-5, a time-dependent increase in the lag phase and delay in the propagation phase of oxidation of LDL by Cu+2 and endothelial cells was seen. Lag phases at baseline and after 6, 12, and 18 weeks of MAK-4 and MAK-5 ingestion were 6.66 hours +/- 0.19 (mean +/- standard error of mean), 6.77 hours +/- 0.31, 7.22 hours +/- 0.24, and 18.00 hours +/- 0.73, respectively, for Cu(+2)-catalyzed LDL oxidation. Lag phases were 14.89 hours +/- 0.77, 13.33 hours +/- 0.50, 20.22 hours +/- 0.76, and 20.00 hours +/- 0.79, respectively, for endothelial cell-induced LDL oxidation. The levels of plasma lipid peroxide did not change significantly. No significant changes were seen in the plasma lipoproteins and the levels of apolipoprotein A, apolipoprotein B, and lipoprotein (a). The results show that MAK-4 and MAK-5 inhibit LDL oxidation in patients with hyperlipidemia. Therefore, MAK-4 and MAK-5 may be useful in the prevention and treatment of atherosclerosis. PMID:9365332

  12. Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-κB/LOX-1 Pathway

    PubMed Central

    Liu, Zhi-Hua; Cao, Yong-Jun; Liu, Chun-Feng; Zhang, Yan-Lin; Xie, Ying

    2016-01-01

    Background Lectin-like oxidized low-density lipoprotein-1 (LOX-1) is the major receptor for oxidized low density lipoprotein (ox-LDL) uptake in human umbilical vein endothelial cells (HUVECs). Previously, we found that rapamycin inhibited ox-LDL accumulation in HUVECs, and this effect was related to its role in increasing the activity of autophagy-lysosome pathway. In this study, we determined whether rapamycin could also reduce ox-LDL uptake in HUVECs and investigated the underlying signaling mechanisms. Results Flow cytometry and live cell imaging showed that rapamycin reduced Dil-ox-LDL accumulation in HUVECs. Furthermore, rapamycin reduced the ox-LDL-induced increase in LOX-1 mRNA and protein levels. Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and IκBα phosphorylation triggered by ox-LDL. Flow cytometry implied that mTOR, NF-κB knockdown and NF-κB inhibitors significantly reduced Dil-ox-LDL uptake. Moreover, immunofluorescent staining showed that rapamycin reduced the accumulation of p65 in the nucleus after ox-LDL treatment for 30 h. mTOR knockdown decreased LOX-1 protein production and IκBα phosphorylation induced by ox-LDL. NF-κB knockdown and NF-κB inhibitors reduced LOX-1 protein production, but did not inhibit mTOR phosphorylation stimulated by ox-LDL. Conclusions These findings demonstrate that rapamycin reduce mTOR phosphorylation and subsequently inhibit NF-κB activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs. PMID:26752047

  13. Antioxidant capacity of oat (Avena sativa L.) extracts. 1. Inhibition of low-density lipoprotein oxidation and oxygen radical absorbance capacity.

    PubMed

    Handelman, G J; Cao, G; Walter, M F; Nightingale, Z D; Paul, G L; Prior, R L; Blumberg, J B

    1999-12-01

    Milled oat groat pearlings, trichomes, flour, and bran were extracted with methanol and the fractions tested in vitro for antioxidant capacity against low-density lipoprotein (LDL) oxidation and R-phycoerythrin protein oxidation in the oxygen radical absorbance capacity (ORAC) assay. The oxidative reactions were generated by 2,2'-azobis(2-amidinopropane) HCl (AAPH) or Cu(2+) in the LDL assay and by AAPH or Cu(2+) + H(2)O(2) in the ORAC assay and calibrated against a Trolox standard to calculate Trolox equivalents (1 Trolox equivalent = 1 TE = activity of 1 micromol of Trolox). The antioxidant capacity of the oat fractions was generally consistent with a potency rank of pearlings (2.89-8.58 TE/g) > flour (1.00-3.54 TE/g) > trichome (1.74 TE/g) = bran (1.02-1.62 TE/g) in both LDL and ORAC assays regardless of the free radical generator employed. A portion of the oat antioxidant constituents may be heat labile as the greatest activity was found among non-steam-treated pearlings. The contribution of oat tocols from the fractions accounted for <5% of the measured antioxidant capacity. AAPH-initiated oxidation of LDL was inhibited by the oat fractions in a dose-dependent manner, although complete suppression was not achieved with the highest doses tested. In contrast, Cu(2+)-initiated oxidation of LDL stimulated peroxide formation with low oat concentrations but completely inhibited oxidation with higher doses. Thus, oats possess antioxidant capacity most of which is likely derived from polar phenolic compounds in the aleurone. PMID:10606548

  14. A1M/α1-microglobulin is proteolytically activated by myeloperoxidase, binds its heme group and inhibits low density lipoprotein oxidation

    PubMed Central

    Cederlund, Martin; Deronic, Adnan; Pallon, Jan; Sørensen, Ole E.; Åkerström, Bo

    2015-01-01

    α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a regulator of its activity. The results show that A1M is proteolytically cleaved, with formation of t-A1M, after exposure to MPO, and that t-A1M contains iron and heme-degradation products. The reaction is dependent of pH, time and concentration of substrates and a pH-value around 7 is shown to be optimal for cleavage. Furthermore, A1M inhibits MPO- and hydrogen peroxide-induced oxidation of LDL. The results suggest that A1M may have a role as an inhibitor of the damaging effects of the neutrophil respiratory burst on bystander tissue components. PMID:25698971

  15. Oxidative degradation of cholesteryl esters in low-density lipoproteins: analysis by liquid chromatography-light scattering and protection by a new synthetic antioxidant, S20478.

    PubMed

    Arborati, M; Benchorba, D; Lesieur, I; Bizot-Espiard, J G; Guardiola-Lemaitre, B; Chapman, M J; Ninio, E

    1997-01-01

    Cholesteryl esters in the hydrophobic core of low-density lipoprotein (LDL) particles constitute a major molecular target during copper-mediated oxidation. To facilitate the rapid analysis and quantitation of the oxidative degradation of LDL cholesteryl esters, we describe a new approach based on light scattering detection following separation by HPLC. We have applied this approach to the evaluation of the protective capacity of a new synthetic antioxidant, S20478, during oxidation of LDL in the presence of copper ions. HPLC separation of cholesterol and the four major molecular species of cholesteryl esters (C16:0, C18:1, C18:2 and C20:4) of LDL was achieved in a single run of 20 min with high sensitivity (50 ng) and low background. Time course studies of the oxidative modification of LDL (ratio LDL protein: copper, 100 micrograms/mL: 1 microM) revealed that the content of unsaturated cholesteryl esters (C20:4 and C18:2) decreased (-30% and -15%, respectively) within 90 min of copper-mediated oxidation, while only minor degradation (up to 15%) of monounsaturated (C18:1) and saturated (C16:0) esters occurred. At 24 hours of oxidation, only traces (< 5%) of the C20:4 and C18:2 esters were detectable; whereas 52% of the C18:1 ester remained (P < 0.01). Of the saturated esters, only minor proportions (35% or less) underwent oxidative modification. In addition, some 81% of free cholesterol was conserved as the native sterol. The synthetic antioxidant, S20478 (50 microM) was capable of inhibiting the initiation and the propagation of copper-mediated LDL oxidation as determined by the time- and dose-dependent inhibition of the formation of conjugated dienes and thiobarbituric acid-reactive substances, as well as the conservation of the net electrical charge of LDL; indeed S20478 conserved cholesteryl esters in their native form up to 24 hours. However, after prolonged exposure to copper ions (48 hours), only 47% of the unsaturated esters remained (C18:2, P < 0

  16. Low density solid ozone

    SciTech Connect

    Teolis, B. D.; Fama, M.; Baragiola, R. A.

    2007-08-21

    We report a very low density ({approx}0.5 g/cm{sup 3}) structure of solid ozone. It is produced by irradiation of solid oxygen with 100 keV protons at 20 K followed by heating to sublime unconverted oxygen. Upon heating to 47 K the porous ozone compacts to a density of {approx}1.6 g/cm{sup 3} and crystallizes. We use a detailed analysis of the main infrared absorption band of the porous ozone to interpret previous research, where solid oxygen was irradiated by UV light and keV electrons.

  17. Oxide-free InAs(111)A interface in metal-oxide-semiconductor structure with very low density of states prepared by anodic oxidation

    SciTech Connect

    Valisheva, N. A. Aksenov, M. S.; Golyashov, V. A.; Levtsova, T. A.; Kovchavtsev, A. P.; Gutakovskii, A. K.; Tereshchenko, O. E.; Khandarkhaeva, S. E.; Kalinkin, A. V.; Prosvirin, I. P.; Bukhtiyarov, V. I.

    2014-10-20

    In this letter, we present structural, compositional, and electrical characteristics of anodic oxide layer-based metal-oxide-semiconductor (MOS) capacitors on n-type InAs(111)A, along with the effect of a thin fluorinated interfacial passivation layer. Electrochemical oxidation in acid electrolyte with addition of fluorine (NH{sub 4}F) led to the formation of oxygen free well-ordered wide gap fluorinated interfacial layer at InAs(111)A with the fixed charge (Q{sub fix}) and density of interface states (D{sub it}) in the range of (4–6) × 10{sup 10 }cm{sup −2} and (2–12) × 10{sup 10 }eV{sup −1 }cm{sup −2}, respectively. We found that MOS capacitors showed excellent capacitance-voltage characteristics with very small frequency dispersion (<1% and <15 mV). Fluorinated interfacial layer consists of crystalline isostructural compound with the InAs substrate, which remains intact with the atomic smoothness and sharpness that explain unpinned behavior of the Fermi level.

  18. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    PubMed

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (P<0.01) and reduced the disappearance of Vitamin E in a concentration-dependent manner. Incubation of HDL with VAO-PE significantly increased the fluidity of the HDL phospholipidic bilayer (P=0.0004) and HDL-mediated cholesterol efflux from THP-1 macrophages. These results suggest that Virgin argan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL. PMID:16019008

  19. Correlation between Chemical Composition of Curcuma domestica and Curcuma xanthorrhiza and Their Antioxidant Effect on Human Low-Density Lipoprotein Oxidation

    PubMed Central

    Jantan, Ibrahim; Saputri, Fadlina Chany; Qaisar, Muhammad Naeem; Buang, Fhataheya

    2012-01-01

    The antioxidant activity of the curcuminoids of Curcuma domestica L. and C. xanthorrhiza Roxb. and eight compounds which are prevalent constituents of their rhizome oils were investigated in an effort to correlate human low-density lipoprotein (LDL) antioxidant activity with the effect of the herbs and their components. The antioxidant activity was examined using thiobarbituric acid reactive substances (TBARSs) assay with human LDL as the oxidation substrate. The methanol extracts and rhizome oils of C. xanthorrhiza and C. domestica showed strong inhibitory activity on copper-mediated oxidation of LDL. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin, isolated from the methanol extracts of both plants, exhibited stronger activity than probucol (IC50 value 0.57 μmol/L) as reference, with IC50 values ranging from 0.15 to 0.33 μmol/L. Xanthorrhizol, the most abundant component (31.9%) of the oil of C. xanthorrhiza, showed relatively strong activity with an IC50 value of 1.93 μmol/L. The major components of C. domestica, ar-turmerone (45.8%) and zerumbone (3.5%), exhibited IC50 values of 10.18 and 24.90 μmol/L, respectively. The high levels of curcuminoids in the methanol extracts and xanthorrhizol, ar-turmerone and zerumbone in the oils, and in combination with the minor components were responsible for the high LDL antioxidant activity of the herbs. PMID:23243446

  20. Cannabidiol-2',6'-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro.

    PubMed

    Takeda, Shuso; Hirayama, Akari; Urata, Shino; Mano, Nobutaka; Fukagawa, Keiko; Imamura, Midori; Irii, Ayumi; Kitajima, Satomi; Masuyama, Tomoko; Nomiyama, Mai; Tatei, Sachiko; Tomita, Saari; Kudo, Taichi; Noguchi, Momoko; Yamaguchi, Yasuhiro; Okamoto, Yoshiko; Amamoto, Toshiaki; Fukunishi, Yoshifumi; Watanabe, Kazuhito; Omiecinski, Curtis John; Aramaki, Hironori

    2011-01-01

    15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu(2+)) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2',6'-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al., Drug Metab. Dispos., 37, 1733-1737 (2009)). In the LDL, linoleic acid is present as cholesteryl linoleate, the major fatty acid esterified to cholesterol, and is susceptible to oxidative modification by 15-LOX or Cu(2+). In this investigation, we examined the efficacy of CBDD on i) 15-LOX-catalyzed oxygenation of cholesteryl linoleate, and ii) ox-LDL formation catalyzed by 15-LOX versus Cu(2+)-mediated non-enzymatic generation of this important mediator. The results obtained demonstrate that CBDD is a potent and selective inhibitor of ox-LDL formation generated by the 15-LOX pathway. These studies establish CBDD as both an important experimental tool for characterizing 15-LOX-mediated ox-LDL formation, and as a potentially useful therapeutic agent for treatment of atherosclerosis. PMID:21804214

  1. A Fluorescence-Labeled Heptapeptide, (FITC)KP6, as an Efficient Probe for the Specific Detection of Oxidized and Minimally Modified Low-Density Lipoprotein.

    PubMed

    Sato, Akira; Ueda, Chiemi; Kimura, Ryu; Kobayashi, Chisato; Yamazaki, Yoji; Ebina, Keiichi

    2016-05-01

    Two oxidized forms of low-density lipoprotein (LDL), oxidized LDL (ox-LDL) and minimally modified LDL (MM-LDL), are believed to play a major role in the pathogenesis of atherosclerosis. Recently, we reported that a heptapeptide (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6) coupled through the ε-amino group of N-terminus Lys to fluorescein isothiocyanate, (FITC)KP6, bound to ox-LDL but not to LDL. In the present study, we investigated whether (FITC)KP6 could be used as a fluorescent probe for the specific detection of MM-LDL and ox-LDL. Results from polyacrylamide gel electrophoresis and surface plasmon resonance proved that (FITC)KP6 could efficiently bind to MM-LDL as well as ox-LDL in a dose-dependent manner and with high affinity (K D = 3.16 and 3.54 ng/mL protein for MM-LDL and ox-LDL, respectively). (FITC) KP6 bound to lysophosphatidylcholine and oxidized phosphatidylcholine, both present abundantly in ox-LDL and MM-LDL, respectively. In vitro, (FITC)KP6 was detected on the surface and/or in the cytosol of human THP-1-derived macrophages incubated with ox-LDL and MM-LDL, but not LDL. These results suggest that (FITC)KP6 could be an efficient fluorescent probe for the specific detection of ox-LDL and MM-LDL and can therefore contribute to the identification, diagnosis, prevention, and treatment of atherosclerosis. PMID:27063871

  2. Model IgG Monoclonal Autoantibody–Anti-Idiotype Pair for Dissecting the Humoral Immune Response to Oxidized Low Density Lipoprotein

    PubMed Central

    Chang, Shang-Hung; Johns, Michael; Boyle, Joseph J.; McConnell, Ellen; Kirkham, Paul A.; Bicknell, Colin; Zahoor-ul-Hassan Dogar, M.; Edwards, Robert J.; Gale-Grant, Oliver; Khamis, Ramzi; Ramkhelawon, Kurrun V.V.

    2012-01-01

    Increasing evidence implicates IgG autoantibodies against oxidized forms of low density lipoprotein (oxLDL) in the pathophysiology of atherosclerotic arterial disease. However, insufficient knowledge of their structure and function is a key gap. Using an elderly LDL receptor-deficient atherosclerotic mouse, we isolated a novel IgG3k against oxLDL (designated MAb LO1). LO1 reacts with copper-oxidized LDL, but minimally with native LDL. Further analysis showed that MAb LO1 also reacts in vitro with malondialdehyde-conjugated LDL (MDA-LDL), a known key epitope in copper-oxidized LDL preparations. By screening a phage library expressing single chain variable region antibodies (scFv), we selected an anti-idiotype scFv (designated H3) that neutralizes MAb LO1 binding to MDA-LDL. Amino acid substitutions between H3 and an irrelevant control scFv C12 showed that residues in the H3 CDRH2, CDRH3, and CDRL2 are all critical for MAb LO1 binding, consistent with a conformational epitope on H3 involving both heavy and light chains. Comparison of amino acids in H3 CDRH2 and CDRL2 with apoB, the major LDL protein, showed homologous sequences, suggesting H3 has structural similarities to the MAb LO1 binding site on MDA-LDL. Immunocytochemical staining showed that MAb LO1 binds epitopes in mouse and human atherosclerotic lesions. The MAb LO1-H3 combination therefore provides a very promising model for analyzing the structure and function of an individual IgG autoantibody in relation to atherosclerosis. PMID:22509912

  3. Effects of Bulbus allii macrostemi on clinical outcomes and oxidized low-density lipoprotein and plasminogen in unstable angina/non-ST-segment elevation myocardial infarction patients.

    PubMed

    Liu, Yan; Zhang, Lei; Liu, Yun-Fang; Yan, Fang-Fang; Zhao, Yu-Xia

    2008-11-01

    Unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) is associated with an increased risk of cardiac death and an efficacious drug with few side effects is necessary. The study aimed to evaluate the effects of Bulbus allii macrostemi (B. macrostemi) on UA/NSTEMI patients as well as to elucidate possible mechanisms. 79 patients were randomly divided into two groups: the trial group received B. macrostemi plus baseline therapy, the control group was given placebo plus baseline therapy. The trial lasted 8 weeks. The evaluation involved main clinical symptoms, changes of electrocardiogram and biochemical examination. After treatment, the trial group showed more significant improvement on clinical manifestation. The plasma oxidized low-density lipoprotein (ox-LDL) level decreased significantly in the trial group (p < 0.01); the plasminogen activator inhibitor-1 (PAI-1) level decreased in both groups and it decreased more significantly in the trial group (p < 0.01). In contrast, the activity of plasminogen (PLG) increased in both groups and the change was more marked in the trial group (p < 0.01). The results suggested that B. macrostemi combined with baseline therapy could improve clinical symptoms of UA/NSTEMI patients by decreasing the ox-LDL and PAI-1 levels and enhancing the activity of PLG. PMID:18688814

  4. Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces cardiac fibroblast proliferation by suppressing GATA Binding Protein 4.

    PubMed

    Liu, Bin; Liu, Ning-Ning; Liu, Wei-Hua; Zhang, Shuang-Wei; Zhang, Jing-Zhi; Li, Ai-Qun; Liu, Shi-Ming

    2016-07-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and GATA Binding Protein 4 (GATA4) are important for the growth of cardiac fibroblasts (CFs). When deregulated, LOX-1 and GATA4 can cause cardiac remodeling. In the present study, we found novel evidence that GATA4 was required for the LOX-1 regulation of CF proliferation. The inhibition of LOX-1 by RNA interference LOX-1 lentivirus resulted in the loss of PI3K/Akt activation and GATA4 protein expression. The overexpression of LOX-1 by lentivirus rescued CF proliferation, PI3K/Akt activation, and GATA4 protein expression. Moreover, GATA4 overexpression enhanced CF proliferation with LOX-1 inhibition. We also found that the inhibition of PI3K/Akt activation by LY294002, a PI3K inhibitor, reduced cell proliferation and protein level of GATA4. In summary, GATA4 may play an important role in the LOX-1 and PI3K/Akt regulation of CF proliferation. PMID:27216460

  5. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

    PubMed Central

    Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

    2015-01-01

    A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved. PMID:26697490

  6. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    PubMed Central

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease. PMID:27488468

  7. Inhibition of p38 Mitogen-Activated Protein Kinase Enhances the Apoptosis Induced by Oxidized Low-Density Lipoprotein in Endothelial Progenitor Cells.

    PubMed

    Tie, Guodong; Yan, Jinglian; Messina, Julia A; Raffai, Robert L; Messina, Louis M

    2015-01-01

    Oxidized low-density lipoprotein (oxLDL) is an important risk factor in the development of atherosclerosis. oxLDL has been shown to decrease endothelial progenitor cell (EPC) number by inducing apoptosis. p38 mitogen-activated protein kinase (MAPK) was shown to be activated by oxLDL and participated in the regulation of EPC number and function. However, the role of p38 remains unknown. Here, we show that oxLDL-induced p38 phosphorylation in EPCs is time and dose dependent. Treatment with antioxidant N-acetyl cysteine restored oxLDL-induced p38 phosphorylation to basal levels. LOX-1-blocking antibody also significantly decreased oxLDL-induced p38 phosphorylation. Interestingly, TUNEL staining showed that pretreatment with the p38 inhibitor SB203580 further increased oxLDL-induced apoptosis in EPCs. In accordance with these findings, pretreatment with SB203580 further attenuated Akt phosphorylation in EPCs challenged with oxLDL, indicating an interaction between Akt and p38 MAPK pathways. In agreement, inhibition of p38 MAPK further attenuated Akt phosphorylation and increased apoptosis in EPCs isolated from hypercholesterolemic ApoE-/- mice. In conclusion, p38 MAPK serves as an anti-apoptotic pathway by supporting Akt activity when EPCs are challenged with oxLDL. PMID:27031525

  8. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    NASA Astrophysics Data System (ADS)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  9. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

    PubMed

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease. PMID:27488468

  10. Pressurized water versus ethanol as a Silybum marianum extraction solvent for inhibition of low-density lipoprotein oxidation mediated by copper and J774 macrophage cells.

    PubMed

    Wallace, Sunny N; Raible, Jennifer; Carrier, Danielle Julie; Vaughn, Katherine L; Griffis, Carl L; Clausen, Edgar C; Nagarajan, Shanmugam

    2007-09-01

    Silybum marianum contains flavonolignans, termed silymarin (SM), that are therapeutic agents for many inflammation-based diseases including atherosclerosis. Oxidation of human low-density lipoprotein was induced by CuSO4 or J774 macrophage cells and measured by the formation of thiobarbituric acid reactive substances (TBARS). SM was extracted by pressurized hot water (PHWE) or ethanol, and the effects of these extracts on TBARS formation were evaluated in comparison with those of SM preparations made from blending masses of individual flavonolignan standards in ratios identical to those of the water and ethanol extracts. Ethanol-extracted SM and its blended counterpart inhibited the generation of TBARS by 82% and 43%, respectively, at 150 mumol/L doses. TBARS levels in the presence of 150 micromol/L of the PHWE and its blended SM counterpart were reduced by 84% and 38%, respectively. Extracts from milk thistle fruit displayed higher protective effects than blended SM solutions of the same concentration with an identical compositional makeup. The appearance of degradation peaks in the water extract did not create any cytotoxic effects. Results of this study confirm that PHWE can be used to extract flavonolignans from milk thistle and that these extracts may possess therapeutic potential different from or beyond that of traditional organic solvent preparations. PMID:18066135

  11. Inhibition of Glutathione Production Induces Macrophage CD36 Expression and Enhances Cellular-oxidized Low Density Lipoprotein (oxLDL) Uptake.

    PubMed

    Yang, Xiaoxiao; Yao, Hui; Chen, Yuanli; Sun, Lei; Li, Yan; Ma, Xingzhe; Duan, Shengzhong; Li, Xiaoju; Xiang, Rong; Han, Jihong; Duan, Yajun

    2015-09-01

    The glutathione (GSH)-dependent antioxidant system has been demonstrated to inhibit atherosclerosis. Macrophage CD36 uptakes oxidized low density lipoprotein (oxLDL) thereby facilitating foam cell formation and development of atherosclerosis. It remains unknown if GSH can influence macrophage CD36 expression and cellular oxLDL uptake directly. Herein we report that treatment of macrophages with l-buthionine-S,R-sulfoximine (BSO) decreased cellular GSH production and ratios of GSH to glutathione disulfide (GSH/GSSG) while increasing production of reactive oxygen species. Associated with decreased GSH levels, macrophage CD36 expression was increased, which resulted in enhanced cellular oxLDL uptake. In contrast, N-acetyl cysteine and antioxidant enzyme (catalase or superoxide dismutase) blocked BSO-induced CD36 expression as well as oxLDL uptake. In vivo, administration of mice with BSO increased CD36 expression in peritoneal macrophages and kidneys. BSO had no effect on CD36 mRNA expression and promoter activity but still induced CD36 protein expression in macrophages lacking peroxisome proliferator-activated receptor γ expression, suggesting it induced CD36 expression at the translational level. Indeed, we determined that BSO enhanced CD36 translational efficiency. Taken together, our study demonstrates that cellular GSH levels and GSH/GSSG status can regulate macrophage CD36 expression and cellular oxLDL uptake and demonstrate an important anti-atherogenic function of the GSH-dependent antioxidant system by providing a novel molecular mechanism. PMID:26187465

  12. Characterization of a natural mouse monoclonal antibody recognizing epitopes shared by oxidized low-density lipoprotein and chaperonin 60 of Aggregatibacter actinomycetemcomitans.

    PubMed

    Wang, Chunguang; Kankaanpää, Jari; Kummu, Outi; Turunen, S Pauliina; Akhi, Ramin; Bergmann, Ulrich; Pussinen, Pirkko; Remes, Anne M; Hörkkö, Sohvi

    2016-06-01

    Natural antibodies are predominantly antibodies of the IgM isotype present in the circulation of all vertebrates that have not been previously exposed to exogenous antigens. They are often directed against highly conserved epitopes and bind to ligands of varying chemical composition with low affinity. In this study we cloned and characterized a natural mouse monoclonal IgM antibody selected by binding to malondialdehyde acetaldehyde epitopes on low-density lipoprotein (LDL). Interestingly, the IgM antibody cross-reacted with Aggregatibacter actinomycetemcomitans (Aa) bacteria, a key pathogenic microbe in periodontitis reported to be associated with risk factor for atherosclerosis, thus being named as Aa_Mab. It is more intriguing that the binding molecule of Aa to Aa_Mab IgM was found to be Aa chaperonin 60 or HSP60, a member of heat-shock protein family, behaving not only as a chaperone for correct protein folding but also as a powerful virulence factor of the bacteria for inducing bone resorption and as a putative pathogenic factor in atherosclerosis. The findings will highlight the question of whether molecular mimicry between pathogen components and oxidized LDL could lead to atheroprotective immune activity, and also would be of great importance in potential application of immune response-based preventive and therapeutic strategies against atherosclerosis and periodontal disease. PMID:26786003

  13. Pdcd4 Is Involved in the Formation of Stress Granule in Response to Oxidized Low-Density Lipoprotein or High-Fat Diet.

    PubMed

    Bai, Yang; Dong, Zhaojing; Shang, Qianwen; Zhao, Hui; Wang, Liyang; Guo, Chun; Gao, Fei; Zhang, Lining; Wang, Qun

    2016-01-01

    Stress granules (SGs) in response to various stresses have been reported in many diseases. We previously reported the implication of programmed cell death 4 (Pdcd4) in obesity-induced stress responses, but the possible link between Pdcd4 and SGs remains lacking. In this study we showed that oxidized low-density lipoprotein (ox-LDL) or high-fat diet (HFD) induced SG formation in mouse macrophages and liver tissues, and Pdcd4 deficiency in mice remarkably reduced its formation. In response to ox-LDL, either endogenous or ectopic Pdcd4 displayed granule-like expression and co-localized with SG markers including T-cell-restricted intracellular antigen-1, fragile X mental retardation-related protein 1, and eukaryotic initiation factor 4A. Ectopic expression of truncated Pdcd4 that depleted specific RNA-binding motif significantly disrupted the SG formation, suggesting the direct involvement of Pdcd4 in ox-LDL-induced SGs through its RNA-binding activity. Additionally, Pdcd4 deficiency drove AKT activation and suppression of eIF2α phosphorylation, thereby contributing to the resistance to ox-LDL or HFD-induced SG formation. Collectively, our data suggest that Pdcd4 as a crucial regulator in SGs induced by ox-LDL or HFD maybe a potential target for mitigating SG-associated stress responses in obesity and related diseases. PMID:27454120

  14. Pdcd4 Is Involved in the Formation of Stress Granule in Response to Oxidized Low-Density Lipoprotein or High-Fat Diet

    PubMed Central

    Bai, Yang; Dong, Zhaojing; Shang, Qianwen; Zhao, Hui; Wang, Liyang; Guo, Chun; Gao, Fei; Zhang, Lining; Wang, Qun

    2016-01-01

    Stress granules (SGs) in response to various stresses have been reported in many diseases. We previously reported the implication of programmed cell death 4 (Pdcd4) in obesity-induced stress responses, but the possible link between Pdcd4 and SGs remains lacking. In this study we showed that oxidized low-density lipoprotein (ox-LDL) or high-fat diet (HFD) induced SG formation in mouse macrophages and liver tissues, and Pdcd4 deficiency in mice remarkably reduced its formation. In response to ox-LDL, either endogenous or ectopic Pdcd4 displayed granule-like expression and co-localized with SG markers including T-cell-restricted intracellular antigen-1, fragile X mental retardation-related protein 1, and eukaryotic initiation factor 4A. Ectopic expression of truncated Pdcd4 that depleted specific RNA-binding motif significantly disrupted the SG formation, suggesting the direct involvement of Pdcd4 in ox-LDL-induced SGs through its RNA-binding activity. Additionally, Pdcd4 deficiency drove AKT activation and suppression of eIF2α phosphorylation, thereby contributing to the resistance to ox-LDL or HFD-induced SG formation. Collectively, our data suggest that Pdcd4 as a crucial regulator in SGs induced by ox-LDL or HFD maybe a potential target for mitigating SG-associated stress responses in obesity and related diseases. PMID:27454120

  15. Analysis of human CD36 gene sequence alterations in the oxidized low-density lipoprotein-binding region using denaturing high-performance liquid chromatography.

    PubMed

    Rać, Monika Ewa; Suchy, Janina; Kurzawski, Grzegorz; Safranow, Krzysztof; Jakubowska, Katarzyna; Olszewska, Maria; Garanty-Bogacka, Barbara; Rać, Michał; Poncyljusz, Wojciech; Chlubek, Dariusz

    2010-08-01

    Denaturing high-performance liquid chromatography (DHPLC) has been employed as a prescreening tool to reduce the amount of DNA sequencing. It could be a simple and cost-effective screening method for mutations and polymorphisms in exons 4, 5, and 6 of the CD36 gene, which encode the protein region responsible for the removal of oxidized low-density lipoprotein. Genomic DNA was isolated from 306 Caucasian infants of Polish origin. Six single-nucleotide substitutions were detected by DHPLC and confirmed by direct sequencing. The A591T, G550A, and C572T alterations have not been described so far. Each of two nonsynonymous substitutions (Asp184Asn, Pro191Leu) was found in one subject (0.2% minor allele frequency). The results suggest that nonsynonymous alterations in the analyzed CD36 region are rare in Caucasians. DHPLC is a specific and cost-effective technique that may prove to be particularly useful for the identification of polymorphisms and mutations in the CD36 gene. PMID:20722468

  16. Lectin-like oxidized low-density lipoprotein receptor-1 abrogation causes resistance to inflammatory bone destruction in mice, despite promoting osteoclastogenesis in the steady state.

    PubMed

    Nakayachi, Mai; Ito, Junta; Hayashida, Chiyomi; Ohyama, Yoko; Kakino, Akemi; Okayasu, Mari; Sato, Takuya; Ogasawara, Toru; Kaneda, Toshio; Suda, Naoto; Sawamura, Tatsuya; Hakeda, Yoshiyuki

    2015-06-01

    Inflammatory bone diseases have been attributed to increased bone resorption by augmented and activated bone-resorbing osteoclasts in response to inflammation. Although the production of diverse proinflammatory cytokines is induced at the inflamed sites, the inflammation also generates reactive oxygen species that modify many biological compounds, including lipids. Among the oxidized low-density lipoprotein (LDL) receptors, lectin-like oxidized LDL receptor-1 (LOX-1), which is a key molecule in the pathogenesis of multifactorial inflammatory atherosclerosis, was downregulated with osteoclast differentiation. Here, we demonstrate that LOX-1 negatively regulates osteoclast differentiation by basically suppressing the cell-cell fusion of preosteoclasts. The LOX-1-deleted (LOX-1(-/-)) mice consistently decreased the trabecular bone mass because of elevated bone resorption during the growing phase. In contrast, when the calvaria was inflamed by a local lipopolysaccharide-injection, the inflammation-induced bone destruction accompanied by the elevated expression of osteoclastogenesis-related genes was reduced by LOX-1 deficiency. Moreover, the expression of receptor activator of NF-κB ligand (RANKL), a trigger molecule for osteoclast differentiation, evoked by the inflammation was also abrogated in the LOX-1(-/-) mice. Osteoblasts, the major producers of RANKL, also expressed LOX-1 in response to proinflammatory agents, interleukin-1β and prostaglandin E2. In the co-culture of LOX-1(-/-) osteoblasts and wild-type osteoclast precursors, the osteoclastogenesis induced by interleukin-1β and prostaglandin E2 decreased; this process occurred in parallel with the downregulation of osteoblastic RANKL expression. Collectively, LOX-1 abrogation results in resistance to inflammatory bone destruction, despite promoting osteoclastogenesis in the steady state. Our findings indicate the novel involvement of LOX-1 in physiological bone homeostasis and inflammatory bone diseases

  17. MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 macrophages.

    PubMed

    Huang, Ri-sheng; Hu, Guan-qiong; Lin, Bin; Lin, Zhi-yi; Sun, Cheng-chao

    2010-12-01

    It has been proposed that the inflammatory response of monocytes/macrophages induced by oxidized low-density lipoprotein (oxLDL) is a key event in the pathogenesis of atherosclerosis. MicroRNA-155 (miR-155) is an important regulator of the immune system and has been shown to be involved in acute inflammatory response. However, the function of miR-155 in oxLDL-stimulated inflammation and atherosclerosis remains unclear. Here, we show that the exposure of human THP-1 macrophages to oxLDL led to a marked up-regulation of miR-155 in a dose-dependent manner. Silencing of endogenous miR-155 in THP-1 cells using locked nucleic acid-modified antisense oligonucleotides significantly enhanced oxLDL-induced lipid uptake, up-regulated the expression of scavenger receptors (lectinlike oxidized LDL receptor-1, cluster of differentiation 36 [CD36], and CD68), and promoted the release of several cytokines including interleukin (IL)-6, -8, and tumor necrosis factor α (TNF-α). Luciferase reporter assay showed that targeting miR-155 promoted nuclear factor-kappa B (NF-κB) nuclear translocation and potentiated the NF-κB-driven transcription activity. Moreover, miR-155 knockdown resulted in a marked increase in the protein amount of myeloid differentiation primary response gene 88 (MyD88), an important adapter protein used by Toll-like receptors to activate the NF-κB pathway. Our data demonstrate that miR-155 serves as a negative feedback regulator in oxLDL-stimulated THP-1 inflammatory responses and lipid uptake and thus might have potential therapeutic implications in atherosclerosis. PMID:21030878

  18. Very-low and low-density lipoproteins induce neutral lipid accumulation and impair migration in monocyte subsets

    PubMed Central

    Jackson, William D.; Weinrich, Tobias W.; Woollard, Kevin J.

    2016-01-01

    Blood monocytes are heterogeneous effector cells of the innate immune system. In circulation these cells are constantly in contact with lipid-rich lipoproteins, yet this interaction is poorly characterised. Our aim was to examine the functional effect of hyperlipidaemia on blood monocytes. In the Ldlr−/− mouse monocytes rapidly accumulate cytoplasmic neutral lipid vesicles during hyperlipidaemia. Functional analysis in vivo revealed impaired monocyte chemotaxis towards peritonitis following high fat diet due to retention of monocytes in the greater omentum. In vitro assays using human monocytes confirmed neutral lipid vesicle accumulation after exposure to LDL or VLDL. Neutral lipid accumulation did not inhibit phagocytosis, endothelial adhesion, intravascular crawling and transmigration. However, lipid loading led to a migratory defect towards C5a and disruption of cytoskeletal rearrangement, including an inhibition of RHOA signaling. These data demonstrate distinct effects of hyperlipidaemia on the chemotaxis and cytoskeletal regulation of monocyte subpopulations. These data emphasise the functional consequences of blood monocyte lipid accumulation and reveal important implications for treating inflammation, infection and atherosclerosis in the context of dyslipidaemia. PMID:26821597

  19. Very-low and low-density lipoproteins induce neutral lipid accumulation and impair migration in monocyte subsets.

    PubMed

    Jackson, William D; Weinrich, Tobias W; Woollard, Kevin J

    2016-01-01

    Blood monocytes are heterogeneous effector cells of the innate immune system. In circulation these cells are constantly in contact with lipid-rich lipoproteins, yet this interaction is poorly characterised. Our aim was to examine the functional effect of hyperlipidaemia on blood monocytes. In the Ldlr(-/-) mouse monocytes rapidly accumulate cytoplasmic neutral lipid vesicles during hyperlipidaemia. Functional analysis in vivo revealed impaired monocyte chemotaxis towards peritonitis following high fat diet due to retention of monocytes in the greater omentum. In vitro assays using human monocytes confirmed neutral lipid vesicle accumulation after exposure to LDL or VLDL. Neutral lipid accumulation did not inhibit phagocytosis, endothelial adhesion, intravascular crawling and transmigration. However, lipid loading led to a migratory defect towards C5a and disruption of cytoskeletal rearrangement, including an inhibition of RHOA signaling. These data demonstrate distinct effects of hyperlipidaemia on the chemotaxis and cytoskeletal regulation of monocyte subpopulations. These data emphasise the functional consequences of blood monocyte lipid accumulation and reveal important implications for treating inflammation, infection and atherosclerosis in the context of dyslipidaemia. PMID:26821597

  20. Low density microcellular foams

    DOEpatents

    Aubert, James H.; Clough, Roger L.; Curro, John G.; Quintana, Carlos A.; Russick, Edward M.; Shaw, Montgomery T.

    1987-01-01

    Low density, microporous polymer foams are provided by a process which comprises forming a solution of polymer and a suitable solvent followed by rapid cooling of the solution to form a phase-separated system and freeze the phase-separated system. The phase-separated system comprises a polymer phase and a solvent phase, each of which is substantially continuous within the other. The morphology of the polymer phase prior to and subsequent to freezing determine the morphology of the resultant foam. Both isotropic and anisotropic foams can be produced. If isotropic foams are produced, the polymer and solvent are tailored such that the solution spontaneously phase-separates prior to the point at which any component freezes. The morphology of the resultant polymer phase determines the morphology of the resultant foam and the morphology of the polymer phase is retained by cooling the system at a rate sufficient to freeze one or both components of the system before a change in morphology can occur. Anisotropic foams are produced by forming a solution of polymer and solvent that will not phase separate prior to freezing of one or both components of the solution. In such a process, the solvent typically freezes before phase separation occurs. The morphology of the resultant frozen two-phase system determines the morphology of the resultant foam. The process involves subjecting the solution to essentially one-dimensional cooling. Means for subjecting such a solvent to one-dimensional cooling are also provided. Foams having a density of less than 0.1 g/cc and a uniform cell size of less than 10 .mu.m and a volume such that the foams have a length greater than 1 cm are provided.

  1. Low density microcellular foams

    DOEpatents

    Aubert, J.H.; Clough, R.L.; Curro, J.G.; Quintana, C.A.; Russick, E.M.; Shaw, M.T.

    1985-10-02

    Low density, microporous polymer foams are provided by a process which comprises forming a solution of polymer and a suitable solvent followed by rapid cooling of the solution to form a phase-separated system and freeze the phase-separated system. The phase-separated system comprises a polymer phase and a solvent phase, each of which is substantially continuous within the other. The morphology of the polymer phase prior to and subsequent to freezing determine the morphology of the resultant foam. Both isotropic and anisotropic foams can be produced. If isotropic foams are produced, the polymer and solvent are tailored such that the solution spontaneously phase-separates prior to the point at which any component freezes. The morphology of the resultant polymer phase determines the morphology of the reusltant foam and the morphology of the polymer phase is retained by cooling the system at a rate sufficient to freeze one or both components of the system before a change in morphology can occur. Anisotropic foams are produced by forming a solution of polymer and solvent that will not phase separate prior to freezing of one or both components of the solution. In such a process, the solvent typically freezes before phase separation occurs. The morphology of the resultant frozen two-phase system determines the morphology of the resultant foam. The process involves subjecting the solution to essentially one-dimensional cooling. Foams having a density of less than 0.1 g/cc and a uniform cell size of less than 10 ..mu..m and a volume such that the foams have a length greater than 1 cm are provided.

  2. Human serum amyloid A3 (SAA3) protein, expressed as a fusion protein with SAA2, binds the oxidized low density lipoprotein receptor.

    PubMed

    Tomita, Takeshi; Ieguchi, Katsuaki; Sawamura, Tatsuya; Maru, Yoshiro

    2015-01-01

    Serum amyloid A3 (SAA3) possesses characteristics distinct from the other serum amyloid A isoforms, SAA1, SAA2, and SAA4. High density lipoprotein contains the latter three isoforms, but not SAA3. The expression of mouse SAA3 (mSAA3) is known to be up-regulated extrahepatically in inflammatory responses, and acts as an endogenous ligand for the toll-like receptor 4/MD-2 complex. We previously reported that mSAA3 plays an important role in facilitating tumor metastasis by attracting circulating tumor cells and enhancing hyperpermeability in the lungs. On the other hand, human SAA3 (hSAA3) has long been regarded as a pseudogene, which is in contrast to the abundant expression levels of the other isoforms. Although the nucleotide sequence of hSAA3 is very similar to that of the other SAAs, a single oligonucleotide insertion in exon 2 causes a frame-shift to generate a unique amino acid sequence. In the present study, we identified that hSAA3 was transcribed in the hSAA2-SAA3 fusion transcripts of several human cell lines. In the fusion transcript, hSAA2 exon 3 was connected to hSAA3 exon 1 or hSAA3 exon 2, located approximately 130kb downstream from hSAA2 exon 3 in the genome, which suggested that it is produced by alternative splicing. Furthermore, we succeeded in detecting and isolating hSAA3 protein for the first time by an immunoprecipitation-enzyme linked immune assay system using monoclonal and polyclonal antibodies that recognize the hSAA3 unique amino acid sequence. We also demonstrated that hSAA3 bound oxidized low density lipoprotein receptor (oxLDL receptor, LOX-1) and elevated the phosphorylation of ERK, the intracellular MAP-kinase signaling protein. PMID:25738827

  3. Multi-radionuclide digital autoradiography of the intra-aortic atherosclerotic plaques using a monoclonal antibody targeting oxidized low-density lipoprotein.

    PubMed

    Orbom, Anders; Jansson, Bo; Schiopu, Alexandru; Evans-Axelsson, Susan; Nilsson, Jan; Fredrikson, Gunilla Nordin; Strand, Sven-Erik

    2014-01-01

    The aim of this study was to use multi-radionuclide autoradiography to compare the different distributions of three radiolabelled tracers in an atherosclerotic mouse model. This method, along with immunohistochemistry, was applied to investigate the intra-aortic distribution of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), (131)I/(125)I labeled anti-oxidized Low Density Lipoprotein (oxLDL), and non-binding control antibodies. Aortas were isolated from a total of 12 apoB-100/LDL receptor deficient mice 73 h post injection of radioiodine-labeled anti-oxLDL and control antibody and 1 h post injection of (18)F-FDG. A solid-state real-time digital autoradiography system was used to image the slide mounted aortas. Contributions from each radionuclide were separated by half-life and emission energy and the aortas were subsequently stained with Oil Red O for plaque to aorta contrast ratios. Immunohistochemical staining was performed to detect anti-oxLDL and control antibody localization. Radiolabeled anti-oxLDL showed increased total activity uptake in the aorta over control antibody and immunohistochemical analysis of plaques indicated increased binding of the specific antibody compared to control. The intra-aortic activity distribution of the anti-oxLDL antibody was however very similar to that of the control antibody although both had higher atherosclerotic plaques to aorta wall ratios than (18)F-FDG. Given the right choice of radionuclides, multi-radionuclide digital autoradiography can be employed to compare several tracers ex vivo in the same animal. The distribution of anti-oxLDL antibodies did not significantly differ from the control antibody but it did appear to have a better plaque to aorta contrast at 73 h post injection than (18)F-FDG at 1 h post injection. PMID:24753983

  4. Usefulness of Antibodies to Oxidized Low-Density Lipoproteins as Predictors of Morbidity and Prognosis in Heart Failure Patients Aged ≥65 Years.

    PubMed

    Charach, Gideon; Michowitz, Yoav; Rogowski, Ori; Charach, Lior; Argov, Ori; George, Jacob; Grosskopf, Itamar

    2015-11-01

    Elevated level of antibodies to oxidized low-density lipoproteins (OxLDL-Ab) was shown to reliably predict morbidity and mortality in patients with heart failure (HF). Two hundred and eleven patients aged ≥65 years treated at the Heart Failure Unit, Tel Aviv-Sourasky Medical Center, were included in this retrospective study. The end points were time to the first hospitalization (morbidity), all-cause mortality, and a combination of the two (composite outcome). HF duration ranged from 8 to 10.5 years. Mean follow-up was 5.2 ± 1.9 years. The mean number of clinical visits was 18.3 ± 2.4. Participants were divided according to OxLDL-Ab level. Group 1 had Ox LDL-Ab level <200 arbitrary U/ml. Group 2 had OxLDL-Ab level ≥200 arbitrary U/ml. The mean time to the first hospitalization was 25.8 ± 17.0 months. The mortality rate was 44.1%. Combined mortality and hospitalization rate was 58.8%. Adjusted hazard ratios of OxLDL-Ab for hospitalization were 3.16, p <0.001, 95% confidence interval 1.740 to 5.736 and for composite outcome 2.67, p <0.001, 95% confidence interval 1.580 to 4.518. In conclusion, OxLDL-Ab level was the best predictor for both hospitalization and composite outcome. It may, thus, serve as a useful clue for early and more accurate detection of poorly controlled HF and as a marker for imminent exacerbations of thereof. PMID:26372212

  5. Monocytic expression of osteoclast-associated receptor (OSCAR) is induced in atherosclerotic mice and regulated by oxidized low-density lipoprotein in vitro.

    PubMed

    Sinningen, Kathrin; Rauner, Martina; Goettsch, Claudia; Al-Fakhri, Nadia; Schoppet, Michael; Hofbauer, Lorenz C

    2013-07-26

    The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a potential link between bone metabolism and vascular biology. Previously, we identified OSCAR as an endothelial cell-derived target of the proatherogenic factor oxidized low density lipoprotein (oxLDL). Since monocytes play an important role in the progression of atherosclerosis, we assessed whether atherogenic stimuli also regulate the expression of OSCAR on monocytes. Four-week-old male wild-type (WT), apolipoprotein e knockout (apoe KO), and LDL receptor knockout (ldlr KO) mice were fed a high-fat diet or normal chow for 6weeks. Peripheral blood mononuclear cells (PBMCs) isolated from the spleen were stained with antibodies against CD14 and OSCAR for subsequent flow cytometric analysis. OSCAR surface expression on CD14-positive monocytes increased 2-fold in PBMCs from apoe KO mice compared to WT mice. Feeding a high-fat diet further increased OSCAR surface expression 1.5-fold in apoe KO mice compared to normal diet. Moreover, OSCAR-positive macrophages were detected in atherosclerotic plaques of apoe KO mice. Interestingly, monocytic OSCAR expression was not altered in ldlr KO mice. In the murine macrophage cell line RAW 264.7, TNFα and oxLDL induced OSCAR mRNA expression by 2-fold and 5-fold (p<0.01), respectively. Blocking the oxLDL receptor LOX-1 and inhibiting the NF-κB pathway prevented OSCAR induction. In conclusion, OSCAR expression in monocytic cells is regulated by proatherogenic stimuli further pointing towards a role in vascular inflammation or plaque vulnerability during atherosclerosis. PMID:23817038

  6. Human Serum Amyloid A3 (SAA3) Protein, Expressed as a Fusion Protein with SAA2, Binds the Oxidized Low Density Lipoprotein Receptor

    PubMed Central

    Tomita, Takeshi; Ieguchi, Katsuaki; Sawamura, Tatsuya; Maru, Yoshiro

    2015-01-01

    Serum amyloid A3 (SAA3) possesses characteristics distinct from the other serum amyloid A isoforms, SAA1, SAA2, and SAA4. High density lipoprotein contains the latter three isoforms, but not SAA3. The expression of mouse SAA3 (mSAA3) is known to be up-regulated extrahepatically in inflammatory responses, and acts as an endogenous ligand for the toll-like receptor 4/MD-2 complex. We previously reported that mSAA3 plays an important role in facilitating tumor metastasis by attracting circulating tumor cells and enhancing hyperpermeability in the lungs. On the other hand, human SAA3 (hSAA3) has long been regarded as a pseudogene, which is in contrast to the abundant expression levels of the other isoforms. Although the nucleotide sequence of hSAA3 is very similar to that of the other SAAs, a single oligonucleotide insertion in exon 2 causes a frame-shift to generate a unique amino acid sequence. In the present study, we identified that hSAA3 was transcribed in the hSAA2-SAA3 fusion transcripts of several human cell lines. In the fusion transcript, hSAA2 exon 3 was connected to hSAA3 exon 1 or hSAA3 exon 2, located approximately 130kb downstream from hSAA2 exon 3 in the genome, which suggested that it is produced by alternative splicing. Furthermore, we succeeded in detecting and isolating hSAA3 protein for the first time by an immunoprecipitation-enzyme linked immune assay system using monoclonal and polyclonal antibodies that recognize the hSAA3 unique amino acid sequence. We also demonstrated that hSAA3 bound oxidized low density lipoprotein receptor (oxLDL receptor, LOX-1) and elevated the phosphorylation of ERK, the intracellular MAP-kinase signaling protein. PMID:25738827

  7. Serum Lipid, Lipoprotein and Oxidatively Modified Low Density Lipoprotein Levels in Active or Inactive Patients with Behçet's Disease

    PubMed Central

    Cimen, Fuat; Yildirmak, Sembol Turken; Ergen, Andac; Cakmak, Mustafa; Dogan, Serkan; Yenice, Necati; Sezgin, Funda

    2012-01-01

    Aim: To determine serum lipid, lipoproteins and oxidized low density lipoprotein (oxLDL) levels in Behçet's disease (BD) and to evaluate the relationship of these parameters with the clinical activity of the disease. Materials and Methods: Sixty-two patients (25 active, 37 inactive) and —26 healthy controls were included in the study. We measured serum oxLDL levels using the enzyme-linked immunosorbent assay method, and serum total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) levels by spectrophotometric method. Results: Serum TG (108±70 mg/dL and 79±40 mg/dL, respectively; P<0.05), LDL-C (124±35 mg/dL and 108±26 mg/dL, respectively; P<0.05) and oxLDL (65±19 U/L and 53±10 U/L, respectively; P<0.01) levels were significantly higher in patients than in controls, but HDL-C levels were significantly lower in patients than in controls (39±11 mg/dL and 50±13 mg/dL, respectively; P<0.05). The levels of oxLDL in patients were found to correlate with those of TC and LDL-C. Neither the lipid parameters nor the oxLDL levels in the patients with active disease (n=25) were different than those in the patients who were in inactive stage (n=37). Serum levels of oxLDL in the patients with active and inactive disease were significantly higher than those in controls (66±19 U/L, 65±19 U/L, and 53±10 U/L, respectively; P<0.05). Conclusions: We conclude that the increase of TG, LDL-C and oxLDL levels and the decrease of HDL-levels may indicate that there is a tendency to atherothrombotic process in patients with BD. Inflammation and immunologic reactions in BD may be caused by a response to elevated oxLDL. TG, LDL-C and oxLDL are not useful markers for the severity of the disease activity. PMID:22615503

  8. BMP4 is increased in the aortas of diabetic ApoE knockout mice and enhances uptake of oxidized low density lipoprotein into peritoneal macrophages

    PubMed Central

    2013-01-01

    Background BMP4, a member of the transforming growth factor-beta superfamily, is upregulated in the aortas of diabetic db/db mice. However, little is known about its role in diabetic atherosclerosis. Therefore, we examined the roles of BMP4 in the formation of diabetic atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and in the uptake of oxidized low density lipoprotein (oxLDL) in peritoneal macrophages of wild-type mice. Methods To induce diabetes, ApoE KO mice were intraperitoneally injected with streptozotocin. Diabetic and non-diabetic ApoE KO mice were then fed a high-fat diet for 4 weeks. Next, to investigate a role of BMP4 in the peritoneal macrophages, we examined the uptake of oxLDL in BMP4-treated macrophages. Results Diabetic ApoE KO mice showed accelerated progression of aortic plaques accompanied by increased luminal plaque area. Western blot analysis showed that BMP4 expression in the whole aorta was greatly increased in diabetic ApoE KO mice, than non-diabetic mice. Western blot analysis showed that the BMP4/SMAD1/5/8 signaling pathway was strongly activated in the aorta from diabetic ApoE KO mice, compared with control ApoE KO mice. Double immunofluorescence staining showed that BMP4 was expressed in MOMA2-labeled macrophage in the aortic lesions of ApoE KO mice. BMP4 significantly increased the uptake of oxLDL into peritoneal macrophages in vitro. Conclusion We show that in the aorta of diabetic ApoE KO mice, BMP4 is increased and activates SMAD1/5/8. Our in vitro findings indicate that BMP4 enhances oxLDL uptake in mouse peritoneal macrophages, suggesting BMP4 may be involved in aortic plaque formation in diabetic ApoE KO mice. Targeting BMP4 may offer a new strategy for inhibition of plaque progression and stabilization of atherosclerotic lesions. PMID:24107300

  9. Impact of hydrogenated fat consumption on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein to oxidation in moderately hypercholesterolemic individuals.

    PubMed

    Cuchel, M; Schwab, U S; Jones, P J; Vogel, S; Lammi-Keefe, C; Li, Z; Ordovas, J; McNamara, J R; Schaefer, E J; Lichtenstein, A H

    1996-02-01

    The effects of replacing corn oil with corn oil margarine in stick form on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein (LDL) to oxidation were assessed in 14 middle-aged and elderly men and women aged 63 +/- 12 years (mean +/- SD) with moderate hypercholesterolemia (mean LDL-cholesterol [LDL-C], 4.24 +/- 0.59 mmol/L at the time of recruitment). Subjects consumed each of two diets for 32-day periods, one enriched in corn oil, which contained 30% of energy as fat (7% saturated fatty acid [SFA], 9% monounsaturated fatty acid [MUFA] [0.4% 18:1n9 trans], and 11% polyunsaturated fatty acid [PUFA]) and 85 mg cholesterol/4.2 MJ, and one enriched in stick corn oil margarine, which contained 30% fat (8% SFA, 12% MUFA [4.2% 18:1n9trans], and 8% PUFA) and 77 mg cholesterol/4.2 MJ. Both diets were isocaloric and supplied by a metabolic research kitchen. Mean total cholesterol levels were lowest (P = .039) when subjects consumed the corn oil-enriched diet (5.01 +/- 0.51 mmol/L) as compared with the margarine-enriched diet (5.30 +/- 0.58 mmol/L). LDL-C levels were 3.24 +/- 0.51 and 3.50 +/- 0.54 mmol/L when subjects consumed corn oil-and margarine-enriched diets, respectively (P = .058). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) or triglyceride concentrations between the two experimental periods. Consumption of the margarine-enriched diet versus the corn oil-enriched diet tended to result in lower cholesterol fractional synthetic rates ([C-FSRs] 0.0466 +/- 0.0175 and 0.0668 +/- 0.0298, respectively, P = .080) and cholesterol absolute synthetic rates ([C-ASRs] 1.1761 +/- 0.5375 and 1.6954 +/- 0.8685, respectively, P = .092); however, differences did not reach statistical significance. Consumption of the margarine-enriched diet versus the corn oil-enriched diet resulted in a significantly higher concentration of alpha-tocopherol in both plasma and LDL(P = .004 and P = .011, respectively). LDL particle

  10. Complex of vitamins and antioxidants protects low-density lipoproteins in blood plasma from free radical oxidation and activates antioxidants enzymes in erythrocytes from patients with coronary heart disease.

    PubMed

    Konovalova, G G; Lankin, V Z; Tikhaze, A K; Nezhdanova, I B; Lisina, M O; Kukharchuk, V V

    2003-08-01

    We studied the effect of a complex containing antioxidant vitamins C and E, provitamin A, and antioxidant element selenium on the contents of primary (lipid peroxides) and secondary products (malonic dialdehyde) of free radical lipid oxidation in low-density lipoproteins isolated from the plasma of patients with coronary heart disease and hypercholesterolemia by means of preparative ultracentrifugation. Activity of key antioxidant enzymes in the blood was measured during treatment with the antioxidant preparation. Combination treatment with antioxidant vitamins and antioxidant element selenium sharply decreased the contents of primary and secondary free radical oxidation products in circulating low-density lipoproteins and increased activity of antioxidant enzymes in erythrocytes. Activities of superoxide dismutase and selenium-containing glutathione peroxidase increased 1 and 2 months after the start of therapy, respectively. PMID:14631494

  11. Antiatherogenic and antitumoral properties of Opuntia cladodes: inhibition of low density lipoprotein oxidation by vascular cells, and protection against the cytotoxicity of lipid oxidation product 4-hydroxynonenal in a colorectal cancer cellular model.

    PubMed

    Keller, Julia; Camaré, Caroline; Bernis, Corinne; Astello-García, Marizel; de la Rosa, Ana-Paulina Barba; Rossignol, Michel; del Socorro Santos Díaz, María; Salvayre, Robert; Negre-Salvayre, Anne; Guéraud, Françoise

    2015-09-01

    Opuntia species have been used for thousands of years as a folk medicine in the treatment of diseases. However, the components and protective mechanisms are still unclear. We make the hypothesis that Opuntia species may protect the development of oxidative stress-associated diseases, such as atherosclerosis or colon cancer, via their antioxidant properties. We investigated the protective effect of Opuntia cladode powder against the oxidation of low-density lipoprotein (LDL) evoked by vascular endothelial cells, an important risk factor for atherosclerosis development, and the toxicity of 4-hydroxynonenal (a major lipid peroxidation product) on normal (Apc +/+) and preneoplastic (Apc min/+) immortalized epithelial colon cells. Various Opuntia species classified according to their degree of domestication, from the wildest (Opuntia streptacantha, Opuntia hyptiacantha, Opuntia megacantha), medium (Opuntia albicarpa), to the most domesticated (Opuntia ficus-indica) were tested. Cladode powders prepared from these Opuntia species significantly inhibited LDL oxidation induced by incubation with murine endothelial cells and the subsequent foam cell formation of RAW 264.7 murine macrophages and cytotoxicity on murine endothelial cells. Moreover, Opuntia cladode powder blocked the promotion of colon cancer development on an in vitro model of colonocytes. It may be noted that the phenolic acid and flavonoids content, the antioxidant capacity, and the protective effect were relatively similar in all the cladode powders from wild (O. streptacantha) and domesticated Opuntia. Altogether, these data confirm the therapeutic potential of Opuntia cladodes in diseases associated with oxidative stress. PMID:25840808

  12. Binding and uptake of 125iodine-labelled, oxidized low density lipoprotein by macrophages: comparison of the effects of alpha-tocopherol, probucol, pyridoxal-5'-phosphate and magnesium-pyridoxal-5'-phosphate-glutamate.

    PubMed

    Selmer, D; Senekowitsch-Schmidtke, R; Schneider, W; Elstner, E F

    1997-01-01

    Specific and unspecific binding and uptake (internalization) by macrophages of 125iodine-labelled, copper-oxidized human low density lipoprotein is differently influenced by the anti-oxidants alpha-tocopherol (alpha-Toc), probucol (Prob), pyridoxal-5'-phosphate (PP) and the magnesium-pyridoxal-5'-phosphate glutamate complex (MPPG). Binding as well as internalization, mediated by the so-called "scavenger receptor" is lower in the presence of MPPG whereas both specific binding and internalization are enhanced. The comparison of the effects in vitro allows a rating of the potentially anti-atherogenic and thus protective effects of the tested substances as follows: MPPG > PP > alpha-Toc > Prob. PMID:9090072

  13. The influence of magnesium-pyridoxal-5'-phosphate-glutamate in comparison with probucol, alpha-tocopherol and trolox on copper-induced oxidation of human low density lipoprotein in vitro.

    PubMed

    Kögl, C; Schneider, W; Elstner, E F

    1994-06-15

    Low density lipoprotein (LDL) in the presence of magnesium-pyridoxal-5'-phosphate-glutamate (MPPG), pyridoxal-5'-phosphate (PP), alpha-tocopherol, probucol or trolox is more resistant against copper-induced oxidation as control-LDL in vitro. The efficiency of the drugs is: probucol > MPPG > trolox > alpha-tocopherol > PP. LDL oxidation is determined by its increasing negative surface charge, fragmentation of apolipoprotein B-100 and changes of the fatty acid content of LDL. The protection of the drugs depends on their concentration and incubation time. Different experiments point to the fact that copper-induced oxidation of LDL in vitro starts with the binding of copper at the apolipoprotein B-100, resulting in an increasing negative surface charge and fragmentation of the apolipoprotein B-100. Afterwards a decrease of LDL-bound linoleic acid (18:2) is measurable. PMID:8031313

  14. Human suction blister interstitial fluid prevents metal ion-dependent oxidation of low density lipoprotein by macrophages and in cell-free systems.

    PubMed Central

    Dabbagh, A J; Frei, B

    1995-01-01

    LDL in the circulation is well protected against oxidation by the highly efficient antioxidant defense mechanisms of human plasma. LDL oxidation contributing to atherosclerosis, therefore, has been hypothesized to take place in the interstitial fluid of the arterial wall. We investigated the antioxidant composition and the capacity to inhibit LDL oxidation of human suction blister interstitial fluid (SBIF), a suitable representative of interstitial fluid. We found that the concentrations in SBIF of the aqueous small-molecule antioxidants ascorbate and urate were, respectively, significantly higher (P < 0.05) and identical to plasma concentrations. In contrast, lipoprotein-associated lipids and lipid-soluble antioxidants (alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene) were present at only 8-23% of the concentrations in plasma. No lipid hydroperoxides could be detected ( < 5 nM) in either fluid. The capacity of serum and SBIF to protect LDL from oxidation was investigated in three metal ion-dependent systems: copper, iron, and murine macrophages in Ham's F-10 medium. In all three systems, addition of > or = 6% (vol/vol) of either serum or SBIF inhibited LDL oxidation by > 90%. The concentration that inhibited macrophage-mediated LDL oxidation by 50% was as low as 0.3% serum and 0.7% SBIF. The enzymatic or physical removal of ascorbate or urate and other low molecular weight components did not affect the ability of either fluid to prevent LDL oxidation, and the high molecular weight fraction was as protective as whole serum or SBIF. These data demonstrate that both serum and SBIF very effectively protect LDL from metal ion-dependent oxidation, most probably because of a cumulative metal-binding effect of several proteins. Our data suggest that LDL in the interstitial fluid of the arterial wall is very unlikely to get modified by metal ion-mediated oxidation. Images PMID:7560088

  15. Low density metal hydride foams

    DOEpatents

    Maienschein, Jon L.; Barry, Patrick E.

    1991-01-01

    Disclosed is a low density foam having a porosity of from 0 to 98% and a density less than about 0.67 gm/cc, prepared by heating a mixture of powered lithium hydride and beryllium hydride in an inert atmosphere at a temperature ranging from about 455 to about 490 K for a period of time sufficient to cause foaming of said mixture, and cooling the foam thus produced. Also disclosed is the process of making the foam.

  16. Comparative studies on the antioxidant activities of nine common food legumes against copper-induced human low-density lipoprotein oxidation in vitro.

    PubMed

    Xu, B J; Yuan, S H; Chang, S K C

    2007-09-01

    Epidemiological studies demonstrated that the consumption of dietary antioxidant was associated with the prevention of atherosclerosis. The aim of this study was to investigate the antioxidant activities of the hydrophilic extracts from 9 selected legumes based on copper-induced human LDL oxidation model in vitro. The antioxidant activities were assessed on the basis of the formation of conjugated dienes (lag time of oxidation) and thiobarbituric acid reactive substances (TBARS) as the early and later stage markers of LDL oxidation. The results showed that the extracts of black beans (Phaseolus vulgaris L.), lentils (Lens culinaris), black soybeans (Glycine max), and red kidney beans (Phaseolus vulgaris L.) had significant (P < 0.05) longer LDL oxidation lag times (128.8, 124.2, 107.7, and 111.1 min, respectively) than the LDL control group (94.9 min). No significant lag-time lengthening was observed in other tested legume extracts. On the other hand, black beans, lentils, black soybeans, red kidney beans, and pinto beans exhibited higher antioxidant capacities (Trolox equivalents) than yellow peas, green peas, chickpea, and yellow soybeans in both LDL-conjugated dienes assay and LDL-TBARS assay. Meanwhile, the antioxidant activities of these legumes against LDL-lipid peroxidation in the above assays were found to correlate very significantly (P < 0.01) with their phenolic substances, and DPPH radical scavenging activity and ORAC (oxygen radical absorbance capacity). These results suggest that consuming black beans, lentils, black soybeans, and red kidney beans may have potential in preventing the development of atherosclerosis from the perspective of inhibiting LDL oxidation. PMID:17995667

  17. Lemon grass (Cymbopogon citratus (D.C) Stapf) polyphenols protect human umbilical vein endothelial cell (HUVECs) from oxidative damage induced by high glucose, hydrogen peroxide and oxidised low-density lipoprotein.

    PubMed

    Campos, J; Schmeda-Hirschmann, G; Leiva, E; Guzmán, L; Orrego, R; Fernández, P; González, M; Radojkovic, C; Zuñiga, F A; Lamperti, L; Pastene, E; Aguayo, C

    2014-05-15

    The aromatic herb Cymbopogon citratus Stapf is widely used in tropical and subtropical countries in cooking, as a herbal tea, and in traditional medicine for hypertension and diabetes. Some of its properties have been associated with the in vitro antioxidant effect of polyphenols isolated from their aerial parts. However, little is known about C. citratus effects on endothelial cells oxidative injury. Using chromatographic procedures, a polyphenol-rich fraction was obtained from C. citratus (CCF) and their antioxidant properties were assessed by cooper-induced LDL oxidation assay. The main constituents of the active CCF, identified by high-performance liquid chromatography with diode-array detection and mass spectrometry (HPLC-DAD-MS), were chlorogenic acid, isoorientin and swertiajaponin. CCF 10 and 100 μg/ml diminishes reactive oxidative species (ROS) production in human umbilical vein endothelial cell (HUVECs), challenged with high D-glucose (60% inhibition), hydrogen peroxide (80% inhibition) or oxidised low-density lipoprotein (55% inhibition). CCF 10 or 100 μg/ml did not change nitric oxide (NO) production. However, CCF was able to inhibit vasoconstriction induced by the thromboxane A2 receptor agonist U46619, which suggest a NO-independent vasodilatador effect on blood vessels. Our results suggest that lemon grass antioxidant properties might prevent endothelial dysfunction associated to an oxidative imbalance promoted by different oxidative stimuli. PMID:24423518

  18. Low-density ionization behavior

    SciTech Connect

    Baker, G.A. Jr.

    1995-04-01

    As part of a continuing study of the physics of matter under extreme conditions, I give some results on matter at extremely low density. In particular I compare a quantum mechanical calculation of the pressure for atomic hydrogen with the corresponding pressure given by Thomas-Fermi theory. (This calculation differs from the ``confined atom`` approximation in a physically significant way.) Since Thomas-Fermi theory in some sense, represents the case of infinite nuclear charge, these cases should represent extremes. Comparison is also made with Saha theory, which considers ionization from a chemical point of view, but is weak on excited-state effects. In this theory, the pressure undergoes rapid variation as electron ionization levels are passed. This effect is in contrast to the smooth behavior of the Thomas-Fermi fixed temperature, complete ionization occurs in the low density limit, I study the case where the temperature goes appropriately to zero with the density. Although considerable modification is required, Saha theory is closer to the actual results for this case than is Thomas-Fermi theory.

  19. Oxidized low-density lipoprotein attenuated desmoglein 1 and desmocollin 2 expression via LOX-1/Ca(2+)/PKC-β signal in human umbilical vein endothelial cells.

    PubMed

    Li, Yuan-Bin; Zhang, Qing-Hai; Chen, Zhuang; He, Zhi-Jun; Yi, Guang-Hui

    Numerous studies have reported the presence of oxidized LDL (ox-LDL) and expression of its lectin-like receptor, LOX-1, have been shown in atherosclerotic regions. The present study aims to investigate the effects of ox-LDL on expression of desmoglein 1 (DSG1) and desmocollin 2 (DSC2) in endothelial cells, and to explore the role of LOX-1 mediated signal in the permeability injury associated with DSG1 and DSC2 disruption induced by oxidized lipoprotein. RT-PCR and Western blotting were applied to determine the mRNA and protein expression levels of DSG1 and DSC2 in human umbilical vein endothelial cells (HUVECs) respectively. Immunoreactivities of DSG1 and DSC2 were detected by laser scanning confocal microscope (LSCM). HUVEC monolayers permeability was evaluated by FITC-labeled LDL in transwell assay system. The possible signal was assessed using in vitro blocking LOX-1 or Ca(2+) channel or PKC. The DSG1 and DSC2 expression were decreased by ox-LDL in concentration- and time-dependent manner. The effects of ox-LDL were mediated by its endothelial receptor, LOX-1. In parallel experiments, ox-LDL increased the influx of extracellular calcium, activation of protein kinase C (PKC) and permeability to LDL, which was inhibited by the LOX-1blocking antibody (10 μg/ml), Ca(2+) channel blocker (Diltiazem, 50 μmol/L) and PKC-β inhibitor (hispidin, 4 μmol/L). These results suggested that ox-LDL-induced decrease in DSG1 and DSC2 expression and monolayer barrier injury via calcium uptake and PKC-β activation following up-regulation of LOX-1 is one of the mechanisms of inducing greater permeability in HUVECs. PMID:26498522

  20. Low molecular weight phenolics of grape juice and winemaking byproducts: antioxidant activities and inhibition of oxidation of human low-density lipoprotein cholesterol and DNA strand breakage.

    PubMed

    de Camargo, Adriano Costa; Regitano-d'Arce, Marisa Aparecida Bismara; Biasoto, Aline Camarão Telles; Shahidi, Fereidoon

    2014-12-17

    Bioactive compounds belonging to phenolic acids, flavonoids, and proanthocyanidins of grape juice and winemaking byproducts were identified and quantified by HPLC-DAD-ESI-MS(n). The concentration of phenolic compounds in different grape cultivars was in the order Tempranillo > Cora > Syrah > Isabel. The insoluble-bound fraction was most prominent, contributing 63 and 79% to the total for Isabel and Tempranillo, respectively. Juice-processing byproducts had a higher content of free than esterified phenolics, but the opposite was noted for winemaking byproducts. Insoluble-bound phenolics were up to 15 and 10 times more effective as antioxidants than those of free and esterified fractions, respectively, as evaluated by the DPPH, ABTS, and H2O2 scavenging activities and reducing power determinations. In general, insoluble-bound phenolics (100 ppm) were more effective in inhibiting copper-induced human LDL-cholesterol oxidation than free and esterified phenolics, exhibiting equal or higher efficacy than catechin. Phenolic extracts from all fractions inhibited peroxyl radical-induced DNA strand breakage. These findings shed further light for future studies and industrial application of grape byproducts, which may focus not only on the soluble phenolics but also on the insoluble-bound fraction. PMID:25417599

  1. Sevelamer Does Not Decrease Lipopolysaccharide or Soluble CD14 Levels But Decreases Soluble Tissue Factor, Low-Density Lipoprotein (LDL) Cholesterol, and Oxidized LDL Cholesterol Levels in Individuals With Untreated HIV Infection

    PubMed Central

    Sandler, Netanya G.; Zhang, Xinyan; Bosch, Ronald J.; Funderburg, Nicholas T.; Choi, Andrew I.; Robinson, Janet K.; Fine, Derek M.; Coombs, Robert W.; Jacobson, Jeffrey M.; Landay, Alan L.; Douek, Daniel C.; Tressler, Randall; Read, Sarah W.; Wilson, Cara C.; Deeks, Steven G.; Lederman, Michael M.; Gandhi, Rajesh T.

    2014-01-01

    Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)–infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits. Clinical Trials Registration. NCT 01543958. PMID:24864123

  2. Application of saturation dye 2D-DIGE proteomics to characterize proteins modulated by oxidized low density lipoprotein treatment of human macrophages.

    PubMed

    Dupont, Annabelle; Chwastyniak, Maggy; Beseme, Olivia; Guihot, Anne-Laure; Drobecq, Hervé; Amouyel, Philippe; Pinet, Florence

    2008-08-01

    Macrophages are believed to play a crucial role in atherogenesis and atherosclerotic plaque progression, mainly through their role in the accumulation of large amounts of cholesteryl ester and foam cell formation after the uptake into the arterial intima of oxidized LDL (oxLDL) particles known to be proatherogenic. The aim of this study was to use a differential proteomic approach to identify the response of human monocyte-derived macrophages after treatment with oxLDL for 24 h. Mass spectrometry analysis (MALDI-TOF) of 2D-DIGE gels made it possible to identify 9 intracellular and 3 secreted proteins that were up-regulated, 11 intracellular and 1 secreted proteins that were down-regulated, and 2 secreted proteins that were induced. This methodological approach not only confirmed the differential expression levels of proteins known to be regulated by oxLDL in macrophages, such as catalase and pyruvate kinase, but also identified oxLDL modulation of other proteins for the first time, including heat shock proteins (HSP) and Actin cytoskeletal proteins. Semiquantitative Western blot confirmed their role. The HSPs identified included heat shock cognate 71 kDa protein (Hsc70), 75 kDa glucose-regulated protein (GRP75), heat shock 70 kDa protein (Hsp70), and 60 kDa (Hsp60) proteins. These highly conserved intracellular protein chaperones, commonly seen in atherosclerotic plaques, appear to participate in protection against cellular stress. Interestingly, oxLDL also modulated several F-Actin capping proteins involved in Actin polymerization and motility: gelsolin, CapG, and CapZ. In conclusion, we have demonstrated the effects of oxLDL in the modulation of several proteins in human macrophages and established a functional profile of the human macrophage during the atherosclerotic process. PMID:18549265

  3. Heat Shock Protein 70B′ (HSP70B′) Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages*

    PubMed Central

    Smith, Kent J.; Twal, Waleed O.; Soodavar, Farzan; Virella, Gabriel; Lopes-Virella, Maria F.; Hammad, Samar M.

    2010-01-01

    Heat shock proteins (HSPs) have been implicated in the activation and survival of macrophages. This study examined the role of HSP70B′, a poorly characterized member of the HSP70 family, in response to oxidatively modified LDL (oxLDL) and immune complexes prepared with human oxLDL and purified human antibodies to oxLDL (oxLDL-IC) in monocytic and macrophage cell lines. Immunoblot analysis of cell lysates and conditioned medium from U937 cells treated with oxLDL alone revealed an increase in intracellular HSP70B′ protein levels accompanied by a concomitant increase in HSP70B′ extracellular levels. Fluorescence immunohistochemistry and confocal microscopy, however, demonstrated that oxLDL-IC stimulated the release of HSP70B′, which co-localized with cell-associated oxLDL-IC. In HSP70B′-green fluorescent protein-transfected mouse RAW 264.7 cells, oxLDL-IC-induced HSP70B′ co-localized with membrane-associated oxLDL-IC as well as the lipid moiety of internalized oxLDL-IC. Furthermore, the data demonstrated that HSP70B′ is involved in cell survival, and this effect could be mediated by sphingosine kinase 1 (SK1) activation. An examination of regularly implicated cytokines revealed a significant relationship between HSP70B′ and the release of the anti-inflammatory cytokine interleukin-10 (IL-10). Small interfering RNA knockdown of HSP70B′ resulted in a corresponding decrease in SK1 mRNA levels and SK1 phosphorylation as well as increased release of IL-10. In conclusion, these findings suggest that oxLDL-IC induce the synthesis and release of HSP70B′, and once stimulated, HSP70B′ binds to the cell-associated and internalized lipid moiety of oxLDL-IC. The data also implicate HSP70B′ in key cellular functions, such as regulation of SK1 activity and release of IL-10, which influence macrophage activation and survival. PMID:20348092

  4. Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: Lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein

    SciTech Connect

    Freeman, M. Massachusetts General Hospital, Boston ); Ekkel, Y.; Rohrer, L.; Penman, M.; Freedman, N.J.; Krieger, M. ); Chisolm, G.M. )

    1991-06-01

    Type I and type II scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-associated functions, differ only by the presence in the type I receptor of an extracellular cysteine-rich C-terminal domain. Stable Chinese hamster ovary (CHO) cell transfectants expressing high levels of either the type I or type II bovine scavenger receptors have been generated. Type I and type II receptors in these cells mediated high-affinity saturable endocytosis of both {sup 125}I-labeled acetylated low density lipoprotein (LDL) and {sup 125}I-labeled oxidized LDL with the distinctive broad ligand specificity characteristic of scavenger receptors. After incubation for 2 days with acetylated LDL, the transfected cells accumulated oil red O-staining lipid droplets reminiscent of those in macrophage foam cells, whereas untransfected CHO cells did not. Thus, macrophage-specific gene products other than the scavenger receptor are not required for modified-LDL-induced intracellular lipid accumulation. In transfected cells, acetylated LDL efficiently competed for both its own endocytosis and that of oxidized LDL. This nonreciprocal cross competition suggests that these ligands may bind to nonidentical but interacting sites on a single receptor. Results were similar for transfectants expressing either type I or type II scavenger receptors. The nonreciprocal cross competition seen in the transfected CHO cells differs from that previously observed with cultured macrophages.

  5. The relationship between concentrations of magnesium and oxidized low-density lipoprotein and Beta2-microglobulin in the serum of patients on the end-stage of renal disease.

    PubMed

    Raikou, Vaia D; Kyriaki, Despina

    2016-05-01

    The end-stage of renal disease is associated with increased oxidative stress and oxidative modification of low-density lipoproteins (LDLs). Beta2 microglobulin (beta2M) is accumulated in the serum of dialysis patients. Magnesium (Mg) plays a protective role in the development of oxidative stress in healthy subjects. We studied the relationship between concentrations of magnesium and oxidized LDL (ox-LDL) and beta2M in the serum of patients on the end stage of renal disease. In 96 patients on on-line- predilution hemodiafiltration, beta2M and intact parathormone were measured by radioimmunoassays. High-sensitivity C-reactive protein (hsCRP) and ox-LDL were measured using ΕLISA. Serum bicarbonate levels were measured in the blood gas analyser gas machine. We performed logistic regression analysis models to investigate Mg as an important independent predictor of elevated ox-LDL and high beta2M serum concentrations, after adjustment to traditional and specific for dialysis patients' factors. We observed a positive correlation of Mg with ox-LDL (r = 0.383, P = 0.001), but the association of Mg with beta2M, hsCRP, and serum bicarbonate levels was significantly inverse (r = -0.252, P = 0.01, r = -0.292, P = 0.004, and r = -0.282, P = 0.04 respectively). The built logistic-regression analysis showed that Mg act as a significant independent factor for the elevated ox-LDL and beta2M serum concentrations adjusting to traditional and specific factors for these patients. We observed a positive relationship between magnesium and acidosis status- related ox-LDL concentrations, but the inverse association between magnesium and beta2M serum concentrations in hemodialysis patients. PMID:27215248

  6. Platycodon grandiflorum root attenuates vascular endothelial cell injury by oxidized low-density lipoprotein and prevents high-fat diet-induced dyslipidemia in mice by up-regulating antioxidant proteins.

    PubMed

    Chung, Mi Ja; Kim, Soo-Hyun; Park, Jeong-Won; Lee, Young Jin; Ham, Seung-Shi

    2012-05-01

    We hypothesized that a Platycodon grandiflorum root (PG) ethyl acetate extract (PGEA) would help reduce the vascular cell injury caused by oxidized low-density lipoprotein (oxLDL) and prevent high-fat (HF) diet-induced dyslipidemia and oxidative stress by up-regulating antioxidant proteins. We investigated the protective effects of PGEA against vascular endothelial cell injury induced by oxLDL and dyslipidemia induced by an HF diet, and the mechanisms underlying these effects were studied. The protective effects of PGEA were investigated with respect to calf pulmonary arterial endothelial (CPAE) cell viability and the lactate dehydrogenase release during oxLDL treatment. The in vivo effects of PGEA were examined using C57BL/6 mice, which were fed an HF diet for 9 weeks. The HF diet was supplemented with 0, 25, or 75 mg/kg PGEA during the last 4 weeks of the experimental period. Histologic analyses of hepatic lipid accumulation were performed. The changes in antioxidant protein levels induced by PGEA, which protects against HF diet-induced oxidative stress, were measured using a proteomics approach. We found that PGEA exhibited antioxidant activity. In CPAE cells, PGEA inhibited both oxLDL-induced cell death and lactate dehydrogenase release. In the HF diet-induced obese mice that received PGEA, we observed significantly reduced plasma and hepatic lipid levels, demonstrating that PGEA has beneficial effects on hyperlipidemia. In addition, we found that PGEA caused the up-regulation of antioxidant proteins. These findings suggest that the antioxidant effects of PGEA may protect against oxidative stress-related diseases. PMID:22652376

  7. The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68.

    PubMed Central

    Ramprasad, M P; Fischer, W; Witztum, J L; Sambrano, G R; Quehenberger, O; Steinberg, D

    1995-01-01

    We have previously reported the partial purification of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that binds oxidatively modified low density lipoprotein (OxLDL) and phosphatidylserine-rich liposomes. We have now identified that protein as macrosialin, a previously cloned macrophage-restricted membrane protein in the lysosomal-associated membrane protein family (mouse homologue of human CD68). Early in the course of purification of the 94- to 97-kDa protein, a new OxLDL-binding band at 190-200 kDa appeared and copurified with the 94- to 97-kDa protein. The HPLC pattern of tryptic peptides from this higher molecular mass ligand-binding band closely matched that derived from the 94- to 97-kDa band. Specifically, the same three macrosialin-derived tryptic peptides (9, 9, and 15 residues) were present in the purified 94- to 97-kDa band and in the 190- to 200-kDa band and antisera raised against peptide sequences in macrosialin recognized both bands. An antiserum against macrosialin precipitated most of the 94- to 97-kDa OxLDL-binding material. We conclude that the binding of OxLDL to mouse macrophage membranes is in part attributable to macrosialin. Our previous studies show that OxLDL competes with oxidized red blood cells and with apoptotic thymocytes for binding to mouse peritoneal macrophages. Whether macrosialin plays a role in recognition of OxLDL and oxidatively damaged cells by intact macrophages remains uncertain. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7568176

  8. Low-Density Lipoprotein Apheresis

    PubMed Central

    2007-01-01

    Executive Summary Objective To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). Background on Familial Hypercholesterolemia Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death. Familial hypercholesterolemia occurs in both HTZ and HMZ forms. Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals1. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario. In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death. In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL

  9. Method of synthesizing a low density material

    DOEpatents

    Lorensen, L.E.; Monaco, S.B.

    1987-02-27

    A novel method of synthesizing a polymeric material of low density of the order of 50mg/cc or less. Such a low density material has applications in many areas including laser target fabrication. The method comprises preparing a polymer blend of two incompatible polymers as a major and a minor phase by mixing them and extruding the mixture, and then selectively extracting the major component, to yield a fine, low density structure.

  10. Time-course studies by synchrotron X-ray solution scattering of the structure of human low-density lipoprotein during Cu(2+)-induced oxidation in relation to changes in lipid composition.

    PubMed

    Meyer, D F; Nealis, A S; Macphee, C H; Groot, P H; Suckling, K E; Bruckdorfer, K R; Perkins, S J

    1996-10-01

    Low-density lipoproteins (LDLs) in plasma are constructed from a single molecule of apolipoprotein B-100 (apoB) (M(r) 512,000) in association with lipid [approximate M(r) (2-3) x 10(6)]. LDL oxidation is an important process in the development of atherosclerosis, and can be imitated by the addition of Cu2+ ions. Synchrotron X-ray scattering of LDL yields curves without radiation damage effects at concentrations close to physiological. The radius of gyration RG for preparations of LDL from different donors ranged between 12.1 and 16.0 nm, with a mean of 13.9 nm. At 4 degrees C, the distance distribution curve P(r) indicated a maximum dimension of 25-27 nm for LDL, a peak at 19.5 nm which corresponds to a surface shell of protein and phospholipid head groups in LDL, and submaxima between 1.7 and 13.5 nm, which correspond to an ordered lipid core in LDL. LDL from different donors exhibited distinct P(r) curves. For oxidation studies of LDL by X-rays, data are best obtained at 4 degrees C at a concentration of > or = 2 mg of LDL protein/ml together with controls based on non-oxidized LDL. LDL oxidation (2 mg of apoB/ml) was studied at 37 degrees C in the presence of 6.4, 25.6 and 51.2 mu of Cu2+/g of apoB. Large changes in P(r) were reproducibly observed in the inter-particle distance range between 13 and 16 nm shortly after initiation of oxidation. This corresponds to the phospholipid hydrocarbon in LDL, which has either increased in electron density during oxidation or become increasingly disordered. After 25 h, the structural changes subsequently spread to regions of the P(r) curves assigned to surface apoB and the central core of cholesteryl esters and triacyl-glycerols. Lipid analyses were carried out under the same solution conditions. The alpha-tocopherol and beta-carotene antioxidant contents of LDL were consumed within 1-2 h. Analyses of the formation of thiobarbituric acid-reactive substances and lipid hydroperoxides indicated that arachidonic acid was

  11. A Phytochemical-rich Multivitamin-multimineral Supplement Is Bioavailable and Reduces Serum Oxidized Low-density Lipoprotein, Myeloperoxidase, and Plasminogen Activator Inhibitor-1 in a Four-week Pilot trial of Healthy Individuals

    PubMed Central

    Desai, Anuradha; Lamb, Joseph J.; Chang, Jyh-Lurn; Darland, Gary; Konda, Veera R.

    2014-01-01

    Background: A multivitamin-multimineral supplement combined with a diverse blend of bioactive phytochemicals may provide additional antioxidant capacity and anti-inflammatory property for overall health. This convenient feature may be useful for individuals who want to increase their intake of phytochemicals. Methods: We conducted a pilot study in 15 healthy individuals (8 women and 7 men, mean age 41.7±14.9 years, mean body mass index 28.0±5.6) to investigate the effects of this novel formulation on biomarkers associated with oxidative stress and inflammation. After a 2-week diet that limited intake of fruits and vegetables to 2 servings/day, participants continued with the same restricted diet but began consuming 2 tablets of the study product for the subsequent 4 weeks. Fasting blood samples collected at Week 2 and Week 6 were analyzed and compared using paired t-tests for levels of carotenoids, folate, vitamin B12, homocysteine, oxidized low-density lipoprotein cholesterol (oxLDL), high-sensitivity C-reactive protein (hs-CRP), F2-isoprostane, plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase. Noninvasive peripheral arterial tonometry (EndoPAT) was also measured. Results: After 4 weeks of supplementation, plasma levels of carotenoids, folate, and vitamin B12, but not homocysteine, were significantly increased (P<.05). Serum levels of oxLDL, PAI-1 and myeloperoxidase were significantly reduced (P<.05), but F2-isoprostane, hs-CRP, and EndoPAT measures were unchanged compared with baseline. The study product was well tolerated. Conclusions: This nutritional supplement is bioavailable as indicated by the significant increase in plasma carotenoids, vitamin B12, and folate levels and may provide health benefits by significantly reducing serum levels of oxLDL, myeloperoxidase, and PAI-1 in healthy individuals. PMID:24808980

  12. Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor κB (NF-κB) Pathway*

    PubMed Central

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X.; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-01-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation. PMID:24550391

  13. Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen: A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR)γ-DEPENDENT MECHANISM.

    PubMed

    Yu, Miao; Jiang, Meixiu; Chen, Yuanli; Zhang, Shuang; Zhang, Wenwen; Yang, Xiaoxiao; Li, Xiaoju; Li, Yan; Duan, Shengzhong; Han, Jihong; Duan, Yajun

    2016-08-12

    Macrophage CD36 binds and internalizes oxidized low density lipoprotein (oxLDL) to facilitate foam cell formation. CD36 expression is activated by peroxisome proliferator-activated receptor γ (PPARγ). Tamoxifen, an anti-breast cancer medicine, has demonstrated pleiotropic functions including cardioprotection with unfully elucidated mechanisms. In this study, we determined that treatment of ApoE-deficient mice with tamoxifen reduced atherosclerosis, which was associated with decreased CD36 and PPARγ expression in lesion areas. At the cellular level, we observed that tamoxifen inhibited CD36 protein expression in human THP-1 monocytes, THP-1/PMA macrophages, and human blood monocyte-derived macrophages. Associated with decreased CD36 protein expression, tamoxifen reduced cellular oxLDL accumulation in a CD36-dependent manner. At the transcriptional level, tamoxifen decreased CD36 mRNA expression, promoter activity, and the binding of the PPARγ response element in CD36 promoter to PPARγ protein. Tamoxifen blocked ligand-induced PPARγ nuclear translocation and CD36 expression, but it increased PPARγ phosphorylation, which was due to that tamoxifen-activated ERK1/2. Furthermore, deficiency of PPARγ expression in macrophages abolished the inhibitory effect of tamoxifen on CD36 expression or cellular oxLDL accumulation both in vitro and in vivo Taken together, our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARγ signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen. PMID:27358406

  14. Clinical association of baseline levels of conjugated dienes in low-density lipoprotein and nitric oxide with aggressive B-cell non-Hodgkin lymphoma and their relationship with immunoglobulins and Th1-to-Th2 ratio

    PubMed Central

    Haddouche, Mustapha; Meziane, Warda; Hadjidj, Zeyneb; Mesli, Naima; Aribi, Mourad

    2016-01-01

    Objective The aim of this study was to highlight the clinical association of baseline levels of conjugated dienes in low-density lipoprotein (LDL-BCD) and nitric oxide (NO) with immunoglobulins (Igs) and T helper (Th)1/Th2 ratio in patients with newly diagnosed B-cell non-Hodgkin lymphoma (NHL). Patients and methods Thirty-two newly diagnosed patients with aggressive B-cell NHL and 25 age-, sex-, and body-mass-index-matched healthy controls were randomly selected for a cross-sectional case–control study conducted at the Hematology Department of Tlemcen Medical Centre University (northwest of Algeria). Results Circulating levels of LDL-BCD and NO and those of IgA and IgM were significantly higher in patients than in controls. The levels of Th1/Th2 ratio and plasma total antioxidant capacity were significantly lower in patients compared with controls, while malondialdehyde and protein carbonyl levels were significantly higher in patients. B-cell NHL was significantly associated with high levels of LDL-BCD from 25th to 75th percentile (25th percentile: relative risk [RR] =2.26, 95% confidence interval [CI] 1.42–3.59, P=0.014; 50th percentile: RR =2.84, 95% CI 1.72–4.68, P<0.001; 75th percentile: RR =5.43, 95% CI 2.58–11.42, P<0.001). Similarly, the disease was significantly associated with high levels of NO production from 25th to 75th percentile (25th percentile: RR =2.07, 95% CI 1.25–3.44, P=0.024; 50th percentile: RR =2.78, 95% CI 1.63–4.72, P<0.001; 75th percentile: RR =4.68, 95% CI 2.21–9.91, P<0.001). Moreover, LDL-BCD levels were positively and significantly correlated with interferon (IFN)-γ, whereas NO levels were inversely and significantly correlated with IFN-γ and Th1/Th2 ratio. Conclusion LDL-BCD and NO production seem to be associated with aggressive B-cell NHL and alteration of Th1/Th2 ratio. Our results have to be examined using ex vivo mechanistic studies leading to further investigations of these parameters, with an interest in the

  15. Oxidized Lipoprotein as a Major Vessel Cell Proliferator in Oxidized Human Serum

    PubMed Central

    Noguchi, Noriko

    2016-01-01

    Oxidative stress is correlated with the incidence of several diseases such as atherosclerosis and cancer, and oxidized biomolecules have been determined as biomarkers of oxidative stress; however, the detailed molecular relationship between generated oxidation products and the promotion of diseases has not been fully elucidated. In the present study, to clarify the role of serum oxidation products in vessel cell proliferation, which is related to the incidence of atherosclerosis and cancer, the major vessel cell proliferator in oxidized human serum was investigated. Oxidized human serum was prepared by free radical exposure, separated using gel chromatography, and then each fraction was added to several kinds of vessel cells including endothelial cells and smooth muscle cells. It was found that a high molecular weight fraction in oxidized human serum specifically induced vessel cell proliferation. Oxidized lipids were contained in this high molecular weight fraction, while cell proliferation activity was not observed in oxidized lipoprotein-deficient serum. Oxidized low-density lipoproteins induced vessel cell proliferation in a concentration-dependent manner. Taken together, these results indicate that oxidized lipoproteins containing lipid oxidation products function as a major vessel cell proliferator in oxidized human serum. These findings strongly indicate the relevance of determination of oxidized lipoproteins and lipid oxidation products in the diagnosis of vessel cell proliferation-related diseases such as atherosclerosis and cancer. PMID:27483438

  16. Study of low density air transportation concepts

    NASA Technical Reports Server (NTRS)

    Webb, H. M.

    1972-01-01

    Low density air transport refers to air service to sparsely populated regions. There are two major objectives. The first is to examine those characteristics of sparsely populated areas which pertain to air transportation. This involves determination of geographical, commercial and population trends, as well as those traveler characteristics which affect the viability of air transport in the region. The second objective is to analyze the technical, economic and operational characteristics of low density air service. Two representative, but diverse arenas, West Virginia and Arizona, were selected for analysis: The results indicate that Arizona can support air service under certain assumptions whereas West Virginia cannot.

  17. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, R.W.

    1989-10-10

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer clusters. The covalent crosslinking of these clusters produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density [<=]100 mg/cc; cell size [<=]0.1 microns). The aerogels are transparent, dark red in color and consist of interconnected colloidal-like particles with diameters of about 100 [angstrom]. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron.

  18. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, Richard W.

    1991-01-01

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer "Clusters". The covalent crosslinking of these "clusters" produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density.ltoreq.100 mg/cc; cell size .ltoreq.0.1 microns). The aerogels are transparent, dark red in color and consist of interconnected colloidal-like particles with diameters of about 100.circle.. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron.

  19. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, R.W.

    1988-05-26

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer ''clusters''. The covalent crosslinking of these ''clusters'' produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density less than or equal to100 mg/cc; cell size less than or equal to0.1 microns). The aerogels are transparent,dark red in color and consist of interconnected colloidal-like particles with diameters of about 100 A/degree/. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron. 1 fig., 1 tab.

  20. Low density, resorcinol-formaldehyde aerogels

    DOEpatents

    Pekala, Richard W.

    1989-01-01

    The polycondensation of resorcinol with formaldehyde under alkaline conditions results in the formation of surface functionalized polymer "clusters". The covalent crosslinking of these "clusters" produces gels which when processed under supercritical conditions, produce low density, organic aerogels (density .ltoreq.100 mg/cc; cell size .ltoreq.0.1 microns). The aerogels are transparent, dark red in color and consist of interconnected colloidal-like particles with diameters of about 100 .ANG.. These aerogels may be further carbonized to form low density carbon foams with cell size of about 0.1 micron.

  1. Herbicide dissipation from low density polyethylene mulch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Field and laboratory studies were conducted to examine herbicide dissipation when applied to low density polyethylene (LDPE) mulch for dry scenarios vs. washing off with water. In field studies, halosulfuron, paraquat, carfentrazone, glyphosate, and flumioxazin were applied to black 1.25-mil LDPE at...

  2. Natural phenylpropanoids inhibit lipoprotein-induced endothelin-1 secretion by endothelial cells.

    PubMed

    Martin-Nizard, Françoise; Sahpaz, Sevser; Kandoussi, Abdelmejid; Carpentier, Marie; Fruchart, Jean-Charles; Duriez, Patrick; Bailleul, François

    2004-12-01

    There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL) might be involved in the pathogenesis of atherosclerosis and it has been reported that polyphenols inhibit LDL peroxidation and atherosclerosis. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide isolated from endothelial cells and it induces smooth muscle cell proliferation. ET-1 secretion is increased in atheroma and induces deleterious effects such as vasospasm and atherosclerosis. The goal of this study was to test the effect of four natural phenolic compounds against copper-oxidized LDL (Cu-LDL)-induced ET-1 liberation by bovine aortic endothelial cells (BAEC). The tested compounds were phenylpropanoid glycosides previously isolated from the aerial parts of Marrubium vulgare L. (acteoside 1, forsythoside B 2, arenarioside 3 and ballotetroside 4). ET-1 secretion increased when cells were incubated with Cu-LDL but the compounds 1-4 inhibited this increase. These results were confirmed by quantitative-polymerase chain reaction (QPCR) analysis. Since ET-1 plays an important role in atherosclerosis development, our work suggests that the tested phenylpropanoids could have a beneficial effect in inhibiting atherosclerosis development. PMID:15563769

  3. Ionization transition in low-density plasma

    SciTech Connect

    Triger, S. A.; Khomkin, A. L.; Shumikhin, A. S.

    2011-09-15

    Ionization equilibrium in low-density low-temperature plasma is considered. It is demonstrated using hydrogen and cesium as examples that the Saha equation predicts an almost jump-like change in the electron density on isochors in a narrow temperature range. Thus, in contrast to a smooth rise in the degree of ionization with increasing temperature at high plasma densities, an increase in the temperature in low-density plasma should result in a sharp transition from a neutral state to a fully ionized plasma. This transition is accompanied by a jump-like increase in the electric conductivity. The relation of these effects to the recombination transition in the model of the early Universe is discussed. The possibility of observing such a transition experimentally and the problems concerning the time of plasma relaxation into an equilibrium state at long free path lengths of plasma particles are considered.

  4. Fabrication of low density ceramic material

    DOEpatents

    Meek, T.T.; Blake, R.D.; Sheinberg, H.

    1985-01-01

    A precursor mixture and a method of making a low-density ceramic structural material are disclosed. The precursor mixture includes hollow microballoons, typically made of glass, together with a cementing agent capable of being cured by microwave irradiation. A preferred cementing agent is liquid hydrated potassium silicate, which is mixed with the glass microballoons to form a slurry. Upon irradiation the potassium silicate is dehydrated to form a solid porous matrix in which the microballoons are evenly distributed. Ground glass or other filling agents may be included in the slurry to enhance the properties of the final product. Low-density structural ceramics having densities on the order of 0.1 to 0.3 are obtained.

  5. Shock compression of low-density foams

    SciTech Connect

    Holmes, N.C.

    1993-07-01

    Shock compression of very low density micro-cellular materials allows entirely new regimes of hot fluid states to be investigated experimentally. Using a two-stage light-gas gun to generate strong shocks, temperatures of several eV are readily achieved at densities of roughly 0.5--1 g/cm{sup 3} in large, uniform volumes. The conditions in these hot, expanded fluids are readily found using the Hugoniot jump conditions. We will briefly describe the basic methodology for sample preparation and experimental measurement of shock velocities. We present data for several materials over a range of initial densities. This paper will explore the applications of these methods for investigations of equations of state and phase diagrams, spectroscopy, and plasma physics. Finally, we discus the need for future work on these and related low-density materials.

  6. A New Approach of Designing Superalloys for Low Density

    NASA Technical Reports Server (NTRS)

    MacKay, Rebecca A.; Gabb, Timothy P.; Smialek, James L.; Nathal, Michael V.

    2010-01-01

    New low-density single-crystal (LDS) alloy, have bee. developed for turbine blade applications, which have the potential for significant improvements in the thrust-to-weight ratio over current production superalloys. An innovative alloying strategy was wed to achieve alloy density reductions, high-temperature creep resistance, microstructural stability, and cyclic oxidation resistance. The alloy design relies on molybdenum as a potent. lower-density solid-solution strengthener in the nickel-based superalloy. Low alloy density was also achieved with modest rhenium levels tmd the absence of tungsten. Microstructural, physical mechanical, and environmental testing demonstrated the feasibility of this new LDS superalloy design.

  7. Low density, microcellular foams, preparation, and articles

    DOEpatents

    Young, Ainslie T.; Marsters, Robert G.; Moreno, Dawn K.

    1984-01-01

    A microcellular low density foam of poly(4-methyl-1-pentene) which is particularly useful for forming targets for inertial confinement fusion has been developed. Articles made from the foam have been machined to tolerances of 0.0001 inch, although the densities of the fragile foam are low (about 10 to about 100 mg/cc) and the cell sizes are small (about 10 to about 30 .mu.m). Methods for forming the foam and articles are given; and the yield strength of the foam of the invention is higher than was obtained in other structures of this same material.

  8. Relativistic Plasmas in Low Density Environments

    SciTech Connect

    Rudnick, Lawrence

    2009-12-18

    We have been developing techniques over the last several years to identify and study relativistic plasmas in low density environments. These relativistic plasmas may be the best or only available indicators of diffuse baryons in portions of the Warm-Hot Intergalactic Medium outside of rich galaxy clusters. Studying such faint radio synchrotron sources requires removal of confusion from both background radio galaxies and the foreground Milky Way. In these proceedings, we briefly summarize the techniques we are developing and some of our initial results. Our discoveries likely represent the ''tip of the iceberg'' to be exploited by the nascent generation of radio telescopes.

  9. Low density, microcellular foams, preparation, and articles

    DOEpatents

    Young, A.T.

    1982-03-03

    A microcellular low-density foam of poly(4-methyl-1-pentene) particularly useful for forming targets for inertial confinement fusion has been developed. Articles made from the foam have been machined to tolerances of 0.0001 inch, although the densities of the fragile foam are low (about 10 to about 100 mg/cc) and the cell sizes are small (about 10 to about 30 ..mu..m). Methods for forming the foam and articles are given. The yield strength of the foam of the invention is higher than was obtained in other structures of this same material.

  10. Sprayable low density ablator and application process

    NASA Technical Reports Server (NTRS)

    Sharpe, M. H.; Hill, W. E.; Simpson, W. G.; Carter, J. M.; Brown, E. L.; King, H. M.; Schuerer, P. H.; Webb, D. D. (Inventor)

    1978-01-01

    A sprayable, low density ablative composition is described consisting esentially of: (1) 100 parts by weight of a mixture of 25-65% by weight of phenolic microballoons, 0-20% by weight of glass microballoons, 4-10% by weight of glass fibers, 25-45% by weight of an epoxy-modified polyurethane resin, 2-4% by weight of a bentonite dispersing aid, and 1-2% by weight of an alcohol activator for the bentonite; (2) 1-10 parts by weight of an aromatic amine curing agent; and (3) 200-400 parts by weight of a solvent.

  11. Hydrogen crystallization in low-density aerogels.

    PubMed

    Kucheyev, S O; Van Cleve, E; Johnston, L T; Gammon, S A; Worsley, M A

    2015-04-01

    Crystallization of liquids confined in disordered low-density nanoporous scaffolds is poorly understood. Here, we use relaxation calorimetry to study the liquid-solid phase transition of H2 in a series of silica and carbon (nanotube- and graphene-based) aerogels with porosities ≳94%. Results show that freezing temperatures of H2 inside all the aerogels studied are depressed but do not follow predictions of the Gibbs-Thomson theory based on average pore diameters measured by conventional gas sorption techniques. Instead, we find that, for each material family investigated, the depression of average freezing temperatures scales linearly with the ratio of the internal surface area (measured by gas sorption) and the total pore volume derived from the density of aerogel monoliths. The slope of such linear dependences is, however, different for silica and carbon aerogels, which we attribute to microporosity of carbons and the presence of macropores in silica aerogels. Our results have important implications for the analysis of pore size distributions of low-density nanoporous materials and for controlling crystallization of fuel layers in targets for thermonuclear fusion energy applications. PMID:25781182

  12. Low Density Supersonic Decelerator Parachute Decelerator System

    NASA Technical Reports Server (NTRS)

    Gallon, John C.; Clark, Ian G.; Rivellini, Tommaso P.; Adams, Douglas S.; Witkowski, Allen

    2013-01-01

    The Low Density Supersonic Decelerator Project has undertaken the task of developing and testing a large supersonic ringsail parachute. The parachute under development is intended to provide mission planners more options for parachutes larger than the Mars Science Laboratory's 21.5m parachute. During its development, this new parachute will be taken through a series of tests in order to bring the parachute to a TRL-6 readiness level and make the technology available for future Mars missions. This effort is primarily focused on two tests, a subsonic structural verification test done at sea level atmospheric conditions and a supersonic flight behind a blunt body in low-density atmospheric conditions. The preferred method of deploying a parachute behind a decelerating blunt body robotic spacecraft in a supersonic flow-field is via mortar deployment. Due to the configuration constraints in the design of the test vehicle used in the supersonic testing it is not possible to perform a mortar deployment. As a result of this limitation an alternative deployment process using a ballute as a pilot is being developed. The intent in this alternate approach is to preserve the requisite features of a mortar deployment during canopy extraction in a supersonic flow. Doing so will allow future Mars missions to either choose to mortar deploy or pilot deploy the parachute that is being developed.

  13. Low Density Expansion for Lyapunov Exponents

    NASA Astrophysics Data System (ADS)

    Schulz-Baldes, Hermann

    A perturbative formula for the Lyapunov exponent of a one-dimensional random medium for weakly coupled disorder was first given by Thouless [12] and then proven rigorously by Pastur and Figotin [9]. Anomalies in the perturbation theory at the band center were discovered by Kappus and Wegner [7] and further discussed by various other authors [2,3,11]. The Lyapunov exponent is then identified with the inverse localization length of the system. This short note concerns the behavior of the Lyapunov exponent for a low density of impurities, each of which may, however, be large. The presented method is as [6,10,11] a further application of diagonalizing the transfer matrices without perturbation (here the low density of impurities) and then rigorously controlling the error terms by means of oscillatory sums of rotating modi- fied Prüfer phases. Some of the oscillatory sums remain large if the rotation phases (here the quasi-momenta) are rational. This leads to supplementary contributions of the Kappus-Wegner type.

  14. Ideal magnetohydrodynamic interchanges in low density plasmas

    SciTech Connect

    Huang Yimin; Goel, Deepak; Hassam, A.B.

    2005-03-01

    The ideal magnetohydrodynamic equations are usually derived under the assumption V{sub A}<low density plasmas wherein V{sub A} can be comparable to or greater than c. This involves relaxation of the usual charge quasineutrality assumption and the inclusion of electromagnetic momentum on par with plasma momentum. The extended system is applied to interchange instabilities in 'line-tied' slab geometry as well as to centrifugally confined plasmas. It is found that interchange growth rates are reduced by a factor of 1+V{sub A}{sup 2}/c{sup 2}, corresponding to a larger effective mass resulting from the extra electromagnetic momentum. Line tying is unaffected.

  15. Low-density lipoprotein apheresis: an overview.

    PubMed

    Bambauer, Rolf; Schiel, Ralf; Latza, Reinhard

    2003-08-01

    Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement

  16. Kepler-79's low density planets

    SciTech Connect

    Jontof-Hutter, Daniel; Lissauer, Jack J.; Rowe, Jason F.; Fabrycky, Daniel C.

    2014-04-10

    Kepler-79 (KOI-152) has four planetary candidates ranging in size from 3.5 to 7 times the size of the Earth, in a compact configuration with orbital periods near a 1:2:4:6 chain of commensurability, from 13.5 to 81.1 days. All four planets exhibit transit timing variations with periods that are consistent with the distance of each planet to resonance with its neighbors. We perform a dynamical analysis of the system based on transit timing measurements over 1282 days of Kepler photometry. Stellar parameters are obtained using a combination of spectral classification and the stellar density constraints provided by light curve analysis and orbital eccentricity solutions from our dynamical study. Our models provide tight bounds on the masses of all four transiting bodies, demonstrating that they are planets and that they orbit the same star. All four of Kepler-79's transiting planets have low densities given their sizes, which is consistent with other studies of compact multiplanet transiting systems. The largest of the four, Kepler-79 d (KOI-152.01), has the lowest bulk density yet determined among sub-Saturn mass planets.

  17. Low density gas dynamic wall boundary conditions

    NASA Technical Reports Server (NTRS)

    Collins, F. G.

    1986-01-01

    Low density nozzles or large expansion ratio nozzles used in space experience rarefaction effects near their exit in the form of velocity slip and temperature jump at the walls. In addition, the boundary layers become very thick and there is a very strong viscous/inviscid interaction. For these reasons no existing design technique has been found to accurately predict the nozzle flow properties up to the nozzle exit. The objective of this investigation was to examine the slip boundary conditions and formulate them in a form appropriate for use with a full Navier-Stokes numerical code. The viscous/inviscid interaction would automatically be accounted for by using a compressible Navier-Stokes code. Through examination of the interaction of molecules with solid surfaces, a model for the distribution function of the reflected molecules has been determined and this distribution function has been used to develop a new slip boundary condition that can be shown to yield more realistic surface boundary conditions.

  18. Radiance Measurement for Low Density Mars Entry

    NASA Technical Reports Server (NTRS)

    Cruden, Brett A.

    2012-01-01

    We report measurements of radiance behind a shock wave in Martian simulant (96% CO2, 4% N2) atmosphere at conditions relevant for aerodynamic decelerators. Shock waves are generated in the NASA Ames Electric Arc Shock Tube (EAST) facility at velocities from 6-8 km/s and freestream densities from 1.2-5.9 x 10(exp -4) kilograms per cubic meter (0.05-0.25 Torr, corresponding to 35-50 km altitude). Absolute radiance is measured as a function of wavelength and position in the shock. Radiance measurements extend from the vacuum ultraviolet to near infrared (120-1650 nm). As at higher density/velocity, radiation is dominate by CO 4th positive radiation in the vacuum ultraviolet, though CN contribution is also significant. At most low density conditions, the shock does not relax to equilibrium over several centimeters. A small number of measurements in the mid-infrared were performed to quantify radiation from the fundamental vibrational transition in CO, and this is found to be a minor contributor to the overall radiance at these speeds. Efforts to extend test time and reliability in the 60 cm (24) shock tube will be discussed in the full paper.

  19. Systems evaluation of low density air transportation concepts

    NASA Technical Reports Server (NTRS)

    Bruce, R. W.; Webb, H. M.

    1972-01-01

    Methods were studied for improving air transportation to low-density population regions in the U.S. through the application of new aeronautical technology. The low-density air service concepts are developed for selected regions, and critical technologies that presently limit the effective application of low-density air transportation systems are identified.

  20. Native low density lipoprotein promotes lipid raft formation in macrophages

    PubMed Central

    SONG, JIAN; PING, LING-YAN; DUONG, DUC M.; GAO, XIAO-YAN; HE, CHUN-YAN; WEI, LEI; WU, JUN-ZHU

    2016-01-01

    Oxidized low-density lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cell-mediated LDL oxidation remain to be elucidated. The present study investigated whether native-LDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methyl-β-cyclodextrin (MβCD), LDL-stimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MβCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to label-free quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following native-LDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that native-LDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation. PMID:26781977

  1. Study on ternary low density polyethylene/linear low density polyethylene/thermoplastic starch blend films.

    PubMed

    Sabetzadeh, Maryam; Bagheri, Rouhollah; Masoomi, Mahmood

    2015-03-30

    In this work, low-density polyethylene/linear low-density polyethylene/thermoplastic starch (LDPE/LLDPE/TPS) films are prepared with the aim of obtaining environmentally friendly materials containing high TPS content with required packaging properties. Blending of LDPE/LLDPE (70/30 wt/wt) with 5-20 wt% of TPS and 3 wt% of PE-grafted maleic anhydride (PE-g-MA) is performed in a twin-screw extruder, followed by the blowing process. Differential scanning calorimetric results indicate starch has more pronounced effect on crystallization of LLDPE than LDPE. Scanning electron micrograph shows a fairly good dispersion of TPS in PE matrices. Fourier transfer infrared spectra confirm compatibility between polymers using PE-g-MA as the compatibilizer. Storage modulus, loss modulus and complex viscosity increase with incorporation of starch. Tensile strength and elongation-at-break decrease from 18 to 10.5 MPa and 340 to 200%, respectively when TPS increases from 5 to 20%. However, the required mechanical properties for packaging applications are attained when 15 wt% starch is added, as specified in ASTM D4635. Finally 12% increase in water uptake is achieved with inclusion of 15 wt% starch. PMID:25563952

  2. Recycling of vitamin E in human low density lipoproteins.

    PubMed

    Kagan, V E; Serbinova, E A; Forte, T; Scita, G; Packer, L

    1992-03-01

    Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptor-dependent uptake is believed to account for cholesterol deposition in macrophage-derived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be achieved by reducing its chromanoxyl radicals, i.e., by vitamin E recycling. In this study we demonstrate that: i) chromanoxyl radicals of endogenous vitamin E and of exogenously added alpha-tocotrienol, alpha-tocopherol or its synthetic homologue with a 6-carbon side-chain, chromanol-alpha-C6, can be directly generated in human LDL by ultraviolet (UV) light, or by interaction with peroxyl radicals produced either by an enzymic oxidation system (lipoxygenase + linolenic acid) or by an azo-initiator, 2,2'-azo-bis(2,4-dimethylvaleronitrile) (AMVN; ii) ascorbate can recycle endogenous vitamin E and exogenously added chromanols by direct reduction of chromanoxyl radicals in LDL; iii) dihydrolipoic acid is not efficient in direct reduction of chromanoxyl radicals but recycles vitamin E by synergistically interacting with ascorbate (reduces dehydroascorbate thus maintaining the steady-state concentration of ascorbate); and iv) beta-carotene is not active in vitamin E recycling but may itself be protected against oxidative destruction by the reductants of chromanoxyl radicals. We suggest that the recycling of vitamin E and other phenolic antioxidants by plasma reductants may be an important mechanism for the enhanced antioxidant protection of LDL. PMID:1314881

  3. Low-density microfilaraemia in subperiodic bancroftian filariasis in Samoa*

    PubMed Central

    Kimura, E.; Penaia, L.; Samarawickrema, W. A.; Spears, G. F. S.

    1985-01-01

    Among microfilaria (mf) carriers of subperiodic bancroftian filariasis in Samoa, the low-density level of microfilaraemia was defined as 1-20 mf/ml, and the occurrence of low-density carriers (90 in the present study) was analysed by age, sex, and village in relation to the microfilarial prevalence rate. The low-density carriers were more numerous among those under 20 years and over 60 years old than in other age groups. The ratio of low-density carriers to the total of mf-positive subjects in a village decreased as the prevalence rate of Wuchereria bancrofti in the village increased. The epidemiological significance of low-density carriers was assessed in connection with the infectivity of vector mosquitos (Aedes polynesiensis) produced by them, the possible change of these carriers to carriers of a higher density, and the production of new low-density carriers by diethylcarbamazine citrate (DEC-C) treatment. The mosquito infectivity produced by the low-density carriers accounted for only 2.16% of the total infectivity produced by all the carriers, suggesting that these carriers are of minor importance in the transmission of filariasis. The change of microfilarial count over time among untreated mf-positive subjects was not remarkable during a 60-252-day observation period. However, the low-density carrier group showed a mean increase of 36%, the younger such carriers (under 30 years old) showing a 132% increase. The production of low-density carriers by DEC-C single-dose treatment (6 mg/kg body weight) was not as great as expected. PMID:3914924

  4. Modern trends in low-density materials for fusion

    NASA Astrophysics Data System (ADS)

    Orekhov, A. S.; Akunets, A. A.; Borisenko, L. A.; Gromov, A. I.; Merkuliev, Yu. A.; Pimenov, V. G.; Sheveleva, E. E.; Vasiliev, V. G.; Borisenko, N. G.

    2016-03-01

    Low-density targets continue to yield new experimental data and to put new unsolved questions for driver-plasma experiments. The experiments with such targets are presented in the paper by “Low-density targets that worked in direct and indirect experiments with laser and particle beams” by L.A. Borisenko et. al. ibid. Here we concentrate on nano structured and aerogel targets’ fabrication and characterization. These configurations establish certain standards for contemporary shot experiments.

  5. Lipid composition of circulating multiple-modified low density lipoprotein.

    PubMed

    Zakiev, E R; Sukhorukov, V N; Melnichenko, A A; Sobenin, I A; Ivanova, E A; Orekhov, A N

    2016-01-01

    Atherogenic modified low- density lipoprotein (LDL) induces pronounced accumulation of cholesterol and lipids in the arterial wall, while native LDL seems to lack such capability. Therefore, modified LDL appears to be a major causative agent in the pathogenesis of atherosclerosis. Possible modifications of LDL particles include changes in size and density, desialylation, oxidation and acquisition of negative charge. Total LDL isolated from pooled plasma of patients with coronary atherosclerosis, as well as from healthy subjects contains two distinct subfractions: normally sialylated LDL and desialylated LDL, which can be isolated by binding to a lectin affinity column. We called the desialylated LDL subfraction circulating modified LDL (cmLDL). In this study, we focused on lipid composition of LDL particles, analysing the total LDL preparation and two LDL subfractions: cmLDL and native LDL. The composition of LDL was studied using thin-layer chromatography. We found that cmLDL subfraction had decreased levels of free and esterified cholesterol, triglycerides, phospholipids (except for lysophosphatidylcholine) and sphingomyelin in comparison to native LDL. On the other hand, levels of mono-, and diglycerides, lysophosphatidylcholine and free fatty acids were higher in cmLDL than in native LDL. Our study demonstrated that lipid composition of cmLDL from atherosclerotic patients was altered in comparison to healthy subjects. In particular, phospholipid content was decreased, and free fatty acids levels were increased in cmLDL. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression. PMID:27558696

  6. Thermal stability of human plasma electronegative low-density lipoprotein: A paradoxical behavior of low-density lipoprotein aggregation.

    PubMed

    Rull, Anna; Jayaraman, Shobini; Gantz, Donald L; Rivas-Urbina, Andrea; Pérez-Cuellar, Montserrat; Ordóñez-Llanos, Jordi; Sánchez-Quesada, Jose Luis; Gursky, Olga

    2016-09-01

    Low-density lipoprotein (LDL) aggregation is central in triggering atherogenesis. A minor fraction of electronegative plasma LDL, termed LDL(-), plays a special role in atherogenesis. To better understand this role, we analyzed the kinetics of aggregation, fusion and disintegration of human LDL and its fractions, LDL(+) and LDL(-). Thermal denaturation of LDL was monitored by spectroscopy and electron microscopy. Initially, LDL(-) aggregated and fused faster than LDL(+), but later the order reversed. Most LDL(+) disintegrated and precipitated upon prolonged heating. In contrast, LDL(-) partially retained lipoprotein morphology and formed soluble aggregates. Biochemical analysis of all fractions showed no significant degradation of major lipids, mild phospholipid oxidation, and an increase in non-esterified fatty acid (NEFA) upon thermal denaturation. The main baseline difference between LDL subfractions was higher content of NEFA in LDL(-). Since NEFA promote lipoprotein fusion, increased NEFA content can explain rapid initial aggregation and fusion of LDL(-) but not its resistance to extensive disintegration. Partial hydrolysis of apoB upon heating was similar in LDL subfractions, suggesting that minor proteins importantly modulate LDL disintegration. Unlike LDL(+), LDL(-) contains small amounts of apoA-I and apoJ. Addition of exogenous apoA-I to LDL(+) hampered lipoprotein aggregation, fusion and precipitation, while depletion of endogenous apoJ had an opposite effect. Therefore, the initial rapid aggregation of LDL(-) is apparently counterbalanced by the stabilizing effects of minor proteins such as apoA-I and apoJ. These results help identify key determinants for LDL aggregation, fusion and coalescence into lipid droplets in vivo. PMID:27233433

  7. Alloy Design Challenge: Development of Low Density Superalloys for Turbine Blade Applications

    NASA Technical Reports Server (NTRS)

    MacKay, Rebecca A.; Gabb, Timothy P.; Smialek, James L.; Nathal, Michael V.

    2009-01-01

    New low density single crystal (LDS) alloys have been developed for turbine blade applications, which have the potential for significant improvements in the thrust to weight ratio over current production alloys. An innovative alloying strategy was identified to achieve high temperature creep resistance, alloy density reductions, microstructural stability, and cyclic oxidation resistance. The approach relies on the use of molybdenum (Mo) as a potent solid solution strengthener for the nickel (Ni)-base superalloy; Mo has a density much closer to Ni than other refractory elements, such as rhenium (Re) or tungsten (W). A host of testing and microstructural examinations was conducted on the superalloy single crystals, including creep rupture testing, microstructural stability, cyclic oxidation, and hot corrosion. The paper will provide an overview of the single crystal properties that were generated in this new superalloy design space. The paper will also demonstrate the feasibility of this innovative approach of low density single crystal superalloy design. It will be shown that the best LDS alloy possesses the best attributes of three generations of single crystal alloys: the low density of first-generation single crystal alloys, the excellent oxidation resistance of second-generation single crystal alloys, and a creep strength which exceeds that of second and third generation alloys.

  8. Numerical Simulation of Low-Density Shock-Wave Interactions

    NASA Technical Reports Server (NTRS)

    Glass, Christopher E.

    1999-01-01

    Computational Fluid Dynamics (CFD) numerical simulations of low-density shock-wave interactions for an incident shock impinging on a cylinder have been performed. Flow-field density gradient and surface pressure and heating define the type of interference pattern and corresponding perturbations. The maximum pressure and heat transfer level and location for various interaction types (i.e., shock-wave incidence with respect to the cylinder) are presented. A time-accurate solution of the Type IV interference is employed to demonstrate the establishment and the steadiness of the low-density flow interaction.

  9. Low density microcellular carbon foams and method of preparation

    DOEpatents

    Arnold, C. Jr.; Aubert, J.H.; Clough, R.L.; Rand, P.B.; Sylwester, A.P.

    1988-06-20

    A low density, open-celled microcellular carbon foam is disclosed which is prepared by dissolving a carbonizable polymer or copolymer in a solvent, pouring the solution into a mold, cooling the solution, removing the solvent, and then carbonizing the polymer or copolymer in a high temperature oven to produce the foam. If desired, an additive can be introduced in order to produce a doped carbon foam, and the foams can be made isotropic by selection of a suitable solvent. The low density, microcellular foams produced by this process are particularly useful in the fabrication of inertial confinement fusion targets, but can also be used as catalysts, absorbents, and electrodes.

  10. Aircraft Configured for Flight in an Atmosphere Having Low Density

    NASA Technical Reports Server (NTRS)

    Croom, Mark A. (Inventor); Smith, Stephen C. (Inventor); Gelhausen, Paul A. (Inventor); Guynn, Mark D. (Inventor); Hunter, Craig A. (Inventor); Paddock, David A. (Inventor); Riddick, Steven E. (Inventor); Teter, Jr., John E. (Inventor)

    2012-01-01

    An aircraft is configured for flight in an atmosphere having a low density. The aircraft includes a fuselage, a pair of wings, and a rear stabilizer. The pair of wings extends from the fuselage in opposition to one another. The rear stabilizer extends from the fuselage in spaced relationship to the pair of wings. The fuselage, the wings, and the rear stabilizer each present an upper surface opposing a lower surface. The upper and lower surfaces have X, Y, and Z coordinates that are configured for flight in an atmosphere having low density.

  11. Low density microcellular carbon foams and method of preparation

    DOEpatents

    Arnold, Jr., Charles; Aubert, James H.; Clough, Roger L.; Rand, Peter B.; Sylwester, Alan P.

    1989-01-01

    A low density, open-celled microcellular carbon foam is disclosed which is prepared by dissolving a carbonizable polymer or copolymer in a solvent, pouring the solution into a mold, cooling the solution, removing the solvent, and then carbonizing the polymer or copolymer in a high temperature oven to produce the foam. If desired, an additive can be introduced in order to produce a doped carbon foam, and the foams can be made isotropic by selection of a suitable solvent. The low density, microcellular foams produced by this process are particularly useful in the fabrication of inertial confinement fusion targets, but can also be used as catalysts, absorbents, and electrodes.

  12. Dynamics and diffusion mechanism of low-density liquid silicon

    SciTech Connect

    Shen, B.; Wang, Z. Y.; Dong, F.; Guo, Y. R.; Zhang, R. J.; Zheng, Y. X.; Wang, S. Y.; Wang, C. Z.; Ho, K. M.; Chen, L. Y.

    2015-11-05

    A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid–liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using the classical Stillinger–Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Here, our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid–liquid phase transition such as carbon and germanium.

  13. Plasma probe characteristics in low density hydrogen pulsed plasmas

    NASA Astrophysics Data System (ADS)

    Astakhov, D. I.; Goedheer, W. J.; Lee, C. J.; Ivanov, V. V.; Krivtsun, V. M.; Zotovich, A. I.; Zyryanov, S. M.; Lopaev, D. V.; Bijkerk, F.

    2015-10-01

    Probe theories are only applicable in the regime where the probe’s perturbation of the plasma can be neglected. However, it is not always possible to know, a priori, that a particular probe theory can be successfully applied, especially in low density plasmas. This is especially difficult in the case of transient, low density plasmas. Here, we applied probe diagnostics in combination with a 2D particle-in-cell model, to an experiment with a pulsed low density hydrogen plasma. The calculations took into account the full chamber geometry, including the plasma probe as an electrode in the chamber. It was found that the simulations reproduce the time evolution of the probe IV characteristics with good accuracy. The disagreement between the simulated and probe measured plasma density is attributed to the limited applicability of probe theory to measurements of low density pulsed plasmas on a similarly short time scale as investigated here. Indeed, in the case studied here, probe measurements would lead to, either a large overestimate, or underestimate of the plasma density, depending on the chosen probe theory. In contrast, the simulations of the plasma evolution and the probe characteristics do not suffer from such strict applicability limits. These studies show that probe theory cannot be justified through probe measurements. However, limiting cases of probe theories can be used to estimate upper and lower bounds on plasma densities. These theories include and neglect orbital motion, respectively, with different collisional terms leading to intermediate estimates.

  14. Graphical Quantum Low-Density Parity-Check Codes

    NASA Astrophysics Data System (ADS)

    Li, Yuan; Xu, Mantao; Meng, Yinkuo; Guo, Ying

    2012-08-01

    Graphical approach provides a direct way to construct error correction codes. Motivated by its good properties, associating low-density parity-check (LDPC) codes, in this paper we present families of graphical quantum LDPC codes which contain no girth of four. Because of the fast algorithm of constructing for graphical codes, the proposed quantum codes have lower encoding complexity.

  15. Effective thermal conductivity determination for low-density insulating materials

    NASA Technical Reports Server (NTRS)

    Williams, S. D.; Curry, D. M.

    1978-01-01

    That nonlinear least squares can be used to determine effective thermal conductivity was demonstrated, and a method for assessing the relative error associated with these predicted values was provided. The differences between dynamic and static determination of effective thermal conductivity of low-density materials that transfer heat by a combination of conduction, convection, and radiation were discussed.

  16. Low-density microarray technologies for rapid human norovirus genotyping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human noroviruses cause up to 21 million cases of foodborne disease in the United States annually and are the most common cause of acute gastroenteritis in industrialized countries. To reduce the burden of foodborne disease associated with viruses, the use of low density DNA microarrays in conjuncti...

  17. Dynamics and diffusion mechanism of low-density liquid silicon

    DOE PAGESBeta

    Shen, B.; Wang, Z. Y.; Dong, F.; Guo, Y. R.; Zhang, R. J.; Zheng, Y. X.; Wang, S. Y.; Wang, C. Z.; Ho, K. M.; Chen, L. Y.

    2015-11-05

    A first-order phase transition from a high-density liquid to a low-density liquid has been proposed to explain the various thermodynamic anomies of water. It also has been proposed that such liquid–liquid phase transition would exist in supercooled silicon. Computer simulation studies show that, across the transition, the diffusivity drops roughly 2 orders of magnitude, and the structures exhibit considerable tetrahedral ordering. The resulting phase is a highly viscous, low-density liquid silicon. Investigations on the atomic diffusion of such a novel form of liquid silicon are of high interest. Here we report such diffusion results from molecular dynamics simulations using themore » classical Stillinger–Weber (SW) potential of silicon. We show that the atomic diffusion of the low-density liquid is highly correlated with local tetrahedral geometries. We also show that atoms diffuse through hopping processes within short ranges, which gradually accumulate to an overall random motion for long ranges as in normal liquids. There is a close relationship between dynamical heterogeneity and hopping process. We point out that the above diffusion mechanism is closely related to the strong directional bonding nature of the distorted tetrahedral network. Here, our work offers new insights into the complex behavior of the highly viscous low density liquid silicon, suggesting similar diffusion behaviors in other tetrahedral coordinated liquids that exhibit liquid–liquid phase transition such as carbon and germanium.« less

  18. Herbicide dissipation from low density polyethylene mulch utilizing analytical techniques

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Georgia, most of the low density polyethylene mulch (LDPM) is laid for spring vegetable production followed by a second crop in the autumn, with a potential third crop the following spring. Between these vegetable plantings, farmers often use contact and residual herbicides to control weeds that ...

  19. In-situ probing of Low Density Porous Materials

    NASA Astrophysics Data System (ADS)

    Hawreliak, James

    2013-06-01

    The shock response of porous materials is of interest in High Energy Density Physics because the PdV heating from void closure allows off principle Hugoniot states for modeling many astrophysical processes. While continuum models exists of shockwave propagation in foams the relevant physical phenomena spans three different length scales: the micro-length scale defined by the pore size and length between solid structures in the foam (10 to 1000 nm), the shock front thickness which determines material and energy flow (0.1 to 100 nm), and the hydrodynamic length scale associated with the expanding spherical wave (>10 μm), all of which impact the shock response of the low density foam. With the advent of new HED experimental facilities for generating shockwaves at x-ray light sources this gives new tools for performing pump probe experiments to understand the microstructural response of low density materials. Currently, we have used x-ray radiograph to make Hugoniot EOS measurements the of shock compressed low density SiO2 and Carbon based foams. We will show recent result of measurements of experiments conducted on the Omega laser facility and discuss imaging shockwaves in low density foams on the soon to be commissioned DCS end station at APS and the MEC end station at LCLS. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  20. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  1. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  2. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  3. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  4. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system....5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein...

  5. The antigenic similarity of human low density lipoproteins.

    PubMed

    LEVINE, L; KAUFFMAN, D L; BROWN, R K

    1955-08-01

    THE FOLLOWING HUMAN LOW DENSITY LIPOPROTEINS WERE PREPARED: beta-lipoproteins of densities greater than 1.040 (A, B,C) a beta-lipoprotein of -S(1.063) = 5 (D), a lipoprotein of -S(1.063) = 19 (E), and a lipoprotein of -S(1.063) = 70 (F). Data are presented which show the immunochemical homogeneity of the D lipoprotein rabbit-anti-D lipoprotein system. Cross-reactions between antibody to A and D lipoproteins and the above lipoproteins have been demonstrated by quantitative precipitation, quanitative complement fixation, and single and double diffusion in agar. The antigenic similarities appear to be associated with the protein portions of the molecule. The antisera produced did not differentiate the low density lipoprotein classes. PMID:13242737

  6. Low-density microcellular foam and method of making same

    DOEpatents

    Rinde, James A.

    1977-01-01

    Low-density microcellular foam having a cell size of not greater than 2 .mu.m and method of making by dissolving cellulose acetate in an acetone-based solvent, gelling the solution in a water bath maintained at 0.degree.-10.degree. C for a selected period of time to allow impurities to diffuse out, freezing the gel, and then freeze-drying wherein water and solvents sublime and the gel structure solidifies into low-density microcellular foam. The foam has a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3 and cell size of about 0.3 to 2 .mu.m. The small cell size foam is particularly applicable for encapsulation of laser targets.

  7. Method of making a cellulose acetate low density microcellular foam

    DOEpatents

    Rinde, James A.

    1978-01-01

    Low-density microcellular foam having a cell size of not greater than 2 .mu.m and method of making by dissolving cellulose acetate in an acetone-based solvent, gelling the solution in a water bath maintained at 0-10.degree. C for a selected period of time to allow impurities to diffuse out, freezing the gel, and then freeze-drying wherein water and solvents sublime and the gel structure solidifies into low-density microcellular foam. The foam has a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3 and cell size of about 0.3 to 2 .mu.m. The small cell size foam is particularly adaptable for encapsulation of laser targets.

  8. A low-density boundary-layer wind tunnel facility

    NASA Technical Reports Server (NTRS)

    White, B. R.

    1987-01-01

    This abstract describes a low-density wind-tunnel facility that was established at NASA Ames in order to aid interpretation and understanding of data received from the Mariner and Viking spacecraft through earth-based simulation. The wind tunnel is a boundary-layer type which is capable of operating over a range of air densities ranging from 0.01 to 1.24 kg/cu m, with the lower values being equivalent to the near-surface density of the planet Mars. Although the facility was developed for space and extraterrestrial simulation, it also can serve as a relatively large-scale, low-density aerodynamic test facility. A description of this unique test facility and some Pitot-tube and hot-wire anemometry data acquired in the facility are presented.

  9. Characteristics of the low density corneal endothelial monolayer.

    PubMed

    Singh, Jorawer S; Haroldson, Thomas A; Patel, Sangita P

    2013-10-01

    Corneal endothelial cells form a leaky barrier on the posterior surface of the cornea, allowing influx of nutrient-carrying aqueous humor through the paracellular space and efflux of excess fluid. Corneal edema arises when the density of these non-proliferative endothelial cells declines from endothelial disease or intraocular surgery. The cellular changes occurring at low densities are ill-defined. We therefore investigated the paracellular pathway of corneal endothelial cell monolayers of varying density to determine alterations occurring in paracellular permeability and monolayer morphology. Primary cultures of bovine corneal endothelial cells (BCECs) were passaged onto permeable supports under varying culture conditions to obtain confluent monolayers of <1000, 1000-1999 and >2000 cells/mm(2). Culture growth was monitored by transendothelial electrical resistance measurements. Diffusional permeability to sodium fluorescein, FITC-dextran MW 4000 or FITC-dextran MW 20,000 was measured. Confluent cultures were also analyzed by immunofluorescence localization of the tight junction protein ZO-1 and by transmission electron microscopy. For comparison, we evaluated ZO-1 for low and high density human corneal endothelium. Our results showed that all BCEC cultures grew to the same final transendothelial electrical resistance regardless of final density. In the diffusional permeability assay, permeability increased significantly only for the smallest tracer molecule (sodium fluorescein) in the lowest density monolayers (<1000 cells/mm(2)). ZO-1 immunofluorescence distinctly localized to intercellular junctions in high density BCEC cultures but had more diffuse localization at lower densities. Transmission electron microscopy imaging revealed cells with thinner cross-sectional profiles and longer overlapping intercellular processes at low density relative to high density cultures. Low density human corneal endothelium lacked the diffuse ZO-1 distribution seen in BCECs

  10. Silylation of low-density silica and bridged polysilsesquioxane aerogels

    SciTech Connect

    DeFriend, K. A.; Loy, D. A.; Salazar, K. V.; Wilson, K. V.

    2004-01-01

    Silica and bridged polysilsesquioxane aerogels are low-density materials that are attractive for applications such as thermal insulation, porous separation media or catalyst supports, adsorbents, and cometary dust capture agents. However, aerogels are notoriously weak and brittle making it difficult to handle and machine monoliths into desired forms. This complication prevents the development of many applications that would otherwise benefit from the use of the low-density materials. Here, we will describe our efforts to chemically modify and mechanically enhance silica-based aerogels using chemical vapor techniques without sacrificing their characteristic low densities. Monolithic silica and organic-bridged polysilsesquioxane aerogels were prepared by sol-gel polymerization of the respective methoxysilane monomers followed by supercritical carbon dioxide drying of the gels. Then the gels were reactively modified with silylating agents to demonstrate the viability of CVD modification of aerogels, and to determine the effects of silylation of surface silanols on the morphology, surface area, and mechanical properties of the resulting aerogels.

  11. Performance of Low-Density Parity-Check Coded Modulation

    NASA Technical Reports Server (NTRS)

    Hamkins, Jon

    2010-01-01

    This paper reports the simulated performance of each of the nine accumulate-repeat-4-jagged-accumulate (AR4JA) low-density parity-check (LDPC) codes [3] when used in conjunction with binary phase-shift-keying (BPSK), quadrature PSK (QPSK), 8-PSK, 16-ary amplitude PSK (16- APSK), and 32-APSK.We also report the performance under various mappings of bits to modulation symbols, 16-APSK and 32-APSK ring scalings, log-likelihood ratio (LLR) approximations, and decoder variations. One of the simple and well-performing LLR approximations can be expressed in a general equation that applies to all of the modulation types.

  12. Clouds in Low-mass, Low-density Planets

    NASA Astrophysics Data System (ADS)

    Morley, Caroline; Fortney, J.; Marley, M.; Kempton, E.; Visscher, C.; Zahnle, K.

    2013-10-01

    The Kepler Space Telescope has revealed huge populations of low-mass, low-density planets, but their compositions remain elusive. For example, the density of GJ 1214b is consistent with either a water-world with a water atmosphere or a rock-iron core with a H/He envelope. Other super-Earths must contain hydrogen and helium to match their observed masses and radii. To understand this population of objects, we must be able to characterize their compositions through spectroscopy. The formation of clouds in exoplanet atmospheres significantly changes their observable spectra. For exoplanets, the opacity of hazes or clouds has been invoked as a possible explanation for the observed flat transmission spectrum of transiting super-Earth GJ 1214b as well as for the strong Rayleigh scattering feature in HD 189733b, the best-studied hot Jupiter. Here, we examine the effect of clouds on low-mass, low-density exoplanet spectra. We include the condensates that are present in chemical equilibrium for objects at these temperatures (500-900 K) which include minerals like sulfides and alkali salts. The most important of these clouds are sodium sulfide, potassium chloride, and zinc sulfide. These clouds should be most prominent at low surface gravity, strongly super-solar atmospheric abundances, and at the slant viewing geometry appropriate for transits. Hence they could be quite important for affecting the transmission spectra of cool low density super-Earth and Neptune-class planets. Another class of clouds may also dramatically alter the spectra of irradiated planets: photochemical hazes. We additionally include a hydrocarbon haze layer similar to the tholin haze in Titan’s atmosphere. We calculate the location and density of the haze layer using photochemical models from Kempton et al. 2012. We present new results that show that for enhanced metallicity atmospheres, either the clouds that form in equilibrium or a hydrocarbon haze layer could become sufficiently optically thick

  13. Preparation, testing, and delivery of low density polyimide foam panels

    NASA Technical Reports Server (NTRS)

    Ball, G. L., III; Post, L. K.; Salyer, I. O.

    1975-01-01

    Plastic foams based on polyimide resins were shown to be stable at relatively high temperatures, and to possess very low flame spread and smoke generation characteristics. A system and process were developed to prepare low-density polyimide foam from a liquid formulation. The system is based on the reaction of micropulverized grade pyromellitic dianhydride with a polymeric diisocyanate. The panels produced were postcured at elevated temperatures to achieve maximum thermal and fire resistance, and incorporation of a fire retardant into the formulation was considered. The effects of a flame retardant (Flameout 5600B1) were investigated, but eliminated in preference to the postcuring approach.

  14. Advanced Porous Coating for Low-Density Ceramic Insulation Materials

    NASA Technical Reports Server (NTRS)

    Leiser, Daniel B.; Churchward, Rex; Katvala, Victor; Stewart, David; Balter, Aliza

    1988-01-01

    The need for improved coatings on low-density reusable surface insulation (RSI) materials used on the space shuttle has stimulated research into developing tougher coatings. The processing of a new porous composite "coating" for RST called toughened unipiece fibrous insulation Is discussed. Characteristics including performance in a simulated high-speed atmospheric entry, morphological structure before and after this exposure, resistance to Impact, and thermal response to a typical heat pulse are described. It is shown that this coating has improved impact resistance while maintaining optical and thermal properties comparable to the previously available reaction-cured glass coating.

  15. Critical noise levels for low-density parity check decoding

    NASA Astrophysics Data System (ADS)

    Mourik, J. Van; Saad, D.; Kabashima, Y.

    2002-08-01

    We determine the critical noise level for decoding low-density parity check error-correcting codes based on the magnetization enumerator (M), rather than on the weight enumerator (W) employed in the information theory literature. The interpretation of our method is appealingly simple, and the relation between the different decoding schemes such as typical pairs decoding, MAP, and finite temperature decoding (MPM) becomes clear. In addition, our analysis provides an explanation for the difference in performance between MN and Gallager codes. Our results are more optimistic than those derived using the methods of information theory and are in excellent agreement with recent results from another statistical physics approach.

  16. Development of Low Density, Flexible Carbon Phenolic Ablators

    NASA Technical Reports Server (NTRS)

    Stackpoole, Mairead; Thornton, Jeremy; Fan, Wendy; Covington, Alan; Doxtad, Evan; Beck, Robin; Gasch, Matt; Arnold, Jim

    2012-01-01

    Phenolic Impregnated Carbon Ablator (PICA) was the enabling TPS material for the Stardust mission where it was used as a single piece heatshield. PICA has the advantages of low density (approximately 0.27 grams per cubic centimeter) coupled with efficient ablative capability at high heat fluxes. Due to its brittle nature and low strain to failure recent efforts at NASA ARC have focused on alternative architectures to yield flexible and more conformal carbon phenolic materials with comparable densities to PICA. This presentation will discuss flexible alternatives to PICA and include preliminary mechanical and thermal properties as well as recent arc jet and LHMEL screening test results.

  17. Microcraters formed in glass by low density projectiles

    NASA Technical Reports Server (NTRS)

    Mandeville, J.-C.; Vedder, J. F.

    1971-01-01

    Microcraters were produced in soda-lime glass by the impact of low density projectiles of polystyrene (p = 1.06 g/cu cm) with masses between 0.7 and 62 picograms and velocities between 2 and 14 km/s. The morphology of the craters depended on the velocity and the angle of incidence of the projectiles and these are discussed in detail. It was found that the transitions in morphology of the craters formed by polystyrene spheres occurred at higher velocities than they did for more dense projectiles.

  18. Microcraters formed in glass by low density projectiles

    NASA Technical Reports Server (NTRS)

    Mandeville, J.-C.; Vedder, J. F.

    1971-01-01

    Microcraters were produced in soda-lime glass by the impact of low density projectiles of polystyrene with masses between 0.7 and 62 picograms and velocities between 2 and 14 kilometers per second. The morphology of the craters depends on the velocity and angle of incidence of the projectiles. The transitions in morphology of the craters formed by polystyrene spheres occur at higher velocities than they do for more dense projectiles. For oblique impact, the craters are elongated and shallow with the spallation threshold occuring at higher velocity. For normal incidence, the total displaced mass of the target material per unit of projectile kinetic energy increases slowly with the energy.

  19. Venting and High Vacuum Performance of Low Density Multilayer Insulation

    NASA Astrophysics Data System (ADS)

    Riesco, M. E.; McLean, C. H.; Mills, G. L.; Buerger, S.; Meyer, M. L.

    2010-04-01

    The NASA Exploration Program is currently studying the use liquid oxygen, liquid methane and liquid hydrogen for propulsion in future spacecraft for Exploration of the Moon and Mars. This will require the efficient long term, on-orbit storage of these cryogenic propellants. Multilayer Insulation (MLI) will be critical to achieving the required thermal performance since it has much lower heat transfer than any other insulation when used in a vacuum. MLI with a low density (⩽10 layers/cm) has been shown in previous work to be the most mass efficient. The size and mass constraints of these propulsion systems will not allow a structural shell to be used to provide vacuum for the MLI during ground hold and launch. The baseline approach is to purge the MLI during ground hold with an inert gas which is then vented during launch ascent and on-orbit. This paper presents the results on experimental tests and modeling performed by Ball Aerospace on low density, non-perforated MLI used to insulate a cryogenic tank simulating an Exploration cryogenic propellant storage vessel. These include measurements of the rate of venting and of the heat transfer of gas filled insulation, fully evacuated insulation and during the transition in between. Results of transient computer modeling of the MLI venting and heat transfer process are also presented. Previous work by some of the authors performed vent testing using MLI with perforations and slits and a slow pump down rate.

  20. Low-density foamed Portland cements fill variety of needs

    SciTech Connect

    Montman, R.; Harms, W.M.; Mody, B.G.; Sutton, D.L.

    1982-07-26

    Several important conclusions can be stated as follows. Foam cement offers many attractive properties whenever there is a need for ultra-low density cements in the oil field. Among these properties are high strengths and reasonably low permeabilities. Foam cement can be accurately prepared, placed, and cured both in the laboratory and in the field. Certain guidelines must be followed to provide good results from foam cement jobs. These have been identified and are achievable. Foam cement has proven to be very effective in remedying pressure parting lost circulation. However, one must recognize that large volumes of foam slurry can easily be lost into a fractured formation because most foam slurries have low API fluid loss values and a very low solid volume/ slurry volume ratio-the exact properties desired for an effective fracturing fluid. Therefore, successful lost circulation control with foam cement depends mainly on its low density thixotropic properties. By contrast, light weight slurries that contain micro-spheres, gilsonite or walnut hulls owe much of their lost circulation control to their fracture plugging ability. For this reason, it is advantageous to incorporate solid lost circulation materials into foam cement slurries. Cellophane flakes have been routinely used.

  1. Low-Density, Aerogel-Filled Thermal-Insulation Tiles

    NASA Technical Reports Server (NTRS)

    Santos, Maryann; Heng, Vann; Barney, Andrea; Oka, Kris; Droege, Michael

    2005-01-01

    Aerogel fillings have been investigated in a continuing effort to develop low-density thermal-insulation tiles that, relative to prior such tiles, have greater dimensional stability (especially less shrinkage), equal or lower thermal conductivity, and greater strength and durability. In preparation for laboratory tests of dimensional and thermal stability, prototypes of aerogel-filled versions of recently developed low-density tiles have been fabricated by impregnating such tiles to various depths with aerogel formations ranging in density from 1.5 to 5.6 lb/ft3 (about 53 to 200 kg/cu m). Results available at the time of reporting the information for this article showed that the thermal-insulation properties of the partially or fully aerogel- impregnated tiles were equivalent or superior to those of the corresponding non-impregnated tiles and that the partially impregnated tiles exhibited minimal (<1.5 percent) shrinkage after multiple exposures at a temperature of 2,300 F (1,260 C). Latest developments have shown that tiles containing aerogels at the higher end of the density range are stable after multiple exposures at the said temperature.

  2. A Langevin model for low density pedestrian dynamics

    NASA Astrophysics Data System (ADS)

    Corbetta, Alessandro; Lee, Chung-Min; Benzi, Roberto; Muntean, Adrian; Toschi, Federico

    The dynamics of pedestrian crowds shares deep connections with statistical physics and fluid dynamics. Reaching a quantitative understanding, not only of the average behaviours but also of the statistics of (rare) fluctuations would have major impact, for instance, on the design and safety of civil infrastructures. A key feature of pedestrian dynamics is its strong intrinsic variability, that we can already observe at the single individual level. In this work we aim at a quantitative characterisation of this statistical variability by studying individual fluctuations. We consider experimental observations of low-density pedestrian flows in a corridor within a building at Eindhoven University of Technology. Few hundreds of thousands of pedestrian trajectories with high space and time resolutions have been collected via a Microsoft Kinect 3D-range sensor and automatic head tracking techniques. From these observations we model pedestrians as active Brownian particles by means of a generalised Langevin equation. With this model we can quantitatively reproduce the observed dynamics including the statistics of ordinary pedestrian fluctuations and of rarer U-turn events. Low density, pair-wise interactions between pedestrians are also discussed.

  3. Low-Density Lipoprotein Sensor Based on Molecularly Imprinted Polymer.

    PubMed

    Chunta, Suticha; Suedee, Roongnapa; Lieberzeit, Peter A

    2016-01-19

    Increased level of low-density lipoprotein (LDL) strongly correlates with incidence of coronary heart disease. We synthesized novel molecularly imprinted polymers (MIP) as biomimetic specific receptors to establish rapid analysis of LDL levels. For that purpose the ratios of monomers acrylic acid (AA), methacrylic acid (MAA), and N-vinylpyrrolidone (VP), respectively, were screened on 10 MHz dual-electrode quartz crystal microbalances (QCM). Mixing MAA and VP in the ratio 3:2 (m/m) revealed linear sensor characteristic to LDL cholesterol (LDL-C) from 4 to 400 mg/dL or 0.10-10.34 mmol/L in 100 mM phosphate-buffered saline (PBS) without significant interference: high-density lipoprotein (HDL) yields 4-6% of the LDL signal, very-low-density-lipoprotein (VLDL) yields 1-3%, and human serum albumin (HSA) yields 0-2%. The LDL-MIP sensor reveals analytical accuracy of 95-96% at the 95% confidence interval with precision at 6-15%, respectively. Human serum diluted 1:2 with PBS buffer was analyzed by LDL-MIP sensors to demonstrate applicability to real-life samples. The sensor responses are excellently correlated to the results of the standard technique, namely, a homogeneous enzymatic assay (R(2) = 0.97). This demonstrates that the system can be successfully applied to human serum samples for determining LDL concentrations. PMID:26643785

  4. Relationship between Exploding Bridgewire & Spark Initiation of Low Density PETN

    NASA Astrophysics Data System (ADS)

    Lee, Elizabeth; Drake, Rod

    2015-06-01

    Recent work has shown that the energy delivered after bridgewire burst affects the function time of an EBW detonator. The spark which is formed post bridgewire burst is the means by which the remaining fireset energy is delivered into the detonator. Therefore, by studying the characteristics of spark-gap detonators insight into the contribution of spark initiation to the functioning of EBW detonators may be achieved. Spark initiation of low density explosives consists of; (i) spark formation, (ii) spark interaction with the bed, and (iii) ignition and growth of reaction. Experiments were performed in which beds of an inert simulant were used to study the formation and propagation of sparks. The effect of the spark on inert porous beds was studied over a limited delivered energy range. The disruption of the bed was found to be dependent on the particle size / pore structure of the bed. The effect of spark initiation on a low density PETN bed was then examined, the relationship between delivered energy and function time was found to be the same as for EBW detonators. This necessitated the development of electrical diagnostic techniques to measure the energy delivered to the spark.

  5. Cryoelectron microscopy of low density lipoprotein in vitreous ice.

    PubMed Central

    Spin, J M; Atkinson, D

    1995-01-01

    In this report, images of low density lipoprotein (LDL) in vitreous ice at approximately 30 A resolution are presented. These images show that LDL is a quasi-spherical particle, approximately 220-240 A in diameter, with a region of low density (lipid) surrounded by a ring (in projection) of high density believed to represent apolipoprotein B-100. This ring is seen to be composed of four or five (depending on view) large regions of high density material that may represent protein superdomains. Analysis of LDL images obtained at slightly higher magnification reveals that areas of somewhat lower density connect these regions, in some cases crossing the projectional interiors of the LDL particles. Preliminary image analysis of LDL covalently labeled at Cys3734 and Cys4190 with 1.4-nm Nanogold clusters demonstrates that this methodology will provide an important site-specific marker in studies designed to map the organization of apoB at the surface of LDL. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 6 PMID:7612855

  6. Long term hemodialysis aggravates lipolytic activity reduction and very low density, low density lipoproteins composition in chronic renal failure patients

    PubMed Central

    Mekki, Khedidja; Prost, Josiane; Remaoun, Mustapha; Belleville, Jacques; Bouchenak, Malika

    2009-01-01

    Background Dyslipidemia, particularly hypertriglyceridemia is common in uremia, and represents an independent risk factor for atherosclerosis. Methods To investigate the effects of hemodialysis (HD) duration on very low density lipoprotein (VLDL) and low density lipoprotein (LDL) compositions and lipopolytic activities, 20 patients on 5 to 7 years hemodialysis were followed-up during 9 years. Blood samples were drawn at T0 (beginning of the study), T1 (3 years after initiating study), T2 (6 years after initiating study) and T3 (9 years after initiating study). T0 was taken as reference. Results Triacylglycerols (TG) values were correlated with HD duration (r = 0.70, P < 0.05). An increase of total cholesterol was noted at T2 and T3. Lowered activity was observed for lipoprotein lipase (LPL) (-44%) at T3 and hepatic lipase (HL) (-29%) at T1, (-64%) at T2 and (-73%) at T3. Inverse relationships were found between HD duration and LPL activity (r = -0.63, P < 0.05), and HL activity (r = -0.71, P < 0.01). At T1, T2 and T3, high VLDL-amounts and VLDL-TG and decreased VLDL-phospholipids values were noted. Increased LDL-cholesteryl esters values were noted at T1 and T2 and in LDL-unesterified cholesterol at T2 and T3. Conclusion Despite hemodialysis duration, VLDL-LDL metabolism alterations are aggravated submitting patients to a greater risk of atherosclerosis. PMID:19709414

  7. Effect of nanoclay on the properties of low density polyethylene/linear low density polyethylene/thermoplastic starch blend films.

    PubMed

    Sabetzadeh, Maryam; Bagheri, Rouhollah; Masoomi, Mahmood

    2016-05-01

    The aim of this work is to study effect of nanoclay (Cloisite(®)15A) on morphology and properties of low-density polyethylene/linear low-density polyethylene/thermoplastic starch (LDPE/LLDPE/TPS) blend films. LDPE/LLDPE blend (70/30wt/wt) containing 15wt.% TPS in the presence of PE-grafted maleic anhydride (PE-g-MA, 3wt.%) with 1, 3 and 5phr of nanoclay are compounded in a twin-screw extruder and then film blown using a blowing machine. Nanocomposites with intercalated structures are obtained, based on the X-ray diffraction (XRD) and transmission electron microscopy (TEM) studies. However, some exfoliated single platelets in the samples are also observable. Scanning electron microscopic (SEM) images confirm the ability of both exfoliated nanoclay and PE-g-MA to reduce the size of TPS domains and deform their particles within the PE matrices. As the nanoclay content increases from 1 to 5phr, the tensile strength, tear resistance and impact strength of the films increase, whereas a slight decrease in the elongation at break is observed. The film samples with 5phr nanoclay possess the required packaging properties, as specified by ASTM D4635. These films provide desired optical transparency and surface roughness which are more attractive for packaging applications. PMID:26876998

  8. Dot-blot assay for the low density lipoprotein receptor

    SciTech Connect

    Maggi, F.M.; Catapano, A.L.

    1987-01-01

    We describe a new method for detecting the interaction of low density lipoprotein with its receptor using unmodified nitrocellulose as support for membrane protein. The method is specific and sensitive down to 3 micrograms of membrane protein. Unlabeled LDL, but not HDL, competes with /sup 125/I-labeled LDL for binding, and binding is abolished by pretreatment of the membranes with pronase and is dependent upon the presence of Ca2+. Furthermore, modification of arginine or lysine residues on LDL abolishes the lipoprotein interaction with the receptor protein supported on the nitrocellulose. When the membranes are solubilized with octyl glucoside, purification steps of the receptor can be directly followed with no interference of the detergent, therefore eliminating the need for its removal. The increased expression of LDL receptors on liver membranes from estradiol-treated rats was also demonstrated. We suggest, therefore, that this method can be used to detect the presence of LDL receptors on minute amounts of membrane protein.

  9. Ballistics considerations for small-caliber, low-density projectiles

    SciTech Connect

    Gouge, M.J.; Baylor, L.R.; Combs, S.K.; Fisher, P.W.; Foster, C.A.; Foust, C.R.; Milora, S.L.; Qualls, A.L.

    1993-11-01

    One major application for single- and two-stage light gas guns is for fueling magnetic fusion confinement devices. Powder guns are not a feasible alternative due to possible plasma contamination by residual powder gases and the eventual requirement of steady-state operation at {approximately} 1 Hz, which will dictate a closed gas handling system where propellant gases are recovered, processed and recompressed. Interior ballistic calculations for single-stage light gas guns, both analytical and numerical, are compared to an extensive data base for low density hydrogenic projectiles (pellets). Some innovative range diagnostics are described for determining the size and velocity of these small (several mm) size projectiles. A conceptual design of a closed cycle propellant gas system is presented including tradeoffs between different light propellant gases.

  10. KEPLER-7b: A TRANSITING PLANET WITH UNUSUALLY LOW DENSITY

    SciTech Connect

    Latham, David W.; Buchhave, Lars A.; Furesz, Gabor; Geary, John C.; Borucki, William J.; Koch, David G.; Lissauer, Jack J.; Rowe, Jason F.; Brown, Timothy M.; Basri, Gibor; Batalha, Natalie M.; Caldwell, Douglas A.; Jenkins, Jon M.; Cochran, William D.; Dunham, Edward W.; Gautier, Thomas N.; Howell, Steve B.; Marcy, Geoffrey W.; Monet, David G.

    2010-04-20

    We report on the discovery and confirmation of Kepler-7b, a transiting planet with unusually low density. The mass is less than half that of Jupiter, M {sub P} = 0.43 M {sub J}, but the radius is 50% larger, R {sub P} = 1.48 R {sub J}. The resulting density, {rho}{sub P} = 0.17 g cm{sup -3}, is the second lowest reported so far for an extrasolar planet. The orbital period is fairly long, P = 4.886 days, and the host star is not much hotter than the Sun, T {sub eff} = 6000 K. However, it is more massive and considerably larger than the Sun, M {sub *} = 1.35 M {sub sun} and R {sub *} = 1.84 R {sub sun}, and must be near the end of its life on the main sequence.

  11. Monitoring low density avian populations: An example using Mountain Plovers

    USGS Publications Warehouse

    Dreitz, V.J.; Lukacs, P.M.; Knopf, F.L.

    2006-01-01

    Declines in avian populations highlight a need for rigorous, broad-scale monitoring programs to document trends in avian populations that occur in low densities across expansive landscapes. Accounting for the spatial variation and variation in detection probability inherent to monitoring programs is thought to be effort-intensive and time-consuming. We determined the feasibility of the analytical method developed by Royle and Nichols (2003), which uses presence-absence (detection-non-detection) field data, to estimate abundance of Mountain Plovers (Charadrius montanus) per sampling unit in agricultural fields, grassland, and prairie dog habitat in eastern Colorado. Field methods were easy to implement and results suggest that the analytical method provides valuable insight into population patterning among habitats. Mountain Plover abundance was highest in prairie dog habitat, slightly lower in agricultural fields, and substantially lower in grassland. These results provided valuable insight to focus future research into Mountain Plover ecology and conservation. ?? The Cooper Ornithological Society 2006.

  12. Low Density Parity Check Codes: Bandwidth Efficient Channel Coding

    NASA Technical Reports Server (NTRS)

    Fong, Wai; Lin, Shu; Maki, Gary; Yeh, Pen-Shu

    2003-01-01

    Low Density Parity Check (LDPC) Codes provide near-Shannon Capacity performance for NASA Missions. These codes have high coding rates R=0.82 and 0.875 with moderate code lengths, n=4096 and 8176. Their decoders have inherently parallel structures which allows for high-speed implementation. Two codes based on Euclidean Geometry (EG) were selected for flight ASIC implementation. These codes are cyclic and quasi-cyclic in nature and therefore have a simple encoder structure. This results in power and size benefits. These codes also have a large minimum distance as much as d,,, = 65 giving them powerful error correcting capabilities and error floors less than lo- BER. This paper will present development of the LDPC flight encoder and decoder, its applications and status.

  13. Effect of polarization on superfluidity in low density neutron matter

    NASA Technical Reports Server (NTRS)

    Clark, J. W.; Kallman, C.-G.; Yang, C.-H.; Chakkalakal, D. A.

    1976-01-01

    The singlet-state quasi-particle interaction in neutron matter is examined on the basis of results of a detailed evaluation of the Landau Fermi-liquid parameters for pure neutron effects, including polarization effects. This means that the interaction induced by exchange of density and spin-density excitations is taken into account. It is shown that polarization actually works to suppress the pairing matrix elements, owing to the spin dependence of the quasi-particle interaction and, ultimately, the balance of attraction, repulsion, and spin dependence in the fundamental two-neutron interaction. Since the isotropic energy gap and the condensation energy in low-density neutron-star matter are extremely sensitive functions of the pairing matrix elements, they will also be suppressed by the polarizability of the neutron medium.

  14. Experimental Determination of Thermal Conductivity of Low-Density Ice

    NASA Technical Reports Server (NTRS)

    Coles, Willard D.

    1954-01-01

    The thermal conductivity of low-density ice has been computed from data obtained in an experimental investigation of the heat transfer and mass transfer by sublimation for an iced surface on a flat plate in a high-velocity tangential air stream. The results are compared with data from several sources on the thermal conductivity of packed snow and solid glaze ice. The results show good agreement with the equations for the thermal conductivity of packed snow as a function of snow density. The agreement of the curves for packed snow near the solid ice regime with the values of thermal conductivity, of ice indicates that the curves are applicable over the entire-ice-density range.

  15. The tethered satellite system for low density aerothermodynamics studies

    NASA Technical Reports Server (NTRS)

    Carlomagno, Giovanni M.; De Luca, Luigi; Siemers, P. M., III; Wood, George M., Jr.

    1986-01-01

    The feasibility of the operation of the Tethered Satellite System (TSS) as a continuous open wind tunnel for low-density aerothermodynamic studies (applicable to the design of hypersonic space vehicles including STARFAC, AOTV, and ERV) is considered. The Shuttle Continuous Open Wind Tunnel (SCOWT) program, for the study of the energy and momentum transfer between the tethered satellite and its environmental medium during the TSS/2 mission, is described. Instrumentation and TSS design requirements to meet SCOWT objectives are also considered. SCOWT will provide information on the gasdynamic processes occurring downstream of the bow wave standing in front of the TS, the chemistry and physics of the upper atmosphere related to satellite aerothermodynamics, and TSS's overall experimental envelope of operation.

  16. Ultra-low density microcellular polymer foam and method

    DOEpatents

    Simandl, Ronald F.; Brown, John D.

    1996-01-01

    An ultra-low density, microcellular open-celled polymer foam and a method for making such foam. A polymer is dissolved in a heated solution consisting essentially of at least one solvent for the dissolution of the polymer in the heated solution and the phase inversion of the dissolved polymer to a liquid gel upon sufficient cooling of the heated solution. The heated solution is contained in a containment means provided with a nucleating promoting means having a relatively rough surface formed of fixed nucleating sites. The heated solution is cooled for a period of time sufficient to form a liquid gel of the polymer by phase inversion. From the gel, a porous foam having a density of less than about 12.0 mg/cm.sup.3 and open porosity provided by well interconnected strut morphology is formed.

  17. Ultra-low density microcellular polymer foam and method

    DOEpatents

    Simandl, R.F.; Brown, J.D.

    1996-03-19

    An ultra-low density, microcellular open-celled polymer foam and a method for making such foam are disclosed. A polymer is dissolved in a heated solution consisting essentially of at least one solvent for the dissolution of the polymer in the heated solution and the phase inversion of the dissolved polymer to a liquid gel upon sufficient cooling of the heated solution. The heated solution is contained in a containment means provided with a nucleating promoting means having a relatively rough surface formed of fixed nucleating sites. The heated solution is cooled for a period of time sufficient to form a liquid gel of the polymer by phase inversion. From the gel, a porous foam having a density of less than about 12.0 mg/cm{sup 3} and open porosity provided by well interconnected strut morphology is formed.

  18. DSC melting behavior of irradiated low density polyethylenes containing antioxidants

    NASA Astrophysics Data System (ADS)

    Gal, O.; Kostoski, D.; Babić, D.; Stannett, V. T.

    The effect of antioxidants (0.5 wt% content) on the melting behaviour of low density polyethylenes, one branched and one linear, was examined with data obtained by DSC. The two polyethylenes exhibit noticeable differences in pure form; LLDPE has a higher melting point, lower heat of fusion and a more complex fusion endotherm than LDPE. The addition of antioxidants has a scarcely noticeable influence on the melting behaviour of LDPE whether irradiated or not, while in the case of LLDPE the effect is more visible. However, a careful analysis of the observed characteristics, peak temperatures and lamellae thickness distribution as well as heat of fusion, show that the observed effects are appearing as the consequence of chemical processes, scission and crosslinking, which occur in PE under either thermomechanical action (mixing in the course of the sample preparation), or radiation.

  19. Synthesis of Low-Density, Carbon-Doped, Porous Hexagonal Boron Nitride Solids.

    PubMed

    Gautam, Chandkiram; Tiwary, Chandra Sekhar; Jose, Sujin; Brunetto, Gustavo; Ozden, Sehmus; Vinod, Soumya; Raghavan, Prasanth; Biradar, Santoshkumar; Galvao, Douglas Soares; Ajayan, Pulickel M

    2015-12-22

    Here, we report the scalable synthesis and characterization of low-density, porous, three-dimensional (3D) solids consisting of two-dimensional (2D) hexagonal boron nitride (h-BN) sheets. The structures are synthesized using bottom-up, low-temperature (∼300 °C), solid-state reaction of melamine and boric acid giving rise to porous and mechanically stable interconnected h-BN layers. A layered 3D structure forms due to the formation of h-BN, and significant improvements in the mechanical properties were observed over a range of temperatures, compared to graphene oxide or reduced graphene oxide foams. A theoretical model based on Density Functional Theory (DFT) is proposed for the formation of h-BN architectures. The material shows excellent, recyclable absorption capacity for oils and organic solvents. PMID:26580810

  20. FORMATION AND STRUCTURE OF LOW-DENSITY EXO-NEPTUNES

    SciTech Connect

    Rogers, Leslie A.; Seager, Sara; Bodenheimer, Peter

    2011-09-01

    Kepler has found hundreds of Neptune-size (2-6 R{sub +}) planet candidates within 0.5 AU of their stars. The nature of the vast majority of these planets is not known because their masses have not been measured. Using theoretical models of planet formation, evolution, and structure, we explore the range of minimum plausible masses for low-density exo-Neptunes. We focus on highly irradiated planets with T{sub eq} {>=} 500 K. We consider two separate formation pathways for low-mass planets with voluminous atmospheres of light gases: core-nucleated accretion and outgassing of hydrogen from dissociated ices. We show that Neptune-size planets at T{sub eq} = 500 K with masses as small as a few times that of Earth can plausibly be formed by core-nucleated accretion coupled with subsequent inward migration. We also derive a limiting low-density mass-radius relation for rocky planets with outgassed hydrogen envelopes but no surface water. Rocky planets with outgassed hydrogen envelopes typically have computed radii well below 3 R{sub +}. For both planets with H/He envelopes from core-nucleated accretion and planets with outgassed hydrogen envelopes, we employ planet interior models to map the range of planet mass-envelope mass-equilibrium temperature parameter space that is consistent with Neptune-size planet radii. Atmospheric mass loss mediates which corners of this parameter space are populated by actual planets and ultimately governs the minimum plausible mass at a specified transit radius. We find that Kepler's 2-6 R{sub +} planet candidates at T{sub eq} = 500-1000 K could potentially have masses {approx}< 4 M{sub +}. Although our quantitative results depend on several assumptions, our qualitative finding that warm Neptune-size planets can have masses substantially smaller than those given by interpolating the masses and radii of planets within our Solar System is robust.

  1. Application of low density foam pigs offshore Brazil

    SciTech Connect

    Lima, P.C.R.; Alves, S.J.

    1995-12-31

    In complex offshore installations, such as in the Campos Basin, it is relatively common to encounter pipeline systems where conventional pigs can not be run due to several factors. Changing pipe diameters, and presence of wet X-mas trees and manifolds are the most troublesome ones. In this work a new successful concept of using low cost and low density foam pigs for both liquid removal in wet-gas pipelines, and paraffin removal in oil and multiphase flow pipelines, is presented. Experimental work conducted in a 4 in laboratory facility, including a small scale glass manifold and a 6 in steel manifold, proved these pigs to be very effective. The performance of almost all kind of flexible polyurethane foams manufactured in Brazil is evaluated. Three field tests are also reported. The first low density foam pig operation was performed on a 127 mile long, 16 in diameter wet-gas offshore pipeline where the foam pig showed even higher liquid removal efficiency than the conventional inflatable spheres. The second operation was performed on a 6 mile long, 12 in diameter multiphase production offshore pipeline, which has never been pigged during its 9 year operation, and resulted in the removal of approximately 200 tons of paraffin. Finally, the third successful case is the cleaning of a 2 mile long flexible flow line of a subsea completed satellite well, in which the foam pigs were sent through a 2.5 in gas lift line, through a wet x-mas tree, not designed to be pigged, and then back through the 4 in production flow line. In spite of the fact that this paper is focusing on condensate and paraffin removal in pipeline, the basic principles can be applied to several kinds of operations: general pipeline cleaning; products separation in pipeline; corrosion evaluation; chemical product application.

  2. Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression.

    PubMed Central

    Liao, W; Rudling, M; Angelin, B

    1996-01-01

    Endotoxin induces hyperlipidaemia in experimental animals. In the current study, we investigated whether endotoxin alters hepatic low-density lipoprotein (LDL) receptor expression in rats. Endotoxin treatment suppressed hepatic LDL receptor expression in a dose- and time-dependent manner. Eighteen hours after intraperitoneal injection of increasing amounts of endotoxin, LDL receptor and its mRNA levels were determined by ligand blot and solution hybridization respectively. LDL receptor expression was inhibited by about 70% at a dose of 500 micrograms/100 g body weight. However, LDL receptor mRNA levels were markedly increased in all endotoxin-treated groups at this time point (by 83-136%; P < 0.001). Time-course experiments showed that LDL receptor expression was already reduced by 48% 4 h after endotoxin injection and was maximally reduced (by 63-65%) between 8 and 18 h. Changes in hepatic LDL receptor mRNA showed a different pattern. By 4 h after endotoxin injection, LDL receptor mRNA had decreased by 78% (P < 0.001). However, by 8 h after endotoxin injection, LDL receptor mRNA had returned to levels similar to controls, and 18 and 24 h after endotoxin injection, they were increased by about 60% (P < 0.05). Separation of plasma lipoproteins by FPLC demonstrated that endotoxin-induced changes in plasma triacylglycerols and cholesterol were due to accumulation of plasma apolipoprotein B-containing lipoproteins among very-low-density lipoprotein, intermediate-density lipoprotein and LDL. It is concluded that endotoxin suppresses hepatic LDL receptor expression in vivo in rats. PMID:8611169

  3. STANDING WAVE PROBES FOR DIMENSIONAL METROLOGY OF LOW DENSITY FOAMS

    SciTech Connect

    Seugling, R M; Woody, S C; Bauza, M B

    2010-03-23

    Typically, parts and geometries of interest to LLNL are made from a combination of complex geometries and a wide array of different materials ranging from metals and ceramics to low density foams and plastic foils. These parts are combined to develop physics experiments for studying material properties, equation of state (EOS) and radiation transport. Understanding the dimensional uncertainty of the parts contained within an experiment is critical to the physical understanding of the phenomena being observed and represents the motivation for developing probe metrology capability that can address LLNL's unique problems. Standing wave probes were developed for measuring high aspect ratio, micrometer scaled features with nanometer resolution. Originally conceived of for the use in the automotive industry for characterizing fuel injector bores and similar geometries, this concept was investigated and improved for use on geometries and materials important to LLNL needs within target fabrication. As part of the original project, detailed understanding of the probe dynamics and interactions with the surface of the sample was investigated. In addition, the upgraded system was utilized for measuring fuel injector bores and micro-lenses as a means of demonstrating capability. This report discusses the use of the standing wave probe for measuring features in low density foams, 55 mg/cc SiO{sub 2} and 982 mg/cc (%6 relative density) copper foam respectively. These two foam materials represent a difficult metrology challenge because of their material properties and surface topography. Traditional non-contact metrology systems such as normal incident interferometry and/or confocal microscopy have difficulty obtaining a signal from the relatively absorptive characteristics of these materials. In addition to the foam samples, a solid copper and plastic (Rexolite{trademark}) sample of similar geometry was measured with the standing wave probe as a reference for both conductive and

  4. Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

    PubMed Central

    Vanhamme, Luc; Roumeguère, Thierry; Zouaoui Boudjeltia, Karim

    2013-01-01

    Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis. PMID:23983406

  5. Properties of Dwarf Ellipticals in Low-Density Environments

    NASA Astrophysics Data System (ADS)

    Sur, Debnil; Guhathakurta, P.; Toloba, E.

    2013-01-01

    Dwarf elliptical galaxies have been studied only in dense cluster environments, where they are the most common type of object. While this suggests that their location affects their formation and evolution, the role of distance is not fully understood. Thus, to investigate the physical processes that shape these galaxies, we have conducted a study of dwarf elliptical galaxies (dEs) in low-density environments to compare their properties with those in clusters. Catalogs of such objects have not been created; thus, we have developed a novel objective method to find new dEs through comparing photometric properties with those of galaxies in the Virgo Cluster Catalog. This method utilizes optical colors, surface brightness and ellipticity, and it confirms smoothness through visual classification. In this last step, we found a very low contamination rate, which suggests the procedure’s utility in finding dEs. Through the NSA Sloan Atlas, we have analyzed the spectrophotometric properties of the dE candidates as a function of distance to the nearest massive galaxy, which we refer to as their host. We have found that these dEs are younger and more actively forming stars than dEs in denser regions. This is consistent with a transformation scenario in which low luminosity spiral galaxies are affected by the environment and transformed into quiescent galaxies. This low density regime contains objects in an intermediate state between the spiral galaxy and the classical dE in Virgo, where no star formation is ongoing. The correlation of the studied properties with the distance to the host galaxy provides new evidence that the dEs are created by a process called ram-pressure stripping: the interstellar medium of a host galaxy removes the gas of a smaller star-forming galaxy and provokes its quenching. We are currently analysing Keck/DEIMOS spectroscopy of some of the dE candidates from our catalog to explore in more detail their connection to cluster dEs. Possible similarities

  6. Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic applications.

    PubMed

    Lee, Jeong Yu; Kim, Jin-Ho; Bae, Ki Hyun; Oh, Mi Hwa; Kim, Youngwook; Kim, Jee Seon; Park, Tae Gwan; Park, Keunchil; Lee, Jung Hee; Nam, Yoon Sung

    2015-01-14

    This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low-density lipoproteins, for the tumor-targeted co-delivery of anti-cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co-encapsulated within folate-functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about -40 mV. The folate-functionalized LNPs enable the targeted detection of MCF-7, human breast adenocarcinoma expressing folate receptors, in T2 -weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel-free LNPs show no significant cytotoxicity up to 0.2 mg mL(-1) , indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti-tumor activities of the LNPs in a mouse tumor model suggest that the low-density lipoprotein-mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor-targeted co-delivery of various anti-cancer agents. PMID:25137631

  7. Heterogeneity of serum low density lipoproteins in normal human subjects

    SciTech Connect

    Shen, M.M.S.; Krauss, R.M.; Lindgren, F.T.; Forte, T.M.

    1981-01-01

    Equilibrium density gradient ultracentrifugation of serum low density lipoprotein (LDL) from twelve healthy human subjects was used to separate six subfractions with mean dinsity ranging from 1.0268 to 1.0597 g/ml. Mean corrected peak flotation rate (S/sup o//sub f/) measured by analytic ultracentrifugation, and mean particle diameter determined by negative staining electron microscopy, both declined significantly with increasing density of the subfractions. Major differences in chemical composition of the subfractions were noted, including a singnificantly lower triglyceride content and higher ratio of cholesteryl ester to triglyceride in the middle fractions compared with those of highest and lowest density. Concentration of fraction 2 correlated positively with HDL (P < 0.01) and negatively with VLDL (P < 0.001); concentration of fraction 4 correlated negatively with HDL (P < 0.05) and positively with VLDL (P < 0.001) and IDL (P < 0.01). LDL may thus include subspecies of differing structure and composition which might also have different metabolic and atherogenic roles.

  8. Simulated Tip Rub Testing of Low-Density Metal Foam

    NASA Technical Reports Server (NTRS)

    Bowman, Cheryl L.; Jones, Michael G.

    2009-01-01

    Preliminary acoustic studies have indicated that low-density, open-cell, metal foams may be suitable acoustic liner material for noise suppression in high by-pass engines. Metal foam response under simulated tip rub conditions was studied to assess whether its durability would be sufficient for the foam to serve both as a rub strip above the rotor as well as an acoustic treatment. Samples represented four metal alloys, nominal cell dimensions ranging from 60 to 120 cells per inch (cpi), and relative densities ranging from 3.4 to 10 percent. The resulting rubbed surfaces were relatively smooth and the open cell structure of the foam was not adversely affected. Sample relative density appeared to have significant influence on the forces induced by the rub event. Acoustic responses of various surface preparations were measured using a normal incidence tube. The results of this study indicate that the foam s open-cell structure was retained after rubbing and that the acoustic absorption spectra variation was minimal.

  9. Low-density foamed Portland cements fill variety of needs

    SciTech Connect

    Montman, R.; Harms, W.M.; Mody, B.G.; Sutton, D.L.

    1982-07-26

    Foam cement has proven to be very effective in remedying pressure parting lost circulation. However, one must recognize that large volumes of foam slurry can easily be lost into a fractured formation because most foam slurries have low API fluid loss values and a very low solid volume/ slurry volume ratio--the exact properties desired for an effective fracturing fluid. Therefore: Successful lost circulation control with foam cement depends mainly on its low density thixotropic properties. By contrast, light weight slurries that contain micro-spheres, gilsonite or walnut hulls owe much of their lost circulation control to their fracture plugging ability. For this reason, it is advantageous to incorporate solid lost circulation materials into foam cement slurries. Cellophane flakes have been routinely used. In addition to overcoming the density limitations mandated by breakdown gradients, the successful foam cement job should always meet two general objectives. It should provide sufficient hydrostatic pressure to prevent entry of fluids or gas into the annulus. It should provide good cement soundness and sufficiently low permeability to prevent corrosive water and/ or gas from penetrating the cement sheath and affecting the casing.

  10. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.

    PubMed

    Atrahimovich, Dana; Khatib, Soliman; Sela, Shifra; Vaya, Jacob; Samson, Abraham O

    2016-01-01

    High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25-4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels. PMID:27516832

  11. Alcohol alters low density lipoprotein composition and metabolism

    SciTech Connect

    Hoinacki, J.; Brown, J.; Dawson, M.; Deschenes, R.; Mulligan, J. )

    1991-03-11

    Two separate studies were conducted to examine the effect of ethanol (EtOH) dose on atherogenic low density lipoprotein (LDL) subfractions and LDL metabolism in vivo. In the first study, male, atherosclerosis-susceptible squirrel monkeys were divided in three treatments: controls fed liquid diet, and low and high alcohol groups given liquid diet with vodka substituted for carbohydrate at 12% and 24% of calories, respectively. After 6 months, LDL subclasses (LDL{sub 1a}, LDL{sub 1b} and LDL{sub 2}) were isolated by density gradient ultracentrifugation and polyacrylamide gradient gel electrophoresis, and their lipid and protein composition was determined. Low dose EtOH had no effect on LDL subfraction distribution while 24% EtOH resulted in an increase in the larger (LDL{sub 1a} and LDL{sub 1b}), buoyant subspecies without affecting the level of the more atherogenic, smaller, denser LDL{sub 2} particles. In the second study, {sup 125}I-LDL apolipoprotein B (apo B) was injected intravenously into Control and High EtOH monkeys and kinetic analyses were performed. Although the absolute catabolic rate (LDL production) was not altered, High EtOH primates showed a reduction in the fractional catabolic rate and a longer LDL apoB residence time.

  12. Transport coefficients for driven granular mixtures at low density

    NASA Astrophysics Data System (ADS)

    Khalil, Nagi; Garzó, Vicente

    2013-11-01

    The transport coefficients of a granular binary mixture driven by a stochastic bath with friction are determined from the inelastic Boltzmann kinetic equation. A normal solution is obtained via the Chapman-Enskog method for states near homogeneous steady states. The mass, momentum, and heat fluxes are determined to first order in the spatial gradients of the hydrodynamic fields, and the associated transport coefficients are identified. They are given in terms of the solutions of a set of coupled linear integral equations. As in the monocomponent case, since the collisional cooling cannot be compensated for locally by the heat produced by the external driving, the reference distributions (zeroth-order approximations) fi(0) (i=1,2) for each species depend on time through their dependence on the pressure and the temperature. Explicit forms for the diffusion transport coefficients and the shear viscosity coefficient are obtained by assuming the steady-state conditions and by considering the leading terms in a Sonine polynomial expansion. A comparison with previous results obtained for granular Brownian motion and by using a (local) stochastic thermostat is also carried out. The present work extends previous theoretical results derived for monocomponent dense gases [Garzó, Chamorro, and Vega Reyes, Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.87.032201 87, 032201 (2013)] to granular mixtures at low density.

  13. Transport coefficients for driven granular mixtures at low density.

    PubMed

    Khalil, Nagi; Garzó, Vicente

    2013-11-01

    The transport coefficients of a granular binary mixture driven by a stochastic bath with friction are determined from the inelastic Boltzmann kinetic equation. A normal solution is obtained via the Chapman-Enskog method for states near homogeneous steady states. The mass, momentum, and heat fluxes are determined to first order in the spatial gradients of the hydrodynamic fields, and the associated transport coefficients are identified. They are given in terms of the solutions of a set of coupled linear integral equations. As in the monocomponent case, since the collisional cooling cannot be compensated for locally by the heat produced by the external driving, the reference distributions (zeroth-order approximations) f(i)((0)) (i=1,2) for each species depend on time through their dependence on the pressure and the temperature. Explicit forms for the diffusion transport coefficients and the shear viscosity coefficient are obtained by assuming the steady-state conditions and by considering the leading terms in a Sonine polynomial expansion. A comparison with previous results obtained for granular Brownian motion and by using a (local) stochastic thermostat is also carried out. The present work extends previous theoretical results derived for monocomponent dense gases [Garzó, Chamorro, and Vega Reyes, Phys. Rev. E 87, 032201 (2013)] to granular mixtures at low density. PMID:24329253

  14. Low Density Lipid Nanoparticles for Solid Tumor Targeting

    PubMed Central

    Shrivastava, Mayank; Jain, Aviral; Gulbake, Arvind; Hurkat, Pooja; Jain, Neeti; Vijayraghwan, R.; Jain, Sanjay K.

    2014-01-01

    Abstract One of the most significant characteristics of cancer cells is their rapid dividing ability and overexpression of LDL receptors, which offers an opportunity for the selective targeting of these cells. 5-Fluorouracil (5-FU)-encapsulated low density lipid nanoparticles (LDLN) were prepared by the emulsion congealing method which mimics the plasma-derived LDL by acquiring the apolipoprotein B-100 from the blood. The average particle size, transmission electron microscope (TEM), and drug content of the prepared LDLN dispersion were found to be 161±3.5 nm, with spherical shape, and 0.370±0.05 mg/mL, respectively. In vitro release studies revealed a sustained profile which decreased with a lapse of time. In vivo studies of 5-FU serum concentration and biodistribution revealed a 5-FU serum concentration of 8.5% in tumor cells and about 2.1% in the liver at the end of 24 hr from LDLN. Tumor growth suppression studies showed 185.42% average tumor growth and 89.76% tumor height as compared to the control exhibiting tumor growth at 1166.47% and tumor height at 176.07%. On the basis of these collective data, it is suggested that a higher accumulation of LDLN, when given as an IV, in solid tumors is attributed to the active uptake of LDLN via LDL receptors via apolipoprotein B-100. PMID:26279976

  15. Low-density carbonized resorcinol-formaldehyde foams. Final report

    SciTech Connect

    Kong, F.M.; Buckley, S.R.; Giles, C.L. Jr.; Haendler, B.L.; Hair, L.M.; Letts, S.A.; Overturf, G.E. III; Price, C.W.; Cook, R.C.

    1991-07-04

    This report documents research and development on resorcinol- formaldehyde-based foam materials conducted between 1986 and June 1990, when the effort was discontinued. The foams discussed are resorcinol-formaldehyde (RF) foam, carbonized RF (CRF) foam, and two composite foams, a polystyrene/RF (PS/RF) foam and its carbonized derivative (CPR). The RF foams are synthesized by the polycondensation of resorcinol with formaldehyde in a slightly basic solution. Their structure and density depend strongly on the concentration of the sodium carbonate catalyst. The have an interconnected bead structure similar to that of silica aerogels; bead sizes range from 30 to 130 {Angstrom}, and cell sizes are less than 0.1 {mu}m. We have achieved densities of 16 to 200 mg/cm{sup 3}. The RF foams can be pyrolyzed in an inert atmosphere to form a vitreous carbon foam (CRF), which has a similar microstructure but much higher mechanical strength. The PS/RF foams are obtained by filling the 2- to 3-{mu}m cells of PS foam (a low-density hydrocarbon foam we have developed) with RF. The resultant foams have the outstanding handling and machinability of the PS foam matrix and the small cell size of RF. Pyrolyzing PS/RF foams causes depolymerization and loss of the PS; the resulting CPR foams have a structure similar to the PS foams in which CRF both replicates and fills the PS cells.

  16. Low-density carbonized resorcinol-formaldehyde foams

    SciTech Connect

    Kong, F.M.; Buckley, S.R.; Giles, C.L. Jr.; Haendler, B.L.; Hair, L.M.; Letts, S.A.; Overturf, G.E. III; Price, C.W.; Cook, R.C.

    1991-07-04

    This report documents research and development on resorcinol- formaldehyde-based foam materials conducted between 1986 and June 1990, when the effort was discontinued. The foams discussed are resorcinol-formaldehyde (RF) foam, carbonized RF (CRF) foam, and two composite foams, a polystyrene/RF (PS/RF) foam and its carbonized derivative (CPR). The RF foams are synthesized by the polycondensation of resorcinol with formaldehyde in a slightly basic solution. Their structure and density depend strongly on the concentration of the sodium carbonate catalyst. The have an interconnected bead structure similar to that of silica aerogels; bead sizes range from 30 to 130 {Angstrom}, and cell sizes are less than 0.1 {mu}m. We have achieved densities of 16 to 200 mg/cm{sup 3}. The RF foams can be pyrolyzed in an inert atmosphere to form a vitreous carbon foam (CRF), which has a similar microstructure but much higher mechanical strength. The PS/RF foams are obtained by filling the 2- to 3-{mu}m cells of PS foam (a low-density hydrocarbon foam we have developed) with RF. The resultant foams have the outstanding handling and machinability of the PS foam matrix and the small cell size of RF. Pyrolyzing PS/RF foams causes depolymerization and loss of the PS; the resulting CPR foams have a structure similar to the PS foams in which CRF both replicates and fills the PS cells.

  17. Novel Therapies for Low-Density Lipoprotein Cholesterol Reduction.

    PubMed

    Toth, Peter P

    2016-09-15

    Although many clinical trials and meta-analyses have demonstrated that lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with proportionately greater reductions in the risk of cardiovascular disease events, not all patients with hypercholesterolemia are able to attain risk-stratified LDL-C goals with statin monotherapy. Elucidation of the pathophysiology of genetic disorders of lipid metabolism (e.g., familial hypercholesterolemia) has led to the development of several novel lipid-lowering strategies, including blocking the degradation of hepatic LDL-C receptors that are important in LDL-C clearance, or the inhibition of apoprotein synthesis and lipidation. Mipomersen and lomitapide are highly efficacious new agents available for the treatment of patients with homozygous familial hypercholesterolemia. The recent introduction of PCSK9 inhibitors (alirocumab and evolocumab) have made it possible for many patients to achieve very low LDL-C concentrations (e.g., <40 mg/dl) that are usually not attainable with statin monotherapy. Ongoing clinical trials are examining the impact of very low LDL-C levels on cardiovascular disease event rates and the long-term safety of this approach. PMID:27620356

  18. Development of Low Density Flexible Carbon Phenolic Ablators

    NASA Technical Reports Server (NTRS)

    Stackpole, Mairead; Thornton, Jeremy; Fan, Wendy; Agrawal, Parul; Doxtad, Evan; Gasch, Matt

    2011-01-01

    Phenolic Impregnated Carbon Ablator (PICA) was the enabling TPS material for the Stardust mission where it was used as a single piece heatshield. PICA has the advantages of low density (0.27g/cm3) coupled with efficient ablative capability at high heat fluxes. Under the Orion program, PICA was also shown to be capable of both ISS and lunar return missions however some unresolved issues remain for its application in a tiled configuration for the Orion-specific design. In particular, the problem of developing an appropriate gap filler resulted in the Orion program selecting AVCOAT as the primary heatshield material over PICA. We are currently looking at alternative architectures to yield flexible and more conformal carbon phenolic materials with comparable densities to PICA that will address some of the design issues faced in the application of a tiled PICA heat shield. These new materials are viable TPS candidates for upcoming NASA missions and as material candidates for private sector Commercial Orbital Transportation Services (COTS). This presentation will discuss flexible alternatives to PICA and include preliminary mechanical and thermal properties as well as arc jet and LHMEL screening test results.

  19. Electrical conduction in irradiated low-density polyethylene

    NASA Astrophysics Data System (ADS)

    Banford, H. M.; Fouracre, R. A.; Chen, G.; Tedford, D. J.

    A programme of experiments has been undertaken to examine transient charging/discharging currents and steady state currents in low-density polyethylene (LDPE) under the application of direct fields. This has been undertaken for pristine material and for material which has received doses of radiation between 10 4 and 10 6 Gy from either a 60Co γ-source or a research reactor. The material was irradiated in ambient air or dry nitrogen. Measurements were made for applied fields in the range 6.7 × 10 5-5.3 × 10 7 V m -1 and temperatures between ambient and 90°C. With pristine material at low fields, transient charging/discharging currents decreased monotonically with time. However, the mechanism changed at higher fields with a peak occurring in the charging transient indicating a space-charge limited process. Substantial charge injection was also in evidence as demonstrated by anomalous discharging currents. This transient response was echoed by the current/voltage characteristics of steady state behaviour. Gamma and neutron irradiation brought about a change in this situation and the charge transport mechanism altered gradually from space-charge-limited conduction to an ohmic process with increasing dose. The role played by charge traps appears to be significant.

  20. Modeling shock-driven reaction in low density PMDI foam

    NASA Astrophysics Data System (ADS)

    Brundage, Aaron; Alexander, C. Scott; Reinhart, William; Peterson, David

    Shock experiments on low density polyurethane foams reveal evidence of reaction at low impact pressures. However, these reaction thresholds are not evident over the low pressures reported for historical Hugoniot data of highly distended polyurethane at densities below 0.1 g/cc. To fill this gap, impact data given in a companion paper for polymethylene diisocyanate (PMDI) foam with a density of 0.087 g/cc were acquired for model validation. An equation of state (EOS) was developed to predict the shock response of these highly distended materials over the full range of impact conditions representing compaction of the inert material, low-pressure decomposition, and compression of the reaction products. A tabular SESAME EOS of the reaction products was generated using the JCZS database in the TIGER equilibrium code. In particular, the Arrhenius Burn EOS, a two-state model which transitions from an unreacted to a reacted state using single step Arrhenius kinetics, as implemented in the shock physics code CTH, was modified to include a statistical distribution of states. Hence, a single EOS is presented that predicts the onset to reaction due to shock loading in PMDI-based polyurethane foams. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE-AC04-94AL85000.

  1. Three-Dimensional, Nondestructive Imaging of Low Density Materials

    SciTech Connect

    Kinney, J.H.; Haupt, D.L.; Lemay, J.D.

    1999-10-29

    The goal of this study was to develop a three-dimensional imaging method for studies of deformation in low-density materials during loading, and to implement finite element solutions of the elastic equations based on the images. Specimens of silica-reinforced polysiloxane foam pads, 15 mm in diameter by 1 mm thick, were used for this study. The nominal pore density was 50%, and the pores approximated interconnected spheres. The specimens were imaged with microtomography at {approx}16{micro}m resolution. A rotating stage with micrometer driven compression allowed imaging of the foams during deformation with precise registration of the images. A finite element mesh, generated from the image voxels, was used to calculate the mechanical properties of the structure, and the results were compared with conventional mechanical testing. The foam exhibited significant nonlinear behavior with compressive loading. The finite-element calculations from the images, which were in excellent agreement with experimental data, suggested that nonlinear behavior in the load displacement curves arises from buckling of the cell walls during compression and not from any nonlinear properties of the base elastomer. High-resolution microtomography, coupled with efficient finite-element modeling, shows promise for improving our understanding of the deformation behavior of cellular materials.

  2. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages

    PubMed Central

    Atrahimovich, Dana; Khatib, Soliman; Sela, Shifra; Vaya, Jacob

    2016-01-01

    High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels. PMID:27516832

  3. Catabolism of low density lipoproteins by perfused rabbit livers: cholestyramine promotes receptor-dependent hepatic catabolism of low density lipoproteins.

    PubMed

    Chao, Y S; Yamin, T T; Alberts, A W

    1982-07-01

    Rabbits fed a wheat starch/casein diet develop a marked hypercholesterolemia accompanied by a decrease in the number of EDTA-sensitive binding sites on plasma membrane fractions of the liver for low density lipoproteins (LDL) and beta-migrating very low density lipoproteins [Chao, Y.-S., Yamin, T.-T. & Alberts, A. W. (1982) J. Biol. Chem., in press]. Inclusion of 1% cholestyramine resin in this diet prevents the increase in plasma cholesterol, increases the removal of LDL from plasma, and increases the number of hepatic plasma membrane LDL-binding sites. To determine the functional role of hepatic LDL-binding sites in the catabolism of LDL, we studied the catabolism of (125)I-labeled LDL ((125)I-LDL) by in situ perfused rabbit livers in a recirculating system. The rate of catabolism was measured from the increment of nonprotein-bound radioiodine in the perfusate. The receptor-dependent catabolism of LDL by the liver was calculated from the difference of hepatic catabolism of (125)I-LDL and catabolism of (125)I-labeled cyclohexanedione-modified LDL, which does not bind to LDL receptors. The data show that about 74% of LDL catabolized by perfused livers from chow-fed rabbits is through the receptor-dependent pathway and 26% is through the receptor-independent pathway. In rabbits fed a cholesterol diet, the hepatic catabolism of (125)I-LDL is reduced, and the receptor-dependent catabolism of (125)I-LDL is abolished. In rabbits fed the wheat starch/casein diet, the receptor-dependent catabolism of (125)I-LDL is reduced by 40% when compared with hepatic catabolism in chow-fed rabbits. Perfused livers from rabbits fed the wheat starch/casein diet supplemented with 1% cholestyramine show a 5,4-fold increase of receptor-dependent catabolism of (125)I-LDL when compared with that of livers from rabbits fed the wheat starch/casein diet alone. Thus, these studies demonstrate that the change in the number of rabbit hepatic membrane LDL receptors induced by dietary manipulation

  4. Bonding Low-density Nanoporous Metal Foams Using Sputtered Solder

    SciTech Connect

    Bono, M; Cervantes, O; Akaba, C; Hamza, A; Foreman, R; Teslich, N

    2007-08-21

    A method has been developed for bonding low-density nanoporous metal foam components to a substrate using solder that is sputtered onto the surfaces. Metal foams have unusual properties that make them excellent choices for many applications, and as technologies for processing these materials are evolving, their use in industry is increasing dramatically. Metal foams are lightweight and have advantageous dynamic properties, which make them excellent choices for many structural applications. They also provide good acoustic damping, low thermal conductivity, and excellent energy absorption characteristics. Therefore, these materials are commonly used in the automotive, aerospace, construction, and biomedical industries. The synthesis of nanoporous metal foams with a cell size of less then 1 {micro}m is an emerging technology that is expected to lead to widespread application of metal foams in microdevices, such as sensors and actuators. One of the challenges to manufacturing components from metal foams is that they can be difficult to attach to other structures without degrading their properties. For example, traditional liquid adhesives cannot be used because they are absorbed into foams. The problem of bonding or joining can be particularly difficult for small-scale devices made from nanoporous foam, due to the requirement for a thin bond layer. The current study addresses this problem and develops a method of soldering a nanoporous metal foam to a substrate with a bond thickness of less than 2 {micro}m. There are many applications that require micro-scale metal foams precisely bonded to substrates. This study was motivated by a physics experiment that used a laser to drive a shock wave through an aluminum foil and into a copper foam, in order to determine the speed of the shock in the copper foam. To avoid disturbing the shock, the interface between the copper foam and the aluminum substrate had to be as thin as possible. There are many other applications that

  5. Hypercholesterolemia, low density lipoprotein receptor and proprotein convertase subtilisin/kexin-type 9

    PubMed Central

    Gu, Hong-mei; Zhang, Da-wei

    2015-01-01

    Abstract Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world. Plasma levels of low density lipoprotein cholesterol (LDL-C) are positively correlated with the risk of atherosclerosis. High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries, which becomes oxidized and promotes the formation of foam cells, consequently initiating atherosclerosis. Plasma LDL is mainly cleared through the LDL receptor (LDLR) pathway. Mutations in the LDLR cause familiar hypercholesterolemia and increase the risk of premature coronary heart disease. The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2 (SREBP-2) and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9 (PCSK9) and inducible degrader of the LDLR (IDOL). In this review, we summarize the latest advances in the studies of PCSK9. PMID:26445568

  6. High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis?

    PubMed

    de Munter, Wouter; van der Kraan, Peter M; van den Berg, Wim B; van Lent, Peter L E M

    2016-01-01

    There is increasing evidence that low-density lipoprotein (LDL) cholesterol plays a role in the pathology of OA. Specifically, oxidized LDL (oxLDL), which has been shown to play an essential role during development of atherosclerosis, could be involved in processes such as synovial inflammation, cartilage destruction and bone deformations. OxLDL can activate synovial cells such as macrophages, endothelial cells and synovial fibroblasts, resulting in release of growth factors, MMP and pro-inflammatory cytokines. In this review article, we discuss the role of LDL and oxLDL in OA joint pathology and share our viewpoint of possible mechanisms by which these proteins could influence the development and progression of OA. The proposed theory could provide insight into the aetiopathology of OA and give rise to new potential treatments. PMID:26231344

  7. Low density lipoprotein subclasses in Asian and Caucasian adolescent boys.

    PubMed

    Raschke, Verena; Elmadfa, Ibrahim; Bermingham, Margaret A; Steinbeck, Kate

    2006-01-01

    South Asian adults are known to have very high rates of Coronary heart disease (CHD) and insulin resistance and, even as adolescents, may show higher risk factors for CHD. The aim of this study was to investigate the prevalence of small, dense low density lipoprotein (sdLDL) subclasses in a cohort of adolescent boys. The specific objective was to investigate the relationship between measures of fatness, ethnicity and LDL diameter in this cohort. Preformed native (non-denaturing) polyacrylamide 3-13% gradient gels and a multipurpose vertical electrophoresis system were used for the separation of LDL sub-fractions in a single school year cohort of boys aged 15-16 years (n=135). Latex beads and thyroglobulin standards were used to construct a calibration curve in order to calculate LDL particle diameters by regression (Total Lab Software v1.11). ANOVA was used to compare LDL size among different ethnic groups (SPSS and Stat View). The study sample was comprised of 45.2% Caucasians, 41.5% East Asians and 13.3% from the Indian subcontinent (South Asians). There was a non-significant trend for South Asians to have a lower LDL diameter than either Caucasians or East Asian boys which was independent of % total body fat (%TBF) and body mass index (BMI). This is the first adolescent cohort to examine sdLDL which included Caucasians, East and South Asians. It appears that the higher risk profile for CHD and diabetes noted in South Asian adults may be evident even during adolescence. PMID:17077065

  8. Morphology Effects on Space Charge Characteristics of Low Density Polyethylene

    NASA Astrophysics Data System (ADS)

    Zhou; Yuanxiang; Wang; Yunshan; Zahn, Markus; Wang; Ninghua; Sun; Qinghua; Liang; Xidong; Guan; Zhichen

    2011-01-01

    Low density polyethylene (LDPE) film samples with different morphology were prepared by three kinds of annealing methods which were different in cooling rates in this study. A pulsed electro-acoustic (PEA) space charge measurement system was improved to solve the surface discharge problems for small samples applied with a high voltage. Negative direct current (DC) fields from 50 to above 220 kV/mm were applied to the samples. The influences of morphologies on space charge and space charge packet characteristics were measured by the improved high voltage withstand (HVW) PEA system. Mobility and trap depth of released charges were calculated by space charge decay. It was found that there is a different probability of space charge packet initiation under applied field from -60 to -100 kV/mm. Average velocity and mobility of the space charge packets were calculated by space charge packet dynamics. It was found that the lower cooling rate samples have higher crystallinity, more homo-charge accumulation, lower mobility and deeper trap depth. The mechanism of morphological effects on space charge phenomena have been presumed to give a plausible explanation for their inherent relationships. The morphology in the metal-dielectric interface and in the bulk is convincingly suggested to be responsible for the injection and propagation processes of space charge. A model of positive space charge initiation in LDPE samples was also suggested and analyzed. The mechanism of morphological effects and the charge injection model are well fit with the injection and propagation processes of space charge. The different effects of morphology in the metal-dielectric interface and in the bulk of polymers are stressed.

  9. Low Density Lipoprotein transport in the normal human aortic arch

    PubMed Central

    Soulis, JV; Dimitrakopoulou, M; Giannoglou, GD

    2014-01-01

    Background: To understand the genesis and progression of atherosclerosis is essential to elucidate the blood flow and the transport of molecules in the cardiovascular system. The purpose of this computational study is to elucidate the relationship between low wall shear stress (WSS) - high site concentration of low density lipoproteins (LDL) and atherosclerotic sites in the normal human aortic arch under physiological flow and mass transport conditions. Methods: The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall in terms of blood-side concentration. The blood is considered to be non-Newtonian fluid obeying to the power law. Suitable mass transport conditions are specified at the wall. Results: Aortic arch walls are exposed to cholesterolemic environment although the applied mass and flow conditions refer to normal human geometry and normal mass-flow conditions. The luminal surface LDL concentration varies inversely with the WSS. Regions of high LDL luminal surface concentration do not necessarily co-locate to the sites of lowest WSS. Concave sides of the aortic arch exhibit, relatively to the convex sides, elevated concentration of the LDL. The area averaged normalized LDL concentration over the entire normal aortic arch is 1.267. The daughter aortic arch vessels exhibit, relatively to the main aorta, elevated LDL concentrations. Conclusions: The near wall paths of the velocities might be the most important factor for the elevated LDL concentration at areas located either at the vicinity of bifurcations regions or at high curvature regions. Hippokratia 2014; 18 (3): 221-225. PMID:25694755

  10. Two Transiting Low Density Sub-Saturns from K2

    NASA Astrophysics Data System (ADS)

    Petigura, Erik A.; Howard, Andrew W.; Lopez, Eric D.; Deck, Katherine M.; Fulton, Benjamin J.; Crossfield, Ian J. M.; Ciardi, David R.; Chiang, Eugene; Lee, Eve J.; Isaacson, Howard; Beichman, Charles A.; Hansen, Brad M. S.; Schlieder, Joshua E.; Sinukoff, Evan

    2016-02-01

    We report the discovery and confirmation of K2-24 b and c, two sub-Saturn planets orbiting a bright (V = 11.3), metal-rich ([Fe/H] = 0.42 ± 0.04 dex) G3 dwarf in the K2 Campaign 2 field. The planets are 5.68 ± 0.56 {R}\\oplus and 7.82 ± 0.72 {R}\\oplus and have orbital periods of 20.8851 ± 0.0003 days and 42.3633 ± 0.0006 days, near the 2:1 mean-motion resonance. We obtained 32 radial velocities with Keck/HIRES and detected the reflex motion due to K2-24 b and c. These planets have masses of 21.0 ± 5.4 {M}\\oplus and 27.0 ± 6.9 {M}\\oplus , respectively. With low densities of 0.63 ± 0.25 g cm-3 and 0.31 ± 0.12 g cm-3, respectively, the planets require thick envelopes of H/He to explain their large sizes and low masses. Interior structure models predict that the planets have fairly massive cores of 17.6+/- 4.3 {M}\\oplus and 16.1+/- 4.2 {M}\\oplus , respectively. They may have formed exterior to their present locations, accreted their H/He envelopes at large orbital distances, and migrated in as a resonant pair. The proximity to resonance, large transit depths, and host star brightness offers rich opportunities for TTV follow-up. Finally, the low surface gravities of the K2-24 planets make them favorable targets for transmission spectroscopy by Hubble Space Telescope, Spitzer, and James Webb Space Telescope.

  11. Development of Low Density Titanium Alloys for Structural Applications

    NASA Technical Reports Server (NTRS)

    Froes, F. H.; Suryanarayana, C.; Powell, C.; Ward-Close, C. Malcolm; Wilkes, D. M. J.

    1996-01-01

    In this report the results of a program designed to reduce the density of titanium by adding magnesium are presented. Because these two elements are immiscible under conventional ingot metallurgy techniques, two specialized powder metallurgy methods namely, mechanical alloying (MA) and physical vapor deposition (PVD) were implemented. The mechanical alloying experiments were done both at the University of Idaho and at the Defense Research Agency in UK. Since titanium is reactive with interstitial elements, a secondary goal of this research was to correlate solubility extensions with interstitial contamination content, especially oxygen and nitrogen. MA was carried out in SPEX 8000 shaker mils and different milling containers were utilized to control the level of contamination. Results showed that solubilities of Mg in Ti were obtained up to 28 at.% (16.4 wt. %) Mg in Ti for Ti-39.6 at. % (25 wt. %) Mg alloys, which greatly exceed those obtained under equilibrium conditions. This reflects a density reduction of approximately 26 %. Contamination of oxygen and nitrogen seemed to increase the solubility of magnesium in titanium in some cases; however, we were not able to make a clear correlation between contamination levels with solubilities. Work at the DRA has emphasized optimization of present PVD equipment, specifically composition and temperature control. Preliminary PVD data has shown Ti-Mg deposits have successfully been made up to 2 mm thick and that solubility extensions were achieved. The potential for density reduction of titanium by alloying with magnesium has been demonstrated; however, this work has only scratched the surface of the development of such low density alloys. Much research is needed before such alloys could be implemented into industry. Further funding is required in order to optimize the MA/PVD processes including contamination control, determination of optimal alloy compositions, microstructure development, and mechanical property

  12. Accuracy of genomic prediction using low-density marker panels.

    PubMed

    Zhang, Z; Ding, X; Liu, J; Zhang, Q; de Koning, D-J

    2011-07-01

    Genomic selection has been widely implemented in national and international genetic evaluation in the dairy cattle industry, because of its potential advantages over traditional selection methods and the availability of commercial high-density (HD) single nucleotide polymorphism (SNP) panels. However, this method may not be cost-effective for cow selection and for other livestock species, because the cost of HD SNP panels is still relatively high. One possible solution that can enable other species to benefit from this promising method is genomic selection with low-density (LD) SNP panels. In this simulation study, LD SNP panels designed with different strategies and different SNP densities were compared. The effects of number of quantitative trait loci, heritability, and effective population size were evaluated in the framework of genomic selection with LD SNP panels. Methodologies of Bayesian variable selection; BLUP with a trait-specific, marker-derived relationship matrix; and BLUP with a realized relationship matrix were employed to predict genomic estimated breeding values with both HD and LD SNP panels. Up to 95% of accuracy obtained by using an HD panel can be obtained by using only a small proportion of markers. The LD panel with markers selected on the basis of their effects always performs better than the LD panel with evenly spaced markers. Both the genetic architecture of the trait and the effective population size have a significant effect on the performance of the LD panels. We concluded that, to implement genomic selection with LD panels, a training population of sufficient size and genotyped with an HD panel is necessary. The trade-off between the LD panels with evenly spaced markers and selected markers must be considered, which depends on the number of target traits in a breeding program and the genetic architecture of these traits. Genomic selection with LD panels could be feasible and cost-effective, though before implementation, a further

  13. Metabolism of apoprotein B of plasma very low density lipoproteins in the rat.

    PubMed Central

    Faergeman, O; Sata, T; Kane, J P; Havel, R J

    1975-01-01

    As an extension of metabolic studies of the cholesteryl ester component of rat very low density lipoproteins, we have studied the metabolism of the B apoprotein component labeled by intravenous injection of [3H]lysine. The B apoprotein separated from other apoproteins by delipidation and selective precipitation with tetramethylurea could not be distinguished from B apoprotein prepared by the conventional gel filtration technique. After injection of [3H]lysine, specific activity of B apoprotein was maximal in very low density and low density lipoproteins 1 and 11/2-h later, respectively, in a manner consistent with a precursor-product relationship. When protein-labeled very low density lipoproteins were injected into rats, the relationships of specific activity again indicated that B apoprotein of very low density lipoproteins may be the sole precursor of that of low density lipoproteins. However, less than 10% of the B apoprotein that disappeared from very low density lipoproteins appeared in density lipoproteins. To evaluate the sites of removal of B aproprotein of very low density lipoproteins from plasma, protein-labeled very low density lipoproteins were incubated with unlabeled high density lipoproteins to reduce radioactivity in non-B apoproteins selectively by molecular exchange. Most of the B apoprotein was rapidly removed by the liver. The extensive hepatic uptake of both the cholesteryl ester and B apoprotein components of rat very low density lipoproteins may explain the characteristically low concentrations of plasma low density lipoproteins in the rat. PMID:172530

  14. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    PubMed

    Meeusen, Jeffrey W; Snozek, Christine L; Baumann, Nikola A; Jaffe, Allan S; Saenger, Amy K

    2015-08-15

    Aggressive low-density lipoprotein cholesterol (LDL-C)-lowering strategies are recommended for prevention of cardiovascular events in high-risk populations. Guidelines recommend a 30% to 50% reduction in at-risk patients even when LDL-C concentrations are between 70 and 130 mg/dl (1.8 to 3.4 mmol/L). However, calculation of LDL-C by the Friedewald equation is the primary laboratory method for routine LDL-C measurement. We compared the accuracy and reproducibility of calculated LDL-C <130 mg/dl (3.4 mmol/L) to LDL-C measured by β quantification (considered the gold standard method) in 15,917 patients with fasting triglyceride concentrations <400 mg/dl (4.5 mmol/L). Both variation and bias of calculated LDL-C increased at lower values of measured LDL-C. The 95% confidence intervals for a calculated LDL-C of 70 mg/dl (1.8 mmol/L) and 30 mg/dl (0.8 mmol/L) were 60 to 86 mg/dl (1.6 to 2.2 mmol/L) and 24 to 60 mg/dl (0.6 to 1.6 mmol/L), respectively. Previous recommendations have emphasized the requirement for a fasting sample with triglycerides <400 mg/dl (4.5 mmol/L) to calculate LDL-C by the Friedewald equation. However, no recommendations have addressed the appropriate lower reportable limit for calculated LDL-C. In conclusion, calculated LDL-C <30 mg/dl (0.8 mmol/L) should not be reported because of significant deviation from the gold standard measured LDL-C results, and caution is advised when using calculated LDL-CF values <70 mg/dl (1.8 mmol/L) to make treatment decisions. PMID:26059865

  15. An efficient decoding for low density parity check codes

    NASA Astrophysics Data System (ADS)

    Zhao, Ling; Zhang, Xiaolin; Zhu, Manjie

    2009-12-01

    Low density parity check (LDPC) codes are a class of forward-error-correction codes. They are among the best-known codes capable of achieving low bit error rates (BER) approaching Shannon's capacity limit. Recently, LDPC codes have been adopted by the European Digital Video Broadcasting (DVB-S2) standard, and have also been proposed for the emerging IEEE 802.16 fixed and mobile broadband wireless-access standard. The consultative committee for space data system (CCSDS) has also recommended using LDPC codes in the deep space communications and near-earth communications. It is obvious that LDPC codes will be widely used in wired and wireless communication, magnetic recording, optical networking, DVB, and other fields in the near future. Efficient hardware implementation of LDPC codes is of great interest since LDPC codes are being considered for a wide range of applications. This paper presents an efficient partially parallel decoder architecture suited for quasi-cyclic (QC) LDPC codes using Belief propagation algorithm for decoding. Algorithmic transformation and architectural level optimization are incorporated to reduce the critical path. First, analyze the check matrix of LDPC code, to find out the relationship between the row weight and the column weight. And then, the sharing level of the check node updating units (CNU) and the variable node updating units (VNU) are determined according to the relationship. After that, rearrange the CNU and the VNU, and divide them into several smaller parts, with the help of some assistant logic circuit, these smaller parts can be grouped into CNU during the check node update processing and grouped into VNU during the variable node update processing. These smaller parts are called node update kernel units (NKU) and the assistant logic circuit are called node update auxiliary unit (NAU). With NAUs' help, the two steps of iteration operation are completed by NKUs, which brings in great hardware resource reduction. Meanwhile

  16. Combining Ratio Estimation for Low Density Parity Check (LDPC) Coding

    NASA Technical Reports Server (NTRS)

    Mahmoud, Saad; Hi, Jianjun

    2012-01-01

    The Low Density Parity Check (LDPC) Code decoding algorithm make use of a scaled receive signal derived from maximizing the log-likelihood ratio of the received signal. The scaling factor (often called the combining ratio) in an AWGN channel is a ratio between signal amplitude and noise variance. Accurately estimating this ratio has shown as much as 0.6 dB decoding performance gain. This presentation briefly describes three methods for estimating the combining ratio: a Pilot-Guided estimation method, a Blind estimation method, and a Simulation-Based Look-Up table. The Pilot Guided Estimation method has shown that the maximum likelihood estimates of signal amplitude is the mean inner product of the received sequence and the known sequence, the attached synchronization marker (ASM) , and signal variance is the difference of the mean of the squared received sequence and the square of the signal amplitude. This method has the advantage of simplicity at the expense of latency since several frames worth of ASMs. The Blind estimation method s maximum likelihood estimator is the average of the product of the received signal with the hyperbolic tangent of the product combining ratio and the received signal. The root of this equation can be determined by an iterative binary search between 0 and 1 after normalizing the received sequence. This method has the benefit of requiring one frame of data to estimate the combining ratio which is good for faster changing channels compared to the previous method, however it is computationally expensive. The final method uses a look-up table based on prior simulated results to determine signal amplitude and noise variance. In this method the received mean signal strength is controlled to a constant soft decision value. The magnitude of the deviation is averaged over a predetermined number of samples. This value is referenced in a look up table to determine the combining ratio that prior simulation associated with the average magnitude of

  17. Fluvial entrainment of low density peat blocks (block carbon)

    NASA Astrophysics Data System (ADS)

    Warburton, Jeff

    2014-05-01

    In many fluvial environments low density materials are transported in significant quantities and these form an important part of the stream load and /or have a distinct impact on sedimentation in these environments. However, there are significant gaps in understanding of how these materials are entrained and transported by streams and rivers. Eroding upland peatland environments in particular, frequently have fluvial systems in which large eroded peat blocks, often exceeding 1 m in length; form an important component of the stream material flux. Transport of this material is significant in determining rates of erosion but also has important impacts in terms of damage to infrastructure and carbon loss. This paper describes a field experiment designed to establish for the first time the conditions under which large peat blocks (c. > 0.1 m b axis) are initially entrained from a rough gravel bed. The field site is Trout Beck, in the North Pennines, Northern England which is an upland wandering river channel with occasional lateral and mid channel bars. Mean low flow stage is typically 0.2 m but during flood can rapidly rise, in one to two hours, to over 1.5 m. To study peat block entrainment a bespoke data acquisition system consisting of two pressure transducers, four release triggers and time lapse camera was set up. The pressure transducers provided a record of local depth and the release triggers were embedded in peat blocks to record initial motion and arranged on the rough stream bed. The time lapse camera provided verification of timing of block entrainment (during daylight hours) and also provided information on the mechanism of initial movement. Peat blocks were cut from a local source and were equidimensional, ranging in size from 0.1 to 0.7 m. The derived entrainment function is related to a critical depth of entrainment. Results demonstrate that peat blocks are entrained when the local depth approximates the height of the peat block. Blocks frequently shift

  18. The Conductor-Dielectric Junctions in a Low Density Plasma

    NASA Technical Reports Server (NTRS)

    Vayner, Boris; Galofaro, Joel; Ferguson, Dale; deGroot, Wim; Thomson, Clint; Dennison, J. R.; Davies, Robert

    1999-01-01

    chromic acid anodized aluminum plate immersed in low density argon and xenon plasmas. Analysis of these spectra confirms our earlier findings that aluminum atoms are ejected from the arc site. Moreover, it is found that chromium atoms are also quite abundant in the arc plasma. It is believed that the latter results contribute considerably to the understanding of processes of plasma contamination caused by arcing.

  19. Cholesterol transfer from normal and atherogenic low density lipoproteins to Mycoplasma membranes

    SciTech Connect

    Mitschelen, J.J.; St. Clair, R.W.; Hester, S.H.

    1981-01-01

    The purpose of this study was to determine whether the free cholesterol of hypercholesterolemic low density lipoprotein from cholesterol-fed nonhuman primates has a greater potential for surface transfer to cell membranes than does the free cholesterol of normal low density lipoprotein. The low density lipoproteins were isolated from normal and hypercholesterolemic rhesus and cynomolgus monkeys, incubated with membranes from Acholeplasma laidlawii, a mycoplasma species devoid of cholesterol in its membranes, and the mass transfer of free cholesterol determined by measuring membrane cholesterol content. Since these membranes neither synthesize nor esterify cholesterol, nor degrade the protein or cholesterol ester moieties of low density lipoprotein, they are an ideal model with which to study differences in the cholesterol transfer potential of low density lipoprotein independent of the uptake of the intact low density lipoprotein particle. These studies indicate that, even though there are marked differences in the cholesterol composition of normal and hypercholesterolemic low density lipoproteins, this does not result in a greater chemical potential for surface transfer of free cholesterol. Consequently, if a difference in the surface transfer of free cholesterol is responsible for the enhanced ability of hypercholesterolemic low density lipoprotein to promote cellular cholesterol accumulation and, perhaps, also atherosclerosis, it must be the result of differences in the interaction to the hypercholesterolemic low density lipoprotein with the more complicated mammalian cell membranes, rather than differences in the chemical potential for cholesterol transfer.

  20. Impaired stimulation of glucose transport in cardiac myocytes exposed to very low-density lipoproteins.

    PubMed

    Papageorgiou, I; Viglino, C; Brulhart-Meynet, M-C; James, R W; Lerch, R; Montessuit, C

    2016-07-01

    We recently observed that free fatty acids impair the stimulation of glucose transport into cardiomyocytes in response to either insulin or metabolic stress. In vivo, fatty acids for the myocardium are mostly obtained from triglyceride-rich lipoproteins (chylomicrons and Very Low-Density Lipoproteins). We therefore determined whether exposure of cardiac myocytes to VLDL resulted in impaired basal and stimulated glucose transport. Primary adult rat cardiac myocytes were chronically exposed to VLDL before glucose uptake was measured in response to insulin or metabolic stress, provoked by the mitochondrial ATP synthase inhibitor oligomycin. Exposure of cardiac myocytes to VLDL reduced both insulin-and oligomycin-stimulated glucose uptake. The reduction of glucose uptake was associated with a moderately reduced tyrosine phosphorylation of the insulin receptor. No reduction of the phosphorylation of the downstream effectors of insulin signaling Akt and AS160 was however observed. Similarly only a modest reduction of the activating phosphorylation of the AMP-activated kinase (AMPK) was observed in response to oligomycin. Similar to our previous observations with free fatty acids, inhibition of fatty acid oxidation restored oligomycin-stimulated glucose uptake. In conclusions, VLDL-derived fatty acids impair stimulated glucose transport in cardiac myocytes by a mechanism that seems to be mediated by a fatty acid oxidation intermediate. Thus, in the clinical context of the metabolic syndrome high VLDL may contribute to enhancement of ischemic injury by reduction of metabolic stress-stimulated glucose uptake. PMID:27052924

  1. Lipoprotein Lipase releases esterified oxylipins from Very Low Density Lipoproteins

    PubMed Central

    Shearer, Gregory C.; Newman, John W.

    2009-01-01

    We previously demonstrated that defects in lipoprotein metabolism alter the distribution of oxygenated polyunsaturated fatty acids (PUFAs) in lipoprotein particles. If these oxidation products are released by lipoprotein lipase (LpL), then their delivery to peripheral tissues with bulk lipids could influence cellular function. Using 26 week old normolipidemic and hyperlipidemic Zucker rats, we measured PUFA alcohols, epoxides, diols, ketones and triols (i.e. oxylipins) in esterified and non-esterified fractions of whole plasma, VLDL, and LpL-generated VLDL-lipolysates. Whole plasma, VLDL, and lipolysate oxylipin profiles were distinct and altered by hyperlipidemia. While >90% of the whole plasma oxylipins were esterified, the fraction of each oxylipin class in the VLDL varied: 46% of alcohols, 30% of epoxides, 19% of diols, <10% of ketones, <1% triols. Whole plasma was dominated by arachidonate alcohols, while the linoleate alcohols, epoxides and ketones showed an increased prevalence in VLDL. LpL-mediated VLDL lipolysis of PUFA alcohols, diols and ketones was detected and the relative abundance of oxygenated linoleates was enhanced in the lipolysates, relative to their corresponding VLDL. In summary esterified oxylipins were seen to be LpL substrates with heterogeneous distributions among lipoprotein classes. Moreover, oxylipin distributions are changes within the context of obesity-associated dyslipidemia. These results support the notion that the VLDL-LpL axis may facilitate the delivery of plasma oxylipins to the periphery. The physiological implication of these findings are yet to be elucidated, however these molecules are plausible indicators of systemic oxidative stress, and could report this status to the peripheral tissues. PMID:19042114

  2. Explosively driven low-density foams and powders

    DOEpatents

    Viecelli, James A.; Wood, Lowell L.; Ishikawa, Muriel Y.; Nuckolls, John H.; Pagoria, Phillip F.

    2010-05-04

    Hollow RX-08HD cylindrical charges were loaded with boron and PTFE, in the form of low-bulk density powders or powders dispersed in a rigid foam matrix. Each charge was initiated by a Comp B booster at one end, producing a detonation wave propagating down the length of the cylinder, crushing the foam or bulk powder and collapsing the void spaces. The PdV work done in crushing the material heated it to high temperatures, expelling it in a high velocity fluid jet. In the case of boron particles supported in foam, framing camera photos, temperature measurements, and aluminum witness plates suggest that the boron was completely vaporized by the crush wave and that the boron vapor turbulently mixed with and burned in the surrounding air. In the case of PTFE powder, X-ray photoelectron spectroscopy of residues recovered from fragments of a granite target slab suggest that heating was sufficient to dissociate the PTFE to carbon vapor and molecular fluorine which reacted with the quartz and aluminum silicates in the granite to form aluminum oxide and mineral fluoride compounds.

  3. Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.

    PubMed Central

    Berliner, J A; Territo, M C; Sevanian, A; Ramin, S; Kim, J A; Bamshad, B; Esterson, M; Fogelman, A M

    1990-01-01

    The effect of minimally modified LDL (MM-LDL) on the ability of large vessel endothelial cells (EC) to interact with monocytes and neutrophils was examined. These LDL preparations, obtained by storage or by mild iron oxidation, were indistinguishable from native LDL to the LDL receptor and were not recognized by the scavenger receptor. Treatment of EC with as little as 0.12 micrograms/ml MM-LDL caused a significant increase in the production of chemotactic factor for monocytes (sevenfold) and increased monocyte binding (three- to fivefold). Monocyte binding was maximal after 4 h of EC exposure to MM-LDL, persisted for 48 h, and was inhibited by cycloheximide. In contrast, neutrophil binding was not increased after 1-24 h of exposure. Activity in the MM-LDL preparations was found primarily in the polar lipid fraction. MM-LDL was toxic for EC from one rabbit but not toxic for the cells from another rabbit or any human umbilical vein EC. The resistant cells became sensitive when incubated with lipoprotein in the presence of cycloheximide, whereas the sensitive strain became resistant when preincubated with sublethal concentrations of MM-LDL. We conclude that exposure of EC to sublethal levels of MM-LDL enhances monocyte endothelial interactions and induces resistance to the toxic effects of MM-LDL. Images PMID:2318980

  4. Fabrication of very-low-density, high-stiffness carbon fiber/aluminum hybridized composite with ultra-low density and high stiffness (M-11)

    NASA Technical Reports Server (NTRS)

    Suzuki, Tomoo

    1993-01-01

    Fabrication of a composite material with ultra-low density and high stiffness in microgravity is the objective of the investigation. The composite structure to be obtained is a random three-dimensional array of high modulus, short carbon fibers bonded at contact points by an aluminum alloy coated on the fibers. The material is highly porous and thus has a very low density. The motivation toward the investigation, simulation experiments, choice of the component materials, and on-flight experiment during ballistic trajectory of a NASDA rocket, are described.

  5. Aggregation and fusion of low-density lipoproteins in vivo and in vitro

    PubMed Central

    Gursky, Olga

    2014-01-01

    Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions. PMID:25197325

  6. The behavior of high-purity, low-density air plasma sprayed thermal barrier coatings

    SciTech Connect

    Helminiak, Yanar NM

    2009-12-01

    Research on the behavior of high-purity, low-density (85%) air plasma sprayed (APS) thermal barrier coatings (TBC) with NiCoCrAlY bond coats deposited by argon-shrouded plasma spraying is described. The microstructure of the APS topcoats is one variable in this study intended to maximize the coating thicknesses that can be applied without spallation and to minimize the thermal conduction through the YSZ layer. The specimens were evaluated using cyclic oxidation tests and important properties of the TBCs, such as resistance to sintering and phase transformation, were determined. The high purity resulted in top coats which are highly resistant to sintering and transformation from the metastable tetragonal phase to the equilibrium mixture of monoclinic and cubic phases. The porous topcoat microstructure also resulted in significant durability during thermal cycling. The actual failure mechanisms of the APS coatings were found to depend on topcoat thickness, CTE of the superalloy substrate and the nature of the thermal exposure.

  7. Low density lipoprotein aged in plasma forms clusters resembling subendothelial droplets: aggregation via surface sites.

    PubMed

    De Spirito, Marco; Brunelli, Roberto; Mei, Giampiero; Bertani, Francesca R; Ciasca, Gabriele; Greco, Giulia; Papi, Massimiliano; Arcovito, Giuseppe; Ursini, Fulvio; Parasassi, Tiziana

    2006-06-01

    In early phases of atherogenesis, droplets and vesicles accumulate in the subendothelial extracellular space of arterial intima. There is much evidence to suggest that these droplets, ranging between 100 and 400 nm, derive from modified low-density lipoprotein (LDL). In investigations of the formation mechanism of these droplets, LDL fusion was previously induced in vitro by proteolysis, lipolysis, oxidation, and vigorous shaking, but all treatments failed to reproduce the size distribution range of in vivo droplets, mostly resulting, instead, in particles with a diameter intermediate between that of one and two LDL. Our approach was meant to mimic LDL aging in plasma. LDL isolated from plasma that was incubated overnight at 37 degrees C is slightly modified in the secondary structure of its protein component and is primed to form very large aggregates according to a reaction-limited mechanism. This mechanism requires interactions between selected surface sites, whereas massive fusion is ruled out. In the frame of the general theory for colloids, the aggregation of LDL aged in plasma fulfills all the requirements of the reaction-limited mechanism, encompassing 1), exponential growth; 2), fractal structure, with the dimension of elementary constituent still consistent with a single LDL; and 3), extreme polydispersity of aggregates, with shape and dimension very close to that of droplets observed in vivo. PMID:16533854

  8. Low Density Lipoprotein Aged in Plasma Forms Clusters Resembling Subendothelial Droplets: Aggregation via Surface Sites

    PubMed Central

    De Spirito, Marco; Brunelli, Roberto; Mei, Giampiero; Bertani, Francesca R.; Ciasca, Gabriele; Greco, Giulia; Papi, Massimiliano; Arcovito, Giuseppe; Ursini, Fulvio; Parasassi, Tiziana

    2006-01-01

    In early phases of atherogenesis, droplets and vesicles accumulate in the subendothelial extracellular space of arterial intima. There is much evidence to suggest that these droplets, ranging between 100 and 400 nm, derive from modified low-density lipoprotein (LDL). In investigations of the formation mechanism of these droplets, LDL fusion was previously induced in vitro by proteolysis, lipolysis, oxidation, and vigorous shaking, but all treatments failed to reproduce the size distribution range of in vivo droplets, mostly resulting, instead, in particles with a diameter intermediate between that of one and two LDL. Our approach was meant to mimic LDL aging in plasma. LDL isolated from plasma that was incubated overnight at 37°C is slightly modified in the secondary structure of its protein component and is primed to form very large aggregates according to a reaction-limited mechanism. This mechanism requires interactions between selected surface sites, whereas massive fusion is ruled out. In the frame of the general theory for colloids, the aggregation of LDL aged in plasma fulfills all the requirements of the reaction-limited mechanism, encompassing 1), exponential growth; 2), fractal structure, with the dimension of elementary constituent still consistent with a single LDL; and 3), extreme polydispersity of aggregates, with shape and dimension very close to that of droplets observed in vivo. PMID:16533854

  9. Biodegradation of low-density polyethylene (LDPE) by isolated fungi in solid waste medium

    SciTech Connect

    Zahra, Sahebnazar; Abbas, Shojaosadati Seyed; Mahsa, Mohammad-Taheri; Mohsen, Nosrati

    2010-03-15

    In this study, biodegradation of low-density polyethylene (LDPE) by isolated landfill-source fungi was evaluated in a controlled solid waste medium. The fungi, including Aspergillus fumigatus, Aspergillus terreus and Fusarium solani, were isolated from samples taken from an aerobic aged municipal landfill in Tehran. These fungi could degrade LDPE via the formation of a biofilm in a submerged medium. In the sterilized solid waste medium, LPDE films were buried for 100 days in a 1-L flask containing 400 g sterile solid waste raw materials at 28 deg. C. Each fungus was added to a separate flask. The moisture content and pH of the media were maintained at the optimal levels for each fungus. Photo-oxidation (25 days under UV-irradiation) was used as a pretreatment of the LDPE samples. The progress of the process was monitored by measurement of total organic carbon (TOC), pH, temperature and moisture. The results obtained from monitoring the process using isolated fungi under sterile conditions indicate that these fungi are able to grow in solid waste medium. The results of FT-IR and SEM analyses show that A. terreus and A. fumigatus, despite the availability of other organic carbon of materials, could utilize LDPE as carbon source. While there has been much research in the field of LDPE biodegradation under solid conditions, this is the first report of degradation of LDPE by A. fumigatus.

  10. Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells

    PubMed Central

    Reynolds, Lacy; Mulik, Rohit S.; Wen, Xiaodong; Dilip, Archana; Corbin, Ian R.

    2014-01-01

    Aim The natural omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has recently been credited for possessing anticancer properties. Herein, we investigate the cytotoxic actions of DHA-loaded low-density lipoprotein (LDL) nanoparticles in normal and liver cancer cells. Materials & methods LDL-DHA nanoparticles were prepared and subjected to extensive biophysical characterization. The therapeutic utility of LDL-DHA nanoparticles was evaluated in normal and malignant murine hepatocyte cell lines, TIB-73 and TIB-75, respectively. Results & discussion The engineered LDL-DHA nanoparticles possessed enhanced physical and oxidative stabilities over native LDL and free DHA. Dose–response studies showed that therapeutic doses of LDL-DHA nanoparticles that completely killed TIB-75 were innocuous to TIB-73. The selective induction of lipid peroxidation and reactive oxygen species in the cancer cells was shown to play a central role in LDL-DHA nanoparticle-mediated cytotoxicity. Conclusion In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma. PMID:24397600

  11. Fluorocarbon seal replaces metal piston ring in low density gas environment

    NASA Technical Reports Server (NTRS)

    Morath, W. D.; Morgan, N. E.

    1967-01-01

    Reinforced fluorocarbon cupseal, which provides an integral lip-type seal, replaces the metal piston rings in piston-cylinder configurations used in the compression of low density gases. The fluorocarbon seal may be used as cryogenic compressor piston seals.

  12. Melt index of low-density polyethylene and its effect on rotational molding

    NASA Astrophysics Data System (ADS)

    Yuldashev, A. Kh.; Negmatov, S. S.; Abed-Negmatova, N. S.; Abdurakhmanov, A. G.; Bozorov, Sh. A.; Eminov, Sh. Sh.; Aripova, A.; Khodjikariev, D. M.

    2012-07-01

    The melt index of low density polyethylene is directly correlated to the "in service" strength. This correlation together with other chemical properties allowed us to select the best material for rotational molding process.

  13. Method of Error Floor Mitigation in Low-Density Parity-Check Codes

    NASA Technical Reports Server (NTRS)

    Hamkins, Jon (Inventor)

    2014-01-01

    A digital communication decoding method for low-density parity-check coded messages. The decoding method decodes the low-density parity-check coded messages within a bipartite graph having check nodes and variable nodes. Messages from check nodes are partially hard limited, so that every message which would otherwise have a magnitude at or above a certain level is re-assigned to a maximum magnitude.

  14. Method and composition for molding low density desiccant syntactic foam articles

    DOEpatents

    Lula, James W.; Schicker, James R.

    1984-01-01

    A method and a composition are provided for molding low density desiccant syntactic foam articles. A low density molded desiccant article may be made as a syntactic foam by blending a thermosetting resin, microspheres and molecular sieve desiccant powder, molding and curing. Such articles have densities of 0.2-0.9 g/cc, moisture capacities of 1-12% by weight, and can serve as light weight structural supports.

  15. Short communication: Imputation performances of 3 low-density marker panels in beef and dairy cattle.

    PubMed

    Dassonneville, R; Fritz, S; Ducrocq, V; Boichard, D

    2012-07-01

    Low-density chips are appealing alternative tools contributing to the reduction of genotyping costs. Imputation enables researchers to predict missing genotypes to recreate the denser coverage of the standard 50K (∼50,000) genotype. Two alternative in silico chips were defined in this study that included markers selected to optimize minor allele frequency and spacing. The objective of this study was to compare the imputation accuracy of these custom low-density chips with a commercially available 3K chip. Data consisted of genotypes of 4,037 Holstein bulls, 1,219 Montbéliarde bulls, and 991 Blonde d'Aquitaine bulls. Criteria to select markers to include in low-density marker panels are described. To mimic a low-density genotype, all markers except the markers present on the low-density panel were masked in the validation population. Imputation was performed using the Beagle software. Combining the directed acyclic graph obtained with Beagle with the PHASEBOOK algorithm provides fast and accurate imputation that is suitable for routine genomic evaluations based on imputed genotypes. Overall, 95 to 99% of alleles were correctly imputed depending on the breed and the low-density chip used. The alternative low-density chips gave better results than the commercially available 3K chip. A low-density chip with 6,000 markers is a valuable genotyping tool suitable for both dairy and beef breeds. Such a tool could be used for preselection of young animals or large-scale screening of the female population. PMID:22720970

  16. Improving GLOBALlAND30 Artificial Type Extraction Accuracy in Low-Density Residents

    NASA Astrophysics Data System (ADS)

    Hou, Lili; Zhu, Ling; Peng, Shu; Xie, Zhenlei; Chen, Xu

    2016-06-01

    GlobalLand 30 is the first 30m resolution land cover product in the world. It covers the area within 80°N and 80°S. There are ten classes including artificial cover, water bodies, woodland, lawn, bare land, cultivated land, wetland, sea area, shrub and snow,. The TM imagery from Landsat is the main data source of GlobalLand 30. In the artificial surface type, one of the omission error happened on low-density residents' part. In TM images, hash distribution is one of the typical characteristics of the low-density residents, and another one is there are a lot of cultivated lands surrounded the low-density residents. Thus made the low-density residents part being blurred with cultivated land. In order to solve this problem, nighttime light remote sensing image is used as a referenced data, and on the basis of NDBI, we add TM6 to calculate the amount of surface thermal radiation index TR-NDBI (Thermal Radiation Normalized Difference Building Index) to achieve the purpose of extracting low-density residents. The result shows that using TR-NDBI and the nighttime light remote sensing image are a feasible and effective method for extracting low-density residents' areas.

  17. Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis.

    PubMed

    Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

    2016-01-01

    Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients.The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1-L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function.Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01-3.53), with a near-linear dose-response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction.Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

  18. Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice.

    PubMed

    Song, Guohua; Zong, Chuanlong; Zhang, Zhaoqiang; Yu, Yang; Yao, Shutong; Jiao, Peng; Tian, Hua; Zhai, Lei; Zhao, Hui; Tian, Shuyan; Zhang, Xiangjian; Wu, Yun; Sun, Xuejun; Qin, Shucun

    2015-10-01

    Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H(2) on atherosclerotic plaque stability. Low-density lipoprotein receptor-knockout (LDLR(-/-)) mice fed an atherogenic diet were dosed daily with H(2) and/or simvastatin. In vitro studies were carried out in an oxidized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H(2). H(2) or simvastatin significantly enhanced plaque stability by increasing levels of collagen, as well as reducing macrophage and lipid levels in plaques. The decreased numbers of dendritic cells and increased numbers of regulatory T cells in plaques further supported the stabilizing effect of H(2) or simvastatin. Moreover, H(2) treatment decreased serum ox-LDL level and apoptosis in plaques with concomitant inhibition of endoplasmic reticulum stress (ERS) and reduction of reactive oxygen species (ROS) accumulation in the aorta. In vitro, like the ERS inhibitor 4-phenylbutyric acid, H(2) inhibited ox-LDL- or tunicamycin (an ERS inducer)-induced ERS response and cell apoptosis. In addition, like the ROS scavenger N-acetylcysteine, H(2) inhibited ox-LDL- or Cu(2+) (an ROS inducer)-induced reduction in cell viability and increase in cellular ROS. Also, H(2) increased Nrf2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrf2 small interfering RNA abolished the protective effect of H(2) on ox-LDL-induced cellular ROS production. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability. PMID:26117323

  19. Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis

    PubMed Central

    Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

    2016-01-01

    Abstract Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients. The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1–L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function. Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01–3.53), with a near-linear dose–response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction. Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

  20. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  1. Apolipoprotein B mediates the capacity of low density lipoprotein to suppress neutrophil stimulation by particulates.

    PubMed

    Terkeltaub, R; Martin, J; Curtiss, L K; Ginsberg, M H

    1986-11-25

    Low density lipoprotein (LDL) inhibits phagocytosis of certain negatively charged particulates and also inhibits subsequent cellular secretory and oxidative responses to these particulates. In the present work, we have defined the structural features of LDL involved in this activity. Starch-heptane extraction depleted greater than 95% of neutral lipids but had little effect on the capacity of LDL to inhibit monosodium urate crystal- or polystyrene latex bead-induced neutrophil chemiluminescence (CL). Liposomes containing gamma-palmitoyl-beta-oleoylphosphatidylcholine (PC) with unesterified cholesterol (PC:cholesterol = 2:1), PC and sphingomyelin (PC:sphingomyelin = 2.3:1), or PC alone lacked the capacity to inhibit urate-induced CL. However, incorporation of apoB-100 into liposomes via cholate dialysis rendered them nearly as inhibitory for urate-induced neutrophil CL as LDL on a protein weight basis. Moreover, delipidated apoB-100, containing less than 3% residual phospholipid, inhibited neutrophil responses to urate crystals or latex beads (degranulation and superoxide anion release) in a stimulus-specific manner. Modifications of the lysine residues of apoB (e.g. acetylation) reduced both the capacity of LDL to inhibit urate crystal-induced CL and to bind to urate crystals. The effects of apoB lysine residue modification were reversible, proportional to the extent of modification, and were not attributable to alteration of the net charge of apoB. Thus, the apoB-100 of LDL both mediates and shares the capacity of native LDL to inhibit certain neutrophil responses to particulates. PMID:3096995

  2. Preliminary Analysis of Modified Low-Density Lipoproteins in the Serum of Healthy and Obese Dogs and Cats

    PubMed Central

    Mori, Nobuko; Okada, Yuki; Tsuchida, Naoto; Hatano, Yutaka; Habara, Makoto; Ishikawa, Shingo; Yamamoto, Ichiro; Arai, Toshiro

    2015-01-01

    Oxidized low-density lipoprotein (LDL) is thought to play an important role in the inflammatory response associated with human obesity. The purpose of this preliminary study was to determine oxidized LDL concentrations in healthy dogs and cats, and to evaluate whether obesity affects oxidized LDL concentration, using 39 cats and 19 dogs that had visited two different veterinary clinics in Japan. We hypothesized that oxidized LDL concentrations measured against body condition score (BCS) may have a potential value in evaluating the qualities of accumulated or circulating lipids in obese dogs and cats that do not show signs of metabolic diseases. The mean oxidized LDL value in BCS3 dogs (2.4 ± 0.9 μg/dl) was very similar to that of BCS5 dogs (2.2 ± 0.3 μg/dl). The mean oxidized LDL value of BCS4 dogs was 7.2 ± 10.3 μg/dl and the highest among three groups. BCS4 dogs included two dogs whose oxidized LDL values were higher than the mean oxidized LDL value of healthy humans (11.2 ± 0.3 μg/dl). On the other hand, the mean oxidized LDL value of BCS3 cats was 2.5 ± 0.9 μg/dl, and those of BCS4 and 5 cats were higher than that of BCS3, but there was no significant difference. The BCS4 cat group included one cat with a higher oxidized LDL value, and the BCS5 group also included two cats with oxidized LDL values higher than the mean oxidized LDL value of healthy humans. Interestingly, the oxidized LDL values in two obese dogs and three obese cats were indeed higher than the mean oxidized LDL value of humans with coronary artery disease (20.1 ± 1.1 μg/dl). In conclusion, this preliminary study showed reference ranges of oxidized dogs and cats against BCS. Obesity alone does not appear to have any direct effect on serum oxidized LDL values in healthy dogs and cats. PMID:26664963

  3. The non-thermal origin of the tokamak low-density stability limit

    NASA Astrophysics Data System (ADS)

    Paz-Soldan, C.; La Haye, R. J.; Shiraki, D.; Buttery, R. J.; Eidietis, N. W.; Hollmann, E. M.; Moyer, R. A.; Boom, J. E.; Chapman, I. T.; Contributors, JET

    2016-05-01

    DIII-D plasmas at very low density exhibit the onset of n  =  1 error field (EF) penetration (the ‘low-density locked mode’) not at a critical density or EF, but instead at a critical level of runaway electron (RE) intensity. Raising the density during a discharge does not avoid EF penetration, so long as RE growth proceeds to the critical level. Penetration is preceded by non-thermalization of the electron cyclotron emission, anisotropization of the total pressure, synchrotron emission shape changes, as well as decreases in the loop voltage and bulk thermal electron temperature. The same phenomena occur despite various types of optimal EF correction, and in some cases modes are born rotating. Similar phenomena are also found at the low-density limit in JET. These results stand in contrast to the conventional interpretation of the low-density stability limit as being due to residual EFs and demonstrate a new pathway to EF penetration instability due to REs. Existing scaling laws for penetration project to increasing EF sensitivity as bulk temperatures decrease, though other possible mechanisms include classical tearing instability, thermo-resistive instability, and pressure-anisotropy driven instability. Regardless of the first-principles mechanism, known scaling laws for Ohmic energy confinement combined with theoretical RE production rates allow rough extrapolation of the RE criticality condition, and thus the low-density limit, to other tokamaks. The extrapolated low-density limit by this pathway decreases with increasing machine size and is considerably below expected operating conditions for ITER. While likely unimportant for ITER, this effect can explain the low-density limit of existing tokamaks operating with small residual EFs.

  4. Characterization of in Vitro Modified Human Very Low-Density Lipoprotein Particles and Phospholipids by Capillary Electrophoresis

    PubMed Central

    Liu, Yi-Ning; Shu, Ting-Yu; Xie, Huai-Guang; Lai, Wei-Ting; Liao, Yi-Han; Su, Mei-Yu; Lin, You-Sian; Chen, Yen-Yi; Lin, Yi-Jyun; Chong, Chin-Pong; Liu, Mine-Yine

    2012-01-01

    A simple capillary zone electrophoresis (CZE) method was used to characterize human very low-density lipoprotein (VLDL) particles for four healthy donors. One major peak was observed for native, in vitro oxidized and glycated VLDL particles. The effective mobilities and peak areas of the capillary electrophoresis (CE) profiles showed good reproducibility and precision. The mobility of the oxidized VLDL peak was higher than that of the native VLDL. The mobility of the glycated VLDL peak was similar to that of the native VLDL. Phospholipids isolated from VLDL particles were analyzed by our recently developed micellar electrokinetic chromatography (MEKC) with a high-salt stacking method. At absorbance 200 nm, the native VLDL phospholipids showed a major peak and a minor peak for each donor. For oxidized VLDL phospholipids, the area of the major peak reduced for three donors, possibly due to phospholipid decomposition. For glycated VLDL phospholipids, the peak mobilities were more positive than native VLDL phospholipids for two donors, possibly due to phospholipid-linked advanced glycation end products (AGEs). Very interestingly, at absorbance 234 nm, the major peak of oxidized VLDL phospholipids was resolved as two peaks for each donor, possibly due to conjugated dienes formed upon oxidation. PMID:23208377

  5. Low-Density Lipoprotein Receptor-Related Protein-1 Protects Against Hepatic Insulin Resistance and Hepatic Steatosis.

    PubMed

    Ding, Yinyuan; Xian, Xunde; Holland, William L; Tsai, Shirling; Herz, Joachim

    2016-05-01

    Low-density lipoprotein receptor-related protein-1 (LRP1) is a multifunctional uptake receptor for chylomicron remnants in the liver. In vascular smooth muscle cells LRP1 controls reverse cholesterol transport through platelet-derived growth factor receptor β (PDGFR-β) trafficking and tyrosine kinase activity. Here we show that LRP1 regulates hepatic energy homeostasis by integrating insulin signaling with lipid uptake and secretion. Somatic inactivation of LRP1 in the liver (hLRP1KO) predisposes to diet-induced insulin resistance with dyslipidemia and non-alcoholic hepatic steatosis. On a high-fat diet, hLRP1KO mice develop a severe Metabolic Syndrome secondary to hepatic insulin resistance, reduced expression of insulin receptors on the hepatocyte surface and decreased glucose transporter 2 (GLUT2) translocation. While LRP1 is also required for efficient cell surface insulin receptor expression in the absence of exogenous lipids, this latent state of insulin resistance is unmasked by exposure to fatty acids. This further impairs insulin receptor trafficking and results in increased hepatic lipogenesis, impaired fatty acid oxidation and reduced very low density lipoprotein (VLDL) triglyceride secretion. PMID:27322467

  6. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family.

    PubMed

    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A; Gliemann, Jørgen; Ryan, Robert O; Olivecrona, Gunilla

    2007-03-27

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited by the receptor associated protein, a known ligand for members of the low density lipoprotein receptor family. Preincubation with heparin decreased the receptor binding of apolipoprotein A-V, indicating that overlap exists between the recognition sites for these receptors and for heparin. A double mutant, apolipoprotein A-V (Arg210Glu/Lys211Gln), showed decreased binding to heparin and decreased ability to bind the low density lipoprotein receptor-related protein. Association of apolipoprotein A-V with the low density lipoprotein receptor-related protein or SorLA resulted in enhanced binding of human chylomicrons to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins. PMID:17326667

  7. Influence of Pro-Oxidant on Photodegradation of a Low-Density Polyethylene-Nanosilica Composite

    EPA Science Inventory

    Use of polymer nanocomposites is burgeoning and they represent one of the fastest growing components of the manufactured nanomaterials market. Incorporation of nanoscale fillers in these plastics significantly improves their stiffness and other key mechanical properties. Although...

  8. Enhanced oxidation of air contaminants on an ultra-low density UV-accessible aerogel photocatalyst

    SciTech Connect

    Dreyer, M.; Newman, G.K.; Lobban, L.; Kersey, S.J.; Wang, R.; Harwell, J.H.

    1997-12-31

    This research developed new forms of photocatalysts that could potentially move photocatalytic degradation of air contaminants into the main stream of industrially used remediation technologies. Tests of the photocatalytic activity of the TiO{sub 2} aerogel catalysts have been carried out using both acetone and methane as the air contaminant. For comparison, the same tests were carried out on a standard (non-aerogel) anatase powder. Despite having very low crystallinity, the aerogel decontaminates the air far more effectively than an equal volume of the anatase powder which indicates that a much larger fraction of the aerogel is activated by the UV light. Experimental data were used to determine adsorption equilibrium constants for acetone, and to determine reaction rate constants assuming a Langmuir-Hinshelwood type rate expression.

  9. Low-Density Graphite Grains and Mixing in Type II Supernovae

    NASA Astrophysics Data System (ADS)

    Travaglio, Claudia; Gallino, Roberto; Amari, Sachiko; Zinner, Ernst; Woosley, Stan; Lewis, Roy S.

    1999-01-01

    Primitive meteorites contain presolar grains that originated in stellar outflows and supernova ejecta. Low-density graphite grains from the Murchison carbonaceous meteorite were analyzed for the isotopic compositions of C, N, O, Mg, Si, K, Ca, and Ti by ion microprobe mass spectrometry. The grains are characterized by a large range of 12C/13C ratios (from 3.6 to 7200 compared to the solar ratio of 89), excesses in 15N (15N/14N up to 10 times solar) and 18O (18O/16O up to 185 times solar), large inferred 26Al/27Al ratios (from 26Mg excesses) ranging up to 0.15, a large range in Si isotopic ratios (from 50% deficits in 29Si and 30Si relative to 28Si up to more than 120% excesses), large excesses in 41K and 44Ca from the prior presence of now-extinct 41Ca (T1/2=105 yr) and 44Ti (T1/2=59 yr), respectively, and excesses in 42Ca, 43Ca relative to 40Ca, and 49Ti, and 50Ti relative to 48Ti. Several of these isotopic signatures indicate a supernova origin. In particular, the initial presence of 44Ti and excesses of 28Si as well as the size of the inferred 41Ca/40Ca ratios are proof that the carrier grains formed in supernova ejecta. We explored the possibility that the low-density graphite grains originated from C-rich ejecta of Type II supernovae. In such stars 44Ti and 28Si are produced in the inner layers and the presence of these two isotopes in carbonaceous grains is evidence for extensive mixing of different supernova layers in the explosion. We performed mixing calculations of different layers of the SN models by Woosley & Weaver under the imposed boundary condition that C>=O and compare the resulting isotopic ratios with the isotopic ratios measured in the meteoritic grains. The mixing model can explain the observed 12C/13C, 16O/18O, 30Si/28Si, and 44Ti and 41Ca fairly well as long as jets of material from the Si-rich zone, carrying 44Ti and pure 28Si, are assumed to penetrate the O-rich zone and are ejected into and mixed with the C-rich layers, where carbonaceous

  10. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity.

    PubMed

    Kwiterovich, Peter O

    2002-10-17

    Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to

  11. Phase Stability of Low-Density, Multiprincipal Component Alloys Containing Aluminum, Magnesium, and Lithium

    NASA Astrophysics Data System (ADS)

    Yang, X.; Chen, S. Y.; Cotton, J. D.; Zhang, Y.

    2014-10-01

    A series of low-density, multiprincipal component alloys containing high concentrations of Al, Mg, Li, Zn, Cu and/or Sn was designed using a strategy based on high-entropy alloys (HEAs). The alloys were prepared by induction melting under high-purity argon atmosphere, and the resulting microstructures were characterized in the as-cast condition. The resulting microstructures are multiphase and complex and contain significant volume fractions of disordered solutions and intermetallic compounds. By analyzing the atomic size difference, enthalpy of mixing, entropy of mixing, electronegativity difference, and valence electron concentration among the constituent elements, modified phase formation rules are developed for low-density multiprincipal component alloys that are more restrictive than previously established limits based on more frequently studied HEAs comprising mostly transition metals. It is concluded that disordered solid solution phases are generally less stable than competing ordered compounds when formulated from low-density elements including Al, Mg, and Li.

  12. Viscous linear stability of axisymmetric low-density jets: Parameters influencing absolute instability

    NASA Astrophysics Data System (ADS)

    Srinivasan, V.; Hallberg, M. P.; Strykowski, P. J.

    2010-02-01

    Viscous linear stability calculations are presented for model low-density axisymmetric jet flows. Absolute growth transitions for the jet column mode are mapped out in a parametric space including velocity ratio, density ratio, Reynolds number, momentum thickness, and subtle differences between velocity and density profiles. Strictly speaking, the profiles used in most jet stability studies to date are only applicable to unity Prandtl numbers and zero pressure gradient flows—the present work relaxes this requirement. Results reveal how subtle differences between the velocity and density profiles generally used in jet stability theory can dramatically alter the absolute growth rate of the jet column mode in these low-density flows. The results suggest heating/cooling or mass diffusion at the outer nozzle surface can suppress absolute instability and potentially global instability in low-density jets.

  13. Low density aerothermodynamics studies performed by means of the tethered satellite system

    NASA Technical Reports Server (NTRS)

    Carlomagno, Giovanni M.; De Luca, Luigi; Siemers, Paul M.; Wood, George M., Jr.

    1986-01-01

    Low density gas flow modeling and current ground wind-tunnel technologies are not presently able to produce fully reliable data concerning low density flow regimes. In order to answer some of these issues, the Shuttle Continuous Open Wind Tunnel (SCOWT) program has been proposed, which makes use of the tethered satellite system (TSS). SCOWT's objective is to investigate the energy and momentum transfer between the tethered satellite and its environmental medium within the range of the thermofluid-dynamic conditions experienced by TSS during its atmospheric flights. The feasibility and capability of SCOWT to perform low density aerothermodynamics studies are investigated. Some of the results, obtained by means of a tether simulation program, and the instrumentation and TSS design main requirements to meet SCOWT objectives are described.

  14. Low density GaAs /AlGaAs quantum dots grown by modified droplet epitaxy

    NASA Astrophysics Data System (ADS)

    Mantovani, V.; Sanguinetti, S.; Guzzi, M.; Grilli, E.; Gurioli, M.; Watanabe, K.; Koguchi, N.

    2004-10-01

    Low temperature photoluminescence spectroscopy is used to analyze the effects of the Ga coverage and of the postgrowth thermal annealing on the electronic properties of low density (≈1×109cm-2) self-assembled GaAs /AlGaAs quantum dots (QDs) grown by modified droplet epitaxy (MDE). We demonstrate that with the MDE method it is possible to obtain low density and high efficiency QD samples with high photoluminescence efficiency. Large modifications of the photoluminescence band, which depend on Ga coverage and thermal annealing, are found and quantitatively interpreted by means of a simple model based on the Al-Ga interdiffusion.

  15. Measurement of Rydberg atom formation in low-density ultracold neutral plasmas

    NASA Astrophysics Data System (ADS)

    Chen, Wei-Ting; Witte, Craig; Roberts, Jacob

    2016-05-01

    Rydberg atoms are formed in ultracold neutral plasmas primarily through three-body recombination for typical experimental conditions. At low densities the relative importance of electron-Rydberg state-changing collisions in the dynamical evolution of the Rydberg atom state populations is increased, leading to temperature scalings significantly different from the usual T - 9 / 2 scaling associated with the three-body recombination rate. We report our measurement of Rydberg atoms in low-density ultracold neutral plasmas and discuss their utility in calibrating the electron temperature and determining the amount of heating due to continuum lowering that occurs during the formation of the ultracold plasma. This work supported by the AFOSR.

  16. Mars north polar dunes: possible formation from low-density sediment aggregates

    SciTech Connect

    Saunders, R.S.; Blewett, D.T.

    1987-10-01

    Low-density aggregates, composed of submicron clay aerosols, have been formed experimentally as the sublimation residues of masses of dust-nucleated ice. These ice-dust mixtures are possible analogues of materials of Martian north polar deposits. Low-density (0.002 g/cm/sup 3/) spheroidal pellets formed from these materials in wind tunnel experiments have been examined as possible candidates for forming north polar dunes on Mars. It is shown that these particles move like sand grains under conditions of saltation and, given a sufficient supply, would be capable of forming the dunes observed in the north circumpolar erg.

  17. Experimental demonstration of laser to x-ray conversion enhancements with low density gold targets

    DOE PAGESBeta

    Shang, Wanli; Yang, Jiamin; Zhang, Wenhai; Li, Zhichao; Deng, Bo; Dong, Yunsong; Zhu, Tuo; Huang, Chengwu; Zhan, Xiayu; Mei, Yu; et al

    2016-02-12

    The enhancement of laser to x-ray conversion efficiencies using low density gold targets [W. L. Shang, J. M. Yang, and Y. S. Dong, Appl. Phys. Lett. 102, 094105 (2013)] is demonstrated. Laser to x-ray conversion efficiencies with 6.3% and 12% increases are achieved with target densities of 1 and 0.25 g/cm3, when compared with that of a solid gold target (19.3 g/cm3). Experimental data and numerical simulations are in good agreement. Lastly, the enhancement is caused by larger x-ray emission zone lengths formed in low density targets, which is in agreement with the simulation results.

  18. Direct Monte Carlo Simulations of Hypersonic Low-Density Flows about an ASTV Including Wake Structure

    NASA Technical Reports Server (NTRS)

    Dogra, V. K.; Moss, J. N.; Wilmoth, R. G.; Price, J. M.

    1992-01-01

    Results of a numerical study concerning flow past a 70-deg blunted cone in hypersonic low-density flow environments are presented using the direct simulation Monte-Carlo method. The flow conditions simulated are those that can be obtained in existing low-density hypersonic wind tunnels. Results indicate that a stable vortex forms in the near wake at and below a freestream Knudsen number (based on cone diameter) of 0.01 and the size of the vortex increases with decreasing Knudsen number. The base region of the flow remains in thermal nonequilibrium for all cases considered herein.

  19. Low-Density Silica Xerogel Capture of Leonids Meteor Storm Dust Candidates by Stratospheric Balloon Return

    NASA Technical Reports Server (NTRS)

    Noever, David; Phillips, Tony; Horack, John; Myszka, Ed; Porter, Linda; Jerman, Greg

    1999-01-01

    High altitude balloon (20 km) and low-density capture media were explored to return meteor-related dust during the November 1998 Leonids meteor storm. One 20-30 micron particle captured showed a characteristic signature of extraterrestrial origin, featuring high aluminum, magnesium and other non-volatile metals. The technique of balloon capture will be optimized for March and November 1999 reflights.

  20. Low density biodegradable shape memory polyurethane foams for embolic biomedical applications

    PubMed Central

    Singhal, Pooja; Small, Ward; Cosgriff-Hernandez, Elizabeth; Maitland, Duncan J; Wilson, Thomas S

    2014-01-01

    Low density shape memory polymer foams hold significant interest in the biomaterials community for their potential use in minimally invasive embolic biomedical applications. The unique shape memory behavior of these foams allows them to be compressed to a miniaturized form, which can be delivered to an anatomical site via a transcatheter process, and thereafter actuated to embolize the desired area. Previous work in this field has described the use of a highly covalently crosslinked polymer structure for maintaining excellent mechanical and shape memory properties at the application-specific ultra low densities. This work is aimed at further expanding the utility of these biomaterials, as implantable low density shape memory polymer foams, by introducing controlled biodegradability. A highly covalently crosslinked network structure was maintained by use of low molecular weight, symmetrical and polyfunctional hydroxyl monomers such as Polycaprolactone triol (PCL-t, Mn 900 g), N,N,N0,N0-Tetrakis (hydroxypropyl) ethylenediamine (HPED), and Tris (2-hydroxyethyl) amine (TEA). Control over the degradation rate of the materials was achieved by changing the concentration of the degradable PCL-t monomer, and by varying the material hydrophobicity. These porous SMP materials exhibit a uniform cell morphology and excellent shape recovery, along with controllable actuation temperature and degradation rate. We believe that they form a new class of low density biodegradable SMP scaffolds that can potentially be used as “smart” non-permanent implants in multiple minimally invasive biomedical applications. PMID:24090987

  1. Securing the Extremely Low-Densities of Low-Mass Planets Characterized by Transit Timing Variations

    NASA Astrophysics Data System (ADS)

    Ford, Eric B.

    2015-12-01

    Transit timing variations (TTVs) provide an excellent tool to characterize the masses and orbits of dozens of small planets, including many at orbital periods beyond the reach of both Doppler surveys and photoevaporation-induced atmospheric loss. Dynamical modeling of these systems has identified low-mass planets with surprisingly large radii and low densities (e.g., Kepler-79d, Jontof-Hutter et al. 2014; Kepler-51, Masuda 2014; Kepler-87c, Ofir et al. 2014). Additional low-density, low-mass planets will likely become public before ESS III (Jontof-Hutter et al. in prep). Collectively, these results suggest that very low density planets with masses of 2-6 MEarth are not uncommon in compact multiple planet systems. Some astronomers have questioned whether there could be an alternative interpretation of the TTV observations. Indeed, extraordinary claims require extraordinary evidence. While the physics of TTVs is rock solid, the statistical analysis of Kepler observations can be challenging, due to the complex interactions between model parameters and high-dimensional parameter spaces that must be explored. We summarize recent advances in computational statistics that enable robust characterization of planetary systems using TTVs. We present updated analyses of a few particularly interesting systems and discuss the implications for the robustness of extremely low densities for low-mass planets. Such planets pose an interesting challenge for planet formation theory and are motivating detailed theoretical studies (e.g., Lee & Chiang 2015 and associated ESS III abstracts).

  2. Highly Shocked Low Density Sedimentary Rocks from the Haughton Impact Structure, Devon Island, Nunavut, Canada

    NASA Technical Reports Server (NTRS)

    Osinski, G. R.; Spray, J. G.

    2001-01-01

    We present the preliminary results of a detailed investigation of the shock effects in highly shocked, low density sedimentary rocks from the Haughton impact structure. We suggest that some textural features can be explained by carbonate-silicate immiscibility. Additional information is contained in the original extended abstract.

  3. Low-density nanoporous iron foams synthesized by sol-gel autocombustion

    PubMed Central

    2012-01-01

    Nanoporous iron metal foams were synthesized by an improved sol-gel autocombustion method in this report. It has been confirmed to be pure phase iron by X-ray diffraction measurements. The nanoporous characteristics were illustrated through scanning electron microscope and transmission electron microscope images. Very low density and quite large saturation magnetization has been performed in the synthesized samples. PMID:22333555

  4. Single-drop impact damage prediction for low density, coated ceramic materials. [rain erosion

    NASA Technical Reports Server (NTRS)

    Mustelier, D.

    1984-01-01

    A technique utilizing finite element analysis, liquid impact kinematics, and momentum theory is described and compared to single-drop impact test data performed on various configurations of coated ceramic material. The method correlates well with test data and is useful in predicting the single-drop impact damage velocity threshold for low-density, coated ceramic materials.

  5. Use of Low-Density DNA Microarrays and Photopolymerization for Genotyping Foodborne-Associated Noroviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human noroviruses cause up to 21 million cases of foodborne disease in the United States annually and are the most common cause of acute gastroenteritis in industrialized countries. To reduce the burden of foodborne disease associated with viruses, the use of low density DNA microarrays in conjunct...

  6. Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not ...

  7. Optimal design of low-density SNP arrays for genomic prediction: algorithm and applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for their optimal design. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optim...

  8. Autumn vegetable response to residual herbicides applied the previous spring under low density polyethylene mulch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Field studies were conducted in 2002 and 2005 to evaluate autumn vegetable tolerance to residual herbicides applied the previous spring under low density polyethylene (LDPE) mulch. Spring applications of 1.12 kg/ha S-metolachlor, 0.027 kg/ha halosulfuron, 0.28 kg/ha sulfentrazone, and 1.12 kg/ha S...

  9. Residual herbicide dissipation for bare soil versus soil under low density polyethylene mulch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Yellow nutsedge and purple nutsedge are the most common and troublesome vegetable weeds in the Southern US. Herbicides in low density polyethylene (LDPE) mulch systems are potential methyl bromide alternatives for nutsedge control. Halosulfuron-methyl, sulfentrazone, and s-metolachlor all have nutse...

  10. Mechanical and electrical properties of low density polyethylene filled with carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Sabet, Maziyar; Soleimani, Hassan

    2014-08-01

    Carbon nanotubes (CNTs) reveal outstanding electrical and mechanical properties in addition to nanometer scale diameter and high aspect ratio, consequently, making it an ideal reinforcing agent for high strength polymer composites. Low density polyethylene (LDPE)/CNT composites were prepared via melt compounding. Mechanical and electrical properties of (LDPE)/CNT composites with different CNT contents were studied in this research.

  11. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  12. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...

  13. A Leap above Friedewald Formula for Calculation of Low-Density Lipoprotein-Cholesterol

    PubMed Central

    Kapoor, Reema; Chakraborty, Montosh; Singh, Navpreet

    2015-01-01

    Purpose: The purpose was to compare the different calculated methods of low-density lipoprotein cholesterol (LDL-C) estimation and to determine which of them correlate best with the direct method. Materials and Methods: The records of 480 samples for lipid profile were analyzed. Apart from the direct method, LDL-C was calculated by Friedewald low-density lipoprotein cholesterol method (F-LDL-C), modified Friedewald low-density lipoprotein cholesterol method (MF-LDL-C), and Anandaraja low-density lipoprotein cholesterol method (A-LDL-C). Paired t-test and Pearson correlation were evaluated between the different methods. Degree of agreement between the calculated methods and direct method was detected by Bland–Altman graphical plots. Results: A strong correlation was found between all calculated LDL-C methods and direct low-density lipoprotein cholesterol method (D-LDL-C) assay, that is, F-LDL-C versus D-LDL-C = 0.94; A-LDL-C versus D-LDL-C = 0.93 and MF-LDL-C versus D-LDL-C = 0.95. No statistically significant difference was found between D-LDL-C and MF-LDL-C. Bland–Altman plot for MF-LDL-C showed minimal negative bias. Conclusions: The study pointed out that MF-LDL-C correlated maximally with D-LDL-C estimation at all levels of triglycerides and MF-LDL-C can be used in place of D-LDL-C when the direct method cannot be afforded. PMID:25949053

  14. Impairment of Nitrergic System and Delayed Gastric Emptying in Low Density Lipoprotein Receptor (LDLR) Deficient Female Mice

    PubMed Central

    Gangula, Pandu R.; Chinnathambi, Vijayakumar; Hale, Ashley B.; Mukhopadhyay, Sutapa; Channon, Keith M.; Ravella, Kalpana

    2011-01-01

    Background In the current study, we have investigated whether low density lipoprotein receptor knockout mice (LDLR-KO), moderate oxidative stress model and cholesteremia burden display gastroparesis and if so whether nitrergic system is involved in this setting. In addition, we have investigated if sepiapterin (SEP) supplementation attenuated impaired nitrergic system and delayed gastric emptying. Methods Gastric emptying and nitrergic relaxation were measured in overnight fasting mice. nNOSα dimerization, anti-oxidant markers such as Nrf2, GCLM, GCLC, HO-1, catalase (CAT) and superoxide dismutase (SOD1) were measured using standard methods. Biopterin levels and intestinal transit time were measured using HPLC and dye migration assay, respectively. Wild type (WT) and LDLR-KO were supplemented with SEP. Key Results In LDLR null stomachs, 1) significant reduction in rate of gastric emptying, gastric pyloric and fundus nitrergic relaxation & nNOSα dimerization, 2) elevated oxidized biopterins and reduced ratio of BH4/BH2+B, 3) reduced Nrf2 and GCLC protein expression & no change in GCLM, HO-1, Cat, Sod1 and 4) accelerated small intestinal motility were noticed. Supplementation of SEP restored delayed gastric emptying, impaired pyloric and fundus nitrergic relaxation with restoration of nNOS dimerization and nNOS expression. Conclusions and Inferences This novel data suggests that hyperlipidemia and/or suppression of selective antioxidants may be a potential cause of developing gastroparesis in diabetic patients. PMID:21414103

  15. Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract.

    PubMed

    Hwang, J; Hodis, H N; Sevanian, A

    2001-01-01

    Postmenopausal women have an increased risk of coronary heart disease. Oxidation of low-density lipoprotein (LDL) has been implicated in atherogenesis, and the presence of modified LDL (LDL(-)) in plasma appears to represent LDL oxidation in vivo. Because previous studies have demonstrated a strong antiatherogenic effect of estrogen due to its antioxidant activity and similar antioxidant activity was found for specific isoflavones derived from soy extract, the antioxidant activity of a phytoestrogen extract derived from soy and alfalfa was studied. Copper-mediated LDL oxidation was inhibited in the presence of soy and alfalfa extracts, and this effect was further enhanced in the presence of acerola cherry extract, which is rich in ascorbic acid. Male rabbit aortic endothelial cells pretreated with soy extract were resistant to the toxic effects of high levels of LDL and LDL(-), and a lesser, but significant protection, was also afforded by alfalfa extract. Cell-mediated oxidation of LDL, measured by LDL(-) formation, was inhibited in the presence of soy extract but not alfalfa extract. However, in the presence of acerola cherry extract, both soy and alfalfa extracts potently inhibited the formation of LDL(-). These findings show that acerola cherry extract can enhance the antioxidant activity of soy and alfalfa extracts in a variety of LDL oxidation systems. The protective effect of these extracts is attributed to the presence of flavonoids in soy and alfalfa extracts and ascorbic acid in acerola cherry extract, which may act synergistically as antioxidants. It is postulated that this synergistic interaction among phytoestrogens, flavonoids, and ascorbic acid is due to the "peroxidolitic" action of ascorbic acid, which facilitates the copper-dependent decomposition of LDL peroxides to nonradical products; this synergy is complemented by a mechanism in which phytoestrogens stabilize the LDL structure and suppress the propagation of radical chain reactions. The

  16. The removal of partially metabolized very-low-density lipoproteins by the perfused rat liver.

    PubMed Central

    Suri, B S; Targ, M E; Robinson, D S

    1981-01-01

    1. Donor perfused rat livers were used to prepare VLD (very-low-density) lipoproteins, labelled in their triacylglycerol and protein components with [1-14C]oleic acid and L-[4,5-3H]leucine respectively. Partially metabolized VLD lipoproteins, similarly labelled, were obtained from supradiaphragmatic rats injected with the parent VLD lipoproteins. 2. The triacylglycerol and protein components of the partially metabolized VLD lipoproteins were removed by recipient perfused rat livers at rates much higher than those of the parent VLD lipoproteins. No degradation of the partially metabolized VLD lipoproteins to LD (low-density) lipoproteins occurred during the perfusions. 3. Removal of hepatic lipase from the livers did not significantly affect the rate of removal of the partially metabolized VLD lipoproteins. PMID:7317016

  17. Improved tunable external filter for Langmuir probe measurement at low density plasmas

    NASA Astrophysics Data System (ADS)

    Chang, Yoon-Min; Lee, Hyo-Chang; Jeon, Sang-Bum; Kim, Dong-Hwan; Kim, Ju-Ho; Chung, Chin-Wook; Department of Electrical Engineering Team; Department of Nanoscale Semiconductor Engineering Team

    2015-09-01

    Measurement of the electron energy probability function (EEPF) at low density plasma, especially in molecular gas discharge, is difficult due to large RF fluctuation. To overcome the problem, an improved tunable external filter was developed. In contrast to an internal filter, the external filter can tune the resonance frequency of the choke filter. However, conventional external filter has low impedance due to a large stray capacitance between a probe tip and the external filter. To reduce the effect of the stray capacitance, an appropriate inductor was connected to the probe tip, and the external filter was designed to tune the first and the second harmonic frequencies independently. Using our filter, the EEPFs were measured at low density plasma with various gases, and the results show the improved performance of the filter as compared to the previous studies.

  18. Distinct Hepatic Receptors for Low Density Lipoprotein and Apolipoprotein E in Humans

    NASA Astrophysics Data System (ADS)

    Hoeg, Jeffrey M.; Demosky, Stephen J.; Gregg, Richard E.; Schaefer, Ernst J.; Brewer, H. Bryan

    1985-02-01

    Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

  19. Thermodynamics of the low-density excluded-volume hadron gas

    NASA Astrophysics Data System (ADS)

    Redlich, Krzysztof; Zalewski, Kacper

    2016-01-01

    We consider the thermodynamics of excluded-volume particles at finite temperature and chemical potential in the low-density approximation. We assume Boltzmann statistics and study the influence of the excluded volume on an ideal gas thermodynamics at the same temperature, pressure, and number of particles. We show that considering the change of the free enthalpy due to the excluded volume, and using the Maxwell identities, one can derive relevant thermodynamic functions and parameters of multicomponent gases. The derivation is quite general, because particles may have different sizes and shapes which can also depend on their momenta. Besides its simplicity and generality, our approach has the advantage of eliminating the transcendental equations occurring in earlier studies. A representative example of the excluded-volume thermodynamics is the single-component gas of hard spheres. For this case, using a virial expansion, the validity limits of the low-density approximation are also discussed.

  20. Growth-interruption-induced low-density InAs quantum dots on GaAs

    SciTech Connect

    Li, L. H.; Alloing, B.; Chauvin, N.; Fiore, A.; Patriarche, G.

    2008-10-15

    We investigate the use of growth interruption to obtain low-density InAs quantum dots (QDs) on GaAs. The process was realized by Ostwald-type ripening of a thin InAs layer. It was found that the optical properties of the QDs as a function of growth interruption strongly depend on InAs growth rate. By using this approach, a low density of QDs (4 dots/{mu}m{sup 2}) with uniform size distribution was achieved. As compared to QDs grown without growth interruption, a larger energy separation between the QD confined levels was observed, suggesting a situation closer to the ideal zero-dimensional system. Combining with an InGaAs capping layer such as In-rich QDs enable 1.3 {mu}m emission at 4 K.

  1. Interaction of laser radiation with a low-density structured absorber

    NASA Astrophysics Data System (ADS)

    Rozanov, V. B.; Barishpol'tsev, D. V.; Vergunova, G. A.; Demchenko, N. N.; Ivanov, E. M.; Aristova, E. N.; Zmitrenko, N. V.; Limpouch, I.; Ulschmidt, I.

    2016-02-01

    A theoretical model is proposed for computing simulations of laser radiation interaction with inhomogeneous foam materials doped with heavy elements and undoped materials. The model satisfactorily describes many experiments on the interaction of the first and third harmonics of a 200 J pulsed PALS iodine laser with low-density porous cellulose triacetate targets. The model can be used to analyze experimental data and estimate the reality of experimental results.

  2. Simulation of Low-density Nozzle Plumes in Non-zero Ambient Pressures

    NASA Technical Reports Server (NTRS)

    Chung, Chan-Hong; Dewitt, Kenneth J.; Stubbs, Robert M.; Penko, Paul F.

    1994-01-01

    The direct simulation Monte-Carlo (DSMC) method was applied to the analysis of low-density nitrogen plumes exhausting from a small converging-diverging nozzle into finite ambient pressures. Two cases were considered that simulated actual test conditions in a vacuum facility. The numerical simulations readily captured the complicated flow structure of the overexpanded plumes adjusting to the finite ambient pressures, including Mach disks and barrel shaped shocks. The numerical simulations compared well to experimental data of Rothe.

  3. Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer

    SciTech Connect

    Alexander, J.J.; Miguel, R.; Graham, D. )

    1991-03-01

    To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process.

  4. Derivation of the Fick's Law for the Lorentz Model in a Low Density Regime

    NASA Astrophysics Data System (ADS)

    Basile, G.; Nota, A.; Pezzotti, F.; Pulvirenti, M.

    2015-06-01

    We consider the Lorentz model in a slab with two mass reservoirs at the boundaries. We show that, in a low density regime, there exists a unique stationary solution for the microscopic dynamics, which converges to the stationary solution of the heat equation, namely to the linear profile of the density. In the same regime, the macroscopic current in the stationary state is given by the Fick's law, with the diffusion coefficient determined by the Green-Kubo formula.

  5. Low density, microcellular, dopable, agar/gelatin foams for pulsed power experiments

    SciTech Connect

    McNamara, W.F.; Aubert, J.H.

    1997-04-01

    Low-density, microcellular foams prepared from the natural polymers agar and gelatin have been developed for pulsed-power physics experiments. Numerous experiments were supported with foams having densities at or below 10 mg/cm{sup 3}. For some of the experiments, the agar/gelatin foam was uniformly doped with metallic elements using soluble salts. Depending on the method of preparation, cell sizes were typically below 10 microns and for one process were below 1.0 micron.

  6. The Low Density Matter (LDM) beamline at FERMI: optical layout and first commissioning

    PubMed Central

    Svetina, Cristian; Grazioli, Cesare; Mahne, Nicola; Raimondi, Lorenzo; Fava, Claudio; Zangrando, Marco; Gerusina, Simone; Alagia, Michele; Avaldi, Lorenzo; Cautero, Giuseppe; de Simone, Monica; Devetta, Michele; Di Fraia, Michele; Drabbels, Marcel; Feyer, Vitaliy; Finetti, Paola; Katzy, Raphael; Kivimäki, Antti; Lyamayev, Viktor; Mazza, Tommaso; Moise, Angelica; Möller, Thomas; O’Keeffe, Patrick; Ovcharenko, Yevheniy; Piseri, Paolo; Plekan, Oksana; Prince, Kevin C.; Sergo, Rudi; Stienkemeier, Frank; Stranges, Stefano; Coreno, Marcello; Callegari, Carlo

    2015-01-01

    The Low Density Matter (LDM) beamline has been built as part of the FERMI free-electron laser (FEL) facility to serve the atomic, molecular and cluster physics community. After the commissioning phase, it received the first external users at the end of 2012. The design and characterization of the LDM photon transport system is described, detailing the optical components of the beamline. PMID:25931066

  7. Simulation of low-density nozzle plumes in non-zero ambient pressures

    NASA Astrophysics Data System (ADS)

    Chung, Chan-Hong; Dewitt, Kenneth J.; Stubbs, Robert M.; Penko, Paul F.

    1994-02-01

    The direct simulation Monte-Carlo (DSMC) method was applied to the analysis of low-density nitrogen plumes exhausting from a small converging-diverging nozzle into finite ambient pressures. Two cases were considered that simulated actual test conditions in a vacuum facility. The numerical simulations readily captured the complicated flow structure of the overexpanded plumes adjusting to the finite ambient pressures, including Mach disks and barrel shaped shocks. The numerical simulations compared well to experimental data of Rothe.

  8. Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients

    PubMed Central

    Ballard, Kevin D.; Mah, Eunice; Guo, Yi; Bruno, Richard S.; Taylor, Beth A.; Beam, Jo Ellen; Polk, Donna M.; Thompson, Paul D.

    2016-01-01

    Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- and γ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y). Results. Relative to Pre, total cholesterol (7.8 ± 1.5 mmol/L) and LDL-cholesterol (6.2 ± 1.2 mmol/L) were 61% and 70% lower (P < 0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P < 0.01), and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia. PMID:26998360

  9. Protection by polyphenols of postprandial human plasma and low-density lipoprotein modification: the stomach as a bioreactor.

    PubMed

    Kanner, Joseph; Gorelik, Shlomit; Roman, Sirota; Kohen, Ron

    2012-09-12

    Recent studies dramatically showed that the removal of circulating modified low-density lipoprotein (LDL) results in complete prevention of atherosclerosis. The gastrointestinal tract is constantly exposed to food, some of it containing oxidized compounds. Lipid oxidation in the stomach was demonstrated by ingesting heated red meat in rats. Red wine polyphenols added to the rats' meat diet prevented lipid peroxidation in the stomach and absorption of malondialdehyde (MDA) in rat plasma. In humans, postprandial plasma MDA levels rose by 3-fold after a meal of red meat cutlets. MDA derived from meat consumption caused postprandial plasma LDL modification in human. The levels of plasma MDA showed a 75% reduction by consumption of red wine polyphenols during the meat meal. Locating the main biological site of action of polyphenols in the stomach led to a revision in the understanding of how antioxidants work in vivo and may help to elucidate the mechanism involved in the protective effects of polyphenols in human health. PMID:22530973

  10. Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans.

    PubMed

    Mateos, Raquel; Martínez-López, Sara; Baeza Arévalo, Gema; Amigo-Benavent, Miryam; Sarriá, Beatriz; Bravo-Clemente, Laura

    2016-08-15

    Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non-enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA-glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. PMID:27006237

  11. Membrane receptors for very low density lipoprotein (VLDL) inhibitor of lymphocyte proliferation

    SciTech Connect

    Yi, P.I.; Beck, G.; Zucker, S.

    1981-06-01

    Physiologic concentrations of human plasma very low density lipoproteins inhibit the DNA synthesis of lymphocytes stimulated by allogeneic cells or lectins. In this report reachers have compared the effects of isolated lipoproteins (very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)) and lipoprotein-depleted plasma (LDP) on DNA synthesis by phytohemagglutinin-stimulated human lymphocytes. The relative potency for the inhibition of lymphocyte proliferation was VLDL greater than LDL greater than HDL greater than LDP. Fifty percent inhibition of DNA synthesis was observed at a VLDL protein concentration of 1.5--2.0 microgram/ml. Researchers have further demonstrated the presence of specific receptors for VLDL on human lymphocytes. Native VLDL was more effective than LDL in competing for 125I-VLDL binding sites. Subsequent to binding to lymphocytes, 125I-VLDL was internalized and degraded to acid-soluble products. Based on a Scatchard analysis of VLDL binding at 4 degrees C, the number of VLDL receptors per lymphocyte was estimated at 28,000 +/- 1300. Based on an estimated mean binding affinity for the VLDL receptor complex at half saturation of approximately 8.8 X 10(7) liter/mole, it is estimated that 91% of lymphocyte VLDL receptors are occupied at physiologic VLDL concentrations in blood. Although the immune regulatory role of plasma lipoproteins is uncertain, researchers suggest tha VLDL and LDL-In may maintain circulating blood lymphocytes in a nonproliferative state via their respective cell receptor mechanisms.

  12. Pairs of galaxies in low density regions of a combined redshift catalog

    NASA Technical Reports Server (NTRS)

    Charlton, Jane C.; Salpeter, Edwin E.

    1990-01-01

    The distributions of projected separations and radial velocity differences of pairs of galaxies in the CfA and Southern Sky Redshift Survey (SSRS) redshift catalogs are examined. The authors focus on pairs that fall in low density environments rather than in clusters or large groups. The projected separation distribution is nearly flat, while uncorrelated galaxies would have given one linearly rising with r sub p. There is no break in this curve even below 50 kpc, the minimum halo size consistent with measured galaxy rotation curves. The significant number of pairs at small separations is inconsistent with the N-body result that galaxies with overlapping halos will rapidly merge, unless there are significant amounts of matter distributed out to a few hundred kpc of the galaxies. This dark matter may either be in distinct halos or more loosely distributed. Large halos would allow pairs at initially large separations to head toward merger, replenishing the distribution at small separations. In the context of this model, the authors estimate that roughly 10 to 25 percent of these low density galaxies are the product of a merger, compared with the elliptical/SO fraction of 18 percent, observed in low density regions of the sample.

  13. Galaxy clusters and cold dark matter - A low-density unbiased universe?

    NASA Technical Reports Server (NTRS)

    Bahcall, Neta A.; Cen, Renyue

    1992-01-01

    Large-scale simulations of a universe dominated by cold dark matter (CDM) are tested against two fundamental properties of clusters of galaxies: the cluster mass function and the cluster correlation function. We find that standard biased CDM models are inconsistent with these observations for any bias parameter b. A low-density, low-bias CDM-type model, with or without a cosmological constant, appears to be consistent with both the cluster mass function and the cluster correlations. The low-density model agrees well with the observed correlation function of the Abell, Automatic Plate Measuring Facility (APM), and Edinburgh-Durham cluster catalogs. The model is in excellent agreement with the observed dependence of the correlation strength on cluster mean separation, reproducing the measured universal dimensionless cluster correlation. The low-density model is also consistent with other large-scale structure observations, including the APM angular galaxy-correlations, and for lambda = 1-Omega with the COBE results of the microwave background radiation fluctuations.

  14. Requirements for low density riming and two stage growth on atmospheric particles

    NASA Astrophysics Data System (ADS)

    Levi, Laura; Castellano, Nesvit E.; Nasello, Olga B.; Prodi, Franco

    A theoretical study is carried out of the conditions that can be expected to determine low density riming on atmospheric ice particles. Using a growth simulation model, critical liquid water contents Lwc and air temperatures Ta are calculated, which correspond to a density ρ=0.5 g/cm 3 for rime deposit on ice particles with radii varying from 1 to 10 mm. Their dependence on the used laws for the ice density as a function of Macklin's parameter and for the drag coefficient as a function of Reynolds number, is discussed. The evolution of the density and related parameters for free falling particles growing by accretion from initial values of the radius R and density ρ is studied in different environmental conditions. It is shown that the temperature of the deposit Ts increases with R, up to the transition to wet growth, represented by Ts=0°C. Only for Lwc≥2 g/m 3 the transition from low density ice to wet growth is found to occur rapidly, at a distance from the center R≤1 cm. This distance is considered to represent the maximum radius of regions where two-stage growth, due to water penetration and freezing into pores of low-density layers, can be responsible for rapid variations of the particle density and consequently of its free-fall speed, which would characterize the effect of hail growth via microphysical recycling.

  15. Response of ecosystem metabolism to low densities of spawning Chinook salmon

    USGS Publications Warehouse

    Benjamin, Joseph R.; Bellmore, James R.; Watson, Grace A.

    2016-01-01

    Marine derived nutrients delivered by large runs of returning salmon are thought to subsidize the in situ food resources that support juvenile salmon. In the Pacific Northwest, USA, salmon have declined to <10% of their historical abundance, with subsequent declines of marine derived nutrients once provided by large salmon runs. We explored whether low densities (<0.001 spawners/m2) of naturally spawning Chinook Salmon (Oncorhynchus tshawytscha) can affect ecosystem metabolism. We measured gross primary production (GPP) and ecosystem respiration (ER) continuously before, during, and after salmon spawning. We compared downstream reaches with low densities of spawning salmon to upstream reaches with fewer or no spawners in 3 mid-sized (4th-order) rivers in northern Washington. In addition, we measured chemical, physical, and biological factors that may be important in controlling rates of GPP and ER. We observed that low densities of spawning salmon can increase GPP by 46% during spawning, but values quickly return to those observed before spawning. No difference in ER was observed between up- and downstream reaches. Based on our results, salmon density, temperature, and the proximity to salmon redds were the most important factors controlling rates of GPP, whereas temperature was most important for ER. These results suggest that even at low spawning densities, salmon can stimulate basal resources that may propagate up the food web. Understanding how recipient ecosystems respond to low levels of marine derived nutrients may inform nutrient augmentation studies aimed at enhancing fish populations.

  16. In vivo low-density bone apposition on different implant surface materials.

    PubMed

    Braceras, I; De Maeztu, M A; Alava, J I; Gay-Escoda, C

    2009-03-01

    During osseointegration, new bone may be laid down on the implant surface and/or on the old bone surface; the former is known as contact osteogenesis and the latter as distance osteogenesis. Implant surface topography and material composition affect this process. The present study evaluates Ca and P apposition onto three different dental implant material surfaces (carbon monoxide (CO) ion implantation on Ti6Al4V, sand blasting and acid etching on commercially pure titanium and untreated Ti6Al4V) on the mandibles of beagles after healing periods of 3 and 6 months. Energy dispersive spectroscopy is useful for identifying low-density bone relative to surrounding mature bone, allowing for discrimination of the osteogenesis source. Low-density bone was only found at the apical end; there was none on the surface of untreated implants. Low-density bone arising from mature bone towards the implant at month 3 (i.e. distance osteogenesis) was only present on the CO ion implanted samples, due to the modification of the surface nano-topography and the chemistry and structure of the material. PMID:19200692

  17. Low-density lipoprotein cholesterol level and statin use among Medicare beneficiaries with diabetes mellitus.

    PubMed

    Qualls, Laura G; Hammill, Bradley G; Maciejewski, Matthew L; Curtis, Lesley H; Jones, W Schuyler

    2016-05-01

    At the time of this study, guidelines recommended a primary goal of low-density lipoprotein cholesterol level less than 100 mg/dL for all patients, an optional goal of low-density lipoprotein cholesterol less than 70 mg/dL for patients with overt cardiovascular disease and statins for patients with diabetes and overt cardiovascular disease and patients 40 years and older with diabetes and at least one risk factor for cardiovascular disease. This study examined statin use and achievement of lipid goals among 111,730 Medicare fee-for-service beneficiaries 65 years and older in 2011. Three-quarters of patients met the low-density lipoprotein cholesterol goal of less than 100 mg/dL. Patients with cardiovascular disease were more likely to meet the goal than those without, not controlling for other differences. Patients on a statin were more likely to meet the goal. There is considerable opportunity for improvement in cholesterol management in high-risk patients with diabetes mellitus. PMID:26802221

  18. [THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND APOC-III].

    PubMed

    Rozhkova, T A; Titov, V N; Amelyushkina, V A; Kaba, S I; Kukhartchuk, V V

    2015-12-01

    According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein. It is reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL These LDL increase plasma contents of TG and LDL-cholesterol and form small dense palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an indicator of accumulation of non-physiological palmitic LDL and atherosclerosis-atheromatosis risk factor ApoE content ofpalmitic LDL increases together with apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100 endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to evaluate the efficiency of

  19. N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

    PubMed Central

    Zhang, Chun-ge; Zhu, Qiao-ling; Zhou, Yi; Liu, Yang; Chen, Wei-liang; Yuan, Zhi-Qiang; Yang, Shu-di; Zhou, Xiao-feng; Zhu, Ai-jun; Zhang, Xue-nong; Jin, Yong

    2014-01-01

    N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor. PMID:24966673

  20. N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors.

    PubMed

    Zhang, Chun-ge; Zhu, Qiao-ling; Zhou, Yi; Liu, Yang; Chen, Wei-liang; Yuan, Zhi-Qiang; Yang, Shu-di; Zhou, Xiao-feng; Zhu, Ai-jun; Zhang, Xue-nong; Jin, Yong

    2014-01-01

    N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor. PMID:24966673

  1. Beneficial effect of Lisosan G on cultured human microvascular endothelial cells exposed to oxidised low density lipoprotein

    PubMed Central

    Lubrano, Valter; Baldi, Simona; Napoli, Debora; Longo, Vincenzo

    2012-01-01

    Background & objectives: Nutritional compounds which display anti-inflammatory and antioxidant effects have specific applications in preventing oxidative stress and endothelial dysfunction. In this study we evaluated the effect of Lisosan G (powder of Triticum sativum grains) on human microvascular endothelial cells (HMEC-1) exposed to oxidized low density lipoprotein (ox-LDL). Methods: The protective effects of Lisosan G were evaluated on human microvascular endothelial cells exposed to ox-LDL. Intercellular adhesion molecular-1 (ICAM-1), endothelin-1 (ET-1), and interleukin-6 (IL-6) concentrations and the expression of the respective genes were evaluated in response to incubation with ox-LDL, after co-incubation with ox-LDL and Lisosan G or exposed to Lisosan G alone. The analysis of LOX-1 gene was performed with RT-PCR semi quantitative method. The degree of oxidation induced in relation to control, was established by measurement of malondialdehyde (MDA) production. Results: The incubation with ox-LDL induced a significant increase in ICAM-1, IL-6 and ET-1 levels compared to the basal condition (P<0.01, P<0.05, and P<0.01, respectively), while in presence of Lisosan G, ICAM-1 levels showed a significant reduction both compared to the cultures treated with ox-LDL and control (P<0.01). IL-6 levels did not show any difference; ET-1 levels showed a partial reduction after co-treatment with Lisosan G, and also with Lisosan G alone, reduced the concentration below control (P<0.01). The modulation of these markers was confirmed by RT-PCR analysis. An association between MDA formation and the three markers production was observed. Semi-quantitative analysis of LOX-1 gene expression showed a significant up-regulation only after ox-LDL exposure. Interpretation & conclusions: The results demonstrate that Lisosan G may have an important role in the prevention of microcirculatory dysfunction. PMID:22885268

  2. Modified low-density lipoproteins and high-density lipoproteins. From investigation tools to real in vivo players.

    PubMed

    Koller, Elisabeth; Volf, Ivo; Gurvitz, Aner; Koller, Franz

    2006-01-01

    It has long been known that the oxidative state of the various plasma lipoproteins modulates platelet aggregability, thereby contributing to atherogenesis. Low-density lipoprotein (LDL), occurring in vivo both in the native and oxidised forms, interacts directly with platelets, by binding to specific receptors. While the identity of the receptors for native LDL and some subfractions of high-density lipoproteins (HDL) remains disputed, apoE-containing HDL(2) binds to LRP8. The nature of these interactions as well as the distinction between candidate receptor proteins was elucidated using covalently modified apolipoproteins, which pointed to the participation of apolipoproteins in high affinity binding. However, the platelet effects initiated by binding of native lipoproteins remain controversial. Some of this ambiguity can be traced to the fact that native LDL inevitably undergoes substantial oxidisation upon modification, including by radiolabelling. The platelet-activating effects provoked by oxidised LDL are irrefutable, but many details remain unknown. The role of CD36 in platelet binding by oxidised LDL is well established, although additional receptors may exist. Much less is known about the interaction of oxidised HDL with platelets, since platelet activation was observed in some, but not all studies. Various frequently applied in vitro oxidation methods produce modified lipoprotein species that may not be relevant in vivo. Based on the reported modifications obtained by in vitro oxidation of LDL, early investigations focused mainly on the formation and the eventual effects of oxidised lipids. More recently, alterations to lipoproteins performed using hypochloric acid and myeloperoxidase redirected the attention to the role of modified apoproteins in triggering platelet responses. PMID:16877881

  3. Brittle intermetallic compound makes ultrastrong low-density steel with large ductility.

    PubMed

    Kim, Sang-Heon; Kim, Hansoo; Kim, Nack J

    2015-02-01

    Although steel has been the workhorse of the automotive industry since the 1920s, the share by weight of steel and iron in an average light vehicle is now gradually decreasing, from 68.1 per cent in 1995 to 60.1 per cent in 2011 (refs 1, 2). This has been driven by the low strength-to-weight ratio (specific strength) of iron and steel, and the desire to improve such mechanical properties with other materials. Recently, high-aluminium low-density steels have been actively studied as a means of increasing the specific strength of an alloy by reducing its density. But with increasing aluminium content a problem is encountered: brittle intermetallic compounds can form in the resulting alloys, leading to poor ductility. Here we show that an FeAl-type brittle but hard intermetallic compound (B2) can be effectively used as a strengthening second phase in high-aluminium low-density steel, while alleviating its harmful effect on ductility by controlling its morphology and dispersion. The specific tensile strength and ductility of the developed steel improve on those of the lightest and strongest metallic materials known, titanium alloys. We found that alloying of nickel catalyses the precipitation of nanometre-sized B2 particles in the face-centred cubic matrix of high-aluminium low-density steel during heat treatment of cold-rolled sheet steel. Our results demonstrate how intermetallic compounds can be harnessed in the alloy design of lightweight steels for structural applications and others. PMID:25652998

  4. Brittle intermetallic compound makes ultrastrong low-density steel with large ductility

    NASA Astrophysics Data System (ADS)

    Kim, Sang-Heon; Kim, Hansoo; Kim, Nack J.

    2015-02-01

    Although steel has been the workhorse of the automotive industry since the 1920s, the share by weight of steel and iron in an average light vehicle is now gradually decreasing, from 68.1 per cent in 1995 to 60.1 per cent in 2011 (refs 1, 2). This has been driven by the low strength-to-weight ratio (specific strength) of iron and steel, and the desire to improve such mechanical properties with other materials. Recently, high-aluminium low-density steels have been actively studied as a means of increasing the specific strength of an alloy by reducing its density. But with increasing aluminium content a problem is encountered: brittle intermetallic compounds can form in the resulting alloys, leading to poor ductility. Here we show that an FeAl-type brittle but hard intermetallic compound (B2) can be effectively used as a strengthening second phase in high-aluminium low-density steel, while alleviating its harmful effect on ductility by controlling its morphology and dispersion. The specific tensile strength and ductility of the developed steel improve on those of the lightest and strongest metallic materials known, titanium alloys. We found that alloying of nickel catalyses the precipitation of nanometre-sized B2 particles in the face-centred cubic matrix of high-aluminium low-density steel during heat treatment of cold-rolled sheet steel. Our results demonstrate how intermetallic compounds can be harnessed in the alloy design of lightweight steels for structural applications and others.

  5. Does nitrogen gas bubbled through a low density polymer gel dosimeter solution affect the polymerization process?

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Gholami, Mehrdad; Pourfallah, Tayyeb Allahverdi; Keshtkar, Mohammad

    2015-01-01

    Background: On account of the lower electron density in the lung tissue, the dose distribution in the lung cannot be verified with the existing polymer gel dosimeters. Thus, the aims of this study are to make a low density polymer gel dosimeter and investigate the effect of nitrogen gas bubbles on the R2 responses and its homogeneity. Materials and Methods: Two different types of low density polymer gel dosimeters were prepared according to a composition proposed by De Deene, with some modifications. In the first type, no nitrogen gas was perfused through the gel solution and water. In the second type, to expel the dissolved oxygen, nitrogen gas was perfused through the water and gel solution. The post-irradiation times in the gels were 24 and 5 hours, respectively, with and without perfusion of nitrogen gas through the water and gel solution. Results: In the first type of gel, there was a linear correlation between the doses and R2 responses from 0 to 12 Gy. The fabricated gel had a higher dynamic range than the other low density polymer gel dosimeter; but its background R2 response was higher. In the second type, no difference in R2 response was seen in the dose ranges from 0 to 18 Gy. Both gels had a mass density between 0.35 and 0.45 g.cm-3 and CT values of about -650 to -750 Hounsfield units. Conclusion: It appeared that reactions between gelatin-free radicals and monomers, due to an increase in the gel temperature during rotation in the household mixer, led to a higher R2-background response. In the second type of gel, it seemed that the collapse of the nitrogen bubbles was the main factor that affected the R2-responses. PMID:26015914

  6. Experimental static aerodynamics of a regular hexagonal prism in a low density hypervelocity flow

    NASA Technical Reports Server (NTRS)

    Guy, R. W.; Mueller, J. N.; Lee, L. P.

    1972-01-01

    A regular hexagonal prism, having a fineness ratio of 1.67, has been tested in a wind tunnel to determine its static aerodynamic characteristics in a low-density hypervelocity flow. The prism tested was a 1/4-scale model of the graphite heat shield which houses the radioactive fuel for the Viking spacecraft auxiliary power supply. The basic hexagonal prism was also modified to simulate a prism on which ablation of one of the six side flats had occurred. This modified hexagonal prism was tested to determine the effects on the aerodynamic characteristics of a shape change caused by ablation during a possible side-on stable reentry.

  7. A monochromatic x-ray imaging system for characterizing low-density foams

    SciTech Connect

    Lanier, Nicholas E.; Taccetti, Jose M.; Hamilton, Christopher E.

    2012-05-04

    In High Energy Density (HED) laser experiments, targets often require small, low-density, foam components. However, their limited size can preclude single component characterization, forcing one to rely solely on less accurate bulk measurements. We have developed a monochromatic imaging a system to characterize both the density and uniformity of single component low-mass foams. This x-ray assembly is capable of determining line-averaged density variations near the 1% level, and provides statistically identical results to those obtained at the Brookhaven's NSLS. This system has the added benefit of providing two-dimensional density data, allowing an assessment of density uniformity.

  8. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    SciTech Connect

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

    2006-06-14

    This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

  9. Structured Low-Density Parity-Check Codes with Bandwidth Efficient Modulation

    NASA Technical Reports Server (NTRS)

    Cheng, Michael K.; Divsalar, Dariush; Duy, Stephanie

    2009-01-01

    In this work, we study the performance of structured Low-Density Parity-Check (LDPC) Codes together with bandwidth efficient modulations. We consider protograph-based LDPC codes that facilitate high-speed hardware implementations and have minimum distances that grow linearly with block sizes. We cover various higher- order modulations such as 8-PSK, 16-APSK, and 16-QAM. During demodulation, a demapper transforms the received in-phase and quadrature samples into reliability information that feeds the binary LDPC decoder. We will compare various low-complexity demappers and provide simulation results for assorted coded-modulation combinations on the additive white Gaussian noise and independent Rayleigh fading channels.

  10. Hardware implementation and characterization of a low density parity check (LDPC) decoder

    NASA Astrophysics Data System (ADS)

    Shoup, Ryan

    2006-08-01

    The hardware implementation of a low complexity Low Density Parity Check (LDPC) decoder is described. The design of the LDPC decoder optimized on minimizing the amount of hardware resources necessary for implementation. In addition to implementation details, design tradeoffs considered in the development of the LDPC decoder are discussed. The intended application of the LDPC decoder is a nonlinear satellite communications channel. The nonlinearities and communications signal perturbations include Additive White Gaussian Noise (AWGN), phase noise, phase imbalance, and a model satellite high power amplifier nonlinearity. The LDPC decoder performance is then characterized in the satellite channel.

  11. Isotope-specific detection of low density materials with mono-energetic (gamma)-rays

    SciTech Connect

    Albert, F; Anderson, S G; Gibson, D J; Hagmann, C A; Johnson, M S; Messerly, M J; Semenov, V A; Shverdin, M Y; Tremaine, A M; Hartemann, F V; Siders, C W; McNabb, D P; Barty, C J

    2009-03-16

    The first demonstration of isotope-specific detection of a low-Z, low density object, shielded by a high-Z and high density material using mono-energetic gamma-rays is reported. Isotope-specific detection of LiH shielded by Pb and Al is accomplished using the nuclear resonance fluorescence line of {sup 7}Li at 0.478 MeV. Resonant photons are produced via laser-based Compton scattering. The detection techniques are general and the confidence level obtained is shown to be superior to that yielded by conventional x-ray/{gamma}-ray techniques in these situations.

  12. Extreme ultraviolet source at 6.7 nm based on a low-density plasma

    SciTech Connect

    Higashiguchi, Takeshi; Yugami, Noboru; Otsuka, Takamitsu; Jiang, Weihua; Endo, Akira; Li Bowen; Kilbane, Deirdre; Dunne, Padraig; O'Sullivan, Gerry

    2011-11-07

    We demonstrate an efficient extreme ultraviolet (EUV) source for operation at {lambda} = 6.7 nm by optimizing the optical thickness of gadolinium (Gd) plasmas. Using low initial density Gd targets and dual laser pulse irradiation, we observed a maximum EUV conversion efficiency (CE) of 0.54% for 0.6% bandwidth (BW) (1.8% for 2% BW), which is 1.6 times larger than the 0.33% (0.6% BW) CE produced from a solid density target. Enhancement of the EUV CE by use of a low-density plasma is attributed to the reduction of self-absorption effects.

  13. Thermoelectric power in low-density interstitial-free iron-aluminium alloys

    NASA Astrophysics Data System (ADS)

    Rana, Radhakanta; Liu, Cheng

    2013-09-01

    Thermoelectric power (TEP) studies on low-density interstitial-free iron-aluminium alloys reveal that the TEP decreases with increase in the aluminium content on account of the introduction of lattice dispersion centres. The TEP coefficients, determined from the Nordheim-Gorter law, for 6.8 and 8.1 wt.% aluminium additions to α-iron are found to be higher than values reported in previous literature for small aluminium additions. The grain size has a very weak effect on the TEP of these alloys.

  14. Development and scale-up of the low density core process for Ti-64

    SciTech Connect

    Schwartz, D.S.; Shih, D.S.; Lederich, R.J.; Martin, R.L.; Deuser, D.A.

    1998-12-31

    The Low Density Core (LDC) process is a method for making metallic structures with solid surfaces covering a porous core. The development of the LDC process for making Ti-64 sheet based structures is described. Sheets {approximately}2000 x 1200 x 4 mm{sup 3} have been made with {approximately}40 vol.% core porosity levels, and several forming techniques have been demonstrated. The LDC billet breakdown and forming behavior was found to be similar to conventional Ti-64 processes, so LDC Ti-64 sheet has the advantage that it can be fabricated into structures using well-established methods.

  15. RAPID COMMUNICATION: Influence of temperature treatment on the electrical properties of low-density polyethylene

    NASA Astrophysics Data System (ADS)

    Boudou, L.; Guastavino, J.

    2000-11-01

    The influence of temperature from 298 K to 353 K on the electrical conduction of low-density polyethylene is reported. Conduction current and differential scanning calorimetry (DSC) measurements show a correlation between the structural change due to the temperature treatment and the change in the activation energy of the conduction mechanism involved. When the temperature is greater than 318 K, an activation energy decrease from 0.94 eV to 0.68 eV and a DSC exothermic peak are observed. This temperature threshold is correlated with a facilitated detrapping of charges stored during polarization.

  16. Note: Low density and long plasma channels generated by laser transversely ignited ablative capillary discharges.

    PubMed

    Liu, Mingwei; Deng, Aihua; Liu, Jiansheng; Li, Ruxin; Xu, Jiancai; Xia, Changquan; Wang, Cheng; Shen, Baifei; Xu, Zhizhan; Nakajima, K

    2010-03-01

    A technique is developed to reduce the jitter associated with ablative capillary discharges. A laser pulse propagating perpendicularly to the axis of the capillary and focused onto a copper wire creates a plasma that initiates the discharge. This transverse laser ignition method has several advantages over previous techniques employing a laser pulse collinear with the capillary, including increased capillary lifetime and simpler arrangement of the igniting and the driving pulses for laser-wakefield acceleration. Using this technique long, low density plasma channels are produced with low jitter. PMID:20370230

  17. High excitation power photoluminescence studies of ultra-low density GaAs quantum dots

    SciTech Connect

    Sonnenberg, D.; Graf, A.; Paulava, V.; Heyn, Ch.; Hansen, W.

    2013-12-04

    We fabricate GaAs epitaxial quantum dots (QDs) by filling of self-organized nanoholes in AlGaAs. The QDs are fabricated under optimized process conditions and have ultra-low density in the 10{sup 6} cm{sup −2} regime. At low excitation power the optical emission of single QDs exhibit sharp excitonic lines, which are attributed to the recombination of excitonic and biexcitonic states. High excitation power measurements reveal surprisingly broad emission lines from at least six QD shell states.

  18. Evaluation of a low-density polyimide foam in a dynamic, high temperature environment

    NASA Technical Reports Server (NTRS)

    Pittman, C. M.; Brown, R. D.

    1977-01-01

    A low density polyimide foam material was tested in an arc tunnel to determine its potential for heat shield application on aerospace vehicles. The results show that the material has some reuse potential at surface temperatures as high as 750 K. When a black refractory paint was applied to the surface of the material, the surface recession was negligible at 750 K. An analytical thermal conductivity was derived for this material which, combined with measured thermal property values, can be used to make preliminary design thickness calculations for heat shield applications.

  19. The utility of low-density genotyping for imputation in the Thoroughbred horse

    PubMed Central

    2014-01-01

    Background Despite the dramatic reduction in the cost of high-density genotyping that has occurred over the last decade, it remains one of the limiting factors for obtaining the large datasets required for genomic studies of disease in the horse. In this study, we investigated the potential for low-density genotyping and subsequent imputation to address this problem. Results Using the haplotype phasing and imputation program, BEAGLE, it is possible to impute genotypes from low- to high-density (50K) in the Thoroughbred horse with reasonable to high accuracy. Analysis of the sources of variation in imputation accuracy revealed dependence both on the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and on the underlying linkage disequilibrium structure. Whereas equidistant spacing of the SNPs on the low-density panel worked well, optimising SNP selection to increase their minor allele frequency was advantageous, even when the panel was subsequently used in a population of different geographical origin. Replacing base pair position with linkage disequilibrium map distance reduced the variation in imputation accuracy across SNPs. Whereas a 1K SNP panel was generally sufficient to ensure that more than 80% of genotypes were correctly imputed, other studies suggest that a 2K to 3K panel is more efficient to minimize the subsequent loss of accuracy in genomic prediction analyses. The relationship between accuracy and genotyping costs for the different low-density panels, suggests that a 2K SNP panel would represent good value for money. Conclusions Low-density genotyping with a 2K SNP panel followed by imputation provides a compromise between cost and accuracy that could promote more widespread genotyping, and hence the use of genomic information in horses. In addition to offering a low cost alternative to high-density genotyping, imputation provides a means to combine datasets from different genotyping platforms, which is becoming

  20. Enzymatic modification of plasma low density lipoproteins in rabbits: a potential treatment for hypercholesterolemia.

    PubMed Central

    Labeque, R; Mullon, C J; Ferreira, J P; Lees, R S; Langer, R

    1993-01-01

    Phospholipase A2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels. PMID:8475095

  1. Bogolubov-Hartree-Fock Theory for Strongly Interacting Fermions in the Low Density Limit

    NASA Astrophysics Data System (ADS)

    Bräunlich, Gerhard; Hainzl, Christian; Seiringer, Robert

    2016-06-01

    We consider the Bogolubov-Hartree-Fock functional for a fermionic many-body system with two-body interactions. For suitable interaction potentials that have a strong enough attractive tail in order to allow for two-body bound states, but are otherwise sufficiently repulsive to guarantee stability of the system, we show that in the low-density limit the ground state of this model consists of a Bose-Einstein condensate of fermion pairs. The latter can be described by means of the Gross-Pitaevskii energy functional.

  2. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    NASA Astrophysics Data System (ADS)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

  3. Converging shock generation with cone target filled with low density foam

    NASA Astrophysics Data System (ADS)

    Shigemori, K.; Yamamoto, T.; Hironaka, Y.; Kawashima, T.; Hattori, S.; Nagatomo, H.; Kato, H.; Sato, N.; Watari, T.; Takagi, M.

    2016-05-01

    We have been developing an alternative scheme of fast ignition of inertial confinement targets with converging shock. Experiments were carried out on GEKKO-XII laser facility at ILE, Osaka University. We employed Au cone targets filled with low- density RF foam (2 mg/cm3). The foam-filled cone targets were irradiated by three beams of the GEKKO-XII, with pulse duration of 1.3 ns, intensity of ∼ 1014 W/cm2 in 2 :λ(ω0.527μm). Self-emission at the tip of cone was observed by one-dimensional streaked optical pyrometer (SOP) and two-dimensional images.

  4. Gravitational Effects on Flow Instability and Transition in Low Density Jets

    NASA Technical Reports Server (NTRS)

    Agrawal A. K.; Parthasarathy, K.; Pasumarthi, K.; Griffin, D. W.

    2000-01-01

    Recent experiments have shown that low-density gas jets injected into a high-density ambient gas undergo an instability mode, leading to highly-periodic oscillations in the flow-field for certain conditions. The transition from laminar to turbulent flow in these jets is abrupt, without the gradual change in scales. Even the fine scale turbulent structure repeats itself with extreme regularity from cycle to cycle. Similar observations were obtained in buoyancy-dominated and momentum-dominated jets characterized by the Richardson numbers, Ri = [gD(rho(sub a)-rho(sub j))/rho(sub j)U(sub j)(exp 2) ] where g is the gravitational acceleration, D is the jet diameter, rho(sub a) and rho(sub a) are, respectively, the free-stream and jet densities, and U(sub j) is the mean jet exit velocity. At high Richardson numbers, the instability is presumably caused by buoyancy since the flow-oscillation frequency (f) or the Strouhal number, St = [fD/U(sub j)] scales with Ri. In momentum-dominated jets, however, the Strouhal number of the oscillating flow is relatively independent of the Ri. In this case, a local absolute instability is predicted in the potential core of low-density jets with S [= rho(sub j)/rho(sub a)] < 0.7, which agrees qualitatively with experiments. Although the instability in gas jets of high Richardson numbers is attributed to buoyancy, direct physical evidence has not been acquired in experiments. If the instability is indeed caused by buoyancy, the near-field flow structure of the jet will change significantly when the buoyancy is removed, for example, in the microgravity environment. Thus, quantitative data on the spatial and temporal evolutions of the instability, length and time scale of the oscillating mode and its effects on the mean flow and breakdown of the potential core are needed in normal and microgravity to delineate gravitational effects in buoyant jets. In momentum dominated low-density jets, the instability is speculated to originate in the

  5. [Consecutive formation of the functions of high-, low-density and very-low-density lipoproteins during phylogenesis. Unique algorithm of the effects of lipid-lowering drugs].

    PubMed

    Titov, V N; Rozhkova, T A; Aripovsky, A V

    2015-01-01

    During phylogenesis, all fatty acids (FA) were initially transported to cells by apoA-I high-density lipoproteins (HDL) in polar lipids. Later, active cellular uptake of saturated, monoenoic and unsaturated FA occurred via triglycerides (TG) in low-density lipoproteins (LDL). Active uptake of polyenoic FA (PUFA) required the following: a) PUFA re-esterified from polar phospholipids into nonpolar cholesteryl polyesters (poly-CLE), b) a novel protein, cholesteryl ester transfer protein (CETP), initiated poly-CLE transformation from HDL to LDL. CETP formed blood HDL-CETP-LDL complexes in which poly-CLE spontaneously came from polar lipids of TG in HDL to nonpolar TG in LDL. Then ligand LDLs formed and the cells actively absorbed PUFA via apoB-100 endocytosis. Some animal species (rats, mice, dogs) developed a spontaneous CETP-minus mutation followed by population death from atherosclerosis. However, there was another active CETP-independent uptake formed during phylogenesis; the cells internalized poly-CLE in HDL. Since apoA-I had no domain-ligand, another apoE/A-I ligand formed; the cells began synthesizing apoE/A-1 receptors. In cells of rabbits and primates absorbed cells PUFA consecutively: HDL-->LDL-->apoB-100 endocytosis; those of rats and dogs did HDL directly: HDL-->anoE/A-I endocytosis. In the rabbits, CETP was high, apoE in HDL was low, and the animals were sensitive to exogenous hypercholesterolemia. In the rats, CETP was low and ApoE in HDL-was high, and the animals were resistant to hypercholesterolemia. Reduced bioavailability of PUFA during their consecutive cellular uptake and develdpment of intercellular PUFA deficiency are fundamental to the pathogenesis of atherosclerosis. PMID:26591564

  6. Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium avium in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis

    PubMed Central

    Caire-Brändli, Irène; Papadopoulos, Alexia; Malaga, Wladimir; Marais, David; Canaan, Stéphane; Thilo, Lutz

    2014-01-01

    During the dormant phase of tuberculosis, Mycobacterium tuberculosis persists in lung granulomas by residing in foamy macrophages (FM) that contain abundant lipid bodies (LB) in their cytoplasm, allowing bacilli to accumulate lipids as intracytoplasmic lipid inclusions (ILI). An experimental model of FM is presented where bone marrow-derived mouse macrophages are infected with M. avium and exposed to very-low-density lipoprotein (VLDL) as a lipid source. Quantitative analysis of detailed electron microscope observations showed the following results. (i) Macrophages became foamy, and mycobacteria formed ILI, for which host triacylglycerides, rather than cholesterol, was essential. (ii) Lipid transfer occurred via mycobacterium-induced fusion between LB and phagosomes. (iii) Mycobacteria showed a thinned cell wall and became elongated but did not divide. (iv) Upon removal of VLDL, LB and ILI declined within hours, and simultaneous resumption of mycobacterial division restored the number of mycobacteria to the same level as that found in untreated control macrophages. This showed that the presence of ILI resulted in a reversible block of division without causing a change in the mycobacterial replication rate. Fluctuation between ILI either partially or fully extending throughout the mycobacterial cytoplasm was suggestive of bacterial cell cycle events. We propose that VLDL-driven FM constitute a well-defined cellular system in which to study changed metabolic states of intracellular mycobacteria that may relate to persistence and reactivation of tuberculosis. PMID:24478064

  7. The effects of high energy electron beam irradiation on the thermal and structural properties of low density polyethylene

    NASA Astrophysics Data System (ADS)

    Murray, Kieran A.; Kennedy, James E.; McEvoy, Brian; Vrain, Olivier; Ryan, Damien; Higginbotham, Clement L.

    2012-08-01

    Radiation is currently being exploited to modify polyethylene in order to improve properties for various applications such as hip replacements. This paper thoroughly examines the effects of high energy electron beam irradiation (10 MeV) on low density polyethylene (LDPE) material. ASTM (American Society for Testing and Materials) testing specimens were manufactured from LDPE and subjected to a broad range of doses ranging between 25 and 400 kGy at room temperature in an air atmosphere. Extensive characterisation techniques such as modulated differential scanning calorimetry (MDSC) and the Fourier transform infrared spectroscopy (FTIR) were conducted on the non-irradiated and irradiated samples. While considering the semicrystalline nature of LDPE during the MDSC experiment, the melting temperature (Tm) and the temperature crystallinity (Tc) were calculated. This revealed that the Tm and the Tc decreased in temperature as the irradiation dose increased. The FTIR analysis was implemented to evaluate the presence of polar species such as carbonyl groups and trans-vinylene double bond groups. The IR spectra illustrated that the concentration of characteristic bands for trans-vinylene bonds increased with increasing radiation dose indicating the formation of carbonyl bond groups. Furthermore, the results demonstrated an occurrence of oxidative degradation due to the formation of carbonyl groups at 1718 cm-1.

  8. Realization of a label-free electrochemical immunosensor for detection of low density lipoprotein using NiO thin film.

    PubMed

    Kaur, Gurpreet; Tomar, Monika; Gupta, Vinay

    2016-06-15

    A label-free electrochemical immunosensor, based on nickel oxide (NiO) thin film, for the detection of low density lipoprotein (LDL) has been proposed. P-type semiconducting NiO thin film was deposited by RF sputtering technique and its properties were investigated by X-ray diffraction and Fourier transform infrared spectroscopy. The NiO thin film was utilized as an efficient matrix for the covalent immobilization of apolipoprotein B-100 antibody using EDC/NHS chemistry. The immunoelectrode, thus prepared, was studied using differential pulse voltammetry, cyclic voltammetry and electrochemical impedance spectroscopy. The impedimetric response of the immunosensor exhibited a high sensitivity of 12 kΩ μM(-1) over a wide linear range (0.018-0.5 μM) of LDL. The long shelf life (18 weeks) and enhanced performance characteristics of the immunosensor demonstrate the excellent ability of the NiO matrix for quantification of LDL at commercial level. PMID:26852197

  9. Recognition of Porphyromonas gingivalis Gingipain Epitopes by Natural IgM Binding to Malondialdehyde Modified Low-Density Lipoprotein

    PubMed Central

    Turunen, S. Pauliina; Kummu, Outi; Harila, Kirsi; Veneskoski, Marja; Soliymani, Rabah; Baumann, Marc; Pussinen, Pirkko J.; Hörkkö, Sohvi

    2012-01-01

    Objective Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL) and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA) modified LDL. Methods and Results Mouse monoclonal IgM (MDmAb) specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR−/− mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp) by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans. Conclusion Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis. PMID:22496875

  10. Comparison of High and Low Density Airborne LIDAR Data for Forest Road Quality Assessment

    NASA Astrophysics Data System (ADS)

    Kiss, K.; Malinen, J.; Tokola, T.

    2016-06-01

    Good quality forest roads are important for forest management. Airborne laser scanning data can help create automatized road quality detection, thus avoiding field visits. Two different pulse density datasets have been used to assess road quality: high-density airborne laser scanning data from Kiihtelysvaara and low-density data from Tuusniemi, Finland. The field inventory mainly focused on the surface wear condition, structural condition, flatness, road side vegetation and drying of the road. Observations were divided into poor, satisfactory and good categories based on the current Finnish quality standards used for forest roads. Digital Elevation Models were derived from the laser point cloud, and indices were calculated to determine road quality. The calculated indices assessed the topographic differences on the road surface and road sides. The topographic position index works well in flat terrain only, while the standardized elevation index described the road surface better if the differences are bigger. Both indices require at least a 1 metre resolution. High-density data is necessary for analysis of the road surface, and the indices relate mostly to the surface wear and flatness. The classification was more precise (31-92%) than on low-density data (25-40%). However, ditch detection and classification can be carried out using the sparse dataset as well (with a success rate of 69%). The use of airborne laser scanning data can provide quality information on forest roads.

  11. A microfluidic device for the automated electrical readout of low-density glass-slide microarrays.

    PubMed

    Díaz-González, María; Salvador, J Pablo; Bonilla, Diana; Marco, M Pilar; Fernández-Sánchez, César; Baldi, Antoni

    2015-12-15

    Microarrays are a powerful platform for rapid and multiplexed analysis in a wide range of research fields. Electrical readout systems have emerged as an alternative to conventional optical methods for microarray analysis thanks to its potential advantages like low-cost, low-power and easy miniaturization of the required instrumentation. In this work an automated electrical readout system for low-cost glass-slide microarrays is described. The system enables the simultaneous conductimetric detection of up to 36 biorecognition events by incorporating an array of interdigitated electrode transducers. A polydimethylsiloxane microfluidic structure has been designed that creates microwells over the transducers and incorporates the microfluidic channels required for filling and draining them with readout and cleaning solutions, thus making the readout process fully automated. Since the capture biomolecules are not immobilized on the transducer surface this readout system is reusable, in contrast to previously reported electrochemical microarrays. A low-density microarray based on a competitive enzymatic immunoassay for atrazine detection was used to test the performance of the readout system. The electrical assay shows a detection limit of 0.22±0.03 μg L(-1) similar to that obtained with fluorescent detection and allows the direct determination of the pesticide in polluted water samples. These results proved that an electrical readout system such as the one presented in this work is a reliable and cost-effective alternative to fluorescence scanners for the analysis of low-density microarrays. PMID:26210466

  12. Uniform electron gases. III. Low-density gases on three-dimensional spheres

    SciTech Connect

    Agboola, Davids; Knol, Anneke L.; Gill, Peter M. W. Loos, Pierre-François

    2015-08-28

    By combining variational Monte Carlo (VMC) and complete-basis-set limit Hartree-Fock (HF) calculations, we have obtained near-exact correlation energies for low-density same-spin electrons on a three-dimensional sphere (3-sphere), i.e., the surface of a four-dimensional ball. In the VMC calculations, we compare the efficacies of two types of one-electron basis functions for these strongly correlated systems and analyze the energy convergence with respect to the quality of the Jastrow factor. The HF calculations employ spherical Gaussian functions (SGFs) which are the curved-space analogs of Cartesian Gaussian functions. At low densities, the electrons become relatively localized into Wigner crystals, and the natural SGF centers are found by solving the Thomson problem (i.e., the minimum-energy arrangement of n point charges) on the 3-sphere for various values of n. We have found 11 special values of n whose Thomson sites are equivalent. Three of these are the vertices of four-dimensional Platonic solids — the hyper-tetrahedron (n = 5), the hyper-octahedron (n = 8), and the 24-cell (n = 24) — and a fourth is a highly symmetric structure (n = 13) which has not previously been reported. By calculating the harmonic frequencies of the electrons around their equilibrium positions, we also find the first-order vibrational corrections to the Thomson energy.

  13. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    PubMed

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors. PMID:27133571

  14. Apolipoprotein E on Hepatitis C Virion Facilitates Infection through Interaction with Low Density Lipoprotein Receptor

    PubMed Central

    Owen, David M.; Huang, Hua; Ye, Jin; Gale, Michael

    2009-01-01

    Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-I, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that β-VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry. Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated ligand uptake and reduced HCV infection of cells, whereas infection was rescued upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV demonstrate that apoE is associated with HCV virions exhibiting peak infectivity and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a cooperative HCV co-receptor that supports viral entry and infectivity through interaction with apoE ligand present in an infectious HCV/lipoprotein complex comprising the virion. Disruption of HCV/LDL-R interactions by altering lipoprotein metabolism may therefore represent a focus for future therapy. PMID:19751943

  15. DSMC Simulation and Experimental Validation of Shock Interaction in Hypersonic Low Density Flow

    PubMed Central

    2014-01-01

    Direct simulation Monte Carlo (DSMC) of shock interaction in hypersonic low density flow is developed. Three collision molecular models, including hard sphere (HS), variable hard sphere (VHS), and variable soft sphere (VSS), are employed in the DSMC study. The simulations of double-cone and Edney's type IV hypersonic shock interactions in low density flow are performed. Comparisons between DSMC and experimental data are conducted. Investigation of the double-cone hypersonic flow shows that three collision molecular models can predict the trend of pressure coefficient and the Stanton number. HS model shows the best agreement between DSMC simulation and experiment among three collision molecular models. Also, it shows that the agreement between DSMC and experiment is generally good for HS and VHS models in Edney's type IV shock interaction. However, it fails in the VSS model. Both double-cone and Edney's type IV shock interaction simulations show that the DSMC errors depend on the Knudsen number and the models employed for intermolecular interaction. With the increase in the Knudsen number, the DSMC error is decreased. The error is the smallest in HS compared with those in the VHS and VSS models. When the Knudsen number is in the level of 10−4, the DSMC errors, for pressure coefficient, the Stanton number, and the scale of interaction region, are controlled within 10%. PMID:24672360

  16. Effect of proteolysis of low-density serum lipoproteins on their interaction with macrophages

    SciTech Connect

    Karmanskii, I.M.; Kovaleva, G.G.; Viktorova, L.N.; Shpikiter, V.O.

    1987-01-01

    The authors previously postulated, on the basis of changes observed in the structural stability of low-density lipoproteins during treatment with pepsin or aortic cathepsin, that enzymatic modifications may lead to potentiation of the atherogenic properties of the lipoproteins. They also reported that treatment of lipoproteins with trypsin causes an increase in their binding with aortic glycosaminoglycans and to increased degradation by fibroblasts of patients with hereditary hypercholesterolemia. Limited proteolysis of lipoproteins with pepsin facilitated their binding with fibronectin. In this paper the authors investigate the uptake and degradation of low-density lipoproteins by macrophages after their limited hydrolysis by pepsin, an analog of tissue cathepsin D. The lipoproteins were isolated from the serum of healthy blood donors by ultracentrifugation. Iodination of the proteins with I 125 was carried out by the iodine monochloride method. Uptake and retention of the labelled lipoprotein were measured with a gamma counter. The increased uptake of the proteins, partially hydrolized by pepsin, was accompanied by their more intense degradation by macrophages.

  17. Novel mutations of low-density lipoprotein receptor gene in China patients with familial hypercholesterolemia.

    PubMed

    Fan, Liang-liang; Lin, Min-jie; Chen, Ya-qin; Huang, Hao; Peng, Dao-quan; Xia, Kun; Zhao, Shui-ping; Xiang, Rong

    2015-05-01

    Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder, associated with elevated level of serum low-density lipoprotein-cholesterol (LDL-C), which can lead to premature cardiovascular disease (CVD). Mutations in low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have been identified to be the underlying cause of this disease. Genetic research of FH has already been extensively studied all over the world. However, reports of FH mutations in the Chinese population are still limited. In this paper, 20 unrelated FH families were enrolled to detect the candidate gene variants in Chinese FH population by DNA direct sequencing. We identified 12 LDLR variants in 13 FH probands. Importantly, we first reported two unique mutations (c.2000_2000 delG/p.C667LfsX6 and c.605T>C/p.F202S) in LDLR gene. Our discoveries expand the spectrum of LDLR mutations and contribute to the genetic diagnosis and counseling for FH patients. PMID:25846081

  18. Preparation of highly uniform low density polystyrene foams and their characterization

    SciTech Connect

    Steckle, W. P. , Jr.; Smith, M. E.; Sebring, R. J.; Wilson, K. V.; Nobile, A. , Jr.

    2004-01-01

    High Internal Phase Emulsion polystyrene foams have been made at Los Alamos National Laboratory for the past decade. As target designs become more complex the demands placed on the foams are more stringent. Parts need to be machined from 30 mg/cm{sup 3} foams to a thickness of 50 {micro}m within a couple of microns. Containing upwards of 97% air, these foams are to withstand extraction with ethanol to remove the wax utilized as a machining aid yet retain their dimensional stability. At low densities, less than 50 mg/cm{sup 3}, voids are a problem. To determine a formulation that reduces void content and allows minimum shrinkage, experimental design was utilized. We also developed image analysis techniques that allow us to quantify the amount of voids in the system and the surface finish of the foam. In order to machine these low density foams to the tolerance required with an optimum surface finish, the foams are backfilled with Brij{reg_sign} 78, an alcohol soluble wax. After a part is machined the Brij{reg_sign} is leached out with ethanol. The dimensional stability of the foam was found to be independent of the formulation of the foam. The filler that was used to aid in machining did have a significant impact on the final properties of a machined part.

  19. Radiation grafting of acrylamide onto starch-filled low density polyethylene

    NASA Astrophysics Data System (ADS)

    Bagheri, Rouhallah; Naimian, Franak; Sheikh, Nassrin

    1997-04-01

    Acrylamide (AAm) was grafted on the surface of starch-filled low density polyethylene (SLDPE) and low density polyethylene (LDPE) films by the mutual irradiation technique at doses from 0.75 to 5 kGy. The effect of dose, solvents and dihydroxybenzoquinone on the degree of grafting was studied by Fourier transform infrared spectroscopy and the weight measurement method of extracted films at a constant monomer concentration (10% w/w). An ultraviolet spectrophotometer was also used to elucidate the results of the above methods. Grafting on SLDPE and LDPE samples reaches a maximum followed by a slight decrease with increasing dose. A higher degree of grafting was obtained on SLDPE samples compared with that on LDPE. An induction period was observed in the case of the samples prepared in tetrahdyrfuran (THF) as the solvent compared with those in chloroform. Addition of benzene to chloroform and THF (50% v/v) accelerates the rate of AAm grafting on the samples. Dihydroxybenzoquinone inhibits the grafting reactions of the samples especially in the THF solutions. The water uptake measurement of the samples correlates with the degree of grafting.

  20. Thermal and catalytic degradation of high and low density polyethylene into fuel oil

    SciTech Connect

    Uddin, Azhar; Koizumi, Kazuo; Sakata, Yusaku

    1996-12-31

    The degradation of four different types of polyethylene (PE) namely high density PE (HDPE), low density PE (LDPE), linear low density PE (LLDPE), and cross-linked PE (XLPE) was carried out at 430 {degrees}C by batch operation using silica-alumina as a solid acid catalyst and thermally without any catalyst. For thermal degradation, both HDPE and XLPE produced significant amount of wax-like compounds and the yield of liquid products were lower than that of LDPE and LLDPE. LDPE and LLDPE also produced small amount of wax-like compounds. Thus the structure of the degrading polymers influenced the product yields. The liquid products from thermal degradation were broadly distributed in the carbon fraction of n-C{sub 5} to n-C{sub 25} (boiling point range, 36-405 C). With silica-alumina, the polyethylenes were converted to liquid products with high yields (77-83 wt%) and without any wax production. The liquid products were distributed in the range of n-C{sub 5} to n-C{sub 20} (Mostly C{sub 5}-C{sub 12}). Solid acid catalyst indiscriminately degraded the various types of polyethylene into light fuel oil. 5 refs., 4 figs., 1 tab.

  1. Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

    NASA Astrophysics Data System (ADS)

    Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

    2016-04-01

    Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

  2. Shock Initiation Experiments with Ignition and Growth Modeling on Low Density Composition B

    NASA Astrophysics Data System (ADS)

    Vandersall, Kevin S.; Garcia, Frank; Tarver, Craig M.

    2015-06-01

    Shock initiation experiments on low density (~1.2 and ~1.5 g/cm3) Composition B were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (~1.2 g/cm3) confined in Teflon rings or sample disks pressed to low density (~1.5 g/cm3) . The shock sensitivity was found to increase with decreasing density as expected. Ignition and Growth model parameters were derived that yielded reasonable agreement with the experimental data at both initial densities. The shock sensitivity at the tested densities will be compared to prior work published as near full density material. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. This work was funded in part by the Joint DoD-DOE Munitions Program.

  3. Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in Yucatan pigs

    PubMed Central

    Richardson, Matthew R.; Lai, Xianyin; Dixon, Joseph L.; Sturek, Michael; Witzmann, Frank A.

    2010-01-01

    Although low-density lipoprotein (LDL) plays a predominant role in atherogenesis, the low-density lipoproteome has not been fully characterized. Moreover, alterations from a Western diet, diabetes, and physical inactivity on this proteome have yet to be determined. Accordingly, relative quantification was determined in LDL proteins from male Yucatan diabetic dyslipidemic (DD) swine in the early stages of atherosclerosis compared to healthy control (C) and non-diabetic hyperlipidemic (H) swine. Importantly, coronary vascular dysfunction was prevented by aerobic exercise training in these animals (DDX) without altering total LDL concentration. Using 2-DE, Western blot, label-free quantitative MS, and selected reaction monitoring, alterations in the abundance of apolipoproteins A-I, B, C-III, D, E, and J and noncovalently associated proteins were determined in LDL isolated using fast protein liquid chromatography. At least 28 unique proteins, many of which were novel, were identified with high confidence. An apolipoprotein E isoform demonstrated stronger correlation to disease (percent of coronary artery segments with intimal thickening) than some traditional risk factors (total cholesterol, LDL cholesterol, and LDL/HDL cholesterol). Taken together, this work identifies new possible biomarkers, potential therapeutic targets for atherosclerosis, and generates new hypotheses regarding the role of LDL in atherogenesis. PMID:19402046

  4. Importance of Having Low-Density Functional Groups for Generating High-Performance Semiconducting Polymer Dots

    PubMed Central

    Zhang, Xuanjun; Yu, Jiangbo; Wu, Changfeng; Jin, Yuhui; Rong, Yu; Ye, Fangmao

    2012-01-01

    Semiconducting polymers with low-density side-chain carboxylic acid groups were synthesized to form stable, functionalized, and highly fluorescent polymer dots (Pdots). The influence of the molar fraction of hydrophilic side-chains on Pdot properties and performance was systematically investigated. Our results show that the density of side-chain carboxylic acid groups significantly affects Pdot stability, internal structure, fluorescence brightness, and nonspecific binding in cellular labeling. Fluorescence spectroscopy, single-particle imaging, and a dye-doping method were employed to investigate the fluorescence brightness and the internal structure of the Pdots. The results of these experiments indicate that semiconducting polymers with low density of side-chain functional groups can form stable, compact, and highly bright Pdots as compared to those with high density of hydrophilic side-chains. The functionalized polymer dots were conjugated to streptavidin (SA) by carbodiimide-catalyzed coupling and the Pdot-SA probes effectively and specifically labeled the cancer cell-surface marker Her2 in human breast cancer cells. The carboxylate-functionalized polymer could also be covalently modified with small functional molecules to generate Pdot probes for click chemistry-based bioorthogonal labeling. This study presents a promising approach for further developing functional Pdot probes for biological applications. PMID:22607220

  5. Generation in Human Plasma of Misfolded, Aggregation-Prone Electronegative Low Density Lipoprotein

    PubMed Central

    Greco, Giulia; Balogh, Gabor; Brunelli, Roberto; Costa, Graziella; De Spirito, Marco; Lenzi, Laura; Mei, Giampiero; Ursini, Fulvio; Parasassi, Tiziana

    2009-01-01

    Abstract Human plasma contains small amounts of a low density lipoprotein in which apoprotein is misfolded. Originally identified and isolated by means of anion-exchange chromatography, this component was subsequently described as electronegative low density lipoprotein (LDL)(−), with increased concentrations associated with elevated cardiovascular disease risk. It has been recognized recently as the trigger of LDL amyloidogenesis, which produces aggregates similar to subendothelial droplets observed in vivo in early atherogenesis. Although LDL(−) has been produced in vitro through various manipulations, the mechanisms involved in its generation in vivo remain obscure. By using a more physiological model, we demonstrate spontaneous, sustained and noticeable production of LDL(−) during incubation of unprocessed human plasma at 37°C. In addition to a higher fraction of amyloidogenic LDL(−), LDL purified from incubated plasma contains an increased level of lysophospholipids and free fatty acids; analysis of LDL lipids packing shows their loosening. As a result, during plasma incubation, lipid destabilization and protein misfolding take place, and aggregation-prone particles are generated. All these phenomena can be prevented by inhibiting calcium-dependent secretory phospholipases A2. Our plasma incubation model, without removal of reaction products, effectively shows a lipid-protein interplay in LDL, where lipid destabilization after lipolysis threatens the apoprotein's structure, which misfolds and becomes aggregation-prone. PMID:19619478

  6. Analysis of Compaction Shock Interactions During DDT of Low Density HMX

    NASA Astrophysics Data System (ADS)

    Rao, Pratap; Gonthier, Keith

    2015-06-01

    Deflagration-to-Detonation Transition (DDT) within low density HMX often occurs by a complex mechanism that involves compaction shock interactions. Piston driven DDT experiments indicate that detonation can be abruptly triggered by the interaction of a strong combustion driven shock and a lead piston supported shock, where the nature of the interaction depends on initial density and lead shock strength. These shocks induce dissipation and thermomechanical fluctuations at the meso-scale due to pore collapse resulting in hot-spots. Inert meso-scale simulations of successive shock loading of low density HMX are performed to examine how dissipation and hot-spot formation are affected by initial density, and lead and trailing shock strength. Emphasis is placed on interpreting solutions in a phase space expressed in terms of effective pressure and dissipative work because of their relevance to hot-spot formation. Meso-scale predictions are shown to compare favorably to those given by a macro-scale theory. This information is being used to formulate a dissipation-dependent reactive burn model to describe shock desensitization and DDT. Preliminary redictions will be presented that illustrate how initial density and input shock strength can affect the transition mechanism. This research is supported by the Defense Threat Reduction Agency (DTRA) under sponsor Award Number HDTRA1-10-1-0018, and the Air Force Research Laboratory (AFRL-RWME) under sponsor Award Number FA8651-09-0021.

  7. Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters

    SciTech Connect

    Eisenberg, S.

    1985-04-01

    The effect of lipid transfer proteins on the exchange and transfer of cholesteryl esters from rat plasma HDL2 to human very low (VLDL) and low density (LDL) lipoprotein populations was studied. The use of a combination of radiochemical and chemical methods allowed separate assessment of (/sup 3/H)cholesteryl ester exchange and of cholesteryl ester transfer. VLDL-I was the preferred acceptor for transferred cholesteryl esters, followed by VLDL-II and VLDL-III. LDL did not acquire cholesteryl esters. The contribution of exchange of (/sup 3/H)cholesteryl esters to total transfer was highest for LDL and decreased in reverse order along the VLDL density range. Inactivation of lecithin: cholesterol acyltransferase (LCAT) and heating the HDL2 for 60 min at 56 degrees C accelerated transfer and exchange of (/sup 3/H)cholesteryl esters. Addition of lipid transfer proteins increased cholesterol esterification in all systems. The data demonstrate that large-sized, triglyceride-rich VLDL particles are preferred acceptors for transferred cholesteryl esters. It is suggested that enrichment of very low density lipoproteins with cholesteryl esters reflects the triglyceride content of the particles.

  8. Uptake and processing of remnants of chylomicrons and very low density lipoproteins by rat liver

    SciTech Connect

    Jones, A.L.; Hradek, G.T.; Hornick, C.; Renaud, G.; Windler, E.E.; Havel, R.J.

    1984-11-01

    In the rat, chylomicron remnants and very low density lipoprotein (VLDL) remnants are taken up into the liver by high affinity processes and appear to undergo degradation by lysosomes. The relationship of this catabolic process to the known pathways of uptake and degradation of low density lipoproteins (LDL) and the involvement of nonparenchymal cells are addressed in these studies. The authors have utilized both light and electron microscopic radioautography to determine whether the pathway of intracellular transport and catabolism resembles that established for LDL in hepatocytes. Radioiodinated plasma VLDL remnants and lymph chylomicron remnants were injected into femoral veins of rats and the livers were fixed by perfusion 3 to 30 minutes later. Quantitative light microscopic radioautography showed little or no accumulation of grains over Kupffer cells. Electromicroscopic radioautography confirmed these observations and, in addition, demonstrated that very few grains were associated with endothelial cells. The processing of the remnant particles closely resembled that of LDL. Following an initial association of grains with the parenchymal cell plasma membrane, frequently in regions in close proximity to clathrin-coated endocytic pits, the grains were found in endocytic vesicles just beneath the plasma membrane. By 15 minutes the grains were found over multivesicular bodies located in the Golgi-lysosome region of the cell. Thirty minutes after injection, radioautographic grains began to be associated with secondary lysosomes.

  9. Dynamical aspects of intermolecular proton transfer in liquid water and low-density amorphous ices.

    PubMed

    Tahat, Amani; Martí, Jordi

    2014-05-01

    The microscopic dynamics of an excess proton in water and in low-density amorphous ices has been studied by means of a series of molecular dynamics simulations. Interaction of water with the proton species was modelled using a multistate empirical valence bond Hamiltonian model. The analysis of the effects of low temperatures on proton diffusion and transfer rates has been considered for a temperature range between 100 and 298 K at the constant density of 1 g cm(-3). We observed a marked slowdown of proton transfer rates at low temperatures, but some episodes are still seen at 100 K. In a similar fashion, mobility of the lone proton gets significantly reduced when temperature decreases below 273 K. The proton transfer in low-density amorphous ice is an activated process with energy barriers between 1-10 kJ/mol depending of the temperature range considered and eventually showing Arrhenius-like behavior. Spectroscopic data indicated the survival of both Zundel and Eigen structures along the whole temperature range, revealed by significant spectral frequency shifts. PMID:25353762

  10. Imaging of hepatic low density lipoprotein receptors by radionuclide scintiscanning in vivo.

    PubMed

    Huettinger, M; Corbett, J R; Schneider, W J; Willerson, J T; Brown, M S; Goldstein, J L

    1984-12-01

    The low density lipoprotein (LDL) receptor mediates the cellular uptake of plasma lipoproteins that are derived from very low density lipoproteins (VLDL). Most of the functional LDL receptors in the body are located in the liver. Here, we describe a radionuclide scintiscanning technique that permits the measurement of LDL receptors in the livers of intact rabbits. 123I-labeled VLDL were administered intravenously, and scintigraphic images of the liver and heart were obtained at intervals thereafter. In seven normal rabbits, radioactivity in the liver increased progressively between 1 and 20 min after injection, while radioactivity in the heart (reflecting that in plasma) decreased concomitantly. In Watanabe-heritable hyperlipidemic rabbits, which lack LDL receptors on a genetic basis, there was little uptake of 123I-labeled VLDL into the liver and little decrease in cardiac radioactivity during this interval. These findings demonstrate that the LDL receptor is necessary for the hepatic uptake of VLDL-derived lipoproteins in the rabbit. Two conditions that diminish hepatic LDL receptor activity, cholesterol-feeding and prolonged fasting, also reduced the uptake of 123I-labeled VLDL in the liver as measured by scintiscanning. The data suggest that radionuclide scintiscanning can be used as a noninvasive method to quantify the number of LDL receptors expressed in the liver in vivo. PMID:6594702

  11. Low-Density Nozzle Flow by the Direct Simulation Monte Carlo and Continuum Methods

    NASA Technical Reports Server (NTRS)

    Chung, Chang-Hong; Kim, Sku C.; Stubbs, Robert M.; Dewitt, Kenneth J.

    1994-01-01

    Two different approaches, the direct simulation Monte Carlo (DSMC) method based on molecular gasdynamics, and a finite-volume approximation of the Navier-Stokes equations, which are based on continuum gasdynamics, are employed in the analysis of a low-density gas flow in a small converging-diverging nozzle. The fluid experiences various kinds of flow regimes including continuum, slip, transition, and free-molecular. Results from the two numerical methods are compared with Rothe's experimental data, in which density and rotational temperature variations along the centerline and at various locations inside a low-density nozzle were measured by the electron-beam fluorescence technique. The continuum approach showed good agreement with the experimental data as far as density is concerned. The results from the DSMC method showed good agreement with the experimental data, both in the density and the rotational temperature. It is also shown that the simulation parameters, such as the gas/surface interaction model, the energy exchange model between rotational and translational modes, and the viscosity-temperature exponent, have substantial effects on the results of the DSMC method.

  12. Reactive decomposition of low density PMDI foam subject to shock compression

    NASA Astrophysics Data System (ADS)

    Alexander, Scott; Reinhart, William; Brundage, Aaron; Peterson, David

    Low density polymethylene diisocyanate (PMDI) foam with a density of 5.4 pounds per cubic foot (0.087 g/cc) was tested to determine the equation of state properties under shock compression over the pressure range of 0.58 - 3.4 GPa. This pressure range encompasses a region approximately 1.0-1.2 GPa within which the foam undergoes reactive decomposition resulting in significant volume expansion of approximately three times the volume prior to reaction. This volume expansion has a significant effect on the high pressure equation of state. Previous work on similar foam was conducted only up to the region where volume expansion occurs and extrapolation of that data to higher pressure results in a significant error. It is now clear that new models are required to account for the reactive decomposition of this class of foam. The results of plate impact tests will be presented and discussed including details of the unique challenges associated with shock compression of low density foams. Sandia National Labs is a multi-program lab managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corp., for the U.S. Dept. of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  13. DSMC simulation and experimental validation of shock interaction in hypersonic low density flow.

    PubMed

    Xiao, Hong; Shang, Yuhe; Wu, Di

    2014-01-01

    Direct simulation Monte Carlo (DSMC) of shock interaction in hypersonic low density flow is developed. Three collision molecular models, including hard sphere (HS), variable hard sphere (VHS), and variable soft sphere (VSS), are employed in the DSMC study. The simulations of double-cone and Edney's type IV hypersonic shock interactions in low density flow are performed. Comparisons between DSMC and experimental data are conducted. Investigation of the double-cone hypersonic flow shows that three collision molecular models can predict the trend of pressure coefficient and the Stanton number. HS model shows the best agreement between DSMC simulation and experiment among three collision molecular models. Also, it shows that the agreement between DSMC and experiment is generally good for HS and VHS models in Edney's type IV shock interaction. However, it fails in the VSS model. Both double-cone and Edney's type IV shock interaction simulations show that the DSMC errors depend on the Knudsen number and the models employed for intermolecular interaction. With the increase in the Knudsen number, the DSMC error is decreased. The error is the smallest in HS compared with those in the VHS and VSS models. When the Knudsen number is in the level of 10(-4), the DSMC errors, for pressure coefficient, the Stanton number, and the scale of interaction region, are controlled within 10%. PMID:24672360

  14. Spatio-spectral filters for low-density surface electromyographic signal classification.

    PubMed

    Huang, Gan; Zhang, Zhiguo; Zhang, Dingguo; Zhu, Xiangyang

    2013-05-01

    In this paper, we proposed to utilize a novel spatio-spectral filter, common spatio-spectral pattern (CSSP), to improve the classification accuracy in identifying intended motions based on low-density surface electromyography (EMG). Five able-bodied subjects and a transradial amputee participated in an experiment of eight-task wrist and hand motion recognition. Low-density (six channels) surface EMG signals were collected on forearms. Since surface EMG signals are contaminated by large amount of noises from various sources, the performance of the conventional time-domain feature extraction method is limited. The CSSP method is a classification-oriented optimal spatio-spectral filter, which is capable of separating discriminative information from noise and, thus, leads to better classification accuracy. The substantially improved classification accuracy of the CSSP method over the time-domain and other methods is observed in all five able-bodied subjects and verified via the cross-validation. The CSSP method can also achieve better classification accuracy in the amputee, which shows its potential use for functional prosthetic control. PMID:23385330

  15. Uniform electron gases. III. Low-density gases on three-dimensional spheres

    NASA Astrophysics Data System (ADS)

    Agboola, Davids; Knol, Anneke L.; Gill, Peter M. W.; Loos, Pierre-François

    2015-08-01

    By combining variational Monte Carlo (VMC) and complete-basis-set limit Hartree-Fock (HF) calculations, we have obtained near-exact correlation energies for low-density same-spin electrons on a three-dimensional sphere (3-sphere), i.e., the surface of a four-dimensional ball. In the VMC calculations, we compare the efficacies of two types of one-electron basis functions for these strongly correlated systems and analyze the energy convergence with respect to the quality of the Jastrow factor. The HF calculations employ spherical Gaussian functions (SGFs) which are the curved-space analogs of Cartesian Gaussian functions. At low densities, the electrons become relatively localized into Wigner crystals, and the natural SGF centers are found by solving the Thomson problem (i.e., the minimum-energy arrangement of n point charges) on the 3-sphere for various values of n. We have found 11 special values of n whose Thomson sites are equivalent. Three of these are the vertices of four-dimensional Platonic solids — the hyper-tetrahedron (n = 5), the hyper-octahedron (n = 8), and the 24-cell (n = 24) — and a fourth is a highly symmetric structure (n = 13) which has not previously been reported. By calculating the harmonic frequencies of the electrons around their equilibrium positions, we also find the first-order vibrational corrections to the Thomson energy.

  16. A robust method for handling low density regions in hybrid simulations for collisionless plasmas

    SciTech Connect

    Amano, Takanobu Higashimori, Katsuaki; Shirakawa, Keisuke

    2014-10-15

    A robust method to handle vacuum and near vacuum regions in hybrid simulations for space and astrophysical plasmas is presented. The conventional hybrid simulation model dealing with kinetic ions and a massless charge-neutralizing electron fluid is known to be susceptible to numerical instability due to divergence of the whistler-mode wave dispersion, as well as division-by-density operation in regions of low density. Consequently, a pure vacuum region is not allowed to exist in the simulation domain unless some ad hoc technique is used. To resolve this difficulty, an alternative way to introduce finite electron inertia effect is proposed. Contrary to the conventional method, the proposed one introduces a correction to the electric field rather than the magnetic field. It is shown that the generalized Ohm's law correctly reduces to Laplace's equation in a vacuum which therefore does not involve any numerical problems. In addition, a variable ion-to-electron mass ratio is introduced to reduce the phase velocity of high frequency whistler waves at low density regions so that the stability condition is always satisfied. It is demonstrated that the proposed model is able to handle near vacuum regions generated as a result of nonlinear self-consistent development of the system, as well as pure vacuum regions set up at the initial condition, without losing the advantages of the standard hybrid code.

  17. Application of adaptive cluster sampling to low-density populations of freshwater mussels

    USGS Publications Warehouse

    Smith, D.R.; Villella, R.F.; Lemarie, D.P.

    2003-01-01

    Freshwater mussels appear to be promising candidates for adaptive cluster sampling because they are benthic macroinvertebrates that cluster spatially and are frequently found at low densities. We applied adaptive cluster sampling to estimate density of freshwater mussels at 24 sites along the Cacapon River, WV, where a preliminary timed search indicated that mussels were present at low density. Adaptive cluster sampling increased yield of individual mussels and detection of uncommon species; however, it did not improve precision of density estimates. Because finding uncommon species, collecting individuals of those species, and estimating their densities are important conservation activities, additional research is warranted on application of adaptive cluster sampling to freshwater mussels. However, at this time we do not recommend routine application of adaptive cluster sampling to freshwater mussel populations. The ultimate, and currently unanswered, question is how to tell when adaptive cluster sampling should be used, i.e., when is a population sufficiently rare and clustered for adaptive cluster sampling to be efficient and practical? A cost-effective procedure needs to be developed to identify biological populations for which adaptive cluster sampling is appropriate.

  18. Fast magnetic reconnection in low-density electron-positron plasmas

    SciTech Connect

    Bessho, Naoki; Bhattacharjee, A.

    2010-10-15

    Two-dimensional particle-in-cell simulations have been performed to study magnetic reconnection in low-density electron-positron plasmas without a guide magnetic field. Impulsive reconnection rates become of the order of unity when the background density is much smaller than 10% of the density in the initial current layer. It is demonstrated that the outflow speed is less than the upstream Alfven speed, and that the time derivative of the density must be taken into account in the definition of the reconnection rate. The reconnection electric fields in the low-density regime become much larger than the ones in the high-density regime, and it is possible to accelerate the particles to high energies more efficiently. The inertial term in the generalized Ohm's law is the most dominant term that supports a large reconnection electric field. An effective collisionless resistivity is produced and tracks the extension of the diffusion region in the late stage of the reconnection dynamics, and significant broadening of the diffusion region is observed. Because of the broadening of the diffusion region, no secondary islands, which have been considered to play a role to limit the diffusion region, are generated during the extension of the diffusion region in the outflow direction.

  19. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

    PubMed Central

    Harris, H W; Grunfeld, C; Feingold, K R; Rapp, J H

    1990-01-01

    Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. Images PMID:2394827

  20. Novel low density granular adsorbents - properties of a composite matrix from zeolitisation of vermiculite.

    PubMed

    Johnson, Christopher D; Worrall, Fred

    2007-06-01

    This paper reports the preparation and properties of a new low density granular absorbent material based on a zeolite/vermiculite composite. The composite prepared addresses a number of important issues relating to the use of zeolites in environmental and waste management applications. The material prepared has large particle size due to binderless adhesion of zeolite crystals within the protective lamellar matrix provided by the vermiculite granule. Additionally, the porous nature of new material ensures that it outperforms natural zeolite grains in ion-exchange tests. The material was shown to have a low bulk density (0.75 g cm(-3)) adding the benefit that the majority of grains float on water for over 15 h. The conclusion of the study is that the use of composite matrices enable the preparation of materials which show the physical properties of the host, (e.g., granular and low density), whilst maintaining the powder-like properties (e.g., high ion-exchange and small crystal size) of the active component. The resulting material can be easily handled and separated from aqueous waste streams using either flotation or exploiting its granular nature. PMID:17368511

  1. Effects of low-density feeding on elk–fetus contact rates on Wyoming feedgrounds

    USGS Publications Warehouse

    Creech, Tyler G.; Cross, Paul C.; Scurlock, Brandon M.; Maichak, Eric J.; Rogerson, Jared D.; Henningsen, John C.; Creel, Scott

    2012-01-01

    High seroprevalance for Brucella abortus among elk on Wyoming feedgrounds suggests that supplemental feeding may influence parasite transmission and disease dynamics by altering the rate at which elk contact infectious materials in their environment. We used proximity loggers and video cameras to estimate rates of elk-to-fetus contact (the primary source of brucellosis transmission) during winter supplemental feeding. We compared contact rates during high-density and low-density (LD) feeding treatments that provided the same total amount of food distributed over different areas. Low-density feeding led to >70% reductions in total number of contacts and number of individuals contacting a fetus. Proximity loggers and video cameras provided similar estimates of elk–fetus contact rates. Elk contacted fetuses and random control points equally, suggesting that elk were not attracted to fetuses but encountered them incidentally while feeding. The modeled relationship between contact rate and disease prevalence is nonlinear and LD feeding may result in large reductions in brucellosis prevalence, but this depends on the amount of transmission that occurs on and off feedgrounds.

  2. Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

    PubMed Central

    Bays, Harold E

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy. PMID:25045281

  3. Competing quantum Hall phases in the second Landau level in low density limit

    NASA Astrophysics Data System (ADS)

    Pan, Wei; Serafin, A.; Xia, J. S.; Yin, L.; Sullivan, N. S.; Baldwin, K. W.; West, K. W.; Pfeiffer, L. N.; Tsui, D. C.

    2015-03-01

    We present here the results from two high quality, low density GaAs quantum wells. In sample A of electron density n = 5.0 x 1010 cm-2, anisotropic electronic transport behavior was observed at ν = 7/2 in the second Landau level. We believe that the anisotropy is due to the large Landau level mixing effect in this sample. In sample B of density 4.1 x 1010 cm-2, strong 8/3, 5/2, and 7/3 fractional quantum Hall states were observed. Furthermore, our energy gap data obtained in various samples of different densities suggest that the 5/2 state may be spin unpolarized in the low density limit. The results from both samples show that the strong electron-electron interactions and a large Landau level mixing effect play an import role in the competing ground states in the second landau level. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division.

  4. Ordering of low-density Ge quantum dot on patterned Si substrate

    NASA Astrophysics Data System (ADS)

    Ma, Y. J.; Zeng, C.; Zhou, T.; Huang, S. F.; Fan, Y. L.; Zhong, Z.; Yang, X. J.; Xia, J. S.; Jiang, Z. M.

    2014-12-01

    We present a study on the growth of a low-density ordered Ge quantum dot (QD) on a nanohole patterned Si (0 0 1) substrate with periods in the order of microns by molecular beam epitaxy. Ordered Ge QDs with different periods were realized, the largest period being 15 µm. From the height-profile evolution of the QD with Ge deposition, it was found that the nanohole filling started at the initial Ge deposition, indicating an immediate nucleation and growth of QDs inside the nanoholes. Such a phenomenon is attributed to a lower surface chemical potential (SCP) inside the nanoholes, which is supported by calculated results on SCP evolution with growth and verified by the observation that the Ge adatoms around the nanoholes exhibited a higher probability of being incorporated into the nanoholes. In this scenario, low density ordered Ge QDs with any large periods could be achieved. The optical properties of the Ge QDs showed a remarkable improvement after a post-growth rapid thermal annealing treatment.

  5. Partial characterization of low density lipoprotein preparations isolated from fresh and frozen plasma after radiolabeling by seven different methods

    SciTech Connect

    Atsma, D.E.; Kempen, H.J.; Nieuwenhuizen, W.; van 't Hooft, F.M.; Pauwels, E.K. )

    1991-01-01

    Four {sup 99m}Tc and three {sup 123}I labeling methods were evaluated for their suitability to label low density lipoproteins (LDL) for the purpose of scintigraphic biodistribution studies. For {sup 99m}Tc these methods were: direct incorporation in LDL of {sup 99m}TcO4- using sodium dithionite (dithionite method); a method using first N,N-dimethylformamide to prepare a {sup 99m}Tc-complex reacting with LDL in a subsequent step (DMF method); a technique in which {sup 99m}TcO4- is first coupled to a diamide dithiolate derivative of pentanoic acid by reduction with dithionite, followed by coupling of this ligand to LDL (N2S2 method); and a method using sodium borohydride and stannous chloride as reducing agents (borohydride method). The iodination techniques were based on oxidation of I(-)----I+, using iodine monochloride (ICl method), 1,3,4,6-tetrachloro-3,6-diphenylglycoluril (Iodogen method), and N-bromosuccinimide (NBS method) as oxidants. We studied labeling yields, modification of LDL caused by the labeling procedures using agarose-gel electrophoresis, and radiochemical stability of the labeled LDL complex upon incubation in plasma at 37 degrees C for 15 h. We used Sepharose CL6B chromatography to separate LDL from other plasma proteins. We also examined whether LDL isolated from frozen plasma (Pool-LDL) gave results similar to LDL obtained from freshly prepared plasma (Fresh-LDL). Pool-LDL radiolabeled by the dithionite, DMF, NBS, and Iodogen methods lost its label upon incubation with plasma. This also happened with Fresh-LDL when the DMF, NBS and Iodogen methods were used. Upon agarose-gel electrophoresis, no modification of LDL was observed with all methods when the radionuclide/LDL ratio was kept low.

  6. On the feasibility of increasing the energy of laser-accelerated protons by using low-density targets

    NASA Astrophysics Data System (ADS)

    Brantov, A. V.; Bychenkov, V. Yu.

    2015-06-01

    Optimal regimes of proton acceleration in the interaction of short high-power laser pulses with thin foils and low-density targets are determined by means of 3D numerical simulation. It is demonstrated that the maximum proton energy can be increased by using low-density targets in which ions from the front surface of the target are accelerated most efficiently. It is shown using a particular example that, for the same laser pulse, the energy of protons accelerated from a low-density target can be increased by one-third as compared to a solid-state target.

  7. On the feasibility of increasing the energy of laser-accelerated protons by using low-density targets

    SciTech Connect

    Brantov, A. V. Bychenkov, V. Yu.

    2015-06-15

    Optimal regimes of proton acceleration in the interaction of short high-power laser pulses with thin foils and low-density targets are determined by means of 3D numerical simulation. It is demonstrated that the maximum proton energy can be increased by using low-density targets in which ions from the front surface of the target are accelerated most efficiently. It is shown using a particular example that, for the same laser pulse, the energy of protons accelerated from a low-density target can be increased by one-third as compared to a solid-state target.

  8. [THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    PubMed

    Titov, V N; Malyshev, P P; Amelyushkina, V A; Aripovsky, A V; Smirnov, G P; Polevaya, T Yu; Kabo, S I; Kukhartchuk, V V

    2015-10-01

    The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and

  9. HATS-8b: A Low-density Transiting Super-Neptune

    NASA Astrophysics Data System (ADS)

    Bayliss, D.; Hartman, J. D.; Bakos, G. Á.; Penev, K.; Zhou, G.; Brahm, R.; Rabus, M.; Jordán, A.; Mancini, L.; de Val-Borro, M.; Bhatti, W.; Espinoza, N.; Csubry, Z.; Howard, A. W.; Fulton, B. J.; Buchhave, L. A.; Henning, T.; Schmidt, B.; Ciceri, S.; Noyes, R. W.; Isaacson, H.; Marcy, G. W.; Suc, V.; Lázár, J.; Papp, I.; Sári, P.

    2015-08-01

    HATS-8b is a low density transiting super-Neptune discovered as part of the HATSouth project. The planet orbits its solar-like G-dwarf host (V = 14.03+/- 0.10, {T}{eff} = 5679+/- 50 K) with a period of 3.5839 days. HATS-8b is the third lowest-mass transiting exoplanet to be discovered from a wide-field ground-based search, and with a mass of 0.138+/- 0.019 {M}{{J}} it is approximately halfway between the masses of Neptune and Saturn. However, HATS-8b has a radius of {0.873}-0.075+0.123 {R}{{J}}, resulting in a bulk density of just 0.259+/- 0.091 {{g}} {{cm}}-3. The metallicity of the host star is super-solar ([{Fe}/{{H}}] = 0.210+/- 0.080), providing evidence against the idea that low-density exoplanets form from metal-poor environments. The low density and large radius of HATS-8b results in an atmospheric scale height of almost 1000 km, and in addition to this there is an excellent reference star of nearly equal magnitude at just 19″ separation in the sky. These factors make HATS-8b an exciting target for future atmospheric characterization studies, particularly for long-slit transmission spectroscopy. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey site is operated in conjunction with MPIA, and the station at Siding Spring Observatory is operated jointly with ANU. This paper includes data gathered with the 6.5 m Magellan Telescopes located in LCO, Chile. The work is based in part on observations made with the MPG 2.2 m Telescope and the ESO 3.6 m Telescope at the ESO Observatory in La Silla. This paper uses observations obtained using the facilities of the Las Cumbres Observatory Global Telescope.

  10. Testing the Low-density Hypothesis for Reversed Sex Change in Polygynous Fish: Experiments in Labroides dimidiatus

    PubMed Central

    Kuwamura, Tetsuo; Kadota, Tatsuru; Suzuki, Shohei

    2014-01-01

    Hermaphroditism is ubiquitous among plants and widespread in the animal kingdom. It is an unsolved problem why reversed sex change has evolved in polygynous and protogynous reef fish. We have previously suggested that facultative monogamy occurs in low-density populations of polygynous species and that males that become single as a result of accidental mate loss may change sex when they meet larger males. In this study, to test this ‘low-density hypothesis', we conducted field experiments with the coral reef fish Labroides dimidiatus in which a portion of females were removed to create a low-density situation. The ‘widowed' males moved to search for a new mate when no male, female or juvenile fish migrated into their territories and paired with nearby single fish, whether male or female. Alternatively, males expanded their territories to take over the nearest pair whose male was much smaller. These results support our low-density hypothesis. PMID:24621782

  11. Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion

    SciTech Connect

    Rodriguez, Jennifer N.; Miller, Matthew W.; Boyle, Anthony; Horn, John; Yang, Cheng-Kang; Wilson, Thomas S.; Ortega, Jason M.; Small, Ward; Nash, Landon; Skoog, Hunter; Maitland, Duncan J.

    2014-08-11

    Recently, predominantly closed-cell low density shape memory polymer (SMP) foam was reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching. Lastly, reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede the shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model.

  12. Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion

    DOE PAGESBeta

    Rodriguez, Jennifer N.; Miller, Matthew W.; Boyle, Anthony; Horn, John; Yang, Cheng-Kang; Wilson, Thomas S.; Ortega, Jason M.; Small, Ward; Nash, Landon; Skoog, Hunter; et al

    2014-08-11

    Recently, predominantly closed-cell low density shape memory polymer (SMP) foam was reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching.more » Lastly, reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede the shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model.« less

  13. Ultra Low Density Shape Memory Polymer Foams With Tunable Physicochemical Properties for Treatment of intracranial Aneurysms

    SciTech Connect

    Singhal, Pooja

    2013-12-01

    Shape memory polymers (SMPs) are a rapidly emerging class of smart materials that can be stored in a deformed temporary shape, and can actively return to their original shape upon application of an external stimulus such as heat, pH or light. This behavior is particularly advantageous for minimally invasive biomedical applications comprising embolic/regenerative scaffolds, as it enables a transcatheter delivery of the device to the target site. The focus of this work was to exploit this shape memory behavior of polyurethanes, and develop an efficient embolic SMP foam device for the treatment of intracranial aneurysms.In summary, this work reports a novel family of ultra low density polymer foams which can be delivered via a minimally invasive surgery to the aneurysm site, actuated in a controlled manner to efficiently embolize the aneurysm while promoting physiological fluid/blood flow through the reticulated/open porous structure, and eventually biodegrade leading to complete healing of the vasculature.

  14. Cryogenic mechanical properties of low density superplastically formable Al-Li alloys

    NASA Technical Reports Server (NTRS)

    Verzasconi, S. L.; Morris, J. W., Jr.

    1989-01-01

    The aerospace industry is considering the use of low density, superplastically formable (SPF) materials, such as Al-Li alloys in cryogenic tankage. SPF modifications of alloys 8090, 2090, and 2090+In were tested for strength and Kahn tear toughness. The results were compared to those of similar tests of 2219-T87, an alloy currently used in cryogenic tankage, and 2090-T81, a recently studied Al-Li alloy with exceptional cryogenic properties (1-9). With decreasing temperature, all materials showed an increase in strength, while most materials showed an increase in elongation and decrease in Kahn toughness. The indium addition to 2090 increased alloy strength, but did not improve the strength-toughness combination. The fracture mode was predominantly intergranular along small, recrystallized grains, with some transgranular fracture, some ductile rupture, and some delamination on large, unrecrystallized grains.

  15. Density equalisation in supercooled high- and low-density water mixtures

    NASA Astrophysics Data System (ADS)

    English, Niall J.; Kusalik, Peter G.; Tse, John S.

    2013-08-01

    The temporal evolution of two model high-density/low-density (HDL/LDL) interfaces was examined from molecular dynamics (MD) calculations at temperatures close to the predicted second critical point of water for three water models. In all cases, interfacial density equalisation occurred rapidly showing no preference for inhomogenous distribution. A uniform density (of ca. 0.99-1.067 g/cm3, depending on the potential) was always observed at the interface, indicating the free energy of water in low- and high-density forms is metastable, and that LDL and HDL should not coexist as independent entities at thermodynamic equilibrium. It is reckoned that previous MD studies supporting the "two-liquid" model have an explicit, if inappropriate, assumption of mechanical equilibrium between the two phases. The present result challenges the notion that a second critical point exists, and that LDL/HDL mixtures could be even kinetically metastable.

  16. Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion

    PubMed Central

    Rodriguez, Jennifer N.; Miller, Matthew W.; Boyle, Anthony; Horn, John; Yang, Cheng-Kang; Wilson, Thomas S.; Ortega, Jason M.; Small, Ward; Nash, Landon; Skoog, Hunter; Maitland, Duncan J.

    2014-01-01

    Predominantly closed-cell low density shape memory polymer (SMP) foam was recently reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching. Reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model. PMID:25222869

  17. Mechanical properties of low-density polyethylene filled by graphite nanoplatelets.

    PubMed

    Carotenuto, G; De Nicola, S; Palomba, M; Pullini, D; Horsewell, A; Hansen, T W; Nicolais, L

    2012-12-01

    The mechanical properties of GNP/LDPE nanocomposites (graphite nanoplatelets/low density polyethylene) have been investigated, in order to establish the effect of nanoscale reinforcement within the polymer matrix. Results show that the presence of the filler does not involve a change in the microscopic structure of the polymer. However, on a macroscopic scale, GNPs limit the mobility of the polymer chains, resulting in an increase in stiffness for the final composite. Orientation of GNPs within the LDPE matrix is also an important issue that affects mechanical properties and it has been evaluated by testing nanocomposites made by different manufacturing techniques (compression moulding and blown extrusion). The comparison between the experimental data and the Halpin-Tsai model shows that the orientation of GNPs due to the extrusion process leads to values of tensile modulus higher than that obtained with the randomly oriented disposition resulting from the compression moulding technique. PMID:23128320

  18. Instability Analysis of a Low-Density Gas Jet Injected into a High-Density Gas

    NASA Technical Reports Server (NTRS)

    Lawson, Anthony Layiwola

    2001-01-01

    The objective of this study was to determine the effects of buoyancy on the absolute instability of low-density gas jets injected into high-density gas mediums. Most of the existing analyses of low-density gas jets injected into a high-density ambient have been carried out neglecting effects of gravity. In order to investigate the influence of gravity on the near-injector development of the flow, a linear temporal stability analysis and a spatio-temporal stability analysis of a low-density round jet injected into a high-density ambient gas were performed. The flow was assumed to be isothermal and locally parallel; viscous and diffusive effects were ignored. The variables were represented as the sum of the mean value and a normal-mode small disturbance. An ordinary differential equation governing the amplitude of the pressure disturbance was derived. The velocity and density profiles in the shear layer, and the Froude number (signifying the effects of gravity) were the three important parameters in this equation. Together with the boundary conditions, an eigenvalue problem was formulated. Assuming that the velocity and density profiles in the shear layer to be represented by hyperbolic tangent functions, the eigenvalue problem was solved for various values of Froude number. The temporal growth rates and the phase velocity of the disturbances were obtained. It was found that the presence of variable density within the shear layer resulted in an increase in the temporal amplification rate of the disturbances and an increase in the range of unstable frequencies, accompanied by a reduction in the phase velocities of the disturbances. Also, the temporal growth rates of the disturbances were increased as the Froude number was reduced (i.e. gravitational effects increased), indicating the destabilizing role played by gravity. The spatio-temporal stability analysis was performed to determine the nature of the absolute instability of the jet. The roles of the density ratio

  19. Improvement of impact strength in linear low density polyethylene (LLDPE) by blending with amorphous polymers

    SciTech Connect

    Mirabella, F.M. Jr.

    1996-12-31

    The objective of the current work was to improve the film impact strength of commercial linear low density polyethylene (LLDPE) resins, while maintaining or improving other desirable properties. The approach used was to blend rubber-like (i.e. essentially noncrystalline) polymer resins with the base resin LLDPE. The choice of the rubber-like components was largely dictated by their commercial availability. The rubber-like polymers chosen were poly (ethylene-vinyl acetate) [EVA], poly (ethylene-n-butyl acrylate) [EnBA], and poly (ethylene-propylene) rubber [EPR]. The weight percent range of addition of the rubber-like component was restricted to 5% - 20%. The preferred range was only up to 10%. The structure of the base LLDPE resin, rubber-like components and the blends thereof was characterized. The physical and mechanical properties of the blown films of the resin blends were measured and correlations between structure and properties were determined.

  20. Nature and Nurture of Early-Type Dwarf Galaxies in Low Density Environments

    NASA Astrophysics Data System (ADS)

    Grützbauch, R.; Annibali, F.; Rampazzo, R.; Bressan, A.; Zeilinger, W. W.

    We study stellar population parameters of a sample of 13 dwarf galaxies located in poor groups of galaxies using high resolution spectra observed with VIMOS at the ESO-VLT [Grützbauch et al., A&A 502, 473 (2009)]. LICK-indices were compared with Simple Stellar Population models to derive ages, metallicities and [α/Fe]-ratios. Comparing the dwarfs with a sample of giant ETGs residing in comparable environments we find that the dwarfs are on average younger, less metal-rich, and less enhanced in alpha-elements than giants. Age, Z, and [α/Fe] ratios are found to correlate both with velocity dispersion and with morphology. We also find possible evidence that low density environment (LDE) dwarfs experienced more prolonged star formation histories than Coma dwarfs, however, larger samples are needed to draw firm conclusions.

  1. Low Density Lipoprotein Receptor Related Proteins as Regulators of Neural Stem and Progenitor Cell Function

    PubMed Central

    Landowski, Lila M.; Young, Kaylene M.

    2016-01-01

    The central nervous system (CNS) is a highly organised structure. Many signalling systems work in concert to ensure that neural stem cells are appropriately directed to generate progenitor cells, which in turn mature into functional cell types including projection neurons, interneurons, astrocytes, and oligodendrocytes. Herein we explore the role of the low density lipoprotein (LDL) receptor family, in particular family members LRP1 and LRP2, in regulating the behaviour of neural stem and progenitor cells during development and adulthood. The ability of LRP1 and LRP2 to bind a diverse and extensive range of ligands, regulate ligand endocytosis, recruit nonreceptor tyrosine kinases for direct signal transduction and signal in conjunction with other receptors, enables them to modulate many crucial neural cell functions. PMID:26949399

  2. The low density lipoprotein receptor-related protein (LRP) 1 and its function in lung diseases.

    PubMed

    Wujak, L; Markart, P; Wygrecka, M

    2016-07-01

    The low density lipoprotein receptor-related protein (LRP) 1 is a ubiquitously expressed, versatile cell surface transmembrane receptor involved in embryonic development and adult tissue homeostasis. LRP1 binds and endocytoses a broad spectrum of over 40 ligands identified thus far, including lipoproteins, extracellular matrix proteins, proteases and protease/inhibitor complexes and growth factors. Interactions with other membrane receptors and intracellular adaptors/scaffolding proteins allow LRP1 to modulate cell migration, survival, proliferation and (trans) differentiation. Because LRP1 displays a wide-range of interactions and activities, its expression and function is temporally and spatially tightly controlled. It is not, therefore, surprising that deregulation of LRP1 production and/or activity is observed in several diseases. In this review, we will systematically examine the evidence for the role of LRP1 in human pathologies placing special emphasis on LRP1-mediated pathogenesis of the lung. PMID:26926950

  3. Thomson scattering measurements in low-density plasmas in the TST-2 spherical tokamak

    NASA Astrophysics Data System (ADS)

    Togashi, H.; Ejiri, A.; Homma, H.; Shinya, T.; Takase, Y.; Toida, K.; Tsujii, N.; Yamaguchi, T.; Yoshida, Y.; Furui, H.; Sonehara, M.; Nakamura, K.; Takahashi, W.; Takeuchi, T.; Yajima, S.; Yamazaki, H.; Hasegawa, M.; Nagashima, Y.; Tojo, H.

    2015-12-01

    Thomson scattering (TS) diagnostics have been widely used in fusion studies to measure profiles of electron temperature Te and electron density ne. In order to measure the low-density plasmas (ne <= 1018 m-3) in TST-2, which is sustained by lower hybrid wave power, the signal-to-noise ratio in TS measurement has been improved by various means. For instance, optimization of the detecting system, accumulation of TS data obtained from reproducible discharges, and application of a coaxial multi-pass scheme were carried out. As a result, the profiles have been measured successfully and a peaked ne profile and a hollow Te profile were obtained. Additionally, isotropy of Te near the plasma center was confirmed by coaxial double-pass TS measurement.

  4. Low-density resin impregnated ceramic article and method for making the same

    NASA Technical Reports Server (NTRS)

    Tran, Huy K. (Inventor); Henline, William D. (Inventor); Hsu, Ming-ta S. (Inventor); Rasky, Daniel J. (Inventor); Riccitiello, Salvatore R. (Inventor)

    1997-01-01

    A low-density resin impregnated ceramic article advantageously employed as a structural ceramic ablator comprising a matrix of ceramic fibers. The fibers of the ceramic matrix are coated with an organic resin film. The organic resin can be a thermoplastic resin or a cured thermosetting resin. In one embodiment, the resin is uniformly distributed within the ceramic article. In a second embodiment, the resin is distributed so as to provide a density gradient along at least one direction of the ceramic article. The resin impregnated ceramic article is prepared by providing a matrix of ceramic fibers; immersing the matrix of ceramic fibers in a solution of a solvent and an organic resin infiltrant; and removing the solvent to form a resin film on the ceramic fibers.

  5. Degradation assessment of natural weathering on low density polyethylene/thermoplastic soya spent powder blends

    NASA Astrophysics Data System (ADS)

    Nuradibah, M. A.; Sam, S. T.; Noriman, N. Z.; Ragunathan, S.; Ismail, H.

    2015-07-01

    Soya spent powder was blended with low density polyethylene (LDPE) ranging from 5-25 wt%. Glycerol was added to soya spent powder (SSP) for preparation of thermoplastic soya spent powder (TSSP). Then, the blends were exposed to natural weathering for 6 months. The susceptibility of the LDPE/soya spent powder blends based on its tensile, morphological properties and structural changes was measured every three months. The tensile strength of LDPE/TSSP blends after 6 months of weathering was the lowest compared to the other blends whereas LDPE/SSP blends after 6 months of weathering demonstrated the lowest elongation at break (Eb). Large pore can be seen on the surface of 25 wt% of LDPE/SSP blends.

  6. Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients.

    PubMed Central

    Rudling, M J; Ståhle, L; Peterson, C O; Skoog, L

    1986-01-01

    The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients. PMID:3081176

  7. Current initiation in low-density foam z-pinch plasmas

    SciTech Connect

    Derzon, M.; Nash, T.; Allshouse, G.

    1996-07-01

    Low density agar and aerogel foams were tested as z-pinch loads on the SATURN accelerator. In these first experiments, we studied the initial plasma conditions by measuring the visible emission at early times with a framing camera and 1-D imaging. At later time, near the stagnation when the plasma is hotter, x-ray imaging and spectral diagnostics were used to characterize the plasma. Filamentation and arcing at the current contacts was observed. None of the implosions were uniform along the z-axis. The prime causes of these problems are believed to be the electrode contacts and the current return configuration and these are solvable. Periodic phenomena consistent with the formation of instabilities were observed on one shot, not on others, implying that there may be a way of controlling instabilities in the pinch. Many of the issues involving current initiation may be solvable. Solutions are discussed.

  8. DSMC Grid Methodologies for Computing Low-Density, Hypersonic Flows About Reusable Launch Vehicles

    NASA Technical Reports Server (NTRS)

    Wilmoth, Richard G.; LeBeau, Gerald J.; Carlson, Ann B.

    1996-01-01

    Two different grid methodologies are studied for application to DSMC simulations about reusable launch vehicles. One method uses an unstructured, tetrahedral grid while the other uses a structured, variable-resolution Cartesian grid. The relative merits of each method are discussed in terms of accuracy, computational efficiency, and overall ease of use. Both methods are applied to the computation of a low-density, hypersonic flow about a winged single-stage-to-orbit reusable launch vehicle concept at conditions corresponding to an altitude of 120 km. Both methods are shown to give comparable results for both surface and flowfield quantities as well as for the overall aerodynamic behavior. For the conditions simulated, the flowfield about the vehicle is very rarefied but the DSMC simulations show significant departure from free-molecular predictions for the surface friction and heat transfer as well as certain aerodynamic quantities.

  9. Elastic properties of low density core (LDC) Ti-6Al-4V sandwich cores

    SciTech Connect

    Queheillalt, D.T.; Wadley, H.N.G.; Schwartz, D.S.

    1998-12-31

    Lightweight, structurally efficient low density core (LDC) sandwich structures can be produced by entrapping argon gas within a finely dispersed distribution of pores in a microstructure and using a high temperature anneal to cause pore growth by gas expansion. This results in a porous microstructure with a relative density as low as {approximately}0.70. Laser ultrasonic methods have been used to measure the longitudinal and shear wave velocities and hence the elastic properties of LDC Ti-6Al-4V cores prior to, and after gas expansion treatments of up to 48 hr at 920 C. The data were compared with several analytical models for predicting the volume fraction of porosity dependent elastic properties of porous materials.

  10. Observation of Henry's Law in Low-Density Measurements of Adsorption on Carbon Nanotubes

    NASA Astrophysics Data System (ADS)

    Dzyubenko, Boris; Schmitz, Denise; Lee, Hao-Chun; Vilches, Oscar E.; Cobden, David H.

    2014-03-01

    We have studied the adsorption of noble gases on pristine suspended single-walled carbon nanotubes at low temperatures in the limit of low density (coverage), as determined from the shift of the mechanical resonance frequency of the nanotube due to mass loading. The high homogeneity of the nanotube substrate and the sensitivity of the technique allow us to observe Henry's law, in which the coverage is proportional to the gas pressure. In this limit the adsorption isotherm is determined by single-atom effects, allowing unprecedentedly accurate (+/- 2%) determination of the single-particle binding energies to a nanotube. Also, by measuring the deviation from Henry's law as coverage increases we obtain information about the pairwise interactions between the adsorbed atoms using the virial expansion.

  11. The thermal and mechanical properties of a low density elastomeric ablation material

    NASA Technical Reports Server (NTRS)

    Engelke, W. T.; Robertson, R. W.; Bush, A. L.; Pears, C. D.

    1973-01-01

    Thermal and mechanical properties data were obtained for a low density elastomeric resin based ablation material with phenolic-glass honeycomb reinforcement. Data were obtained for the material in the charred and uncharred state. Ablation material specimens were charred in a laboratory furnace at temperatures in the range from 600 K to 1700 K to obtain char specimens representative of the ablation char layer formed during reentry. These specimens were then used to obtain effective thermal conductivity, heat capacity, porosity, and permeability data at the char formation temperature. This provided a boxing of the data which enables the prediction of the transient response of the material during ablation. Limited comparisons were made between the furnace charred specimens and specimens which had been exposed to simulated reentry conditions.

  12. Low density of threading dislocations in AlN grown on sapphire

    NASA Astrophysics Data System (ADS)

    Faleev, Nikolai; Lu, Hai; Schaff, William J.

    2007-05-01

    We report on high resolution x-ray diffraction studies of the crystalline perfection and the relaxation of elastic strain in AlN grown by MBE on sapphire(0001). Thin (200-300 nm thick) AlN layers were grown with a very low density of threading screw dislocations. A density of 1.75-8.5×105 cm-2, the lowest value ever reported for III-Nitride epitaxial layers, was observed in a surface layer formed over a defective nucleation layer. Residual elastic strain was found in investigated AlN layers. Stress was found to be close to that expected from thermal expansion mismatch between the AlN and sapphire(0001). A model for the structural transformation of crystalline defects accounts for these observations.

  13. Low-density open-cell foams in the NiTi system

    NASA Astrophysics Data System (ADS)

    Grummon, David S.; Shaw, John A.; Gremillet, Antoine

    2003-04-01

    It is shown that open-cell metallic foams having very low density, and that display martensite transformations required for shape memory and superelastic behavior, can be fabricated using a powder-metallurgy technique. Results are presented on experiments in which a polymeric precursor foam was coated with an equiatomic NiTi powder slurry and subsequently sintered to yield foams with relative densities as low as 0.039. Although contaminated with interstitial impurities, they displayed unambiguous calorimetric signature of the B2→B19' transformation. The results are of considerable significance to potential applications requiring ultralightweight structures with the unusual dissipative and strain-recovery properties of NiTi shape-memory materials.

  14. Statistical mechanics of low-density parity check error-correcting codes over Galois fields

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Kabashima, Y.; Saad, D.

    2001-11-01

    A variation of low-density parity check (LDPC) error-correcting codes defined over Galois fields (GF(q)) is investigated using statistical physics. A code of this type is characterised by a sparse random parity check matrix composed of C non-zero elements per column. We examine the dependence of the code performance on the value of q, for finite and infinite C values, both in terms of the thermodynamical transition point and the practical decoding phase characterised by the existence of a unique (ferromagnetic) solution. We find different q-dependence in the cases of C = 2 and C >= 3; the analytical solutions are in agreement with simulation results, providing a quantitative measure to the improvement in performance obtained using non-binary alphabets.

  15. Low density lipoprotein bionanoparticles: From cholesterol transport to delivery of anti-cancer drugs

    PubMed Central

    Harisa, Gamaleldin I.; Alanazi, Fars K.

    2013-01-01

    In this review article, we highlight the importance of low-density lipoprotein (LDL) and its implications in the field of drug delivery to cancer cells. LDL is naturally occurring bionanoparticles (BNP) with a size of 18–25 nm. These BNPs specifically transport cholesterol to cells expressing the LDL receptors (LDLRs). Several tumors overexpress LDLRs, presumably to provide cholesterol for sustaining a high rate of membrane synthesis. LDL BNPs are biocompatible and biodegradable, favorably bind hydrophobic and amphiphilic drugs, are taken up by a receptor-mediated mechanism, have a half-life of 2–4 days, and can be rerouted. Drugs can be loaded onto LDL BNPs by surface loading, core loading, and apoprotein interaction. LDL may be used as a drug carrier for treatment of atherosclerosis, cancer, and in photodynamic therapies. PMID:25561862

  16. Low-density, high-strength intermetallic matrix composites by XD (trademark) synthesis

    NASA Technical Reports Server (NTRS)

    Kumar, K. S.; Dipietro, M. S.; Brown, S. A.; Whittenberger, J. D.

    1991-01-01

    A feasibility study was conducted to evaluate the potential of particulate composites based on low-density, L1(sub 2) trialuminide matrices for high-temperature applications. The compounds evaluated included Al22Fe3Ti8 (as a multiphase matrix), Al67Ti25Cr8, and Al66Ti25Mn9. The reinforcement consisted of TiB2 particulates. The TiB2 composites were processed by ingot and powder metallurgy techniques. Microstructural characterization and mechanical testing were performed in the hot-pressed and hot-isostatic-pressed condition. The casting were sectioned and isothermally forged into pancakes. All the materials were tested in compression as a function of temperature, and at high temperatures as a function of strain rate. The test results are discussed.

  17. Thermal inertia and radar reflectivity of the Martian north polar ERG: Low-density aggregates

    NASA Technical Reports Server (NTRS)

    Herkenhoff, K. E.

    1993-01-01

    The north polar layered deposits on Mars appear to be the source of the dark material that comprises the north polar erg. The physical properties and chemical composition of the erg material therefore have important implications for the origin and evolution of the Martian layered deposits. Viking bistatic radar and infrared thermal mapping (IRTM) data indicate that the bulk density of the erg material is lower than that of the average Martian surface. These data are consistent with hypotheses involving formation of filamentary sublimation residue (FSR) particles from erosion of the layered deposits. The color and albedo of the erg and of the layered deposits, and the presence of magnetic material on Mars, suggest that the dark material is composed of low-density aggregates of magnetic dust grains, perhaps similar to FSR particles created in laboratory experiments.

  18. Low density microcellular carbon or catalytically impregnated carbon foams and process for their prepartion

    DOEpatents

    Hopper, Robert W.; Pekala, Richard W.

    1988-01-01

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  19. Stemflow in low-density and hedgerow olive orchards in Portugal

    NASA Astrophysics Data System (ADS)

    Dias, Pedro D.; Valente, Fernanda; Pereira, Fernando L.; Abreu, Francisco G.

    2015-04-01

    Stemflow (Sf) is responsible for a localized water and solute input to soil around tree's trunks, playing an important eco-hydrological role in forest and agricultural ecosystems. Sf was monitored for seven months in 25 Olea europaea L. trees distributed in three orchards managed in two different ways, traditional low-density and super high density hedgerow. The orchards were located in central Portugal in the regions of Santarém (Várzea and Azóia) and Lisboa (Tapada). Seven olive varieties were analysed: Arbequina, Galega, Picual, Maçanilha, Cordovil, Azeiteira, Negrinha and Blanqueta. Measured Sf ranged from 7.5 to 87.2 mm (relative to crown-projected area), corresponding to 1.2 and 16.7% of gross rainfall (Pg). To understand better the variables that affect Sf and to be able to predict its value, linear regression models were fitted to these data. Whenever possible, the linear models were simplified using the backward stepwise algorithm based on the Akaike information criterion. For each tree, multiple linear regressions were adjusted between Sf and the duration, volume and intensity of rainfall episodes and maximum evaporation rate. In the low-density Várzea grove the more relevant explanatory variables were the three rainfall characteristics. In the super high density Azóia orchard only rainfall volume and intensity were considered relevant. In the low-density Tapada's grove all trees had a different sub-model with Pg being the only common variable. To try to explain differences between trees and to improve the quality of the modeling in each orchard, another set of explanatory variables was added: canopy volume, tree and trunk heights and trunk perimeter at the height of the first branches. The variables present in all sub-models were rainfall volume and intensity and the tree and trunk heights. Canopy volume and rainfall duration were also present in the sub-models of the two low-density groves (Tapada and Várzea). The determination coefficient (R2

  20. Low-density parity-check codes for volume holographic memory systems.

    PubMed

    Pishro-Nik, Hossein; Rahnavard, Nazanin; Ha, Jeongseok; Fekri, Faramarz; Adibi, Ali

    2003-02-10

    We investigate the application of low-density parity-check (LDPC) codes in volume holographic memory (VHM) systems. We show that a carefully designed irregular LDPC code has a very good performance in VHM systems. We optimize high-rate LDPC codes for the nonuniform error pattern in holographic memories to reduce the bit error rate extensively. The prior knowledge of noise distribution is used for designing as well as decoding the LDPC codes. We show that these codes have a superior performance to that of Reed-Solomon (RS) codes and regular LDPC counterparts. Our simulation shows that we can increase the maximum storage capacity of holographic memories by more than 50 percent if we use irregular LDPC codes with soft-decision decoding instead of conventionally employed RS codes with hard-decision decoding. The performance of these LDPC codes is close to the information theoretic capacity. PMID:12593489