An atypical proprotein convertase in Giardia lamblia differentiation.

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Davids, B J; Gilbert, M A; Liu, Q; Reiner, D S; Smith, A J; Lauwaet, T; Lee, C; McArthur, A G; Gillin, F D

2011-02-01

Proteolytic activity is important in the lifecycles of parasites and their interactions with hosts. Cysteine proteases have been best studied in Giardia, but other protease classes have been implicated in growth and/or differentiation. In this study, we employed bioinformatics to reveal the complete set of putative proteases in the Giardia genome. We identified 73 peptidase homologs distributed over 5 catalytic classes in the genome. Serial analysis of gene expression of the G. lamblia lifecycle found thirteen protease genes with significant transcriptional variation over the lifecycle, with only one serine protease transcript upregulated late in encystation. The translated gene sequence of this encystation-specific transcript was most similar to eukaryotic subtilisin-like proprotein convertases (SPC), although the typical catalytic triad was not identified. Epitope-tagged gSPC protein expressed in Giardia under its own promoter was upregulated during encystation with highest expression in cysts and it localized to encystation-specific secretory vesicles (ESV). Total gSPC from encysting cells produced proteolysis in gelatin gels that co-migrated with the epitope-tagged protease in immunoblots. Immuno-purified gSPC also had gelatinase activity. To test whether endogenous gSPC activity is involved in differentiation, trophozoites and cysts were exposed to the specific serine proteinase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF). After 21 h encystation, a significant decrease in ESV was observed with 1mM AEBSF and by 42 h the number of cysts was significantly reduced, but trophozoite growth was not inhibited. Concurrently, levels of cyst wall proteins 1 and 2, and AU1-tagged gSPC protein itself were decreased. Excystation of G. muris cysts was also significantly reduced in the presence of AEBSF. These results support the idea that serine protease activity is essential for Giardia encystation and excystation. Copyright © 2010 Elsevier B

Chemical Constituents with Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression Inhibitory Activity from Dried Immature Morus alba Fruits.

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Pel, Pisey; Chae, Hee-Sung; Nhoek, Piseth; Kim, Young-Mi; Chin, Young-Won

2017-07-05

Phytochemical investigation for a chloroform-soluble extract of dried Morus alba fruits, selected by proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression monitoring assay in HepG2 cells, led to the isolation of a new benzofuran, isomoracin D (1), and a naturally occurring compound, N-(N-benzoyl-l-phenylalanyl)-l-phenylalanol (2), along with 13 known compounds (3-15). All of the structures were established by NMR spectroscopic data as well as MS analysis. Of the isolates, moracin C (7) was found to inhibit PCSK9 mRNA expression with an IC 50 value of 16.8 μM in the HepG2 cells.

Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia.

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Sultan Alvi, Sahir; Ansari, Irfan A; Khan, Imran; Iqbal, Johar; Khan, M Salman

2017-07-01

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression. Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular informatics approach to assess the dual mode of action of lycopene in LDL-R recycling and increased removal of circulatory LDL-C. We for the first time deciphered that lycopene treatment significantly down-regulates the expression of hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up-regulated. Furthermore, lycopene ameliorated inflammation stimulated expression of PCSK-9 via suppressing the expression of inflammatory markers. The results from our molecular informatics studies confirmed that lycopene, while occupying the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A complex. Based on above results, it can be concluded that lycopene exhibits potent hypolipidemic activities via molecular mechanisms that are either identical (HMGR inhibition) or distinct from that of statins (down-regulation of PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report that lycopene has this specific

Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

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Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes; Radler, David; Joshi, Rajendra; Thomas, Gary; Shinde, Ujwal

2012-10-12

The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.

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Williamson, Danielle M; Elferich, Johannes; Shinde, Ujwal

2015-09-18

The propeptides of proprotein convertases (PCs) regulate activation of cognate protease domains by sensing pH of their organellar compartments as they transit the secretory pathway. Earlier experimental work identified a conserved histidine-encoded pH sensor within the propeptide of the canonical PC, furin. To date, whether protonation of this conserved histidine is solely responsible for PC activation has remained unclear because of the observation that various PC paralogues are activated at different organellar pH values. To ascertain additional determinants of PC activation, we analyzed PC1/3, a paralogue of furin that is activated at a pH of ∼5.4. Using biophysical, biochemical, and cell-based methods, we mimicked the protonation status of various histidines within the propeptide of PC1/3 and examined how such alterations can modulate pH-dependent protease activation. Our results indicate that whereas the conserved histidine plays a crucial role in pH sensing and activation of this protease an additional histidine acts as a "gatekeeper" that fine-tunes the sensitivity of the PC1/3 propeptide to facilitate the release inhibition at higher proton concentrations when compared with furin. Coupled with earlier analyses that highlighted the enrichment of the amino acid histidine within propeptides of secreted eukaryotic proteases, our work elucidates how secreted proteases have evolved to exploit the pH of the secretory pathway by altering the spatial juxtaposition of titratable groups to regulate their activity in a spatiotemporal fashion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Impact of diet and exercise on proprotein convertase subtilisin/kexin 9: A mini-review.

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Saely, Christoph H; Drexel, Heinz

2016-12-01

Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) plays an important role in the regulation of blood cholesterol levels, and inhibition of PCSK9 with monoclonal antibodies reduces LDL cholesterol by more than 50% over and above what can be achieved with statins or ezetimibe alone. Diet and exercise influence PCSK9 levels; however data on this issue are scarce. Regarding diet, a high oleic canola/docosahexaenoic acid oil blend, marine n-3 polyunsaturated fatty acids, vegetable n-6 polyunsaturated fatty acids, a Mediterranean style diet and acute fasting, but not necessarily weight reduction are associated with low PCSK9 concentrations, whereas a high fructose diet is associated with high PCSK9 concentrations. Animal data regarding the effect of diet on PCSK9 must be interpreted with caution, because even between rodent species, significant differences become apparent. Regarding exercise, a decrease in PCSK9 has been reported in one investigation along with an intervention promoting active use of stairs rather than elevators. Reports from sparse animal studies regarding the effect of exercise on PCSK9 have yielded varying results. Copyright © 2016. Published by Elsevier Inc.

Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy.

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Gönç, E. Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

2017-09-01

Proprotein convertase 1/3 (PC1/3) deficiency is a very rare disease characterized by severe intractable diarrhea in the first years of life, followed by obesity and several hormonal deficiencies later. Diabetes mellitus requiring insulin treatment and diabetic ketoacidosis have not been reported in this disorder. We herein present a girl with PC1/3 deficiency who has been followed from birth to 17 years of age. She developed deficiencies of all pituitary hormones over time as well as diabetes mellitus while receiving growth hormone (GH) therapy. She was complicated with diabetic ketoacidosis during dietary management of diabetes mellitus, thus insulin treatment was initiated. Insulin requirement to regulate hyperglycemia was short-lived. Repeat oral glucose tolerance test five years later was normal. The findings of this patient show that diabetes mellitus can develop at any time during follow-up of cases with proportein convertase 1/3 deficiency especially under GH therapy.

Transgenic Overexpression of the Proprotein Convertase Furin Enhances Skin Tumor Growth

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Jian Fu

2012-04-01

Full Text Available Furin, one of the members of the family of proprotein convertases (PCs, ubiquitously expressed as a type I membrane-bound proteinase, activates several proteins that contribute to tumor progression. In vitro studies using cancer cell lines and clinical specimens demonstrated that furin processes important substrates such as insulin-like growth factor 1 receptor (IGF-1R and transforming growth factor β, leading to increased tumor growth and progression. Despite the numerous studies associating furin with tumor development, its effects in preclinical models has not been comprehensively studied. In this study, we sought to determine the protumorigenic role of furin in vivo after a two-stage chemical carcinogenesis protocol in transgenic mice in which furin expression was targeted to the epidermal basal layer. We found that processing of the PC substrate IGF-1R and the proliferation rate of mouse epidermis was enhanced in transgenic mice when compared with their WT counterparts. Histopathologic diagnoses of the tumors demonstrated that furin transgenic mice (line F47 developed twice as many squamous carcinomas as the control, WT mice (P < .002. Similarly, tumors cells from transgenic mice were able to process PC substrates more efficiently than tumor cells from WT mice. Furthermore, furin expression resulted in a higher SCC volume in transgenic mice as well as an increase in the percentage of high-grade SCC, including poorly differentiated and spindle cell carcinomas. In conclusion, expression of furin in the basal layer of the epidermis increased tumor development and enhanced tumor growth, supporting the consideration of furin as a potential target for cancer treatment.

Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia-Brief Report.

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Thedrez, Aurélie; Sjouke, Barbara; Passard, Maxime; Prampart-Fauvet, Simon; Guédon, Alexis; Croyal, Mikael; Dallinga-Thie, Geesje; Peter, Jorge; Blom, Dirk; Ciccarese, Milco; Cefalù, Angelo B; Pisciotta, Livia; Santos, Raul D; Averna, Maurizio; Raal, Frederick; Pintus, Paolo; Cossu, Maria; Hovingh, Kees; Lambert, Gilles

2016-08-01

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured by flow cytometry and confocal microscopy was higher in ARH than in control lymphocytes. PCSK9 significantly reduced LDL receptor expression in ARH lymphocytes albeit to a lower extent than in control lymphocytes (25% versus 76%, respectively), an effect reversed by alirocumab. Fluorescent LDL cellular uptake, also measured by flow cytometry, was reduced in ARH lymphocytes compared with control lymphocytes. PCSK9 significantly lowered LDL cellular uptake in ARH lymphocytes, on average by 18%, compared with a 46% reduction observed in control lymphocytes, an effect also reversed by alirocumab. Overall, the effects of recombinant PCSK9, and hence of alirocumab, on LDL receptor expression and function were significantly less pronounced in ARH than in control cells. PCSK9 inhibition with alirocumab on top of statin treatment has the potential to lower LDL cholesterol in some autosomal recessive hypercholesterolemia patients. © 2016 American Heart Association, Inc.

Dietary high oleic canola oil supplemented with docosahexaenoic acid attenuates plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in participants with cardiovascular disease risk: A randomized control trial.

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Pu, Shuaihua; Rodríguez-Pérez, Celia; Ramprasath, Vanu Ramkumar; Segura-Carretero, Antonio; Jones, Peter J H

2016-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel circulating protein which plays an important role in regulation of cholesterol metabolism by promoting hepatic LDL receptor degradation. However, the action of dietary fat composition on PCSK9 levels remains to be fully elucidated. The objective was to investigate the action of different dietary oils on circulating PCSK9 levels in the Canola Oil Multicenter Intervention Trial (COMIT). COMIT employed a double-blinded crossover randomized control design, consisting of five 30-d treatment periods. Diets were provided based on a 3000Kcal/d intake, including a 60g/d treatment of conventional canola oil (Canola), a high oleic canola/DHA oil blend (CanolaDHA), a corn/safflower oil blend (CornSaff), a flax/safflower oil blend (FlaxSaff) or a high oleic canola oil (CanolaOleic). Plasma PCSK9 levels were assessed using ELISA at the end of each phase. Lipid profiles (n=84) showed that CanolaDHA feeding resulted in the highest (P<0.05) serum total cholesterol (TC, 5.06±0.09mmol/L) and LDL-cholesterol levels (3.15±0.08mmol/L) across all five treatments. CanolaDHA feeding also produced the lowest (P<0.05) plasma PCSK9 concentrations (216.42±8.77ng/mL) compared to other dietary oil treatments. Plasma PCSK9 levels positively correlated (P<0.05) with serum TC, LDL-cholesterol, apolipoprotein A, and apolipoprotein B levels but did not correlate to HDL-cholesterol levels. Results indicate that post-treatment response in PCSK9 may be altered with the CanolaDHA diet. In conclusion, the elevated LDL-C levels from a DHA oil treatment may not be relevant for the observed decline in PCSK9 levels. Copyright © 2016 Elsevier Inc. All rights reserved.

[Blood Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Men from Different Population Groups and Its Relation to Unfavorable Long-Term Prognosis].

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Ragino, Yu I; Astrakova, K S; Shakhtshneider, E V; Stakhneva, E M; Gafarov, V V; Bogatyrev, S N; Voevoda, M I

2017-04-01

of the study was to investigate blood levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in men from different population subgroups, their associations with cardiovascular risk factors and with unfavorable 7-years long-term prognosis. The study included three subgroups of men from a population sample of residents of Novosibirsk, 44-73 years old, not receiving lipid-lowering drugs: subgroup of population proper (183 men), subgroup with hypercholesterolemia (46 men), and subgroup with hypocholesterolemia (18 men). Blood level of PCSK9 was determined by ELISA using the test-systems "Human Proprotein Convertase 9/PCSK9 Immunoassay". Study endpoints (myocardial infarction, cardiovascular death) were registered during 7 years after baseline examination of subgroups using the data of the Registers of myocardial infarction and cardiovascular mortality. Distribution of PCSK9 protein in subgroups with hyper- and hypocholesterolemia was normal. In the subgroup of population proper it was abnormal with leftward shift. PCSK9 protein concentration in the subgroup with hypercholesterolemia was 1.2 times higher than in the population subgroup. PCSK9 protein level correlated significantly with blood levels of total cholesterol (CH), low density lipoprotein (LDL) CH, and glucose. Only 15% of PCSK9 variability was due to the influence of other factors (R Square=0.155, pblood level of PCSK9 protein were levels of high density lipoprotein CH (=0.238, p=0.023), triglycerides (=0.253, p=0.049) and LDL CH (=0.751, p=0.009). Multivariate regression analysis revealed significant independent association of PCSK9 protein levels with cardiovascular death during period of registration (7-years) (p=0.048, OR=1.01). This result indicates that in men increase of blood level of PCSK9 protein by 1ng/ml independently of other parameters increases relative risk of cardiovascular death during following 7 years by 1%.

Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function

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DeVay, Rachel M.; Yamamoto, Lynn; Shelton, David L.; Liang, Hong

2015-01-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a soluble protein that directs membrane-bound receptors to lysosomes for degradation. In the most studied example of this, PCSK9 binding leads to the degradation of low density lipoprotein receptor (LDLR), significantly affecting circulating LDL-C levels. The mechanism mediating this degradation, however, is not completely understood. We show here that LDLR facilitates PCSK9 interactions with amyloid precursor like protein 2 (APLP2) at neutral pH leading to PCSK9 internalization, although direct binding between PCSK9 and LDLR is not required. Moreover, binding to APLP2 or LDLR is independently sufficient for PCSK9 endocytosis in hepatocytes, while LDL can compete with APLP2 for PCSK9 binding to indirectly mediate PCSK9 endocytosis. Finally, we show that APLP2 and LDLR are also required for the degradation of another PCSK9 target, APOER2, necessitating a general role for LDLR and APLP2 in PCSK9 function. Together, these findings provide evidence that PCSK9 has at least two endocytic epitopes that are utilized by a variety of internalization mechanisms and clarifies how PCSK9 may direct proteins to lysosomes. PMID:25905719

Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin

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Rotwein Peter

2008-04-01

Full Text Available Abstract Background Repulsive guidance molecule c (RGMc or hemojuvelin, a glycosylphosphatidylinositol-linked glycoprotein expressed in liver and striated muscle, plays a central role in systemic iron balance. Inactivating mutations in the RGMc gene cause juvenile hemochromatosis (JH, a rapidly progressing iron storage disorder with severe systemic manifestations. RGMc undergoes complex biosynthetic steps leading to membrane-bound and soluble forms of the protein, including both 50 and 40 kDa single-chain species. Results We now show that pro-protein convertases (PC are responsible for conversion of 50 kDa RGMc to a 40 kDa protein with a truncated COOH-terminus. Unlike related molecules RGMa and RGMb, RGMc encodes a conserved PC recognition and cleavage site, and JH-associated RGMc frame-shift mutants undergo COOH-terminal cleavage only if this site is present. A cell-impermeable peptide PC inhibitor blocks the appearance of 40 kDa RGMc in extra-cellular fluid, as does an engineered mutation in the conserved PC recognition sequence, while the PC furin cleaves 50 kDa RGMc in vitro into a 40 kDa molecule with an intact NH2-terminus. Iron loading reduces release of RGMc from the cell membrane, and diminishes accumulation of the 40 kDa species in cell culture medium. Conclusion Our results define a role for PCs in the maturation of RGMc that may have implications for the physiological actions of this critical iron-regulatory protein.

Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a).

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Turpeinen, Hannu; Oksanen, Anna; Kivinen, Virpi; Kukkurainen, Sampo; Uusimäki, Annemari; Rämet, Mika; Parikka, Mataleena; Hytönen, Vesa P; Nykter, Matti; Pesu, Marko

2013-12-20

Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system-related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFβ1a. Consequently, tgfβ1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development.

The Proprotein Convertase KPC-1/Furin Controls Branching and Self-avoidance of Sensory Dendrites in Caenorhabditis elegans

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Bülow, Hannes E.

2014-01-01

Animals sample their environment through sensory neurons with often elaborately branched endings named dendritic arbors. In a genetic screen for genes involved in the development of the highly arborized somatosensory PVD neuron in C. elegans, we have identified mutations in kpc-1, which encodes the homolog of the proprotein convertase furin. We show that kpc-1/furin is necessary to promote the formation of higher order dendritic branches in PVD and to ensure self-avoidance of sister branches, but is likely not required during maintenance of dendritic arbors. A reporter for kpc-1/furin is expressed in neurons (including PVD) and kpc-1/furin can function cell-autonomously in PVD neurons to control patterning of dendritic arbors. Moreover, we show that kpc-1/furin also regulates the development of other neurons in all major neuronal classes in C. elegans, including aspects of branching and extension of neurites as well as cell positioning. Our data suggest that these developmental functions require proteolytic activity of KPC-1/furin. Recently, the skin-derived MNR-1/menorin and the neural cell adhesion molecule SAX-7/L1CAM have been shown to act as a tripartite complex with the leucine rich transmembrane receptor DMA-1 on PVD mechanosensory to orchestrate the patterning of dendritic branches. Genetic analyses show that kpc-1/furin functions in a pathway with MNR-1/menorin, SAX-7/L1CAM and DMA-1 to control dendritic branch formation and extension of PVD neurons. We propose that KPC-1/furin acts in concert with the ‘menorin’ pathway to control branching and growth of somatosensory dendrites in PVD. PMID:25232734

Activation of Adiponectin Receptor Regulates Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Inhibits Lesions in ApoE-Deficient Mice.

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Sun, Lei; Yang, Xiaoxiao; Li, Qi; Zeng, Peng; Liu, Ying; Liu, Lipei; Chen, Yuanli; Yu, Miao; Ma, Chuanrui; Li, Xiaoju; Li, Yan; Zhang, Rongxin; Zhu, Yan; Miao, Qing Robert; Han, Jihong; Duan, Yajun

2017-07-01

The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown. At cellular levels, AdipoR agonists (ADP355 and AdipoRon) induced PCSK9 transcription/expression that solely depended on activation of PPAR-responsive element in the PCSK9 promoter. AdipoR agonists induced PPARγ expression; thus, the AdipoR agonist-activated PCSK9 expression/production was impaired in PPARγ deficient hepatocytes. Meanwhile, AdipoR agonists transcriptionally activated LDLR expression by activating SRE in the LDLR promoter. Moreover, AMP-activated protein kinase α (AMPKα) was involved in AdipoR agonist-activated PCSK9 expression. In wild-type mice, ADP355 increased PCSK9 and LDLR expression and serum PCSK9 levels, which was associated with activation of PPARγ, AMPKα and SREBP2 and reduction of LDL-cholesterol levels. In contrast, ADP355 reduced PCSK9 expression/secretion in apoE-deficient (apoE -/- ) mice, but it still activated hepatic LDLR, PPARγ, AMPKα, and SREBP2. More importantly, ADP355 inhibited lesions in en face aortas and sinus lesions in aortic root in apoE -/- mice with amelioration of lipid profiles. Our study demonstrates that AdipoR activation by agonists regulated PCSK9 expression differently in wild-type and apoE -/- mice. However, ADP355 activated hepatic LDLR expression and ameliorated lipid metabolism in both types of mice and inhibited atherosclerosis in apoE -/- mice. © 2017 American Heart Association, Inc.

Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

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Hyrina, Anastasia; Olmstead, Andrea D; Steven, Paul; Krajden, Mel; Tam, Edward; Jean, François

2017-09-01

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

NARCIS (Netherlands)

Sjouke, B.; Yahya, R.; Tanck, M.W.T.; Defesche, J.C.; Graaf, J. de; Wiegman, A.; Kastelein, J.J.; Mulder, M.T.; Hovingh, G.K.; Roeters van Lennep, J.E.

2017-01-01

BACKGROUND: Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and

Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

NARCIS (Netherlands)

Sjouke, Barbara; Yahya, Reyhana; Tanck, Michael W. T.; Defesche, Joep C.; de Graaf, Jacqueline; Wiegman, Albert; Kastelein, John J. P.; Mulder, Monique T.; Hovingh, G. Kees; Roeters van Lennep, Jeanine E.

2017-01-01

Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and in some

Induction of atherosclerosis in mice and hamsters without germline genetic engineering

DEFF Research Database (Denmark)

Bjørklund, Martin Mæng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup

2014-01-01

RATIONALE: Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. OBJECTIVE......: To develop a method for induction of atherosclerosis without germline genetic engineering. METHODS AND RESULTS: Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector...... injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions...

Inhibitory proproteinowej konwertazy subtylizyny/keksyny 9 nowym, przełomowym narzędziem terapeutycznym w leczeniu dyslipidemii = Proprotein convertase subtilisin/kexin type 9 inhibitors are a new, groundbreaking therapeutic tool in the treatment of dyslipidemia

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Łukasz Wołowiec

2016-07-01

 concentartion of LDL cholesterol. Proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors (a  new class of drugs  that regulate the concentration of LDL cholesterol receptor seem to be a  new and effective therapeutic tool used to reach the target level of LDL cholesterol. The aim of the study was to present the cholesterol metabolism in human body, the significance of an effective therapy for lipid disorders as well as the current knowledge of the PCSK9 protein and its inhibitors.   Key words: cholesterol, proprotein convertase subtilisin/kexin type (PCSK9, PCSK9 inhibitors.

'LDL-C' = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering.

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Yeang, Calvin; Witztum, Joseph L; Tsimikas, Sotirios

2015-06-01

The measurement that is termed 'LDL-cholesterol' (LDL-C) includes the cholesterol content of lipoprotein(a) [Lp(a)-C], which can contribute approximately 30-45% to measured LDL-C levels as a percentage of its mass. We review the implications of achieved very low LDL-C levels in patients treated with potent LDL-C-lowering agents in the context of varying Lp(a) levels. Combination therapy with statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can lower LDL-C to unprecedentedly low levels. Recent PCSK9 trials have shown that routine achievement of mean LDL-C less than 50 mg/dl is feasible, along with the modest reductions in Lp(a). Many patients will achieve LDL-C less than 25 mg/dl with concomitantly elevated Lp(a) levels that contribute substantially to the measured 'LDL-C'. Therefore, it is possible that some of these patients may have little to no circulating LDL-C. As the new era of ultralow LDL-C levels ensues, it is imperative to understand the contribution of Lp(a)-C to measured LDL-C and the consequences of achieving ultralow or potentially absent LDL-C in the setting of elevated Lp(a) levels and possibly free apo(a). We review this concept and suggest avenues of research, including analyses of existing datasets in current clinical trials and new research studies, to understand its pathophysiological and clinical significance.

Association of a 3' untranslated region polymorphism in proprotein convertase subtilisin/kexin type 9 with HIV viral load and CD4+ levels in HIV/hepatitis C virus coinfected women.

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Kuniholm, Mark H; Liang, Hua; Anastos, Kathryn; Gustafson, Deborah; Kassaye, Seble; Nowicki, Marek; Sha, Beverly E; Pawlowski, Emilia J; Gange, Stephen J; Aouizerat, Bradley E; Pushkarsky, Tatiana; Bukrinsky, Michael I; Prasad, Vinayaka R

2017-11-28

To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women. Six SNPs were associated with both HIV viral load and CD4 T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3' untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n = 408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P = 0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P = 0.76) women in adjusted analysis. PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.

Hepatic S1P deficiency lowers plasma cholesterol levels in apoB-containing lipoproteins when LDLR function is compromised.

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Basu, Debapriya; Huq, Afroza; Iqbal, Jahangir; Hussain, M Mahmood; Jiang, Xian-Cheng; Jin, Weijun

2015-01-01

Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR. A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation. A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9

A phase 1 study to evaluate the safety and LDL cholesterol-lowering effects of RG7652, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9.

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Baruch, Amos; Luca, Diana; Kahn, Robert S; Cowan, Kyra J; Leabman, Maya; Budha, Nageshwar R; Chiu, Cecilia P C; Wu, Yan; Kirchhofer, Daniel; Peterson, Andrew; Davis, John C; Tingley, Whittemore G

2017-07-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates low-density lipoprotein (LDL) receptors, thereby leading to a rise in circulating LDL cholesterol (LDL-C). RG7652 is a fully human monoclonal antibody against PCSK9. This placebo-controlled, phase 1 ascending-dose study in healthy subjects evaluated the safety of RG7652 and its efficacy as a potential LDL-C-lowering drug. Anti-PCSK9 antibody therapy safely and effectively reduces LDL-C. Subjects (N = 80) were randomized into 10 cohorts. Six sequential single-dose cohorts received 10, 40, 150, 300, 600, or 800 mg of RG7652 via subcutaneous injection. Four multiple-dose cohorts received 40 or 150 mg of RG7652 once weekly for 4 weeks, either with or without statin therapy (atorvastatin). Adverse events (AEs) were generally mild; the most common AEs were temporary injection-site reactions. No serious AEs, severe AEs, AEs leading to study-drug discontinuation, or dose-limiting toxicities were reported. RG7652 monotherapy reduced mean LDL-C levels by up to 64% and as much as 100 mg/dL at week 2; the effect magnitude and duration increased with dose (≥57 days following a single RG7652 dose ≥300 mg). Exploratory analyses showed reduced oxidized LDL, lipoprotein(a), and lipoprotein-associated phospholipase A2 with RG7652. Antidrug antibody against RG7652 tested positive in 2 of 60 (3.3%) RG7652-treated and in 4 of 20 (20.0%) placebo-treated subjects. Simultaneous atorvastatin administration did not appear to impact the pharmacokinetic profile or lipid-lowering effects of RG7652. Overall, RG7652 elicited substantial and sustained dose-related LDL-C reductions with an acceptable safety profile and minimal immunogenicity. © 2017 Wiley Periodicals, Inc.

Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

OpenAIRE

Bonde, Ylva; Breuer, Olof; L?tjohann, Dieter; Sj?berg, Stefan; Angelin, Bo; Rudling, Mats

2014-01-01

Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyr...

A novel method for direct measurement of complement convertases activity in human serum.

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Blom, A M; Volokhina, E B; Fransson, V; Strömberg, P; Berghard, L; Viktorelius, M; Mollnes, T E; López-Trascasa, M; van den Heuvel, L P; Goodship, T H; Marchbank, K J; Okroj, M

2014-10-01

Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases and ischaemia-reperfusion injury. An assay for direct measurement of activity of the convertases in patient sera is not available. Existing assays testing convertase function are based on purified complement components and, thus, convertase formation occurs under non-physiological conditions. We designed a new assay, in which C5 blocking compounds enabled separation of the complement cascade into two phases: the first ending at the stage of C5 convertases and the second ending with membrane attack complex formation. The use of rabbit erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for convertase formation enabled easy readout based on measurement of haemolysis. Thus, properties of patient sera could be studied directly regarding convertase activity and membrane attack complex formation. Another advantage of this assay was the possibility to screen for host factors such as C3 nephritic factor and other anti-complement autoantibodies, or gain-of-function mutations, which prolong the half-life of complement convertases. Herein, we present proof of concept, detailed description and validation of this novel assay. © 2014 British Society for Immunology.

Proprotein Convertases in Human Breast Cancer

Science.gov (United States)

2001-03-01

virgin mouse mammary glands (although further increase occurs during pregancy and lactation), a finding that is consistent with the fact that the MMTV-LTR...mM nude mice in response to estrogen and the NaC1, sodium deoxycholate (0-5%), SDS (0-1%), antiestrogen tamoxifen. NP40 (0-5%) and 100kIU/ml Trasylol

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

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Ridker, Paul M; Revkin, James; Amarenco, Pierre

2017-01-01

BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In tw...

Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events

NARCIS (Netherlands)

Robinson, Jennifer G.; Farnier, Michel; Krempf, Michel; Bergeron, Jean; Luc, Gérald; Averna, Maurizio; Stroes, Erik S.; Langslet, Gisle; Raal, Frederick J.; El Shahawy, Mahfouz; Koren, Michael J.; Lepor, Norman E.; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Kastelein, John J. P.; Caccavo, Alberto; Codutti, Oscar; Gelersztein, Elisabeth; Vico, Marisa; Zaidman, Cesar; Majul, Claudio; Balthazar, Yohan; Capiau, Luc; Vrolix, Mathias; Vermeersch, Paul; Gotchev, Dobromir; Todorov, Georgi; Tumbev, Haralin; Tzekova, Maria; Gronkova, Naydenka; Dimov, Bojidar; Nikolaeva, Antonoaneta; Devedzhiev, Tsvetan; Mincheva, Valentina; D'Ignazio, Giuseppe; Dzongowski, Peter; Elliott, Thomas; Hart, Randy; Hoag, Gordon; Martinho, Valdemar; O'Mahony, Michael; Tellier, Guy; Pandey, Shekhar; Heaton, Kenneth; Constance, Christian; Phaneuf, Denis-Carl; Shu, Daniel; Narvaez, Nancy Cardenas; Cañon, Claudia Olivares

2015-01-01

BACKGROUND Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE

NARCIS (Netherlands)

Ason, B.; Hoorn, J.W.A. van der; Chan, J.; Lee, E.; Pieterman, E.J.; Nguyen, K.K.; Di, M.; Shetterly, S.; Tang, J.; Yeh, W.C.; Schwarz, M.; Jukema, J.W.; Scott, R.; Wasserman, S.M.; Princen, H.M.G.; Jackson, S.

2014-01-01

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower

The PCSK9 decade

NARCIS (Netherlands)

Lambert, Gilles; Sjouke, Barbara; Choque, Benjamin; Kastelein, John J. P.; Hovingh, G. Kees

2012-01-01

PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) is a crucial protein in LDL cholesterol (LDL-C) metabolism by virtue of its pivotal role in the degradation of the LDL receptor. In recent years, both in vitro and in vivo studies have greatly supplemented our understanding of the (patho)

Identifying low density lipoprotein cholesterol associated variants in the Annexin A2 (ANXA2) gene

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Fairoozy, Roaa Hani; Cooper, Jackie; White, Jon

2017-01-01

Background and aims: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulat...

Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

Science.gov (United States)

Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

Exome sequencing finds a novel PCSK1 mutation in a child with generalized malabsorptive diarrhea and diabetes insipidus.

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Yourshaw, Michael; Solorzano-Vargas, R Sergio; Pickett, Lindsay A; Lindberg, Iris; Wang, Jiafang; Cortina, Galen; Pawlikowska-Haddal, Anna; Baron, Howard; Venick, Robert S; Nelson, Stanley F; Martín, Martín G

2013-12-01

Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis. We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry. Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis. Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations.

Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

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Mbikay Majambu

2008-06-01

Full Text Available Abstract Background Proprotein convertase subtilisin kexin-like 9 (PCSK9 is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC by negatively regulating low density lipoprotein receptor (LDLR levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men. Results Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013. Atorvastatin administration (HMGCoA reductase inhibitor significantly increased plasma PCSK9 (7.40%, p = 0.033 and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012. Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6× vs 1.5×, respectively at 10 μM, while fenofibrate did not induce changes in either. Conclusion These results suggest that in vivo (1 statins directly increase PCSK9 expression while (2 fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3 that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy

PCSK9: Regulation and Target for Drug Development for Dyslipidemia.

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Burke, Amy C; Dron, Jacqueline S; Hegele, Robert A; Huff, Murray W

2017-01-06

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic.

Regulation of PCSK9 by nutraceuticals.

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Momtazi, Amir Abbas; Banach, Maciej; Pirro, Matteo; Katsiki, Niki; Sahebkar, Amirhossein

2017-06-01

PCSK9 (proprotein convertase subtilisin kexin type 9) is a liver secretory enzyme that regulates plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR) density on the surface of hepatocytes. Inhibition of PCSK9 using monoclonal antibodies can efficiently lower plasma LDL-C, non-high-density lipoprotein cholesterol and lipoprotein (a). PCSK9 inhibition is also an effective adjunct to statin therapy; however, the cost-effectiveness of currently available PCSK9 inhibitors is under question. Nutraceuticals offer a safe and cost-effective option for PCSK9 inhibition. Several nutraceuticals have been reported to modulate PCSK9 levels and exert LDL-lowering activity. Mechanistically, those nutraceuticals that inhibit PCSK9 through a SREBP (sterol-responsive element binding protein)-independent pathway can be more effective in lowering plasma LDL-C levels compared with those inhibiting PCSK9 through the SREBP pathway. The present review aims to collect available data on the nutraceuticals with PCSK9-inhibitory effect and the underlying mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic Rescue of Glycosylation-deficient Fgf23 in the Galnt3 Knockout Mouse

OpenAIRE

Ichikawa, Shoji; Gray, Amie K.; Padgett, Leah R.; Allen, Matthew R.; Clinkenbeard, Erica L.; Sarpa, Nicole M.; White, Kenneth E.; Econs, Michael J.

2014-01-01

Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like proprotein convertase recognition sequence (176RHTR179↓) is protected by O-glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3 mutations render FGF23 susceptible to proteolysis, thereby reducing circulating intact hormone levels and leading to hyperphosphatemic familial tumoral calcinosis. To further delineat...

A novel method for direct measurement of complement convertases activity in human serum

NARCIS (Netherlands)

Blom, A.M.; Volokhina, E.B.; Fransson, V.; Stromberg, P.; Berghard, L.; Viktorelius, M.; Mollnes, T.E.; Lopez-Trascasa, M.; Heuvel, B. van den; Goodship, T.H.; Marchbank, K.J.; Okroj, M.

2014-01-01

Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or

Developmental expression of proprotein convertase 1/3 in the rat

DEFF Research Database (Denmark)

Lee, Y C; Damholt, A B; Billestrup, N

1999-01-01

demonstrated that it was relatively abundant in whole brain, lung and spleen, but not detectable in kidney, testis and heart. Using probes consisting of either the coding region or the 3' end sequences, the mRNA transcripts identified were 5.0, 3.0 and 8.5 kb. The 8.5 kb transcript detected has not been....../3 expression were detected in fetal lung, whereas low and constant expression was detected in fetal liver. Double immuno-staining showed that PC1/3 was co-localised with insulin throughout development, and at mid-gestation, PC1/3 immunoreactivity could also be detected within glucagon-producing cells...

The Crystal Structure of Cobra Venom Factor, a Cofactor for C3- and C5-Convertase CVFBb

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Vengadesan; Ponnuraj, Karthe; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V.L.; (Madras); (UAB)

2009-05-26

Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. Unlike the latter, CVFBb is a stable complex and an efficient C5 convertase. We solved the crystal structure of CVF, isolated from Naja naja kouthia venom, at 2.6 {angstrom} resolution. The CVF crystal structure, an intermediate between C3b and C3c, lacks the TED domain and has the CUB domain in an identical position to that seen in C3b. The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B.

Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

OpenAIRE

Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Nichols, Timothy C.; Camire, Rodney M.; Arruda, Valder R.

2016-01-01

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by fu...

Payer Perspectives on PCSK9 Inhibitors: A Conversation with Stephen Gorshow, MD, and James T. Kenney, RPh, MBA.

Science.gov (United States)

Mehr, Stanton R

2016-02-01

The new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can have significant budget effects, depending on the breadth of the US Food and Drug Administration (FDA)'s approved labeling. American Health & Drug Benefits asked Stephen Gorshow, MD, Regional Medical Director, UnitedHealthcare, and James T. Kenney, RPh, MBA, Manager, Specialty and Pharmacy Contracts, Harvard Pilgrim Health Care, to participate in a teleconference to better understand how payers are approaching the management of these agents.

Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

Science.gov (United States)

Bonde, Ylva; Breuer, Olof; Lütjohann, Dieter; Sjöberg, Stefan; Angelin, Bo; Rudling, Mats

2014-01-01

Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. PMID:25172631

Enzyme activity assays within microstructured optical fibers enabled by automated alignment.

Science.gov (United States)

Warren-Smith, Stephen C; Nie, Guiying; Schartner, Erik P; Salamonsen, Lois A; Monro, Tanya M

2012-12-01

A fluorescence-based enzyme activity assay has been demonstrated within a small-core microstructured optical fiber (MOF) for the first time. To achieve this, a reflection-based automated alignment system has been developed, which uses feedback and piezoelectric actuators to maintain optical alignment. The auto-alignment system provides optical stability for the time required to perform an activity assay. The chosen assay is based on the enzyme proprotein convertase 5/6 (PC6) and has important applications in women's health.

Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor

DEFF Research Database (Denmark)

Ugleholdt, Randi; Poulsen, Marie-Louise H; Holst, Peter J

2006-01-01

The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest. Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intesti......The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest. Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage....../3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells....

Increased half-life and enhanced potency of Fc-modified human PCSK9 monoclonal antibodies in primates.

Directory of Open Access Journals (Sweden)

Yijun Shen

Full Text Available Blocking proprotein convertase subtilisin kexin type 9 (PCSK9 binding to low-density lipoprotein receptor (LDLR can profoundly lower plasma LDL levels. Two anti-PCKS9 monoclonal antibodies (mAbs, alirocumab and evolocumab, were approved by the FDA in 2015. The recommended dose is 75 mg to 150 mg every two weeks for alirocumab and 140mg every two weeks or 420 mg once a month for evolocumab. This study attempted to improve the pharmacokinetic properties of F0016A, an IgG1 anti-PCKS9 mAb, to generate biologically superior molecules. We engineered several variants with two or three amino acid substitutions in the Fc fragment based on prior knowledge. The Fc-modified mAbs exhibited increased binding to FcRn, resulting in prolonged serum half-life and enhanced efficacy in vivo. These results demonstrate that Fc-modified anti-PCKS9 antibodies may enable less frequent or lower dosing of antibodies by improved recycling into the blood.

The role of proprotein convertase subtilisin/kexin type 9 inhibitors in ...

African Journals Online (AJOL)

antioxidant. Oxidative stress is believed to be a major cause of. Abstract ... density lipoprotein (LDL), increase the risk of cardiovascular disease. Familial ..... the working group on coronary pathophysiology and microcirculation of the. European ...

Zymogen Activation and Subcellular Activity of Subtilisin Kexin Isozyme 1/Site 1 Protease*

Science.gov (United States)

da Palma, Joel Ramos; Burri, Dominique Julien; Oppliger, Joël; Salamina, Marco; Cendron, Laura; de Laureto, Patrizia Polverino; Seidah, Nabil Georges; Kunz, Stefan; Pasquato, Antonella

2014-01-01

The proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) plays crucial roles in cellular homeostatic functions and is hijacked by pathogenic viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P involves sequential autocatalytic processing of its N-terminal prodomain at sites B′/B followed by the herein newly identified C′/C sites. We found that SKI-1/S1P autoprocessing results in intermediates whose catalytic domain remains associated with prodomain fragments of different lengths. In contrast to other zymogen proprotein convertases, all incompletely matured intermediates of SKI-1/S1P showed full catalytic activity toward cellular substrates, whereas optimal cleavage of viral glycoproteins depended on B′/B processing. Incompletely matured forms of SKI-1/S1P further process cellular and viral substrates in distinct subcellular compartments. Using a cell-based sensor for SKI-1/S1P activity, we found that 9 amino acid residues at the cleavage site (P1–P8) and P1′ are necessary and sufficient to define the subcellular location of processing and to determine to what extent processing of a substrate depends on SKI-1/S1P maturation. In sum, our study reveals novel and unexpected features of SKI-1/S1P zymogen activation and subcellular specificity of activity toward cellular and pathogen-derived substrates. PMID:25378398

Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

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Cariou Bertrand

2013-01-01

Full Text Available Abstract Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9 is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2 and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D patients that are more prone to develop insulin resistance, including: i acute post-prandial hyperlipidemic challenge (n=10, ii 4 days of high-fat (HF or high-fat/high-protein (HFHP (n=10, iii 7 (HFruc1, n=16 or 6 (HFruc2, n=9 days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1. Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05 in healthy volunteers and by 34% (p=0.001 in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p Conclusions Plasma PCSK9 concentrations vary

PCSK9 and triglyceride-rich lipoprotein metabolism.

Science.gov (United States)

Druce, I; Abujrad, H; Ooi, T C

2015-07-20

Pro-protein convertase subtilisin-kexin 9 (PCSK9) is known to affect low-density lipoprotein (LDL) metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipoproteins, especially triglyceride-rich lipoproteins (TRL). This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of (1) a correlation between plasma PCSK9 and triglyceride (TG) levels in health and disease, (2) a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, (3) an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, (4) an effect of PCSK9 on postprandial lipemia, (5) an effect of PCSK9 on adipose tissue biology, (6) an effect of PCSK9 on apolipoprotein B production from the liver and intestines, (7) an effect of PCSK9 on receptors other than low density lipoprotein receptor (LDLR) that are involved in TRL metabolism, and (8) an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge. © 2015 the Journal of Biomedical Research. All rights reserved.

Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin.

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Peng, Minhua; Watanabe, Satoru; Chan, Kitti Wing Ki; He, Qiuyan; Zhao, Ya; Zhang, Zhongde; Lai, Xiaoping; Luo, Dahai; Vasudevan, Subhash G; Li, Geng

2017-07-01

In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the "heat clearing" class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent advances in preventing stroke recurrence [version 1; referees: 2 approved

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J David Spence

2017-06-01

Full Text Available Recent advances in secondary stroke prevention include new evidence in hypertension, nutrition, anticoagulation, antiplatelet therapy, intracranial stenosis, percutaneous closure of patent foramen ovale, and lipid-lowering therapy. Individualized therapy for hypertension based on phenotyping with plasma renin and aldosterone markedly improves blood pressure control in patients with resistant hypertension. A Mediterranean diet can reduce the risk of stroke by nearly half. The diagnosis and treatment of metabolic vitamin B12 deficiency, and B vitamins to lower homocysteine, can reduce the risk of stroke by approximately 30%. There are problems with clopidogrel that can be overcome by using ticagrelor, and new anticoagulant drugs markedly improve anticoagulation for stroke prevention, particularly in atrial fibrillation. There are pharmacokinetic problems with dabigatran that deserve attention. Intensive medical therapy is better than stenting for intracranial stenosis, and new therapies directed at proprotein convertase subtilisin–kexin type 9 (PCSK9 will revolutionize lipid-lowering therapy. In the past, it was estimated that rational therapy could reduce recurrent stroke by about 80%. With recent advances, we should be able to do even better.

Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1

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Ugleholdt, Randi; Zhu, Xiaorong; Deacon, Carolyn F

2003-01-01

proglucagon processing showed marked defects. Tissue proglucagon levels in null mice were elevated, and proglucagon processing to glicentin, oxyntomodulin, and glucagon-like peptide-1 and -2 (GLP-1 and GLP-2) was markedly decreased, indicating that PC1 is essential for the processing of all the intestinal...... proglucagon cleavage sites. This includes the monobasic site R(77) and, thereby, production of mature, biologically active GLP-1. We also found elevated glucagon levels, suggesting that factors other than PC1 that are capable of processing to mature glucagon are present in the secretory granules of the L cell......The neuroendocrine prohormone convertases 1 and 2 (PC1 and PC2) are expressed in endocrine intestinal L cells and pancreatic A cells, respectively, and colocalize with proglucagon in secretory granules. Mice lacking PC2 have multiple endocrinopathies and cannot process proglucagon to mature...

The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Vengadesan [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Xu, Yuanyuan [Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Macon, Kevin [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Volanakis, John E. [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Narayana, Sthanam V. L., E-mail: narayana@uab.edu [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

2009-03-01

The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg{sup 2+}-dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein.

The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

International Nuclear Information System (INIS)

Krishnan, Vengadesan; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V. L.

2009-01-01

The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg 2+ -dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein

PCSK9 Antibodies for the Treatment of Hypercholesterolemia

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Ioanna Gouni-Berthold

2014-12-01

Full Text Available The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9 binds to the low-density lipoprotein (LDL receptor (LDLR and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145 and alirocumab (REGN727/SAR236553, have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk.

PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

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Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

2017-09-01

Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

Sensitive radiometric assay for enkephalin convertase and other carboxypeptidase B-like enzymes

International Nuclear Information System (INIS)

Stack, G.; Fricker, L.D.; Snyder, S.H.

1984-01-01

A sensitive radiometric assay for carboxypeptidase B-like enzymes has been developed using enkephalin convertase, an enkephalin synthesizing carboxypeptidase. The assay is based on the differential solubility of 3 H-labeled substrate and product in chloroform. The substrates 3 H-benzoyl-Phe-Ala-Arg or 3 H-benzoyl-Phe-Leu-Arg are poorly soluble in chloroform due to the charged arginine. The products of carboxypeptidase B-like activity on these substrates, 3 H-benzoyl-Phe-Ala or 3 H-benzoyl Phe-Leu partition quantitatively into chloroform, allowing rapid separation of product from substrate. This assay is approximately 100 times more sensitive than a similar fluorometric assay utilizing dansyl-Phe-Ala-Arg as a substrate

Sensitive radiometric assay for enkephalin convertase and other carboxypeptidase B-like enzymes

Energy Technology Data Exchange (ETDEWEB)

Stack, G.; Fricker, L.D.; Snyder, S.H.

1984-01-09

A sensitive radiometric assay for carboxypeptidase B-like enzymes has been developed using enkephalin convertase, an enkephalin synthesizing carboxypeptidase. The assay is based on the differential solubility of /sup 3/H-labeled substrate and product in chloroform. The substrates /sup 3/H-benzoyl-Phe-Ala-Arg or /sup 3/H-benzoyl-Phe-Leu-Arg are poorly soluble in chloroform due to the charged arginine. The products of carboxypeptidase B-like activity on these substrates, /sup 3/H-benzoyl-Phe-Ala or /sup 3/H-benzoyl Phe-Leu partition quantitatively into chloroform, allowing rapid separation of product from substrate. This assay is approximately 100 times more sensitive than a similar fluorometric assay utilizing dansyl-Phe-Ala-Arg as a substrate.

Circulating PCSK9 is lowered acutely following surgery.

Science.gov (United States)

Druce, Irena; Abujrad, Hussein; Chaker, Seham; Meggison, Hilary; Hill, Andrew; Raymond, Angela; Mayne, Janice; Ooi, Teik Chye

2017-11-17

A decrease in serum low-density lipoprotein cholesterol (LDL-C) is well documented after acute stress. Plasma proprotein convertase subtilisin kexin 9 (PCSK9), which promotes degradation of low-density lipoprotein receptor (LDL-R) resulting in reduced plasma clearance of low-density lipoproteins (LDL) and an increase in serum LDL-C, would be predicted to decrease. Yet, a few studies have demonstrated an increase 1-8 days after acute stress. Our objective was to assess the earlier status of plasma PCSK9, within the first 24 hours of onset of stress. We measured serum lipids and plasma PCSK9 in 39 patients before and soon after an elective surgical procedure (abdominal aortic aneurysm (AAA) repair). We observed an early decrease in PCSK9 following surgery, as well as a decrease in total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TG). Unlike other studies which showed an increase in PCSK9 after the onset of stress, our study detected a fall in PCSK9 following acute surgical stress. The observed difference is likely due to the earlier timing of PCSK9 measurement in our study. Further studies involving serial poststress measurements for several days are needed to determine whether PCSK9 behaves as an acute-phase reactant, whether it displays a biphasic response to acute stress, and whether changes in circulating PCSK9 are responsible for lipoprotein changes observed after surgical stress. (Clinical Trial Registration: ClinicalTrials.gov study ID NCT00493389). © 2017 Wiley Periodicals, Inc.

Cardiology update 2017: The first quarter

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Sridharan Umapathy

2017-01-01

Full Text Available In the first quarter of 2017, proprotein convertase subtilisin/kexin type 9's role got defined further with a number of trials such as FOURIER, ORION-1, and SPIRE 1 and 2. TAVI proves safe in intermediate-risk patients in the Surgical Replacement and Transcatheter Aortic Valve Implantation study. Newer anticoagulants extended their role to valvular heart disease. Bioabsorbable stent showed problems (ABSORB 2 and 3. New guidelines have been released for syncope and transcatheter aortic valve replacement implantation. Clinical outcome studies involving instantaneous wave-free ratio (IFR showed IFR to be noninferior to fractional flow reserve. Optimal medical therapy proves noninferior to percutaneous coronary intervention in single vessel chronic total occlusion.

[PCSK-9 inhibitors, effects on LDL-C and future implications: What you should know].

Science.gov (United States)

Corral, P; Ruiz, A J

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in 2003 in families with familial hypercholesterolemia (HF) later generated the development of pharmacological strategies in order to inhibit this protein. Twelve years after this discovery, the first two biological compounds (monoclonal antibodies) were approved, which have been shown to substantially decrease LDL-C and other lipid subfractions. The objective of the present article is to review the history of the discovery of PCSK9, its physiology and pathophysiology and subsequent pharmacological development. The objectives and goals reached to date and the pending questions regarding the efficacy and safety of its clinical use are presented. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases

International Nuclear Information System (INIS)

Rimoldi, M.T.; Sher, A.; Heiny, A.; Lituchy, A.; Hammer, C.H.; Joiner, K.

1988-01-01

The authors recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 99 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also activate the alternative pathway poorly, might produce a molecule capable of interfering with factor B binding to C3b. They now demonstrate that CMT and TCT lysates, as well as molecules spontaneously shed from CMT and TCT but not Epi, accelerate decay of 125 I-labeled factor Bb from the alternative-pathway C3 convertase (C3bBb) assembled on zymosan or Epi and also accelerate decay of the classical-pathway C3 convertase (C4b2a) on sheep erythrocytes. Parasites metabolically labeled with [ 35 S]methionine spontaneously shed a limited number of radioactive components, ranging in molecular mass from 86 to 155 kDa for trypomastigotes and 25 to 80 kDa for Epi. Decay-accelerating activity within supernatants is inactivated by papain and is coeluted with 35 S-containing polypeptides on FPLC anion-exchange chromatography, suggesting that the active constituents are protein molecules. Molecules with decay-accelerating activity may explain the developmentally regulated resistance to complement-mediated lysis in infective and vertebrate stages for T. cruzi life cycle

Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

Science.gov (United States)

Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway

DEFF Research Database (Denmark)

Møller-Kristensen, Mette; Thiel, Steffen; Sjöholm, Anders

2007-01-01

The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-pha....... Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration...

Circulating PCSK9 affects serum LDL and cholesterol levels more than SREBP-2 expression.

Science.gov (United States)

Mohammadi, Asghar; Shabani, Mohamad; Naseri, Faezeh; Hosseni, Bita; Soltanmohammadi, Elham; Piran, Sadegh; Najafi, Mohammad

2017-07-01

Cholesterol homeostasis is dependent upon the sterol regulatory element binding protein 2 (SREBP-2) regulatory system and the functioning of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). Many studies have also reported that low density lipoprotein receptor (LDLR) levels in cellular membranes are related to the functioning of these proteins. The aim of this study was to investigate the association of lipid profiles with circulating PCSK9 protein values and SREBP-2 expression levels in normal subjects. The study involved 120 randomly chosen healthy subjects. Their lipid profiles were measured using routine laboratory techniques, and the plasma PCSK9 protein and SREBP-2 expression levels were determined by ELISA and real time quantitative PCR methods, respectively. A statistical analysis was carried out using a statistical software package. Linear regression analyses showed a significant correlation between total cholesterol and PCSK9 (3.54 ± 1.31 ng/mL), as well as between total cholesterol and SREBP-2 (0.1-35.38) (p = 0.002 and p = 0.02, respectively). Furthermore, multiple regression analyses showed strict correlations between PCSK9 and cholesterol-related parameters especially the total cholesterol/HDL-C ratio (β = 3.53, p = 0.001). There was no significant correlation between circulating PCSK9 and SREBP-2 expression levels (r = 1.2, p = 0.3). The study results revealed that serum cholesterol-related parameters are strictly associated with plasma PCSK9 values, suggesting that PCSK9 function has a greater effect on serum total cholesterol levels than SREBP-2 expression does. Furthermore, the total cholesterol/HDL-C ratio was a better indicator for evaluating PCSK9 level than total cholesterol.

Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte activation by decreasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone.

Science.gov (United States)

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2014-12-01

Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The mechanism by which a propeptide-encoded pH sensor regulates spatiotemporal activation of furin.

Science.gov (United States)

Williamson, Danielle M; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

2013-06-28

The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation.

The Mechanism by Which a Propeptide-encoded pH Sensor Regulates Spatiotemporal Activation of Furin*

Science.gov (United States)

Williamson, Danielle M.; Elferich, Johannes; Ramakrishnan, Parvathy; Thomas, Gary; Shinde, Ujwal

2013-01-01

The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation. PMID:23653353

Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

Directory of Open Access Journals (Sweden)

Beth A. Taylor

2014-01-01

Full Text Available The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9 levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4% were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5% and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%. Free PCSK9 was marginally higher in nonresponders at baseline (P=0.07 and significantly higher in atorvastatin responders after 6 months of treatment (P=0.04. The change in free PCSK9 over 6 months with statin treatment was higher (P<0.01 in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy than in either the nonresponders (39.9 ± 87.8 ng/mL or placebo subjects (27.8 ± 97.6 ng/mL. Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment.

Tissue distribution and effects of fasting and obesity on the ghrelin axis in mice.

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Morash, Michael G; Gagnon, Jeffrey; Nelson, Stephanie; Anini, Younes

2010-08-09

Ghrelin is a 28 amino acid peptide hormone derived from the 117 amino acid proghrelin, following cleavage by proprotein convertase 1 (PC1). In this study, we comprehensively assessed the tissue distribution and the effect of fasting and obesity on preproghrelin, Exon-4D, PC1 and GOAT expression and proghrelin-derived peptide (PGDP) secretion. The stomach was the major source of preproghrelin expression and PDGPs, followed by the small intestine. The remaining peripheral tissues (including the brain and pancreas) contained negligible expression levels. We detected obestatin in all stomach proghrelin cells, however, 22% of proghrelin cells in the small intestine did not express obestatin. There were strain differences in ghrelin secretion in response to fasting between CD1 and C57BL/6 mice. After a 24 hour-fast, CD1 mice had increased plasma levels of total ghrelin and obestatin with no change in preproghrelin mRNA or PGDP tissues levels. C57BL/6 mice showed a different response to a 24 hour-fast having increased proghrelin mRNA expression, stomach acylated ghrelin peptide and no change in plasma obestatin in C57BL/6 mice. In obese mice (ob/ob and diet-induced obesity (DIO)) there was a significant increase in preproghrelin mRNA levels while tissue and plasma PGDP levels were significantly reduced. Fasting did not affect PGDP in obese mice. Obese models displayed differences in GOAT expression, which was elevated in DIO mice, but reduced in ob/ob mice. We did not find co-localization of the leptin receptor in ghrelin expressing stomach cells, ruling out a direct effect of leptin on stomach ghrelin synthesis and secretion. Copyright (c) 2010 Elsevier B.V. All rights reserved.

The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16.

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Dundar, Halil; Brede, Dag A; La Rosa, Sabina Leanti; El-Gendy, Ahmed Osama; Diep, Dzung B; Nes, Ingolf F

2015-07-01

A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. The fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelE-sprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the

Chemical structure and properties of low-molecular furin inhibitors

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T. V. Osadchuk

2016-12-01

Full Text Available The review is devoted to the analysis of the relationship between a chemical structure and properties of low-molecular weight inhibitors of furin, the most studied proprotein convertase, which is involved in the development of some pathologies, such as oncologic diseases, viral and bacterial infections, etc. The latest data concerning the influence of peptides, pseudo-peptides, aromatic and heterocyclic compounds, some natural ones such as flavonoids, coumarins, and others on enzyme inactivation are considered. The power of furin inhibition is shown to rise with the increasing number of positively charged groups in the structure of these compounds. Peptidomimetics (Ki = 5-8 pM are shown to be the most effective furin inhibitors. The synthesized substances, however, have not been used in practical application yet. Nowadays it is very important to find more selective inhibitors, improve their stability, bioavailability and safety for the human organism.

PCSK9: From Basic Science Discoveries to Clinical Trials.

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Shapiro, Michael D; Tavori, Hagai; Fazio, Sergio

2018-05-11

Unknown 15 years ago, PCSK9 (proprotein convertase subtilisin/kexin type 9) is now common parlance among scientists and clinicians interested in prevention and treatment of atherosclerotic cardiovascular disease. What makes this story so special is not its recent discovery nor the fact that it uncovered previously unknown biology but rather that these important scientific insights have been translated into an effective medical therapy in record time. Indeed, the translation of this discovery to novel therapeutic serves as one of the best examples of how genetic insights can be leveraged into intelligent target drug discovery. The PCSK9 saga is unfolding quickly but is far from complete. Here, we review major scientific understandings as they relate to the role of PCSK9 in lipoprotein metabolism and atherosclerotic cardiovascular disease and the impact that therapies designed to inhibit its action are having in the clinical setting. © 2018 American Heart Association, Inc.

Spatiotemporal expression of endogenous opioid processing enzymes in mouse uterus at peri-implantation.

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Wu, Weiwei; Kong, Shuangbo; Wang, Bingyan; Chen, Yongjie; Wang, Haibin

2016-02-01

Successful implantation requires intimate interactions between a competent blastocyst and a receptive uterus. We recently demonstrated that the aberrant activation of opioid signaling by exogenous ligands adversely affects preimplantation embryonic development and subsequent implantation in mice. However, the underlying machinery governing the dynamic homeostasis of the endogenous opioid system in the uterus during early pregnancy remains elusive. We now show that all three major endogenous opioid precursors are spatiotemporally expressed in the uterus during early pregnancy. Moreover, we observe the well-coordinated expression of the synthetic enzyme prohormone convertases 1/3 (PC1/3) at lower levels and of its inhibitor proprotein convertase subtilisin/kexin type 1 inhibitor (Pcsk1n) and the degrading enzyme membrane metallo-endopeptidase (MME) at higher levels in the receptive uterus. Both estrogen and progestin tend to reduce the uterine levels of opioid ligand precursors in the ovariectomized mouse model. This tight regulation of the endogenous opioid system by PC1/3, Pcsk1n and MME has been further confirmed in physiologically related pseudopregnancy and delayed implantation mouse models. The coordinated regulation of opioid precursor biosynthesis and metabolism helps to create appropriate opioid signaling ensuring uterine receptivity for implantation. Thus, endogenous uterine opioid levels are primarily determined by the coordinated expressions of PC1/3, Pcsk1n and MME under the influence of ovarian progestin and estrogen. Our findings raise an additional cautionary note regarding the effects of opioid abuse on early pregnancy events.

Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II-Induced Abdominal Aortic Aneurysms in C57BL/6 Mice-Brief Report.

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Lu, Hong; Howatt, Deborah A; Balakrishnan, Anju; Graham, Mark J; Mullick, Adam E; Daugherty, Alan

2016-09-01

Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was to determine whether infection of normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation of mouse PCSK9 increased angiotensin II (AngII)-induced abdominal aortic aneurysms. In an initial study, male C57BL/6 mice were injected intraperitoneally with either an empty vector or PCSK9 gain-of-function mutation (D377Y). AAV at 3 doses and fed a saturated fat-enriched diet for 6 weeks. Two weeks after AAV injection, mice were infused with AngII for 4 weeks. Plasma PCSK9 concentrations were increased dose dependently in mice injected with AAV containing PCSK9D377Y mutation and positively associated with elevations of plasma cholesterol concentrations. Infection with intermediate and high doses of PCSK9D377Y.AAV led to equivalent increases of maximal width of abdominal aortas in C57BL/6 mice infused with AngII. Therefore, the intermediate dose was used in subsequent experiments. We then determined effects of PCSK9D377Y.AAV infection on 5 normolipidemic mouse strains, demonstrating that C57BL/6 mice were the most susceptible to this AAV infection. PCSK9D377Y.AAV infected male C57BL/6 mice were also compared with age-matched male low-density lipoprotein receptor(-/-) mice. Although plasma cholesterol concentrations were lower in mice infected with PCSK9D377Y.AAV, these mice had equivalent abdominal aortic aneurysmal formation, compared to low-density lipoprotein receptor(-/-) mice. In a separate study, reduced plasma PCSK9 concentrations by PCSK9 antisense oligonucleotides in male low-density lipoprotein receptor(-/-) mice did not influence AngII-induced abdominal aortic aneurysms. AAV-mediated infection with a mouse PCSK9 gain-of-function mutation is a rapid, easy, and efficient approach for inducing hypercholesterolemia and promoting abdominal aortic aneurysms in C57BL/6 mice infused with Ang

Rational Design of a Highly Potent and Selective Peptide Inhibitor of PACE4 by Salt Bridge Interaction with D160 at Position P3.

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Dianati, Vahid; Shamloo, Azar; Kwiatkowska, Anna; Desjardins, Roxane; Soldera, Armand; Day, Robert; Dory, Yves L

2017-08-08

PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH 2 . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal. Moreover, the β-branched nature of the new P3 residue favors the extended β-sheet conformation usually associated with substrates of proteases. This work provides new insight for better understanding of β-sheet backbone-backbone interactions between serine proteases and their peptidic ligands. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

PCSK9 Inhibitors: Treating the Right Patients in Daily Practice.

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King, Peta; Nicholls, Stephen J

2017-08-01

Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as a novel approach to low-density lipoprotein cholesterol (LDL-C) lowering. The potential role of PCSK9 inhibitors in clinical practice will be reviewed. Clinical trials have demonstrated that PCSK9 inhibitors produce robust LDL-C lowering when administered either as monotherapy or in combination with statins. This provides the opportunity to achieve effective lipid lowering in familial hypercholesterolemia, patients with either established atherosclerotic cardiovascular disease or high risk primary prevention and an important opportunity to treat patients with statin intolerance. The findings from plaque imaging and patients with established atherosclerotic cardiovascular disease suggest that PCSK9 inhibition has favorable outcomes beyond improving lipid profiles, which has the opportunity to expand their use. PCSK9 inhibitors represent a new approach to achieving effective cardiovascular risk reduction in a broader number of patients. How these agents will be taken up in clinical practice remains to be determined.

A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics

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Jeffrey E Ming

2017-06-01

Full Text Available Reduction in low-density lipoprotein cholesterol (LDL-C is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9, significantly reduces LDL-C. Here, we report development of a quantitative systems pharmacology (QSP model integrating peripheral and liver cholesterol metabolism, as well as PCSK9 function, to examine the mechanisms of action of alirocumab and other lipid-lowering therapies, including statins. The model predicts changes in LDL-C and other lipids that are consistent with effects observed in clinical trials of single or combined treatments of alirocumab and other treatments. An exploratory model to examine the effects of lipid levels on plaque dynamics was also developed. The QSP platform, on further development and qualification, may support dose optimization and clinical trial design for PCSK9 inhibitors and lipid-modulating drugs. It may also improve our understanding of factors affecting therapeutic responses in different phenotypes of dyslipidemia and cardiovascular disease.

PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis

DEFF Research Database (Denmark)

Langsted, Anne; Nordestgaard, Børge; Benn, Marianne

2016-01-01

CONTEXT: Novel, low-density lipoprotein (LDL) cholesterol-lowering proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors also lower lipoprotein(a) levels, but the effect on aortic valve stenosis and myocardial infarction is unknown. OBJECTIVE: We tested the hypothesis that the PCSK9 R46L...... individuals of Danish descent. PARTICIPANTS: We studied 103 083 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease Study. MAIN OUTCOME MEASURES: Lipoprotein(a), LDL cholesterol, and PCSK9 R46L genotype and diagnoses of aortic...... P = .02). The corresponding values for LDL cholesterol levels were 124 (101-147) mg/dl, 104 (85-132) mg/dl, and 97 (85-128) mg/dl, respectively (trend P = 2 × 10(-52)). PCSK9 R46L carriers vs noncarriers had an age- and sex-adjusted odds ratio of 0.64 (95% confidence interval, 0.44-0.95) for aortic...

O-Glycosylation Modulates Proprotein Convertase Activation of Angiopoietin-like Protein 3: POSSIBLE ROLE OF POLYPEPTIDE GalNAc-TRANSFERASE-2 IN REGULATION OF CONCENTRATIONS OF PLASMA LIPIDS

DEFF Research Database (Denmark)

Schjoldager, Katrine Ter-Borch Gram; Vester-Christensen, Malene B; Bennett, Eric Paul

2010-01-01

immediately C-terminal (TT(226)). We developed an in vivo model system in CHO ldlD cells that was used to show that O-glycosylation in the processing site blocked processing of ANGPTL3. Genome-wide SNP association studies have identified the polypeptide GalNAc-transferase gene, GALNT2, as a candidate gene...... for low HDL and high triglyceride blood levels. We hypothesized that the GalNAc-T2 transferase performed critical O-glycosylation of proteins involved in lipid metabolism. Screening of a panel of proteins known to affect lipid metabolism for potential sites glycosylated by GalNAc-T2 led to identification...

My Approach to the Patient With Familial Hypercholesterolemia

Science.gov (United States)

Safarova, Maya S.; Kullo, Iftikhar J.

2017-01-01

Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C–lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance. PMID:27261867

Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

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Nabil G Seidah

Full Text Available Proprotein convertase subtilisin/kexin-9 (PCSK9 enhances the degradation of hepatic low-density lipoprotein receptor (LDLR. Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2 as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/- mice revealed: i a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/- tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

Antibodies to watch in 2014.

Science.gov (United States)

Reichert, Janice M

2014-01-01

Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed.

Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution of Bioactive Furin and PC7

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Pierpaolo Ginefra

2018-02-01

Full Text Available Furin trafficking, and that of related proprotein convertases (PCs, may regulate which substrates are accessible for endoproteolysis, but tools to directly test this hypothesis have been lacking. Here, we develop targeted biosensors that indicate Furin activity in endosomes is 10-fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched >3-fold in endosomes compared to the trans-Golgi network (TGN. Endogenous PC7, which resists this inhibitor, was active in distinct vesicles. Only overexpressed PC7 activity reached the cell surface, endosomes, and the TGN. A PLC motif in the cytosolic tail of PC7 was dispensable for endosomal activity, but it was specifically required for TGN recycling and to rescue proActivin-A cleavage in Furin-depleted B16F1 melanoma cells. In sharp contrast, PC7 complemented Furin in cleaving Notch1 independently of PLC-mediated TGN access. Our study provides a proof in principle that compartment-specific biosensors can be used to gain insight into the regulation of PC trafficking and to map the tropism of PC-specific inhibitors.

Evolution of sequence-defined highly functionalized nucleic acid polymers

Science.gov (United States)

Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

2018-03-01

The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

International Nuclear Information System (INIS)

Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel; Igonet, Sebastien; Oldstone, Michael B.A.; Kunz, Stefan

2013-01-01

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

Energy Technology Data Exchange (ETDEWEB)

Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel [Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland); Igonet, Sebastien; Oldstone, Michael B.A. [Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 (United States); Kunz, Stefan, E-mail: Stefan.Kunz@chuv.ch [Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland)

2013-02-05

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

The Potential Mechanisms of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease

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Xiaopeng Zhu

2016-10-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR, a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9 expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research.

Opposite Roles of Furin and PC5A in N-Cadherin Processing

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Deborah Maret

2012-10-01

Full Text Available We recently demonstrated that lack of Furin-processing of the N-cadherin precursor (proNCAD in highly invasive melanoma and brain tumor cells results in the cell-surface expression of a nonadhesive protein favoring cell migration and invasion in vitro. Quantitative polymerase chain reaction analysis of malignant human brain tumor cells revealed that of all proprotein convertases (PCs only the levels of Furin and PC5A are modulated, being inversely (Furin or directly (PC5A correlated with brain tumor invasive capacity. Intriguingly, the N-terminal sequence following the Furin-activated NCAD site (RQKR↓DW161, mouse nomenclature reveals a second putative PC-processing site (RIRSDR↓DK189 located in the first extracellular domain. Cleavage at this site would abolish the adhesive functions of NCAD because of the loss of the critical Trp161. This was confirmed upon analysis of the fate of the endogenous prosegment of proNCAD in human malignant glioma cells expressing high levels of Furin and low levels of PC5A (U343 or high levels of PC5A and negligible Furin levels (U251. Cellular analyses revealed that Furin is the best activating convertase releasing an ∼17-kDa prosegment, whereas PC5A is the major inactivating enzyme resulting in the secretion of an ∼20-kDa product. Like expression of proNCAD at the cell surface, cleavage of the NCAD molecule at RIRSDR↓DK189 renders the U251 cancer cells less adhesive to one another and more migratory. Our work modifies the present view on posttranslational processing and surface expression of classic cadherins and clarifies how NCAD possesses a range of adhesive potentials and plays a critical role in tumor progression.

Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations.

Science.gov (United States)

Cai, Xiao-hui; Zhang, Qing; Ding, Da-fu

2004-12-01

To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newly published X-ray crystallographical structures of mouse furin and yeast kexin as templates. The electrostatic interaction energy of each complex was calculated and the results were compared with the experimentally determined inhibition constants to find the correlation between them. High quality models of furin/kexin-eglin c mutants were obtained and used for calculation of the electrostatic interaction energies between the proteases and their inhibitors. The calculated electrostatic energies of interaction showed a linear correlation to the experimental inhibition constants. The modeled structures give good explanations of the specificity of eglin c mutants to furin/kexin. The electrostatic interactions play important roles in inhibitory activity of eglin c mutants to furin/kexin. The results presented here provided quantitative structural and functional information concerning the role of the charge-charge interactions in the binding of furin/kexin and their inhibitors.

Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

Science.gov (United States)

Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

2015-01-01

Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

[New agents for hypercholesterolemia].

Science.gov (United States)

Pintó, Xavier; García Gómez, María Carmen

2016-02-19

An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

PCSK9 Induces CD36 Degradation and Affects Long-Chain Fatty Acid Uptake and Triglyceride Metabolism in Adipocytes and in Mouse Liver.

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Demers, Annie; Samami, Samaneh; Lauzier, Benjamin; Des Rosiers, Christine; Ngo Sock, Emilienne Tudor; Ong, Huy; Mayer, Gaetan

2015-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptor thereby elevating plasma low-density lipoprotein cholesterol levels and the risk of coronary heart disease. Thus, the use of PCSK9 inhibitors holds great promise to prevent heart disease. Previous work found that PCSK9 is involved in triglyceride metabolism, independently of its action on low-density lipoprotein receptor, and that other yet unidentified receptors could mediate this effect. Therefore, we assessed whether PCSK9 enhances the degradation of CD36, a major receptor involved in transport of long-chain fatty acids and triglyceride storage. Overexpressed or recombinant PCSK9 induced CD36 degradation in cell lines and primary adipocytes and reduced the uptake of the palmitate analog Bodipy FL C16 and oxidized low-density lipoprotein in 3T3-L1 adipocytes and hepatic HepG2 cells, respectively. Surface plasmon resonance, coimmunoprecipitation, confocal immunofluorescence microscopy, and protein degradation pathway inhibitors revealed that PCSK9 directly interacts with CD36 and targets the receptor to lysosomes through a mechanism involving the proteasome. Importantly, the level of CD36 protein was increased by >3-fold upon small interfering RNA knockdown of endogenous PCSK9 in hepatic cells and similarly increased in the liver and visceral adipose tissue of Pcsk9(-/-) mice. In Pcsk9(-/-) mice, increased hepatic CD36 was correlated with an amplified uptake of fatty acid and accumulation of triglycerides and lipid droplets. Our results demonstrate an important role of PCSK9 in modulating the function of CD36 and triglyceride metabolism. PCSK9-mediated CD36 degradation may serve to limit fatty acid uptake and triglyceride accumulation in tissues, such as the liver. © 2015 American Heart Association, Inc.

Molecular cloning and characterization of prohormone convertase 1 gene in abalone (Haliotis diversicolor supertexta).

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Zhou, Jin; Cai, Zhong-hua

2010-03-01

Prohormone convertases (PCs) are calcium-dependent serine endoproteases of the subtilisin family that play a key role in the posttranslational processing of precursors for bioactive peptides. In this study, the cDNA of PC1 from abalone (Haliotis diversicolor supertexta) was cloned and sequenced. The PC1 cDNA consisted of 2216 bp with an open reading frame of 2010 bp encoding a 670 amino acid peptide. Comparative structural analysis revealed that abalone PC1 shared high similarity and identity with most PC counterparts. The profile of deduced peptide of PC1 was composed of an N-terminal signal peptide, a prosegment domain, a catalytic domain and a P domain, which were common in many species. Sequence analysis indicated that the abalone PC1 was highly conserved in catalytic domain, including three conserved serine catalytic signatures that comprised a catalytic triad active center. Also conserved were the potential cleavage site for release of the mature peptide, a cognate integrin binding site RGD in P domain, and four cysteine residues involved in forming an intrachain disulfide bridge. To further investigate the functions of PC1 in abalone, real-time quantitative PCR was performed to determine the expression level of this gene at three different reproduction stages (i.e. pre-, during- and post-breeding). Results indicated that PC1 was expressed throughout the three stages but the expression levels varied with the timepoints and different tissues in abalone. The expression levels of PC1 in digestive gland were much higher than those of the gonad. In female abalone, the expression of PC1 was higher at pre-breeding and during-breeding stages (Pabalone reproduction process (e.g. spawning or sperming). PC1 is a potential prohormone processing enzyme and it may play a critical role in abalone physiological processes related to reproduction. 2009 Elsevier Inc. All rights reserved.

Bioinformatics-Aided Venomics

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Quentin Kaas

2015-06-01

Full Text Available Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future.

The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes

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Shepherd, Dawn; Booth, Sarah; Waithe, Dominic; Reis e Sousa, Caetano

2015-01-01

TLR7 mediates innate immune responses to viral RNA in endocytic compartments. Mouse and human (h)TLR7 undergo proteolytic cleavage, resulting in the generation of a C-terminal fragment that accumulates in endosomes and associates with the signaling adaptor MyD88 upon receptor triggering by TLR7 agonists. Although mouse TLR7 is cleaved in endosomes by acidic proteases, hTLR7 processing can occur at neutral pH throughout the secretory pathway through the activity of furin-like proprotein convertases. However, the mechanisms by which cleaved hTLR7 reaches the endosomal compartment remain unclear. In this study, we demonstrate that, after hTLR7 proteolytic processing, the liberated amino (N)-terminal fragment remains bound to the C terminus through disulfide bonds and provides key trafficking information that ensures correct delivery of the complex to endosomal compartments. In the absence of the N-terminal fragment, the C-terminal fragment is redirected to the cell surface, where it is functionally inactive. Our data reveal a novel role for the N terminus of hTLR7 as a molecular chaperone that provides processed hTLR7 with the correct targeting instructions to reach the endosomal compartment, hence ensuring its biological activity and preventing inadvertent cell surface responses to self-RNA. PMID:25917086

Statin non-adherence and residual cardiovascular risk: There is need for substantial improvement.

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Banach, Maciej; Stulc, Tomas; Dent, Ricardo; Toth, Peter P

2016-12-15

Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies.

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Parhofer, Klaus G; Barrett, P Hugh R

2006-08-01

Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.

Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

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Dennis Löffler

2017-03-01

Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System.

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Alain Le Coupanec

Full Text Available Human coronaviruses (HCoV are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43. In an attempt to study the role of this protein in virus spread within the central nervous system (CNS and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G758 to RRSR↓R758, which introduces a putative furin-like cleavage (↓ site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies.

Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice

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Karin eTein

2015-08-01

Full Text Available BackgroundMutations in WFS1 gene cause Wolfram syndrome, which is a rare autosomal recessive disorder, characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy and deafness (DIDMOAD. The WFS1 gene product wolframin is located in the endoplasmic reticulum. Mice lacking this gene exhibit disturbances in the processing and secretion of peptides, such as vasopressin and insulin. In the brain, high levels of the wolframin protein have been observed in the hippocampus, amygdala and limbic structures. The aim of this study was to investigate the effect of Wfs1 knockout on peptide processing in mouse hippocampus. A peptidomic approach was used to characterize individual peptides in the hippocampus of wild-type and Wfs1 knockout mice. ResultsWe identified 126 peptides in hippocampal extracts and the levels of 10 peptides differed between Wfs1 KO and wild-type mice at P<0.05. The peptide with the largest alteration was little-LEN, which level was 25 times higher in the hippocampus of Wfs1 KO mice compared to wild-type mice. Processing (cleavage of little-LEN from the Pcsk1n gene product proSAAS involves prohormone convertase 2 (PC2. Thus, PC2 activity was measured in extracts prepared from the hippocampus of Wfs1 knockout mice. The activity of PC2 in Wfs1 mutant mice was significantly higher (149.9±2.3%, p<0.0001, n=8 than in wild-type mice (100.0±7.0%, n=8. However, Western blot analysis showed that protein levels of 7B2, proPC2 and PC2 were same in both groups, and so were gene expression levels.ConclusionsProcessing of proSAAS is altered in the hippocampus of Wfs1-KO mice, which is caused by increased activity of PC2. Increased activity of PC2 in Wfs1 knockout mice is not caused by alteration in the levels of PC2 protein. Our results suggest a functional link between Wfs1 and PC2. Thus, the detailed molecular mechanism of the role of Wfs1 in the regulation of PC2 activity needs further investigation.

Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

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Anna Maisa

2009-06-01

Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

Emerging biologic therapies for hypercholesterolaemia.

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Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Genetics of Dyslipidemia and Ischemic Heart Disease.

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Sharma, Kavita; Baliga, Ragavendra R

2017-05-01

Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian children.

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Arama, Charles; Diarra, Issa; Kouriba, Bourèma; Sirois, Francine; Fedoryak, Olesya; Thera, Mahamadou A; Coulibaly, Drissa; Lyke, Kirsten E; Plowe, Christopher V; Chrétien, Michel; Doumbo, Ogobara K; Mbikay, Majambu

2018-01-01

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a hepatic secretory protein which promotes the degradation of low-density lipoprotein receptors leading to reduced hepatic uptake of plasma cholesterol. Non-synonymous single-nucleotide polymorphisms in its gene have been linked to hypo- or hyper- cholesterolemia, depending on whether they decrease or increase PCSK9 activity, respectively. Since the proliferation and the infectivity of Plasmodium spp. partially depend on cholesterol from the host, we hypothesize that these PCSK9 genetic polymorphisms could influence the course of malaria infection in individuals who carry them. Here we examined the frequency distribution of one dominant (C679X) and two recessive (A443T, I474V) hypocholesterolemic polymorphisms as well as that of one recessive hypercholesterolemic polymorphism (E670G) among healthy and malaria-infected Malian children. Dried blood spots were collected in Bandiagara, Mali, from 752 age, residence and ethnicity-matched children: 253 healthy controls, 246 uncomplicated malaria patients and 253 severe malaria patients. Their genomic DNA was extracted and genotyped for the above PCSK9 polymorphisms using Taqman assays. Associations of genotype distributions and allele frequencies with malaria were evaluated. The minor allele frequency of the A443T, I474V, E670G, and C679X polymorphisms in the study population sample was 0.12, 0.20, 0.26, and 0.02, respectively. For each polymorphism, the genotype distribution among the three health conditions was statistically insignificant, but for the hypercholesterolemic E670G polymorphism, a trend towards association of the minor allele with malaria severity was observed (P = 0.035). The association proved to be stronger when allele frequencies between healthy controls and severe malaria cases were compared (Odd Ratio: 1.34; 95% Confidence Intervals: 1.04-1.83); P = 0.031). Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible

Pituitary adenylate cyclase-activating polypeptide precursor is processed solely by prohormone convertase 4 in the gonads.

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Li, M; Mbikay, M; Arimura, A

2000-10-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is abundant not only in the brain, but also in the testis. Immunohistochemical studies have shown that PACAP-LI in rat testis is expressed stage specifically in spermatids. This suggests that testicular PACAP participates in the regulatory mechanism of spermatogenesis. Additionally, the ovary contains a relatively small amount of PACAP, conceivably involved in the regulation of folliculogenesis. PACAP is synthesized as a preprohormone and is processed by prohormone convertases, such as PC1, PC2, and PC4. PC4 is expressed only in the testis and ovary, where neither PC1 nor PC2 is expressed. However, whether PC4 is the sole endoprotease for the PACAP precursor in the gonads remains unknown. Recent studies using PC4-transgenic mice revealed that male PC4-null mice exhibited severely impaired fertility, although spermatogenesis appeared to be normal. The female PC4-null mice exhibited delayed folliculogenesis in the ovaries. To examine whether PC4 is the sole processing enzyme for the PACAP precursor in the gonads, we analyzed testicular and ovarian extracts from the PC4-null and wild-type mice for PACAP (PACAP38 and PACAP27) and its messenger RNA using reverse phase HPLC combined with specific RIAs and ribonuclease protection assay, respectively. For RIAs, three different polyclonal antisera with different recognition sites were used to identify PACAP38, PACAP27, and its precursor. Neither the testis nor the ovary from the PC4-null mice expressed PACAP38 or PACAP27, but the levels of PACAP transcripts in the testis and ovary of homozygous PC4-deficient mice were considerably elevated compared with those of the wild-type and heterozygous animals. The findings indicate that PC4 is the sole processing enzyme for the precursor of PACAP in the testis and ovary of mice. The possibility that the absence of bioactive PACAP in the testis and ovary of PC4-null mice caused severely impaired fertility in the males and

Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

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Galia Ramírez-Toloza

2017-09-01

Full Text Available American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68, T. cruzi complement regulatory protein (TcCRP, trypomastigote decay-accelerating factor (T-DAF, C2 receptor inhibitor trispanning (CRIT and T. cruzi calreticulin (TcCRT. Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH and plasma membrane-derived vesicles (PMVs. All these proteins inhibit different steps of the classical (CP, alternative (AP or lectin pathways (LP. Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host

Inhibition of furin results in increased growth, invasiveness and cytokine production of synoviocytes from patients with rheumatoid arthritis.

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Wu, Changshun; Song, Zezhong; Liu, Huiling; Pan, Jihong; Jiang, Huiyu; Liu, Chao; Yan, Zexing; Feng, Hong; Sun, Shui

2017-07-01

Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes. In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated. The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1β and tumor necrosis factor-α secretion of synoviocytes. Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models

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Siner, Joshua I.; Samelson-Jones, Benjamin J.; Crudele, Julie M.; French, Robert A.; Lee, Benjamin J.; Zhou, Shanzhen; Merricks, Elizabeth; Raymer, Robin; Camire, Rodney M.; Arruda, Valder R.

2016-01-01

Processing by the proprotein convertase furin is believed to be critical for the biological activity of multiple proteins involved in hemostasis, including coagulation factor VIII (FVIII). This belief prompted the retention of the furin recognition motif (amino acids 1645–1648) in the design of B-domain–deleted FVIII (FVIII-BDD) products in current clinical use and in the drug development pipeline, as well as in experimental FVIII gene therapy strategies. Here, we report that processing by furin is in fact deleterious to FVIII-BDD secretion and procoagulant activity. Inhibition of furin increases the secretion and decreases the intracellular retention of FVIII-BDD protein in mammalian cells. Our new variant (FVIII-ΔF), in which this recognition motif is removed, efficiently circumvents furin. FVIII-ΔF demonstrates increased recombinant protein yields, enhanced clotting activity, and higher circulating FVIII levels after adeno-associated viral vector–based liver gene therapy in a murine model of severe hemophilia A (HA) compared with FVIII-BDD. Moreover, we observed an amelioration of the bleeding phenotype in severe HA dogs with sustained therapeutic FVIII levels after FVIII-ΔF gene therapy at a lower vector dose than previously employed in this model. The immunogenicity of FVIII-ΔF did not differ from that of FVIII-BDD as a protein or a gene therapeutic. Thus, contrary to previous suppositions, FVIII variants that can avoid furin processing are likely to have enhanced translational potential for HA therapy. PMID:27734034

[Recommendations of the European Society of Cardiology and the European Atherosclerosis Society on Cardiovascular Disease Prevention and Management of Dyslipidemias. for the Diagnosis of Atherosclerosis and Dyslipidemia Treatment (2016): Basic S.G.

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Bubnova, M G; Kukharchuk, V V

2017-03-01

This review summarizes the main provisions of the new, issued in 2016, recommendations of the European Society of Cardiology and Atherosclerosis Society in cooperation with the European Association on Cardiovascular Prevention and Rehabilitation on Cardiovascular disease prevention and Management of dyslipidemia. In these recommendations, the following trends can be traced distinctly: priority in primary prevention is given to non-drug methods of influence; targets of hypolipidemic therapy are identified not only for low density lipoprotein (LDL) cholesterol (CH), but also for non-high density lipoprotein (HDL) CH, especially in cases of concomitant hypertriglyceridemia. In the field of therapy, in which statins remain the main tool of correction of hyperlipidemia, it is recommended to more widely resort to the use of combination therapy, especially in cases of familial hypercholesterolemia or intolerance to statins; introduction of a new class of drugs- inhibitors of proprotein convertase subtilisin/kexin type 9 makes it possible to further reduce the level of LDLCH, lipoprotein(a) more than 60%. Regarding the wider application of these drugs there are issues related to the relatively limited experience of their use and the lack of data on long-term results and the incidence of side effects. Much attention is paid to more active correction of dyslipidemia in elderly patients, patients with chronic renal failure, diabetes, and several other diseases. The emergence of new European recommendations will undoubtedly serve as a stimulus to the revision of the Russian recommendations, which remain unchanged from 2012.

Assessment of physicians' awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: Is there a gap?

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Batais, Mohammed Ali; Almigbal, Turky H; Bin Abdulhak, Aref A; Altaradi, Hani B; AlHabib, Khalid F

2017-01-01

The scarcity of familial hypercholesterolemia (FH) cases reported in Saudi Arabia might be indicative of a lack of awareness of this common genetic disease among physicians. To assess physicians' awareness, practice, and knowledge of FH in Saudi Arabia. This is a cross-sectional study conducted among physicians at four tertiary hospitals in Riyadh, Saudi Arabia between March 2016 and May 2016 using a self-administered questionnaire. A total of 294 physicians completed the survey (response rate 90.1%). Overall, 92.9% of the participants have poor knowledge of FH while only 7.1% have acceptable knowledge. The majority (68.7%) of physicians rated their familiarity with FH as average or above average, and these had higher mean knowledge scores than participants with self-reported below average familiarity (mean 3.4 versus 2.6) (P knowledge scores compared to those without FH patients in their care (3.5 versus 2.9) (P = 0.006). In addition, there were statistically significant differences between physicians' mean knowledge scores and their ages, levels of training, and years in practice. Moreover, a substantial deficit was identified in the awareness of various clinical algorithms to diagnose patients with FH, cascade screening, specialist lipid services, and the existence of statin alternatives, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A substantial deficit was found in the awareness, knowledge, practice, and detection of FH among physicians in Saudi Arabia. Extensive educational programs are required to raise physician awareness and implement best practices; only then can the impact of these interventions on FH management and patient outcome be assessed.

Determining the binding affinity of therapeutic monoclonal antibodies towards their native unpurified antigens in human serum.

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Christine Bee

Full Text Available Monoclonal antibodies (mAbs are a growing segment of therapeutics, yet their in vitro characterization remains challenging. While it is essential that a therapeutic mAb recognizes the native, physiologically occurring epitope, the generation and selection of mAbs often rely on the use of purified recombinant versions of the antigen that may display non-native epitopes. Here, we present a method to measure both, the binding affinity of a therapeutic mAb towards its native unpurified antigen in human serum, and the antigen's endogenous concentration, by combining the kinetic exclusion assay and Biacore's calibration free concentration analysis. To illustrate the broad utility of our method, we studied a panel of mAbs raised against three disparate soluble antigens that are abundant in the serum of healthy donors: proprotein convertase subtilisin/kexin type 9 (PCSK9, progranulin (PGRN, and fatty acid binding protein (FABP4. We also determined the affinity of each mAb towards its purified recombinant antigen and assessed whether the interactions were pH-dependent. Of the six mAbs studied, three did not appear to discriminate between the serum and recombinant forms of the antigen; one mAb bound serum antigen with a higher affinity than recombinant antigen; and two mAbs displayed a different affinity for serum antigen that could be explained by a pH-dependent interaction. Our results highlight the importance of taking pH into account when measuring the affinities of mAbs towards their serum antigens, since the pH of serum samples becomes increasingly alkaline upon aerobic handling.

Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

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Gergana Galabova

Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

Science.gov (United States)

da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

2016-01-01

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. PMID:26645686

Sample-to-SNP kit: a reliable, easy and fast tool for the detection of HFE p.H63D and p.C282Y variations associated to hereditary hemochromatosis.

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Nielsen, Peter B; Petersen, Maja S; Ystaas, Viviana; Andersen, Rolf V; Hansen, Karin M; Blaabjerg, Vibeke; Refstrup, Mette

2012-10-01

Classical hereditary hemochromatosis involves the HFE-gene and diagnostic analysis of the DNA variants HFE p.C282Y (c.845G>A; rs1800562) and HFE p.H63D (c.187C>G; rs1799945). The affected protein alters the iron homeostasis resulting in iron overload in various tissues. The aim of this study was to validate the TaqMan-based Sample-to-SNP protocol for the analysis of the HFE-p.C282Y and p.H63D variants with regard to accuracy, usefulness and reproducibility compared to an existing SNP protocol. The Sample-to-SNP protocol uses an approach where the DNA template is made accessible from a cell lysate followed by TaqMan analysis. Besides the HFE-SNPs other eight SNPs were used as well. These SNPs were: Coagulation factor II-gene F2 c.20210G>A, Coagulation factor V-gene F5 p.R506Q (c.1517G>A; rs121917732), Mitochondria SNP: mt7028 G>A, Mitochondria SNP: mt12308 A>G, Proprotein convertase subtilisin/kexin type 9-gene PCSK9 p.R46L (c.137G>T), Plutathione S-transferase pi 1-gene GSTP1 p.I105V (c313A>G; rs1695), LXR g.-171 A>G, ZNF202 g.-118 G>T. In conclusion the Sample-to-SNP kit proved to be an accurate, reliable, robust, easy to use and rapid TaqMan-based SNP detection protocol, which could be quickly implemented in a routine diagnostic or research facility. Copyright © 2012. Published by Elsevier B.V.

Furin is a chemokine-modifying enzyme: in vitro and in vivo processing of CXCL10 generates a C-terminally truncated chemokine retaining full activity.

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Hensbergen, Paul J; Verzijl, Dennis; Balog, Crina I A; Dijkman, Remco; van der Schors, Roel C; van der Raaij-Helmer, Elizabeth M H; van der Plas, Mariena J A; Leurs, Rob; Deelder, André M; Smit, Martine J; Tensen, Cornelis P

2004-04-02

Chemokines comprise a class of structurally related proteins that are involved in many aspects of leukocyte migration under basal and inflammatory conditions. In addition to the large number of genes, limited processing of these proteins by a variety of enzymes enhances the complexity of the total spectrum of chemokine variants. We have recently shown that the native chemokine CXCL10 is processed at the C terminus, thereby shedding the last four amino acids. The present study was performed to elucidate the mechanism in vivo and in vitro and to study the biological activity of this novel isoform of CXCL10. Using a combination of protein purification and mass spectrometric techniques, we show that the production of C-terminally truncated CXCL10 by primary keratinocytes is inhibited in vivo by a specific inhibitor of pro-protein convertases (e.g. furin) but not by inhibition of matrix metalloproteinases. Moreover, CXCL10 is processed by furin in vitro, which is abrogated by a mutation in the furin recognition site. Using GTPgammaS binding, Ca(2+) mobilization, and chemotaxis assays, we demonstrate that the C-terminally truncated CXCL10 variant is a potent ligand for CXCR3. Moreover, the inverse agonist activity on the virally encoded receptor ORF74 and the direct antibacterial activity of CXCL10 are fully retained. Hence, we have identified furin as a novel chemokine-modifying enzyme in vitro and most probably also in vivo, generating a C-terminally truncated CXCL10, which fully retains its (inverse) agonistic properties.

Critical role of bioanalytical strategies in investigation of clinical PK observations, a Phase I case study

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Peng, Kun; Xu, Keyang; Liu, Luna; Hendricks, Robert; Delarosa, Reginald; Erickson, Rich; Budha, Nageshwar; Leabman, Maya; Song, An; Kaur, Surinder; Fischer, Saloumeh K

2014-01-01

RG7652 is a human immunoglobulin 1 (IgG1) monoclonal antibody (mAb) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and is designed for the treatment of hypercholesterolemia. A target-binding enzyme-linked immunosorbent assay (ELISA) was developed to measure RG7652 levels in human serum in a Phase I study. Although target-binding assay formats are generally used to quantify free therapeutic, the actual therapeutic species being measured are affected by assay conditions, such as sample dilution and incubation time, and levels of soluble target in the samples. Therefore, in the presence of high concentrations of circulating target, the choice of reagents and assay conditions can have a significant effect on the observed pharmacokinetic (PK) profiles. Phase I RG7652 PK analysis using the ELISA data resulted in a nonlinear dose normalized exposure. An investigation was conducted to characterize the ELISA to determine whether the assay format and reagents may have contributed to the PK observation. In addition, to confirm the ELISA results, a second orthogonal method, liquid chromatography tandem mass spectrometry (LC-MS/MS) using a signature peptide as surrogate, was developed and implemented. A subset of PK samples, randomly selected from half of the subjects in the 6 single ascending dose (SAD) cohorts in the Phase I clinical study, was analyzed with the LC-MS/MS assay, and the data were found to be comparable to the ELISA data. This paper illustrates the importance of reagent characterization, as well as the benefits of using an orthogonal approach to eliminate bioanalytical contributions when encountering unexpected observations. PMID:25484037

EDITORIAL: Plasma jets and plasma bullets Plasma jets and plasma bullets

Science.gov (United States)

Kong, M. G.; Ganguly, B. N.; Hicks, R. F.

2012-06-01

Plasma plumes, or plasma jets, belong to a large family of gas discharges whereby the discharge plasma is extended beyond the plasma generation region into the surrounding ambience, either by a field (e.g. electromagnetic, convective gas flow, or shock wave) or a gradient of a directionless physical quantity (e.g. particle density, pressure, or temperature). This physical extension of a plasma plume gives rise to a strong interaction with its surrounding environment, and the interaction alters the properties of both the plasma and the environment, often in a nonlinear and dynamic fashion. The plasma is therefore not confined by defined physical walls, thus extending opportunities for material treatment applications as well as bringing in new challenges in science and technology associated with complex open-boundary problems. Some of the most common examples may be found in dense plasmas with very high dissipation of externally supplied energy (e.g. in electrical, optical or thermal forms) and often in or close to thermal equilibrium. For these dense plasmas, their characteristics are determined predominantly by strong physical forces of different fields, such as electrical, magnetic, thermal, shock wave, and their nonlinear interactions [1]. Common to these dense plasma plumes are significant macroscopic plasma movement and considerable decomposition of solid materials (e.g. vaporization). Their applications are numerous and include detection of elemental traces, synthesis of high-temperature materials and welding, laser--plasma interactions, and relativistic jets in particle accelerators and in space [2]-[4]. Scientific challenges in the understanding of plasma jets are exciting and multidisciplinary, involving interweaving transitions of all four states of matter, and their technological applications are wide-ranging and growing rapidly. Using the Web of Science database, a search for journal papers on non-fusion plasma jets reveals that a long initial phase up

Human factor H-related protein 2 (CFHR2 regulates complement activation.

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Hannes U Eberhardt

Full Text Available Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs. Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

Processing of high-molecular-weight form adrenocorticotropin in human adrenocorticotropin-secreting tumor cell line (DMS-79) after transfection of prohormone convertase 1/3 gene.

Science.gov (United States)

Tateno, T; Kato, M; Tani, Y; Yoshimoto, T; Oki, Y; Hirata, Y

2010-02-01

Ectopic ACTH-producing tumors preferentially secrete biologically inactive ACTH precursors and ACTH-related fragments. DMS-79 is known to secrete unprocessed high-molecular-weight (HMW) form ACTH. To determine whether prohormone convertase (PC) 1/3 is involved in the abnormal processing of proopiomelanocortin (POMC), we studied whether PC1/3 and 2 genes are expressed in DMS-79, and whether overexpression of PC1/3 gene affects POMC processing pattern. Steady-state mRNA levels of PC1/3 and 2 were determined by real-time RT-PCR. Molecular weights of ACTH-related peptides were determined by chromatographical analyses coupled with ACTH and beta-endorphin (beta-END) radioimmunoassays. PC1/3 gene was transfected into DMS-79 by retrovirus transduction using pMX-IP vector encoding PC1/3 cDNA. The steady-state mRNA levels of PC1/3 and 2 in DMS-79 were lower than those in ACTH-secreting and nonfunctioning pituitary tumors. DMS-79 predominantly secreted HMW form with both ACTH and beta-END immunoreactivities by size-exclusion chromatography. After purification by immunoaffinity chromatography with anti-ACTH antibody, the apparent molecular weight of HMW form ACTH was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining. After retroviral transfection of PC1/3 cDNA into DMS-79 and puromycin selection, PC1/3 stably-expressing cell line (DMS-79T) secreted two immunoreactive ACTH components, a major one coeluting with ACTH(1-39) and a minor one as a HMW form as well as two beta- END immunoreactive components coeluting with beta-lipotropic hormone and beta-END, respectively. Thus, we have established PC1/3 stably-expressing cell line (DMS-79T) capable of proteolytically processing ACTH precursor molecule(s) into mature ACTH and beta-END.

Electron plasma waves and plasma resonances

International Nuclear Information System (INIS)

Franklin, R N; Braithwaite, N St J

2009-01-01

In 1929 Tonks and Langmuir predicted of the existence of electron plasma waves in an infinite, uniform plasma. The more realistic laboratory environment of non-uniform and bounded plasmas frustrated early experiments. Meanwhile Landau predicted that electron plasma waves in a uniform collisionless plasma would appear to be damped. Subsequent experimental work verified this and revealed the curious phenomenon of plasma wave echoes. Electron plasma wave theory, extended to finite plasmas, has been confirmed by various experiments. Nonlinear phenomena, such as particle trapping, emerge at large amplitude. The use of electron plasma waves to determine electron density and electron temperature has not proved as convenient as other methods.

Bridge between fusion plasma and plasma processing

International Nuclear Information System (INIS)

Ohno, Noriyasu; Takamura, Shuichi

2008-01-01

In the present review, relationship between fusion plasma and processing plasma is discussed. From boundary-plasma studies in fusion devices new applications such as high-density plasma sources, erosion of graphite in a hydrogen plasma, formation of helium bubbles in high-melting-point metals and the use of toroidal plasmas for plasma processing are emerging. The authors would like to discuss a possibility of knowledge transfer from fusion plasmas to processing plasmas. (T. Ikehata)

Genetic spectrum of low density lipoprotein receptor gene variations in South Indian population.

Science.gov (United States)

ArulJothi, K N; Suruthi Abirami, B; Devi, Arikketh

2018-03-01

Low density lipoprotein receptor (LDLR) is a membrane bound receptor maintaining cholesterol homeostasis along with Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) and other genes of lipid metabolism. Any pathogenic variation in these genes alters the function of the receptor and leads to Familial Hypercholesterolemia (FH) and other cardiovascular diseases. This study was aimed at screening the LDLR, APOB and PCSK9 genes in Hypercholesterolemic patients to define the genetic spectrum of FH in Indian population. Familial Hypercholesterolemia patients (n=78) of South Indian Tamil population with LDL cholesterol and Total cholesterol levels above 4.9mmol/l and 7.5mmol/l with family history of Myocardial infarction were involved. DNA was isolated by organic extraction method from blood samples and LDLR, APOB and PCSK9 gene exons were amplified using primers that cover exon-intron boundaries. The amplicons were screened using High Resolution Melt (HRM) Analysis and the screened samples were sequenced after purification. This study reports 20 variations in South Indian population for the first time. In this set of variations 9 are novel variations which are reported for the first time, 11 were reported in other studies also. The in silico analysis for all the variations detected in this study were done to predict the probabilistic effect in pathogenicity of FH. This study adds 9 novel variations and 11 recurrent variations to the spectrum of LDLR gene mutations in Indian population. All these variations are reported for the first time in Indian population. This spectrum of variations was different from the variations of previous Indian reports. Copyright © 2017 Elsevier B.V. All rights reserved.

Phytosterols, Phytostanols, and Lipoprotein Metabolism

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Helena Gylling

2015-09-01

Full Text Available The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein

Phytosterols, Phytostanols, and Lipoprotein Metabolism.

Science.gov (United States)

Gylling, Helena; Simonen, Piia

2015-09-17

The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%-10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be

Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

Science.gov (United States)

da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

2016-01-29

The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Current treatment of dyslipidaemia: PCSK9 inhibitors and statin intolerance.

Science.gov (United States)

Koskinas, Konstantinos; Wilhelm, Matthias; Windecker, Stephan

2016-01-01

Statins are the cornerstone of the management of dyslipidaemias and prevention of cardiovascular disease. Although statins are, overall, safe and well tolerated, adverse events can occur and constitute an important barrier to maintaining long-term adherence to statin treatment. In patients who cannot tolerate statins, alternative treatments include switch to another statin, intermittent-dosage regimens and non-statin lipid-lowering medications. Nonetheless, a high proportion of statin-intolerant patients are unable to achieve recommended low-density lipoprotein (LDL) cholesterol goals, thereby resulting in substantial residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease implicated in LDL receptor degradation and plays a central role in cholesterol metabolism. In recent studies, PCSK9 inhibition by means of monoclonal antibodies achieved LDL cholesterol reductions of 50% to 70% across various patient populations and background lipid-lowering therapies, while maintaining a favourable safety profile. The efficacy and safety of the monoclonal antibodies alirocumab and evolocumab were confirmed in statin-intolerant patients, indicating that PCSK9 inhibitors represent an attractive treatment option in this challenging clinical setting. PCSK9 inhibitors recently received regulatory approval for clinical use and may be considered in properly selected patients according to current consensus documents, including patients with statin intolerance. In this review we summarise current evidence regarding diagnostic evaluation of statin-related adverse events, particularly statin-associated muscle symptoms, and we discuss current recommendations on the management of statin-intolerant patients. In view of emerging evidence of the efficacy and safety of PCSK9 inhibitors, we further discuss the role of monoclonal PCSK9 antibodies in the management of statin-intolerant hypercholesterolaemic patients.

Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer

International Nuclear Information System (INIS)

Liang, Xing-Hua; He, Wen-guang; Huang, Yan-Nian; Zeng, Xian-Cheng; Li, Ling-ling; Wu, Geng-Gang; Xie, Yi-Cheng; Zhang, Guang-Xian; Chen, Wei; Yang, Hai-Feng; Liu, Qi-Long; Li, Wen-Hong

2013-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood. In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells. Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1. Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics

The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol

Directory of Open Access Journals (Sweden)

Poirier S

2013-10-01

Full Text Available Steve Poirier,1,2 Gaétan Mayer1–31Laboratory of Molecular Cell Biology, Montreal Heart Institute, Montréal, QC, Canada; 2Départements de Pharmacologie, 3Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, CanadaAbstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9 directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.Keywords: PCSK9, LDLR, LDL-cholesterol, lipoproteins, coronary heart disease, inhibitors, monoclonal antibody therapy

Measuring the Plasma Density of a Ferroelectric Plasma Source in an Expanding Plasma

International Nuclear Information System (INIS)

Dunaevsky, A.; Fisch, N.J.

2003-01-01

The initial density and electron temperature at the surface of a ferroelectric plasma source were deduced from floating probe measurements in an expanding plasma. The method exploits negative charging of the floating probe capacitance by fast flows before the expanding plasma reaches the probe. The temporal profiles of the plasma density can be obtained from the voltage traces of the discharge of the charged probe capacitance by the ion current from the expanding plasma. The temporal profiles of the plasma density, at two different distances from the surface of the ferroelectric plasma source, could be further fitted by using the density profiles for the expanding plasma. This gives the initial values of the plasma density and electron temperature at the surface. The method could be useful for any pulsed discharge, which is accompanied by considerable electromagnetic noise, if the initial plasma parameters might be deduced from measurements in expanding plasma

Plasma electron losses in a multidipole plasma

International Nuclear Information System (INIS)

Haworth, M.D.

1983-01-01

The magnitude of the plasma electron cusp losses in a multidipole plasma device is determined by using a plasma electron heating technique. This method consists of suddenly generating approximately monoenergetic test electrons inside the multidipole plasma, which is in a steady-state equilibrium prior to the introduction of the test electrons. The Coulomb collisions between the test electrons and the plasma electrons result in heating the plasma electrons. The experimentally measured time evolution of the plasma electron temperature is compared with that predicted by a kinetic-theory model which calculates the time evolution of the test electron and the plasma electron distribution functions. The analytical solution of the plasma electron heating rate when the test electrons are first introduced into the plasma predicts that there is no dependence on ion mass. Experimental results in helium, neon, argon, and krypton multidipole plasmas confirm this prediction. The time-evolved solution of the kinetic equations must be solved numerically, and these results (when coupled with the experimental heating results) show that the plasma electron cusp-loss width is on the order of an electron Larmor radius

Plasma physics and fusion plasma electrodynamics

CERN Document Server

Bers, Abraham

2016-01-01

Plasma is a ubiquitous state of matter at high temperatures. The electrodynamics of plasmas encompasses a large number of applications, from understanding plasmas in space and the stars, to their use in processing semiconductors, and their role in controlled energy generation by nuclear fusion. This book covers collective and single particle dynamics of plasmas for fully ionized as well as partially ionized plasmas. Many aspects of plasma physics in current fusion energy generation research are addressed both in magnetic and inertial confinement plasmas. Linear and nonlinear dynamics in hydrodynamic and kinetic descriptions are offered, making both simple and complex aspects of the subject available in nearly every chapter. The approach of dividing the basic aspects of plasma physics as "linear, hydrodynamic descriptions" to be covered first because they are "easier", and postponing the "nonlinear and kinetic descriptions" for later because they are "difficult" is abandoned in this book. For teaching purpose...

Haemocompatibility evaluation of DLC- and SiC-coated surfaces

Directory of Open Access Journals (Sweden)

Nurdin N.

2003-06-01

Full Text Available Diamond-like carbon (DLC and silicon carbide (SiC coatings are attractive because of low friction coefficient, high hardness, chemical inertness and smooth finish, which they provide to biomedical devices. Silicon wafers (Siwaf and silicone rubber (Sirub plates were coated using plasma-enhanced chemical vapour deposition (PE-CVD techniques. This article describes: 1- the characterization of modified surfaces using attenuated total reflection-Fourier transform infrared spectroscopy (ATR/FTIR and contact angle measurements, 2- the results of three in-vitro haemocompatibility assays. Coated surfaces were compared to uncoated materials and various substrates such as polymethylmethacrylate (PMMA, polyethylene (LDPE, polydimethylsiloxane (PDMS and medical steel (MS. Thrombin generation, blood platelet adhesion and complement convertase activity tests revealed the following classification, from the most to the least heamocompatible surface: Sirub/ DLC-Sirub/ DLC-Siwaf/ LDPE/ PDMS/ SiC-Siwaf/ Siwaf/ PMMA/ MS. The DLC coating surfaces delayed the clotting time, tended to inhibit the platelet and complement convertase activation, whereas SiC-coated silicon wafer can be considered as thrombogenic. This study has taken into account three events of the blood activation: coagulation, platelet activation and inflammation. The response to those events is an indicator of the in vitro haemocompatibility of the different surfaces and it allows us to select biomaterials for further in vivo blood contacting investigations.

Double plasma system with inductively coupled source plasma and quasi-quiescent target plasma

International Nuclear Information System (INIS)

Massi, M.; Maciel, H.S.

1995-01-01

Cold plasmas have successfully been used in the plasma-assisted material processing industry. An understanding of the physicochemical mechanisms involved in the plasma-surface interaction is needed for a proper description of deposition and etching processes at material surfaces. Since these mechanisms are dependent on the plasma properties, the development of diagnostic techniques is strongly desirable for determination of the plasma parameters as well as the characterization of the electromagnetic behaviour of the discharge. In this work a dual discharge chamber, was specially designed to study the deposition of thin films via plasma polymerization process. In the Pyrex chamber an inductively coupled plasma can be excited either in the diffuse low density E-mode or in the high density H-mode. This plasma diffuses into the cylindrical stainless steel chamber which is covered with permanent magnets to produce a multidipole magnetic field configuration at the surface. By that means a double plasma is established consisting of a RF source plasma coupled to a quasi-quiescent target plasma. The preliminary results presented here refer to measurements of the profiles of plasma parameters along the central axis of the double plasma apparatus. Additionally a spectrum analysis performed by means of a Rogowski coil probe immersed into the source plasma is also presented. The discharge is made in argon with pressure varying from 10 -2 to 1 torr, and the rf from 10 to 150 W

Compression of toroidal plasma by imploding plasma-liner

International Nuclear Information System (INIS)

Ikuta, Kazunari.

1979-07-01

A new concept of compressing a plasma in a closed magnetic configuration by a version of liner implosion flux compression technique is considered. The liner consists of a dense plasma cylinder, i.e. the plasma-liner. Maximum compression ratio of toroidal plasma is determined just by the initial density ratio of the toroidal plasma to the liner plasma because of the Rayleigh-Taylor instability. A start-up senario of plasma-liner is also proposed with a possible application of this concept to the creation of a burning plasma in reversed field configurations, i.e. burning plasma vortex. (author)

A new large-scale plasma source with plasma cathode

International Nuclear Information System (INIS)

Yamauchi, K.; Hirokawa, K.; Suzuki, H.; Satake, T.

1996-01-01

A new large-scale plasma source (200 mm diameter) with a plasma cathode has been investigated. The plasma has a good spatial uniformity, operates at low electron temperature, and is highly ionized under relatively low gas pressure of about 10 -4 Torr. The plasma source consists of a plasma chamber and a plasma cathode generator. The plasma chamber has an anode which is 200 mm in diameter, 150 mm in length, is made of 304 stainless steel, and acts as a plasma expansion cup. A filament-cathode-like plasma ''plasma cathode'' is placed on the central axis of this source. To improve the plasma spatial uniformity in the plasma chamber, a disk-shaped, floating electrode is placed between the plasma chamber and the plasma cathode. The 200 mm diameter plasma is measure by using Langmuir probes. As a result, the discharge voltage is relatively low (30-120 V), the plasma space potential is almost equal to the discharge voltage and can be easily controlled, the electron temperature is several electron volts, the plasma density is about 10 10 cm -3 , and the plasma density is about 10% variance in over a 100 mm diameter. (Author)

Review on plasmas in extraordinary media: plasmas in cryogenic conditions and plasmas in supercritical fluids

Science.gov (United States)

Stauss, Sven; Muneoka, Hitoshi; Terashima, Kazuo

2018-02-01

Plasma science and technology has enabled advances in very diverse fields: micro- and nanotechnology, chemical synthesis, materials fabrication and, more recently, biotechnology and medicine. While many of the currently employed plasma tools and technologies are very advanced, the types of plasmas used in micro- and nanofabrication pose certain limits, for example, in treating heat-sensitive materials in plasma biotechnology and plasma medicine. Moreover, many physical properties of plasmas encountered in nature, and especially outer space, i.e. very-low-temperature plasmas or plasmas that occur in high-density media, are not very well understood. The present review gives a short account of laboratory plasmas generated under ’extreme’ conditions: at cryogenic temperatures and in supercritical fluids. The fundamental characteristics of these cryogenic plasmas and cryoplasmas, and plasmas in supercritical fluids, especially supercritical fluid plasmas, are presented with their main applications. The research on such exotic plasmas is expected to lead to further understanding of plasma physics and, at the same time, enable new applications in various technological fields.

ECR plasma photographs as a plasma diagnostic

Energy Technology Data Exchange (ETDEWEB)

Racz, R; Biri, S; Palinkas, J [Institute of Nuclear Research (ATOMKI), H-4026 Debrecen, Bem ter 18/c (Hungary)

2011-04-15

Low, medium or highly charged ions delivered by electron cyclotron resonance (ECR) ion sources all are produced in the ECR plasma. In order to study such plasmas, high-resolution visible light plasma photographs were taken at the ATOMKI ECR ion source. An 8 megapixel digital camera was used to photograph plasmas made from He, methane, N, O, Ne, Ar, Kr, Xe gases and from their mixtures. The analysis of the photo series gave many qualitative and some valuable physical information on the nature of ECR plasmas. A comparison was made between the plasma photos and computer simulations, and conclusions were drawn regarding the cold electron component of the plasma. The warm electron component of similar simulation was compared with x-ray photos emitted by plasma ions. While the simulations are in good agreement with the photos, a significant difference was found between the spatial distribution of the cold and warm electrons.

Plasma Modes

Science.gov (United States)

Dubin, D. H. E.

This chapter explores several aspects of the linear electrostatic normal modes of oscillation for a single-species non-neutral plasma in a Penning trap. Linearized fluid equations of motion are developed, assuming the plasma is cold but collisionless, which allow derivation of the cold plasma dielectric tensor and the electrostatic wave equation. Upper hybrid and magnetized plasma waves in an infinite uniform plasma are described. The effect of the plasma surface in a bounded plasma system is considered, and the properties of surface plasma waves are characterized. The normal modes of a cylindrical plasma column are discussed, and finally, modes of spheroidal plasmas, and finite temperature effects on the modes, are briefly described.

Quiescent plasma machine for plasma investigation

International Nuclear Information System (INIS)

Ferreira, J.L.

1993-01-01

A large volume quiescent plasma device is being developed at INPE to study Langmuir waves and turbulence generated by electron beams (E b ≤ 500 e V) interacting with plasma. This new quiescent plasma machine was designed to allow the performance of several experiments specially those related with laboratory space plasma simulation experiments. Current-driven instabilities and related phenomena such as double-layers along magnetic field lines are some of the many experiments planned for this machine. (author)

Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country.

Science.gov (United States)

Khoo, Kah Lin; Page, Michael M; Liew, Yin Mei; Defesche, Joep C; Watts, Gerald F

2016-01-01

Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH. We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 ± 7.2%, with time-averaged mean lowering of 34.9 ± 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost. LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Transcriptomic Analysis of Neuropeptides and Peptide Hormones in the Barnacle Balanus amphitrite: Evidence of Roles in Larval Settlement

Science.gov (United States)

Yan, Xing-Cheng; Chen, Zhang-Fan; Sun, Jin; Matsumura, Kiyotaka; Wu, Rudolf S. S.; Qian, Pei-Yuan

2012-01-01

The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

Synergistic Cardioprotective Effects of Combined Chromium Picolinate and Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on Some Biochemical Markers.

Science.gov (United States)

Shafik, Noha M; Baalash, Amal; Ebeid, Abla M

2017-12-01

Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 μg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.

A dual-type responsive electrochemical immunosensor for quantitative detection of PCSK9 based on n-C60-PdPt/N-GNRs and Pt-poly (methylene blue) nanocomposites.

Science.gov (United States)

Li, Yan; He, Junlin; Chen, Jun; Niu, Yazhen; Zhao, Yilin; Zhang, Yuchan; Yu, Chao

2018-03-15

In this study, a dual-type responsive electrochemical immunosensor was developed for the quantitative detection of proprotein convertase subtilisin/kexin type 9 (PCSK9), a potential biomarker of cardiovascular disease in serum. N-doped graphene nanoribbons (N-GNRs) with good conductivity were used as the sensing matrix modifying the glassy carbon electrode. Palladium platinum alloy (PdPt) nanoparticles with high catalytic performance toward the reduction of hydrogen peroxide (H 2 O 2 ) were reduced onto amino-functionalized fullerene (n-C 60 -PdPt) and significantly amplified the electrochemical signal recorded by the amperometric i-t curve. Furthermore, staphylococcus protein A (SPA) with antibody orientation function was introduced to improve the immunoreaction efficiency. Accordingly, a label-free immunosensor was fabricated based on n-C 60 -PdPt/N-GNRs for the quick detection of PCSK9. Meanwhile, to realize ultrasensitive detection of PCSK9, Pt-poly (methylene blue) (Pt-PMB) nanocomposites synthesized by a one-pot method for the first time were used as a novel signal label, which exhibited uniform morphology as well as good conductivity and produced an electrochemical signal recorded by differential pulse voltammetry (DPV). Herein, a novel sandwich-type immunosensor was designed using n-C 60 -PdPt/N-GNRs as the sensing matrix and Pt-PMB as the signal label for sensitive detection of PCSK9. Under optimal conditions, the label-free immunosensor showed a linear range of 10pgmL -1 to 100ngmL -1 with a detection limit of 3.33pgmL -1 (S/N=3), and the sandwich-type immunosensor exhibited a linear range of 100 fg mL -1 to 100ngmL -1 with a detection limit of 0.033pgmL -1 (S/N=3) for PCSK9 detection, indicating its potential application in clinical bioassay analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

KAUST Repository

Yan, Xing-Cheng

2012-10-02

The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.

Science.gov (United States)

Thedrez, Aurélie; Blom, Dirk J; Ramin-Mangata, Stéphane; Blanchard, Valentin; Croyal, Mikaël; Chemello, Kévin; Nativel, Brice; Pichelin, Matthieu; Cariou, Bertrand; Bourane, Steeve; Tang, Lihua; Farnier, Michel; Raal, Frederick J; Lambert, Gilles

2018-03-01

Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment. Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab. © 2017 American Heart Association

Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

Directory of Open Access Journals (Sweden)

Xing-Cheng Yan

Full Text Available The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in

Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study.

Science.gov (United States)

Cho, Leslie; Rocco, Michael; Colquhoun, David; Sullivan, David; Rosenson, Robert S; Dent, Ricardo; Xue, Allen; Scott, Rob; Wasserman, Scott M; Stroes, Erik

2016-06-01

Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905). GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS. Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion. Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.

Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms.

Science.gov (United States)

Yang, Danlin; Singh, Ajit; Wu, Helen; Kroe-Barrett, Rachel

2017-04-17

Label-free optical biosensors are powerful tools in drug discovery for the characterization of biomolecular interactions. In this study, we describe the use of four routinely used biosensor platforms in our laboratory to evaluate the binding affinity and kinetics of ten high-affinity monoclonal antibodies (mAbs) against human proprotein convertase subtilisin kexin type 9 (PCSK9). While both Biacore T100 and ProteOn XPR36 are derived from the well-established Surface Plasmon Resonance (SPR) technology, the former has four flow cells connected by serial flow configuration, whereas the latter presents 36 reaction spots in parallel through an improvised 6 x 6 crisscross microfluidic channel configuration. The IBIS MX96 also operates based on the SPR sensor technology, with an additional imaging feature that provides detection in spatial orientation. This detection technique coupled with the Continuous Flow Microspotter (CFM) expands the throughput significantly by enabling multiplex array printing and detection of 96 reaction sports simultaneously. In contrast, the Octet RED384 is based on the BioLayer Interferometry (BLI) optical principle, with fiber-optic probes acting as the biosensor to detect interference pattern changes upon binding interactions at the tip surface. Unlike the SPR-based platforms, the BLI system does not rely on continuous flow fluidics; instead, the sensor tips collect readings while they are immersed in analyte solutions of a 384-well microplate during orbital agitation. Each of these biosensor platforms has its own advantages and disadvantages. To provide a direct comparison of these instruments' ability to provide quality kinetic data, the described protocols illustrate experiments that use the same assay format and the same high-quality reagents to characterize antibody-antigen kinetics that fit the simple 1:1 molecular interaction model.

Stairs instead of elevators at the workplace decreases PCSK9 levels in a healthy population.

Science.gov (United States)

Kamani, Christel H; Gencer, Baris; Montecucco, Fabrizio; Courvoisier, Delphine; Vuilleumier, Nicolas; Meyer, Philippe; Mach, François

2015-10-01

Regular physical activity is recommended to lower low-density lipoprotein cholesterol (LDL-C) in a healthy population. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) was shown to reduce (LDL-C) levels; however, the impact of physical exercise on PCSK9 levels remains unclear. We used data from 67 healthy hospital employees who participated in a 6-month intervention promoting active use of stairs instead of elevators during 3 months, followed by 3 months without recommendation. We confirmed the degree of physical activity with estimated aerobic capacity (VO2 max ) and measured serum PCSK9 levels at baseline, 3 and 6 month. Using a multilevel regression model, we analysed changes of PCSK9 levels over time adjusting for age, gender, aerobic capacity, baseline LDL-C, and LDL-C and body mass index (BMI) changes. At baseline, PCSK9 levels were associated with higher aerobic capacity (P-value = 0·024). At 3 months, we observed a significant decrease in mean PCSK9 levels from 403·6 to 324·3 ng/mL (P-value = 0·001), as well a significant decrease in mean LDL-C levels from 3·5 to 3·3 mM (P-value = 0·01). During this period, mean aerobic capacity (VO2 max ) increased from 37·0 to 40·4 mL/kg/min (P-value < 0·001). Physical activity was independently associated with a decrease in PCSK9 levels after adjustment for age, gender, baseline aerobic capacity, and LDL-C and BMI changes. Daily physical activity at the work place is independently associated with a decrease in PCSK9 levels over time. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production.

Science.gov (United States)

Deshmukh, Hitesh S; McLachlan, Anne; Atkinson, Jeffrey J; Hardie, William D; Korfhagen, Thomas R; Dietsch, Maggie; Liu, Yang; Di, Peter Y P; Wesselkamper, Scott C; Borchers, Michael T; Leikauf, George D

2009-11-01

Induced mainly by cigarette smoking, chronic obstructive pulmonary disease (COPD) is a global public health problem characterized by progressive difficulty in breathing and increased mucin production. Previously, we reported that acrolein levels found in COPD sputum could activate matrix metalloproteinase-9 (MMP9). To determine whether acrolein increases expression and activity of MMP14, a critical membrane-bound endopeptidase that can initial a MMP-activation cascade. MMP14 activity and adduct formation were measured following direct acrolein treatment. MMP14 expression and activity was measured in human airway epithelial cells. MMP14 immunohistochemistry was performed with COPD tissue, and in acrolein- or tobacco-exposed mice. In a cell-free system, acrolein, in concentrations equal to those found in COPD sputum, directly adducted cysteine 319 in the MMP14 hemopexin-like domain and activated MMP14. In cells, acrolein increased MMP14 activity, which was inhibited by a proprotein convertase inhibitor, hexa-d-arginine. In the airway epithelium of COPD subjects, immunoreactive MMP14 protein increased. In mouse lung, acrolein or tobacco smoke increased lung MMP14 activity and protein. In cells, acrolein-induced MMP14 transcripts were inhibited by an epidermal growth factor receptor (EGFR) neutralizing antibody, EGFR kinase inhibitor, metalloproteinase inhibitor, or mitogen-activated protein kinase (MAPK) 3/2 or MAPK8 inhibitors, but not a MAPK14 inhibitor. Decreasing the MMP14 protein and activity in vitro by small interfering (si)RNA to MMP14 diminished the acrolein-induced MUC5AC transcripts. In acrolein-exposed mice or transgenic mice with lung-specific transforming growth factor-alpha (an EGFR ligand) expression, lung MMP14 and MUC5AC levels increased and these effects were inhibited by a EGFR inhibitor, erlotinib. Taken together, these findings implicate acrolein-induced MMP14 expression and activity in mucin production in COPD.

Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

KAUST Repository

Yan, Xing-Cheng; Chen, Zhang-Fan; Sun, Jin; Matsumura, Kiyotaka; Wu, Rudolf S S; Qian, Pei-Yuan

2012-01-01

The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice

Directory of Open Access Journals (Sweden)

Beppu Fumiaki

2012-09-01

Full Text Available Abstract Background Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin. Methods Diabetic/obese KK-Ay mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively. Results Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9, which enhances intracellular degradation of LDLR in lysosomes. Conclusions Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-Ay mice by inducing SREBP expression and reduced cholesterol uptake in the liver via

New developments in atherosclerosis: clinical potential of PCSK9 inhibition

Directory of Open Access Journals (Sweden)

Giunzioni I

2015-08-01

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

PCSK9 inhibitors in the current management of atherosclerosis.

Science.gov (United States)

Whayne, Thomas F

The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors. These observations gave hints and awoke interest that it might be possible to prepare monoclonal antibodies to PCSK9 and decrease its activity, after which there should be more active LDL-C cell receptors. The rest is a fascinating story that currently has resulted in two PCSK9 inhibitors, alirocumab and evolocumab, which, on average, decrease LDL-C approximately 50%. Nevertheless, if there are no contraindications, statins remain the standard of prevention for the high-risk CV patient and this includes both secondary and primary prevention. The new inhibitors are for the patient that does not attain the desired target for LDL-C reduction while taking a maximum statin dose or who does not tolerate any statin dose whatsoever. Atherosclerosis can be considered a metabolic disease and the clinician needs to realize this and think more and more of CV prevention. These inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events. (United States). Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

PCSK9 Inhibitors Show Value for Patients and the US Health Care System.

Science.gov (United States)

Cheng, Wei-Han; Gaudette, Étienne; Goldman, Dana P

2017-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from the use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility and 2) an extended eligibility scenario that includes patients with no pre-existing cardiovascular disease but at high risk. We assumed that the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. Use of PCSK9 inhibitors by individuals covered by current FDA approval would extend life expectancy at the age of 51 years by an estimated 1.1 years and would yield a lifetime net value of $5800 per person. If use was extended to those at high risk for cardiovascular disease, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the US health care system at the current discounted prices. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Microarray-based screening of differentially expressed genes in glucocorticoid-induced avascular necrosis

Science.gov (United States)

Huang, Gangyong; Wei, Yibing; Zhao, Guanglei; Xia, Jun; Wang, Siqun; Wu, Jianguo; Chen, Feiyan; Chen, Jie; Shi, Jingshen

2017-01-01

The underlying mechanisms of glucocorticoid (GC)-induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC-induced ANFH. E-MEXP-2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid-induced ANFH rats compared with 5 placebo-treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC-induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25-Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α-2-macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC-induced ANFH via interacting with VDR. A2M may also be involved in the development of GC-induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC-induced ANFH may provide novel targets for diagnostics and therapeutic treatment. PMID:28393228

Microarray‑based screening of differentially expressed genes in glucocorticoid‑induced avascular necrosis.

Science.gov (United States)

Huang, Gangyong; Wei, Yibing; Zhao, Guanglei; Xia, Jun; Wang, Siqun; Wu, Jianguo; Chen, Feiyan; Chen, Jie; Shi, Jingshen

2017-06-01

The underlying mechanisms of glucocorticoid (GC)‑induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC‑induced ANFH. E‑MEXP‑2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid‑induced ANFH rats compared with 5 placebo‑treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC‑induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25‑Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α‑2‑macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC‑induced ANFH via interacting with VDR. A2M may also be involved in the development of GC‑induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC‑induced ANFH may provide novel targets for diagnostics and therapeutic treatment.

Observation of plasma hole in a rotating plasma

International Nuclear Information System (INIS)

Nagaoka, Kenichi; Ishihara, Tatsuzo; Okamoto, Atsushi; Yoshimura, Shinji; Tanaka, Masayoshi Y.

2001-01-01

Plasma hole, a cylindrical density cavity, formed in a rotating plasma has been investigated experimentally. The plasma hole is characterized by large aspect ratio (length/radius ≥ 30), steep boundary layer between the hole and the ambient plasma (10 ion Larmor radius), and extremely high positive potential (130 V). The flow velocity field associated with plasma hole structure has been measured, and is found to have interesting features: (1) plasma rotates in azimuthal direction at a maximum velocity of order of ion sound speed, (2) plasma flows radially inward across the magnetic field line, (3) there present an axial flow reversal between core and peripheral region. It is found that the flow pattern of the plasma hole is very similar to the that of well-developed typhoon with core. (author)

Plasma heating in collisionless plasma at low plasma density

International Nuclear Information System (INIS)

Wulf, H.O.

1977-01-01

The high frequency heating of a collisionless, fully ionized low density plasma is investigated in the range: 2ωc 2 2 under pumping frequencies. A pulsed 1 MHz transmitter excites a fast standing, magneto-acoustical wave in the plasma, via the high frequency magnetic field of a Stix solenoid. The available modulation degrees are between 0.7 and 7.0%. As power consumption measurements show, there appears at all investigated pumping frequencies an effective energy transfer to the plasma that cannot be explained with the classical MHD models. Measurements with electrostatic probes and further with a miniature counter-field spectrometer yield an electron and ion temperature gain of two to three factors and 15-18, compared to the corresponding values in the initial plasma. (orig./HT) [de

Plasma shutdown device

International Nuclear Information System (INIS)

Hosogane, Nobuyuki; Nakayama, Takahide.

1985-01-01

Purpose: To prevent concentration of plasma currents to the plasma center upon plasma shutdown in a torus type thermonuclear device by the injection of fuels to the plasma center thereby prevent plasma disruption at the plasma center. Constitution: The plasma shutdown device comprises a plasma current measuring device that measures the current distribution of plasmas confined within a vacuum vessel and outputs a control signal for cooling the plasma center when the plasma currents concentrate to the plasma center and a fuel supply device that supplies fuels to the plasma center for cooling the center. The fuels are injected in the form of pellets into the plasmas. The direction and the velocity of the injection are set such that the pellets are ionized at the center of the plasmas. (Horiuchi, T.)

Plasma turbulence

International Nuclear Information System (INIS)

Horton, W.

1998-07-01

The origin of plasma turbulence from currents and spatial gradients in plasmas is described and shown to lead to the dominant transport mechanism in many plasma regimes. A wide variety of turbulent transport mechanism exists in plasmas. In this survey the authors summarize some of the universally observed plasma transport rates

Dusty plasmas

International Nuclear Information System (INIS)

Jones, M.E.; Winske, D.; Keinigs, R.; Lemons, D.

1996-01-01

This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The objective of this project has been to develop a fundamental understanding of dusty plasmas at the Laboratory. While dusty plasmas are found in space in galactic clouds, planetary rings, and cometary tails, and as contaminants in plasma enhanced fabrication of microelectronics, many of their properties are only partially understood. Our work has involved both theoretical analysis and self-consistent plasma simulations to understand basic properties of dusty plasmas related to equilibrium, stability, and transport. Such an understanding can improve the control and elimination of plasma dust in industrial applications and may be important in the study of planetary rings and comet dust tails. We have applied our techniques to the study of charging, dynamics, and coagulation of contaminants in plasma processing reactors for industrial etching and deposition processes and to instabilities in planetary rings and other space plasma environments. The work performed in this project has application to plasma kinetics, transport, and other classical elementary processes in plasmas as well as to plasma waves, oscillations, and instabilities

Plasma Physics An Introduction to Laboratory, Space, and Fusion Plasmas

CERN Document Server

Piel, Alexander

2010-01-01

Plasma Physics gives a comprehensive introduction to the basic processes in plasmas and demonstrates that the same fundamental concepts describe cold gas-discharge plasmas, space plasmas, and hot fusion plasmas. Starting from particle drifts in magnetic fields, the principles of magnetic confinement fusion are explained and compared with laser fusion. Collective processes are discussed in terms of plasma waves and instabilities. The concepts of plasma description by magnetohydrodynamics, kinetic theory, and particle simulation are stepwise introduced. Space charge effects in sheath regions, double layers and plasma diodes are given the necessary attention. The new fundamental mechanisms of dusty plasmas are explored and integrated into the framework of conventional plasmas. The book concludes with a brief introduction to plasma discharges. Written by an internationally renowned researcher in experimental plasma physics, the text keeps the mathematical apparatus simple and emphasizes the underlying concepts. T...

Plasma basic concepts and nitrogen containing plasmas

OpenAIRE

Sanz Lluch, M. del Mar; Tanarro, Isabel

2007-01-01

Basic concepts related to plasmas are described as well as the typical characterization methods currently available. A brief overview about some plasma applications is given, but focusing on plasma used in material processing mainly devoted to the microelectronics industry. Finally, specific applications related to plasma-assisted MBE for nitrides and dilute nitrides are given, showing some interesting research works performed to that purpose, and giving the usual characterization techniques ...

Plasma accelerators

International Nuclear Information System (INIS)

Bingham, R.; Angelis, U. de; Johnston, T.W.

1991-01-01

Recently attention has focused on charged particle acceleration in a plasma by a fast, large amplitude, longitudinal electron plasma wave. The plasma beat wave and plasma wakefield accelerators are two efficient ways of producing ultra-high accelerating gradients. Starting with the plasma beat wave accelerator (PBWA) and laser wakefield accelerator (LWFA) schemes and the plasma wakefield accelerator (PWFA) steady progress has been made in theory, simulations and experiments. Computations are presented for the study of LWFA. (author)

Application of plasma focus device to compression of toroidal plasma

International Nuclear Information System (INIS)

Ikuta, Kazunari

1980-01-01

A new concept of compressing a toroidal plasma using a plasma focus device is considered. Maximum compression ratio of toroidal plasma is determined merely by the initial density ratio of the toroidal plasma to a sheet plasma in a focus device because of the Rayleigh-Taylor instability. An initiation senario of plasma-linear is also proposed with a possible application of this concepts to the creation of a burning plasma in reversed field configurations, i.e., burning plasma vortex. (author)

Plasma physics an introduction to laboratory, space, and fusion plasmas

CERN Document Server

Piel, Alexander

2017-01-01

The enlarged new edition of this textbook provides a comprehensive introduction to the basic processes in plasmas and demonstrates that the same fundamental concepts describe cold gas-discharge plasmas, space plasmas, and hot fusion plasmas. Starting from particle drifts in magnetic fields, the principles of magnetic confinement fusion are explained and compared with laser fusion. Collective processes are discussed in terms of plasma waves and instabilities. The concepts of plasma description by magnetohydrodynamics, kinetic theory, and particle simulation are stepwise introduced. Space charge effects in sheath regions, double layers and plasma diodes are given the necessary attention. The novel fundamental mechanisms of dusty plasmas are explored and integrated into the framework of conventional plasmas. The book concludes with a concise description of modern plasma discharges. Written by an internationally renowned researcher in experimental plasma physics, the text keeps the mathematical apparatus simple a...

Edge plasma physical investigations of tokamak plasmas in CRIP

International Nuclear Information System (INIS)

Bakos, J.; Ignacz, P.; Koltai, L.; Paszti, F.; Petravich, G.; Szigeti, J.; Zoletnik, S.

1988-01-01

The results of the measurements performed in the field of thermonuclear high temperature plasma physics in CRIP (Hungary) are summarized. In the field of the edge plasma physics solid probes were used to test the external zone of plasma edges, and atom beams and balls were used to investigate both the external and internal zones. The plasma density distribution was measured by laser blow-off technics, using Na atoms, which are evaporated by laser pulses. The excitation of Na atom ball by tokamak plasma gives information on the status of the plasma edge. The toroidal asymmetry of particle transport in tokamak plasma was measured by erosion probes. The evaporated and transported impurities were collected on an other part of the plasma edge and were analyzed by SIMS and Rutherford backscattering. The interactions in plasma near the limiter were investigated by a special limiter with implemented probes. Recycling and charge exchange processes were measured. Disruption phenomena of tokamak plasma were analyzed and a special kind of disruptions, 'soft disruptions' and the related preliminary perturbations were discovered. (D.Gy.) 10 figs

Plasma astrophysics

CERN Document Server

Kaplan, S A; ter Haar, D

2013-01-01

Plasma Astrophysics is a translation from the Russian language; the topics discussed are based on lectures given by V.N. Tsytovich at several universities. The book describes the physics of the various phenomena and their mathematical formulation connected with plasma astrophysics. This book also explains the theory of the interaction of fast particles plasma, their radiation activities, as well as the plasma behavior when exposed to a very strong magnetic field. The text describes the nature of collective plasma processes and of plasma turbulence. One author explains the method of elementary

Plasma generator

International Nuclear Information System (INIS)

Omichi, Takeo; Yamanaka, Toshiyuki.

1976-01-01

Object: To recycle a coolant in a sealed hollow portion formed interiorly of a plasma limiter itself to thereby to cause direct contact between the coolant and the plasma limiter and increase of contact area therebetween to cool the plasma limiter. Structure: The heat resulting from plasma generated during operation and applied to the body of the plasma limiter is transmitted to the coolant, which recycles through an inlet and outlet pipe, an inlet and outlet nozzle and a hollow portion to hold the plasma limiter at a level less than a predetermined temperature. On the other hand, the heater wire is, at the time of emergency operation, energized to heat the plasma limiter, but this heat is transmitted to the limiter body to increase the temperature thereof. However, the coolant recycling the hollow portion comes into direct contact with the limiter body, and since the plasma limiter surround the hollow portion, the heat amount transmitted from the limiter body to the coolant increases to sufficiently cool the plasma limiter. (Yoshihara, H.)

Plasma centrifuges

International Nuclear Information System (INIS)

Karchevskij, A.I.; Potanin, E.P.

2000-01-01

The review of the most important studies on the isotope separation processes in the rotating plasma is presented. The device is described and the characteristics of operation of the pulse plasma centrifuges with weakly and strongly ionized plasma as well as the stationary plasma centrifuges with the medium weak ionization and devices, applying the stationary vacuum arc with the high ionization rate and the stationary beam-plasma discharge with complete ionization, are presented. The possible mechanisms of the isotope separation in plasma centrifuges are considered. The specific energy consumption for isotope separation in these devices is discussed [ru

Plasma waves

CERN Document Server

Swanson, DG

1989-01-01

Plasma Waves discusses the basic development and equations for the many aspects of plasma waves. The book is organized into two major parts, examining both linear and nonlinear plasma waves in the eight chapters it encompasses. After briefly discussing the properties and applications of plasma wave, the book goes on examining the wave types in a cold, magnetized plasma and the general forms of the dispersion relation that characterize the waves and label the various types of solutions. Chapters 3 and 4 analyze the acoustic phenomena through the fluid model of plasma and the kinetic effects. Th

Physics of plasma etching and plasma deposition

NARCIS (Netherlands)

Schram, D.C.; Hoog, de F.J.; Bisschops, T.J.; Kroesen, G.M.W.; Howorka, F.; Lindinger, W.; Maerk, T.D.

1986-01-01

The kinetics and mechanism of the title processes are discussed on the basis of a model in which the plasma-surface system is subdivided into 5 regions: (I) plasma prodn., (II) plasma flow plus radicals, (III) gas adsorbed layer, (IV) modified surface, and (V) undisturbed solid (or liq.) state.

Waves in plasmas (part 1 - wave-plasma interaction general background)

International Nuclear Information System (INIS)

Dumont, R.

2004-01-01

This document gathers a series of transparencies presented in the framework of the week-long lectures 'hot plasmas 2004' and dedicated to the physics of wave-plasma interaction. The structure of this document is as follows: 1) wave and diverse plasmas, 2) basic equations (Maxwell equations), 3) waves in a fluid plasma, and 4) waves in a kinetic plasma (collisionless plasma)

Integrated modelling of the edge plasma and plasma facing components

International Nuclear Information System (INIS)

Coster, D.P.; Bonnin, X.; Mutzke, A.; Schneider, R.; Warrier, M.

2007-01-01

Modelling of the interaction between the edge plasma and plasma facing components (PFCs) has tended to place more emphasis on either the plasma or the PFCs. Either the PFCs do not change with time and the plasma evolution is studied, or the plasma is assumed to remain static and the detailed interaction of the plasma and the PFCs are examined, with no back-reaction on the plasma taken into consideration. Recent changes to the edge simulation code, SOLPS, now allow for changes in both the plasma and the PFCs to be considered. This has been done by augmenting the code to track the time-development of the properties of plasma facing components (PFCs). Results of standard mixed-materials scenarios (base and redeposited C; Be) are presented

Miniature Coaxial Plasma injector Diagnostics by Beam Plasma Interaction

International Nuclear Information System (INIS)

El-Tayeb, H.; El-Gamal, H.

2003-01-01

A miniature coaxial gun has been used to study the interaction between plasma beam and low density plasma formed in glow discharge. The peak discharge current flow between the coaxial electrodes was 5.25 kA as a single pulse with pulse width of 60 mu. Investigations are carried out with argon gas at pressure 0.4 Torr. The plasma stream ejected from the coaxial discharge propagates in the neutral argon atoms with mean velocity of 1.2x10 5 cm/s. The plasma stream temperature and density were 4.2 eV and 2.4x10 13 cm -3 respectively. An argon negative glow has been used as base plasma where its electron temperature and density were 2.2 eV and 6.2x10 7 cm -3 respectively. When the plasma stream propagates through the negative glow discharge region its velocity decreased to 8.8 x 10 4 cm/s and also the plasma electron temperature decreased to 3.1 eV, while the stream density remained the same. An excited wave appeared on the electric probe having frequency equal to the plasma frequency of the plasma under consideration. Simulation of the problem showed that this method could be applied for plasma diagnostics within the region of investigation. Those further studies for high temperature, dense, and magnetized plasma will be considered

Plasma sheath in non-Maxwellian plasma

International Nuclear Information System (INIS)

Shimizu, Takuo; Horigome, Takashi

1992-01-01

Reviewing many theoretical and experimental works on the electron-energy distributions (EEDF) of various plasmas, we point out that many plasmas have EEDF of non-Maxwellian in shape. Therefore, the recent treatment of plasma sheath using the Maxwell-Boltzmann distribution approximation should be improved. To do this, we have adopted Rutcher's standard distribution as a generalized form in place of the traditional Maxwellian, and found that the minimum energy of ions entering the sheath edge (Bohm's criterion) varies largely, and have also shown the variation of Debye length with the shape of EEDF. The length is the most important parameter to proceed with more detailed analysis on plasma-sheaths, and also to control them in the future. (author)

Revisiting the plasma sheath—dust in plasma sheath

Energy Technology Data Exchange (ETDEWEB)

Das, G. C. [Mathematical Science Division, IASST, Guwahati 781014 (India); Deka, R.; Bora, M. P., E-mail: mpbora@gauhati.ac.in [Physics Department, Gauhati University, Guwahati 781014 (India)

2016-04-15

In this work, we have considered the formation of warm plasma sheath in the vicinity of a wall in a plasma with considerable presence of dust particles. As an example, we have used the parameters relevant in case of plasma sheath formed around surfaces of various solid bodies in space, though the results obtained in this work can be applied to any other physical situation such as laboratory plasma. In the ion-acoustic time scale, we neglect the dust dynamics. The dust particles affect the sheath dynamics by affecting the Poisson equation which determines the plasma potential in the sheath region. It is important to note that our calculations are valid only when the amount of dust particles is not sufficient so as to affect the plasma dynamics in the dust-acoustic time scale, but enough to affect the plasma sheath. We have assumed the current to a dust particle to be balanced throughout the analysis. This makes the grain potential dependent on plasma potential, which is then incorporated into the Poisson equation. The resultant numerical model becomes an initial value problem, which is described by a 1-D integro-differential equation, which is then solved self-consistently by incorporating the change in plasma potential caused by inclusion of the dust potential in the Poisson equation.

Fusion plasma physics

CERN Document Server

Stacey, Weston M

2012-01-01

This revised and enlarged second edition of the popular textbook and reference contains comprehensive treatments of both the established foundations of magnetic fusion plasma physics and of the newly developing areas of active research. It concludes with a look ahead to fusion power reactors of the future. The well-established topics of fusion plasma physics -- basic plasma phenomena, Coulomb scattering, drifts of charged particles in magnetic and electric fields, plasma confinement by magnetic fields, kinetic and fluid collective plasma theories, plasma equilibria and flux surface geometry, plasma waves and instabilities, classical and neoclassical transport, plasma-materials interactions, radiation, etc. -- are fully developed from first principles through to the computational models employed in modern plasma physics. The new and emerging topics of fusion plasma physics research -- fluctuation-driven plasma transport and gyrokinetic/gyrofluid computational methodology, the physics of the divertor, neutral ...

Structural Basis for Eculizumab-Mediated Inhibition of the Complement Terminal Pathway

DEFF Research Database (Denmark)

Schatz-Jakobsen, Janus Asbjørn; zhang, yuchun; Johnson, Krista

2016-01-01

the structural observations of the interaction are supported by the reduced ability of a subset of these mutated antibodies to inhibit MAC formation as tested in a hemolysis assay. Our results suggest that eculizumab functions by sterically preventing C5 from binding to convertases and explain the exquisite......Eculizumab is a humanized monoclonal antibody approved for treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uraemic syndrome. Eculizumab binds complement component C5 and prevents its cleavage by C5 convertases, inhibiting release of both...

The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine

DEFF Research Database (Denmark)

Hvas, A M; Juul, S; Gerdes, Lars Ulrik

2000-01-01

OBJECTIVE: To examine the relationship between the two diagnostic tests, plasma methylmalonic acid and plasma cobalamins, and their association with plasma creatinine, age and sex. DESIGN: Cross-sectional study of simultaneous laboratory measurements. SETTING: County of Aarhus, Denmark. SUBJECTS......: Records on 1689 patients who had their first plasma methylmalonic acid measurement during 1995 and 1996, and who had a simultaneous measurement of plasma cobalamins. Plasma creatinine values measured within a week of measurements of plasma methylmalonic acid and plasma cobalamins were available for 1255...... of the patients. MAIN OUTCOME MEASURES: Predictors of variation in plasma methylmalonic acid; plasma cobalamins, plasma creatinine, age and sex. RESULTS: Plasma methylmalonic acid was positively correlated with plasma creatinine, even for plasma creatinine within the normal range. These associations remained...

Plasma-wall interaction and plasma facing materials

International Nuclear Information System (INIS)

Tanabe, Tetsuo; Miyahara, Akira.

1990-01-01

The recognition that plasma-wall interaction plays the essential role from both standpoints of energy balance and particle balance for realizing nuclear fusion reactors has become to prevail. However, on how each elementary process acts and what competitive effect the synthetic action brings about, the stage of doing the qualitative discussion has just come, and the quantitative investigation is the problem for the future. In this paper, the plasma-wall interaction as seen from the research field of plasma-facing materials is discussed centering around graphite materials which have been mostly used at present, and the present status of the research and development on the problems of impurities, hydrogen recycling and heat resistance and radiation resistance is mentioned. Moreover, the problems are pointed out, and the course for the future is looked for. The recent experiment with large tokamaks adopted graphite or carbon as the plasma-facing materials, and the reduction of metallic impurities in plasma showed the clear improvement of plasma confinement characteristics. However, for the next device which requires forced cooling, the usability of graphite is doubtful. (K.I.) 51 refs

Plasma transport in the Scrape-off-Layer of magnetically confined plasma and the plasma exhaust

DEFF Research Database (Denmark)

Rasmussen, Jens Juul; Naulin, Volker; Nielsen, Anders Henry

An overview of the plasma dynamics in the Scrape-off-Layer (SOL) of magnetically confined plasma is presented. The SOL is the exhaust channel of the warm plasma from the core, and the understanding of the SOL plasma dynamics is one of the key issues in contemporary fusion research. It is essential...... for operation of fusion experiments and ultimately fusion power plants. Recent results clearly demonstrate that the plasma transport through the SOL is dominated by turbulent intermittent fluctuations organized into filamentary structures convecting particles, energy, and momentum through the SOL region. Thus......, the transport cannot be described and parametrized by simple diffusive type models. The transport leads to strong localized power loads on the first wall and the plasma facing components, which have serious lasting influence....

Plasma properties

International Nuclear Information System (INIS)

Weitzner, H.

1991-06-01

The Magneto-Fluid Dynamics Division continues to study a broad range of problems originating in plasma physics. Its principal focus is fusion plasma physics, and most particularly topics of particular significance for the world magnetic fusion program. During the calendar year 1990 we explored a wide range of topics including RF-induced transport as a plasma control mechanism, edge plasma modelling, further statistical analysis of L and H mode tokamak plasmas, antenna design, simulation of the edge of a tokamak plasma and the L-H transition, interpretation of the CCT experimental results at UCLA, turbulent transport, studies in chaos, the validity of moment approximations to kinetic equations and improved neoclassical modelling. In more basic studies we examined the statistical mechanisms of Coulomb systems and applied plasma ballooning mode theory to conventional fluids in order to obtain novel fluid dynamics stability results. In space plasma physics we examined the problem of reconnection, the effect of Alfven waves in space environments, and correct formulation of boundary conditions of the Earth for waves in the ionosphere

Plasma container

International Nuclear Information System (INIS)

Ebisawa, Katsuyuki.

1985-01-01

Purpose: To enable to easily detect that the thickness of material to be abraded is reduced to an allowable limit from the outerside of the plasma container even during usual operation in a plasma vessel for a thermonuclear device. Constitution: A labelled material is disposed to the inside or rear face of constituent members of a plasma container undergoing the irradiation of plasma particles. A limiter plate to be abraded in the plasma container is composed of an armour member and heat removing plate, in which the armour member is made of graphite and heat-removing plate is made of copper. If the armour member is continuously abraded under the effect of sputtering due to plasma particles, silicon nitride embedded so far in the graphite at last appears on the surface of the limiter plate to undergo the impact shocks of the plasma particles. Accordingly, abrasion of the limiter material can be detected by a detector comprising gas chromatography and it can easily be detected from the outside of the plasma content even during normal operation. (Horiuchi, T.)

Quiescent plasma machine for beam-plasma interaction and wave studies

International Nuclear Information System (INIS)

Ferreira, J.L.

1994-01-01

A quiescent double plasma machine for beam-plasma interaction wave studies is described. A detailed description of several plasma diagnostics used for plasma and wave excitation detection is given. A beam-plasma wave dispersion relation is used to compare theoretical values with the experimentally measured Langmuir wave frequencies and wavelengths. (author). 14 refs, 10 figs

Nonlocality of plasma fluctuations and transport in magnetically confined plasmas nonlocal plasma transport and radial structural formation

International Nuclear Information System (INIS)

Toi, Kazuo

2002-01-01

Experimental evidence and underlying physical processes of nonlocal characters and structural formation in magnetically confined toroidal plasmas are reviewed. Radial profiles of the plasmas exhibit characteristic structures, depending on the various confinement regimes. Profile stiffness subjected to some global constraint and rapid plasma responses to applied plasma perturbation result from nonlocal transport. Once the plasma is free from the constraint, the plasma state can be changed to a new state exhibiting various types of prominent structural formation such as an internal transport barrier. (author)

Plasma chromatography

International Nuclear Information System (INIS)

Anon.

1984-01-01

This book examines the fundamental theory and various applications of ion mobility spectroscopy. Plasma chromatography developed from research on the diffusion and mobility of ions. Topics considered include instrument design and description (e.g., performance, spectral interpretation, sample handling, mass spectrometry), the role of ion mobility in plasma chromatography (e.g., kinetic theory of ion transport), atmospheric pressure ionization (e.g., rate equations), the characterization of isomers by plasma chromatography (e.g., molecular ion characteristics, polynuclear aromatics), plasma chromatography as a gas chromatographic detection method (e.g., qualitative analysis, continuous mobility monitoring, quantitative analysis), the analysis of toxic vapors by plasma chromatography (e.g., plasma chromatograph calibration, instrument control and data processing), the analysis of semiconductor devices and microelectronic packages by plasma chromatography/mass spectroscopy (e.g., analysis of organic surface contaminants, analysis of water in sealed electronic packages), and instrument design and automation (hardware, software)

The Plasma Archipelago: Plasma Physics in the 1960s

Science.gov (United States)

Weisel, Gary J.

2017-09-01

With the foundation of the Division of Plasma Physics of the American Physical Society in April 1959, plasma physics was presented as the general study of ionized gases. This paper investigates the degree to which plasma physics, during its first decade, established a community of interrelated specialties, one that brought together work in gaseous electronics, astrophysics, controlled thermonuclear fusion, space science, and aerospace engineering. It finds that, in some regards, the plasma community was indeed greater than the sum of its parts and that its larger identity was sometimes glimpsed in inter-specialty work and studies of fundamental plasma behaviors. Nevertheless, the plasma specialties usually worked separately for two inter-related reasons: prejudices about what constituted "basic physics," both in the general physics community and within the plasma community itself; and a compartmentalized funding structure, in which each funding agency served different missions.

Plasma physics and engineering

CERN Document Server

Fridman, Alexander

2011-01-01

Part I: Fundamentals of Plasma Physics and Plasma ChemistryPlasma in Nature, in the Laboratory, and in IndustryOccurrence of Plasma: Natural and Man MadeGas DischargesPlasma Applications, Plasmas in IndustryPlasma Applications for Environmental ControlPlasma Applications in Energy ConversionPlasma Application for Material ProcessingBreakthrough Plasma Applications in Modern TechnologyElementary Processes of Charged Species in PlasmaElementary Charged Particles in Plasma and Their Elastic and Inelastic CollisionsIonization ProcessesMechanisms of Electron Losses: The Electron-Ion RecombinationEl

Plasma device

International Nuclear Information System (INIS)

Thode, L.E.

1981-01-01

A method is described for electron beam heating of a high-density plasma to drive a fast liner. An annular or solid relativistic electron beam is used to heat a plasma to kilovolt temperatures through streaming instabilities in the plasma. Energy deposited in the plasma then converges on a fast liner to explosively or ablatively drive the liner to implosion. (U.K.)

Dusty plasma phase in a steady state plasma device

International Nuclear Information System (INIS)

Liang Xiaoping; Zheng Jian; Ma Jinxiu; Liu Wangdong; Zhuang Ge; Xie Jinlin; Wang Congrong; Yu Changxuan

2000-01-01

A DC discharge dusty plasma device used for study of waves in dusty plasma is introduced. A dusty plasma column is produced with about 30 cm in length and about 8.4 cm in diameter. The electron saturation current of Langmuir probe is obviously decreasing while the dust grains are present in the plasma. The negative charge on dust grains is directly proportional to the rotation rate of the dispenser. And the dust grains carry up to 40% of the negative charges in the whole plasma

Transition in plasma fluctuation between attached and detached plasmas

International Nuclear Information System (INIS)

Okazaki, Katsuya; Ohno, Noriyasu; Kajita, Shin; Tanaka, Hirohiko

2012-01-01

The static and dynamic behaviors of detached plasmas have received considerable attention because the use of a detached divertor is thought to provide a promising method for reducing the heat flux to plasma-facing components. In this study, fluctuations were measured with an electrostatic probe as the plasma was changed from attached to detached states by increasing the neutral gas pressure. The transition from an attached plasma to a detached plasma was found to change the phase relation between the density and the potential. (author)

Plasma simulation in space propulsion : the helicon plasma thruster

OpenAIRE

Navarro Cavallé, Jaume

2017-01-01

The Helicon Plasma Thruster (HPT) is an electrodynamic rocket proposed in the early 2000s. It matches an Helicon Plasma Source (HPS), which ionizes the neutral gas and heats up the plasma, with aMagneticNozzle (MN),where the plasma is supersonically accelerated resulting in thrust. Although the core of this thruster inherits the knowledge on Helicon Plasma sources, dated from the seventies, the HPT technology is still not developed and remains below TRL 4. A deep review of the HPT State-of-ar...

Experimental investigation of plasma relaxation using a compact coaxial magnetized plasma gun in a background plasma

Science.gov (United States)

Zhang, Yue; Lynn, Alan; Gilmore, Mark; Hsu, Scott; University of New Mexico Collaboration; Los Alamos National Laboratory Collaboration

2013-10-01

A compact coaxial plasma gun is employed for experimental studies of plasma relaxation in a low density background plasma. Experiments are being conducted in the linear HelCat device at UNM. These studies will advance the knowledge of basic plasma physics in the areas of magnetic relaxation and space and astrophysical plasmas, including the evolution of active galactic jets/radio lobes within the intergalactic medium. The gun is powered by a 120pF ignitron-switched capacitor bank which is operated in a range of 5-10 kV and ~100 kA. Multiple diagnostics are employed to investigate plasma relaxation process. Magnetized Argon plasma bubbles with velocities ~1.2Cs and densities ~1020 m-3 have been achieved. Different distinct regimes of operation with qualitatively different dynamics are identified by fast CCD camera images, with the parameter determining the operation regime. Additionally, a B-dot probe array is employed to measure the spatial toroidal and poloidal magnetic flux evolution to identify detached plasma bubble configurations. Experimental data and analysis will be presented.

Streaming metal plasma generation by vacuum arc plasma guns

International Nuclear Information System (INIS)

MacGill, R.A.; Dickinson, M.R.; Anders, A.; Monteiro, O.R.; Brown, I.G.

1998-01-01

We have developed several different embodiments of repetitively pulsed vacuum arc metal plasma gun, including miniature versions, multicathode versions that can produce up to 18 different metal plasma species between which one can switch, and a compact high-duty cycle well-cooled version, as well as a larger dc gun. Plasma guns of this kind can be incorporated into a vacuum arc ion source for the production of high-energy metal ion beams, or used as a plasma source for thin film formation and for metal plasma immersion ion implantation and deposition. The source can also be viewed as a low-energy metal ion source with ion drift velocity in the range 20 - 200 eV depending on the metal species used. Here we describe the plasma sources that we have developed, the properties of the plasma generated, and summarize their performance and limitations. copyright 1998 American Institute of Physics

High-beta plasma blobs in the morningside plasma sheet

Directory of Open Access Journals (Sweden)

G. Haerendel

1999-12-01

Full Text Available Equator-S frequently encountered, i.e. on 30% of the orbits between 1 March and 17 April 1998, strong variations of the magnetic field strength of typically 5–15-min duration outside about 9RE during the late-night/early-morning hours. Very high-plasma beta values were found, varying between 1 and 10 or more. Close conjunctions between Equator-S and Geotail revealed the spatial structure of these "plasma blobs" and their lifetime. They are typically 5–10° wide in longitude and have an antisymmetric plasma or magnetic pressure distribution with respect to the equator, while being altogether low-latitude phenomena  (≤ 15°. They drift slowly sunward, exchange plasma across the equator and have a lifetime of at least 15–30 min. While their spatial structure may be due to some sort of mirror instability, little is known about the origin of the high-beta plasma. It is speculated that the morningside boundary layer somewhat further tailward may be the source of this plasma. This would be consistent with the preference of the plasma blobs to occur during quiet conditions, although they are also found during substorm periods. The relation to auroral phenomena in the morningside oval is uncertain. The energy deposition may be mostly too weak to generate a visible signature. However, patchy aurora remains a candidate for more disturbed periods.Key words. Magnetospheric physics (plasma convection; plasma sheet; plasma waves and instabilities

Plasma probe characteristics in low density hydrogen pulsed plasmas

International Nuclear Information System (INIS)

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

2015-01-01

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. (paper)

Charge dependence of the plasma travel length in atmospheric-pressure plasma

Energy Technology Data Exchange (ETDEWEB)

Yambe, Kiyoyuki; Konda, Kohmei; Masuda, Seiya [Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan)

2016-06-15

Plasma plume is generated using a quartz tube, helium gas, and foil electrode by applying AC high voltage under the atmosphere. The plasma plume is released into the atmosphere from inside of the quartz tube and is seen as the continuous movement of the plasma bullet. The travel length of plasma bullet is defined from plasma energy and force due to electric field. The drift velocity of plasma bullet has the upper limit under atmospheric-pressure because the drift velocity is determined from the balance between electric field and resistive force due to collisions between plasma and air. The plasma plume charge depends on the drift velocity. Consequently, in the laminar flow of helium gas flow state, the travel length of the plasma plume logarithmically depends on the plasma plume charge which changes with both the electric field and the resistive force.

Charge dependence of the plasma travel length in atmospheric-pressure plasma

International Nuclear Information System (INIS)

Yambe, Kiyoyuki; Konda, Kohmei; Masuda, Seiya

2016-01-01

Plasma plume is generated using a quartz tube, helium gas, and foil electrode by applying AC high voltage under the atmosphere. The plasma plume is released into the atmosphere from inside of the quartz tube and is seen as the continuous movement of the plasma bullet. The travel length of plasma bullet is defined from plasma energy and force due to electric field. The drift velocity of plasma bullet has the upper limit under atmospheric-pressure because the drift velocity is determined from the balance between electric field and resistive force due to collisions between plasma and air. The plasma plume charge depends on the drift velocity. Consequently, in the laminar flow of helium gas flow state, the travel length of the plasma plume logarithmically depends on the plasma plume charge which changes with both the electric field and the resistive force.

Plasma rotation study in Tore Supra radio frequency heated plasmas

International Nuclear Information System (INIS)

Chouli, Bilal

2014-01-01

Toroidal flows are found to improve the performance of the magnetic confinement devices with increase of the plasma stability and confinement. In ITER or future reactors, the torque from NBI should be less important than in present-day tokamaks. Consequently, it is of interest to study other intrinsic mechanisms that can give rise to plasma rotation in order to predict the rotation profile in experiments. Intriguing observations of plasmas rotation have been made in radio frequency (RF) heated plasmas with little or no external momentum injection. Toroidal rotation in both the direction of the plasma current (co-current) and in the opposite direction (counter-current) has been observed depending on the heating schemes and plasma performance. In Tore Supra, most observations in L-mode plasmas have been in the counter-current direction. However, in this thesis, we show that in lower hybrid current drive (LHCD), the core toroidal rotation increment is in co- or counter-current direction depending on the plasma current amplitude. At low plasma current the rotation change is in the co-current direction while at high plasma current, the change is in the counter-current direction. In both low and high plasma current cases, rotation increments are found to increase linearly with the injected LH power. Several mechanisms in competition which can induce co- or counter-current rotation in Tore Supra LHCD plasmas are investigated and typical order of magnitude are discussed in this thesis. (author) [fr

Dynamic plasma screening effects on atomic collisions in dense plasmas

International Nuclear Information System (INIS)

Young-Dae Jung

1999-01-01

Dynamic plasma screening effects are investigated on electron-ion collisional excitation and Coulomb Bremsstrahlung processes in dense plasmas. The electron-ion interaction potential is considered by introduction of the plasma dielectric function. The straight-ling trajectory method is applied to the path of the projectile electron. The transition probability including the dynamic plasma screening effect is found to be always greater than that including the static plasma screening effects. It is found that the differential Bremsstrahlung radiation cross section including the dynamic plasma screening effect is also greater than that including the static plasma screening effect. When the projectile velocity is smaller than the electron thermal velocity, the dynamic polarization screening effect becomes the static plasma screening effect. However, when the projectile velocity is greater than the electron thermal velocity, the interaction potential is almost unshielded

High beta plasma operation in a toroidal plasma producing device

International Nuclear Information System (INIS)

Clarke, J.F.

1978-01-01

A high beta plasma is produced in a plasma producing device of toroidal configuration by ohmic heating and auxiliary heating. The plasma pressure is continuously monitored and used in a control system to program the current in the poloidal field windings. Throughout the heating process, magnetic flux is conserved inside the plasma and the distortion of the flux surfaces drives a current in the plasma. As a consequence, the total current increases and the poloidal field windings are driven with an equal and opposing increasing current. The spatial distribution of the current in the poloidal field windings is determined by the plasma pressure. Plasma equilibrium is maintained thereby, and high temperature, high beta operation results

Optical plasma torch electron bunch generation in plasma wakefield accelerators

Directory of Open Access Journals (Sweden)

G. Wittig

2015-08-01

Full Text Available A novel, flexible method of witness electron bunch generation in plasma wakefield accelerators is described. A quasistationary plasma region is ignited by a focused laser pulse prior to the arrival of the plasma wave. This localized, shapeable optical plasma torch causes a strong distortion of the plasma blowout during passage of the electron driver bunch, leading to collective alteration of plasma electron trajectories and to controlled injection. This optically steered injection is more flexible and faster when compared to hydrodynamically controlled gas density transition injection methods.

Vaporized wall material/plasma interaction during plasma disruption

International Nuclear Information System (INIS)

Merrill, B.J.; Carroll, M.C.; Jardin, S.C.

1983-01-01

The purpose of this paper is to discuss a new plasma disruption model that has been developed for analyzing the consequences to the limiter/first wall structures. This model accounts for: nonequilibrium surface vaporization for the ablating structure, nonequilibrium ionization of and radiation emitted from the ablated material in the plasma, plasma particle and energy transport, and plasma electromagnetic field evolution during the disruption event. Calculations were performed for a 5 ms disruption on a stainless steel flat limiter as part of a D-shaped first wall. These results indicated that the effectiveness of the ablated wall material to shield the exposed structure is greater than predicted by earlier models, and that the rate of redeposition of the ablated wall material ions is very dramatic. Impurity transport along magnetic field lines, global plasma motion, and radiation transport in an optically thick plasma are important factors that require additional modeling. Experimental measurements are needed to verify these models

Plasma immersion surface modification with metal ion plasma

International Nuclear Information System (INIS)

Brown, I.G.; Yu, K.M.; Godechot, X.

1991-04-01

We describe here a novel technique for surface modification in which metal plasma is employed and by which various blends of plasma deposition and ion implantation can be obtained. The new technique is a variation of the plasma immersion technique described by Conrad and co-workers. When a substrate is immersed in a metal plasma, the plasma that condenses on the substrate remains there as a film, and when the substrate is then implanted, qualitatively different processes can follow, including' conventional' high energy ion implantation, recoil implantation, ion beam mixing, ion beam assisted deposition, and metallic thin film and multilayer fabrication with or without species mixing. Multiple metal plasma guns can be used with different metal ion species, films can be bonded to the substrate through ion beam mixing at the interface, and multilayer structures can be tailored with graded or abrupt interfaces. We have fabricated several different kinds of modified surface layers in this way. 22 refs., 4 figs

Plasma properties

International Nuclear Information System (INIS)

Weitzner, H.

1990-06-01

This paper discusses the following topics: MHD plasma activity: equilibrium, stability and transport; statistical analysis; transport studies; edge physics studies; wave propagation analysis; basic plasma physics and fluid dynamics; space plasma; and numerical methods

Plasmas for medicine

Science.gov (United States)

von Woedtke, Th.; Reuter, S.; Masur, K.; Weltmann, K.-D.

2013-09-01

Plasma medicine is an innovative and emerging field combining plasma physics, life science and clinical medicine. In a more general perspective, medical application of physical plasma can be subdivided into two principal approaches. (i) “Indirect” use of plasma-based or plasma-supplemented techniques to treat surfaces, materials or devices to realize specific qualities for subsequent special medical applications, and (ii) application of physical plasma on or in the human (or animal) body to realize therapeutic effects based on direct interaction of plasma with living tissue. The field of plasma applications for the treatment of medical materials or devices is intensively researched and partially well established for several years. However, plasma medicine in the sense of its actual definition as a new field of research focuses on the use of plasma technology in the treatment of living cells, tissues, and organs. Therefore, the aim of the new research field of plasma medicine is the exploitation of a much more differentiated interaction of specific plasma components with specific structural as well as functional elements or functionalities of living cells. This interaction can possibly lead either to stimulation or inhibition of cellular function and be finally used for therapeutic purposes. During recent years a broad spectrum of different plasma sources with various names dedicated for biomedical applications has been reported. So far, research activities were mainly focused on barrier discharges and plasma jets working at atmospheric pressure. Most efforts to realize plasma application directly on or in the human (or animal) body for medical purposes is concentrated on the broad field of dermatology including wound healing, but also includes cancer treatment, endoscopy, or dentistry. Despite the fact that the field of plasma medicine is very young and until now mostly in an empirical stage of development yet, there are first indicators of its enormous

Development and application of helicon plasma sources. Evolution of extensive plasma science

International Nuclear Information System (INIS)

Shinohara, Shunjiro

2009-01-01

Recent advances in plasma science are remarkable, and are deeply indebted to the development of sophisticated plasma sources. While numerous methods have been proposed for producing the plasma, helicon plasma sources, capable of generating high density (>10 13 cm -3 ) plasma with high ionization degree (>several ten percent) over a wide range of external control parameters, have been utilized in such broad areas as fundamental and processing plasmas, nuclear fusion, gas laser, modeling of space plasma, plasma acceleration/propulsion, among others. On the other hand, a number of important issues are left unsolved, in particular, those relevant to the wave phenomena and efficient plasma production. Solution to these issues are expected to play key roles in taking full advantage of the helicon plasma sources in the next generation. In this article, we overview our current understanding of the helicon plasma production and recent development of characteristic helicon plasma sources, and discuss possible future advancement of extensive plasma science utilizing them. (author)

ECR Plasma Photos

International Nuclear Information System (INIS)

Racz, R.; Biri, S.; Palinkas, J.

2009-01-01

Complete text of publication follows. In order to observe and study systematically the plasma of electron cyclotron resonance (ECR) ion sources (ECRIS) we made a high number of high-resolution visible light plasma photos and movies in the ATOMKI ECRIS Laboratory. This required building the ECR ion source into an open plasma device, temporarily. An 8MP digital camera was used to record photos of plasmas made from He, methane, N, O, Ne, Ar, Kr, Xe gases and from their mixtures. The effects of the main external setting parameters (gas pressure, gas composition, magnetic field, microwave power, microwave frequency) were studied to the shape, color and structure of the plasma. The double frequency mode (9+14 GHz) was also realized and photos of this special 'star-in-star' shape plasma were recorded. A study was performed to analyze and understand the color of the ECR plasmas. The analysis of the photo series gave us many qualitative and numerous valuable physical information on the nature of ECR plasmas. To our best knowledge our work is the first systematic study of ECR plasmas in the visible light region. When looking in the plasma chamber of an ECRIS we can see an axial image of the plasma (figure 1) in conformity with experimental setup. Most of the quantitative information was obtained through the summarised values of the Analogue Digital Unit (ADU) of pixels. By decreasing the strength of the magnetic trap we clearly observed that the brightness of the central part of the plasma gradually decreases, i.e. the plasma becomes more and more 'empty'. Figure 2 shows a photo series of ECR plasma at decreasing axial magnetic field. The radial size of the plasma increased because of the ascendant resonant zone. By increasing the power of the injected microwave an optimum (or at least saturation) was found in the brightness of the plasma. We found correlation between the gas dosing rates and plasma intensities. When sweeping the frequency of the microwave in a wide region

On non-equilibrium atmospheric pressure plasma jets and plasma bullet

Science.gov (United States)

Lu, Xinpei

2012-10-01

Because of the enhanced plasma chemistry, atmospheric pressure nonequilibrium plasmas (APNPs) have been widely studied for several emerging applications such as biomedical applications. For the biomedical applications, plasma jet devices, which generate plasma in open space (surrounding air) rather than in confined discharge gaps only, have lots of advantages over the traditional dielectric barrier discharge (DBD) devices. For example, it can be used for root canal disinfection, which can't be realized by the traditional plasma device. On the other hand, currently, the working gases of most of the plasma jet devices are noble gases or the mixtures of the noble gases with small amount of O2, or air. If ambient air is used as the working gas, several serious difficulties are encountered in the plasma generation process. Amongst these are high gas temperatures and disrupting instabilities. In this presentation, firstly, a brief review of the different cold plasma jets developed to date is presented. Secondly, several different plasma jet devices developed in our lab are reported. The effects of various parameters on the plasma jets are discussed. Finally, one of the most interesting phenomena of APNP-Js, the plasma bullet is discussed and its behavior is described. References: [1] X. Lu, M. Laroussi, V. Puech, Plasma Sources Sci. Technol. 21, 034005 (2012); [2] Y. Xian, X. Lu, S. Wu, P. Chu, and Y. Pan, Appl. Phys. Lett. 100, 123702 (2012); [3] X. Pei, X. Lu, J. Liu, D. Liu, Y. Yang, K. Ostrikov, P. Chu, and Y. Pan, J. Phys. D 45, 165205 (2012).

High-beta plasma blobs in the morningside plasma sheet

Directory of Open Access Journals (Sweden)

G. Haerendel

Full Text Available Equator-S frequently encountered, i.e. on 30% of the orbits between 1 March and 17 April 1998, strong variations of the magnetic field strength of typically 5–15-min duration outside about 9R_E during the late-night/early-morning hours. Very high-plasma beta values were found, varying between 1 and 10 or more. Close conjunctions between Equator-S and Geotail revealed the spatial structure of these "plasma blobs" and their lifetime. They are typically 5–10^° wide in longitude and have an antisymmetric plasma or magnetic pressure distribution with respect to the equator, while being altogether low-latitude phenomena 
(≤ 15^°. They drift slowly sunward, exchange plasma across the equator and have a lifetime of at least 15–30 min. While their spatial structure may be due to some sort of mirror instability, little is known about the origin of the high-beta plasma. It is speculated that the morningside boundary layer somewhat further tailward may be the source of this plasma. This would be consistent with the preference of the plasma blobs to occur during quiet conditions, although they are also found during substorm periods. The relation to auroral phenomena in the morningside oval is uncertain. The energy deposition may be mostly too weak to generate a visible signature. However, patchy aurora remains a candidate for more disturbed periods.

Key words. Magnetospheric physics (plasma convection; plasma sheet; plasma waves and instabilities

Modeling plasma behavior in a plasma electrode Pockels cell

International Nuclear Information System (INIS)

Boley, C.D.; Rhodes, M.A.

1999-01-01

The authors present three interrelated models of plasma behavior in a plasma electrode Pockels cell (PEPC). In a PEPC, plasma discharges are formed on both sides of a thin, large-aperture electro-optic crystal (typically KDP). The plasmas act as optically transparent, highly conductive electrodes, allowing uniform application of a longitudinal field to induce birefringence in the crystal. First, they model the plasma in the thin direction, perpendicular to the crystal, via a one-dimensional fluid model. This yields the electron temperature and the density and velocity profiles in this direction as functions of the neutral pressure, the plasma channel width, and the discharge current density. Next, they model the temporal response of the crystal to the charging process, combining a circuit model with a model of the sheath which forms near the crystal boundary. This model gives the time-dependent voltage drop across the sheath as a function of electron density at the sheath entrance. Finally, they develop a two-dimensional MHD model of the planar plasma, in order to calculate the response of the plasma to magnetic fields. They show how the plasma uniformity is affected by the design of the current return, by the longitudinal field from the cathode magnetron, and by fields from other sources. This model also gives the plasma sensitivity to the boundary potential at which the top and bottom of the discharge are held. They validate these models by showing how they explain observations in three large Pockels cells built at Lawrence Livermore National Laboratory

Influence of plasma density and plasma sheath dynamics on the ion implantation by plasma immersion technique

OpenAIRE

Ensinger, Wolfgang

1996-01-01

Influence of plasma density and plasma sheath dynamics on the ion implantation by plasma immersion technique / B. Rauschenbach ... - In: Nuclear instruments and methods in physics research. B. 113. 1996. S. 266-269

Momentum transfer to rotating magnetized plasma from gun plasma injection

International Nuclear Information System (INIS)

Shamim, Imran; Hassam, A. B.; Ellis, R. F.; Witherspoon, F. D.; Phillips, M. W.

2006-01-01

Numerical simulations are carried out to investigate the penetration and momentum coupling of a gun-injected plasma slug into a rotating magnetized plasma. An experiment along these lines is envisioned for the Maryland Centrifugal Experiment (MCX) [R. F. Ellis et al., Phys. Plasmas 8, 2057 (2001)] using a coaxial plasma accelerator gun developed by HyperV Technologies Corp. [F. D. Witherspoon et al., Bull. Am. Phys. Soc. 50, LP1 87 (2005)]. The plasma gun would be located in the axial midplane and fired off-axis into the rotating MCX plasma annulus. The numerical simulation is set up so that the initial momentum in the injected plasma slug is of the order of the initial momentum of the target plasma. Several numerical firings are done into the cylindrical rotating plasma. Axial symmetry is assumed. The slug is seen to penetrate readily and deform into a mushroom, characteristic of interchange deformations. It is found that up to 25% of the momentum in the slug can be transferred to the background plasma in one pass across a cylindrical chord. For the same initial momentum, a high-speed low density slug gives more momentum transfer than a low-speed high density slug. Details of the numerical simulations and a scaling study are presented

MHD description of plasma: handbook of plasma physics

International Nuclear Information System (INIS)

Kulsrud, R.M.

1980-10-01

The basic sets of MHD equations for the description of a plasma in various limits are derived and their usefulness and limits of validity are discussed. These limits are: the one fluid collisional plasma, the two fluid collisional plasma, the Chew-Goldberger Low formulation of the guiding center limit of a collisionless plasma and the double-adiabatic limit. Conservation relations are derived from these sets and the mathematics of the concept of flux freezing is given. An example is given illustrating the differences between guiding center theory and double adiabatic theory

Plasma device

International Nuclear Information System (INIS)

Thode, L.E.

1981-01-01

A method is described of providing electron beam heating of a high-density plasma to drive a fast liner to implode a structured microsphere. An annular relativistic electron beam is used to heat an annular plasma to kilovolt temperatures through streaming instabilities in the plasma. Energy deposited in the annular plasma then converges on a fast liner to explosively or ablatively drive the liner to convergence to implode the structured microsphere. (U.K.)

Nonlinear Plasma Waves Excitation by Intense Ion Beams in Background Plasma

International Nuclear Information System (INIS)

Kaganovich, Igor D.; Startsev, Edward A.; Davidson, Ronald C.

2004-01-01

Plasma neutralization of an intense ion pulse is of interest for many applications, including plasma lenses, heavy ion fusion, cosmic ray propagation, etc. An analytical electron fluid model has been developed to describe the plasma response to a propagating ion beam. The model predicts very good charge neutralization during quasi-steady-state propagation, provided the beam pulse duration τ b is much longer than the electron plasma period 2π/ω p , where ω p = (4πe 2 n p /m) 1/2 is the electron plasma frequency and n p is the background plasma density. In the opposite limit, the beam pulse excites large-amplitude plasma waves. If the beam density is larger than the background plasma density, the plasma waves break. Theoretical predictions are compared with the results of calculations utilizing a particle-in-cell (PIC) code. The cold electron fluid results agree well with the PIC simulations for ion beam propagation through a background plasma. The reduced fluid description derived in this paper can provide an important benchmark for numerical codes and yield scaling relations for different beam and plasma parameters. The visualization of numerical simulation data shows complex collective phenomena during beam entry and exit from the plasma

Nonlinear plasma waves excitation by intense ion beams in background plasma

International Nuclear Information System (INIS)

Kaganovich, Igor D.; Startsev, Edward A.; Davidson, Ronald C.

2004-01-01

Plasma neutralization of an intense ion pulse is of interest for many applications, including plasma lenses, heavy ion fusion, cosmic ray propagation, etc. An analytical electron fluid model has been developed to describe the plasma response to a propagating ion beam. The model predicts very good charge neutralization during quasi-steady-state propagation, provided the beam pulse duration τ b is much longer than the electron plasma period 2π/ω p , where ω p =(4πe 2 n p /m) 1/2 is the electron plasma frequency, and n p is the background plasma density. In the opposite limit, the beam pulse excites large-amplitude plasma waves. If the beam density is larger than the background plasma density, the plasma waves break. Theoretical predictions are compared with the results of calculations utilizing a particle-in-cell (PIC) code. The cold electron fluid results agree well with the PIC simulations for ion beam propagation through a background plasma. The reduced fluid description derived in this paper can provide an important benchmark for numerical codes and yield scaling relations for different beam and plasma parameters. The visualization of numerical simulation data shows complex collective phenomena during beam entry and exit from the plasma

Scattering of electromagnetic waves into plasma oscillations via plasma particles

International Nuclear Information System (INIS)

Lin, A.T.; Dawson, J.M.

1975-01-01

A plasma subjected to an intense electromagnetic wave can exhibit a large number of parametric instabilities. An interesting example which has received little attention is the decay of the electromagnetic wave into a plasma oscillation with the excess energy and momentum being carried off by electrons. This process has been simulated on a one-and-two-halves dimensional electromagnetic code. The incident electromagnetic wave had a frequency near the plasma frequency so that decay into a plasma oscillation and a backscattered electromagnetic wave was excluded. As expected, the threshold for this instability was very large , so it is unlikely that this instability is competitive in most laser plasmas. Nevertheless, the physical mechanism involved provides a means for absorption of laser light and acceleration of particles in a plasma containing large amplitude plasma oscillations

Interaction between electromagnetic waves and plasma waves in motional plasma

International Nuclear Information System (INIS)

Chen, S. Y.; Gao, M.; Tang, C. J.; Peng, X. D.

2009-01-01

The electromagnetic wave (EM wave) behavior and the electromagnetic instability caused by the interaction between an EM wave and a plasma wave in motional plasma are studied. The dispersion relation of EM waves and the dielectric tensor of motional plasma are derived by magnetohydrodynamics, and the wave phenomenon in motional plasma is displayed. As a result, the electromagnetic instability, which is excited by the interaction between the EM waves and the plasma waves, is revealed. The mechanism of the instability is the coupling between high frequency electromagnetic field and the transverse electron oscillation derived from the deflection of longitudinal electron oscillation due to self-magnetic field. The present research is useful with regard to the new type of plasma radiation source, ion-focusing accelerator, and plasma diagnostic technique.

Plasma properties of a modified beam-plasma type ion source

International Nuclear Information System (INIS)

Ishikawa, Junzo; Sano, Fumimichi; Tsuji, Hiroshi; Ektessabi, A.M.; Takagi, Toshinori

1978-01-01

The properties of the plasma produced by beam-plasma discharge were experimentally investigated. The ion source used for this work consists of three parts, that is, the ion-extracting region with an electron gun, the drift space and the collector region. Primary and secondary electron beams are injected in to the drift tube. The interaction between plasma and these electron beams causes production of high density plasma by virtue of the beam-plasma discharge. The gas inlet is located in the middle of the drift tube, so that the gas conductance is high. The energy of the primary and secondary electron beams is transferred to that microwaves through beam-plasma interaction. The microwaves heat the plasma electrons by the cyclotron resonance or other mechanism. The amount of the energetic plasma electrons is much larger than that of the beam electrons, so that neutral gas is ionized. The density of the produced plasma is 10 2 or 10 3 times as large as the plasma produced by impact ionization. With a probe located in the middle of the drift tube, the plasma density and the electron temperature can be measured, and the power and spectra of the microwaves can be detected. The microwave oscillation, the primary electron beam characteristics, and the gas pressure characteristics were studied. Larger current of the high energy primary of secondary electron beam is required for the effective discharge. The ion source has to be operated at the minimum gas pressure. The length of beam-plasma interaction and the magnetic field intensity in the drift tube are also important parameters. (Kato, T.)

Analysis of plasma behavior and electro-magnetic interaction between plasma and device

International Nuclear Information System (INIS)

Kobayashi, Tomofumi

1980-01-01

A simulation program for the analysis of plasma behavior and the electromagnetic interaction between plasma and device has been developed. The program consists of a part for the analysis of plasma behavior (plasma system) and a part for the analysis of the electro-magnetic interaction between plasma and devices (circuit system). The parameters which connect the plasma system and the circuit system are the electric resistance of plasma, the internal inductance, and the plasma current. For the plasma system, the simultaneous equations which describe the density distribution of plasma particles, the temperature distribution of electrons and ions, and the space-time variation of current density distribution were derived. The one-dimensional plasma column in γ-direction was considered. The electric resistance and the internal inductance can be deduced. The circuit components are a current transformer, a vertical field coil, a quadrupole field coil, a vacuum chamber and others. An equation which describes plasma position and the shape of cross section is introduced. The plasma position can be known by solving the Mukhavatov's formula of equilibrium. By using this program, the build-up process of plasma current in JT-60 was analysed. It was found that the expansion of plasma sub radius and the control of current distribution by gas injection are the effective methods to obtain high temperature and high density plasma. The eddy current induced in a vacuum vessel shields 40 percent of magnetic field made in the plasma region by a vertical field coil. (Kato, T.)

Plasma waves in hot relativistic beam-plasma systems: Pt. 1

International Nuclear Information System (INIS)

Magneville, A.

1990-01-01

Dispersion relations of plasma waves in a beam-plasma system are computed in the general case where the plasma and beam temperatures, and the velocity of the beam, may be relativistic. The two asymptotic temperature cases, and different contributions of plasma or beam particles to wave dispersion are considered. (author)

Superconducting plasmas

International Nuclear Information System (INIS)

Ohnuma, Toshiro; Ohno, J.

1994-01-01

Superconducting (SC) plasmas are proposed and investigated. The SC plasmas are not yet familiar and have not yet been studied. However, the existence and the importance of SC plasmas are stressed in this report. The existence of SC plasmas are found as follows. There is a fundamental property of Meissner effect in superconductors, which shows a repulsive effect of magnetic fields. Even in that case, in a microscopic view, there is a region of magnetic penetration. The penetration length λ is well-known as London's penetration depth, which is expressed as δ = (m s /μ 0 n s q s 2 ) 1/2 where m s , n s , q s and μ o show the mass, the density, the charge of SC electron and the permeability in free space, respectively. Because this expression is very simple, no one had tried it into more simple and meaningful form. Recently, one of the authors (T.O.) has found that the length can be expressed into more simple and understandable fundamental form as λ = c/ω ps where c = (ε 0 μ 0 ) -1/2 and ω ps = (n s q s 2 /m s ε 0 ) 1/2 are the light velocity and the superconducting plasma frequency. From this simple expression, the penetration depth of the magnetic field to SC is found as a SC plasma skin depth, that is, the fundamental property of SC can be expressed by the SC plasmas. This discovery indicates an importance of the studies of superconducting plasmas. From these points, several properties (propagating modes et al) of SC plasmas, which consist of SC electrons, normal electrons and lattice ions, are investigated in this report. Observations of SC plasma frequency is also reported with a use of Terahertz electromagnet-optical waves

Plasma focus breeder

International Nuclear Information System (INIS)

Ikuta, Kazunari.

1981-09-01

Instead of using linear accelerators, it is possible to breed fissile fuels with the help of high current plasma focus device. A mechanism of accelerating proton beam in plasma focus device to high energy would be a change of inductance in plasma column because of rapid growth of plasma instability. A possible scheme of plasma focus breeder is also proposed. (author)

Cosmic plasma

Energy Technology Data Exchange (ETDEWEB)

Alfven, H [California Univ., San Diego, La Jolla (USA)

1981-01-01

The properties of space plasmas are analyzed, based on laboratory results and data obtained by in situ measurements in the magnetosphere (including the heliosphere). Attention is given to the question of how much knowledge can be gained by a systematic comparison of different regions of plasma, and plasmas are considered with linear dimensions varying from laboratory size up to the Hubble distance. The traditional magnetic field description of plasmas is supplemented by an electric current description and it is demonstrated that many problems are easier to understand with a dualistic approach. Using the general plasma properties obtained, the origin and evolution of the solar system is summarized and the evolution and present structure of the universe (cosmology) is discussed.

Merging and Splitting of Plasma Spheroids in a Dusty Plasma

Science.gov (United States)

Mikikian, Maxime; Tawidian, Hagop; Lecas, Thomas

2012-12-01

Dust particle growth in a plasma is a strongly disturbing phenomenon for the plasma equilibrium. It can induce many different types of low-frequency instabilities that can be experimentally observed, especially using high-speed imaging. A spectacular case has been observed in a krypton plasma where a huge density of dust particles is grown by material sputtering. The instability consists of well-defined regions of enhanced optical emission that emerge from the electrode vicinity and propagate towards the discharge center. These plasma spheroids have complex motions resulting from their mutual interaction that can also lead to the merging of two plasma spheroids into a single one. The reverse situation is also observed with the splitting of a plasma spheroid into two parts. These results are presented for the first time and reveal new behaviors in dusty plasmas.

Magnetospheric plasma waves

International Nuclear Information System (INIS)

Shawhan, S.D.

1977-01-01

A brief history of plasma wave observations in the Earth's magnetosphere is recounted and a classification of the identified plasma wave phenomena is presented. The existence of plasma waves is discussed in terms of the characteristic frequencies of the plasma, the energetic particle populations and the proposed generation mechanisms. Examples are given for which plasmas waves have provided information about the plasma parameters and particle characteristics once a reasonable theory has been developed. Observational evidence and arguments by analogy to the observed Earth plasma wave processes are used to identify plasma waves that may be significant in other planetary magnetospheres. The similarities between the observed characteristics of the terrestrial kilometric radiation and radio bursts from Jupiter, Saturn and possibly Uranus are stressed. Important scientific problems concerning plasma wave processes in the solar system and beyond are identified and discussed. Models for solar flares, flare star radio outbursts and pulsars include elements which are also common to the models for magnetospheric radio bursts. Finally, a listing of the research and development in terms of instruments, missions, laboratory experiments, theory and computer simulations needed to make meaningful progress on the outstanding scientific problems of plasma wave research is given. (Auth.)

Metallurgical plasma torches

International Nuclear Information System (INIS)

Shapovalov, V.A.; Latash, Yu.V.

2000-01-01

The technological equipment for the plasma heating of metals, plasma melting and plasma treatment of the surface is usually developed on the basis of are plasma torches using direct or alternating current. The reasons which partly restrict the industrial application of the plasma torches are the relatively short service life of the electrode (cathode) on which the arc is supported, and the contamination of the treated metal with the products of failure of the electrode. The aim of this work was to determine the reasons for the occurrence of negative phenomena observed in the process of service of plasma torches, and propose suitable approaches to the design of metallurgical plasma torches characterised by a long service life

Plasma response to electron energy filter in large volume plasma device

International Nuclear Information System (INIS)

Sanyasi, A. K.; Awasthi, L. M.; Mattoo, S. K.; Srivastava, P. K.; Singh, S. K.; Singh, R.; Kaw, P. K.

2013-01-01

An electron energy filter (EEF) is embedded in the Large Volume Plasma Device plasma for carrying out studies on excitation of plasma turbulence by a gradient in electron temperature (ETG) described in the paper of Mattoo et al. [S. K. Mattoo et al., Phys. Rev. Lett. 108, 255007 (2012)]. In this paper, we report results on the response of the plasma to the EEF. It is shown that inhomogeneity in the magnetic field of the EEF switches on several physical phenomena resulting in plasma regions with different characteristics, including a plasma region free from energetic electrons, suitable for the study of ETG turbulence. Specifically, we report that localized structures of plasma density, potential, electron temperature, and plasma turbulence are excited in the EEF plasma. It is shown that structures of electron temperature and potential are created due to energy dependence of the electron transport in the filter region. On the other hand, although structure of plasma density has origin in the particle transport but two distinct steps of the density structure emerge from dominance of collisionality in the source-EEF region and of the Bohm diffusion in the EEF-target region. It is argued and experimental evidence is provided for existence of drift like flute Rayleigh-Taylor in the EEF plasma

Oscillatory processes in plasma

International Nuclear Information System (INIS)

Gallin, E.

1980-01-01

The oscillatory process play an important part in plasma evolution, In hot plasma in particular, the interactions between the oscillation modes are preponderant in relation to the binary collisions between particles. The nonlineary interactions between collective plasma oscillations can generate, in this case, a non-balanced steady state of plasma (steady turbulence). The paper elucidates some aspects of the oscillatory phenomena which contribute to the plasma state evolution, especially of hot plasma. A major part of the paper is devoted to the study of parametric instabilities in plasma and their role in increasing the temperature of plasma components (electrons, ions). Both parametric instabilities in plasma in the vicinity of thermodynamic balance and parametric processes is steady turbulent plasma are analysed - in relation to additional heating of hot plasma. An important result of the thesis refers to the drowing-up of a non-lineary interaction model between the oscillation modes in turbulent plasma, being responsible for the electromagnetic radiation in hot plasma. On the basis of the model suggested in the paper the existence of a low frequency radiative mode in hot plasma in a turbulent state, can be demonstrated. Its frequency could be even lower than plasma frequency in the field of long waves be even lower than plasma frequency in the field of long waves. Such a radiative mode was detected experimentally in focussed plasma installations. (author)

A contoured gap coaxial plasma gun with injected plasma armature.

Science.gov (United States)

Witherspoon, F Douglas; Case, Andrew; Messer, Sarah J; Bomgardner, Richard; Phillips, Michael W; Brockington, Samuel; Elton, Raymond

2009-08-01

A new coaxial plasma gun is described. The long term objective is to accelerate 100-200 microg of plasma with density above 10(17) cm(-3) to greater than 200 km/s with a Mach number above 10. Such high velocity dense plasma jets have a number of potential fusion applications, including plasma refueling, magnetized target fusion, injection of angular momentum into centrifugally confined mirrors, high energy density plasmas, and others. The approach uses symmetric injection of high density plasma into a coaxial electromagnetic accelerator having an annular gap geometry tailored to prevent formation of the blow-by instability. The injected plasma is generated by numerous (currently 32) radially oriented capillary discharges arranged uniformly around the circumference of the angled annular injection region of the accelerator. Magnetohydrodynamic modeling identified electrode profiles that can achieve the desired plasma jet parameters. The experimental hardware is described along with initial experimental results in which approximately 200 microg has been accelerated to 100 km/s in a half-scale prototype gun. Initial observations of 64 merging injector jets in a planar cylindrical testing array are presented. Density and velocity are presently limited by available peak current and injection sources. Steps to increase both the drive current and the injected plasma mass are described for next generation experiments.

A contoured gap coaxial plasma gun with injected plasma armature

International Nuclear Information System (INIS)

Witherspoon, F. Douglas; Case, Andrew; Messer, Sarah J.; Bomgardner, Richard II; Phillips, Michael W.; Brockington, Samuel; Elton, Raymond

2009-01-01

A new coaxial plasma gun is described. The long term objective is to accelerate 100-200 μg of plasma with density above 10 17 cm -3 to greater than 200 km/s with a Mach number above 10. Such high velocity dense plasma jets have a number of potential fusion applications, including plasma refueling, magnetized target fusion, injection of angular momentum into centrifugally confined mirrors, high energy density plasmas, and others. The approach uses symmetric injection of high density plasma into a coaxial electromagnetic accelerator having an annular gap geometry tailored to prevent formation of the blow-by instability. The injected plasma is generated by numerous (currently 32) radially oriented capillary discharges arranged uniformly around the circumference of the angled annular injection region of the accelerator. Magnetohydrodynamic modeling identified electrode profiles that can achieve the desired plasma jet parameters. The experimental hardware is described along with initial experimental results in which approximately 200 μg has been accelerated to 100 km/s in a half-scale prototype gun. Initial observations of 64 merging injector jets in a planar cylindrical testing array are presented. Density and velocity are presently limited by available peak current and injection sources. Steps to increase both the drive current and the injected plasma mass are described for next generation experiments.

Electron density and plasma dynamics of a colliding plasma experiment

Energy Technology Data Exchange (ETDEWEB)

Wiechula, J., E-mail: wiechula@physik.uni-frankfurt.de; Schönlein, A.; Iberler, M.; Hock, C.; Manegold, T.; Bohlender, B.; Jacoby, J. [Plasma Physics Group, Institute of Applied Physics, Goethe University, 60438 Frankfurt am Main (Germany)

2016-07-15

We present experimental results of two head-on colliding plasma sheaths accelerated by pulsed-power-driven coaxial plasma accelerators. The measurements have been performed in a small vacuum chamber with a neutral-gas prefill of ArH{sub 2} at gas pressures between 17 Pa and 400 Pa and load voltages between 4 kV and 9 kV. As the plasma sheaths collide, the electron density is significantly increased. The electron density reaches maximum values of ≈8 ⋅ 10{sup 15} cm{sup −3} for a single accelerated plasma and a maximum value of ≈2.6 ⋅ 10{sup 16} cm{sup −3} for the plasma collision. Overall a raise of the plasma density by a factor of 1.3 to 3.8 has been achieved. A scaling behavior has been derived from the values of the electron density which shows a disproportionately high increase of the electron density of the collisional case for higher applied voltages in comparison to a single accelerated plasma. Sequences of the plasma collision have been taken, using a fast framing camera to study the plasma dynamics. These sequences indicate a maximum collision velocity of 34 km/s.

Frontier of plasma physics. 'Research network on non-equilibrium and extreme state plasmas'

International Nuclear Information System (INIS)

Itoh, Sanae-I.; Fujisawa, Akihide; Kodama, Ryosuke; Sato, Motoyasu; Tanaka, Kazuo A.; Hatakeyama, Rikizo; Itoh, Kimitaka

2011-01-01

Plasma physics and fusion science have been applied to a wide variety of plasmas such as nuclear fusion plasmas, high-energy-density plasmas, processing plasmas and nanobio- plasmas. They are pioneering science and technology frontiers such as new energy sources and new functional materials. A large project 'research network on non-equilibrium and extreme state plasmas' is being proposed to reassess individual plasma researches from a common view of the non-equilibrium extreme plasma and to promote collaboration among plasma researchers all over the country. In the present review, recent collaborative works related to this project are being introduced. (T.I.)

Dust-Plasma Interactions

International Nuclear Information System (INIS)

Rosenberg, Marelene

2005-01-01

Our theoretical research on dust-plasma interactions has concentrated on three main areas: (a)studies of grain charging and applications; (b) waves and instabilities in weakly correlated dusty plasma with applications to space and laboratory plasmas; (c) waves in strongly coupled dusty plasmas.

Large-scale structuring of a rotating plasma due to plasma macroinstabilities

International Nuclear Information System (INIS)

Kikuchi, Toshinori; Ikehata, Takashi; Sato, Naoyuki; Watahiki, Takeshi; Tanabe, Toshio; Mase, Hiroshi

1995-01-01

The formation of coherent structures during plasma macroinstabilities have been of interest in view of the nonlinear plasma physics. In the present paper, we have investigated in detail, the mechanism and specific features of large-scale structuring of a rotating plasma. In the case of weak magnetic field, the plasma ejected from a plasma gun has a high beta value (β > 1) so that it expands rapidly across the magnetic field excluding a magnetic flux from its interior. Then, the boundary between the expanding plasma and the magnetic field becomes unstable against Rayleigh-Taylor instability. This instability has the higher growth rate at the shorter wavelength and the mode appears as flute. These features of the instability are confirmed by the observation of radial plasma jets with the azimuthal mode number m=20-40 in the early time of the plasma expansion. In the case of strong magnetic field, on the other hand, the plasma little expands and rotates at two times the ion sound speed. Especially, we observe spiral jets of m=2 instead of short-wavelength radial jets. This mode appears only when a glass target is installed or a dense neutral gas is introduced around the plasma to give the plasma a frictional force. From these results and with reference to the theory of plasma instabilities, the centrifugal instability caused by a combination of the velocity shear and centrifugal force is concluded to be responsible for the formation of spiral jets. (author)

Beam-plasma discharge in a Kyoto beam-plasma-ion source

International Nuclear Information System (INIS)

Ishikawa, J.; Takagi, T.

1983-01-01

A beam-plasma type ion source employing an original operating principle has been developed by the present authors. The ion source consists of an ion extraction region with an electron gun, a thin long drift tube as the plasma production chamber, and a primary electron beam collector. An electron beam is effectively utilized for the dual purpose of high density plasma production as a result of beam-plasma discharge, and high current ion beam extraction with ion space-charge compensation. A high density plasma of the order of 10 11 --10 13 cm -3 was produced by virtue of the beam-plasma discharge which was caused by the interaction between a space-charge wave on the electron beam and a high frequency plasma wave. The plasma density then produced was 10 2 --10 3 times the density produced only by collisional ionization by the electron beam. In order to obtain a stable beam-plasma discharge, a secondary electron beam emitted from the electron collector should be utilized. The mechanism of the beam-plasma discharge was analyzed by use of a linear theory in the case of the small thermal energy of the electron beam, and by use of a quasilinear theory in the case of the large thermal energy. High current ion beams of more than 0.1 A were extracted even at a low extraction voltage of 1--5 kV

Production of field-reversed mirror plasma with a coaxial plasma gun

Science.gov (United States)

Hartman, C.W.; Shearer, J.W.

The use of a coaxial plasma gun to produce a plasma ring which is directed into a magnetic field so as to form a field-reversed plasma confined in a magnetic mirror. Plasma thus produced may be used as a target for subsequent neutral beam injection or other similarly produced and projected plasma rings or for direct fusion energy release in a pulsed mode.

Production of field-reversed mirror plasma with a coaxial plasma gun

International Nuclear Information System (INIS)

Hartman, C.W.; Shearer, J.W.

1982-01-01

The use of a coaxial plasma gun to produce a plasma ring which is directed into a magnetic field so as to form a field-reversed plasma confined in a magnetic mirror. Plasma thus produced may be used as a target for subsequent neutral beam injection or other similarly produced and projected plasma rings or for direct fusion energy release in a pulsed mode

Plasma heating by non-linear wave-Plasma interaction | Echi ...

African Journals Online (AJOL)

We simulate the non-linear interaction of waves with magnetized tritium plasma with the aim of determining the parameter values that characterize the response of the plasma. The wave-plasma interaction has a non-conservative Hamiltonian description. The resulting system of Hamilton's equations is integrated numerically ...

Plasma physics

CERN Document Server

Drummond, James E

1961-01-01

A historic snapshot of the field of plasma physics, this fifty-year-old volume offers an edited collection of papers by pioneering experts in the field. In addition to assisting students in their understanding of the foundations of classical plasma physics, it provides a source of historic context for modern physicists. Highly successful upon its initial publication, this book was the standard text on plasma physics throughout the 1960s and 70s.Hailed by Science magazine as a ""well executed venture,"" the three-part treatment ranges from basic plasma theory to magnetohydrodynamics and microwa

Studies of the ablated plasma from experimental plasma gun disruption simulations

International Nuclear Information System (INIS)

Rockett, P.D.; Hunter, J.A.; Bradley, J.T. III; Gahl, J.M.; Litunovsky, V.N.; Ovchinnokov, I.B.; Ljublin, B.V.; Kuznetsov, B.E.; Titov, V.A.; Zhitlukhin, A.; Arkhipov, K.; Bakhtin, V.; Toporkov, D.

1995-01-01

Extensive simulations of tokamak disruptions have provided a picture of material erosion that is limited by the transfer of energy from the incident plasma to the armor solid surface through a dense plasma shield. Radiation spectra were recorded in the VUV and in the visible at the Efremov Laboratories on VIKA using graphite targets. The VUV data were recorded with a Sandia Labs transmission grating spectrograph, covering 1-40 nm. Plasma parameters were evaluated with incident plasma energy densities varying from 10-100 MJ/m 2 . A second transmission grating spectrograph was taken to 2MK-200 at TRINITI to study the plasma-material interface in magnetic cusp plasma. Target materials included POCO graphite, ATJ graphite, boron nitride, and plasma-sprayed tungsten. Detailed spectra were recorded with a spatial resolution of similar 1 mm. Time-resolved data with 40-200 ns resolution was also recorded. The data from both plasma gun facilities demonstrated that the hottest plasma region was sitting several millimeters above the armor tile surface. ((orig.))

Plasma universe

International Nuclear Information System (INIS)

Alfven, H.

1986-04-01

Traditionally the views in our cosmic environment have been based on observations in the visual octave of the electromagnetic spectrum, during the last half-century supplemented by infrared and radio observations. Space research has opened the full spectrum. Of special importance are the X-ray-gamma-ray regions, in which a number of unexpected phenomena have been discovered. Radiations in these regions are likely to originate mainly from magnetised cosmic plasma. Such a medium may also emit synchrotron radiation which is observable in the radio region. If we try to base a model of the universe on the plasma phenomena mentioned we find that the plasma universe is drastically different from the traditional visual universe. Information about the plasma universe can also be obtained by extrapolation of laboratory experiments and magnetospheric in situ measurements of plasma. This approach is possible because it is likely that the basic properties of plasma are the same everywhere. In order to test the usefulness of the plasma universe model we apply it to cosmogony. Such an approach seems to be rather successful. For example, the complicated structure of the Saturnian C ring can be accounted for. It is possible to reconstruct certain phenomena 4-5 bilions years ago with an accuracy of better than 1 percent

The plasma position control of ITER EDA plasma

International Nuclear Information System (INIS)

Senda, Ikuo; Nishio, Satoshi; Tsunematsu, Toshihide; Nishino, Toru; Fujieda, Hirobumi.

1994-09-01

The study on the plasma position control of ITER EDA performed by Japan Home Team during the sensitivity study in 1994 is summarized. The controllabilities of plasmas in the Outline Design and elongated version are compared. The model used to describe the motion of the plasma is a rigid model. The PD feedback control is applied with respect to the displacements of the plasma from the equilibrium. Three types of fluctuations, which initiate the motion of the plasma, are examined, namely a finite horizontal fluctuation field, a small horizontal fluctuation field such that the motion of the plasma is governed by the passive structures and an abrupt change of the poloidal beta β p and internal inductance l i . In the simulations of finite horizontal fluctuation fields, controls depend on the strength of the fluctuations, for instance, 3-5V is needed for 5-10G of fluctuation fields in the Outline Design. When the fluctuation field is small and the plasma displacement grows in a characteristic time of the passive structures, a few volt of the control voltage is enough to obtain good controllability. It is shown that the control when (β p , l i ) changes simultaneously is demanding and a large control voltage is required to maintain satisfactory control. Comparing the elongated version with the Outline Design, the control voltage which is larger than the Outline Design by a factor of 2-3 is required to obtain the same controllability in the elongated version. (author)

Experimental studies of collisional plasma shocks and plasma interpenetration via merging supersonic plasma jets

Science.gov (United States)

Hsu, S. C.; Moser, A. L.; Merritt, E. C.; Adams, C. S.

2015-11-01

Over the past 4 years on the Plasma Liner Experiment (PLX) at LANL, we have studied obliquely and head-on-merging supersonic plasma jets of an argon/impurity or hydrogen/impurity mixture. The jets are formed/launched by pulsed-power-driven railguns. In successive experimental campaigns, we characterized the (a) evolution of plasma parameters of a single plasma jet as it propagated up to ~ 1 m away from the railgun nozzle, (b) density profiles and 2D morphology of the stagnation layer and oblique shocks that formed between obliquely merging jets, and (c) collisionless interpenetration transitioning to collisional stagnation between head-on-merging jets. Key plasma diagnostics included a fast-framing CCD camera, an 8-chord visible interferometer, a survey spectrometer, and a photodiode array. This talk summarizes the primary results mentioned above, and highlights analyses of inferred post-shock temperatures based on observations of density gradients that we attribute to shock-layer thickness. We also briefly describe more recent PLX experiments on Rayleigh-Taylor-instability evolution with magnetic and viscous effects, and potential future collisionless shock experiments enabled by low-impurity, higher-velocity plasma jets formed by contoured-gap coaxial guns. Supported by DOE Fusion Energy Sciences and LANL LDRD.

High-beta plasma effects in a low-pressure helicon plasma

International Nuclear Information System (INIS)

Corr, C. S.; Boswell, R. W.

2007-01-01

In this work, high-beta plasma effects are investigated in a low-pressure helicon plasma source attached to a large volume diffusion chamber. When operating above an input power of 900 W and a magnetic field of 30 G a narrow column of bright blue light (due to Ar II radiation) is observed along the axis of the diffusion chamber. With this blue mode, the plasma density is axially very uniform in the diffusion chamber; however, the radial profiles are not, suggesting that a large diamagnetic current might be induced. The diamagnetic behavior of the plasma has been investigated by measuring the temporal evolution of the magnetic field (B z ) and the plasma kinetic pressure when operating in a pulsed discharge mode. It is found that although the electron pressure can exceed the magnetic field pressure by a factor of 2, a complete expulsion of the magnetic field from the plasma interior is not observed. In fact, under our operating conditions with magnetized ions, the maximum diamagnetism observed is ∼2%. It is observed that the magnetic field displays the strongest change at the plasma centre, which corresponds to the maximum in the plasma kinetic pressure. These results suggest that the magnetic field diffuses into the plasma sufficiently quickly that on a long time scale only a slight perturbation of the magnetic field is ever observed

A contoured gap coaxial plasma gun with injected plasma armature

Energy Technology Data Exchange (ETDEWEB)

Witherspoon, F. Douglas; Case, Andrew; Messer, Sarah J.; Bomgardner, Richard II; Phillips, Michael W.; Brockington, Samuel; Elton, Raymond [HyperV Technologies Corp., Chantilly, Virginia 20151 (United States)

2009-08-15

A new coaxial plasma gun is described. The long term objective is to accelerate 100-200 {mu}g of plasma with density above 10{sup 17} cm{sup -3} to greater than 200 km/s with a Mach number above 10. Such high velocity dense plasma jets have a number of potential fusion applications, including plasma refueling, magnetized target fusion, injection of angular momentum into centrifugally confined mirrors, high energy density plasmas, and others. The approach uses symmetric injection of high density plasma into a coaxial electromagnetic accelerator having an annular gap geometry tailored to prevent formation of the blow-by instability. The injected plasma is generated by numerous (currently 32) radially oriented capillary discharges arranged uniformly around the circumference of the angled annular injection region of the accelerator. Magnetohydrodynamic modeling identified electrode profiles that can achieve the desired plasma jet parameters. The experimental hardware is described along with initial experimental results in which approximately 200 {mu}g has been accelerated to 100 km/s in a half-scale prototype gun. Initial observations of 64 merging injector jets in a planar cylindrical testing array are presented. Density and velocity are presently limited by available peak current and injection sources. Steps to increase both the drive current and the injected plasma mass are described for next generation experiments.

International Conference on Plasma Diagnostics. Slides, papers and posters of Plasma Diagnostics 2010

International Nuclear Information System (INIS)

Hartfuss, H.J.; Bonhomme, G.; Grisolia, C.; Hirsch, M.; Klos, Z.; Mazouffre, S.; Musielok, J.; Ratynskaya, S.; Sadowski, M.; Van de Sanden, R.; Sentis, M.; Stroth, U.; Tereshin, V.; Tichy, M.; Unterberg, B.; Weisen, H.; Zoletnik, S.

2011-01-01

Plasma diagnostics 2010 is an International Conference on Diagnostic Methods involved in Research and Applications of Plasmas, originating on combining the 5. German-Polish Conference on Plasma Diagnostics for Fusion and Applications and the 7. French-Polish Seminar on Thermal Plasma in Space and Laboratory. The Scientific Committee of 'Plasma 2007' decided to concentrate the attention of future conferences more on the diagnostic development and diagnostic interpretation in the fields of high and low temperature plasmas and plasma applications. It is aimed at involving all European activities in the fields. The Scientific Program will cover the fields from low temperature laboratory to fusion plasmas of various configurations as well as dusty and astrophysical plasmas and industrial plasma applications

Plasma device

International Nuclear Information System (INIS)

Thode, L.E.

1981-01-01

A relativistic electron beam generator or accelerator produces a high-voltage electron beam which is modulated to initiate electron bunching within the beam which is then applied to a high-density target plasma which typically comprises DT, DD, or similar thermonuclear gas at a density of 10 17 to 10 20 electrons per cubic centimeter. As a result, relativistic streaming instabilities are initiated within the high-density target plasma causing the relativistic electron beam to efficiently deposit its energy into a small localized region of the high-density plasma target. The high-temperature plasma can be used to heat a high Z material to generate radiation. Alternatively, a tunable radiation source is produced by using a moderate Z gas or a mixture of high Z and low Z gas as the target plasma. (author)

Experimental plasma physics

International Nuclear Information System (INIS)

Dreicer, H.; Banton, M.E.; Ingraham, J.C.; Wittman, F.; Wright, B.L.

1976-01-01

The Experimental Plasma Physics group's main efforts continue to be directed toward the understanding of the mechanisms of electromagnetic energy absorption in a plasma, and the resultant plasma heating and energy transport. The high-frequency spectrum of plasma waves parametrically excited by the microwave signal at high powers has been measured. The absorption of a small test microwave signal in a plasma made parametrically unstable by a separate high-power driver microwave signal was also studied

Scaling relations for plasma production and acceleration of rotating plasma flows

International Nuclear Information System (INIS)

Ikehata, Takashi; Tanabe, Toshio; Mase, Hiroshi; Sekine, Ryusuke; Hasegawa, Kazuyuki.

1989-01-01

Scaling relations are investigated theoretically and experimentally of the plasma production and acceleration in the rotating plasma gun which has been developed as a new means of plasma centrifuge. Two operational modes: the gas-discharge mode for gaseous elements and the vacuum-discharge mode for solid elements are studied. Relations of the plasma density and velocities to the discharge current and the magnetic field are derived. The agreement between experiment and theory is quite well. It is found that fully-ionized rotating plasmas produced in the gas-discharge mode is most advantageous to realize efficient plasma centrifuge. (author)

Plasmas and fluids

International Nuclear Information System (INIS)

Anon.

1986-01-01

Plasma and fluid physics includes the fields of fusion research and space investigation. This book discusses the most important advances in these areas over the past decade and recommends a stronger commitment to basic research in plasma and fluid physics. The book recommends that plasma and fluid physics be included in physics curriculums because of their increasing importance in energy and defense. The book also lists recent accomplishments in the fields of general plasma physics, fusion plasma confinement and heating, space and astrophysical plasmas, and fluid physics and lists research opportunities in these areas. A funding summary explains how research monies are allocated and suggests ways to improve their effectiveness

BOOK REVIEW: Kinetic theory of plasma waves, homogeneous plasmas

Science.gov (United States)

Porkolab, Miklos

1998-11-01

The linear theory of plasma waves in homogeneous plasma is arguably the most mature and best understood branch of plasma physics. Given the recently revised version of Stix's excellent Waves in Plasmas (1992), one might ask whether another book on this subject is necessary only a few years later. The answer lies in the scope of this volume; it is somewhat more detailed in certain topics than, and complementary in many fusion research relevant areas to, Stix's book. (I am restricting these comments to the homogeneous plasma theory only, since the author promises a second volume on wave propagation in inhomogeneous plasmas.) This book is also much more of a theorist's approach to waves in plasmas, with the aim of developing the subject within the logical framework of kinetic theory. This may indeed be pleasing to the expert and to the specialist, but may be too difficult to the graduate student as an `introduction' to the subject (which the author explicitly states in the Preface). On the other hand, it may be entirely appropriate for a second course on plasma waves, after the student has mastered fluid theory and an introductory kinetic treatment of waves in a hot magnetized `Vlasov' plasma. For teaching purposes, my personal preference is to review the cold plasma wave treatment using the unified Stix formalism and notation (which the author wisely adopts in the present book, but only in Chapter 5). Such an approach allows one to deal with CMA diagrams early on, as well as to provide a framework to discuss electromagnetic wave propagation and accessibility in inhomogeneous plasmas (for which the cold plasma wave treatment is perfectly adequate). Such an approach does lack some of the rigour, however, that the author achieves with the present approach. As the author correctly shows, the fluid theory treatment of waves follows logically from kinetic theory in the cold plasma limit. I only question the pedagogical value of this approach. Otherwise, I welcome this

Capillary plasma jet: A low volume plasma source for life science applications

Energy Technology Data Exchange (ETDEWEB)

Topala, I., E-mail: ionut.topala@uaic.ro, E-mail: tmnagat@ipc.shizuoka.ac.jp [Alexandru Ioan Cuza University of Iasi, Faculty of Physics, Iasi Plasma Advanced Research Center (IPARC), Bd. Carol I No. 11, Iasi 700506 (Romania); Nagatsu, M., E-mail: ionut.topala@uaic.ro, E-mail: tmnagat@ipc.shizuoka.ac.jp [Graduate School of Science and Technology, Shizuoka University, 3-5-1 Johoku, Naka-ku, Hamamatsu 432-8561 (Japan)

2015-02-02

In this letter, we present results from multispectroscopic analysis of protein films, after exposure to a peculiar plasma source, i.e., the capillary plasma jet. This plasma source is able to generate very small pulsed plasma volumes, in kilohertz range, with characteristic dimensions smaller than 1 mm. This leads to specific microscale generation and transport of all plasma species. Plasma diagnosis was realized using general electrical and optical methods. Depending on power level and exposure duration, this miniature plasma jet can induce controllable modifications to soft matter targets. Detailed discussions on protein film oxidation and chemical etching are supported by results from absorption, X-ray photoelectron spectroscopy, and microscopy techniques. Further exploitation of principles presented here may consolidate research interests involving plasmas in biotechnologies and plasma medicine, especially in patterning technologies, modified biomolecule arrays, and local chemical functionalization.

Capillary plasma jet: A low volume plasma source for life science applications

Science.gov (United States)

Topala, I.; Nagatsu, M.

2015-02-01

In this letter, we present results from multispectroscopic analysis of protein films, after exposure to a peculiar plasma source, i.e., the capillary plasma jet. This plasma source is able to generate very small pulsed plasma volumes, in kilohertz range, with characteristic dimensions smaller than 1 mm. This leads to specific microscale generation and transport of all plasma species. Plasma diagnosis was realized using general electrical and optical methods. Depending on power level and exposure duration, this miniature plasma jet can induce controllable modifications to soft matter targets. Detailed discussions on protein film oxidation and chemical etching are supported by results from absorption, X-ray photoelectron spectroscopy, and microscopy techniques. Further exploitation of principles presented here may consolidate research interests involving plasmas in biotechnologies and plasma medicine, especially in patterning technologies, modified biomolecule arrays, and local chemical functionalization.

Structural and functional characterization of human complement factor P

DEFF Research Database (Denmark)

Pedersen, Dennis

not yet been resolved. This PhD-thesis provide structural understanding of the FP mediated stabilization of the AP C3 convertase. Furthermore, functional studies involving oligomeric and monomeric FP variants have helped us to understand the importance of FP oligomerization for the primary functions of FP...... of complement by stabilizing the C3 convertase complex (C3bBb). FP has also been suggested to serve as a pattern recognition molecule for the initiation of the alternative pathway. However, the molecular mechanisms of FP remain unclear due to its oligomeric nature and hence the atomic structure of FP has...

Plasma waves in an inhomogeneous cylindrical plasma

International Nuclear Information System (INIS)

Pesic, S.S.

1976-01-01

The complete dispersion equation governing small amplitude plasma waves propagating in an inhomogeneous cylindrical plasma confined by a helical magnetic field is solved numerically. The efficiency of the wave energy thermalization in the lower hybrid frequency range is studied

Plasma equilibrium control during slow plasma current quench with avoidance of plasma-wall interaction in JT-60U

Science.gov (United States)

Yoshino, R.; Nakamura, Y.; Neyatani, Y.

1997-08-01

In JT-60U a vertical displacement event (VDE) is observed during slow plasma current quench (Ip quench) for a vertically elongated divertor plasma with a single null. The VDE is generated by an error in the feedback control of the vertical position of the plasma current centre (ZJ). It has been perfectly avoided by improving the accuracy of the ZJ measurement in real time. Furthermore, plasma-wall interaction has been avoided successfully during slow Ip quench owing to the good performance of the plasma equilibrium control system

Applied plasma physics

International Nuclear Information System (INIS)

Anon.

1978-01-01

Applied Plasma Physics is a major sub-organizational unit of the MFE Program. It includes Fusion Plasma Theory and Experimental Plasma Research. The Fusion Plasma Theory group has the responsibility for developing theoretical-computational models in the general areas of plasma properties, equilibrium, stability, transport, and atomic physics. This group has responsibility for giving guidance to the mirror experimental program. There is a formal division of the group into theory and computational; however, in this report the efforts of the two areas are not separated since many projects have contributions from members of both. Under the Experimental Plasma Research Program, we are developing the intense, pulsed neutral-beam source (IPINS) for the generation of a reversed-field configuration on 2XIIB. We are also studying the feasibility of utilizing certain neutron-detection techniques as plasma diagnostics in the next generation of thermonuclear experiments

Elements of plasma technology

CERN Document Server

Wong, Chiow San

2016-01-01

This book presents some fundamental aspects of plasma technology that are important for beginners interested to start research in the area of plasma technology . These include the properties of plasma, methods of plasma generation and basic plasma diagnostic techniques. It also discusses several low cost plasma devices, including pulsed plasma sources such as plasma focus, pulsed capillary discharge, vacuum spark and exploding wire; as well as low temperature plasmas such as glow discharge and dielectric barrier discharge which the authors believe may have potential applications in industry. The treatments are experimental rather than theoretical, although some theoretical background is provided where appropriate. The principles of operation of these devices are also reviewed and discussed.

Study of plasma-maser instability in an inhomogeneous plasma

International Nuclear Information System (INIS)

Singh, Mahinder

2006-01-01

The plasma-maser, an interesting nonlinear process in plasmas, is an effective means of energy up-conversion in frequency from low-frequency turbulence to a high-frequency wave. A theoretical study is made of the amplification mechanism of an electrostatic Bernstein mode wave in presence of Langmuir wave turbulence in a magnetized inhomogeneous plasma on the basis of a plasma-maser interaction. It is shown that a test high-frequency electrostatic Bernstein mode wave is unstable in the presence of low-frequency Langmuir wave turbulence. The growth rate of a test high-frequency Bernstein mode wave is calculated with the involvement of a spatial density gradient parameter. A comparative study on the role of density gradient in the generation of the Bernstein mode on the basis of the plasma-maser effect is presented

A review on ion–ion plasmas created in weakly magnetized electronegative plasmas

International Nuclear Information System (INIS)

Aanesland, A; Bredin, J; Chabert, P

2014-01-01

Ion–Ion plasmas are electronegative plasmas where the electron density is several orders of magnitude lower than the negative ion density. These plasmas have been scarcely observed and investigated since the 1960s and are formed as a transient state of pulsed plasmas or in separate regions in magnetized plasmas. In this review we focus on the latter case of continuous formation of ion–ion plasmas created at the periphery of magnetized plasma columns or downstream localized magnetic barriers. We bring together and review experimental results already published elsewhere and complement them with new results to illustrate the physics important in ion–ion plasma formation and highlight in particular unanswered questions. We show that with a good design the density in the ion–ion region is dropping only by a factor of 2–3 from the initial plasma density. These plasmas can therefore be well suited for various ion source applications when both fluxes or beams of positive and negative ions are desired, and when electrons can cause harmful effects. (paper)

Contemporary plasma physics

International Nuclear Information System (INIS)

Sodha, M.S.; Tewari, D.P.; Subbarao, D.

1983-01-01

The book consists of review articles on some selected contemporary aspects of plasma physics. The selected topics present a panoramic view of contemporary plasma physics and applications to fusion, space and MHD power generation. Basic non-linear plasma theory is also covered. The book is supposed to be useful for M.S./M.Sc. students specialising in plasma physics and for those beginning research work in plasma physics. It will also serve as a valuable reference book for more advanced research workers. (M.G.B.)

Mirror plasma apparatus

International Nuclear Information System (INIS)

Moir, R.W.

1981-01-01

A mirror plasma apparatus which utilizes shielding by arc discharge to form a blanket plasma and lithium walls to reduce neutron damage to the wall of the apparatus. An embodiment involves a rotating liquid lithium blanket for a tandem mirror plasma apparatus wherein the first wall of the central mirror cell is made of liquid lithium which is spun with angular velocity great enough to keep the liquid lithium against the first material wall, a blanket plasma preventing the lithium vapor from contaminating the plasma

Plasma Post Oxidation of Plasma Nitrocarburized SKD 61 Steel

Institute of Scientific and Technical Information of China (English)

无

2008-01-01

Plasma nitrocarburizing and plasma oxidizing treatments were performed to improve the wear and corrosion resistance of SKD 61 steel. Plasma nitrocarburizing was conducted for 12 h at 540℃ in the nitrogen,hydrogen and methane atmosphere to produce the ε-Fe,2-3(N,C) phase. The compound layer produced by plasma nitrocarburising was predominantly composed of ε-phase, with a small proportion of γ′-Fe4(N,C) phase.The thickness of the compound layer and the diffusion layer are about 10 μm and about 200μm, respectively.Plasma post oxidation was performed on the nitrocarburized samples with various oxygen/hydrogen ratio at constant temperature of 500℃ for 1 h. The very thin magnetite (Fe3O4) layer of 1-2μm in thickness on top of the compound layer was obtained. Anodic polarization test revealed that plasma nitrocarburizing process contributed a significant improvement of corrosion resistance of SKD 61 steel. However, the corrosion characteristics of the nitrocarburized compound layer was deteriorated by oxidation treatment.

Project of experimental study on plasma waves and plasma turbulence

International Nuclear Information System (INIS)

Ferreira, J.L.

1990-09-01

The objective of this project is to perform experiments with wave phenomena on plasmas. Particular attention will be given to Langmuir and whistler waves due to its relations with several phenomena occuring on space and laboratory plasmas. The new concepts of particle acceleration with electromagnetic waves, the auroral phenomena on the polar regions and the charged particle precipitation to the atmosphere through anomalies of the earth magnetic field are examples where these waves have an important role. In this project we intend to study the propagation of these waves in a quiescent plasma machine. This machine is able to produce a plasma with density and temperature with values similar to what is met in the ionosphere. This project will be a part of the activities of the basic plasma group of the INPE's Associated Plasma Laboratory (LAP). It will have the collaboration of the departments of Aeronomy and Geophysics also from INPE, and the collaboration of the Plasma and Gas Physics Laboratory from University of Paris - South, in France. (author)

Plasmas: from space to laboratory. 'Introduction to plasma physics' course

International Nuclear Information System (INIS)

Savoini, Philippe

2011-01-01

This course addresses the different basic concepts of plasma physics. After an introduction which addresses the plasma state, basic equations, the different theoretical approaches (orbitals, kinetic, multi-fluid, magnetohydrodynamics), and the different characteristic scales, waves are addressed and presented as a disordered electromagnetism: existence of plasma waves, generalities on waves, relationship of formal dispersion of plasmas, plasma without magnetic field (longitudinal, transverse, or low frequency wave), plasma with magnetic field (parallel, perpendicular, or arbitrary propagation). The next parts present various approaches: the particle-based approach (case of constant and uniform magnetic fields, case of non-uniform magnetic fields), the statistical approach (elements of kinetic theory, the collision phenomenon, the equilibrium state), and the fluid approach (fluid equations according to the multi-fluid theory, comparison with the particle-based approach, presentation of magnetohydrodynamics as the single-fluid model, validity of MHD)

Applied plasma physics

International Nuclear Information System (INIS)

Anon.

1979-01-01

Applied Plasma Physics is a major sub-organizational unit of the Magnetic Fusion Energy (MFE) Program. It includes Fusion Plasma Theory and Experimental Plasma Research. The Fusion Plasma Theory group has the responsibility for developing theoretical-computational models in the general areas of plasma properties, equilibrium, stability, transport, and atomic physics. This group has responsibility for giving guidance to the mirror experimental program. There is a formal division of the group into theory and computational; however, in this report the efforts of the two areas are not separated since many projects have contributions from members of both. Under the Experimental Plasma Research Program we are developing a neutral-beam source, the intense, pulsed ion-neutral source (IPINS), for the generation of a reversed-field configuration on 2XIIB. We are also studying the feasibility of using certain neutron-detection techniques as plasma diagnostics in the next generation of thermonuclear experiments

Particle modeling of plasmas computational plasma physics

International Nuclear Information System (INIS)

Dawson, J.M.

1991-01-01

Recently, through the development of supercomputers, a powerful new method for exploring plasmas has emerged; it is computer modeling of plasmas. Such modeling can duplicate many of the complex processes that go on in a plasma and allow scientists to understand what the important processes are. It helps scientists gain an intuition about this complex state of matter. It allows scientists and engineers to explore new ideas on how to use plasma before building costly experiments; it allows them to determine if they are on the right track. It can duplicate the operation of devices and thus reduce the need to build complex and expensive devices for research and development. This is an exciting new endeavor that is in its infancy, but which can play an important role in the scientific and technological competitiveness of the US. There are a wide range of plasma models that are in use. There are particle models, fluid models, hybrid particle fluid models. These can come in many forms, such as explicit models, implicit models, reduced dimensional models, electrostatic models, magnetostatic models, electromagnetic models, and almost an endless variety of other models. Here the author will only discuss particle models. He will give a few examples of the use of such models; these will be taken from work done by the Plasma Modeling Group at UCLA because he is most familiar with work. However, it only gives a small view of the wide range of work being done around the US, or for that matter around the world

PlasmaPy: initial development of a Python package for plasma physics

Science.gov (United States)

Murphy, Nicholas; Leonard, Andrew J.; Stańczak, Dominik; Haggerty, Colby C.; Parashar, Tulasi N.; Huang, Yu-Min; PlasmaPy Community

2017-10-01

We report on initial development of PlasmaPy: an open source community-driven Python package for plasma physics. PlasmaPy seeks to provide core functionality that is needed for the formation of a fully open source Python ecosystem for plasma physics. PlasmaPy prioritizes code readability, consistency, and maintainability while using best practices for scientific computing such as version control, continuous integration testing, embedding documentation in code, and code review. We discuss our current and planned capabilities, including features presently under development. The development roadmap includes features such as fluid and particle simulation capabilities, a Grad-Shafranov solver, a dispersion relation solver, atomic data retrieval methods, and tools to analyze simulations and experiments. We describe several ways to contribute to PlasmaPy. PlasmaPy has a code of conduct and is being developed under a BSD license, with a version 0.1 release planned for 2018. The success of PlasmaPy depends on active community involvement, so anyone interested in contributing to this project should contact the authors. This work was partially supported by the U.S. Department of Energy.

Studies of the ablated plasma from experimental plasma gun disruption simulations

International Nuclear Information System (INIS)

Rockett, P.D.; Hunter, J.A.; Bradley, J.T.

1994-01-01

Extensive simulations of Tokamak disruptions have provided a picture of material erosion that is limited by the transfer of energy from the incident plasma to the armor solid surface through a dense vapor shield. Radiation spectra were recorded in the VUV and in the visible at the Efremov Laboratories on VIKA using graphite targets. The VUV data were recorded with a Sandia Labs transmission grating spectrograph, covering 1--40 nm. Plasma parameters were evaluated with incident plasma energy densities varying from 1--10 kJ/cm 2 . A second transmission grating spectrograph was taken to 2MK-200 at TRINITI to study the plasma-material interface in magnetic cusp plasma. Target materials included POCO graphite, ATJ graphite, boron nitride, and plasma-sprayed tungsten. Detailed spectra were recorded with a spatial resolution of ∼1 mm resolution. Time-resolved data with 40--200 ns resolution was also recorded. The data from both plasma gun facilities demonstrated that the hottest plasma region was sitting several millimeters above the armor tile surface

Plasma Diagnostics

Energy Technology Data Exchange (ETDEWEB)

Zaveryaev, V [Kurchatov Institute, Moscow (Russian Federation); others, and

2012-09-15

The success in achieving peaceful fusion power depends on the ability to control a high temperature plasma, which is an object with unique properties, possibly the most complicated object created by humans. Over years of fusion research a new branch of science has been created, namely plasma diagnostics, which involves knowledge of almost all fields of physics, from electromagnetism to nuclear physics, and up-to-date progress in engineering and technology (materials, electronics, mathematical methods of data treatment). Historically, work on controlled fusion started with pulsed systems and accordingly the methods of plasma parameter measurement were first developed for short lived and dense plasmas. Magnetically confined hot plasmas require the creation of special experimental techniques for diagnostics. The diagnostic set is the most scientifically intensive part of a plasma device. During many years of research operation some scientific tasks have been solved while new ones arose. New tasks often require significant changes in the diagnostic system, which is thus a very flexible part of plasma machines. Diagnostic systems are designed to solve several tasks. As an example here are the diagnostic tasks for the International Thermonuclear Experimental Reactor - ITER: (1) Measurements for machine protection and basic control; (2) Measurements for advanced control; (3) Additional measurements for performance evaluation and physics. Every new plasma machine is a further step along the path to the main goal - controlled fusion - and nobody knows in advance what new phenomena will be met on the way. So in the planning of diagnostic construction we should keep in mind further system upgrading to meet possible new scientific and technical challenges. (author)

Study of plasma-material surface interaction using langmuir probe technique during plasma treatment

International Nuclear Information System (INIS)

Saloum, S.; Akel, M.

2012-01-01

In this study, we tried to understand the plasma-surface interactions by using Langmuir probes. Two different types of plasmas were studied, the first is the electropositive plasma in Argon and the second is the electronegative plasma in Sulfur Hexafluoride. In the first type, the effects of Argon gas pressure, the injection of Helium in the remote zone and the substrate bias on the measurements of the Electron Energy Probability Function (EEPF) and on the plasma parameters (electron density (n e ), effective electron temperature (T e ff), plasma potential (V p ) and floating potential (V f )) have been investigated. The obtained EEPFs and plasma parameters have been used to control two remote plasma processes. The first is the remote Plasma Enhanced Chemical Vapor Deposition (PE-CVD) of thin films, on silicon wafers, from Hexamethyldisiloxane (HMDSO) precursor diluted in the remote Ar-He plasma. The second is the pure Argon remote plasma treatment of polymethylmethacrylate (PMMA) polymer surface. In the second type, the plasma diagnostics were performed in the remote zone as a function of SF 6 flow rate, where relative concentrations of fluorine atoms were measured using actinometry optical emission spectroscopy; electron density, electron temperature and plasma potential were determined using single cylindrical Langmuir probe, positive ion flux and negative ion fraction were determined using an planar probe. The silicon etching process in SF 6 plasma was studied. (author)

Study of plasma-material surface interaction using Langmuir probe technique during plasma treatment

International Nuclear Information System (INIS)

Saloum, S.; Akel, M.

2009-06-01

In this study, we tried to understand the plasma-surface interactions by using Langmuir probes. Two different types of plasmas were studied, the first is the electropositive plasma in Argon and the second is the electronegative plasma in Sulfur Hexafluoride. In the first type, the effects of Argon gas pressure, the injection of Helium in the remote zone and the substrate bias on the measurements of the Electron Energy Probability Function (EEPF) and on the plasma parameters (electron density (n e ), effective electron temperature (T e ff), plasma potential (V p ) and floating potential (V f )) have been investigated. The obtained EEPFs and plasma parameters have been used to control two remote plasma processes. The first is the remote Plasma Enhanced Chemical Vapor Deposition (PE-CVD) of thin films, on silicon wafers, from Hexamethyldisoloxane (HMDSO) precursor diluted in the remote Ar-He plasma. The second is the pure Argon remote plasma treatment of polymethylmethacrylate (PMMA) polymer surface. In the second type, the plasma diagnostics were performed in the remote zone as a function of SF 6 flow rate, where relative concentrations of fluorine atoms were measured using actinometry optical emission spectroscopy; electron density, electron temperature and plasma potential were determined using single cylindrical Langmuir probe, positive ion flux and negative ion fraction were determined using an planar probe. The silicon etching process in SF 6 plasma was studied. (author)

Plasma Turbulence General Topics

Energy Technology Data Exchange (ETDEWEB)

Kadomtsev, B. B. [Nuclear Energy Institute, Academy of Sciences of the USSR, Moscow, USSR (Russian Federation)

1965-06-15

It is known that under experimental conditions plasma often shows chaotic motion. Such motion, when many degrees of freedom are excited to levels considerably above the thermal level, will be called turbulent. The properties of turbulent plasma in many respects differ from the properties of laminar plasma. It can be said that the appearance of various anomalies in plasma behaviour indicates the presence of turbulence in plasma. In order to verify directly the presence of turbulent motion in plasma we must, however, measure the fluctuation of some microscopic parameters in plasma.

Introduction to plasma dynamics

CERN Document Server

Morozov, A I

2013-01-01

As the twenty-first century progresses, plasma technology will play an increasing role in our lives, providing new sources of energy, ion-plasma processing of materials, wave electromagnetic radiation sources, space plasma thrusters, and more. Studies of the plasma state of matter not only accelerate technological developments but also improve the understanding of natural phenomena. Beginning with an introduction to the characteristics and types of plasmas, Introduction to Plasma Dynamics covers the basic models of classical diffuse plasmas used to describe such phenomena as linear and shock w

Complete plasma dropouts at Vela satellites during thinning of the plasma sheet

International Nuclear Information System (INIS)

Lui, A.T.Y.; Hones, E.W. Jr.; Venkatesan, D.; Akasofu, S.; Bame, S.J.

1975-01-01

Five satellite years of Vela data are examined for plasma sheet thinnings. Complete proton disappearances (plasma dropouts) are the main subject here. During such times, the Vela satellite is temporarily in the high-latitude tail lobe. The distribution of such plasma dropouts within the magnetotail suggests that the semithickness of the plasma sheet near midnight seldom reaches less than 1 R/sub E/ during substorms and that the dawn and dusk portions of the plasma sheet remain thicker than the midnight portion. But it is also shown that the plasma sheet occasionally becomes very thin near the dusk magnetopause. No such severe thinnings of the plasma sheet are found near the dawn magnetopause. Plasma dropouts can occur regardless of the sign of the Z component of the IMF, but their frequency of occurrence seems to be greater when the Z component is negative.Three plasma dropouts which occurred in the midnight sector at unusually large distances from the estimated position of the neutral sheet were observed during geomagnetic storms. It is likely that the midnight sector of the plasma sheet can become very thick (approx.18 R/sub E/) at certain times during the main phase of storms. Detailed measurements in the plasma sheet were obtained near the beginning of a geomagnetic storm whose sc triggered a substorm. A compression of the plasma sheet at X/sub SM/approx. =-15 R/sub E/ occurred about 10 min after the sc onset at the earth and about 5 min after the start of plasma sheet thinning associated with the sc-related substorm. If compression-thinning of the plasma sheet initiated this substorm, the triggering action must have occurred earthward of X/sub SM/approx. =-15 R/sub E/

Plasma Immersion Ion Implantation in Radio Frequency Plasma

International Nuclear Information System (INIS)

Bora, B.; Bhuyan, H.; Wyndham, E.

2013-01-01

Plasma immersion ion implantation (PIII) has attracted wide interests since it emulates conventional ion-beam ion implantation (IBII) in niche applications. For instance, the technique has very high throughput, the implantation time is independent of the sample size, and samples with an irregular shape can be implanted without complex beam scanning or sample manipulation. For uniform ion implantation and deposition on to different substrates, like silicon, stainless steel etc., a capacitive coupled Radio frequency (RF), 13.6 MHz, plasma is used. During the PIII process, the physical parameters which are expected to play crucial rule in the deposition process like RF power, Negative pulse voltage and pulse duration, gas type and gas mixture, gas flow rates and the implantation dose are studied. The ion dose is calculated by dynamic sheath model and the plasma parameters are calculated from the V-I characteristic and power balance equation by homogeneous model of rf plasma discharge considering Ohmic as well as Stochastic heating. The correlations between the yield of the implantation process and the physical parameters as well as plasma parameters are discussed. (author)

Integrated models for plasma/material interaction during loss of plasma confinement

International Nuclear Information System (INIS)

Hassanein, A.

1998-01-01

A comprehensive computer package, High Energy Interaction with General Heterogeneous Target Systems (HEIGHTS), has been developed to evaluate the damage incurred on plasma-facing materials during loss of plasma confinement. The HEIGHTS package consists of several integrated computer models that follow the start of a plasma disruption at the scrape-off layer (SOL) through the transport of the eroded debris and splashed target materials to nearby locations as a result of the energy deposited. The package includes new models to study turbulent plasma behavior in the SOL and predicts the plasma parameters and conditions at the divertor plate. Full two-dimensional comprehensive radiation magnetohydrodynamic models are coupled with target thermodynamics and liquid hydrodynamics to evaluate the integrated response of plasma-facing materials. A brief description of the HEIGHTS package and its capabilities are given in this work with emphasis on turbulent plasma behavior in the SOL during disruptions

Development of high energy pulsed plasma simulator for plasma-lithium trench experiment

Science.gov (United States)

Jung, Soonwook

To simulate detrimental events in a tokamak and provide a test-stand for a liquid lithium infused trench (LiMIT) device, a pulsed plasma source utilizing a theta pinch in conjunction with a coaxial plasma accelerator has been developed. An overall objective of the project is to develop a compact device that can produce 100 MW/m2 to 1 GW/m2 of plasma heat flux (a typical heat flux level in a major fusion device) in ~ 100 mus (≤ 0.1 MJ/m2) for a liquid lithium plasma facing component research. The existing theta pinch device, DEVeX, was built and operated for study on lithium vapor shielding effect. However, a typical plasma energy of 3 - 4 kJ/m2 is too low to study an interaction of plasma and plasma facing components in fusion devices. No or little preionized plasma, ringing of magnetic field, collisions of high energy particles with background gas have been reported as the main issues. Therefore, DEVeX is reconfigured to mitigate these issues. The new device is mainly composed of a plasma gun for a preionization source, a theta pinch for heating, and guiding magnets for a better plasma transportation. Each component will be driven by capacitor banks and controlled by high voltage / current switches. Several diagnostics including triple Langmuir probe, calorimeter, optical emission measurement, Rogowski coil, flux loop, and fast ionization gauge are used to characterize the new device. A coaxial plasma gun is manufactured and installed in the previous theta pinch chamber. The plasma gun is equipped with 500 uF capacitor and a gas puff valve. The increase of the plasma velocity with the plasma gun capacitor voltage is consistent with the theoretical predictions and the velocity is located between the snowplow model and the weak - coupling limit. Plasma energies measured with the calorimeter ranges from 0.02 - 0.065 MJ/m2 and increases with the voltage at the capacitor bank. A cross-check between the plasma energy measured with the calorimeter and the triple probe

Characterization of pulsed atmospheric-pressure plasma streams (PAPS) generated by a plasma gun

Science.gov (United States)

Robert, E.; Sarron, V.; Riès, D.; Dozias, S.; Vandamme, M.; Pouvesle, J.-M.

2012-06-01

An experimental study of atmospheric-pressure rare gas plasma propagation in a high-aspect-ratio capillary is reported. The plasma is generated with a plasma gun device based on a dielectric barrier discharge (DBD) reactor powered by either nanosecond or microsecond rise-time high-voltage pulses at single-shot to multi-kHz frequencies. The influence of the voltage waveform, pulse polarity, pulse repetition rate and capillary material have been studied using nanosecond intensified charge-coupled device imaging and plasma-front velocity measurements. The evolution of the plasma appearance during its propagation and the study of the role of the different experimental parameters lead us to suggest a new denomination of pulsed atmospheric-pressure plasma streams to describe all the plasma features, including the previously so-called plasma bullet. The unique properties of such non-thermal plasma launching in capillaries, far from the primary DBD plasma, are associated with a fast ionization wave travelling with velocity in the 107-108 cm s-1 range. Voltage pulse tailoring is shown to allow for a significant improvement of such plasma delivery. Thus, the plasma gun device affords unique opportunities in biomedical endoscopic applications.

Characterization of pulsed atmospheric-pressure plasma streams (PAPS) generated by a plasma gun

International Nuclear Information System (INIS)

Robert, E; Sarron, V; Riès, D; Dozias, S; Vandamme, M; Pouvesle, J-M

2012-01-01

An experimental study of atmospheric-pressure rare gas plasma propagation in a high-aspect-ratio capillary is reported. The plasma is generated with a plasma gun device based on a dielectric barrier discharge (DBD) reactor powered by either nanosecond or microsecond rise-time high-voltage pulses at single-shot to multi-kHz frequencies. The influence of the voltage waveform, pulse polarity, pulse repetition rate and capillary material have been studied using nanosecond intensified charge-coupled device imaging and plasma-front velocity measurements. The evolution of the plasma appearance during its propagation and the study of the role of the different experimental parameters lead us to suggest a new denomination of pulsed atmospheric-pressure plasma streams to describe all the plasma features, including the previously so-called plasma bullet. The unique properties of such non-thermal plasma launching in capillaries, far from the primary DBD plasma, are associated with a fast ionization wave travelling with velocity in the 10 7 –10 8 cm s −1 range. Voltage pulse tailoring is shown to allow for a significant improvement of such plasma delivery. Thus, the plasma gun device affords unique opportunities in biomedical endoscopic applications. (paper)

All Plasma Products Are Not Created Equal: Characterizing Differences Between Plasma Products

Science.gov (United States)

2015-06-01

Research and the US Department of Defense. The pooling and solvent detergent treatment processes performed to manufacture the Octaplas and Kedrion products ...All plasma products are not created equal: Characterizing differences between plasma products Philip C. Spinella, MD, Elfaridah Frazier, PhD, Heather... products that may affect efficacy and safety. METHODS: Four different plasma products were analyzed to include fresh frozen plasma (FFP), liquid plasma

Plasma-wall interaction

International Nuclear Information System (INIS)

Reichle, R.

2004-01-01

This document gathers the 43 slides presented in the framework of the week long lecture 'hot plasmas 2004' and dedicated to plasma-wall interaction in a tokamak. This document is divided into 4 parts: 1) thermal load on the wall, power extraction and particle recovery, 2) basic edge plasma physics, 3) processes that drive the plasma-solid interaction, and 4) material conditioning (surface treatment...) for ITER

Study of single and binary ion plasma expansion into laboratory-generated plasma wakes

International Nuclear Information System (INIS)

Wright, K.H. Jr.

1988-02-01

Plasma expansion into the wake of a large rectangular plate immersed in a collisionless, supersonic plasma was investigated in laboratory experiments. The experimental conditions address both single ion and binary ion plasma flows for the case of a body whose size is large in comparison with the Debye length, when the potential difference between the body and the plasma is relatively small. A new plasma source was developed to generate equi-velocity, binary ion plasma flows, which allows access to new parameter space that have previously been unavailable for laboratory studies. Specifically, the new parameters are the ionic mass ratio and the ionic component density ratio. In a series of experiments, a krypton-neon plasma is employed where the ambient density ratio of neon to krypton is varied more than an order of magnitude. The expansion in both the single ion and binary ion plasma cases is limited to early times, i.e., a few ion plasma periods, by the combination of plasma density, plasma drift speed, and vacuum chamber size, which prevented detailed comparison with self-similar theory

The 2017 Plasma Roadmap: Low temperature plasma science and technology

Science.gov (United States)

Adamovich, I.; Baalrud, S. D.; Bogaerts, A.; Bruggeman, P. J.; Cappelli, M.; Colombo, V.; Czarnetzki, U.; Ebert, U.; Eden, J. G.; Favia, P.; Graves, D. B.; Hamaguchi, S.; Hieftje, G.; Hori, M.; Kaganovich, I. D.; Kortshagen, U.; Kushner, M. J.; Mason, N. J.; Mazouffre, S.; Mededovic Thagard, S.; Metelmann, H.-R.; Mizuno, A.; Moreau, E.; Murphy, A. B.; Niemira, B. A.; Oehrlein, G. S.; Petrovic, Z. Lj; Pitchford, L. C.; Pu, Y.-K.; Rauf, S.; Sakai, O.; Samukawa, S.; Starikovskaia, S.; Tennyson, J.; Terashima, K.; Turner, M. M.; van de Sanden, M. C. M.; Vardelle, A.

2017-08-01

Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.

The 2017 Plasma Roadmap: Low temperature plasma science and technology

International Nuclear Information System (INIS)

Adamovich, I; Baalrud, S D; Bogaerts, A; Bruggeman, P J; Cappelli, M; Colombo, V; Czarnetzki, U; Ebert, U; Eden, J G; Favia, P; Graves, D B; Hamaguchi, S; Hieftje, G; Hori, M

2017-01-01

Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges. (topical review)

Plasma Free Metanephrines

Science.gov (United States)

... Links Patient Resources For Health Professionals Subscribe Search Plasma Free Metanephrines Send Us Your Feedback Choose Topic ... Images View Sources Ask Us Also Known As Plasma Metanephrines Formal Name Fractionated Plasma Free Metanephrines (Metanephrine ...

TFTR plasma feedback systems

International Nuclear Information System (INIS)

Efthimion, P.; Hawryluk, R.J.; Hojsak, W.; Marsala, R.J.; Mueller, D.; Rauch, W.; Tait, G.D.; Taylor, G.; Thompson, M.

1985-01-01

The Tokamak Fusion Test Reactor employs feedback control systems for four plasma parameters, i.e. for plasma current, for plasma major radius, for plasma vertical position, and for plasma density. The plasma current is controlled by adjusting the rate of change of current in the Ohmic Heating (OH) coil system. Plasma current is continuously sensed by a Rogowski coil and its associated electronics; the error between it and a preprogrammed reference plasma current history is operated upon by a ''proportional-plusintegral-plus-derivative'' (PID) control algorithm and combined with various feedforward terms, to generate compensating commands to the phase-controlled thyristor rectifiers which drive current through the OH coils. The plasma position is controlled by adjusting the currents in Equilibrium Field and Horizontal Field coil systems, which respectively determine the vertical and radial external magnetic fields producing J X B forces on the plasma current. The plasma major radius position and vertical position, sensed by ''B /sub theta/ '' and ''B /sub rho/ '' magnetic flux pickup coils with their associated electronics, are controlled toward preprogrammed reference histories by allowing PID and feedforward control algorithms to generate commands to the EF and HF coil power supplies. Plasma density is controlled by adjusting the amount of gas injected into the vacuum vessel. Time-varying gains are used to combine lineaveraged plasma density measurements from a microwave interferometer plasma diagnostic system with vacuum vessel pressure measurements from ion gauges, with various other measurements, and with preprogrammed reference histories, to determine commands to piezoelectric gas injection valves

Plasma Channel Lenses and Plasma Tornadoes for Optical Beam Focusing and Transport

Science.gov (United States)

Hubbard, R. F.; Kaganovich, D.; Johnson, L. A.; Gordon, D. F.; Penano, J. R.; Hafizi, B.; Helle, M. H.; Mamonau, A. A.

2017-10-01

Shaped plasmas offer the possibility of manipulating laser pulses at intensities far above the damage limits for conventional optics. An example is the plasma channel, which is a cylindrical plasma column with an on-axis density minimum. Long plasma channels have been widely used to guide intense laser pulses, particularly in laser wakefield accelerators. A new concept, the ``plasma tornado'', offers the possibility of creating long plasma channels with no nearby structures and at densities lower than can be achieved by capillary discharges. A short plasma channel can focus a laser pulse in much the same manner as a conventional lens or off-axis parabola. When placed in front of the focal point of an intense laser pulse, a plasma channel lens (PCL) can reduce the effective f-number of conventional focusing optics. When placed beyond the focal point, it can act as a collimator. We will present experimental and modeling results for a new plasma tornado design, review experimental methods for generating short PCLs, and discuss potential applications. Supported by the Naval Research Laboratory Base Program.

Properties of the Dense Plasma Produced in Plasma Focus

International Nuclear Information System (INIS)

Peacock, N.J.; Wilcock, P.D.; Speer, R.J.; Morgan, P.D.

1969-01-01

The plasma produced by the focus or quasi-cylindrical magnetic compression which occurs at the open end of a metal-walled, coaxial plasma gun has been studied, using the electrical waveforms and the electromagnetic and reaction particle, emission. The electromagnetic radiation in the XUV region of the spectrum has previously been briefly reported, and the present paper describes further more detailed analyses of the line emission at wavelengths shorter than 10 Å when impurities are added to the gas filling. The emission is characteristic of a plasma with a temperature of a few keV and a density greater than 10 19 cm -3 , while the appearance of optical transitions in highly stripped ions, e. g. A XVIII, gives a measure of the thermalization in the plasma. The stored electrical energy has been doubled and the scaling of the neutron emission with the applied voltage and the initial particle density is presented. The duration of the neutron and X-ray emission is considerably longer than the observed instability growth time in the plasma filament. Calculations of the mode of heating and the confinement of the plasma are compared with experimental observations. (author)

Interaction of multiple plasma plumes in an atmospheric pressure plasma jet array

International Nuclear Information System (INIS)

Ghasemi, M; Olszewski, P; Bradley, J W; Walsh, J L

2013-01-01

Plasma jet arrays are considered a viable means to enhance the scale of a downstream surface treatment beyond that possible using a single plasma jet. Of paramount importance in many processing applications is the uniformity of the plasma exposure on the substrate, which can be compromised when multiple plasma jets are arranged in close proximity due to their interaction. This contribution explores a dielectric barrier plasma jet array consisting of multiple individually ballasted jets. It is shown that capacitive ballasting is a promising technique to allow simultaneous operation of the plasma plumes without the losses associated with resistive ballasting. The interaction between adjacent plasma plumes and the background gas is investigated with Schlieren imaging; it is shown that the strong repulsive force between each plasma plume causes a divergence in propagation trajectory and a reduction in the laminar flow length with significant ramifications for any downstream surface treatment.

Measurement of toroidal plasma current in RF heated helical plasmas

International Nuclear Information System (INIS)

Besshou, Sakae

1993-01-01

This report describes the measurement of toroidal plasma current by a semiflexible Rogowski coil in a helical vacuum chamber. A Rogowski coil measures the toroidal plasma current with a resolution of 0.1 kA, frequency range of up to 1 kHz and sensitivity of 6.5 x 10 -9 V · s/A. We measured the spontaneous toroidal plasma current (from -1.2 to +1.2 kA) under electron cyclotron resonance heating at 0.94 T toroidal field in the Heliotron-E device. We found that the measured direction of toroidal plasma current changes its sign as in the predicted behavior of a neoclassical diffusion-driven bootstrap current, depending on the horizontal position of the plasma column. We explain the observed plasma currents in terms of the compound phenomenon of an ohmic current and a neoclassical diffusion-driven current. The magnitude of the neoclassical current component is smaller than the value predicted by a collisionless neoclassical theory. (author)

Electron plasma waves in CO/sub 2/ laser plasma interactions

International Nuclear Information System (INIS)

Baldis, H.A.; Villeneuve, D.M.; Walsh, C.J.

1984-01-01

During the past few years, the use of Thomson scattering in CO/sub 2/ laser produced plasmas has permitted the identification and study of electron plasma waves and ion waves, driven by various instabilities in the plasma corona, such as Stimulated Raman Scattering (SRS), two plasmon decay, and Stimulated Brillouin Scattering (SBS). Since these instabilities may coexist in the plasma, the density fluctuations associated with one wave may influence the behaviour of one or more of the other instabilities. The authors discuss the experimental evidence of such effects and, in particular, the consequences of a recent experiment in which the ion waves driven by SBS were observed to adversely affect the production of the electron plasma waves driven by SRS. In that experiment, a strong correlation was observed between the onset of SBS and the disappearance of the electron plasma waves driven by SRS at low densities (n/sub e/ n/sub e/ > 0.05 n/sub c/)

FOREWORD: 23rd National Symposium on Plasma Science & Technology (PLASMA-2008)

Science.gov (United States)

Das, A. K.

2010-01-01

The Twentieth Century has been a defining period for Plasma Science and Technology. The state of ionized matter, so named by Irving Langmuir in the early part of twentieth century, has now evolved in to a multidisciplinary area with scientists and engineers from various specializations working together to exploit the unique properties of the plasma medium. There have been great improvements in the basic understanding of plasmas as a many body system bound by complex collective Coulomb interactions of charges, atoms, molecules, free radicals and photons. Simultaneously, many advanced plasma based technologies are increasingly being implemented for industrial and societal use. The emergence of the multination collaborative project International Thermonuclear Experimental Reactor (ITER) project has provided the much needed boost to the researchers working on thermonuclear fusion plasmas. In addition, the other plasma applications like MHD converters, hydrogen generation, advanced materials (synthesis, processing and surface modification), environment (waste beneficiation, air and water pollution management), nanotechnology (synthesis, deposition and etching), light production, heating etc are actively being pursued in governmental and industrial sectors. For India, plasma science and technology has traditionally remained an important area of research. It was nearly a century earlier that the Saha ionization relation pioneered the way to interpret experimental data from a vast range of near equilibrium plasmas. Today, Indian research contributions and technology demonstration capabilities encompass thermonuclear fusion devices, nonlinear plasma phenomena, plasma accelerators, beam plasma interactions, dusty and nonneutral plasmas, industrial plasmas and plasma processing of materials, nano synthesis and structuring, astrophysical and space plasmas etc. India's participation in the ITER programme is now reflected in increased interest in the research and development

Magnetohydrodynamic simulation study of plasma jets and plasma-surface contact in coaxial plasma accelerators

Science.gov (United States)

Subramaniam, Vivek; Raja, Laxminarayan L.

2017-06-01

Recent experiments by Loebner et al. [IEEE Trans. Plasma Sci. 44, 1534 (2016)] studied the effect of a hypervelocity jet emanating from a coaxial plasma accelerator incident on target surfaces in an effort to mimic the transient loading created during edge localized mode disruption events in fusion plasmas. In this paper, we present a magnetohydrodynamic (MHD) numerical model to simulate plasma jet formation and plasma-surface contact in this coaxial plasma accelerator experiment. The MHD system of equations is spatially discretized using a cell-centered finite volume formulation. The temporal discretization is performed using a fully implicit backward Euler scheme and the resultant stiff system of nonlinear equations is solved using the Newton method. The numerical model is employed to obtain some key insights into the physical processes responsible for the generation of extreme stagnation conditions on the target surfaces. Simulations of the plume (without the target plate) are performed to isolate and study phenomena such as the magnetic pinch effect that is responsible for launching pressure pulses into the jet free stream. The simulations also yield insights into the incipient conditions responsible for producing the pinch, such as the formation of conductive channels. The jet-target impact studies indicate the existence of two distinct stages involved in the plasma-surface interaction. A fast transient stage characterized by a thin normal shock transitions into a pseudo-steady stage that exhibits an extended oblique shock structure. A quadratic scaling of the pinch and stagnation conditions with the total current discharged between the electrodes is in qualitative agreement with the results obtained in the experiments. This also illustrates the dominant contribution of the magnetic pressure term in determining the magnitude of the quantities of interest.

Plasma metallization

International Nuclear Information System (INIS)

Crowther, J.M.

1997-09-01

Many methods are currently used for the production of thin metal films. However, all of these have drawbacks associated with them, for example the need for UHV conditions, high temperatures, exotic metal precursors, or the inability to coat complex shaped objects. Reduction of supported metal salts by non-isothermal plasma treatment does not suffer from these drawbacks. In order to produce and analyse metal films before they become contaminated, a plasma chamber which could be attached directly to a UHV chamber with XPS capability was designed and built. This allowed plasma treatment of supported metal salts and surface analysis by XPS to be performed without exposure of the metal film to the atmosphere. Non-equilibrium plasma treatment of Nylon 66 supported gold(lll) chloride using hydrogen as the feed gas resulted in a 95% pure gold film, the remaining 5% of the film being carbon. If argon or helium were used as the feed gases during plasma treatment the resultant gold films were 100% pure. Some degree of surface contamination of the films due to plasma treatment was observed but was easily removed by argon ion cleaning. Hydrogen plasma reduction of glass supported silver(l) nitrate and palladium(ll) acetate films reveals that this metallization technique is applicable to a wide variety of metal salts and supports, and has also shown the ability of plasma reduction to retain the complex 'fern-like' structures seen for spin coated silver(l) nitrate layers. Some metal salts are susceptible to decomposition by X-rays. The reduction of Nylon 66 supported gold(lll) chloride films by soft X-rays to produce nanoscopic gold particles has been studied. The spontaneous reduction of these X-ray irradiated support gold(lll) chloride films on exposure to the atmosphere to produce gold rich metallic films has also been reported. (author)

Some aspects of plasma thermodynamics

International Nuclear Information System (INIS)

Gorgoraki, V.I.

1986-01-01

The objective reasons which have inhibited the development of a plasma-thermodynamics theory are discussed and the authors formulate the fundamental principles which can be the basis of a common plasma-thermodynamics theory. Two kinds of thermodynamic equilibrium plasmas are discussed, an isothermal plasma and a nonisothermal plasma. An isothermal plasma is a high-temperature plasma; the Saha-Eggert equation describes its behavior. A nonisothermal plasma is a low-temperature plasma, and the reactions taking place therein are purely plasma-chemical. The ionization equilibrium and the composition of such a plasma can be found with the aid of the equations presented in this paper

Particle beams and plasmas

International Nuclear Information System (INIS)

Hofmann, A.; Messerschmid, E.; Lawson, J.D.

1976-01-01

These lectures present a survey of some of the concepts of plasma physics and look at some situations familiar to particle-accelerator physicists from the point of view of a plasma physicist, with the intention of helping to link together the two fields. At the outset, basic plasma concepts are presented, including definitions of a plasma, characteristic parameters, magnetic pressure and confinement. This is followed by a brief discussion on plasma kinetic theory, non-equilibrium plasma, and the temperature of moving plasmas. Examples deal with beams in the CERN Intersecting Storage Rings as well as with non-steady beams in cyclic accelerators and microwave tubes. In the final chapters, time-varying systems are considered: waves in free space and the effect of cylinder bounds, wave motion in cold stationary plasmas, and waves in plasmas with well-defined streams. The treatment throughout is informal, with emphasis on the essential physical properties of continuous beams in accelerators and storage rings in relation to the corresponding problems in plasma physics and microwave tubes. (Author)

Dense Plasma Focus - From Alternative Fusion Source to Versatile High Energy Density Plasma Source for Plasma Nanotechnology

Science.gov (United States)

Rawat, R. S.

2015-03-01

The dense plasma focus (DPF), a coaxial plasma gun, utilizes pulsed high current electrical discharge to heat and compress the plasma to very high density and temperature with energy densities in the range of 1-10 × 1010 J/m3. The DPF device has always been in the company of several alternative magnetic fusion devices as it produces intense fusion neutrons. Several experiments conducted on many different DPF devices ranging over several order of storage energy have demonstrated that at higher storage energy the neutron production does not follow I4 scaling laws and deteriorate significantly raising concern about the device's capability and relevance for fusion energy. On the other hand, the high energy density pinch plasma in DPF device makes it a multiple radiation source of ions, electron, soft and hard x-rays, and neutrons, making it useful for several applications in many different fields such as lithography, radiography, imaging, activation analysis, radioisotopes production etc. Being a source of hot dense plasma, strong shockwave, intense energetic beams and radiation, etc, the DPF device, additionally, shows tremendous potential for applications in plasma nanoscience and plasma nanotechnology. In the present paper, the key features of plasma focus device are critically discussed to understand the novelties and opportunities that this device offers in processing and synthesis of nanophase materials using, both, the top-down and bottom-up approach. The results of recent key experimental investigations performed on (i) the processing and modification of bulk target substrates for phase change, surface reconstruction and nanostructurization, (ii) the nanostructurization of PLD grown magnetic thin films, and (iii) direct synthesis of nanostructured (nanowire, nanosheets and nanoflowers) materials using anode target material ablation, ablated plasma and background reactive gas based synthesis and purely gas phase synthesis of various different types of

Dense Plasma Focus - From Alternative Fusion Source to Versatile High Energy Density Plasma Source for Plasma Nanotechnology

International Nuclear Information System (INIS)

Rawat, R S

2015-01-01

The dense plasma focus (DPF), a coaxial plasma gun, utilizes pulsed high current electrical discharge to heat and compress the plasma to very high density and temperature with energy densities in the range of 1-10 × 10 10 J/m 3 . The DPF device has always been in the company of several alternative magnetic fusion devices as it produces intense fusion neutrons. Several experiments conducted on many different DPF devices ranging over several order of storage energy have demonstrated that at higher storage energy the neutron production does not follow I 4 scaling laws and deteriorate significantly raising concern about the device's capability and relevance for fusion energy. On the other hand, the high energy density pinch plasma in DPF device makes it a multiple radiation source of ions, electron, soft and hard x-rays, and neutrons, making it useful for several applications in many different fields such as lithography, radiography, imaging, activation analysis, radioisotopes production etc. Being a source of hot dense plasma, strong shockwave, intense energetic beams and radiation, etc, the DPF device, additionally, shows tremendous potential for applications in plasma nanoscience and plasma nanotechnology. In the present paper, the key features of plasma focus device are critically discussed to understand the novelties and opportunities that this device offers in processing and synthesis of nanophase materials using, both, the top-down and bottom-up approach. The results of recent key experimental investigations performed on (i) the processing and modification of bulk target substrates for phase change, surface reconstruction and nanostructurization, (ii) the nanostructurization of PLD grown magnetic thin films, and (iii) direct synthesis of nanostructured (nanowire, nanosheets and nanoflowers) materials using anode target material ablation, ablated plasma and background reactive gas based synthesis and purely gas phase synthesis of various different types of

On atmospheric-pressure non-equilibrium plasma jets and plasma bullets

International Nuclear Information System (INIS)

Lu, X; Laroussi, M; Puech, V

2012-01-01

Atmospheric-pressure non-equilibrium plasma jets (APNP-Js), which generate plasma in open space rather than in a confined discharge gap, have recently been a topic of great interest. In this paper, the development of APNP-Js will be reviewed. Firstly, the APNP-Js are grouped based on the type of gas used to ignite them and their characteristics are discussed in detail. Secondly, one of the most interesting phenomena of APNP-Js, the ‘plasma bullet’, is discussed and its behavior described. Thirdly, the very recent developments on the behavior of plasma jets when launched in a controlled environment and pressure are also introduced. This is followed by a discussion on the interaction between plasma jets. Finally, perspectives on APNP-J research are presented. (paper)

Plasma stream transport method (2) Use of charge exchange plasma source

International Nuclear Information System (INIS)

Tsuchimoto, T.

1978-01-01

The plasma stream transport method using a single plasma source has limitations for practical film deposition. Using a charge exchange phenomenon, a new plasma source is devised and tested by the plasma stream transport machine. Metals, silicon dioxide, and nitride films are deposited by this system. The mechanism of deposition under relatively high vacuum surrounding a silicon wafer is discussed as is the effect of radical atoms

Magnetoresistive waves in plasmas

International Nuclear Information System (INIS)

Felber, F.S.; Hunter, R.O. Jr.; Pereira, N.R.; Tajima, T.

1982-01-01

The self-generated magnetic field of a current diffusing into a plasma between conductors can magnetically insulate the plasma. Propagation of magnetoresistive waves in plasmas is analyzed. Applications to plasma opening switches are discussed

Visualization of intermittent blobby plasma transport in attached and detached plasmas of the NAGDIS-II

International Nuclear Information System (INIS)

Ohno, Noriyasu; Furuta, Katsuhiro; Takamura, Shuichi

2004-01-01

We investigated the intermittent convective plasma transport in a attached and/or detached plasma condition of the linear divertor plasma simulator, NAGDIS-II. Images taken by a fast-imaging camera clearly show that in attached plasmas, blobs are peeled off the bulk plasma, and propagate outward with an azimuthal motion. In detached plasmas, plasma turbulence observed near the plasma recombining region drives strong intermittent radial plasma transport, which could broaden the radial density profile. (author)

Plasma processing: Technologies and applications

International Nuclear Information System (INIS)

Naddaf, M.; Saloum, S.

2005-01-01

This study aims to present the fundamentals of physics of plasmas, methods of generation, diagnostics, and applications for processing of materials. The first chapter defines plasma in general as well as its main parameters, the most important differential equations in plasma physics, and classifies the types of plasmas. the various methods and techniques to create and sustain plasma are presented in the second chapter. Chapter 3 focuses on plasma diagnostic methods and tools. While chapter 4 deals with applications of plasma processing such as; surface modification of materials, plasma ashing and etching, plasma cutting, and the environmental applications of plasma. Plasma polymerization and its various applications have been presented in more details in the last chapter. (Author)

Laser-produced aluminum plasma expansion inside a plastic plasma envelope

Czech Academy of Sciences Publication Activity Database

Kasperczuk, A.; Pisarczyk, T.; Chodukowski, T.; Kalinowska, Z.; Parys, P.; Renner, Oldřich; Gus´kov, S.Y.; Demchenko, N. N.; Ullschmied, Jiří; Krouský, Eduard; Pfeifer, Miroslav; Rohlena, Karel; Skála, Jiří

2012-01-01

Roč. 19, č. 9 (2012), s. 1-8 ISSN 1070-664X R&D Projects: GA MŠk(CZ) 7E09092; GA MŠk(CZ) LC528; GA ČR GAP205/10/0814 Grant - others:7FP LASERLAB-EUROPE(XE) 228334 Program:FP7 Institutional research plan: CEZ:AV0Z10100523; CEZ:AV0Z20430508 Keywords : laser-mater interaction * plasma jets production * x-ray spectroscopy * particle plasma diagnosis * ion charge density * plasma temperature Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 2.376, year: 2012

Surge of plasma waves in an inhomogeneous plasma

International Nuclear Information System (INIS)

Benhassine, Mohammed

1985-01-01

The first part of this research thesis addresses the propagation of waves in a plasma. It presents the equation of propagation of an electromagnetic wave in a plasma without magnetic field, and analyses the propagation in an inhomogeneous medium. The second part addresses the wave-particle interaction: interaction between electrons and an electromagnetic wave, between electrons and an electrostatic wave (trapping), and between electrons and a localised electric field. The third chapter presents the analytic theory of oscillations of a cold plasma (macroscopic equations in Lagrangian coordinates, analytic solution before surge). The next chapter discusses physical interpretations before the wave surge, after the wave surge, and about energy exchange (within or outside of resonance). Numerical simulations and their results are then reported and discussed. The sixth chapter addresses the case of an electrostatic wave surge in a hot plasma. It notably addresses the following aspects: equivalence between the description of moments and the Waterbag model, interaction between non linearity and thermal effects, variation of electric field amplitude with temperature. Results of numerical simulations are presented, and the last part addresses experimental predictions for microwaves-plasma interaction and laser-matter interaction [fr

Improved plasma accelerator

Science.gov (United States)

Cheng, D. Y.

1971-01-01

Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

Improved planar radio frequency inductively coupled plasma configuration in plasma immersion ion implantation

International Nuclear Information System (INIS)

Tang, D.L.; Fu, R.K.Y.; Tian, X.B.; Chu, P.K.

2003-01-01

Plasmas with higher density and better uniformity are produced using an improved planar radio frequency (rf) inductively coupled plasma configuration in plasma immersion ion implantation (PIII). An axial magnetic field is produced by external electromagnetic coils outside the discharge chamber. The rf power can be effectively absorbed by the plasma in the vicinity of the electron gyrofrequency due to the enhanced resonant absorption of electromagnetic waves in the whistler wave range, which can propagate nearly along the magnetic field lines thus greatly increases the plasma density. The plasma is confined by a longitudinal multipolar cusp magnetic field made of permanent magnets outside the process chamber. It can improve the plasma uniformity without significantly affecting the ion density. The plasma density can be increased from 3x10 9 to 1x10 10 cm -3 employing an axial magnetic field of several Gauss at 1000 W rf power and 5x10 -4 Torr gas pressure. The nonuniformity of the plasma density is less than 10% and can be achieved in a process chamber with a diameter of 600 mm. Since the plasma generation and process chambers are separate, plasma extinction due to the plasma sheath touching the chamber wall in high-energy PIII can be avoided. Hence, low-pressure, high-energy, and high-uniformity ion implantation can be accomplished using this setup

Determination of plasma spot current and arc discharge plasma current on the system of plasma cathode electron sources using Rogowski coil technique

International Nuclear Information System (INIS)

Wirjoadi; Bambang Siswanto; Lely Susita RM; Agus Purwadi; Sudjatmoko

2015-01-01

It has been done the function test experiments of ignitor electrode system and the plasma generator electrode system to determine the current spot plasma and arc discharge plasma current with Rogowski coil technique. Ignitor electrode system that gets power supply from IDPS system can generate the plasma spot current of 11.68 ampere to the pulse width of about 33 μs, this value is greater than the design probably because of electronic components used in the IDPS system was not as planned. For the plasma generator electrode system that gets power from ADPS system capable of producing an arc discharge plasma current around 103.15 amperes with a pulse width of about 96 μs, and this value as planned. Based on the value of the arc discharge plasma current can be determined plasma electron density, which is about 10.12 10"1"9 electrons/m"3, and with this electron density value, an ignitor electrode system and a plasma generator system is quite good if used as a plasma cathode electron source system. (author)

Stability of plasma cylinder with current in a helical plasma flow

Science.gov (United States)

Leonovich, Anatoly S.; Kozlov, Daniil A.; Zong, Qiugang

2018-04-01

Stability of a plasma cylinder with a current wrapped by a helical plasma flow is studied. Unstable surface modes of magnetohydrodynamic (MHD) oscillations develop at the boundary of the cylinder enwrapped by the plasma flow. Unstable eigenmodes can also develop for which the plasma cylinder is a waveguide. The growth rate of the surface modes is much higher than that for the eigenmodes. It is shown that the asymmetric MHD modes in the plasma cylinder are stable if the velocity of the plasma flow is below a certain threshold. Such a plasma flow velocity threshold is absent for the symmetric modes. They are unstable in any arbitrarily slow plasma flows. For all surface modes there is an upper threshold for the flow velocity above which they are stable. The helicity index of the flow around the plasma cylinder significantly affects both the Mach number dependence of the surface wave growth rate and the velocity threshold values. The higher the index, the lower the upper threshold of the velocity jump above which the surface waves become stable. Calculations have been carried out for the growth rates of unstable oscillations in an equilibrium plasma cylinder with current serving as a model of the low-latitude boundary layer (LLBL) of the Earth's magnetic tail. A tangential discontinuity model is used to simulate the geomagnetic tail boundary. It is shown that the magnetopause in the geotail LLBL is unstable to a surface wave (having the highest growth rate) in low- and medium-speed solar wind flows, but becomes stable to this wave in high-speed flows. However, it can remain weakly unstable to the radiative modes of MHD oscillations.

International conference on plasma physics

International Nuclear Information System (INIS)

Silin, V.P.; Sitenko, A.G.

1985-01-01

A brief report on the 6th International conference on plasma physics and on the 6th International Congress on plasma waves and plasma instabilities, which have taken place in summer 1984 in Losanne, is presented. Main items of the conference are enlightened, such as the general theory of a plasma, laboratory plasma, thermonuclear plasma, cosmic plasma and astrophysics

Theoretical approach for plasma series resonance effect in geometrically symmetric dual radio frequency plasma

International Nuclear Information System (INIS)

Bora, B.; Bhuyan, H.; Favre, M.; Wyndham, E.; Chuaqui, H.

2012-01-01

Plasma series resonance (PSR) effect is well known in geometrically asymmetric capacitively couple radio frequency plasma. However, plasma series resonance effect in geometrically symmetric plasma has not been properly investigated. In this work, a theoretical approach is made to investigate the plasma series resonance effect and its influence on Ohmic and stochastic heating in geometrically symmetric discharge. Electrical asymmetry effect by means of dual frequency voltage waveform is applied to excite the plasma series resonance. The results show considerable variation in heating with phase difference between the voltage waveforms, which may be applicable in controlling the plasma parameters in such plasma.

Lightweight Portable Plasma Medical Device - Plasma Engineering Research Laboratory

Science.gov (United States)

2015-12-01

monocytic leukemia cancer cells ( THP -1) were also tested and the results 19 demonstrate that a preference for apoptosis in plasma treated THP -1...unanswered questions. We have tested the effects of indirect exposure of non-thermal air plasma on monocytic leukemia cancer cells ( THP -1) and deciphering... tested and the results are shown in Fig. above. The results demonstrate that a preference for apoptosis in plasma treated THP -1 cells under

Plasma fluctuation measurements in tokamaks using beam-plasma interactions

International Nuclear Information System (INIS)

Fonck, R.J.; Duperrex, P.A.; Paul, S.F.

1990-01-01

High-frequency observations of light emitted from the interactions between plasma ions and injected neutral beam atoms allow the measurement of moderate-wavelength fluctuations in plasma and impurity ion densities. To detect turbulence in the local plasma ion density, the collisionally excited fluorescence from a neutral beam is measured either separately at several spatial points or with a multichannel imaging detector. Similarly, the role of impurity ion density fluctuations is measured using charge exchange recombination excited transitions emitted by the ion species of interest. This technique can access the relatively unexplored region of long-wavelength plasma turbulence with k perpendicular ρ i much-lt 1, and hence complements measurements from scattering experiments. Optimization of neutral beam geometry and optical sightlines can result in very good localization and resolution (Δx≤1 cm) in the hot plasma core region. The detectable fluctuation level is determined by photon statistics, atomic excitation processes, and beam stability, but can be as low as 0.2% in a 100 kHz bandwidth over the 0--1 MHz frequency range. The choices of beam species (e.g., H 0 , He 0 , etc.), observed transition (e.g., H α , L α , He I singlet or triplet transitions, C VI Δn=1, etc.) are dictated by experiment-specific factors such as optical access, flexibility of beam operation, plasma conditions, and detailed experimental goals. Initial tests on the PBX-M tokamak using the H α emissions from a heating neutral beam show low-frequency turbulence in the edge plasma region

Plasma density measurements on refuelling by solid hydrogen pellets in a rotating plasma

International Nuclear Information System (INIS)

Joergensen, L.W.; Sillesen, A.H.

1978-01-01

The refuelling of a plasma by solid hydrogen pellets situated in the plasma is investigated. Nearly half of the pellet material is evaporated and seems to be completely ionized, resulting in an increase of the amount of plasma equivalent to one third of the total amount of plasma without refuelling. The gross behaviour of the plasma is not changed. (author)

Plasma behavior and plasma-wall interaction in magnetic fusion divices

International Nuclear Information System (INIS)

Ohtsuka, Hideo

1984-10-01

To study the fundamental behavior of plasma in magnetic field is the main subject in the early stage of the magnetic fusion research. At the next stage, it is necessary to overcome some actual problems in order to attain reactor grade plasmas. One of them is to control impurities in the plasma. In these points of view, we carried out several experiments or theoretical analyses. Firstly, anomalous loss mechanisms in magnetic field were investigated in a toroidal multipole device JFT-1 and the role of motions of charged particles in the magnetic field was exhibited. Various measurements of plasma in the scrape-off layer were made in a divertor tokamak JFT-2a and in an ordinary tokamak JFT-2. The former study demonstrated the first successful divertor operation of the tokamak device and the latter one clarified the mechanism of arcing on the tokamak first wall. As to arcing, a new theory which describes the retrograde motion, the well known strange motion of arcs in a magnetic field, was proposed. Good agreement with the experimental results was shown. Finally, by considering a zero-dimensional sputtering model a self-consistent relation between light and metal impurities in tokamak plasmas was obtained. It was shown that the relation well describes some fundamental aspects of the plasma-wall interaction. As a conclusion, the importance of simple behavior of charged particles in magnetic fields was pointed out not only for the plasma confinement but also for the plasma-wall interaction. (author)

Suitability of tunneling ionization produced plasmas for the plasma beat wave accelerator

International Nuclear Information System (INIS)

Leeman, W.P.; Clayton, C.E.; Marsh, K.A.; Dyson, A.; Joshi, C.

1991-01-01

Tunneling ionization can be thought of as the high intensity, low frequency limit of multi-photon ionization (MPI). Extremely uniform plasmas were produced by the latter process at Rutherford lab for beat wave excitation experiments using a 0.5 μm laser. Plasmas with 100% ionization were produced with densities exceeding 10 17 cm -3 . The experiment uses a CO 2 laser (I max ∼ 5 x 10 14 W/cm 2 ) which allows the formation of plasmas via the tunneling process. For the experiments the authors need plasmas with densities in the range of 5 to 10 x 10 16 cm -3 . Using Thomson scattering as a diagnostic they have explored the density and temperature regime of tunneling ionization produced plasmas. They find that plasmas with densities up to 10 16 cm -3 can indeed be produced and that these plasmas are hot. Beyond this density strong refraction of laser radiation occurs due to the radial profile of the plasma. Implications of this work to the Beat Wave Accelerator program will be discussed

Dynamic behavior of plasma-facing materials during plasma instabilities in tokamak reactors

International Nuclear Information System (INIS)

Hassanein, A.; Konkashbaev, I.

1997-01-01

Damage to plasma-facing and nearby components due to plasma instabilities remains a major obstacle to a successful tokamak concept. The high energy deposited on facing materials during plasma instabilities can cause severe erosion, plasma contamination, and structural failure of these components. Erosion damage can take various forms such as surface vaporization, spallation, and liquid ejection of metallic materials. Comprehensive thermodynamic and radiation hydrodynamic codes have been developed, integrated, and used to evaluate the extent of various damage to plasma-facing and nearby components. The eroded and splashed materials will be transported and then redeposited elsewhere on other plasma-facing components. Detailed physics of plasma/solid-liquid/vapor interaction in a strong magnetic field have been developed, optimized, and implemented in a self-consistent model. The plasma energy deposited in the evolving divertor debris is quickly and intensely reradiated, which may cause severe erosion and melting of other nearby components. Factors that influence and reduce vapor-shielding efficiency such as vapor diffusion and turbulence are also discussed and evaluated

Experimental works in plasma developed in INPE (Brazil). 1. Double plasma machine for longitudinal wave study. 2. Plasma centrifuge

International Nuclear Information System (INIS)

Ferreira, J.L.; Ludwig, G.O.; Del Bosco, E.

1982-01-01

This work describes some experiments done at the Plasma Physics Laboratory at INPE. In the first part, the double plasma machine used for the study of ion acoustic wave propagation is described, and the results obtained so far are shown. The second part consists in the description of a plasma centrifuge project. It contains some basic parameters of our apparatus used for isotope separation, throuth electromagtnetic rotation of the plasma. (Author) [pt

Negative ion surface plasma source development for plasma trap injectors in Novosibirsk

International Nuclear Information System (INIS)

Bel'chenko, Yu.I.; Dimov, G.I.; Dudnikov, V.G.; Kupriyanov, A.S.

1989-01-01

Work on high-current ion sources carried out at the Novosibirsk Institute of Nuclear Physics (INP) is presented. The INP investigations on ''pure plasma'' planotron and ''pure surface'' secondary emission systems of H - generation, which preceded the surface-plasma concept developed in Novosibirsk, are described. The physical basis of the surface-plasma method of negative-ion production is considered. The versions and operating characteristics of different surface-plasma sources including the multi-ampere (approx-gt 10A) source are discussed. Research on efficient large-area (∼10 2 cm 2 ) negative ion surface-plasma emitters is described. The INP long-pulse multiaperture surface- plasma generators, with a current of about 1A, are described. 38 refs., 17 figs

Plasma state. The universe's fire

International Nuclear Information System (INIS)

Lehner, Th.

2004-01-01

The plasma is the fourth state of matter, obtained at a very high temperature by the separation of the electrons from their nuclei. Plasma represents 99% of the visible mass of our present day universe and was the unique state of matter at its very beginning. Plasmas are present in the core of stars and in the interstellar environment. More closer to us, they are responsible of spectacular phenomena, like aurora borealis, lightning, comet queues etc.. This book makes a review of the different types of plasmas (electromagnetic, Earth's plasmas, spatial plasmas, solar plasmas, astrophysical plasmas). One chapter presents the thermonuclear fusion as future energy source. Another one treats of the chaos and turbulence inside plasmas. Some applications of plasmas are reviewed: MHD and ionic propulsion systems, MHD energy conversion and MHD generators, thermo-ionic converters, solid-state plasmas, particle accelerators, coherent radiation sources, 'Zeta' machines, X-ray lasers, isotopic separation, non-neutral plasmas and charged beams, free-electrons lasers, electrons and positrons plasmas, industrial applications (etching and cleaning, manufacturing of solar cells, flat screens, industrial reactors, waste treatment, cold plasma-assisted sterilization, effluents decontamination etc.). A last chapter makes an overview of the modern research in plasma physics. (J.S.)

Preliminary scaling laws for plasma current, ion kinetic temperature, and plasma number density in the NASA Lewis bumpy torus plasma

Science.gov (United States)

Roth, J. R.

1976-01-01

Parametric variation of independent variables which may affect the characteristics of bumpy torus plasma have identified those which have a significant effect on the plasma current, ion kinetic temperature, and plasma number density, and those which do not. Empirical power law correlations of the plasma current, and the ion kinetic temperature and number density were obtained as functions of potential applied to the midplane electrode rings, the background neutral gas pressure, and the magnetic field strength. Additional parameters studied included the type of gas, the polarity of the midplane electrode rings, the mode of plasma operation, and the method of measuring the plasma number density. No significant departures from the scaling laws appear to occur at the highest ion kinetic temperatures or number densities obtained to date.

The plasma-wall interaction region: a key low temperature plasma for controlled fusion

International Nuclear Information System (INIS)

Counsell, G F

2002-01-01

The plasma-wall interaction region of a fusion device provides the interface between the hot core plasma and the material surfaces. To obtain acceptably low levels of erosion from these surfaces requires most of the power leaving the core to be radiated. This is accomplished in existing devices by encouraging plasma detachment, in which the hot plasma arriving in the region is cooled by volume recombination and ion-neutral momentum transfer with a dense population of neutrals recycled from the surface. The result is a low temperature (1 eV e e >10 19 m -3 ) but weakly ionized (n 0 >10 20 m -3 , n e /n 0 <0.1) plasma found nowhere else in the fusion environment. This plasma provides many of the conditions found in industrial plasmas exploiting plasma chemistry and the presence of carbon in the region (in the form of carbon-fibre composite used in the plasma facing materials) can result in the formation of deposited hydrocarbon films. The plasma-wall interaction region is therefore among the most difficult in fusion to model, requiring an understanding of atomic, molecular and surface physics issues

Industrial implementation of plasma deposition using the expanding thermal plasma technique

NARCIS (Netherlands)

Sanden, van de M.C.M.; Oever, van den P.J.; Creatore, M.; Schaepkens, M.; Miebach, T.; Iacovangelo, C.D.; Bosch, R.C.M.; Bijker, M.D.; Evers, M.F.J.; Schram, D.C.; Kessels, W.M.M.

2004-01-01

Two successful industrial implementations of the expanding thermal plasma setup, a novel plasma source, obtaining high deposition rate are discussed. The Ar/O2/hexamethyldisiloxane and Ar/O2/octamethyl-cyclosiloxane-fed expanding thermal plasma setup is used to deposit scratch resistant silicone

Plasma membrane ATPases

DEFF Research Database (Denmark)

Palmgren, Michael Broberg; Bækgaard, Lone; Lopez Marques, Rosa Laura

2011-01-01

The plasma membrane separates the cellular contents from the surrounding environment. Nutrients must enter through the plasma membrane in order to reach the cell interior, and toxic metabolites and several ions leave the cell by traveling across the same barrier. Biological pumps in the plasma me...

Progress In Plasma Accelerator Development for Dynamic Formation of Plasma Liners

Science.gov (United States)

Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Cassibry, Jason T.; Griffin, Steven; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a coaxial pulsed plasma thruster (Figure 1). It has been tested experimentally and plasma jet velocities of approx.50 km/sec have been obtained. The plasma jet has been photographed with 10-ns exposure times to reveal a stable and repeatable plasma structure (Figure 2). Data for velocity profile information has been obtained using light pipes and magnetic probes embedded in the gun walls to record the plasma and current transit respectively at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

Spectroscopic measurements of plasma emission light for plasma-based acceleration experiments

International Nuclear Information System (INIS)

Filippi, F.; Mostacci, A.; Palumbo, L.; Anania, M.P.; Biagioni, A.; Chiadroni, E.; Ferrario, M.; Cianchi, A.; Zigler, A.

2016-01-01

Advanced particle accelerators are based on the excitation of large amplitude plasma waves driven by either electron or laser beams. Future experiments scheduled at the SPARC-LAB test facility aim to demonstrate the acceleration of high brightness electron beams through the so-called resonant Plasma Wakefield Acceleration scheme in which a train of electron bunches (drivers) resonantly excites wakefields into a preformed hydrogen plasma; the last bunch (witness) injected at the proper accelerating phase gains energy from the wake. The quality of the accelerated beam depends strongly on plasma density and its distribution along the acceleration length. The measurements of plasma density of the order of 10 16 –10 17  cm −3 can be performed with spectroscopic measurements of the plasma-emitted light. The measured density distribution for hydrogen filled capillary discharge with both Balmer alpha and Balmer beta lines and shot-to-shot variation are here reported.

Spectroscopic measurements of plasma emission light for plasma-based acceleration experiments

Science.gov (United States)

Filippi, F.; Anania, M. P.; Biagioni, A.; Chiadroni, E.; Cianchi, A.; Ferrario, M.; Mostacci, A.; Palumbo, L.; Zigler, A.

2016-09-01

Advanced particle accelerators are based on the excitation of large amplitude plasma waves driven by either electron or laser beams. Future experiments scheduled at the SPARC_LAB test facility aim to demonstrate the acceleration of high brightness electron beams through the so-called resonant Plasma Wakefield Acceleration scheme in which a train of electron bunches (drivers) resonantly excites wakefields into a preformed hydrogen plasma; the last bunch (witness) injected at the proper accelerating phase gains energy from the wake. The quality of the accelerated beam depends strongly on plasma density and its distribution along the acceleration length. The measurements of plasma density of the order of 1016-1017 cm-3 can be performed with spectroscopic measurements of the plasma-emitted light. The measured density distribution for hydrogen filled capillary discharge with both Balmer alpha and Balmer beta lines and shot-to-shot variation are here reported.

Plasma Processing of Metallic and Semiconductor Thin Films in the Fisk Plasma Source

Science.gov (United States)

Lampkin, Gregory; Thomas, Edward, Jr.; Watson, Michael; Wallace, Kent; Chen, Henry; Burger, Arnold

1998-01-01

The use of plasmas to process materials has become widespread throughout the semiconductor industry. Plasmas are used to modify the morphology and chemistry of surfaces. We report on initial plasma processing experiments using the Fisk Plasma Source. Metallic and semiconductor thin films deposited on a silicon substrate have been exposed to argon plasmas. Results of microscopy and chemical analyses of processed materials are presented.

A study of single and binary ion plasma expansion into laboratory-generated plasma wakes

Science.gov (United States)

Wright, Kenneth Herbert, Jr.

1988-01-01

Plasma expansion into the wake of a large rectangular plate immersed in a collisionless, supersonic plasma was investigated in laboratory experiments. The experimental conditions address both single ion and binary ion plasma flows for the case of a body whose size is large in comparison with the Debye length, when the potential difference between the body and the plasma is relatively small. A new plasma source was developed to generate equi-velocity, binary ion plasma flows, which allows access to new parameter space that have previously been unavailable for laboratory studies. Specifically, the new parameters are the ionic mass ratio and the ionic component density ratio. In a series of experiments, a krypton-neon plasma is employed where the ambient density ratio of neon to krypton is varied more than an order of magnitude. The expansion in both the single ion and binary ion plasma cases is limited to early times, i.e., a few ion plasma periods, by the combination of plasma density, plasma drift speed, and vacuum chamber size, which prevented detailed comparison with self-similar theory.

Transport of plasma impurities and the role of the plasma edge layers for the hot plasma production

International Nuclear Information System (INIS)

Drawin, H.W.

1987-01-01

The first problem of impurity transport is removal of alpha particles from the interior outward. The second problem is the control of impurities produced in the plasma-wall interaction. Finally there is the problem of using injected impurities for assessment of transport coefficients. The influence of impurity radiation on the power balance of a DT plasma is considered. Limiters and divertors as impurity sources are mentioned and transport equations for impurities are given. As an example iron impurities transport in a hydrogen plasma is considered. The role of the edge layer is emphasized. Finally requirements for plasma diagnostics are stated. 50 refs., 10 figs. (qui)

Plasma technology

International Nuclear Information System (INIS)

Drouet, M.G.

1984-03-01

IREQ was contracted by the Canadian Electrical Association to review plasma technology and assess the potential for application of this technology in Canada. A team of experts in the various aspects of this technology was assembled and each team member was asked to contribute to this report on the applications of plasma pertinent to his or her particular field of expertise. The following areas were examined in detail: iron, steel and strategic-metals production; surface treatment by spraying; welding and cutting; chemical processing; drying; and low-temperature treatment. A large market for the penetration of electricity has been identified. To build up confidence in the technology, support should be provided for selected R and D projects, plasma torch demonstrations at full power, and large-scale plasma process testing

Effect of Porphyromonas gingivalis infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice

Directory of Open Access Journals (Sweden)

Miyazawa Haruna

2012-09-01

Full Text Available Abstract Background Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9, which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether Porphyromonas gingivalis, a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models. Methods We infected C57BL/6 mice intraperitoneally with Porphyromonas gingivalis, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR gene and protein expression, as well as liver X receptors (Lxrs, inducible degrader of the LDLR (Idol, and sterol regulatory element binding transcription factor (Srebf2 gene expression, were examined in the liver. Results P. gingivalis infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the Pcsk9, Ldlr, and Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice compared with the sham-infected mice. Although Pcsk9 gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP2 (human homologue of Srebf2, whereas Srebf2 is negatively regulated by cholesterol, the elevated expression of Srebf2 found in the infected mice is thought to be mediated by P. gingivalis infection. Conclusions P. gingivalis infection upregulates PCSK9 production via upregulation of Srebf2, independent of cholesterol levels. Further studies

Genetic rescue of glycosylation-deficient Fgf23 in the Galnt3 knockout mouse.

Science.gov (United States)

Ichikawa, Shoji; Gray, Amie K; Padgett, Leah R; Allen, Matthew R; Clinkenbeard, Erica L; Sarpa, Nicole M; White, Kenneth E; Econs, Michael J

2014-10-01

Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like proprotein convertase recognition sequence ((176)RHTR(179)↓) is protected by O-glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3 mutations render FGF23 susceptible to proteolysis, thereby reducing circulating intact hormone levels and leading to hyperphosphatemic familial tumoral calcinosis. To further delineate the role of glycosylation in the Fgf23 function, we generated an inducible FGF23 transgenic mouse expressing human mutant FGF23 (R176Q and R179Q) found in patients with autosomal dominant hypophosphatemic rickets (ADHR) and bred this animal to Galnt3 knockout mice, a model of familial tumoral calcinosis. Due to the low intact Fgf23 level, Galnt3 knockout mice with wild-type Fgf23 alleles were hyperphosphatemic. In contrast, carriers of the mutant FGF23 transgene, regardless of Galnt3 mutation status, had significantly higher serum intact FGF23, resulting in severe hypophosphatemia. Importantly, serum phosphorus and FGF23 were comparable between transgenic mice with or without normal Galnt3 alleles. To determine whether the presence of the ADHR mutation could improve biochemical and skeletal abnormalities in Galnt3-null mice, these mice were also mated to Fgf23 knock-in mice, carrying heterozygous or homozygous R176Q ADHR Fgf23 mutations. The knock-in mice with functional Galnt3 had normal Fgf23 but were slightly hypophosphatemic. The stabilized Fgf23 ADHR allele reversed the Galnt3-null phenotype and normalized total Fgf23, serum phosphorus, and bone Fgf23 mRNA. However, the skeletal phenotype was unaffected. In summary, these data demonstrate that O-glycosylation by ppGaINAc-T3 is only necessary for proper secretion of intact Fgf23 and, once secreted, does not affect Fgf23 function. Furthermore, the more stable Fgf23 ADHR mutant protein could normalize serum phosphorus

Evaluation of the cost-effectiveness of evolocumab in the FOURIER study: a Canadian analysis.

Science.gov (United States)

Lee, Todd C; Kaouache, Mohammed; Grover, Steven A

2018-04-03

Evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, has been shown to reduce low-density lipoprotein levels by up to 60%. Despite the absence of a reduction in overall or cardiovascular mortality in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, some believe that, with longer treatment, such a benefit might eventually be realized. Our aim was to estimate the potential mortality benefit over a patient's lifetime and the cost per year of life saved (YOLS) for an average Canadian with established coronary artery disease. We also sought to estimate the price threshold at which evolocumab might be considered cost-effective for secondary prevention in Canada. We calibrated the Cardio-metabolic Model, a well-validated tool for predicting cardiovascular events and life expectancy, to the reduction in nonfatal events seen in the FOURIER trial. Assuming that long-term treatment will eventually result in mortality benefits, we estimated YOLSs and cost per YOLS with evolocumab treatment plus a statin compared to a statin alone. We then estimated the annual drug costs that would provide a 50% chance of being cost-effective at willingness-to-pay values of $50 000 and $100 000. In secondary prevention in patients similar to those in the FOURIER study, evolocumab treatment would save an average of 0.34 (95% confidence interval [CI] 0.27-0.41) life-years at a cost of $101 899 (95% CI $97 325-$106 473), yielding a cost per YOLS of $299 482. We estimate that to have a 50% probability of achieving a cost per YOLS below $50 000 and $100 000 would require annual drug costs below $1200 and $2300, respectively. At current pricing, the use of evolocumab for secondary prevention is unlikely to be cost-effective in Canada. Copyright 2018, Joule Inc. or its licensors.

A locked nucleic acid antisense oligonucleotide (LNA silences PCSK9 and enhances LDLR expression in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Nidhi Gupta

2010-05-01

Full Text Available The proprotein convertase subtilisin/kexin type 9 (PCSK9 is an important factor in the etiology of familial hypercholesterolemia (FH and is also an attractive therapeutic target to reduce low density lipoprotein (LDL cholesterol. PCSK9 accelerates the degradation of hepatic low density lipoprotein receptor (LDLR and low levels of hepatic PCSK9 activity are associated with reduced levels of circulating LDL-cholesterol.The present study presents the first evidence for the efficacy of a locked nucleic acid (LNA antisense oligonucleotide (LNA ASO that targets both human and mouse PCSK9. We employed human hepatocytes derived cell lines HepG2 and HuH7 and a pancreatic mouse beta-TC3 cell line known to express high endogenous levels of PCSK9. LNA ASO efficiently reduced the mRNA and protein levels of PCSK9 with a concomitant increase in LDLR protein levels after transfection in these cells. In vivo efficacy of LNA ASO was further investigated in mice by tail vein intravenous administration of LNA ASO in saline solution. The level of PCSK9 mRNA was reduced by approximately 60%, an effect lasting more than 16 days. Hepatic LDLR protein levels were significantly up-regulated by 2.5-3 folds for at least 8 days and approximately 2 fold for 16 days. Finally, measurement of liver alanine aminotransferase (ALT levels revealed that long term LNA ASO treatment (7 weeks does not cause hepatotoxicity.LNA-mediated PCSK9 mRNA inhibition displayed potent reduction of PCSK9 in cell lines and mouse liver. Our data clearly revealed the efficacy and safety of LNA ASO in reducing PCSK9 levels, an approach that is now ready for testing in primates. The major significance and take home message of this work is the development of a novel and promising approach for human therapeutic intervention of the PCSK9 pathway and hence for reducing some of the cardiovascular risk factors associated with the metabolic syndrome.

Molecular Characterization of the Processing of Arenavirus Envelope Glycoprotein Precursors by Subtilisin Kexin Isozyme-1/Site-1 Protease

Science.gov (United States)

Burri, Dominique J.; Pasqual, Giulia; Rochat, Cylia; Seidah, Nabil G.

2012-01-01

A crucial step in the life cycle of arenaviruses is the biosynthesis of the mature fusion-active viral envelope glycoprotein (GP) that is essential for virus-host cell attachment and entry. The maturation of the arenavirus GP precursor (GPC) critically depends on proteolytic processing by the cellular proprotein convertase (PC) subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P). Here we undertook a molecular characterization of the SKI-1/S1P processing of the GPCs of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and the pathogenic Lassa virus (LASV). Previous studies showed that the GPC of LASV undergoes processing in the endoplasmic reticulum (ER)/cis-Golgi compartment, whereas the LCMV GPC is cleaved in a late Golgi compartment. Herein we confirm these findings and provide evidence that the SKI-1/S1P recognition site RRLL, present in the SKI-1/S1P prodomain and LASV GPC, but not in the LCMV GPC, is crucial for the processing of the LASV GPC in the ER/cis-Golgi compartment. Our structure-function analysis revealed that the cleavage of arenavirus GPCs, but not cellular substrates, critically depends on the autoprocessing of SKI-1/S1P, suggesting differences in the processing of cellular and viral substrates. Deletion mutagenesis showed that the transmembrane and intracellular domains of SKI-1/S1P are dispensable for arenavirus GPC processing. The expression of a soluble form of the protease in SKI-I/S1P-deficient cells resulted in the efficient processing of arenavirus GPCs and rescued productive virus infection. However, exogenous soluble SKI-1/S1P was unable to process LCMV and LASV GPCs displayed at the surface of SKI-I/S1P-deficient cells, indicating that GPC processing occurs in an intracellular compartment. In sum, our study reveals important differences in the SKI-1/S1P processing of viral and cellular substrates. PMID:22357276

Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale.

Science.gov (United States)

Teramoto, Tamio; Kondo, Akira; Kiyosue, Arihiro; Harada-Shiba, Mariko; Ishigaki, Yasushi; Tobita, Kimimasa; Kawabata, Yumiko; Ozaki, Asuka; Baccara-Dinet, Marie T; Sata, Masataka

2017-06-17

Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone). ClinicalTrials.gov number: NCT02584504.

Induction of sustained hypercholesterolemia by single adeno-associated virus-mediated gene transfer of mutant hPCSK9.

Science.gov (United States)

Roche-Molina, Marta; Sanz-Rosa, David; Cruz, Francisco M; García-Prieto, Jaime; López, Sergio; Abia, Rocío; Muriana, Francisco J G; Fuster, Valentín; Ibáñez, Borja; Bernal, Juan A

2015-01-01

Patients with mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have hypercholesterolemia and are at high risk of adverse cardiovascular events. We aimed to stably express the pathological human D374Y gain-of-function mutant form of PCSK9 (PCSK9(DY)) in adult wild-type mice to generate a hyperlipidemic and proatherogenic animal model, achieved with a single systemic injection with adeno-associated virus (AAV). We constructed an AAV-based vector to support targeted transfer of the PCSK9(DY) gene to liver. After injection with 3.5×10(10) viral particles, mice in the C57BL/6J, 129/SvPasCrlf, or FVB/NCrl backgrounds developed long-term hyperlipidemia with a strong increase in serum low-density lipoprotein. Macroscopic and histological analysis showed atherosclerotic lesions in the aortas of AAV-PCSK9(DY) mice fed a high-fat-diet. Advanced lesions in these high-fat-diet-fed mice also showed evidence of macrophage infiltration and fibrous cap formation. Hepatic AAV-PCSK9(DY) infection did not result in liver damage or signs of immunologic response. We further tested the use of AAV-PCSK9(DY) to study potential genetic interaction with the ApoE gene. Histological analysis of ApoE(-/-) AAV-PCSK9(DY) mice showed a synergistic response to ApoE deficiency, with aortic lesions twice as extensive in ApoE(-/-) AAV-PCSK9(DY)-transexpressing mice as in ApoE(-/-) AAV-Luc controls without altering serum cholesterol levels. Single intravenous AAV-PCSK9(DY) injection is a fast, easy, and cost-effective approach, resulting in rapid and long-term sustained hyperlipidemia and atherosclerosis. We demonstrate as a proof of concept the synergy between PCSK9(DY) gain-of-function and ApoE deficiency. This methodology could allow testing of the genetic interaction of several mutations without the need for complex and time-consuming backcrosses. © 2014 American Heart Association, Inc.

Identification of the IGF-1 processing product human Ec/rodent Eb peptide in various tissues: Evidence for its differential regulation after exercise-induced muscle damage in humans.

Science.gov (United States)

Vassilakos, George; Philippou, Anastassios; Koutsilieris, Michael

2017-02-01

Insulin-like growth factor-1 (IGF-1) is a pleiotropic factor expressed in various tissues and plays a critical role in skeletal muscle physiology. Alternative splicing of the IGF-1 gene gives rise to different precursor polypeptides (isoforms) which could undergo post-translational cleavage, generating the common mature IGF-1 peptide and different carboxyl terminal extension (E-) peptides, with the fate of the latter being, so far, unknown. The objective if this study was to identify the IGF-1Ec forms or processing product(s), other than mature IGF-1, generated in different human and rodent tissues and particularly in human skeletal muscle after exercise-induced damage. Protein lysates from a wide range of human and rodent tissues were immunoblotted with a rabbit anti-human Ec polyclonal antibody raised against the last 24 amino acids of the C-terminal of the Ec peptide. This antibody can recognize the Ec peptide, both as part of IGF-1Ec and alone, and also the corresponding rodent forms, due to the high homology that the human Ec shares with the rodent Eb. We were able to confirm, for the first time, that the human Ec peptide and its rodent homologous Eb peptide are produced simultaneously with their precursor protein (pro-IGF-1Ec/Eb) in vivo, in a wide range of tissues (e.g. muscle, liver, heart). Proprotein convertase furin digestion of human muscle and liver protein lysates confirmed that the higher molecular form, pro-IGF-1Ec, can be cleaved to produce the free Ec peptide. Furthermore, initial evidence is provided that Ec peptide is differentially regulated during the process of muscle regeneration after exercise-induced damage in humans. The findings of this study possibly imply that the post-translational modification of the IGF-1Ec pro-peptide may regulate the bioavailability and activity of the processing product(s). Copyright © 2016. Published by Elsevier Ltd.

Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic Cardiovascular Disease.

Science.gov (United States)

Mallya, Usha G; Boklage, Susan H; Koren, Andrew; Delea, Thomas E; Mullins, C Daniel

2018-01-01

The aim of this study was to assess the budget impact of introducing the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab to market for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). A 3-year model estimated the costs of lipid-modifying therapy (LMT) and CV events to a hypothetical US health plan of 1 million members, comparing two scenarios-with and without the availability of PCSK9i as add-on therapy to statins. Proportions of patients with uncontrolled LDL-C despite receiving statins, and at risk of CV events, were estimated from real-world data. Total undiscounted annual LMT costs (2017 prices, including PCSK9i costs of $14,563.50), dispensing and healthcare costs, including the costs of CV events, were estimated for all prevalent patients in the target population, based on baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according to risk group (following the same pattern as current ezetimibe use), and 5-10% as a secondary scenario, were assumed. Total healthcare budget impacts per target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10), $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively, assuming 5-10% utilization. Results were sensitive to changes in model timeframe, years to maximum PCSK9i utilization and PCSK9i costs. The budget impact of PCSK9i as add-on therapy to statins for patients with hypercholesterolemia is relatively low compared with published estimates for other specialty biologics. Drug cost rebates and discounts are likely to further reduce budget impact.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

Science.gov (United States)

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (PLDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company

The detection of heterozygous familial hypercholesterolemia in Ireland.

LENUS (Irish Health Repository)

O'Kane, Maurice J

2012-05-01

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant condition with a population prevalence of 1 in 500, and is associated with significant cardiovascular morbidity and mortality. It may be caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or proprotein convertase subtilisin\\/kexin type 9 (PCSK9) genes, with over 1,000 causative mutations described. Statin therapy in HeFH is considered effective and safe. Audit data suggest that approximately 80% of the putative HeFH population remains unidentified and, therefore, there is a need to develop a strategy for the identification of affected individuals so that early lipid-lowering treatment may be offered. There is good evidence showing the effectiveness and acceptability of HeFH screening programs in Europe. The authors describe a protocol for an all island approach to HeFH detection in the Republic of Ireland\\/Northern Ireland. Index cases will be identified by opportunistic screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death (MedPed) and World Health Organization (WHO) criteria. Patients identified as "definite," "probable," or "possible" HeFH criteria will be offered genetic testing. The authors expect causative mutations to be identified in approximately 80% of patients with "definite" HeFH but in only approximately 20% of patients with "possible" HeFH. Cascade screening will be undertaken in first-degree relatives of the index case using genetic testing (where a causative mutation has been identified), or otherwise using LDL cholesterol concentration. The establishment of a HeFH screening program on an all-island basis will require: expansion of the existing molecular genetics diagnostic services, the establishment of a cohort of nurses\\/genetic counselors, a HeFH database to support cascade testing, the development of a network of lipid clinics (in a primary or secondary care setting), and an educational

Weakly nonlinear electron plasma waves in collisional plasmas

DEFF Research Database (Denmark)

Pecseli, H. L.; Rasmussen, J. Juul; Tagare, S. G.

1986-01-01

The nonlinear evolution of a high frequency plasma wave in a weakly magnetized, collisional plasma is considered. In addition to the ponderomotive-force-nonlinearity the nonlinearity due to the heating of the electrons is taken into account. A set of nonlinear equations including the effect...

High density plasma gun generates plasmas at 190 kilometers per second

Science.gov (United States)

Espy, P. N.

1971-01-01

Gun has thin metal foil disc which positions or localizes gas to be ionized during electrical discharge cycle, overcoming major limiting factor in obtaining such plasmas. Expanding plasma front travels at 190 km/sec, compared to plasmas of 50 to 60 km/sec previously achieved.

Examples of plasma horizons

International Nuclear Information System (INIS)

Hanni, R.S.

1975-01-01

The concept of the plasma horizon, defined as the boundary of the region in which an infinitely thin plasma can be supported against Coulomb attraction by a magnetic field, shows that the argument of selective accretion does not rule out the existence of charged black holes embedded in a conducting plasma. A detailed account of the covariant definition of plasma horizon is given and some examples of plasma horizons are presented. 7 references

The study of a plasma jet injected by an on-board plasma thruster

International Nuclear Information System (INIS)

Grebnev, I.A.; Ivanov, G.V.; Khodnenko, V.P.

1981-01-01

The injection of a steady plasma jet into the ionosphere results in interactions which were studied in experiments conducted onboard two Meteor satellites in 1977-1979. The jet parameters at the propulsion system output were as follows: propulsive mass: Xe Xe (+) ion density at the nozzle section 3 x 10 to the 11th per cu cm plasma stream divergence: 20 degrees jet velocity: 10-12 km/cm ion energy: 130 eV electron temperature: 1 + 3 eV. A Bennett-type modified radio-frequency mass-spectrometer and a two-channel electromagnetic wave analyzer were used for the measurements. It was found that (1) the injected plasma jet propagation depends on the jet injection pitch angle (2) when the plasma jet was injected along the magnetic field, impactless jet spreading took place without considerable interaction with the ionospheric plasma (3) when the plasma jet was injected across the magnetic field, considerable interaction was observed between the plasma jet/ionospheric plasma and the earth's magnetic field and (4) electromagnetic fields were generated near the satellite by plasma jet interaction

High-frequency plasma oscillations

Energy Technology Data Exchange (ETDEWEB)

Akhiezer, A I; Fainberg, Y B; Sitenko, A G; Stepanov, K; Kurilko, V; Gorbatenko, M; Kirochkin, U [Academy of Sciences of the Ukrainian SSR (USSR)

1958-07-01

It is well known that the electrical conductivity of a plasma, the ion-electron equilibration time, and the time required to heat the electron component of the plasma all increase greatly with increasing temperature. Consequently, the usual method of Joule heating a plasma may be difficult to apply in the region of high temperatures (> 10{sup 6}K), especially if the plasma current alone, without any additional measures, is used to generate magnetic fields for the confinement of the plasma. Therefore, it is of interest to study methods of plasma heating that do not directly use Joule heat, especially methods by which energy is directly supplied to the ion component during the time between collisions. Some of these methods make use of ionic resonance as well as other resonance phenomena which can occur in plasma in an external magnetic field. This paper deals with certain aspects of the theory of high-frequency plasma oscillations.

A model for plasma evolution in Filipov type plasma focus facilities

International Nuclear Information System (INIS)

Siahpoush, V.; Sobhanian, S.; Tafreshi, M. A.; Lamehi, M.

2003-01-01

A model is presented in this paper for the evolution of plasma in Filipov type plasma focus facilities. With the help of this model, one can predict some of the main parameters of the produced plasma and obtain the optimized geometrical an physical properties (anode radius and length, gas pressure, capacitance, bank energy etc) for the primary design purposes. The results obtained by this model will be compared with the experimental data obtained from the 90 kJ plasma focus facility D ena

Computer simulations of plasma-biomolecule and plasma-tissue interactions for a better insight in plasma medicine

Science.gov (United States)

Neyts, Erik C.; Yusupov, Maksudbek; Verlackt, Christof C.; Bogaerts, Annemie

2014-07-01

Plasma medicine is a rapidly evolving multidisciplinary field at the intersection of chemistry, biochemistry, physics, biology, medicine and bioengineering. It holds great potential in medical, health care, dentistry, surgical, food treatment and other applications. This multidisciplinary nature and variety of possible applications come along with an inherent and intrinsic complexity. Advancing plasma medicine to the stage that it becomes an everyday tool in its respective fields requires a fundamental understanding of the basic processes, which is lacking so far. However, some major advances have already been made through detailed experiments over the last 15 years. Complementary, computer simulations may provide insight that is difficult—if not impossible—to obtain through experiments. In this review, we aim to provide an overview of the various simulations that have been carried out in the context of plasma medicine so far, or that are relevant for plasma medicine. We focus our attention mostly on atomistic simulations dealing with plasma-biomolecule interactions. We also provide a perspective and tentative list of opportunities for future modelling studies that are likely to further advance the field.

Plasma-neutral gas interaction in a tokamak divertor: effects of hydrogen molecules and plasma recombination

International Nuclear Information System (INIS)

Krasheninnikov, S.I.; Pigarov, A.Yu.; Soboleva, T.K.; Sigmar, D.J.

1997-01-01

We investigate the influence of hydrogen molecules on plasma recombination using a collisional-radiative model for multispecies hydrogen plasmas and tokamak detached divertor parameters. The rate constant found for molecular activated recombination of a plasma can be as high as 2 x 10 -10 cm 3 /s, confirming our pervious estimates. We investigate the effects of hydrogen molecules and plasma recombination on self-consistent plasma-neutral gas interactions in the recycling region of a tokamak divertor. We treat the plasma flow in a fluid approximation retaining the effects of plasma recombination and employing a Knudsen neutral transport model for a 'gas box' divertor geometry. For the model of plasma-neutral interactions we employ we find: (a) molecular activated recombination is a dominant channel of divertor plasma recombination; and (b) plasma recombination is a key element leading to a decrease in the plasma flux onto the target and substantial plasma pressure drop which are the main features of detached divertor regimes. (orig.)

Plasma-particle interaction effects in induction plasma modelling under dense loading conditions

International Nuclear Information System (INIS)

Proulx, P.; Mostaghimi, J.; Boulos, M.

1983-07-01

The injection of solid particles or aerosol droplets in the fire-ball of an inductively coupled plasma can substantially perturb the plasma and even quench it under high loading conditions. This can be mainly attributed to the local cooling of the plasma by the particles or their vapour cloud, combined with the possible change of the thermodynamic and transport properties of the plasma in the presence of the particle vapour. This paper reports the state-of-the-art in the mathematical modelling of the induction plasma. A particle-in-cell model is used in order to combine the continuum approach for the calculation of the flow, temperature and concentration fields in the plasma, with the stochastic single particle approach, for the calculation of the particle trajectories and temperature histories. Results are given for an argon induction plasma under atmospheric pressure in which fine copper particles are centrally injected in the coil region of the discharge

Adaptation of metal arc plasma source to plasma source ion implantation

International Nuclear Information System (INIS)

Shamim, M.M.; Fetherston, R.P.; Conrad, J.R.

1995-01-01

In Plasma Source Ion Implantation (PSII) a target is immersed in a plasma and a train of high negative voltage pulses is applied to accelerate ions into the target and to modify the properties in the near surface region. In PSII, until now the authors have been using gaseous species to generate plasmas. However metal ion plasma may be used to modify the surface properties of material for industrial applications. Conventionally the ion implantation of metal ions is performed using beam line accelerators which have complex engineering and high cost. The employment of a metal arc source to PSII has tremendous potential due to its ability to process the conformal surfaces, simple engineering and cost effectiveness. They have installed metal arc source for generation of titanium plasma. Currently, they are investigating the properties of titanium plasma and material behavior of titanium implanted aluminum and 52100 steel. The recent results of this investigation are presented

Investigation of Plasma Facing Components in Plasma Focus Operation

Science.gov (United States)

Roshan, M. V.; Babazadeh, A. R.; Kiai, S. M. Sadat; Habibi, H.; Mamarzadeh, M.

2007-09-01

Both aspects of the plasma-wall interactions, counter effect of plasma and materials, have been considered in our experiments. The AEOI plasma focus, Dena, has Filippov-type electrodes. The experimental results verify that neutron production increases using tungsten as an anode insert material, compared to the copper one. The experiments show decrement of the hardness of Aluminum targets outward the sides, from 135 to 78 in Vickers scale. The sputtering yield is about 0.0065 for deuteron energy of 50 keV.

The plasma universe

International Nuclear Information System (INIS)

Faelthammar, C.G.

1989-12-01

The term 'Plasma Universe', coined by Hannes Alfven, emphasices the fact that plasma phenomena discovered in the laboratory and in accessible regions of space. must be important also in the rest of the universe, which consists almost entirely of matter in the plasma state. Relevant aspect of this concept will be discussed. They include the response of the plasma to electric currents, the support of magnetic-field aligned electric fields, violation of the frozen-field condition, rapid release of magnetically stored energy, acceleration of charged particles, chemical separation, and filamentary and cellular structures. (authors)

Single-shot Thomson scattering on argon plasmas created by the Microwave Plasma Torch; evidence for a new plasma class

NARCIS (Netherlands)

Mullen, van der J.J.A.M.; Sande, van de M.J.; Vries, de N.; Broks, B.H.P.; Iordanova, E.I.; Gamero, A.; Torres, J.; Sola, A.

2007-01-01

To determine the fine-structure size of plasmas created by a Microwave Plasma Torch (MPT), single-shot Thomson scattering (TS) measurements were performed. The aim was to find a solution for the long-standing discrepancy between experiments and Global Plasma Models (GPMs). Since these GPMs are based

Dynamic plasma screening effects on semiclassical inelastic electron endash ion collisions in dense plasmas

International Nuclear Information System (INIS)

Jung, Y.

1997-01-01

In dense plasmas, dynamic plasma screening effects are investigated on 1s→2p dipole transition probabilities for electron-impact excitation of hydrogenic ions. The electron endash ion interaction potential is considered by introduction of the plasma dielectric function. A semiclassical straight-line trajectory method is applied to the path of the projectile electron in order to visualize the semiclassical transition probability as a function of the impact parameter, projectile energy, and plasma parameters. The transition probability including the dynamic plasma screening effect is always greater than that including the static plasma screening effect. When the projectile velocity is smaller than the electron thermal velocity, the dynamic polarization screening effect becomes the static plasma screening effect. When the projectile velocity is greater than the electron thermal velocity, then the interaction potential is almost unshielded. The difference between the dynamic and static plasma screening effects is more significant for low-energy projectiles. It is also found that the static plasma screening formula obtained by the Debye endash Hueckel model overestimates the plasma screening effects on the atomic excitation processes in dense plasmas. copyright 1997 American Institute of Physics

Plasma heating

International Nuclear Information System (INIS)

Wilhelm, R.

1989-01-01

Successful plasma heating is essential in present fusion experiments, for the demonstration of DpT burn in future devices and finally for the fusion reactor itself. This paper discusses the common heating systems with respect to their present performance and their applicability to future fusion devices. The comparative discussion is oriented to the various function of heating, which are: - plasma heating to fusion-relevant parameters and to ignition in future machines, -non-inductive, steady-pstate current drive, - plasma profile control, -neutral gas breakdown and plasma build-up. In view of these different functions, the potential of neutral beam injection (NBI) and the various schemes of wave heating (ECRH, LH, ICRH and Alven wave heating) is analyzed in more detail. The analysis includes assessments of the present physical and technical state of these heating methods, and makes suggestions for future developments and about outstanding problems. Specific attention is given to the still critical problem of efficient current drive, especially with respect to further extrapolation towards an economically operating tokamak reactor. Remarks on issues such as reliability, maintenance and economy conclude this comparative overview on plasma heating systems. (author). 43 refs.; 13 figs.; 3 tabs

Dust cloud evolution in sub-stellar atmospheres via plasma deposition and plasma sputtering

Science.gov (United States)

Stark, C. R.; Diver, D. A.

2018-04-01

Context. In contemporary sub-stellar model atmospheres, dust growth occurs through neutral gas-phase surface chemistry. Recently, there has been a growing body of theoretical and observational evidence suggesting that ionisation processes can also occur. As a result, atmospheres are populated by regions composed of plasma, gas and dust, and the consequent influence of plasma processes on dust evolution is enhanced. Aim. This paper aims to introduce a new model of dust growth and destruction in sub-stellar atmospheres via plasma deposition and plasma sputtering. Methods: Using example sub-stellar atmospheres from DRIFT-PHOENIX, we have compared plasma deposition and sputtering timescales to those from neutral gas-phase surface chemistry to ascertain their regimes of influence. We calculated the plasma sputtering yield and discuss the circumstances where plasma sputtering dominates over deposition. Results: Within the highest dust density cloud regions, plasma deposition and sputtering dominates over neutral gas-phase surface chemistry if the degree of ionisation is ≳10-4. Loosely bound grains with surface binding energies of the order of 0.1-1 eV are susceptible to destruction through plasma sputtering for feasible degrees of ionisation and electron temperatures; whereas, strong crystalline grains with binding energies of the order 10 eV are resistant to sputtering. Conclusions: The mathematical framework outlined sets the foundation for the inclusion of plasma deposition and plasma sputtering in global dust cloud formation models of sub-stellar atmospheres.

Honeycomblike large area LaB6 plasma source for Multi-Purpose Plasma facility

International Nuclear Information System (INIS)

Woo, Hyun-Jong; Chung, Kyu-Sun; You, Hyun-Jong; Lee, Myoung-Jae; Lho, Taihyeop; Choh, Kwon Kook; Yoon, Jung-Sik; Jung, Yong Ho; Lee, Bongju; Yoo, Suk Jae; Kwon, Myeon

2007-01-01

A Multi-Purpose Plasma (MP 2 ) facility has been renovated from Hanbit mirror device [Kwon et al., Nucl. Fusion 43, 686 (2003)] by adopting the same philosophy of diversified plasma simulator (DiPS) [Chung et al., Contrib. Plasma Phys. 46, 354 (2006)] by installing two plasma sources: LaB 6 (dc) and helicon (rf) plasma sources; and making three distinct simulators: divertor plasma simulator, space propulsion simulator, and astrophysics simulator. During the first renovation stage, a honeycomblike large area LaB 6 (HLA-LaB 6 ) cathode was developed for the divertor plasma simulator to improve the resistance against the thermal shock fragility for large and high density plasma generation. A HLA-LaB 6 cathode is composed of the one inner cathode with 4 in. diameter and the six outer cathodes with 2 in. diameter along with separate graphite heaters. The first plasma is generated with Ar gas and its properties are measured by the electric probes with various discharge currents and magnetic field configurations. Plasma density at the middle of central cell reaches up to 2.6x10 12 cm -3 , while the electron temperature remains around 3-3.5 eV at the low discharge current of less than 45 A, and the magnetic field intensity of 870 G. Unique features of electric property of heaters, plasma density profiles, is explained comparing with those of single LaB 6 cathode with 4 in. diameter in DiPS

Echo phenomena in a plasma

International Nuclear Information System (INIS)

Pavlenko, V.N.

1983-01-01

The mechanism of echo phenomenon in different plasma media: laboratory and cosmic plasma, metals and semiconductors is analyzed to get a more comprehensive idea on collective processes in a plasma and for practical applications in radiophysics and plasma diagnostics. The echo phenomenon permitted to confirm a reversible nature of the Landau damping, to prove the fact that the information on perturbation is conserved in a plasma (as non-damping oscillations of the distribution function) even after disappearing of the macroscopic field. The dependence of the diffusion coefficient on the velocity is measured, microturbulences in a plasma are investigated. New ways of the plasma wave conversion are suggested, as well as ''lightning'' of super-critical plasma layers and regions of plasma non-transparency. Prospective advantages of using echo for studying the mechanisms of charged particle interaction with the surface bounding a plasma are revealed

Collisionless plasmas in astrophysics

CERN Document Server

Belmont, Gerard; Mottez, Fabrice; Pantellini, Filippo; Pelletier, Guy

2013-01-01

Collisionless Plasmas in Astrophysics examines the unique properties of media without collisions in plasma physics. Experts in this field, the authors present the first book to concentrate on collisionless conditions in plasmas, whether close or not to thermal equilibrium. Filling a void in scientific literature, Collisionless Plasmas in Astrophysics explains the possibilities of modeling such plasmas, using a fluid or a kinetic framework. It also addresses common misconceptions that even professionals may possess, on phenomena such as "collisionless (Landau) damping". Abundant illustrations

Plasma polymerization by Softplasma

DEFF Research Database (Denmark)

Jiang, J.; Wu, Zhenning; Benter, Maike

2008-01-01

, external electrode, and electrodeless microwave or high frequency reactors. [3] Softplasma™ is an internal electrode plasma setup powered by low frequenc~ gower supply. It was developed in late 90s for surface treatment of silicone rubber. [ ]- 5] It is a low pressure, low electron density, 3D homogenous......In the late 19th century, the first depositions - known today as plasma polymers, were reported. In the last century, more and more research has been put into plasma polymers. Many different deposition systems have been developed. [1, 2] Shi F. F. broadly classified them into internal electrode...... plasma. In this study, we are presenting the surface modification"pf polymers by plasma polymerization using Softplasma™. Softplasma™ can be used for two major types of polymerization: polymerization of vinyl monomers, where plasma acts as initiator; chemical vapour deposition, where plasma acts...

Plasma centrifuge

International Nuclear Information System (INIS)

Ikehata, Takashi; Mase, Hiroshi

1998-01-01

The plasma centrifuge is one of statistical isotope separation processes which uses the centrifugal force of a J x B driven rotating plasma in a magnetic field to give rise to the mass-dependent radial transport of isotopic ions. The system has been developed as an alternative to the gas centrifuge because a much higher rotational velocity and separation factor have been achieved. In this review, the physical aspects of the plasma centrifuge followed by the recent experimental achievements are described, especially in comparison with the gas centrifuge. (author)

Online plasma calculator

Science.gov (United States)

Wisniewski, H.; Gourdain, P.-A.

2017-10-01

APOLLO is an online, Linux based plasma calculator. Users can input variables that correspond to their specific plasma, such as ion and electron densities, temperatures, and external magnetic fields. The system is based on a webserver where a FastCGI protocol computes key plasma parameters including frequencies, lengths, velocities, and dimensionless numbers. FastCGI was chosen to overcome security problems caused by JAVA-based plugins. The FastCGI also speeds up calculations over PHP based systems. APOLLO is built upon the WT library, which turns any web browser into a versatile, fast graphic user interface. All values with units are expressed in SI units except temperature, which is in electron-volts. SI units were chosen over cgs units because of the gradual shift to using SI units within the plasma community. APOLLO is intended to be a fast calculator that also provides the user with the proper equations used to calculate the plasma parameters. This system is intended to be used by undergraduates taking plasma courses as well as graduate students and researchers who need a quick reference calculation.

Physics of partially ionized plasmas

CERN Document Server

Krishan, Vinod

2016-01-01

Plasma is one of the four fundamental states of matter; the other three being solid, liquid and gas. Several components, such as molecular clouds, diffuse interstellar gas, the solar atmosphere, the Earth's ionosphere and laboratory plasmas, including fusion plasmas, constitute the partially ionized plasmas. This book discusses different aspects of partially ionized plasmas including multi-fluid description, equilibrium and types of waves. The discussion goes on to cover the reionization phase of the universe, along with a brief description of high discharge plasmas, tokomak plasmas and laser plasmas. Various elastic and inelastic collisions amongst the three particle species are also presented. In addition, the author demonstrates the novelty of partially ionized plasmas using many examples; for instance, in partially ionized plasma the magnetic induction is subjected to the ambipolar diffusion and the Hall effect, as well as the usual resistive dissipation. Also included is an observation of kinematic dynam...

Dust in flowing magnetized plasma

International Nuclear Information System (INIS)

Pandey, Birendra P.; Samarian, Alex A.; Vladimirov, Sergey V.

2009-01-01

Plasma flows occur in almost every laboratory device and interactions of flowing plasmas with near-wall impurities and/or dust significantly affects the efficiency and lifetime of such devices. The charged dust inside the magnetized flowing plasma moves primarily under the influence of the plasma drag and electric forces. Here, the charge on the dust, plasma potential, and plasma density are calculated self-consistently. The electrons are assumed non-Boltzmannian and the effect of electron magnetization and electron-atom collisions on the dust charge is calculated in a self-consistent fashion. For various plasma magnetization parameters viz. the ratio of the electron and ion cyclotron frequencies to their respective collision frequencies, plasma-atom and ionization frequencies, the evolution of the plasma potential and density in the flow region is investigated. The variation of the dust charge profile is shown to be a sensitive function of plasma parameters. (author)

Space plasma simulation chamber

International Nuclear Information System (INIS)

1986-01-01

Scientific results of experiments and tests of instruments performed with the Space Plasma Simulation Chamber and its facility are reviewed in the following six categories. 1. Tests of instruments on board rockets, satellites and balloons. 2. Plasma wave experiments. 3. Measurements of plasma particles. 4. Optical measurements. 5. Plasma production. 6. Space plasms simulations. This facility has been managed under Laboratory Space Plasma Comittee since 1969 and used by scientists in cooperative programs with universities and institutes all over country. A list of publications is attached. (author)

Model of detached plasmas

International Nuclear Information System (INIS)

Yoshikawa, S.; Chance, M.

1986-07-01

Recently a tokamak plasma was observed in TFTR that was not limited by a limiter or a divertor. A model is proposed to explain this equilibrium, which is called a detached plasma. The model consists of (1) the core plasma where ohmic heating power is lost by anomalous heat conduction and (2) the shell plasma where the heat from the core plasma is radiated away by the atomic processes of impurity ions. A simple scaling law is proposed to test the validity of this model

Introduction to plasma engineering

International Nuclear Information System (INIS)

Roth, J.R.

1988-01-01

The author has begun writing a textbook entitled Introduction to Plasma Engineering, which is intended for upper division undergraduates or professionals who are entering the field. This paper features a detailed topical outline of all 20 chapters of the book. The text is organized so that the first five chapters cover plasma physics and basic principles; the next 13 chapters cover the most important engineering applications of plasmas, in order of increasing plasma energy/number density; and two final chapters cover plasma diagnostics and magnetic coil design

Performance analyses of Elmo Bumpy Torus plasmas and plasma support systems

International Nuclear Information System (INIS)

Fenstermacher, M.E.

1979-01-01

The development and applcation of the OASIS Code (Operational Analysis of ELMO Bumpy Torus Support and Ignition Systems) for the study of EBT device and plasma performance are presented. The code performs a time-independent, zero-dimensional self-consistent calculation of plasma and plasmasupport systems parameters for the physics and engineering of EBT devices. The features of OASIS modeling for the EBT plasma include: (1) particle balance of the bulk toroidal and electron ring plasma components for experimental (H-H, D-D, He-He etc.) as well as reactor (D-T) devices; (2) energy balance in the bulk and ring plasmas for externally heated or ignition devices; (3) alpha particle effects for reactor devices; (4) auxiliary heating effects, including microwave (ECRH), RF heating (e.g., ICRH), and neutral beam methods; and (5) ignition conditions, including fusion power, alpha power and neutron wall loading. The performance studies using OASIS focussed on variation in plasma and device size and on microwave input power and frequency. An additional study was performed to determine the characteristics of an EBT reactor proof-of-principle device operated with a deuterium-tritium plasma. Sensitivity studies were performed for variation in the input microwave power sharing fractions and the dependence of the bulk n tau scaling law on bulk electron temperature

Waves in Space Plasmas Program

Science.gov (United States)

Fredricks, R. W.; Taylor, W. W. L.

1981-01-01

The Waves in Space Plasmas (WISP) program is a joint international effort involving instrumentation to be designed and fabricated by funding from NASA and the National Research Council of Canada. The instrumentation, with a tentatively planned payload for 1986, can be used to perturb the plasma with radio waves to solve problems in ionospheric, atmospheric, magnetospheric, and plasma physics. Among the ionospheric and plasma phenomena to be investigated using WISP instrumentation are VLF wave-particle interactions; ELF/VLF propagation; traveling ionospheric disturbances and gravity wave coupling; equatorial plasma bubble phenomena; plasma wave physics such as mode-coupling, dispersion, and instabilities; and plasma physics of the antenna-plasma interactions.

Waves in Space Plasmas Program

International Nuclear Information System (INIS)

Fredricks, R.W.; Taylor, W.W.L.

1981-01-01

The Waves in Space Plasmas (WISP) program is a joint international effort involving instrumentation to be designed and fabricated by funding from NASA and the National Research Council of Canada. The instrumentation, with a tentatively planned payload for 1986, can be used to perturb the plasma with radio waves to solve problems in ionospheric, atmospheric, magnetospheric, and plasma physics. Among the ionospheric and plasma phenomena to be investigated using WISP instrumentation are VLF wave-particle interactions, ELF/VLF propagation, traveling ionospheric disturbances and gravity wave coupling, equatorial plasma bubble phenomena, plasma wave physics such as mode-coupling, dispersion, and instabilities, and plasma physics of the antenna-plasma interactions

Plasma in astrophysics

International Nuclear Information System (INIS)

Kulsrud, R.M.

1982-10-01

Two examples of plasma phenomena of importance to astrophysics are reviewed. These are examples where astrophysical understanding hinges on further progress in plasma physics understanding. The two examples are magnetic reconnection and the collisionless interaction between a population of energetic particles and a cooler gas or plasma, in particular the interaction between galactic cosmic rays and the interstellar medium

A Taiwanese food frequency questionnaire correlates with plasma docosahexaenoic acid but not with plasma eicosapentaenoic acid levels: questionnaires and plasma biomarkers.

Science.gov (United States)

Chien, Kuo-Liong; Lee, Meei-Shyuan; Tsai, Yi-Tsen; Chen, Pey-Rong; Lin, Hung-Ju; Hsu, Hsiu-Ching; Lee, Yuan-The; Chen, Ming-Fong

2013-02-16

Little evidence is available for the validity of dietary fish and polyunsaturated fatty acid intake derived from interviewer-administered questionnaires and plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration. We estimated the correlation of DHA and EPA intake from both questionnaires and biochemical measurements. Ethnic Chinese adults with a mean (± SD) age of 59.8 (±12.8) years (n = 297) (47% women) who completed a 38-item semi-quantitative food-frequency questionnaire and provided a plasma sample were enrolled. Plasma fatty acids were analyzed by capillary gas chromatography. The Spearmen rank correlation coefficients between the intake of various types of fish and marine n-3 fatty acids as well as plasma DHA were significant, ranging from 0.20 to 0.33 (P food frequency questionnaire, were correlated with the percentages of these fatty acids in plasma, and in particular with plasma DHA. Plasma DHA levels were correlated to dietary intake of long-chain n-3 fatty acids.

Magnum-psi, a plasma generator for plasma-surface interaction research in ITER-like conditions

International Nuclear Information System (INIS)

Groot, B. de; Rooij, G.J. van; Veremiyenko, V.; Hellermann, M.G. von; Eck, H.J.N. van; Barth, C.J.; Kruijtzer, G.L.; Wolff, J.C.; Goedheer, W.J.; Lopes Cardozo, N.J.; Kleyn, A.W.; Smeets, P.H.M.; Brezinsek, S.; Pospieszczyk, A.; Engeln, R.A.H.; Dahiya, R.P.

2005-01-01

The FOM Institute for Plasma Physics is preparing the construction of the linear plasma generator, Magnum-psi. A pilot experiment (Pilot-psi) has been constructed, which we have used to optimize the cascaded arc plasma source and to explore the effect of high magnetic fields on the source operation as well as the expanding plasma beam and the effectiveness of Ohmic heating for manipulating the electron temperature and plasma density after the plasma expansion. Results are presented that demonstrate increasing source efficiency for increasing magnetic fields (up to 1.6 T). Thomson scattering measurements demonstrate that ITER relevant plasma fluxes are presently achieved in Pilot-psi: ∼10 24 m -2 s -1 and that additional heating could elevate the plasma temperature from 1.0 to 1.7 eV

Measurement of performance parameters of plasma source for plasma opening switch on Qiangguang-Ⅰ generator

International Nuclear Information System (INIS)

Luo Weixi; Zeng Zhengzhong; Lei Tianshi; Wang Liangping; Hu Yixiang; Sun Tieping; Huang Tao

2012-01-01

The plasma source (cable guns) of the plasma opening switch (POS) on Qiangguang Ⅰ generator was chosen as the study object. The plasma source performance was investigated by using charge collectors. Experimental results show that the plasma ejection density is positively correlated with the structural parameter, the distance between gun core tip and muzzle plane, and the plasma ejection velocity is negatively correlated with the parameter. The increasing rate of plasma ejection density is less than that of drive current. As far as a plasma source with tens of cable plasma guns is concerned, the influence of single cable gun's discharge dispersancy on plasma uniformity is little. Analysis of uncertainty shows that the uncertainty of measurement can be reduced by increasing the number of experiments and averaging the results. The combined standard uncertainty of plasma ejection density is less than 10%. (authors)

Communication through plasma sheaths

International Nuclear Information System (INIS)

Korotkevich, A. O.; Newell, A. C.; Zakharov, V. E.

2007-01-01

We wish to transmit messages to and from a hypersonic vehicle around which a plasma sheath has formed. For long distance transmission, the signal carrying these messages must be necessarily low frequency, typically 2 GHz, to which the plasma sheath is opaque. The idea is to use the plasma properties to make the plasma sheath appear transparent

Plasma-based accelerator structures

International Nuclear Information System (INIS)

Schroeder, Carl B.

1999-01-01

Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas

Remote operation of the vertical plasma stabilization @ the GOLEM tokamak for the plasma physics education

Energy Technology Data Exchange (ETDEWEB)

Svoboda, V., E-mail: svoboda@fjfi.cvut.cz [Faculty of Nuclear Sciences and Physical Engineering CTU Prague, CZ-115 19 (Czech Republic); Kocman, J.; Grover, O. [Faculty of Nuclear Sciences and Physical Engineering CTU Prague, CZ-115 19 (Czech Republic); Krbec, J.; Stöckel, J. [Faculty of Nuclear Sciences and Physical Engineering CTU Prague, CZ-115 19 (Czech Republic); Institute of Plasma Physics AS CR, CZ-182 21 Prague (Czech Republic)

2015-10-15

Graphical abstract: * Understandable remote operation of a vertical plasma position control system in the tokamak GOLEM for educational purposes.* Two combinable modes of real-time plasma position control: position based feedback and a pre-defined waveform.* More than 20% plasma life prolongation with plasma position control in feedback mode. - Highlights: • Understandable remote operation of a vertical plasma position control system in the tokamak GOLEM for educational purposes. • Two combinable modes of real-time plasma position control: position based feedback and a pre-defined waveform. • More than 20% plasma life prolongation with plasma position control in feedback mode. - Abstract: The GOLEM tokamak at the Czech Technical University has been established as an educational tokamak device for domestic and foreign students. Remote participation in the scope of several laboratory practices, plasma physics schools and workshops has been successfully performed from abroad. A new enhancement allowing understandable remote control of vertical plasma position in two modes (i) predefined and (ii) feedback control is presented. It allows to drive the current in the stabilization coils in any time-dependent scenario, which can include as a parameter the actual plasma position measured by magnetic diagnostics. Arbitrary movement of the plasma column in a vertical direction, stabilization of the plasma column in the center of the tokamak vessel as well as prolongation/shortening of plasma life according to the remotely defined request are demonstrated.

Spectroscopic diagnostics of industrial plasmas

International Nuclear Information System (INIS)

Joshi, N.K.

2004-01-01

Plasmas play key role in modern industry and are being used for processing micro electronic circuits to the destruction of toxic waste. Characterization of industrial plasmas which includes both 'thermal plasmas' and non-equilibrium plasmas or 'cold plasmas' in industrial environment offers quite a challenge. Numerous diagnostic techniques have been developed for the measurement of these partially ionized plasma and/or particulate parameters. The 'simple' non-invasive spectroscopic methods for characterization of industrial plasmas will be discussed in detail in this paper. The excitation temperature in thermal (DC/RF) plasma jets has been determined using atomic Boltzmann technique. The central axis temperature of thermal plasma jets in a spray torch can be determined using modified atomic Boltzmann technique with out using Abel inversion. The Stark broadening of H β and Ar-I (430 nm) lines have been used to determine the electron number density in thermal plasma jets. In low-pressure non-equilibrium argon plasma, electron temperature has been measured using the Corona model from the ratio of line intensities of atomic and ionic transitions. (author)

Design and testing of miniaturized plasma sensor for measuring hypervelocity impact plasmas

Energy Technology Data Exchange (ETDEWEB)

Goel, A., E-mail: ashish09@stanford.edu; Tarantino, P. M.; Lauben, D. S.; Close, S. [Department of Aeronautics and Astronautics, Stanford University, Stanford, California 94305 (United States)

2015-04-15

An increasingly notable component of the space environment pertains to the impact of meteoroids and orbital debris on spacecraft and the resulting mechanical and electrical damages. Traveling at speeds of tens of km/s, when these particles, collectively referred to as hypervelocity particles, impact a satellite, they vaporize, ionize, and produce a radially expanding plasma that can generate electrically harmful radio frequency emission or serve as a trigger for electrostatic discharge. In order to measure the flux, composition, energy distribution, and temperature of ions and electrons in this plasma, a miniaturized plasma sensor has been developed for carrying out in-situ measurements in space. The sensor comprises an array of electrostatic analyzer wells split into 16 different channels, catering to different species and energy ranges in the plasma. We present results from numerical simulation based optimization of sensor geometry. A novel approach of fabricating the sensor using printed circuit boards is implemented. We also describe the test setup used for calibrating the sensor and show results demonstrating the energy band pass characteristics of the sensor. In addition to the hypervelocity impact plasmas, the plasma sensor developed can also be used to carry out measurements of ionospheric plasma, diagnostics of plasma propulsion systems, and in other space physics experiments.

The plasma physics of plasma processing

International Nuclear Information System (INIS)

Shohet, L.

1991-01-01

Plasma processing is used for producing new materials with unusual and superior properties, for developing new chemical compounds and processes, for machining, and for altering and refining materials and surfaces. It has direct applications to semiconductor fabrication, materials synthesis, welding, lighting, polymers, anti-corrosion coatings, machine tools, metallurgy, electrical and electronics devices, hazardous waste removal, high performance ceramics, and many other items in both high-technology and the more traditional industries. Plasma processing takes on a wide variety of apparently different forms in industry, but the techniques share many common characteristics and problems. Control of the generation and flux of ions, electrons and free radicals in the plasma and their incidence on a surface is vital. Diagnostics, sensors, modeling techniques, and associated statistical methods are needed. However, without an in-depth understanding of the variety of phenomena taking place and their application to the industrial environment, advances in this technology, and its efficient use, will occur at a diminishing rate

Plasma Colloquium Travel Grant Program

International Nuclear Information System (INIS)

Hazeltine, R.D.

1998-01-01

OAK B188 Plasma Colloquium Travel Grant Program. The purpose of the Travel Grant Program is to increase the awareness of plasma research. The new results and techniques of plasma research in fusion plasmas, plasma processing space plasmas, basic plasma science, etc, have broad applicability throughout science. The benefits of these results are limited by the relatively low awareness and appreciation of plasma research in the larger scientific community. Whereas spontaneous interactions between plasma scientists and other scientists are useful, a focused effort in education and outreach to other scientists is efficient and is needed. The academic scientific community is the initial focus of this effort, since that permits access to a broad cross-section of scientists and future scientists including undergraduates, graduate students, faculty, and research staff

2XIIB plasma confinement experiments

International Nuclear Information System (INIS)

Coensgen, F.H.; Clauser, J.F.; Correll, D.L.

1976-01-01

This paper reports results of 2XIIB neutral-beam injection experiments with plasma-stream stabilization. The plasma stream is provided either by a pulsed plasma generator located on the field lines outside the plasma region or by ionization of neutral gas introduced at the mirror throat. In the latter case, the gas is ionized by the normal particle flux through the magnetic mirror. A method of plasma startup and sustenance in a steady-state magnetic field is reported in which the plasma stream from the pulsed plasma generator serves as the initial target for the neutral beams. After an energetic plasma of sufficient density is established, the plasma generator stream is replaced by the gas-fed stream. Lifetimes of the stabilized plasma increase with plasma temperature in agreement with the plasma stabilization of the drift-cyclotron loss-cone mode. The following plasma parameters are attained using the pulsed plasma generator for stabilization: n approximately 5 x 10 13 cm -3 , anti W/sub i/ approximately 13 keV, T/sub e/ = 140 eV, and ntau/sub p/ approximately 7 x 10 10 cm -3 .s. With the gas feed, the mean deuterium ion energy is 9 keV and the peak density n approximately 10 14 cm -3 . In the latter case, the energy confinement parameter reaches ntau/sub E/ = 7 x 10 10 cm -3 .s, and the particle confinement parameter reaches ntau/sub p/ = 1 x 10 11 cm -3 .s

Plasma Accelerator Development for Dynamic Formation of Plasma Liners: A Status Report

Science.gov (United States)

Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a pulsed plasma thruster and has been tested experimentally and plasma jet velocities of approximately 50 km/sec have been obtained. The plasma jet structure has been photographed with 10 ns exposure times to reveal a stable and repeatable plasma structure. Data for velocity profile information has been obtained using light pipes embedded in the gun walls to record the plasma transit at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

Plasma waves

National Research Council Canada - National Science Library

Swanson, D. G

1989-01-01

... Swanson, D.G. (Donald Gary), D a t e - Plasma waves. Bibliography: p. Includes index. 1. Plasma waves. QC718.5.W3S43 1989 ISBN 0-12-678955-X I. Title. 530.4'4 88-34388 Printed in the United Sta...

Counter-facing plasma guns for efficient extreme ultra-violet plasma light source

Science.gov (United States)

Kuroda, Yusuke; Yamamoto, Akiko; Kuwabara, Hajime; Nakajima, Mitsuo; Kawamura, Tohru; Horioka, Kazuhiko

2013-11-01

A plasma focus system composed of a pair of counter-facing coaxial guns was proposed as a long-pulse and/or repetitive high energy density plasma source. We applied Li as the source of plasma for improvement of the conversion efficiency, the spectral purity, and the repetition capability. For operation of the system with ideal counter-facing plasma focus mode, we changed the system from simple coaxial geometry to a multi-channel configuration. We applied a laser trigger to make synchronous multi-channel discharges with low jitter. The results indicated that the configuration is promising to make a high energy density plasma with high spectral efficiency.

Counter-facing plasma guns for efficient extreme ultra-violet plasma light source

Directory of Open Access Journals (Sweden)

Kuroda Yusuke

2013-11-01

Full Text Available A plasma focus system composed of a pair of counter-facing coaxial guns was proposed as a long-pulse and/or repetitive high energy density plasma source. We applied Li as the source of plasma for improvement of the conversion efficiency, the spectral purity, and the repetition capability. For operation of the system with ideal counter-facing plasma focus mode, we changed the system from simple coaxial geometry to a multi-channel configuration. We applied a laser trigger to make synchronous multi-channel discharges with low jitter. The results indicated that the configuration is promising to make a high energy density plasma with high spectral efficiency.

Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.

Science.gov (United States)

Maheshwari, Akhil; Voitenok, Nikolai N; Akalovich, Svetlana; Shaik, Sadiq S; Randolph, David A; Sims, Brian; Patel, Rakesh P; Killingsworth, Cheryl R; Fallon, Michael B; Ohls, Robin K

2009-04-01

Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8](77) isoform and another, more potent [ser-IL-8](72) secreted by most other cells; [ala-IL-8](77) can be converted into [ser-IL-8](72) by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8](77). In this study, we show [ala-IL-8](77) is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8](72) as the major isoform. This isoform switch from the less potent [ala-IL-8](77) to [ser-IL-8](72) correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8](72) as the major isoform is likely due to increased plasma [ala-IL-8](77)-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

Computations in plasma physics

International Nuclear Information System (INIS)

Cohen, B.I.; Killeen, J.

1984-01-01

A review of computer application in plasma physics is presented. Computer contribution to the investigation of magnetic and inertial confinement of a plasma and charged particle beam propagation is described. Typical utilization of computer for simulation and control of laboratory and cosmic experiments with a plasma and for data accumulation in these experiments is considered. Basic computational methods applied in plasma physics are discussed. Future trends of computer utilization in plasma reseaches are considered in terms of an increasing role of microprocessors and high-speed data plotters and the necessity of more powerful computer application

Cyclotron waves in plasma

CERN Document Server

Lominadze, D G

2013-01-01

Cyclotron Waves in Plasma is a four-chapter text that covers the basic physical concepts of the theory of cyclotron waves and cyclotron instabilities, brought about by the existence of steady or alternating plasma currents flowing perpendicular to the magnetic field.This book considers first a wide range of questions associated with the linear theory of cyclotron oscillations in equilibrium plasmas and in electron plasmas in metals and semiconductors. The next chapter deals with the parametric excitation of electron cyclotron oscillations in plasma in an alternating electric field. A chapter f

Water-stabilized plasma generators

Czech Academy of Sciences Publication Activity Database

Hrabovský, Milan

1998-01-01

Roč. 70, č. 6 (1998), s. 1157-1162 ISSN 0033-4545 R&D Projects: GA ČR GA102/95/0592; GA ČR GV106/96/K245 Institutional research plan: CEZ:AV0Z2043910 Keywords : thermal plasma, plasma torch, water-stabilized plasma Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.677, year: 1998

Dynamic behavior of detached recombining plasmas during ELM-like plasma heat pulses in the divertor plasma simulator NAGDIS-II

International Nuclear Information System (INIS)

Uesugi, Y.; Hattori, N.; Nishijima, D.; Ohno, N.; Takamura, S.

2001-01-01

It has been recognized that the ELMs associated with a good confinement at the edge, such as H-mode, must bring an enormous energy to the divertor target plate through SOL and detached plasmas. The understanding of the ELM energy transport through SOL to the divertor target is rather poor at the moment, which leads to an ambiguous estimation of the deposited heat load on the divertor target in ITER. In the present work the ELM-like plasma heat pulse is generated by rf heating in a linear divertor plasma simulator. Energetic electrons with an energy range 10-40 eV are effectively generated by rf heating in low temperature plasmas with (T e )< ∼1 eV. It is observed experimentally that the energetic electrons ionize the highly excited Rydberg atoms quickly, bringing a rapid increase of the ion particle flux to the target, and make the detached plasmas attached to the target. Detailed physical processes about the interaction between the heat pulse with conduction and convection, and detached recombining plasmas are discussed

Nonideal plasmas - experimental research

International Nuclear Information System (INIS)

Guenther, K.; Hess, H.; Radtke, R.

1986-01-01

The investigation of nonideal, strongly coupled, or non-Debye plasmas is a new field of the well-known arc plasma physics. The increased pressure and density cause different behaviour of the dense plasma. The paper surveys the main differences between the nonideal and the usual arc plasmas. The electrical conductivity, continuum radiation absorption coefficient, shift and broadening of spectral lines, and plasma phase transition are discussed. The problems of generation and diagnostics of nonideal plasmas are also described. Finally, the importance of the topic is underlined: possible applications in astrophysics and in different fields of technology: light sources, MHD generators, circuit breakers, laser mirrors and shutters, high temperature gas-phase fission reactors, material treatment and laser fusion are mentioned. (D.Gy.)

Comprehensive physical models and simulation package for plasma/material interactions during plasma instabilities

International Nuclear Information System (INIS)

Hassanein, A.; Konkashbaev, I.

1999-01-01

Damage to plasma-facing components (PFCs) from plasma instabilities remains a major obstacle to a successful tokamak concept. The extent of the damage depends on the detailed physics of the disrupting plasma, as well as on the physics of plasma-material interactions. A comprehensive computer package called high energy interaction with general heterogeneous target systems (HEIGHTS) has been developed and consists of several integrated computer models that follow the beginning of a plasma disruption at the scrape-off layer (SOL) through the transport of the eroded debris and splashed target materials to nearby locations as a result of the deposited energy. The package can study, for the first time, plasma-turbulent behavior in the SOL and predict the plasma parameters and conditions at the divertor plate. Full two-dimensional (2-D) comprehensive radiation magnetohydrodynamic (MHD) models are coupled with target thermodynamics and liquid hydrodynamics to evaluate the integrated response of plasma-facing materials. Factors that influence the lifetime of plasma-facing and nearby components, such as loss of vapor cloud confinement and vapor removal due to MHD effects, damage to nearby components due to intense vapor radiation, melt splashing, and brittle destruction of target materials, are also modeled and discussed. (orig.)

Estimation of post disruption plasma temperature for fast current quench Aditya plasma shots

International Nuclear Information System (INIS)

Purohit, S.; Chowdhuri, M.B.; Joisa, Y.S.; Raval, J.V.; Ghosh, J.; Jha, R.

2013-01-01

Characteristics of tokamak current quenches are an important issue for the determination of electromagnetic forces that act on the in-vessel components and vacuum vessel during major disruptions. It is observed that thermal quench is followed by a sharp current decay. Fast current quench disruptive plasma shots were investigated for ADITYA tokamak. The current decay time was determined for the selected shots, which were in the range of 0.8 msec to 2.5 msec. This current decay information was then applied to L/R model, frequently employed for the estimation of the current decay time in tokamak plasmas, considering plasma inductance and plasma resistivity. This methodology was adopted for the estimation of the post disruption plasma temperature using the experimentally observed current decay time for the fast current quench disruptive ADITYA plasma shots. The study reveals that for the identified shots there is a constant increase in the current decay time with the post disruption plasma temperature. The investigations also explore the behavior post disruption plasma temperature and the current decay time as a function of the edge safety factor, Q. Post disruption plasma temperature and the current decay time exhibits a decrease with the increase in the value Q. (author)

Comprehensive physical models and simulation package for plasma/material interactions during plasma instabilities

International Nuclear Information System (INIS)

Hassanein, A.

1998-01-01

Damage to plasma-facing components (PFCS) from plasma instabilities remains a major obstacle to a successful tokamak concept. The extent of the damage depends on the detailed physics of the disrupting plasma, as well as on the physics of plasma-material interactions. A comprehensive computer package called High Energy Interaction with General Heterogeneous Target Systems (HEIGHTS) has been developed and consists of several integrated computer models that follow the beginning of a plasma disruption at the scrape-off layer (SOL) through the transport of the eroded debris and splashed target materials to nearby locations as a result of the deposited energy. The package can study, for the first time, plasma-turbulent behavior in the SOL and predict the plasma parameters and conditions at the divertor plate. Full two-dimensional (2-D) comprehensive radiation magnetohydrodynamic (MHD) models are coupled with target thermodynamics and liquid hydrodynamics to evaluate the integrated response of plasma-facing materials. Factors that influence the lifetime of plasma-facing and nearby components, such as loss of vapor-cloud confinement and vapor removal due to MHD effects, damage to nearby components due to intense vapor radiation, melt splashing, and brittle destruction of target materials, are also modeled and discussed

Plasma fluctuation measurements in tokamaks using beam-plasma interactions (abstract)

International Nuclear Information System (INIS)

Fonck, R.J.; Duperrex, P.A.; Paul, S.F.

1990-01-01

High-frequency observations of light emitted from the interactions between plasma ions and injected neutral beam atoms allow the measurement of moderate-wavelength fluctuations in plasma and impurity ion densities. To detect turbulence in the local plasma ion density, the collisionally excited fluorescence from a neutral beam is measured either separately at several spatial points or with a multichannel imaging detector. Similarly, the role of impurity ion density fluctuations is measured using charge exchange recombination excited transitions emitted by the ion species of interest. This technique can access the relatively unexplored region of long-wavelength plasma turbulence with k perpendicular ρ i much-lt 1, and hence complements measurements from scattering experiments. Optimization of neutral beam geometry and optical sightlines can result in very good localization and resolution (Δx≤1 cm) in the hot plasma core region. The detectable fluctuation level is determined by photon statistics, atomic excitation processes, and beam stability, but can be as low as 0.2% in a 100 kHz bandwidth over the 0--1 MHz frequency range. The choices of beam species (e.g., H 0 , He 0 , etc.), observed transition (e.g., H α , L α , He I singlet or triplet transitions, C VI Δn=1, etc.) are dictated by experiment-specific factors such as optical access, flexibility of beam operation, plasma conditions, and detailed experimental goals. Initial tests on the PBX-M tokamak using the H α emissions from a heating neutral beam show low-frequency turbulence in the edge plasma region

Plasma cleaning for waste minimization

Energy Technology Data Exchange (ETDEWEB)

Ward, P.P.

1993-07-01

Although plasma cleaning is a recognized substitute for solvent cleaning in removing organic contaminants, some universal problems in plasma cleaning processes prevent wider use of plasma techniques. Lack of understanding of the fundamental mechanisms of the process, unreliable endpoint detection techniques, and slow process times make plasma cleaning processes less than desirable. Our approach to address these plasma cleaning problems is described. A comparison of plasma cleaning rates of oxygen and oxygen/sulfur hexafluoride gases shows that fluorine-containing plasmas can enhance etch rates by 400% over oxygen alone. A discussion of various endpoint indication techniques is discussed and compared for application suitability. Work toward a plasma cleaning database is discussed. In addition to the global problems of plasma cleaning, an experiment where the specific mixed-waste problem of removal of machine oils from radioactive scrap metal is discussed.

Plasma physics

International Nuclear Information System (INIS)

1979-01-01

This report contains the papers delivered at the AEB - Natal University summer school on plasma physics held in Durban during January 1979. The following topics were discussed: Tokamak devices; MHD stability; trapped particles in tori; Tokamak results and experiments; operating regime of the AEB Tokamak; Tokamak equilibrium; high beta Tokamak equilibria; ideal Tokamak stability; resistive MHD instabilities; Tokamak diagnostics; Tokamak control and data acquisition; feedback control of Tokamaks; heating and refuelling; neutral beam injection; radio frequency heating; nonlinear drift wave induced plasma transport; toroidal plasma boundary layers; microinstabilities and injected beams and quasilinear theory of the ion acoustic instability

Plasma engineering: a perspective

International Nuclear Information System (INIS)

Gralnick, S.L.

1978-01-01

This review paper will present the authors perspective of the field of Plasma Engineering as it has evolved over the preceding five years. This embrionic discipline has grown in that period of time to the point where it is sufficiently mature to become part of the curriculum, and a speciality within, the discipline of Nuclear Engineering. Plasma Engineering can be distinguished from the underlying science of plasma physics in that in the pursuit of the latter, our goal is the understanding of the fundamental processes governing the behavior of plasmas while the former discipline seeks the embodiment of these concepts in useful devices. Consequent to this goal, the plasma engineer, of necessity, is concerned with the interfaces between a plasma configuration and the device by which it is produced and maintained. These interface problems, often referred to as kitchen physics are multidisciplinary in nature, and their solution requires careful attention to both plasma physics and machine engineering detail

Plasma atomic layer etching using conventional plasma equipment

International Nuclear Information System (INIS)

Agarwal, Ankur; Kushner, Mark J.

2009-01-01

The decrease in feature sizes in microelectronics fabrication will soon require plasma etching processes having atomic layer resolution. The basis of plasma atomic layer etching (PALE) is forming a layer of passivation that allows the underlying substrate material to be etched with lower activation energy than in the absence of the passivation. The subsequent removal of the passivation with carefully tailored activation energy then removes a single layer of the underlying material. If these goals are met, the process is self-limiting. A challenge of PALE is the high cost of specialized equipment and slow processing speed. In this work, results from a computational investigation of PALE will be discussed with the goal of demonstrating the potential of using conventional plasma etching equipment having acceptable processing speeds. Results will be discussed using inductively coupled and magnetically enhanced capacitively coupled plasmas in which nonsinusoidal waveforms are used to regulate ion energies to optimize the passivation and etch steps. This strategy may also enable the use of a single gas mixture, as opposed to changing gas mixtures between steps

Improvement of confinement characteristics of tokamak plasma by controlling plasma-wall interactions

International Nuclear Information System (INIS)

Sengoku, Seio

1985-08-01

Relation between plasma-wall interactions and confinement characteristics of a tokamak plasma with respect to both impurity and fuel particle controls is discussed. Following results are obtained from impurity control studies: (1) Ion sputtering is the dominant mechanism of impurity release in a steady state tokamak discharge. (2) By applying carbon coating on entire first wall of DIVA tokamak, dominant radiative region is concentrated more in boundary plasma resulting a hot peripheral plasma with cold boundary plasma. (3) A physical model of divertor functions about impurity control is empilically obtained. By a computer simulation based on above model with respect to divertor functions for JT-60 tokamak, it is found that the allowable electron temperature of the divertor plasma is not restricted by a condition that the impurity release due to ion sputtering does not increase continuously. (4) Dense and cold divertor plasma accompanied with strong remote radiative cooling was diagnosed along the magnetic field line in the simple poloidal divertor of DOUBLET III tokamak. Strong particle recycling region is found to be localized near the divertor plate. by and from particle control studies: (1) The INTOR scaling on energy confinement time is applicable to high density region when a core plasma is fueled directly by solid deuterium pellet injection in DOUBLET III tokamak. (2) As remarkably demonstrated by direct fueling with pellet injection, energy confinement characteristics can be improved at high density range by decreasing particle deposition at peripheral plasma in order to reduce plasma-wall interaction. (3) If the particle deposition at boundary layer is necessarily reduced, the electron temperature at the boundary or divertor region increases due to decrease of the particle recycling and the electron density there. (J.P.N.)

Effect of single aerosol droplets on plasma impedance in the inductively coupled plasma

Energy Technology Data Exchange (ETDEWEB)

Chan, George C.-Y., E-mail: gcchan@indiana.edu; Zhu, Zhenli; Hieftje, Gary M.

2012-10-15

The impedance of an inductively coupled plasma was indirectly monitored by two different means-through a RF-probe coil placed inside the torch housing and from tapping the phase-detector signal of the impedance-matching network. During single-droplet introduction, temporal spikes in both the RF-probe coil and the phase-detector signals were readily observed, indicating a momentary change in plasma impedance. The changes in plasma impedance were found to be due solely to plasma perturbation by droplet introduction, and not to an artifact caused by imperfect automatic impedance matching. The temporal changes in plasma impedance were found to be directly proportional to the temporally integrated atomic emission of hydrogen, which is assumed in turn to be directly proportional to the volume of the introduced droplet. A small satellite droplet, with an estimated diameter of 27 {mu}m (i.e., {approx} 10 pL in volume), caused a readily measurable change in plasma impedance. By assuming that the change in RF-probe voltage is directly proportional to the variation in RF power delivered by the load coil, the instantaneous power change coupled to the plasma during single-droplet introduction was estimated. Typical increases in peak RF power and total energy coupled to the plasma, for a single 50-{mu}m droplet introduction, were thereby estimated to be around 8 to 11 W and 0.03 to 0.04 J, respectively. This impedance change was also exploited as a trigger to signal the droplet-introduction event into the plasma. This trigger signal was obtained through a combination of the RF-probe and the phase-detector signals and offered typical jitter from 1 to 2 ms. With the proper choice of a trigger threshold, no trigger misfire resulted and the achievable efficiencies of the trigger signal were 99.95, 97.18 and 74.33% for plasma forward power levels of 900, 1200, and 1500 W, respectively. The baseline noise on the RF-probe coil and the phase-detector signals, which increase with plasma

Polar Plasma at Ganymede: Ionospheric outflow and discovery of the plasma sheet

Science.gov (United States)

Collinson, G.; Paterson, W.; Dorelli, J.; Glocer, A.; Sarantos, M.; Wilson, R. J.; Bard, C.

2017-12-01

On the 27th of June 1996, the NASA Galileo spacecraft made humanities first flyby of Jupiter's largest moon, Ganymede, discovering that it is unique to science in being the only moon known to possess an internally generated magnetic dynamo field. Although Galileo carried a plasma spectrometer, the Plasma Subsystem (PLS), converting its highly complex raw data stream into meaningful plasma moments (density, temperature, velocity) is extremely challenging, and was only ever performed for the second (out of six) Ganymede flybys. Resurrecting the original Galileo PLS data analysis software, we processed the raw PLS data from G01, and for the first time present the properties of plasmas encountered. Dense, cold ions were observed outflowing from the moon's north pole (presumed to be dominated by H+ from the icy surface), with more diffuse, warmer field-aligned outflows in the lobes. Dropouts in plasma density combined with velocity perturbations either side of this suggest that Galileo briefly crossed the cusps onto closed magnetic field lines. PLS observations show that upon entry into the magnetosphere, Galileo crossed through the plasma sheet, observing plasma flows consistent with reconnection-driven convection, highly energized 105 eV ions, and a reversal in the magnetic field. The densities of plasmas flowing upwards from Ganymede's ionosphere were higher on open "lobe" field lines than on closed field lines, suggesting that the ionospheric source of these plasmas may be denser at the poles, there may be additional acceleration mechanisms at play, or the balance of ions were outside the energy range of PLS.

Plasma-material interactions

International Nuclear Information System (INIS)

Wilson, K.L.

1984-01-01

Plasma-interactive components must be resistant to erosion processes, efficient in heat removal, and effective in minimizing tritium inventory and permeation. As long as plasma edge temperatures are 50 eV, no one material can satisfy the diverse requirements imposed by these plasma materials interactions. The only solution is the design of duplex, or even more complicated, structures. The material that faces the plasma should be low atomic number, with acceptable erosion and evaporation characteristics. The substrate material must have high thermal conductivity for heat removal. Finally, materials must be selected judiciously for tritium compatibility. In conclusion, materials play a critical role in the achievement of safe and economical magnetic fusion energy. Improvements in materials have already led to many advances in present day device operation, but additional innovative materials solutions are required for the critical plasma materials interaction issues in future power reactors

Interferometric measurements of plasma density in high-β plasmas

International Nuclear Information System (INIS)

Quinn, W.E.

1977-01-01

The coupled-cavity laser interferometer technique is particularly applicable to the measurement of pulsed plasma densities. This technique is based on the fact that if a small fraction of a gas laser's output radiation is reflected into the laser with an external mirror, the intensity of the laser output is modulated. These amplitude or intensity modulations are produced by changes in the laser gain. A rotating corner mirror or an oscillating mirror can be used to produce a continuous feedback modulation of the interferometer which produces a continuous background fringe pattern. The presence of plasma in the outer cavity causes an additional change which results in a phase shift of the regular period of the background fringe pattern. The integral of the plasma density along the line of sight can be evaluated by comparison of the time history of the fringes obtained with and without plasma

A Method to Construct Plasma with Nonlinear Density Enhancement Effect in Multiple Internal Inductively Coupled Plasmas

International Nuclear Information System (INIS)

Chen Zhipeng; Li Hong; Liu Qiuyan; Luo Chen; Xie Jinlin; Liu Wandong

2011-01-01

A method is proposed to built up plasma based on a nonlinear enhancement phenomenon of plasma density with discharge by multiple internal antennas simultaneously. It turns out that the plasma density under multiple sources is higher than the linear summation of the density under each source. This effect is helpful to reduce the fast exponential decay of plasma density in single internal inductively coupled plasma source and generating a larger-area plasma with multiple internal inductively coupled plasma sources. After a careful study on the balance between the enhancement and the decay of plasma density in experiments, a plasma is built up by four sources, which proves the feasibility of this method. According to the method, more sources and more intensive enhancement effect can be employed to further build up a high-density, large-area plasma for different applications. (low temperature plasma)

Laser-pulsed Plasma Chemistry: Laser-initiated Plasma Oxidation Of Niobium

OpenAIRE

Marks R.F.; Pollak R.A.; Avouris Ph.; Lin C.T.; Thefaine Y.J.

1983-01-01

We report the first observation of the chemical modification of a solid surface exposed to an ambient gas plasma initiated by the interaction of laser radiation with the same surface. A new technique, which we designate laser-pulsed plasma chemistry (LPPC), is proposed for activating heterogeneous chemical reactions at solid surfaces in a gaseous ambient by means of a plasma initiated by laser radiation. Results for niobium metal in one atmosphere oxygen demonstrate single-pulse, self-limitin...

Correlations in plasma in thermodynamic equilibrium; Les correlations dans un plasma en equilibre

Energy Technology Data Exchange (ETDEWEB)

Yvon, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1958-07-01

This paper treats of a fully, ionized plasma in thermodynamic equilibrium. An attempt is made at reviewing the calculation of spatial correlations in such a plasma. The equation of recurrence and the principle of superposition are used. The linear approximation is first treated. The next higher approximation is studied in the case of a neutral homogeneous and isotropic plasma. (author) [French] Un plasma completement ionise est en equilibre thermodynamique. On tente une mise au point du calcul des correlations de position dans ce plasma. On utilise les equations de recurrence et le principe de superposition. On expose d'abord l'approximation lineaire. Dans le cas d'un plasma neutre homogene et isotrope l'etude est poursuivie a l'approximation suivante. (auteur)

Atmospheric-pressure plasma technology

International Nuclear Information System (INIS)

Kogelschatz, U

2004-01-01

Major industrial plasma processes operating close to atmospheric pressure are discussed. Applications of thermal plasmas include electric arc furnaces and plasma torches for generation of powders, for spraying refractory materials, for cutting and welding and for destruction of hazardous waste. Other applications include miniature circuit breakers and electrical discharge machining. Non-equilibrium cold plasmas at atmospheric pressure are obtained in corona discharges used in electrostatic precipitators and in dielectric-barrier discharges used for generation of ozone, for pollution control and for surface treatment. More recent applications include UV excimer lamps, mercury-free fluorescent lamps and flat plasma displays

Space plasmas 2

International Nuclear Information System (INIS)

Frankel, N.E.; Hines, K.C.; Kowalenko, V.

1981-01-01

The longitudinal dielectric response of an ultra-degenerate relativistic plasma composed of electrons and positrons is considered. The relativistic Hartree self-consistent field method is used to investigate the dispersion relations and damping parameters of such a plasma in the presence of a magnetic field. These properties must be studied in the various regimes appropriate for a relativistic plasma as detailed by Tsytovich and Jancovici

Introduction to complex plasmas

International Nuclear Information System (INIS)

Bonitz, Michael; Ludwig, Patrick; Horing, Norman

2010-01-01

Complex plasmas differ from traditional plasmas in many ways: these are low-temperature high pressure systems containing nanometer to micrometer size particles which may be highly charged and strongly interacting. The particles may be chemically reacting or be in contact with solid surfaces, and the electrons may show quantum behaviour. These interesting properties have led to many applications of complex plasmas in technology, medicine and science. Yet complex plasmas are extremely complicated, both experimentally and theoretically, and require a variety of new approaches which go beyond standard plasma physics courses. This book fills this gap presenting an introduction to theory, experiment and computer simulation in this field. Based on tutorial lectures at a very successful recent Summer Institute, the presentation is ideally suited for graduate students, plasma physicists and experienced undergraduates. (orig.)

Introduction to Complex Plasmas

CERN Document Server

Bonitz, Michael; Ludwig, Patrick

2010-01-01

Complex plasmas differ from traditional plasmas in many ways: these are low-temperature high pressure systems containing nanometer to micrometer size particles which may be highly charged and strongly interacting. The particles may be chemically reacting or be in contact with solid surfaces, and the electrons may show quantum behaviour. These interesting properties have led to many applications of complex plasmas in technology, medicine and science. Yet complex plasmas are extremely complicated, both experimentally and theoretically, and require a variety of new approaches which go beyond standard plasma physics courses. This book fills this gap presenting an introduction to theory, experiment and computer simulation in this field. Based on tutorial lectures at a very successful recent Summer Institute, the presentation is ideally suited for graduate students, plasma physicists and experienced undergraduates.

Thermal plasma waste treatment

International Nuclear Information System (INIS)

Heberlein, Joachim; Murphy, Anthony B

2008-01-01

Plasma waste treatment has over the past decade become a more prominent technology because of the increasing problems with waste disposal and because of the realization of opportunities to generate valuable co-products. Plasma vitrification of hazardous slags has been a commercial technology for several years, and volume reduction of hazardous wastes using plasma processes is increasingly being used. Plasma gasification of wastes with low negative values has attracted interest as a source of energy and spawned process developments for treatment of even municipal solid wastes. Numerous technologies and approaches exist for plasma treatment of wastes. This review summarizes the approaches that have been developed, presents some of the basic physical principles, provides details of some specific processes and considers the advantages and disadvantages of thermal plasmas in waste treatment applications. (topical review)

Determination of Plasma Screening Effects for Thermonuclear Reactions in Laser-generated Plasmas

Energy Technology Data Exchange (ETDEWEB)

Wu, Yuanbin; Pálffy, Adriana, E-mail: yuanbin.wu@mpi-hd.mpg.de, E-mail: Palffy@mpi-hd.mpg.de [Max-Planck-Institut für Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany)

2017-03-20

Due to screening effects, nuclear reactions in astrophysical plasmas may behave differently than in the laboratory. The possibility to determine the magnitude of these screening effects in colliding laser-generated plasmas is investigated theoretically, having as a starting point a proposed experimental setup with two laser beams at the Extreme Light Infrastructure facility. A laser pulse interacting with a solid target produces a plasma through the Target Normal Sheath Acceleration scheme, and this rapidly streaming plasma (ion flow) impacts a secondary plasma created by the interaction of a second laser pulse on a gas jet target. We model this scenario here and calculate the reaction events for the astrophysically relevant reaction {sup 13}C({sup 4}He, n ){sup 16}O. We find that it should be experimentally possible to determine the plasma screening enhancement factor for fusion reactions by detecting the difference in reaction events between two scenarios of ion flow interacting with the plasma target and a simple gas target. This provides a way to evaluate nuclear reaction cross-sections in stellar environments and can significantly advance the field of nuclear astrophysics.

Injection of a coaxial-gun-produced magnetized plasma into a background helicon plasma

Science.gov (United States)

Zhang, Yue; Lynn, Alan; Gilmore, Mark; Hsu, Scott

2014-10-01

A compact coaxial plasma gun is employed for experimental investigation of plasma bubble relaxation into a lower density background plasma. Experiments are being conducted in the linear device HelCat at UNM. The gun is powered by a 120-uF ignitron-switched capacitor bank, which is operated in a range of 5 to 10 kV and 100 kA. Multiple diagnostics are employed to investigate the plasma relaxation process. Magnetized argon plasma bubbles with velocities 1.2Cs, densities 1020 m-3 and electron temperature 13eV have been achieved. The background helicon plasma has density 1013 m-3, magnetic field from 200 to 500 Gauss and electron temperature 1eV. Several distinct operational regimes with qualitatively different dynamics are identified by fast CCD camera images. Additionally a B-dot probe array has been employed to measure the spatial toroidal and poloidal magnetic flux evolution to identify plasma bubble configurations. Experimental data and analysis will be presented.

Plasma kinetics issues in an ESA study for a plasma laboratory in space

International Nuclear Information System (INIS)

Annaratone, B M; Biancalani, A; Ceccherini, F; Pegoraro, F; Bruno, D; Capitelli, M; Pascale, O de; Longo, S; Daly, E; Hilgers, A; Diomede, P; D'Ammando, G; Marcuccio, S; Mendonca, J T; Nagnibeda, V; Sanmartin, J R

2008-01-01

A study supported by the European Space Agency (ESA), in the context of its General Studies Programme, performed an investigation of the possible use of space for studies in pure and applied plasma physics, in areas not traditionally covered by 'space plasma physics'. A set of experiments have been identified that can potentially provide access to new phenomena and to allow advances in several fields of plasma science. These experiments concern phenomena on a spatial scale (10 1 -10 4 m) intermediate between what is achievable on the ground and the usual solar system plasma observations. Detailed feasibility studies have been performed for three experiments: active magnetic experiments, large-scale discharges and long tether-plasma interactions. The perspectives opened by these experiments are discussed for magnetic reconnection, instabilities, MHD turbulence, atomic excited states kinetics, weakly ionized plasmas, plasma diagnostics, artificial auroras and atmospheric studies. The discussion is also supported by results of numerical simulations and estimates

Plasma Physics Applied (New Book)