Sample records for caveolin-1 enhances fusion

  1. Caveolin-1 enhances resveratrol-mediated cytotoxicity and transport in a hepatocellular carcinoma model

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    Yang Hui-ling


    Full Text Available Abstract Background Resveratrol (RES, an estrogen analog, is considered as a potential cancer chemo-preventive agent. However, it remains unclear how RES is transported into cells. In this study, we observed that Caveolin-1(CAV1 expression can increase the cytotoxic and pro-apoptotic activity of RES in a dose- and time-dependent manner both in vitro and in vivo in a Hepatocellular Carcinoma animal model. Methods High performance liquid chromatography (HPLC demonstrated that RES intra-cellular concentration is increased about 2-fold in cells stably expressing CAV1 or CAVM1 (a scaffolding domain (81-101AA-defective CAV1 mutant compared to the untransduced human Hepatoblastoma cell line (HepG2 or after transduction with the green fluorescent protein (GFP control vector. The increased intra-cellular transport of RES was abolished in cells stably expressing CAVM2 (a cholesterol shuttle domain (143-156AA-defective CAV1 mutant or CAVRNAi. In order to further characterize CAV1-dependent RES transport, we synthesized RES-dansyl chloride derivatives as fluorescent probes to visualize the transport process, which demonstrated a distribution consistent with that of CAV1 in HepG2 cells. Results In addition, RES endocytosis was not mediated by estrogen receptor (ER α and β, as suggested by lack of competitive inhibition by estrogen or Tamoxifen. Pathway analysis showed that RES can up-regulate the expression of endogenous CAV1; this activates further the MAPK pathway and caspase-3 expression. Discussion This study provides novel insights about the role played by CAV1 in modulating cellular sensitivity to RES through enhancement of its internalization and trafficking.

  2. Hyperglycemia and downregulation of caveolin-1 enhance neuregulin-induced demyelination. (United States)

    Yu, Cuijuan; Rouen, Shefali; Dobrowsky, Rick T


    Neuregulins (NRGs) are growth factors which bind to Erb receptor tyrosine kinases that localize to Schwann cells (SCs). Although NRGs can promote cell survival, mitogenesis, and myelination in undifferentiated SCs, they also induce demyelination of myelinated co-cultures of SCs and dorsal root ganglion (DRG) neurons. We have shown previously that Erb B2 activity increased in premyelinating SCs in response to hyperglycemia, and that this correlated with the downregulation of the protein caveolin-1 (Cav-1). As myelinated SCs undergo substantial degeneration in diabetic neuropathy, we used myelinated SC/DRG neuron co-cultures to determine if hyperglycemia and changes in Cav-1 expression could enhance NRG-induced demyelination. In basal glucose, NRG1 caused a 2.4-fold increase in the number of damaged myelin segments. This damage reached 3.8-fold under hyperglycemic conditions, and was also associated with a robust decrease in the expression of Cav-1 and compact myelin proteins. The loss of Cav-1 and compact myelin proteins following hyperglycemia and NRG treatment was not due to neuronal loss, since the axons remained intact and there was no loss of PGP 9.5, an axonal marker protein. To examine if changes in Cav-1 were sufficient to alter the extent of NRG-induced demyelination, SC/DRG neurons co-cultures were infected with antisense or dominant-negative Cav-1(P132L) adenoviruses. Either antisense-mediated downregulation or mis-localization of endogenous Cav-1 by Cav-1(P132L) resulted in a 1.5- to 2.4-fold increase in NRG-induced degeneration compared to that present in control cultures. These data support that hyperglycemia and changes in Cav-1 are sufficient to sensitize myelinated SC/DRG co-cultures to NRG-induced demyelination.

  3. Expression of Caveolin 1 is enhanced by DNA demethylation during adipocyte differentiation. status of insulin signaling. (United States)

    Palacios-Ortega, Sara; Varela-Guruceaga, Maider; Milagro, Fermín Ignacio; Martínez, José Alfredo; de Miguel, Carlos


    Caveolin 1 (Cav-1) is an essential constituent of adipocyte caveolae which binds the beta subunit of the insulin receptor (IR) and is implicated in the regulation of insulin signaling. We have found that, during adipocyte differentiation of 3T3-L1 cells the promoter, exon 1 and first intron of the Cav-1 gene undergo a demethylation process that is accompanied by a strong induction of Cav-1 expression, indicating that epigenetic mechanisms must have a pivotal role in this differentiation process. Furthermore, IR, PKB-Akt and Glut-4 expression are also increased during the differentiation process suggesting a coordinated regulation with Cav-1. Activation of Cav-1 protein by phosphorylation arises during the differentiation process, yet in fully mature adipocytes insulin is no longer able to significantly increase Cav-1 phosphorylation. However, these long-term differentiated cells are still able to respond adequately to insulin, increasing IR and PKB-Akt phosphorylation and glucose uptake. The activation of Cav-1 during the adipocyte differentiation process could facilitate the maintenance of insulin sensitivity by these fully mature adipocytes isolated from additional external stimuli. However, under the influence of physiological conditions associated to obesity, such as chronic inflammation and hypoxia, insulin sensitivity would finally be compromised.

  4. Hepatic caveolin-1 is enhanced in Cyp27a1/ApoE double knockout mice. (United States)

    Zurkinden, Line; Mansour, Yosef T; Rohrbach, Beatrice; Vogt, Bruno; Mistry, Hiten D; Escher, Geneviève


    Sterol 27-hydroxylase (CYP27A1) is involved in bile acid synthesis and cholesterol homoeostasis. Cyp27a1((-/-))/Apolipoprotein E((-/-)) double knockout mice (DKO) fed a western diet failed to develop atherosclerosis. Caveolin-1 (CAV-1), the main component of caveolae, is associated with lipid homoeostasis and has regulatory roles in vascular diseases. We hypothesized that liver CAV-1 would contribute to the athero-protective mechanism in DKO mice. Cyp27a1((+/+))/ApoE((-/-)) (ApoE KO), Cyp27a1((+/-))/ApoE((-/-)) (het), and DKO mice were fed a western diet for 2 months. Atherosclerotic plaque and CAV-1 protein were quantified in aortas. Hepatic Cav-1 mRNA was assessed using qPCR, CAV-1 protein by immunohistochemistry and western blotting. Total hepatic and plasma cholesterol was measured using chemiluminescence. Cholesterol efflux was performed in RAW264.7 cells, using mice plasma as acceptor. CAV-1 protein expression in aortas was increased in endothelial cells of DKO mice and negatively correlated with plaque surface (P < 0.05). In the liver, both CAV-1 protein and mRNA expression doubled in DKO, compared to ApoE KO and het mice (P < 0.001 for both) and was negatively correlated with total hepatic cholesterol (P < 0.05). Plasma from DKO, ApoE KO and het mice had the same efflux capacity. In the absence of CYP27A1, CAV-1 overexpression might have an additional athero-protective role by partly overcoming the defect in CYP27A1-mediated cholesterol efflux.

  5. Rab5 is required in metastatic cancer cells for Caveolin-1-enhanced Rac1 activation, migration and invasion. (United States)

    Díaz, Jorge; Mendoza, Pablo; Ortiz, Rina; Díaz, Natalia; Leyton, Lisette; Stupack, Dwayne; Quest, Andrew F G; Torres, Vicente A


    Rab5 is a small GTPase that regulates early endosome trafficking and other cellular processes, including cell adhesion and migration. Specifically, Rab5 promotes Rac1 activation and cancer cell migration, but little is known about the upstream regulators of Rab5. We have previously shown that the scaffolding protein Caveolin-1 (CAV1) promotes Rac1 activation and migration of cancer cells. Here, we hypothesized that CAV1 stimulates Rab5 activation, leading to increased Rac1 activity and cell migration. Expression of CAV1 in B16-F10 mouse melanoma and HT-29(US) human colon adenocarcinoma cells increased the GTP loading of Rab5, whereas shRNA-mediated targeting of endogenous CAV1 in MDA-MB-231 breast cancer cells decreased Rab5-GTP levels. Accordingly, shRNA-mediated downregulation of Rab5 decreased CAV1-mediated Rac1 activation, cell migration and invasion in B16-F10 and HT-29(US) cells. Expression of CAV1 was accompanied by increased recruitment of Tiam1, a Rac1 guanine nucleotide exchange factor (GEF), to Rab5-positive early endosomes. Using the inhibitor NSC23766, Tiam1 was shown to be required for Rac1 activation and cell migration induced by CAV1 and Rab5. Mechanistically, we provide evidence implicating p85α (also known as PIK3R1), a Rab5 GTPase-activating protein (GAP), in CAV1-dependent effects, by showing that CAV1 recruits p85α, precluding p85α-mediated Rab5 inactivation and increasing cell migration. In summary, these studies identify a novel CAV1-Rab5-Rac1 signaling axis, whereby CAV1 prevents Rab5 inactivation, leading to increased Rac1 activity and enhanced tumor cell migration and invasion.

  6. Caveolin-1 and prostate cancer progression. (United States)

    Freeman, Michael R; Yang, Wei; Di Vizio, Dolores


    Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer. The caveolin-1 protein localizes to vesicular structures called caveolae and has been shown to bind and regulate many signaling proteins involved in oncogenesis. Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol and fatty acid metabolism and can elicit biological responses in a paracrine manner when secreted. Caveolin-1 is also present in the serum of prostate cancer patients and circulating levels correlate with extent of disease. Current evidence indicates that increased expression of caveolin-1 in prostate adenocarcinoma cells and commensurate downregulation of the protein in prostate stroma, mediate progression to the castration-resistant phase of prostate cancer through diverse pathways. This chapter summarizes the current state of our understanding of the cellular and physiologic mechanisms in which caveolin-1 participates in the evolution of prostate cancer cell phenotypes.

  7. Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis

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    Huang Mu-Chiou


    Full Text Available Abstract Background Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma. Results The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine. Conclusion Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.

  8. Expression of caveolin-1 in the early phase of beta-TCP implanted in dog mandible. (United States)

    Chou, Cherng-Tzeh; Bhawal, Ujjal K; Watanabe, Nobuyuki; Kuboyama, Noboru; Chang, Wei-Jen; Lee, Sheng-Yang; Abiko, Yoshimitsu


    Caveolin is an essential and signature protein of caveolae. Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signalling molecules within caveolar membranes. Beta-tricalcium phosphate (β-TCP) has been widely used for scaffold in tissue engineering due to its high biodegradability, osteoconductivity, easy manipulation, and lack of histotoxicity. To better understand the role of caveolin-1 in bone homeostasis and response to β-TCP scaffold, β-TCP was implanted into the dog mandible defects in beagle dogs, and gene expression profiles were examined focused on the molecular components involved in caveolin-1 regulation. Here we showed the quantitative imageology analysis characterized using in vivo micro-computed tomography (CT) images at 4 and 7 days after β-TCP implanted in dog mandibles. The bone reformation by using the β-TCP scaffolds began within 4 days of surgery, and was healing well at 7 days after surgery. Higher mRNA level of caveolin-1 was observed in β-TCP-implanted Beagle dog mandibles compared with controls at day 4 and day 7 post-surgery. The enhancement of caveolin-1 by β-TCP was further confirmed by immunohistochemistry and immunofluorescence analysis. We further revealed increased Smad7 and Phospho Stat3 expression in β-TCP-implanted specimens. Taken together, these results suggest that the enhancement of caveolin-1 play an important role in accelerating bone formation by β-TCP.

  9. Treadmill Exercise Promotes Neurogenesis in Ischemic Rat Brains via Caveolin-1/VEGF Signaling Pathways. (United States)

    Zhao, Yun; Pang, Qiongyi; Liu, Meixia; Pan, Jingzi; Xiang, Bingwu; Huang, Tingting; Tu, Fengxia; Liu, Chan; Chen, Xiang


    Using a model of middle cerebral artery occlusion (MCAO), we have previously demonstrated that treadmill exercise promotes angiogenesis in the ischemic penumbra through caveolin-1/VEGF signaling pathways. However, the function of caveolin-1/VEGF signaling in neurogenesis after MCAO has not been determined. In this study, we aimed to investigate the potential of treadmill exercise to promote neurogenesis after MCAO and whether caveolin-1/VEGF signaling pathways are involved. After MCAO, rats were subjected to a program of treadmill exercise. Daidzein (a specific inhibitor of caveolin-1 protein expression, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated neurogenesis. We found that the total protein expression of both caveolin-1 and VEGF was increased by exercise and consistent with the improved neurological recovery, decreased infarct volumes and increased 5-bromo-2'-deoxyuridine (BrdU) in the ipsilateral Subventricular zone (SVZ), as well as increased numbers of BrdU/DCX and BrdU/Neun-positive cells in the peri-infarct region. Furthermore, we observed that the treadmill exercise-induced increased VEGF expression, improved neurological recovery, decreased infarct volumes, increased BrdU/DCX and BrdU/Neun-positive cells were significantly inhibited by the caveolin-1 inhibitor. Our results indicate that treadmill exercise improves neurological recovery in ischemic rats, possibly by enhancement of SVZ-derived neural stem cell (NSC) proliferation, migration and differentiation in the penumbra. Moreover, caveolin-1/VEGF signaling is involved in exercise-mediated NSC migration and neuronal differentiation.

  10. Calcium regulates caveolin-1 expression at the transcriptional level

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    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Li, Yan [Experimental Animal Center, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Liu, Dan; Zhang, Xue-Cheng [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Sato, Toshinori [Department of Biosciences and Informatics, Keio University, Hiyoshi, Yokohama 223-8522 (Japan); Yamagata, Sadako [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Yamagata, Tatsuya, E-mail: [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China)


    Highlights: Black-Right-Pointing-Pointer Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. Black-Right-Pointing-Pointer An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. Black-Right-Pointing-Pointer Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. Black-Right-Pointing-Pointer Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca{sup 2+}/calcineurin/NFAT.

  11. Nitroglycerin tolerance in caveolin-1 deficient mice.

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    Mao Mao

    Full Text Available Nitrate tolerance developed after persistent nitroglycerin (GTN exposure limits its clinical utility. Previously, we have shown that the vasodilatory action of GTN is dependent on endothelial nitric oxide synthase (eNOS/NOS3 activity. Caveolin-1 (Cav-1 is known to interact with NOS3 on the cytoplasmic side of cholesterol-enriched plasma membrane microdomains (caveolae and to inhibit NOS3 activity. Loss of Cav-1 expression results in NOS3 hyperactivation and uncoupling, converting NOS3 into a source of superoxide radicals, peroxynitrite, and oxidative stress. Therefore, we hypothesized that nitrate tolerance induced by persistent GTN treatment results from NOS3 dysfunction and vascular toxicity. Exposure to GTN for 48-72 h resulted in nitrosation and depletion (>50% of Cav-1, NOS3 uncoupling as measured by an increase in peroxynitrite production (>100%, and endothelial toxicity in cultured cells. In the Cav-1 deficient mice, NOS3 dysfunction was accompanied by GTN tolerance (>50% dilation inhibition at low GTN concentrations. In conclusion, GTN tolerance results from Cav-1 modification and depletion by GTN that causes persistent NOS3 activation and uncoupling, preventing it from participating in GTN-medicated vasodilation.

  12. Nitroglycerin tolerance in caveolin-1 deficient mice. (United States)

    Mao, Mao; Varadarajan, Sudhahar; Fukai, Tohru; Bakhshi, Farnaz R; Chernaya, Olga; Dudley, Samuel C; Minshall, Richard D; Bonini, Marcelo G


    Nitrate tolerance developed after persistent nitroglycerin (GTN) exposure limits its clinical utility. Previously, we have shown that the vasodilatory action of GTN is dependent on endothelial nitric oxide synthase (eNOS/NOS3) activity. Caveolin-1 (Cav-1) is known to interact with NOS3 on the cytoplasmic side of cholesterol-enriched plasma membrane microdomains (caveolae) and to inhibit NOS3 activity. Loss of Cav-1 expression results in NOS3 hyperactivation and uncoupling, converting NOS3 into a source of superoxide radicals, peroxynitrite, and oxidative stress. Therefore, we hypothesized that nitrate tolerance induced by persistent GTN treatment results from NOS3 dysfunction and vascular toxicity. Exposure to GTN for 48-72 h resulted in nitrosation and depletion (>50%) of Cav-1, NOS3 uncoupling as measured by an increase in peroxynitrite production (>100%), and endothelial toxicity in cultured cells. In the Cav-1 deficient mice, NOS3 dysfunction was accompanied by GTN tolerance (>50% dilation inhibition at low GTN concentrations). In conclusion, GTN tolerance results from Cav-1 modification and depletion by GTN that causes persistent NOS3 activation and uncoupling, preventing it from participating in GTN-medicated vasodilation.

  13. Caveolin-1 Expression and Membrane Cholesterol Content Modulate N-Type Calcium Channel Activity in NG108-15 Cells (United States)

    Toselli, M.; Biella, G.; Taglietti, V.; Cazzaniga, E.; Parenti, M.


    Caveolins are the main structural proteins of glycolipid/cholesterol-rich plasmalemmal invaginations, termed caveolae. In addition, caveolin-1 isoform takes part in membrane remodelling as it binds and transports newly synthesized cholesterol from endoplasmic reticulum to the plasma membrane. Caveolin-1 is expressed in many cell types, including hippocampal neurons, where an abundant SNAP25-caveolin-1 complex is detected after induction of persistent synaptic potentiation. To ascertain whether caveolin-1 influences neuronal voltage-gated Ca2+ channel basal activity, we stably expressed caveolin-1 into transfected neuroblastoma × glioma NG108-15 hybrid cells [cav1(+) clone] that lack endogenous caveolins but express N-type Ca2+ channels upon cAMP-induced neuronal differentiation. Whole-cell patch-clamp recordings of cav1(+) cells demonstrated that N-type current density was reduced in size by ∼70% without any significant change in the time course of activation and inactivation and voltage dependence. Moreover, the cav1(+) clone exhibited a significantly increased proportion of membrane cholesterol compared to wild-type NG108-15 cells. To gain insight into the mechanism underlying caveolin-1 lowering of N-current density, and more precisely to test whether this was indirectly caused by caveolin-1-induced enhancement of membrane cholesterol, we compared single N-type channel activities in cav1(+) clone and wild-type NG108-15 cells enriched with cholesterol after exposure to a methyl-β-cyclodextrin-cholesterol complex. A lower Ca2+ channel activity was recorded from cell-attached patches of both cell types, thus supporting the view that the increased proportion of membrane cholesterol is ultimately responsible for the effect. This is due to a reduction in the probability of channel opening caused by a significant decrease of channel mean open time and by an increase of the frequency of null sweeps. PMID:16040758

  14. Phenotypic Modulation of Mesenteric Vascular Smooth Muscle Cells from Type 2 Diabetic Rats is Associated with Decreased Caveolin-1 Expression

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    Maria Alicia Carrillo-Sepulveda


    Full Text Available Aims: Diabetes-induced vascular complications are associated with vascular smooth muscle cell (VSMC phenotypic modulation, switching from a contractile to a synthetic-proliferative phenotype. Loss of caveolin-1 is involved with proliferation of VSMCs. We tested the hypothesis that mesenteric VSMCs from type 2 diabetic Goto-Kakizaki (GK rat undergo phenotypic modulation and it is linked to decreased caveolin-1 expression. Methods: VSMCs were isolated from mesenteric arteries from GK rats and age-matched control Wistar rats. Western blotting was used to determine expression of target proteins such as caveolin-1, calponin (marker of differentiation, and proliferating cell nuclear antigen (PCNA, marker of proliferation. In addition, we measured intracellular reactive oxygen species (ROS production using H2DCF-DA and activation of extracellular signal-regulated kinase (ERK1/2 by western blotting in VSMCs from GK stimulated with lipopolysaccharide (LPS, an endotoxin upregulated in diabetes. Results: Mesenteric VSMCs from diabetic GK rats exhibited decreased caveolin-1 and calponin expression and increased PCNA expression compared to control. Increased levels of ROS and phospho-ERK1/2 expression were also found in GK VSMCs. LPS augmented ROS and phosphorylated ERK1/2 levels to a greater extent in GK VSMCs than in control. Likewise, high glucose decreased caveolin-1 and calponin expression, increased PCNA expression and augmented ROS production in control mesenteric VSMCs. Conclusion: These results suggest that mesenteric VSMCs from diabetic GK rats undergo phenotypic modulation and it is associated with decreased caveolin-1 expression. These alterations may be due to enhanced inflammatory stimuli and glucose levels present in diabetic milieu.

  15. Caveolar fatty acids and acylation of caveolin-1.

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    Qian Cai

    Full Text Available PURPOSE: Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids. METHODS: Caveolae were isolated from Chinese hamster ovary (CHO cells. The caveolar fatty acids were extracted with Folch reagent, methyl esterificated with BF3, and analyzed by gas chromatograph-mass spectrometer (GC/MS. The caveolin-1 bound fatty acids were immunoprecipitated by anti-caveolin-1 IgG and analyzed with GC/MS. RESULTS: In contrast to the whole CHO cell lysate which contained a variety of fatty acids, caveolae mainly contained three types of fatty acids, 0.48 µg palmitic acid, 0.61 µg stearic acid and 0.83 µg oleic acid/caveolae preparation/5 × 10(7 cells. Unexpectedly, GC/MS analysis indicated that caveolin-1 was not acylated by myristic acid; instead, it was acylated by palmitic acid and stearic acid. CONCLUSION: Caveolae contained a special set of fatty acids, highly enriched with saturated fatty acids, and caveolin-1 was acylated by palmitic acid and stearic acid. The unique fatty acid compositions of caveolae and acylation of caveolin-1 may be important for caveolae formation and for maintaining the function of caveolae.

  16. Caveolin-1 associated adenovirus entry into human corneal cells.

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    Mohammad A Yousuf

    Full Text Available The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC, caused by viruses within human adenovirus species D (HAdV-D, is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with

  17. Caveolin-1 regulates contractility in differentiated vascular smooth muscle. (United States)

    Je, Hyun-Dong; Gallant, Cynthia; Leavis, Paul C; Morgan, Kathleen G


    Caveolin is a principal component of caveolar membranes. In the present study, we utilized a decoy peptide approach to define the degree of involvement of caveolin in PKC-dependent regulation of contractility of differentiated vascular smooth muscle. The primary isoform of caveolin in ferret aorta vascular smooth muscle is caveolin-1. Chemical loading of contractile vascular smooth muscle tissue with a synthetic caveolin-1 scaffolding domain peptide inhibited PKC-dependent increases in contractility induced by a phorbol ester or an alpha agonist. Peptide loading also resulted in a significant inhibition of phorbol ester-induced adducin Ser662 phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/2 activation, and Ser789 phosphorylation of the actin binding protein caldesmon. alpha-Agonist-induced ERK1-1/2 activation was also inhibited by the caveolin-1 peptide. Scrambled peptide-loaded tissues or sham-loaded tissues were unaffected with respect to both contractility and signaling. Depolarization-induced activation of contraction was not affected by caveolin peptide loading. Similar results with respect to contractility and ERK1/2 activation during exposure to the phorbol ester or the alpha-agonist were obtained with the cholesterol-depleting agent methyl-beta-cyclodextrin. These results are consistent with a role for caveolin-1 in the coordination of signaling leading to the regulation of contractility of smooth muscle.

  18. Expression and significance of Caveolin-1 in hypopharyngeal carcinoma%Caveolin-1在下咽鳞癌中的表达及其临床意义

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    叶萍; 孙睿杰; 金童; 钱晔; 魏东敏; 潘新良


    Objective To evaluate the expression of caveolin-1 in hypopharyngeal squamous cell carcinoma (HSCC) and investigate its association with pathological features and clinical outcome. Methods Caveolin-1 expression was determined by immunohistochemistry using rabbit polyclonal antibody against caveolin-1 in 69 paraffin embedded primary HSCC and 10 normal hypopharyngeal mucosa specimens. Associations between caveolin-1 expression and pathological features and clinical outcomes were analyzed with a chi-square test. Results The caveolin-1 expression in HSCC was much higher than in the normal mucosa. The positive rate of caveolin-1 was 0% in the normal mucosa but 34.78% in the primary tumors. Increased caveolin-1 expression had been reported to be associated with various pathological parameters, including higher Gleason score and lymph node metastasis. Although no significant association between caveolin-1 expression and gender or primary position was observed, caveolin-1 was distinctively increased in cases with lymph node metastases (P < 0. 05). Conclusion Over-expression of Caveolin-1 could be a common finding in the aggressive types of HSCC. Caveolin-1 might play an important role in invasion and metastatic progression of HSCC.%目的 研究Caveolin-1在下咽鳞癌组织中的表达情况,探讨其在下咽鳞癌发生发展中的作用机制.方法 采用免疫组化法检测Caveolin-1在69例下咽鳞癌及10例癌旁正常组织中的表达,统计分析两者之间的相关性.结果 Caveolin-1在下咽癌组织中的阳性率为34.78%,在对照组中Caveolin-1存在个别表达或无阳性表达,两者表达差异有统计学意义(P<0.05);Caveolin-1的表达程度与病理类型、转移相关,而与下咽鳞癌患者性别、临床分期和原发部位之间差异无统计学意义(P>0.05).结论 下咽鳞癌中Caveolin-1的表达明显增高并与肿瘤的转移行为有关,有可能作为下咽鳞癌预后不良的病理标志之一.

  19. Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

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    Ivana Hitkova

    Full Text Available Caveolin-1 (Cav1 is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori is a major risk factor for human gastric cancer (GC where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS, infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird" compared to AGS cells stably transfected with Cav1 (AGS/Cav1. Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1 to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87 and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1 to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells.

  20. Caveolin-1 expression in benign and malignant lesions of the breast

    Directory of Open Access Journals (Sweden)

    Kiesel Ludwig


    Full Text Available Abstract Background Caveolin-1 is thought to have an important impact on both signal transduction and mediation of intracellular processes. Furthermore, it has been suggested that Caveolin-1 may contribute to certain steps of carcinogenesis in various types of cancer. We examined the potential clinical relevance of Caveolin-1 in normal, benign and malignant breast tissue specimens. Methods Using tissue microarray (TMA technology cases of invasive breast cancer, DCIS, benign breast disease (i.e. fibroadenoma, sclerosing adenosis, ductal hyperplasia and radial scar and normal breast tissue were evaluated for Caveolin-1 expression. Immunohistochemical staining with an anti-Caveolin-1-antibody was performed. Staining intensity was quantified semiquantitatively. In invasive lesions staining results were correlated with clinical and pathological data. Results No Caveolin-1 expression was observed in epithelial cells of normal breast tissue (n = 5, benign breast disease (n = 295 and DCIS (n = 108. However, Caveolin-1 expression was found in 32 of 109 cases of invasive breast carcinomas (29.4%. Caveolin-1 expression in invasive breast cancer could neither be correlated with survival parameters such as overall or disease-free survival nor with established clinical and pathological markers. Conclusion In this study we demonstrated expression of Caveolin-1 in one third of invasive breast cancers. A significant increase in Caveolin-1 expression was observed comparing invasive breast cancer to both benign breast tissue and non-invasive breast cancer. Since inhibitors of Caveolin-1 signalling are available, targeting Caveolin-1 in breast cancer may represent a potential option for future breast cancer treatment.

  1. Caveolin-1 and migration of bone-marrow derived cells in the mouse eye. (United States)

    May, Christian-Albrecht


    Bone marrow derived cells (BMDCs) can be found in almost every tissue showing a distinct turnover and density. Since caveolin-1 regulates junction-associated proteins in endothelial and epithelial cells, its role for BMDC was investigated in the eyes of caveolin-1 knock-out mice transplanted with GFP-marked BMDC. Distribution and turnover of BMDC in connective tissues (cornea, iris, ciliary body and choroid) was not altered. The absence of caveolin-1, however, caused a significant decrease of BMDC turnover in cornea epithelium, ciliary epithelium, and in the retina. This finding emphasizes an important, hitherto unknown role of caveolin-1 in neuronal and epithelial tissues.

  2. Stromal cell expression of caveolin-1 predicts outcome in breast cancer. (United States)

    Sloan, Erica K; Ciocca, Daniel R; Pouliot, Normand; Natoli, Anthony; Restall, Christina; Henderson, Michael A; Fanelli, Mariel A; Cuello-Carrión, Fernando D; Gago, Francisco E; Anderson, Robin L


    Caveolin-1 has been linked to tumor progression and clinical outcome in breast cancer, but a clear resolution of its role as a prognostic marker is lacking. We assessed caveolin-1 levels in normal breast tissue and two breast cancer cohorts for which outcome data were available. We found that caveolin-1 was not expressed in normal breast luminal epithelium but was present in the epithelial compartment of some tumors. We found no association between caveolin-1 expression in the epithelial compartment and clinical outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor, rather than within tumor cells, associated strongly with reduced metastasis and improved survival (P < 0.0001). The onset of mammary tumors driven by Her2/neu overexpression was accelerated in mice lacking caveolin-1, thereby supporting the observation that the presence of caveolin-1 in the tumor microenvironment modulates tumor development. These studies suggest that stromal caveolin-1 expression may be a potential therapeutic target and a valuable prognostic indicator of breast cancer progression.

  3. A role for caveolin-1 in post-injury reactive neuronal plasticity. (United States)

    Gaudreault, Sophie B; Blain, Jean-François; Gratton, Jean-Philippe; Poirier, Judes


    Remodeling and plasticity in the adult brain require cholesterol redistribution and synthesis for the formation of new membrane components. Caveolin-1 is a cholesterol-binding membrane protein involved in cellular cholesterol transport and homeostasis. Evidence presented here demonstrates an up-regulation of caveolin-1 in the hippocampus, which was temporally correlated with an increase in synaptophysin during the reinnervation phase in a mouse model of hippocampal deafferentation. Using an in vitro model of neuronal reactive plasticity, we examined the effect of virally mediated overexpression of caveolin-1 on injured differentiated PC12 cells undergoing terminal remodeling. Three days post lesion, caveolin-1-overexpressing cells revealed increases in synaptophysin and GAP-43, two markers of neurite sprouting and synaptogenesis. Morphologically, caveolin-1-overexpressing cells showed a decrease in primary neurite outgrowth and branching as well as an increase in neurite density. Caveolin-1-overexpressing cells also revealed the presence of terminal swelling and beading along processes, consistent with a possible alteration of microtubules stability. Moreover, a focal enrichment of caveolin-1 immunofluorescence was observed at the bases of axonal and dendritic terminals of mouse primary hippocampal neurons. Altogether, these results indicate that caveolin-1 plays an active role in the regulation of injury-induced synaptic and terminal remodeling in the adult CNS.

  4. Caveolin-1 is enriched in the peroxisomal membrane of rat hepatocytes.

    NARCIS (Netherlands)

    Woudenberg, J.; Rembacz, K.P.; Heuvel, F.A. van den; Woudenberg-Vrenken, T.E.; Buist-Homan, M.; Geuken, M.; Hoekstra, M.; Deelman, L.E.; Enrich, C.; Henning, R.H.; Moshage, H.; Faber, K.N.


    Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression o

  5. Caveolin-1 Is Enriched in the Peroxisomal Membrane of Rat Hepatocytes

    NARCIS (Netherlands)

    Woudenberg, Jannes; Rembacz, Krzysztof P.; van den Heuvel, Fiona A. J.; Woudenberg-Vrenken, Titia E.; Buist-Homan, Manon; Geuken, Mariska; Hoekstra, Mark; Deelman, Leo E.; Enrich, Carlos; Henning, Rob H.; Moshage, Han; Faber, Klaas Nico


    Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression o

  6. Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

    Directory of Open Access Journals (Sweden)

    Shi D


    Full Text Available Dan Shi,1,* Yan Liu,1,* Ronggang Xi,1 Wei Zou,2 Lijun Wu,3 Zhiran Zhang,1 Zhongyang Liu,1 Chao Qu,1 Baoli Xu,1 Xiaobo Wang1 1Department of Pharmacy, The 210th Hospital of People’s Liberation Army, 2College of Life Science, Liaoning Normal University, Dalian, Liaoning, 3Department of Pharmaceutics, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Chronic myelogenous leukemia (CML is characterized by the t(9;22 (q34;q11-associated Bcr-Abl fusion gene, which is an essential element of clinical diagnosis. As a traditional Chinese medicine, realgar has been widely used for the treatment of various diseases for >1,500 years. Inspired by nano-drug, realgar nanoparticles (NPs have been prepared with an average particle size of <100 nm in a previous work. Compared with coarse realgar, the realgar NPs have higher bioavailability. As a principal constituent protein of caveolae, caveolin-1 (Cav-1 participates in regulating various cellular physiological and pathological processes including tumorigenesis and tumor development. In previous studies, it was found that realgar NPs can inhibit several types of tumor cell proliferation. However, the therapeutic effect of realgar NPs on CML has not been fully elucidated. In the present paper, it was demonstrated that realgar NPs can inhibit the proliferation of K562 cells and degrade Bcr-Abl fusion protein effectively. Both apoptosis and autophagy were activated in a dose-dependent manner in realgar NPs treated cells, and the induction of autophagy was associated with class I phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Morphological analysis indicated that realgar NPs induced differentiation effectively in CML cells. Furthermore, it was identified that Cav-1 might play a crucial role in realgar NP therapy. In order to study the effects of Cav-1 on K562 cells during

  7. Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling. (United States)

    Fernández-Rojo, Manuel A; Gongora, Milena; Fitzsimmons, Rebecca L; Martel, Nick; Martin, Sheree D; Nixon, Susan J; Brooks, Andrew J; Ikonomopoulou, Maria P; Martin, Sally; Lo, Harriet P; Myers, Stephen A; Restall, Christina; Ferguson, Charles; Pilch, Paul F; McGee, Sean L; Anderson, Robin L; Waters, Michael J; Hancock, John F; Grimmond, Sean M; Muscat, George E O; Parton, Robert G


    Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1-/- mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1-/- mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARα, FXRα, and SHP) and bile acid signaling.

  8. Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

    Directory of Open Access Journals (Sweden)

    Manuel A. Fernández-Rojo


    Full Text Available Caveolae and caveolin-1 (CAV1 have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1 hepatic lipid homeostasis and (2 nuclear hormone receptor (PPARα, FXRα, and SHP and bile acid signaling.

  9. Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx. (United States)

    Vargas, Leonardo; Nore, Beston F; Berglof, Anna; Heinonen, Juhana E; Mattsson, Pekka T; Smith, C I Edvard; Mohamed, Abdalla J


    Bruton's tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here that Btk interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. In addition, we found that native Bmx, another member of the Tec family kinases, is associated with endogenous caveolin-1 in primary human umbilical vein endothelial cells. Second, in transient transfection assays, expression of caveolin-1 leads to a substantial reduction in the in vivo tyrosine phosphorylation of both Btk and its constitutively active form, E41K. Furthermore, a caveolin-1 scaffolding peptide (amino acids 82--101) functionally suppressed the autokinase activity of purified recombinant Btk protein. Third, we demonstrate that mouse splenic B-lymphocytes express substantial amounts of caveolin-1. Interestingly, caveolin-1 was found to be constitutively phosphorylated on tyrosine 14 in these cells. The expression of caveolin-1 in B-lymphocytes and its interaction with Btk may have implications not only for B cell activation and signaling, but also for antigen presentation.

  10. Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats*******

    Institute of Scientific and Technical Information of China (English)

    Yang Liu; Zhanhua Liang; Jing Liu; Wei Zou; Xiaoyan Li; Yachen Wang; Lijia An


    Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebel um of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged (22-24 month old) rats was significantly lower than that in young (1 month old) and adult (4 months old) rats. pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebel um. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebel um. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.

  11. Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy. (United States)

    Shi, Yin; Tan, Shi-Hao; Ng, Shukie; Zhou, Jing; Yang, Na-Di; Koo, Gi-Bang; McMahon, Kerrie-Ann; Parton, Robert G; Hill, Michelle M; Del Pozo, Miguel A; Kim, You-Sun; Shen, Han-Ming


    CAV1 (caveolin 1, caveolae protein, 22kDa) is well known as a principal scaffolding protein of caveolae, a specialized plasma membrane structure. Relatively, the caveolae-independent function of CAV1 is less studied. Autophagy is a process known to involve various membrane structures, including autophagosomes, lysosomes, and autolysosomes for degradation of intracellular proteins and organelles. Currently, the function of CAV1 in autophagy remains largely elusive. In this study, we demonstrate for the first time that CAV1 deficiency promotes both basal and inducible autophagy. Interestingly, the promoting effect was found mainly in the late stage of autophagy via enhancing lysosomal function and autophagosome-lysosome fusion. Notably, the regulatory function of CAV1 in lysosome and autophagy was found to be caveolae-independent, and acts through lipid rafts. Furthermore, the elevated autophagy level induced by CAV1 deficiency serves as a cell survival mechanism under starvation. Importantly, downregulation of CAV1 and enhanced autophagy level were observed in human breast cancer cells and tissues. Taken together, our data reveal a novel function of CAV1 and lipid rafts in breast cancer development via modulation of lysosomal function and autophagy.

  12. Study on bone Caveolin-1 expression in osteoporosis mice%骨质疏松小鼠模型中骨组织Caveolin-1表达

    Institute of Scientific and Technical Information of China (English)

    郭玉; 龚邵新; 陈志伟; 陈临溪; 刘刚


    目的 探讨骨质疏松小鼠模型中骨组织Caveolin-1表达变化.方法 双侧卵巢切除法建立小鼠骨质疏松模型;用双能X线骨密度仪测骨矿密度;HE染色观察骨组织变化;免疫组织化学法检测骨组织Cave-olin-1表达.结果 去卵巢12周小鼠股骨骨矿密度明显下降,同时其HE染色组织学改变符合骨质疏松症病理变化.骨质疏松组小鼠骨组织Caveolin-1表达明显低于对照组,Caveolin-1在小鼠幼年组表达最高.结论 去卵巢骨质疏松模型小鼠骨组织Caveolin-1表达降低,Caveolin-1信号分子可能具有抑制骨质疏松形成与发展作用.

  13. Increased caveolin-1 expression in Alzheimer's disease brain. (United States)

    Gaudreault, Sophie B; Dea, Doris; Poirier, Judes


    Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and aged-matched control subjects. Our results demonstrate that caveolin protein levels in the hippocampus and caveolin mRNA in the frontal cortex are up-regulated in AD by approximately two-fold, compared to control brains. These results suggest a relationship between caveolin-1 expression levels and a dysregulation of cholesterol homeostasis at the plasma membrane of brain cells. In support of this hypothesis, a significant increase in caveolin protein levels has also been observed in hippocampal tissue from ApoE-deficient (knockout) and aged wild-type mice; two situations associated with modifications of transbilayer distribution of cholesterol in brain synaptic plasma membranes. These results indicate that caveolin over-expression is linked to alterations of cholesterol distribution in the plasma membrane of brain cells and are consistent with the notion of a deterioration of cholesterol homeostasis in AD.

  14. Caveolin-1 interacts with the Gag precursor of murine leukaemia virus and modulates virus production

    Directory of Open Access Journals (Sweden)

    Koester Mario


    Full Text Available Abstract Background Retroviral Gag determines virus assembly at the plasma membrane and the formation of virus-like particles in intracellular multivesicular bodies. Thereby, retroviruses exploit by interaction with cellular partners the cellular machineries for vesicular transport in various ways. Results The retroviral Gag precursor protein drives assembly of murine leukaemia viruses (MLV at the plasma membrane (PM and the formation of virus like particles in multivesicular bodies (MVBs. In our study we show that caveolin-1 (Cav-1, a multifunctional membrane-associated protein, co-localizes with Gag in a punctate pattern at the PM of infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix protein (MA of the Gag precursor. This interaction is mediated by a Cav-1 binding domain (CBD within the N-terminus of MA. Interestingly, the CBD motif identified within MA is highly conserved among most other γ-retroviruses. Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells. Overexpression of a GFP fusion protein containing the putative CBD of the retroviral MA resulted in a considerable decrease in production of infectious retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected retroviral titres significantly. Conclusion This study demonstrates that Cav-1 interacts with MLV Gag, co-localizes with Gag at the PM and affects the production of infectious virus. The results strongly suggest a role for Cav-1 in the process of virus assembly.

  15. Loss of caveolin-1 accelerates neurodegeneration and aging.

    Directory of Open Access Journals (Sweden)

    Brian P Head

    Full Text Available BACKGROUND: The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR, discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1, a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed brains from young (Yg, 3-6 months, middle age (Md, 12 months, aged (Ag, >18 months, and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression. CONCLUSIONS: Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease.

  16. Prognostic and predictive values of SPP1, PAI and caveolin-1 in patients with oral squamous cell carcinoma. (United States)

    Huang, Cong-Fa; Yu, Guang-Tao; Wang, Wei-Ming; Liu, Bing; Sun, Zhi-Jun


    SPP1, PAI and caveolin-1 are known to be closely associated with tumor progression in several kinds of human tumors. This study aimed to investigate the expression of SPP1, PAI and caveolin-1 in oral squamous cell carcinoma (OSCC), and to evaluate their association with the prognosis in oral carcinoma. Immunohistochemical staining was used to examine the expression of SPP1, PAI and caveolin-1 in 17 normal oral mucosa, 6 oral epithelial dysplasia and 43 OSCC specimens by tissue microarrays. High expression of SPP1, PAI and caveolin-1 was found in OSCC patients, and SPP1 and PAI expression were significantly higher in OSCC than in normal oral mucosa. No significant correlations were found between SPP1, PAI and caveolin-1 expression and clinicopathological factors. Expression of SPP1, PAI and caveolin-1 was also not associated with overall survival. Moreover, SPP1 was closely correlated with PAI, caveolin-1 and Keap1, and PAI had significant correlations with caveolin-1, Keap1 and Nrf2, and caveolin-1 was associated with Keap1 by using the Pearson correlation coefficient test. Our findings suggest that overexpressed SPP1, PAI and caveolin-1 were linked to carcinogenesis and progression, and thus they may serve as potential prognostic factors in OSCC.

  17. 蟾蜍Caveolin-1的生物信息学分析及其在肌肉组织中的表达%Bioinformatics analysis of Caveolin-1 in toad and its expression in muscle tissues

    Institute of Scientific and Technical Information of China (English)

    张叶军; 解文放; 李洪艳; 崔玉影; 邹伟


    The Caveolin-1 protein sequence of Xenopus laevis in GenBank was obtained and its struc-ture and function were predicted through various bioinformatics analysis softwares . The results showed that Caveolin-1 of toad and mammals have similar structures and functions .Total protein from muscle tissues of Bufo gargarizans was extracted and the Caveolin-1 had been detected through Western Blot by mouse anti-human Caveolin-1 polyclonal antibody .It was suggested that Caveolin-1 is highly conserved in the long biological evolution process ,and maintains its function as a signal transduction center .%在GenBank中获得非洲爪蟾Caveolin-1蛋白序列,通过多种生物信息学分析软件对其进行分析,预测其结构和功能。以成年中华大蟾蜍为实验材料,提取蟾蜍不同肌肉组织的总蛋白,通过Western Blot技术检测Caveolin-1在肌肉组织中的表达。结果表明:蟾蜍的Caveolin-1与哺乳动物Caveolin-1有着相似的结构和功能;利用本实验室已有的抗人Caveolin-1多克隆抗体在中华大蟾蜍的不同肌肉组织中检测到了Caveolin-1的表达,从另一个角度验证了Caveolin-1的保守性。

  18. Fusion Enhanced Vehicle Level Diagnostic System Project (United States)

    National Aeronautics and Space Administration — Global Technology Connection, Inc. in conjunction with its partner, Vanderbilt University, is proposing to build a Fusion-enhanced Vehicle Diagnostics System (FVDS)...

  19. Caveolin-2 associates with intracellular chlamydial inclusions independently of caveolin-1

    Directory of Open Access Journals (Sweden)

    Norkin Leonard C


    Full Text Available Abstract Background Lipid raft domains form in plasma membranes of eukaryotic cells by the tight packing of glycosphingolipids and cholesterol. Caveolae are invaginated structures that form in lipid raft domains when the protein caveolin-1 is expressed. The Chlamydiaceae are obligate intracellular bacterial pathogens that replicate entirely within inclusions that develop from the phagocytic vacuoles in which they enter. We recently found that host cell caveolin-1 is associated with the intracellular vacuoles and inclusions of some chlamydial strains and species, and that entry of those strains depends on intact lipid raft domains. Caveolin-2 is another member of the caveolin family of proteins that is present in caveolae, but of unknown function. Methods We utilized a caveolin-1 negative/caveolin-2 positive FRT cell line and laser confocal immunofluorescence techniques to visualize the colocalization of caveolin-2 with the chlamydial inclusions. Results We show here that in infected HeLa cells, caveolin-2, as well as caveolin-1, colocalizes with inclusions of C. pneumoniae (Cp, C. caviae (GPIC, and C. trachomatis serovars E, F and K. In addition, caveolin-2 also associates with C. trachomatis serovars A, B and C, although caveolin-1 did not colocalize with these organisms. Moreover, caveolin-2 appears to be specifically, or indirectly, associated with the pathogens at the inclusion membranes. Using caveolin-1 deficient FRT cells, we show that although caveolin-2 normally is not transported out of the Golgi in the absence of caveolin-1, it nevertheless colocalizes with chlamydial inclusions in these cells. However, our results also show that caveolin-2 did not colocalize with UV-irradiated Chlamydia in FRT cells, suggesting that in these caveolin-1 negative cells, pathogen viability and very likely pathogen gene expression are necessary for the acquisition of caveolin-2 from the Golgi. Conclusion Caveolin-2 associates with the chlamydial

  20. Caveolin-1-Mediated Expression and Secretion of Kallikrein 6 in Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Rebecca S. Henkhaus


    Full Text Available Kallikreins are secreted proteases that may play a functional role and/or serve as a serum biomarker for the presence or progression of certain types of cancers. Kallikrein 6 (KLK6 has been shown to be upregulated in several types of cancers, including colon. The aims of this study were to elucidate pathways that influence KLK6 gene expression and KLK6 protein secretion in the HCT116 human colon cancer cells. Our data indicate a central role for caveolin-1 (CAV-1, the main structural protein of caveolae, in both KLK6 gene expression and protein secretion. Sucrose gradient subcellular fractionation reveals that CAV-1 and KLK6 colocalize to lipid raft domains in the plasma membrane of HCT116 cells. Furthermore, we show that CAV-1, although it does not directly interact with the KLK6 molecule, enhances KLK6 secretion from the cells. Deactivation of CAV-1, through SRC-mediated phosphorylation, decreased KLK6 secretion. We also demonstrate that, in colon cancer cells, CAV-1 increased the amount of phosphorylated AKT in cells by inhibiting the activity of the AKT-negative regulators PP1 and PP2A. This study demonstrates that proteins such as CAV-1 and AKT, which are known to be altered in colon cancer, affect KLK6 expression and KLK6 secretion.

  1. Caveolin-1 as a potential new therapeutic target in multiple myeloma. (United States)

    Podar, Klaus; Anderson, Kenneth C


    Caveolae are specialized flask-shaped lipid rafts enriched in cholesterol, sphingolipids, and structural marker proteins termed caveolins. Caveolins are highly conserved hairpin loop-shaped, oligomeric proteins of 22-24 kDa. Besides the plasma cell membrane, caveolins are also present in mitochondria, the endoplasmatic reticulum, the Golgi/trans-Golgi network, and secretory vesicles. They play a critical role in normal vesicular transport, cholesterol homeostasis, and signal transduction. Conversely, dysregulation of caveolin-1 has been associated with several human diseases including multiple myeloma, an incurable malignancy characterized by excess monoclonal plasma cells within the bone marrow. In this mini-review, we characterize the functional role of caveolin-1 in multiple myeloma, and present the preclinical rationale for novel potential therapeutic approaches targeting caveolin-1 in multiple myeloma.

  2. Sensor fusion method for machine performance enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Mou, J.I. [Arizona State Univ., Tempe, AZ (United States); King, C.; Hillaire, R. [Sandia National Labs., Livermore, CA (United States). Integrated Manufacturing Systems Center; Jones, S.; Furness, R. [Ford Motor Co., Dearborn, MI (United States)


    A sensor fusion methodology was developed to uniquely integrate pre-process, process-intermittent, and post-process measurement and analysis technology to cost-effectively enhance the accuracy and capability of computer-controlled manufacturing equipment. Empirical models and computational algorithms were also developed to model, assess, and then enhance the machine performance.

  3. Absence of caveolin-1 alters heat shock protein expression in spontaneous mammary tumors driven by Her-2/neu expression. (United States)

    Ciocca, Daniel R; Cuello-Carrión, F Darío; Natoli, Anthony L; Restall, Christina; Anderson, Robin L


    In a previous study, we measured caveolin-1 protein levels, both in the normal breast and in breast cancer. The study revealed no association between caveolin-1 expression in the epithelial compartment and clinical disease outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor associated strongly with reduced metastasis and improved survival. Using an animal model, we found that the onset of mammary tumors driven by Her-2/neu expression was accelerated in mice lacking caveolin-1. We have analysed the heat shock protein (Hsp) response in the tumors of mice lacking caveolin-1. In all cases, the mammary tumors were estrogen and progesterone receptor negative, and the levels of Her-2/neu (evaluated by immunohistochemistry) were not different between the caveolin-1 +/+ (n = 8) and the caveolin-1 -/- (n = 7) tumors. However, a significant reduction in the extent of apoptosis was observed in mammary tumors from animals lacking caveolin-1. While Bcl-2, Bax, and survivin levels in the tumors were not different, the amount of HSPA (Hsp70) was almost double in the caveolin-1 -/- tumors. In contrast, HSPB1 (Hsp27/Hsp25) levels were significantly lower in the caveolin-1 -/- tumors. The mammary tumors from caveolin-1 null mice expressed more HSPC4 (gp96 or grp94), but HSPC1 (Hsp90), HSPA5 (grp78), HSPD1 (Hsp60), and CHOP were not altered. No significant changes in these proteins were found in the stroma surrounding these tumors. These results demonstrate that the disruption of the Cav-1 gene can cause alterations of specific Hsps as well as tumor development.

  4. Effects of Raloxifene on Caveolin-1 mRNA and Protein Expressions in Vascular Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    Fa-Lin YANG; Hong HE; Xian-Xi LIU; Bing TU; Xian-Wei ZENG; Ji-Xin SU; Xin WANG; Qin HU


    Caveolin-1 is regulated by estrogen in vascular smooth muscle cells. Raloxifene, a selectiveestrogen receptor modulator that possibly has cardioprotective properties without an increased risk of c ancer or other side effects of estrogen, may be used in women with risk of coronary artery disease. However, the relationship between raloxifene and caveolin-1 is still unknown. Therefore, this study was designed to see whether raloxifene regulates caveolin- 1 expression and if so, whether such regulation is mediated by estrogen receptor. Rat aortic smooth muscle cells were cultured in the absence or presence of raloxifene (10-8 to 10-6 M) for 12 or 24 h. Both mRNA and protein levels of caveolin-1 were increased significantly after 24 h treatment with raloxifene. These increases were inhibited by estrogen receptor antagonist ICI 182780 (10-5 M). Results of this study suggest that raloxifene stimulates caveolin- 1 transcription and translation through estrogen receptor mediated mechanisms.

  5. Caveolin1/protein arginine methyltransferase1/sirtuin1 axis as a potential target against endothelial dysfunction. (United States)

    Charles, Soniya; Raj, Vijay; Arokiaraj, Jesu; Mala, Kanchana


    Endothelial dysfunction (ED), an established response to cardiovascular risk factors, is characterized by increased levels of soluble molecules secreted by endothelial cells (EC). Evidence suggest that ED is an independent predictor of cardiac events and that it is associated with a deficiency in production or bioavailability of nitric oxide (NO) and/or an imbalance in the relative contribution of endothelium-derived relaxing and contracting factors. ED can be reversed by treating cardiovascular risk factors, hence, beyond ambiguity, ED contributes to initiation and progression of atherosclerotic disease. Majority of cardiovascular risk factors act by a common pathway, oxidative stress (OS), characterized by an imbalance in bioavailability of NO and reactive oxygen species (ROS). Enhanced ROS, through several mechanisms, alters competence of EC that leads to ED, reducing its potential to maintain homeostasis and resulting in development of cardiovascular disease (CVD). Influential mechanisms that have been implicated in the development of ED include (i) presence of elevated levels of NOS inhibitor, asymmetric dimethylarginine (ADMA) due to augmented enzyme activity of protein arginine methyl transferase-1 (PRMT1); (ii) decrease in NO generation by endothelial nitric oxide synthase (eNOS) uncoupling, or by reaction of NO with free radicals and (iii) impaired post translational modification of protein (PTM) such as eNOS, caveolin-1 (cav1) and sirtuin-1 (SIRT1). However, the inter-related mechanisms that concur to developing ED is yet to be understood. The events that possibly overlay include OS-induced sequestration of SIRT1 to caveolae facilitating cav1-SIRT1 association; potential increase in lysine acetylation of enzymes such as eNOS and PRMT1 leading to enhanced ADMA formation; imbalance in acetylation-methylation ratio (AMR); diminished NO generation and ED. Here we review current literature from research showing interdependent association between cav1-PRMT1

  6. Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1

    Institute of Scientific and Technical Information of China (English)

    Rajamma; Mathew


    A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro-and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor(PPAR) γ, a ligandactivated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1,PPARγ and adipokines in PH and metabolic syndrome.

  7. Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1. (United States)

    Mathew, Rajamma


    A number of disparate diseases can lead to pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro- and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor (PPAR) γ, a ligand-activated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1, PPARγ and adipokines in PH and metabolic syndrome.

  8. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  9. Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism. (United States)

    Karuppiah, Kanchana; Druhan, Lawrence J; Chen, Chun-an; Smith, Travis; Zweier, Jay L; Sessa, William C; Cardounel, Arturo J


    In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase (eNOS) in a calcium/calmodulin-dependent reaction. In the absence of the requisite eNOS cofactor tetrahydrobiopterin (BH(4)), NADPH oxidation is uncoupled from NO generation, leading to the production of superoxide. Although this phenomenon is apparent with purified enzyme, cellular studies suggest that formation of the BH(4) oxidation product, dihydrobiopterin, is the molecular trigger for eNOS uncoupling rather than BH(4) depletion alone. In the current study, we investigated the effects of both BH(4) depletion and oxidation on eNOS-derived superoxide production in endothelial cells in an attempt to elucidate the molecular mechanisms regulating eNOS oxidase activity. Results demonstrated that pharmacological depletion of endothelial BH(4) does not result in eNOS oxidase activity, whereas BH(4) oxidation gave rise to significant eNOS-oxidase activity. These findings suggest that the endothelium possesses regulatory mechanisms, which prevent eNOS oxidase activity from pterin-free eNOS. Using a combination of gene silencing and pharmacological approaches, we demonstrate that eNOS-caveolin-1 association is increased under conditions of reduced pterin bioavailability and that this sequestration serves to suppress eNOS uncoupling. Using small interfering RNA approaches, we demonstrate that caveolin-1 gene silencing increases eNOS oxidase activity to 85% of that observed under conditions of BH(4) oxidation. Moreover, when caveolin-1 silencing was combined with a pharmacological inhibitor of AKT, BH(4) depletion increased eNOS-derived superoxide to 165% of that observed with BH(4) oxidation. This study identifies a critical role of caveolin-1 in the regulation of eNOS uncoupling and provides new insight into the mechanisms through which disease-associated changes in caveolin-1 expression may contribute to endothelial dysfunction.

  10. Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. (United States)

    Phiboonchaiyanan, Preeyaporn Plaimee; Kiratipaiboon, Chayanin; Chanvorachote, Pithi


    Cancer stem cells (CSCs), a subpopulation of cancer cells with high aggressive behaviors, have been identified in many types of cancer including lung cancer as one of the key mediators driving cancer progression and metastasis. Here, we have reported for the first time that ciprofloxacin (CIP), a widely used anti-microbial drug, has a potentiating effect on CSC-like features in human non-small cell lung cancer (NSCLC) cells. CIP treatment promoted CSC-like phenotypes, including enhanced anchorage-independent growth and spheroid formation. The known lung CSC markers: CD133, CD44, ABCG2 and ALDH1A1 were found to be significantly increased, while the factors involving in epithelial to mesenchymal transition (EMT): Slug and Snail, were depleted. Also, self-renewal transcription factors Oct-4 and Nanog were found to be up-regulated in CIP-treated cells. The treatment of CIP on CSC-rich populations obtained from secondary spheroids resulted in the further increase of CSC markers. In addition, we have proven that the mechanistic insight of the CIP induced stemness is through Caveolin-1 (Cav-1)-dependent mechanism. The specific suppression of Cav-1 by stably transfected Cav-1 shRNA plasmid dramatically reduced the effect of CIP on CSC markers as well as the CIP-induced spheroid formation ability. Cav-1 was shown to activate protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways in CSC-rich population; however, such an effect was rarely found in the main lung cancer cells population. These findings reveal a novel effect of CIP in positively regulating CSCs in lung cancer cells via the activation of Cav-1, Akt and ERK, and may provoke the awareness of appropriate therapeutic strategy in cancer patients.

  11. Influence of caveolin-1 on the ET-1-induced VSMC proliferation%Caveolin-1在内皮素-1诱导血管平滑肌细胞增殖中的作用

    Institute of Scientific and Technical Information of China (English)

    谈智; 陈建文; 潘敬运; 王庭槐


    目的:探讨caveolin-1蛋白在VSMC的分布、在ET-1诱导的VSMC增殖中表达的变化情况.方法:在培养的VSMC上,使用[3H]TdR掺入法观察ET-1和BQ123对其DNA合成的影响;用荧光免疫组化方法观察cave-olin-1蛋白在VSMC的分布,ET-1对caveolin-1蛋白表达的影响;用Western blot检测ET-1和BQ123对caveolin-1蛋白表达的影响.结果:ET-1可以呈浓度梯度地刺激VSMC的增殖,ETAR特异性阻断剂BQ123可以抑制ET-1的作用;免疫荧光证实了在VSMC上,caveolin-1分布于细胞表面,在ET-1刺激增殖过程中,VSMC上caveolin-1蛋白荧光强度下降;Westem blot证实ET-1可以抑制caveolin-1蛋白的表达.结论:在VSMC上,caveolin-1主要分布于细胞表面,在ET-1刺激增殖过程中,caveolin-1蛋白表达发生了变化,ET-1可通过ETAR抑制caveolin-1蛋白的表达.

  12. Breast cancer nodal metastasis correlates with tumour and lymph node methylation profiles of Caveolin-1 and CXCR4. (United States)

    Alevizos, Leonidas; Kataki, Agapi; Derventzi, Anastasia; Gomatos, Ilias; Loutraris, Christos; Gloustianou, Georgia; Manouras, Andreas; Konstadoulakis, Manousos M; Zografos, George


    DNA methylation is the best characterised epigenetic change so far. However, its role in breast cancer metastasis has not as yet been elucidated. The aim of this study was to investigate the differences between the methylation profiles characterising primary tumours and their corresponding positive or negative for metastasis lymph nodes (LN) and correlate these with tumour metastatic potential. Methylation signatures of Caveolin-1, CXCR4, RAR-β, Cyclin D2 and Twist gene promoters were studied in 30 breast cancer primary lesions and their corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry. Tumours were typified by methylation of RAR-β and hypermethylation of Cyclin-D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour-infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated between node-negative and metastatic tumours. Nodal metastasis was associated with tumour and lymph node profiles of extended methylation of Caveolin-1 and lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1 expression in stromal cells associated with tumour aggressiveness while strong Caveolin-1 expression in tumour cells correlated with decreased 7-year disease-free survival. Methylation-mediated activation of CXCR4 and inactivation of Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1 expression heterogeneity correlated with disease progression. This evidence contributes to the better understanding and, thereby, therapeutic management of breast cancer metastasis process.

  13. Caveolin-1, E-cadherin and β-catenin in Gastric Carcinoma, Precancerous Tissues and Chronic Non-atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    Guo-yang Sun; Jun-xia Wu; Jian-sheng Wu; Yu-ting Pan; Rong Jin


    Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidinperoxidase (SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage (P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased (P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia (P<0.01).Caveolin-1 expression correlated positively with E-cadherin (r=0.41,P<0.05).Caveolin-1 (r=-0.36,P<0.05) and E-cadherin (r=-0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion:These results suggested that dysregulated expressions of caveolin-1,E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.

  14. Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. (United States)

    Podar, Klaus; Shringarpure, Reshma; Tai, Yu-Tzu; Simoncini, Melissa; Sattler, Martin; Ishitsuka, Kenji; Richardson, Paul G; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C


    We recently demonstrated that caveolae, vesicular flask-shaped invaginations of the plasma membrane, represent novel therapeutic targets in multiple myeloma. In the present study, we demonstrate that vascular endothelial growth factor (VEGF) triggers Src-dependent phosphorylation of caveolin-1, which is required for p130(Cas) phosphorylation and multiple myeloma cell migration. Conversely, depletion of caveolin-1 by antisense methodology abrogates p130(Cas) phosphorylation and VEGF-triggered multiple myeloma cell migration. The proteasome inhibitor bortezomib both inhibited VEGF-triggered caveolin-1 phosphorylation and markedly decreased caveolin-1 expression. Consequently, bortezomib inhibited VEGF-induced multiple myeloma cell migration. Bortezomib also decreased VEGF secretion in the bone marrow microenvironment and inhibited VEGF-triggered tyrosine phosphorylation of caveolin-1, migration, and survival in human umbilical vascular endothelial cells. Taken together, these studies demonstrate the requirement of caveolae for VEGF-triggered multiple myeloma cell migration and identify caveolin-1 in multiple myeloma cells and human umbilical vascular endothelial cells as a molecular target of bortezomib.

  15. Caveolin-1 influences human influenza A virus (H1N1 multiplication in cell culture

    Directory of Open Access Journals (Sweden)

    Hemgård Gun-Viol


    Full Text Available Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1 as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1 strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1 virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK, a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

  16. 结直肠癌及肝转移瘤中Caveolin-1的表达研究

    Institute of Scientific and Technical Information of China (English)

    唐卫中; 李卫; 彭涛; M Laban



  17. Triptolide inhibits the migration and invasion of human prostate cancer cells via Caveolin-1/CD147/MMPs pathway. (United States)

    Yuan, Shiqi; Wang, Liping; Chen, Xixi; Fan, Bo; Yuan, Qingmin; Zhang, Han; Yang, Deyong; Wang, Shujing


    Prostate cancer (PCa) is the second most common type of carcinoma and the 5th leading cause of cancer-related death in males. Triptolide, is a main and effective component of Tripterygium wilfordii Hook F, which exerts an broad-spectrum anti-malignant tumor function. However, the effect of triptolide on migration and invasion of human prostate cancer cells is still poorly understood. In this study, we demonstrated that triptolide significantly inhibited the proliferation, migration and invasion of prostate cancer cells in a time- and dose-dependent manner. Caveolin-1 (Cav-1) is regarded as a major structural protein of caveolae and participated in lipid transport, signal transduction and tumor progression. Triptolide treatment inhibited the expression of tumor promoter Cav-1 and reduced CD147 and MMPs activities at both mRNA and protein levels. Meanwhile, triptolide treatment combined with Cav-1 knockdown in PCa cells enhanced the effects of anti-migration and anti-invasion, and those effects were restored following Cav-1-rescued. Together, our research indicates that triptolide represses the migration and invasion through Cav-1/CD147/MMPs pathway in PCa cells, which gives a better understanding of triptolide in clinical aggressive prostate cancer therapy.

  18. Caveolin-1, caveolin-3 and VEGF expression in the masticatory muscles of mdx mice

    Directory of Open Access Journals (Sweden)

    Alexander Spassov


    Full Text Available Duchenne muscular dystrophy (DMD and murine X-linked muscular dystrophy (mdx, its murine model, are characterized by muscle damage and muscle weakness associated with inflammation and new vessel formation. Caveolins, dystrophin-associated proteins, are involved in the pathogenesis of DMD, because increased numbers of caveolae are found in DMD and mdx hindlimb muscles. Caveolae influence angiogenesis due to their content of vascular endothelial growth factor (VEGF receptors. Orofacial muscles in mdx mice undergo muscle necrosis followed by muscle regeneration. To ascertain the role of caveolins and VEGF in the pathogenesis of dystrophic masticatory muscles, we examined the expression of caveolin-1 (cav-1, caveolin-3 (cav-3 and VEGF in control and mdx mice. In mdx masticatory muscles, no changes in transcript and protein levels of VEGF were found, whereas cav-1 and cav-3 expression was increased. Using immunohistochemistry, a strong sarcolemmal staining of caveolin-3 in regenerated muscle fibers was found. Furthermore, immunohistochemistry with the caveolin-1 antibody showed an increase in the amount of blood vessels in areas with regenerating muscle fibers. Dystrophic masticatory muscles showed changes comparable to those of hindlimb muscles in the expression of cav-1 and cav-3. The angiogenesis seems to be unaffected in the jaw muscles of mdx mice. We speculate that the increased caveolin expression could cause extensive and efficient muscle regeneration. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 291–298

  19. Lipid rafts, caveolae, caveolin-1, and entry by Chlamydiae into host cells. (United States)

    Stuart, Elizabeth S; Webley, Wilmore C; Norkin, Leonard C


    Obligate intracellular bacterial pathogens of the genus Chlamydia are reported to enter host cells by both clathrin-dependent and clathrin-independent processes. C. trachomatis serovar K recently was shown to enter cells via caveolae-like lipid raft domains. We asked here how widespread raft-mediated entry might be among the Chlamydia. We show that C. pneumoniae, an important cause of respiratory infections in humans that additionally is associated with cardiovascular disease, and C. psittaci, an important pathogen in domestic mammals and birds that also infects humans, each enter host cells via cholesterol-rich lipid raft microdomains. Further, we show that C. trachomatis serovars E and F also use these domains to enter host cells. The involvement of these membrane domains in the entry of these organisms was indicated by the sensitivity of their entry to the raft-disrupting agents Nystatin and filipin, and by their intracellular association with caveolin-1, a 22-kDa protein associated with the formation of caveolae in rafts. In contrast, caveolin-marked lipid raft domains do not mediate entry of C. trachomatis serovars A, 36B, and C, nor of LGV serovar L2 and MoPn. Finally, we show that entry of each of these chlamydial strains is independent of cellular expression of caveolin-1. Thus, entry via the Nystatin and filipin-sensitive pathway is dependent on lipid rafts containing cholesterol, rather than invaginated caveolae per se.

  20. Microparticle-Induced Activation of the Vascular Endothelium Requires Caveolin-1/Caveolae.

    Directory of Open Access Journals (Sweden)

    Allison M Andrews

    Full Text Available Microparticles (MPs are small membrane fragments shed from normal as well as activated, apoptotic or injured cells. Emerging evidence implicates MPs as a causal and/or contributing factor in altering normal vascular cell phenotype through initiation of proinflammatory signal transduction events and paracrine delivery of proteins, mRNA and miRNA. However, little is known regarding the mechanism by which MPs influence these events. Caveolae are important membrane microdomains that function as centers of signal transduction and endocytosis. Here, we tested the concept that the MP-induced pro-inflammatory phenotype shift in endothelial cells (ECs depends on caveolae. Consistent with previous reports, MP challenge activated ECs as evidenced by upregulation of intracellular adhesion molecule-1 (ICAM-1 expression. ICAM-1 upregulation was mediated by activation of NF-κB, Poly [ADP-ribose] polymerase 1 (PARP-1 and the epidermal growth factor receptor (EGFR. This response was absent in ECs lacking caveolin-1/caveolae. To test whether caveolae-mediated endocytosis, a dynamin-2 dependent process, is a feature of the proinflammatory response, EC's were pretreated with the dynamin-2 inhibitor dynasore. Similar to observations in cells lacking caveolin-1, inhibition of endocytosis significantly attenuated MPs effects including, EGFR phosphorylation, activation of NF-κB and upregulation of ICAM-1 expression. Thus, our results indicate that caveolae play a role in mediating the pro-inflammatory signaling pathways which lead to EC activation in response to MPs.

  1. Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Hao-yu YUAN; Shuang-yu KUANG; Xing ZHENG; Hong-yan LING; Yun-bo YANG; Peng-ke YAN; Kai LI; Duan-fang LIAO


    Aim: To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. Methods: Morphological changes of atherosclerotic le-sions taken from apoE knockout (apoE-/-) mice were determined by hematoxylin-eosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin-1 was quantified by West-ern blotting. Translocation and the expression of sterol response element-bind-ing protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis. Results: The administration of 20 curcumin to apoE-/1 mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5-fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg.L-1 ox-lipid den-sity lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations (12.5, 25, and 50 μmol.L-1) for different durations (0, 6, 12, 24, and 48 h) significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free choles-terol accompanying the elevation of the caveolin-1 expression level (approximately 3-fold); the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetyl-Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear trans-location of SREBP-1, reduced caveolin-1 expression level, and upregulated cellu-lar lipid levels. Conclusion: Curcumin inhibits ox-LDL-induced cholesterol accu-mulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.

  2. Enhanced Face Recognition using Data Fusion

    Directory of Open Access Journals (Sweden)

    Alaa Eleyan


    Full Text Available In this paper we scrutinize the influence of fusion on the face recognition performance. In pattern recognition task, benefiting from different uncorrelated observations and performing fusion at feature and/or decision levels improves the overall performance. In features fusion approach, we fuse (concatenate the feature vectors obtained using different feature extractors for the same image. Classification is then performed using different similarity measures. In decisions fusion approach, the fusion is performed at decisions level, where decisions from different algorithms are fused using majority voting. The proposed method was tested using face images having different facial expressions and conditions obtained from ORL and FRAV2D databases. Simulations results show that the performance of both feature and decision fusion approaches outperforms the single performances of the fused algorithms significantly.

  3. pcDNA3.1(+)/caveolin-1真核表达质粒的构建及其在MCF-7乳腺癌细胞株中的表达%Construction of pcDNA3.1 (+)/caveolin-1 eukaryotic expression plasmid and its expression in MCF-7 breast cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    马小斌; 康华峰; 包兴; 代志军; 刁岩; 闵卫利; 王西京


    Objective To identify the expression of caveolin-1 in human breast cancer cell line MCF-7 and normal tissues, construct pcDNA3. 1( + )/caveolin-1 expression plasmid and detect its expression. Methods The gene amplification of caveolin-1 in 9 kinds of normal tissues and MCF-7 was detected by RT-PCR; the protein expression of caveolin-1 in MCF-7 cells was detected by Western blotting. Caveolin-1 gene was amplified by RT-PCR with its special primer; PCR products and pcDNA3. 1( + ) plasmid were digested and recycled by EcoR I + Xba I endonuclease, and then pcDNA3. 1 ( + )/caveolin-l recombinant expression plasmid was constructed. The single colonies of pcDNA3. l( + )/caveolin-l were selected and transfected into competent bacteria for PCR identification. Positive colonies were selected and cultured, and restriction endonuclease and sequence identification were carried out. Western blotting was used to detect the protein expression of caveolin-1 in transient transfected MCF-7 cells. Results ① There were gene amplifications of caveolin-1 in all the 9 kinds of normal tissues, but none in MCF-7 cells, so was protein expression. ② When pcDNA3. 1 ( + )/caveolin-1 recombinant expression plasmids were transfected into MCF-7 cells, the caveolin-1 protein was expressed well. Conclusion The pcDNA3. 1( + )/ caveolin-1 recombinant expression plasmid was successfully constructed, and the caveolin-1 protein was expressed stably in transient transfected MCF-7 cells.%目的 明确正常组织和人乳腺癌细胞株MCF-7中caveolin-1的表达情况,构建pcDNA3.1( +)/caveolin-1表达质粒,并鉴定其表达.方法 RT PCR法检测9种正常人体组织及人乳腺癌细胞株MCF-7中caveolin-1基因的扩增情况;Western blotting法检测MCF-7细胞中caveolin-1蛋白的表达情况.设计克隆引物和表达引物,RT-PCR法扩增caveolin-1基因,用EcoRⅠ+XbaⅠ内切酶消化回收PCR产物和质粒pcDNA3.1(+),连接后构建pcDNA3.1(+)/caveolin-1重组表达质粒.挑

  4. 家鸽Caveolin-1基因全长cDNA的克隆、序列和组织表达分析%Cloning and characterization of Caveolin-1 gene in pigeon,Columba livia domestica

    Institute of Scientific and Technical Information of China (English)

    张营; 郁建锋; 杨丽; 王星果; 顾志良


    窖蛋白(Caveolin)是一类构成细胞膜上胞膜窖主要结构的标志蛋白,由Caveolin基因家族编码而成.Caveolin-1基因是Caveolin基因家族的成员之一.该实验采用RT-PCR与RACE(rapid amplification of cDNA ends)技术成功地克隆了家鸽Caveolin-1基因的全长cDNA.该cDNA全长2 605 bp,包含537 bp的完整编码区,编码178个氨基酸;分析发现家鸽Caveolin-1基因编码区与牛、家犬、鸡、褐家鼠等核苷酸同源性为80.1%~93.4%,氨基酸同源性高达85.4%~97.2%;半定量RT-PCR分析表明该基因在家鸽各种组织广泛表达,脂肪中表达量最高,各种肌肉中表达量次之,肝脏中表达量最低.此结果说明家鸽Caveolin-1基因可能与脂肪、肌肉中的某些代谢途径有关.

  5. Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice (United States)

    Sala-Vila, Aleix; Navarro-Lérida, Inmaculada; Sánchez-Alvarez, Miguel; Bosch, Marta; Calvo, Carlos; López, Juan Antonio; Calvo, Enrique; Ferguson, Charles; Giacomello, Marta; Serafini, Annalisa; Scorrano, Luca; Enriquez, José Antonio; Balsinde, Jesús; Parton, Robert G.; Vázquez, Jesús; Pol, Albert; Del Pozo, Miguel A.


    The mitochondria-associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed. PMID:27272971

  6. Reduced caveolin-1 promotes hyper-inflammation due to abnormal heme oxygenase-1 localizationin LPS challenged macrophages with dysfunctional CFTR (United States)

    Zhang, Ping-Xia; Murray, Thomas S.; Villella, Valeria Rachela; Ferrari, Eleonora; Esposito, Speranza; D'Souza, Anthony; Raia, Valeria; Maiuri, Luigi; Krause, Diane S.; Egan, Marie E.; Bruscia, Emanuela M.


    We have previously reported that TLR4 signaling is increased in lipopolysaccharide (LPS) -stimulated Cystic Fibrosis (CF) macrophages (MΦs), contributing to the robust production of pro-inflammatory cytokines. The heme oxygenase (HO-1)/carbon monoxide (CO) pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. Here, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules (CORM2)enhancesCAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations reestablished HO-1 and CAV-1 cell surface localization in CF MΦ's. Consistent with restoration of HO-1/CAV-1 negative regulation of TLR4 signaling, genetic or pharmacological (CORM2)-induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counter-regulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1-dependent mechanism, exacerbating the CF MΦ's response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease. PMID:23606537

  7. Role of caveolin-1 expression in the pathogenesis of pulmonary edema in ventilator-induced lung injury (United States)

    Maniatis, Nikolaos A.; Kardara, Matina; Hecimovich, Dan; Letsiou, Eleftheria; Castellon, Maricela; Roussos, Charalambos; Shinin, Vasily; Votta-Vellis, E. Gina; Schwartz, David E.; Minshall, Richard D.


    Caveolin-1 is a key regulator of pulmonary endothelial barrier function. Here, we tested the hypothesis that caveolin-1 expression is required for ventilator-induced lung injury (VILI). Caveolin-1 gene-disrupted (Cav-1-/-) and age-, sex-, and strain-matched wild-type (WT) control mice were ventilated using two protocols: volume-controlled with protective (8 mL/kg) versus injurious (21 mL/Kg) tidal volume for up to 6 hours; and pressure-controlled with protective (airway pressure = 12 cm H2O) versus injurious (30 cm H2O) ventilation to induce lung injury. Lung microvascular permeability (whole-lung 125I-albumin accumulation, lung capillary filtration coefficient [Kf, c]) and inflammatory markers (bronchoalveolar lavage [BAL] cytokine levels and neutrophil counts) were measured. We also evaluated histologic sections from lungs, and the time course of Src kinase activation and caveolin-1 phosphorylation. VILI induced a 1.7-fold increase in lung 125I-albumin accumulation, fourfold increase in Kf, c, significantly increased levels of cytokines CXCL1 and interleukin-6, and promoted BAL neutrophilia in WT mice. Lung injury by these criteria was significantly reduced in Cav-1-/- mice but fully restored by i.v. injection of liposome/Cav-1 cDNA complexes that rescued expression of Cav-1 in lung microvessels. As thrombin is known to play a significant role in mediating stretch-induced vascular injury, we observed in cultured mouse lung microvascular endothelial cells (MLECs) thrombin-induced albumin hyperpermeability and phosphorylation of p44/42 MAP kinase in WT but not in Cav-1-/- MLECs. Thus, caveolin-1 expression is required for mechanical stretch-induced lung inflammation and endothelial hyperpermeability in vitro and in vivo. PMID:23372929

  8. Effect of FXR on Lipid Metabolism and Caveolin-1 Expression in Hepatocytes%FXR对肝细胞脂质代谢以及Caveolin-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    丁隆; 杨宇; 曲义坤; 夏伟滨; 刘伟新; 张英海; 杨婷; 王凯峰


    [目的]探讨法尼醇X受体(FXR)对肝细胞脂质代谢以及小窝蛋白(Caveolin-1)表达的相关性.[方法]培养肝细胞,分别以10 μmol/L的FXR激动剂 GW4064和100 μmol/L的FXR拮抗剂Guggulsterones干预细胞;RT-PCR和Western blot检测小异二聚体伴侣(SHP)、胆固醇7α-羟化酶(CYP7A1)、胆盐输出泵(BSEP)的表达;试剂盒检测肝细胞中甘油三酯以及胆固醇的水平;Western blot检测Caveolin-1的表达.[结果]与对照组相比FXR激动剂组SHP、BSEP、Caveolin-1表达显著升高(P<0.05),CYP7A1表达显著降低(P<0.05),FXR拮抗剂组SHP、BSEP、Caveolin-1表达显著降低(P<0.05),CYP7A1显著升高(P<0.05).FXR激动剂组甘油三酯水平显著降低,胆固醇含量显著升高,而FXR拮抗剂组甘油三酯显著升高,胆固醇含量显著降低,差异具有统计学意义(P<0.05).[结论]FXR在调控肝细胞代谢中发挥重要作用,并且可能通过对胆固醇代谢的调控影响Caveolin-1的表达.%[Objective] To explore the effect of farnesoid X receptor(FXR) on lipid metabolism and caveolin-1 expression in hepatocytes. [Methods] Hepatocytes were cultured by the treatment with 10μmol/L FXR agonist GW4064 or 100μmol/L FXR antagonist guggulsterones, respectively. The expressions of SHP, CYP7A1 and BSEP were detected by RT-PCR and Western blot. The kit was used to determine the levels of triglyceride and cholesterol in hepatocytes. Western blot was used to detect the expression of caveolin-1. [Results]Compared with control group, the expressions of SHP, BSEP and caveolin-1 markedly increased( P <0.05) and the expression of CYP7A1 markedly decreased in FXR agonist group( P<0. 05). In FXR antagonist group, the expressions of SHP, BSEP and caveolin-1 in decreased markedly( P<0.05), while the expression of CYP7A1 increased marked ly ( P <0. 05). Triglyceride level markedly decreased and cholesterol level markedly increased in FXR agonist group, while riglyceride level markedly increased and cholesterol

  9. Transcriptional repression of Caveolin-1 (CAV1) gene expression by GATA-6 in bladder smooth muscle hypertrophy in mice and human beings. (United States)

    Boopathi, Ettickan; Gomes, Cristiano Mendes; Goldfarb, Robert; John, Mary; Srinivasan, Vittala Gopal; Alanzi, Jaber; Malkowicz, S Bruce; Kathuria, Hasmeena; Zderic, Stephen A; Wein, Alan J; Chacko, Samuel


    Hypertrophy occurs in urinary bladder wall smooth muscle (BSM) in men with partial bladder outlet obstruction (PBOO) caused by benign prostatic hyperplasia (BPH) and in animal models of PBOO. Hypertrophied BSM from the rabbit model exhibits down-regulation of caveolin-1, a structural and functional protein of caveolae that function as signaling platforms to mediate interaction between receptor proteins and adaptor and effector molecules to regulate signal generation, amplification, and diversification. Caveolin-1 expression is diminished in PBOO-induced BSM hypertrophy in mice and in men with BPH. The proximal promoter of the human and mouse caveolin-1 (CAV1) gene was characterized, and it was observed that the transcription factor GATA-6 binds this promoter, causing reduced expression of caveolin-1. Furthermore, caveolin-1 expression levels inversely correlate with the abundance of GATA-6 in BSM hypertrophy in mice and human beings. Silencing of GATA6 gene expression up-regulates caveolin-1 expression, whereas overexpression of GATA-6 protein sustains the transcriptional repression of caveolin-1 in bladder smooth muscle cells. Together, these data suggest that GATA-6 acts as a transcriptional repressor of CAV1 gene expression in PBOO-induced BSM hypertrophy in men and mice. GATA-6-induced transcriptional repression represents a new regulatory mechanism of CAV1 gene expression in pathologic BSM, and may serve as a target for new therapy for BPH-induced bladder dysfunction in aging men.

  10. Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide. (United States)

    Tourkina, Elena; Bonner, Michael; Oates, James; Hofbauer, Ann; Richard, Mathieu; Znoyko, Sergei; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley


    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the

  11. Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide

    Directory of Open Access Journals (Sweden)

    Tourkina Elena


    Full Text Available Abstract Interstitial lung disease (ILD is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc. Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+/collagen I-positive (ColI+, CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12, are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and

  12. Caveolin-1 single nucleotide polymorphism in antineutrophil cytoplasmic antibody associated vasculitis.

    Directory of Open Access Journals (Sweden)

    Sourabh Chand

    Full Text Available OBJECTIVE: Immunosuppression is cornerstone treatment of antineutrophil cytoplasmic antibody associated vasculitis (AAV but is later complicated by infection, cancer, cardiovascular and chronic kidney disease. Caveolin-1 is an essential structural protein for small cell membrane invaginations known as caveolae. Its functional role has been associated with these complications. For the first time, caveolin-1 (CAV1 gene variation is studied in AAV. METHODS: CAV1 single nucleotide polymorphism rs4730751 was analysed in genomic DNA from 187 white patients with AAV from Birmingham, United Kingdom. The primary outcome measure was the composite endpoint of time to all-cause mortality or renal replacement therapy. Secondary endpoints included time to all-cause mortality, death from sepsis or vascular disease, cancer and renal replacement therapy. Validation of results was sought from 589 white AAV patients, from two European cohorts. RESULTS: The primary outcome occurred in 41.7% of Birmingham patients. In a multivariate model, non-CC genotype variation at the studied single nucleotide polymorphism was associated with increased risk from: the primary outcome measure [HR 1.86; 95% CI: 1.14-3.04; p=0.013], all-cause mortality [HR:1.83; 95% CI: 1.02-3.27; p=0.042], death from infection [HR:3.71; 95% CI: 1.28-10.77; p=0.016], death from vascular disease [HR:3.13; 95% CI: 1.07-9.10; p=0.037], and cancer [HR:5.55; 95% CI: 1.59-19.31; p=0.007]. In the validation cohort, the primary outcome rate was far lower (10.4%; no association between genotype and the studied endpoints was evident. CONCLUSIONS: The presence of a CC genotype in Birmingham is associated with protection from adverse outcomes of immunosuppression treated AAV. Lack of replication in the European cohort may have resulted from low clinical event rates. These findings are worthy of further study in larger cohorts.

  13. Image Fusion Techniques for Multispectral Palm Image Enhancement


    Rajashree Bhokare; Deepali Sale; Dr. (Mrs. ) M. A. Joshi; Dr. M. S. Gaikwad


    We proposed the multispectral image enhancement through image fusion by combining the data from the multiple spectrum to address the problem of accuracy and make the system robust against spoofing and to improve the accuracy of recognition, using more discriminating of palm images. Palm line features are clearer in the blue and green bands while red band can reveal some palm vein structure. The NIR band can show the palm vein structure as well as partial line information. Image fusion improve...

  14. Loss of caveolin-1 causes blood-retinal barrier breakdown, venous enlargement, and mural cell alteration. (United States)

    Gu, Xiaowu; Fliesler, Steven J; Zhao, You-Yang; Stallcup, William B; Cohen, Alex W; Elliott, Michael H


    Blood-retinal barrier (BRB) breakdown and related vascular changes are implicated in several ocular diseases. The molecules and mechanisms regulating BRB integrity and pathophysiology are not fully elucidated. Caveolin-1 (Cav-1) ablation results in loss of caveolae and microvascular pathologies, but the role of Cav-1 in the retina is largely unknown. We examined BRB integrity and vasculature in Cav-1 knockout mice and found a significant increase in BRB permeability, compared with wild-type controls, with branch veins being frequent sites of breakdown. Vascular hyperpermeability occurred without apparent alteration in junctional proteins. Such hyperpermeability was not rescued by inhibiting eNOS activity. Veins of Cav-1 knockout retinas exhibited additional pathological features, including i) eNOS-independent enlargement, ii) altered expression of mural cell markers (eg, down-regulation of NG2 and up-regulation of αSMA), and iii) dramatic alterations in mural cell phenotype near the optic nerve head. We observed a significant NO-dependent increase in retinal artery diameter in Cav-1 knockout mice, suggesting that Cav-1 plays a role in autoregulation of resistance vessels in the retina. These findings implicate Cav-1 in maintaining BRB integrity in retinal vasculature and suggest a previously undefined role in the retinal venous system and associated mural cells. Our results are relevant to clinically significant retinal disorders with vascular pathologies, including diabetic retinopathy, uveoretinitis, and primary open-angle glaucoma.

  15. Biomechanical remodeling of the microenvironment by stromal Caveolin-1 favors tumor invasion and metastasis (United States)

    Goetz, Jacky G.; Minguet, Susana; Navarro-Lérida, Inmaculada; Lazcano, Juan José; Samaniego, Rafael; Calvo, Enrique; Tello, Marta; Osteso-Ibáñez, Teresa; Pellinen, Teijo; Echarri, Asier; Cerezo, Ana; Klein-Szanto, Andres J.P.; Garcia, Ricardo; Keely, Patricia J.; Sánchez-Mateos, Paloma; Cukierman, Edna; Del Pozo, Miguel A.


    Summary Mechanotransduction, a key determinant of tissue homeostasis and tumor progression, is driven by intercellular adhesions, cell contractility and forces generated with the microenvironment, dependent on extracellular matrix composition, organization and compliance. Caveolin-1 (Cav1) favors cell elongation in 3D cultures and promotes Rho-and force-dependent contraction, matrix alignment and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1-fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PMID:21729786

  16. Molecular characterization and expression analysis of caveolin-1 in pig tissues

    Institute of Scientific and Technical Information of China (English)


    Members of the caveolin family played important roles during fundamental cellular processes,such as regulation of cell morphology,migration,and gene expression in muscle cells.In this study,caveolin-1 (Cav-1),one of the caveolins,was identified from longissimus dorsi muscle of Large Yorkshire pig and Chinese indigenous Lantang pig based on the results of mRNA differential display analysis.The deduced amino acids sequence of the porcine Cav-1 contained a caveolin domain,and was very conservative among different species.The Cav-1 mRNA was widely expressed in the eight tissues in this study,including heart,liver,kidney,encephalon,spleen,lung,longissimus dorsi muscle,and back fat, and the highest expression quantity was found in back fat of the two pig breeds.The expression quantity of porcine Cav-1 in back fat and longissimus dorsi muscle of Lantang pig was significantly higher than that of Large Yorkshire(P<0.01,and P<0.05,respectively).These results suggested that the Cav-1 might be a candidate gene for carcass traits,and might provide valuable information for understanding the mechanism of caveolae signaling in fat deposition by using the animal model of pig.

  17. Molecular characterization and expression analysis of caveolin-1 in pig tissues

    Institute of Scientific and Technical Information of China (English)

    WANG Chong; MEI YingJie; LI Li; MO DeLin; LI JiaQi; ZHANG Hao; TIAN XingGuo; CHEN YaoSheng


    Members of the caveolin family played important roles during fundamental cellular processes, such as regulation of cell morphology, migration, and gene expression in muscle cells. In this study, caveolin-1 (Cav-1), one of the caveolins, was identified from Iongissimus dorsi muscle of Large Yorkshire pig and Chinese indigenous Lantang pig based on the results of mRNA differential display analysis. The de-duced amino acids sequence of the porcine Cav-1 contained a caveolin domain, and was very conser-vative among different species. The Cav-1 mRNA was widely expressed in the eight tissues in this study, including heart, liver, kidney, encephalon, spleen, lung, Iongissimus dorsi muscle, and back fat, and the highest expression quantity was found in back fat of the two pig breeds. The expression quan-tity of porcine Car-1 in back fat and Iongissimus dorsi muscle of Lantang pig was significantly higher than that of Large Yorkshire (P<0.01, and P<0.05, respectively). These results suggested that the Cav-1 might be a candidate gene for carcass traits, and might provide valuable information for understanding the mechanism of caveolae signaling in fat deposition by using the animal model of pig.

  18. Expression of Caveolin-1 in tongue squamous cell carcinoma by quantum dots

    Directory of Open Access Journals (Sweden)

    J. Xue


    Full Text Available Quantum dots (QDs are a new class of fluorescent probes to detect biomarker expression. The role of caveolin-1 (Cav-1 in tongue squamous cell carcinoma (TSCC is still unknown. This study aimed to investigate the expression profile of Cav-1 in carcinogenesis and development of TSCC by QDs immunofluorescence histochemistry (QDs-IHC and discuss the relationship between the Cav-1 expression and the clinicopathological outcomes. QDs-IHC was used to detect Cav-1 expression in tissue microarrays including normal tongue mucosa (NTM; n=10, hyperplastic tongue mucosa (HTM; n=10, tongue pre-cancer lesions (TPL; n=15 and primary tongue squamous cell carcinoma (PTSCC; n=61. Correlations between the Cav-1 expression and clinicopathologic variables were evaluated statistically. Cells positive for Cav-1 were clearly detected and bright images were obtained in a fine, granular pattern at the cell membrane and cytoplasm using QDs-IHC. The rate of Cav-1 immunoreactivity increased progressively from NTM (0%, HTM (0%, TPL (36% to PTSCC (74%. When compared with each other, there was statistical significance among PTSCC, TPL and NTM as well as among PTSCC, TPL and HTM. Moreover, Cav-1 expression level in PTSCC was correlated positively with clinical stage and histologic grade. QDs-IHC could accurately detect protein location in tongue mucosa. An increased expression of Cav-1 in the stepwise carcinogenesis from NTM, HTM, TPL to PTSCC suggested that Cav-1 might be an oncogene in the development of tongue squamous cell carcinoma.

  19. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma (United States)

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei


    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  20. Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration. (United States)

    Cao, Jingli; Navis, Adam; Cox, Ben D; Dickson, Amy L; Gemberling, Matthew; Karra, Ravi; Bagnat, Michel; Poss, Kenneth D


    In contrast to mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of cardiomyocytes spared from damage. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. Although it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. Here, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin 1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration.

  1. Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2.

    Directory of Open Access Journals (Sweden)

    Christine M Fennessey

    Full Text Available Evidence from multiple studies suggests that Clostridium perfringens ε-toxin is a pore-forming toxin, assembling into oligomeric complexes in the plasma membrane of sensitive cells. In a previous study, we used gene-trap mutagenesis to identify mammalian factors contributing to toxin activity, including caveolin-2 (CAV2. In this study, we demonstrate the importance of caveolin-2 and its interaction partner, caveolin-1 (CAV1, in ε-toxin-induced cytotoxicity. Using CAV2-specific shRNA in a toxin-sensitive human kidney cell line, ACHN, we confirmed that cells deficient in CAV2 exhibit increased resistance to ε-toxin. Similarly, using CAV1-specific shRNA, we demonstrate that cells deficient in CAV1 also exhibit increased resistance to the toxin. Immunoprecipitation of CAV1 and CAV2 from ε-toxin-treated ACHN cells demonstrated interaction of both CAV1 and -2 with the toxin. Furthermore, blue-native PAGE indicated that the toxin and caveolins were components of a 670 kDa protein complex. Although ε-toxin binding was only slightly perturbed in caveolin-deficient cells, oligomerization of the toxin was dramatically reduced in both CAV1- and CAV2-deficient cells. These results indicate that CAV1 and -2 potentiate ε-toxin induced cytotoxicity by promoting toxin oligomerization - an event which is requisite for pore formation and, by extension, cell death.

  2. Caveolin-1 expression level in cancer associated fibroblasts predicts outcome in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Xianda Zhao

    Full Text Available AIMS: Altered expression of epithelial or stromal caveolin-1 (Cav-1 is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs Cav-1 in GC. METHODS AND RESULTS: Quantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM, 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012. Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival. Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features. CONCLUSIONS: Loss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC.

  3. Caveolin-1 Promotes the Imbalance of Th17/Treg in Patients with Chronic Obstructive Pulmonary Disease. (United States)

    Sun, Nina; Wei, Xiaofang; Wang, Jingluan; Cheng, Zhaozhong; Sun, Weihong


    The imbalance of Th17/Treg cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Caveolin-1 (Cav-1) has been regarded as a potential critical regulatory protein in pathological mechanisms of chronic inflammatory respiratory diseases. Therefore, we investigated whether the loss of Cav-1 is involved in the homeostasis of Th17/Treg cells in COPD. We examined the expressions of plasma Cav-1 and circulating Th17, Treg cells, and the related cytokines in patients with COPD. Enzyme-linked immunosorbent assay (ELISA) analyses showed a significant reduction of plasma Cav-1 levels in patients with stable COPD (SCOPD) and acutely exacerbated COPD (AECOPD) compared to smokers without COPD. This loss was associated with an increase in frequency of Treg and decreased in frequency of Th17 cells. To further identify the role of Cav-1, we studied the effects of Cav-1 overexpression or downregulation on frequencies of Treg and Th17 cells in peripheral blood mononuclear cells (PBMCs) from subjects. Interestingly, small interfering RNA (siRNA) downregulation of Cav-1 was accompanied by an augmentation of Treg and reduction of Th17 expression. Together, our study demonstrated that the loss of Cav-1 contributed to the imbalance of Th17/Treg cells in patients with COPD.

  4. Caveolin-1 and ATP binding cassette transporter A1 and G1-mediated cholesterol efflux. (United States)

    Wang, Faqi; Gu, Hong-mei; Zhang, Da-wei


    Atherosclerosis is one major cause of cardiovascular diseases, the leading cause of death in industrialized countries. Reverse cholesterol transport (RCT) is thought to be one primary pathway to protect against atherosclerosis. The first and rate-limiting step of RCT is ATP-binding cassette transport A1 (ABCA1) and ABCG1-mediated cholesterol efflux from the cells. Recently, caveolin-1 (CAV1), a scaffolding protein that organizes and concentrates certain caveolin-interacting signaling molecules and receptors within caveolae membranes, has been shown to regulate ABCA1 and ABCG1-mediated cholesterol efflux probably via interacting with them. In the present review, we summarize the current knowledge and views on the regulatory role of CAV1 on the cholesterol homeostasis with emphasis on the association of CAV1 with ABCA1 and ABCG1. We conclude that the dominance of the positive regulation by CAV1 on the ABCA1 and ABCG1-mediated cholesterol efflux is depending on the species, cell types, as well as the levels of CAV1 expression.

  5. New glimpses of caveolin-1 functions in embryonic development and human diseases

    Institute of Scientific and Technical Information of China (English)

    Saijun MO; Shengli YANG; Zongbin CUI


    Caveolin-1 (Cav-1) isoforms,including Cav-1α and Cav-1β,were identified as integral membrane proteins and the major components of caveolae.Cav-1 proteins are highly conserved during evolution from Caenorhabditis elegans to human and are capable of interacting with many signaling molecules through their caveolin scaffolding domains to regulate the activities of multiple signaling pathways.Thus,Cav-1 plays crucial roles in the regulation of cellular proliferation,differentiation and apoptosis in a cell-specific and contextual manner.In addition,Cav-1 is essential for embryonic development of vertebrates owing to its regulation of BMP,Wnt,TGF-β and other key signaling molecules.Moreover,Cav-1 is mainly expressed in terminally differentiated cells and its abnormal expression is often associated with human diseases,such as tumor progression,cardiovascular diseases,fibrosis,lung regeneration,and diseases related to virus.In this review,we will further discuss the potential of Cav-1 as a target for disease therapy and multiple drug resistance.

  6. The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors



    Objectives: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1) and AT-rich interactive domain 1 alpha (ARID-1A) which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs). Materials and Methods: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ...

  7. Changes of caveolin-1 in the livers of mice with nonalcoholic fatty liver disease caused by highfat diet

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the role of caveolin-1 in nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet.Methods A total of 12 ten-week-old male C57BL/6mice were fed with high-fat and high-cholesterol diet for14 weeks to establish the NAFLD animal model.And six syngeneic mice fed with normal diet at the same time were taken as control.All the mice were sacrificed by

  8. 烟酸对高脂血症兔脂肪组织Caveolin-1mRNA表达的影响%Effect of niacin on Caveolin-1 expression in adipose tissue of hypercholesterolemic rabbits

    Institute of Scientific and Technical Information of China (English)

    李志乐; 徐戈; 雷敏; 欧婷; 王利兵


    Objective To investigate the effect of niacin on caveolin-lexpression in adipose tissue from hypercholesterolemic rabbits. Methods 16 New Zealand white rabbits were fed with high-fat diet for 8 weeks , and then randomly divided into two groups : hyperlipidemia group maintained on high fat diet for 6 weeks ; niacin treatment group:the same fat diet plus niacin [200 mg/(kg-d)] for 6 weeks. Control group was fed with normal diet for 14 weeks. All rabbits were detected the blood lipid and caveolin-1 expression of adipose tissue from groin by FQ-PCR. Results Niacin treatment group showed less serum levels of TC、TG and LDL-C , more level of LDL-C and caveolin-lexpression comparing with hyperlipidemia group. Conclusion Niacin can significantly improve the lipid profile and up-regulate caveolin-lexpression in adipose tissue.%目的:探讨烟酸对高脂血症兔脂肪组织caveolin-1表达的影响.方法:16只健康雄性新西兰大白兔给予高脂饮食8周,随机分为高脂组(继续饲以高脂饲料6周)与烟酸组[在高脂饮食基础上给予烟酸200 mg/(kg·d)6周],另选8只兔予普通饮食14周为正常对照组.实验前后测血脂及采用实时荧光定量PCR检测各组兔腹股沟皮下脂肪组织caveolin-1 mRNA的表达.结果:与高脂组比较,烟酸组TC、TG和LDL-C明显降低,而HDL-C水平明显升高,脂肪组织caveolin-1 mRNA的表达显著升高.结论:烟酸可明显改善血脂谱及上调高脂血症脂肪组织caveolin-1的表达水平.

  9. Static pressure drives proliferation of vascular smooth muscle cells via caveolin-1/ERK1/2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Di-xian, E-mail: [Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Research Center of Life Science, University of South China, Hengyang, Hunan 421001 (China); Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha, Hunan 410083 (China); The First People' s Hospital of Chenzhou City, Chenzhou, Hunan 421001 (China); Cheng, Jiming [Internal Medicine and SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine, 911 N. Rutledge Street, Springfield, IL 62794-9626 (United States); Suzhou Health College of Technology, 20 Shuyuanxiang, Suzhou, Jiangsu 215002 (China); Xiong, Yan [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha, Hunan 410083 (China); Li, Junmo [Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Research Center of Life Science, University of South China, Hengyang, Hunan 421001 (China); Xia, Chenglai [Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Research Center of Life Science, University of South China, Hengyang, Hunan 421001 (China); School of Pharmaceutics, Southern Medical University, Guangzhou, Guangdong 510515 (China); Xu, Canxin; Wang, Chun; Zhu, Bingyang [Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Research Center of Life Science, University of South China, Hengyang, Hunan 421001 (China); Hu, Zhuowei [Institute of Materia Medical, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730 (China); Liao, Duan-fang, E-mail: [Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Research Center of Life Science, University of South China, Hengyang, Hunan 421001 (China)


    Intimal hyperplasia plays an important role in various types of vascular remodeling. Mechanical forces derived from blood flow are associated with the proliferation of vascular smooth muscle cells (VSMC). This contributes to many vascular disorders such as hypertension, atherosclerosis and restenosis after percutaneous transluminal angioplasty (PTA). In this study, we show that static pressure induces the proliferation of VSMC and activates its related signal pathway. VSMC from a rat aorta were treated with different pressures (0, 60, 90, 120, 150 and 180 mm Hg) in a custom-made pressure incubator for 24 h. The most active proliferation of VSMC was detected at a pressure of 120 mm Hg. VSMC was also incubated under a static pressure of 120 mm Hg for different time intervals (0, 2, 4, 8, 12 and 24 h). We found that static pressure significantly stimulates VSMC proliferation. Extracellular signal-regulated kinases 1/2 (ERK1/2) activation showed a peak at the pressure of 120 mm Hg at 4-h time point. Moreover, caveolin-1 expression was significantly inhibited by rising static pressure. Downregulation of VSMC proliferation could be found after PD98059 (ERK1/2 phosphorylation inhibitor) treatment. Our data also showed that a siRNA-mediated caveolin-1 knock down increased ERK1/2 phosphorylation and VSMC proliferation. These results demonstrate that static pressure promotes VSMC proliferation via the Caveolin-1/ERK1/2 pathway.

  10. A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Liu, Yan-Hong [Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang 150081 (China); Li, Yan; Wang, Jia-Ye [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Hattori, Toshio [Department of Emerging Infectious Diseases, Division of Internal Medicine, Graduate School of Medicine, Tohoku University, Sendai 9808574 (Japan); Ling, Hong, E-mail: [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Department of Parasitology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Key Lab of Heilongjiang Province for Infection and Immunity, Key Lab of Heilongjiang Province Education Bureau for Etiology, Harbin, Heilongjiang 150081 (China); Zhang, Feng-Min, E-mail: [Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081 (China); Key Lab of Heilongjiang Province for Infection and Immunity, Key Lab of Heilongjiang Province Education Bureau for Etiology, Harbin, Heilongjiang 150081 (China)


    To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target cell receptors, various cell-cell-fusion assays have been developed. In the present study, we established a novel fusion system. In this system, the expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the target cells was used to evaluate cell fusion event. Simultaneously, constitutively expressed Renilla luciferase (RL) gene was used to monitor effector cell number and viability. FL gave a wider dynamic range than other known reporters and the introduction of RL made the assay accurate and reproducible. This system is especially beneficial for investigation of potential entry-influencing agents, for its power of ruling out the false inhibition or enhancement caused by the artificial cell-number variation. As a case study, we applied this fusion system to observe the effect of a serine protease, thrombin, on HIV Env-mediated cell-cell fusion and have found the fusion enhancement activity of thrombin over two R5-tropic HIV strains.

  11. Caveolin-1 gene silencing promotes the activation of PI3K/AKT dependent on Erα36 and the transformation of MCF10ACE

    Institute of Scientific and Technical Information of China (English)


    ERα36,a variant of estrogen receptor-α,acts as a dominant-negative factor in both estrogen-dependent and estrogen-independent transactivation signaling pathways,and is a key factor in the promotion,progression and prognosis of breast cancers.Caveolin-1,a 22-to 24-kD integral membrane protein,may function as a tumor suppressor in inhibiting of many growth-promoting signaling pathways.It was shown that downregulation of Caveolin-1 strengthens the interaction of ERα and Caveolin-1.In conclusion,Caveolin-1 gene silencing activated the PI3K/AKT signaling pathway in an ERα36-dependent way.Our finding may provide a promising therapeutic target of breast cancer.

  12. Cellular Prion Protein and Caveolin-1 Interaction in a Neuronal Cell Line Precedes Fyn/Erk 1/2 Signal Transduction

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    Mattia Toni


    Full Text Available It has been reported that cellular prion protein (PrPc is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1 participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST-fusion proteins assay, we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11, by confocal microscopy analysis, flotation on density gradient, and coimmunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2 was triggered, suggesting that following translocations from rafts to caveolae or caveolae-like domains PrPc could interact with Cav-1 and induce signal transduction events.

  13. Fusion Enhancement for Neutron-Rich Light Nuclei

    CERN Document Server

    Singh, Varinderjit; Steinbach, T K; Hudan, S; deSouza, R T; Baby, L T; Kuvin, S A; Tripathi, V; Wiedenhover, I


    Measurement of the fusion cross-section for neutron-rich light nuclei is crucial in ascertaining if fusion of these nuclei occurs in the outer crust of a neutron star. The fusion excitation function at near-barrier energies for the $^{19}$O + $^{12}$C system was measured and the experimental results are compared to the fusion excitation function of $^{18}$O + $^{12}$C and $^{16}$O + $^{12}$C. The experiment was performed by utilizing a beam of $^{19}$O, produced via the $^{18}$O(d,p) reaction, to bombard a $^{12}$C target at energies near the Coulomb barrier. Evaporation residues produced in fusion of $^{18,19}$O ions with $^{12}$C target nuclei were detected with good geometric efficiency and identified by measuring their energy and time-of-flight. A significant enhancement is observed in the fusion probability of $^{19}$O ions with a $^{12}$C target as compared to $^{18}$O ions. The larger cross-sections observed at near barrier energies is related to significant narrowing of the fusion barrier indicating a...

  14. Activation of Akt by advanced glycation end products (AGEs: involvement of IGF-1 receptor and caveolin-1.

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    Su-Jung Yang

    Full Text Available Diabetes is characterized by chronic hyperglycemia, which in turn facilitates the formation of advanced glycation end products (AGEs. AGEs activate signaling proteins such as Src, Akt and ERK1/2. However, the mechanisms by which AGEs activate these kinases remain unclear. We examined the effect of AGEs on Akt activation in 3T3-L1 preadipocytes. Addition of AGEs to 3T3-L1 cells activated Akt in a dose- and time-dependent manner. The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(PH oxidase inhibitor DPI, suggesting the involvement of Src and NAD(PH oxidase in the activation of PI3-kinase-Akt pathway by AGEs. AGEs-stimulated Src tyrosine phosphorylation was inhibited by NAC, suggesting that Src is downstream of NAD(PH oxidase. The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R kinase inhibitor AG1024. Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1 levels with siRNAs. Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. These results suggest that AGEs activate NAD(PH oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1

  15. Genetic variation in caveolin-1 correlates with long-term pancreas transplant function. (United States)

    Hamilton, A; Mittal, S; Barnardo, M C N M; Fuggle, S V; Friend, P; Gough, S C L; Simmonds, M J


    Pancreas transplantation is a successful treatment for a selected group of people with type 1 diabetes. Continued insulin production can decrease over time and identifying predictors of long-term graft function is key to improving survival. The aim of this study was to screen subjects for variation in the Caveolin-1 gene (Cav1), previously shown to correlate with long-term kidney transplant function. We genotyped 435 pancreas transplant donors and 431 recipients who had undergone pancreas transplantation at the Oxford Transplant Centre, UK, for all known common variation in Cav1. Death-censored cumulative events were analyzed using Kaplan-Meier and Cox regression. Unlike kidney transplantation, the rs4730751 variant in our pancreas donors or transplant recipients did not correlate with long-term graft function (p = 0.331-0.905). Presence of rs3801995 TT genotype (p = 0.009) and rs9920 CC/CT genotype (p = 0.010) in our donors did however correlate with reduced long-term graft survival. Multivariate Cox regression (adjusted for donor and recipient transplant factors) confirmed the association of rs3801995 (p = 0.009, HR = 1.83;[95% CI = 1.16-2.89]) and rs9920 (p = 0.037, HR = 1.63; [95% CI = 1.03-2.73]) with long-term graft function. This is the first study to provide evidence that donor Cav1 genotype correlates with long-term pancreas graft function. Screening Cav1 in other datasets is required to confirm these pilot results.

  16. Identification, expression pattern, cellular location and potential role of the caveolin-1 gene from Artemia sinica. (United States)

    Li, Xuejie; Yao, Feng; Zhang, Wei; Cheng, Cheng; Chu, Bing; Liu, Yan; Mei, Yanli; Wu, Yang; Zou, Xiangyang; Hou, Lin


    Caveolins are integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Caveolins play an important role in membrane trafficking, signal transduction, substrate transport and endocytosis in differentiated cells. In this study, a caveolin-1 gene from Artemia sinica (As-cav-1) was successfully cloned for the first time. The full-length cDNA of As-cav-1 comprises 974 bp, with a 675 bp open reading frame (ORF) that encodes a polypeptide of 224 amino acids with a caveolin scaffolding domain (CSD) and two transmembrane domains. Multiple sequence alignment revealed that the putative As-CAV-1 protein sequence was relatively conserved across species, especially in the CSD domain. Real-time PCR revealed high levels of the As-cav-1 transcript at 0h of embryo development. Furthermore, As-cav-1 transcripts were highly upregulated under high salinity (200‰) and low temperature stresses (15°C). To further characterize As-cav-1, recombinant pET30a-cav-1 protein was expressed using a prokaryotic expression system. The recombinant protein comprised 290 amino acids with a theoretical molecular weight of 32kDa, and a predicted isoelectric point of 5.6. Western blotting of the expression levels of As-CAV-1 during different embryo development stages revealed that As-CAV-1 levels decreased gradually during development stages from 0 h to 40 h, and increased at 3d. Furthermore, western blotting showed that As-CAV-1 was upregulated to its highest expression level by low temperature stress (15°C) and high salinity. Confocal laser microscopy analysis, using antibodies generated against the recombinant As-CAV-1 protein, showed that As-CAV-1 was mostly located in the cell membrane. Our results suggested that As-cav-1 plays a vital role in protecting embryos from high salt damage and low temperature stress, especially during post-diapause embryonic development.



    Arjun Nelikanti


    Principle objective of Image enhancement is to process an image so that result is more suitable than original image for specific application. Digital image enhancement techniques provide a multitude of choices for improving the visual quality of images. Appropriate choice of such techniques is greatly influenced by the imaging modality, task at hand and viewing conditions. This paper will provide a combination of two concepts, image fusion by DWT and digital image processing techniques. The e...

  18. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kai [Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong Province (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Song, Yong [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Department of Stomatology, Liu Zhou People' s Hospital, Guangxi (China); Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Liu, Ke, E-mail: [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Shang, Zheng-jun, E-mail: [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China)


    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.

  19. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential. (United States)

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-Lin; Liu, Ke; Shang, Zheng-Jun


    Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression.

  20. Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

    Directory of Open Access Journals (Sweden)

    Nils Bohmer


    Full Text Available Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs and silica-coated iron oxide nanoparticles (SCIONs between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

  1. Image fusion for dynamic contrast enhanced magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Leach Martin O


    Full Text Available Abstract Background Multivariate imaging techniques such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI have been shown to provide valuable information for medical diagnosis. Even though these techniques provide new information, integrating and evaluating the much wider range of information is a challenging task for the human observer. This task may be assisted with the use of image fusion algorithms. Methods In this paper, image fusion based on Kernel Principal Component Analysis (KPCA is proposed for the first time. It is demonstrated that a priori knowledge about the data domain can be easily incorporated into the parametrisation of the KPCA, leading to task-oriented visualisations of the multivariate data. The results of the fusion process are compared with those of the well-known and established standard linear Principal Component Analysis (PCA by means of temporal sequences of 3D MRI volumes from six patients who took part in a breast cancer screening study. Results The PCA and KPCA algorithms are able to integrate information from a sequence of MRI volumes into informative gray value or colour images. By incorporating a priori knowledge, the fusion process can be automated and optimised in order to visualise suspicious lesions with high contrast to normal tissue. Conclusion Our machine learning based image fusion approach maps the full signal space of a temporal DCE-MRI sequence to a single meaningful visualisation with good tissue/lesion contrast and thus supports the radiologist during manual image evaluation.

  2. 不同分子区域的Caveolin-1真核表达载体构建及其对Caveolin-1基因敲除小鼠系膜细胞周期的影响%Construction of Caveolin-1 Eukaryotic Expression Plasmid with Different Molecular Regions and the Effect on the Cell Cycle of Caveolin-1 Knockout Mouse Mesangial Cells

    Institute of Scientific and Technical Information of China (English)

    黄丽丽; 张百芳; 叶凤; 伍婷婷; 曹佳; 李小明


    目的:构建含不同分子区域的caveolin-1真核表达质粒,转染caveolin-1基因敲除小鼠(Cav-1-/-)的肾小球系膜细胞,观察能否逆转系膜细胞周期阻滞.方法:首先从pLHCX-N-FLAG2/caveolin-1全长质粒中扩增cave-olin-1 N末端(第1-82位氨基酸)、N末端+脚手架区(第1-101位氨基酸)的cDNA片段,同时在引物两端加上限制性酶切位点Hind Ⅲ及Xho Ⅰ,再与复制缺陷型逆转录病毒表达载体pLHCX-N-FLAG3连接.完成酶切和测序鉴定后将pLHCX-N-FLAG3/cav-1-82和pLHCX-N-FLAG3/cav-1-101分别转染HEK293T细胞,包装产生有感染力的病毒颗粒,再分别感染Car-1-/-系膜细胞,流式细胞分析观察能否逆转细胞周期阻滞.结果:成功构建含caveolin-1 N末端、N末端+脚手架区片段的重组真核表达载体,流式细胞分析发现pLHCX-N-FLAG3/cav-1-82和pLH-CX-N-FLAG3/cav-1-101基因导入Cav-1-/-系膜细胞,可逆转G0/G1细胞周期阻滞.Vcaveolin-1可能主要通过N末端第1-82位氨基酸区域参与细胞周期进程,具体机制还需进一步研究.

  3. 4-cholesten-3-one suppresses lung adenocarcinoma metastasis by regulating translocation of HMGB1, HIF1α and Caveolin-1 (United States)

    Ma, Jinben; Fu, Guobin; Wu, Jing; Han, Shaoxian; Zhang, Lishan; Yang, Ming; Yu, Yong; Zhang, Mengyuan; Lin, Yanliang; Wang, Yibing


    Metastasis is a great challenge in lung adenocarcinoma (ADC) therapy. Cholesterol has been implicated in ADC metastasis. 4-cholesten-3-one, as cholesterol metabolite and analog, can substitute membrane cholesterol and increase membrane fluidity. In this study, we explored the possibility that 4-cholesten-3-one inhibited ADC metastasis. Low-dose 4-cholesten-3-one significantly restrained ADC cells migration and invasion with little effects on cells viabilities. Further investigation showed that 4-cholesten-3-one promoted ROS generation, which transiently activated AMPKα1, increased HIF1α expression, reduced Bcl-2 expression and caused autophagy. AMPKα1 knockdown partly suppressed 4-cholesten-3-one-induced autophagy but, neither prevented 4-cholesten-3-one-induced upregulation of HIF1α or downregulation of Bcl-2. 4-cholesten-3-one-induced autophagy facilitated the release of HMGB1 from nuclei to cytoplasm, blocking nuclear translocation of HIF1α and activation of MMP2 and MMP9. Also, 4-cholesten-3-one induced time-dependent phosphorylation of caveolin-1, Akt and NF-κB. With increasing treatment time, 4-cholesten-3-one accelerated caveolin-1 internalization, but reduced the phosphorylation of Akt and NF-κB, and inhibited the expression of snail and twist. These data suggested that 4-cholesten-3-one could be a potential candidate for anti-metastasis of lung adenocarcinoma. PMID:27899819


    Institute of Scientific and Technical Information of China (English)



    The standard model of sonoluminescence suggests that the coulomb barrer to deuterium fusion may be overcome by high bubble gas temperatures caused by compression heating if the bubble diameter remains spherical during bubble collapse.However,in the more likely collapse geometry of a pancake shape,the temperature rise in the bubbles is negligible.But the collapsing pancake bubble is fund to significantly increase the frequency of the infrared energy available in the vibrational state of the water molecules at ambient temperature.For a collapse to liquied density,ultraviolet radiation at about 10eV is fund.Although the ultraviolet radiation is of a low intensity,higher intensities may be possible if the bubble collapse is enhanced by visible and infrared lases.Neither hot nor cold fusion is predicted in bubble collapse but the ultraviolet energy at about 10eV developed in the bubble is sufficient to provide the basis for a new field of chemistry called ultrasound induced and laser enhanced cold fusion chemistry.

  5. Nerve growth factor blocks the glucose-induced down-regulation of caveolin-1 expression in Schwann cells via p75 neurotrophin receptor signaling. (United States)

    Tan, Wenbin; Rouen, Shefali; Barkus, Kristin M; Dremina, Yelena S; Hui, Dongwei; Christianson, Julie A; Wright, Douglas E; Yoon, Sung Ok; Dobrowsky, Rick T


    Altered neurotrophism in diabetic peripheral neuropathy (DPN) is associated in part with substantial degenerative changes in Schwann cells (SCs) and an increased expression of the p75 neurotrophin receptor (p75NTR). Caveolin-1 (Cav-1) is highly expressed in adult SCs, and changes in its expression can regulate signaling through Erb B2, a co-receptor that mediates the effects of neuregulins in promoting SC growth and differentiation. We examined the hypothesis that hyperglycemia-induced changes in Cav-1 expression and p75NTR signaling may contribute to altered neurotrophism in DPN by modulating SC responses to neuregulins. In an animal model of type 1 diabetes, hyperglycemia induced a progressive decrease of Cav-1 in SCs of sciatic nerve that was reversed by insulin therapy. Treatment of primary neonatal SCs with 20-30 mm d-glucose, but not l-glucose, was sufficient to inhibit transcription from the Cav-1 promoter and decrease Cav-1 mRNA and protein expression. Hyperglycemia prolonged the kinetics of Erb B2 phosphorylation and significantly enhanced the mitogenic response of SCs to neuregulin1-beta1, and this effect was mimicked by the forced down-regulation of Cav-1. Intriguingly, nerve growth factor antagonized the enhanced mitogenic response of SCs to neuregulin1-beta1 and inhibited the glucose-induced down-regulation of Cav-1 transcription, mRNA, and protein expression through p75NTR-dependent activation of JNK. Our data suggest that Cav-1 down-regulation may contribute to altered neurotrophism in DPN by enhancing the response of SCs to neuregulins and that p75NTR-mediated JNK activation may provide a mechanism for the neurotrophic modulation of hyperglycemic stress.

  6. The role of caveolin-1 for carbon black nanoparticles uptake in vitro%Caveolin-1在超微细炭黑颗粒入胞途径中的作用

    Institute of Scientific and Technical Information of China (English)

    余珉; 陈日萍; 贾振宇; 陈钧强; 蒋兆强; 冯玲芳; 张幸


    Objective To investigate the protein expression of caveolin-1 in type Ⅱ alveolar epithelial cells (A549) exposed to carbon black nanoparticles (CB NPs) and the role of caveolin in the endocytosis of CB NPs.Methods A549 cells were exposed to 0,25,50,100,200,and 400 μg/ml CB NPs for 24 h; then,trypan blue assay was applied to determine the cell viability.A549 cells were also exposed to 0,25,50,and 100 μg/ml CB NPs for 24 h,then,transmission electron microscopy (TEM) and flow cytometry were applied to observe the morphological change of cells and cellular side scatter (SSC),and Western blot was used to analyze the effect of CB NPs on the protein expression of caveolin-1.A549 cells were co-exposed to 1 μg/ml filipin and 100 μg/ml CB NPs for 24 h,then,the cellular SSC was observed.Results Compared with controls,the A549 ceils exposed to 200 and 400 μg/ml CB NPs had the cell viability decreased by 38.2% and 46.6%,respectively (P<0.05),while those exposed to 25,50,and 100 μg/ml CB NPs showed no significant decrease in cell vitality (P>0.05).The protein expression of caveolin-1 was significantly higher in the cells exposed to 50 and 100 μg/ml CB NPs than in controls (P<0.05).The TEM showed that plasmalemmal vesicles containing black particles were found in the cytoplasm of the cells exposed to 50 and 100 μg/ml CB NPs.The flow cytometry showed that the cellular SSC ratio increased from 1.007 to 1.331 as the dose of CB NPs rose within 0~100 μg/ml and fell to 1.25 after the cells were co-exposed to 1 μg/ml filipin and 100 μg/ml CB NPs.Conclusion Carbon black nanoparticles can be transferred into A549 cells by endocytosis,but caveolin-mediated endocytic pathway plays a minor role in this process.%目的 探讨超微细炭黑颗粒(Carbon black nanoparticles,CB NPs)对肺泡Ⅱ型上皮细胞(A549)Caveolin-1蛋白的表达的影响及其在入胞过程中的作用.方法 A549细胞接受0、25、50、100、200、400 μg/ml CB NPs染毒24h,

  7. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Di-xian, E-mail: [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); First People' s Hospital of Chenzhou City, Chenzhou 423000, Hunan (China); Xia, Cheng-lai [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Pharmacy, Third Affiliated Hospital Medical College of Guangzhou, Guangzhou 510150, Guangdong (China); Li, Jun-mu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Xiong, Yan [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Yuan, Hao-yu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Lusong Center for Disease Control and Prevention, Zhuzhou 412000, Hunan (China); TANG, Zhen-Wang; Zeng, Yixin [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Liao, Duan-fang, E-mail: [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, Hunan (China)


    Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were

  8. Caveolin-1 directly interacts with UT-A1 urea transporter: the role of caveolae/lipid rafts in UT-A1 regulation at the cell membrane. (United States)

    Feng, Xiuyan; Huang, Haidong; Yang, Yuan; Fröhlich, Otto; Klein, Janet D; Sands, Jeff M; Chen, Guangping


    The cell plasma membrane contains specialized microdomains called lipid rafts which contain high amounts of sphingolipids and cholesterol. Lipid rafts are involved in a number of membrane protein functions. The urea transporter UT-A1, located in the kidney inner medullary collecting duct (IMCD), is important for urine concentrating ability. In this study, we investigated the possible role of lipid rafts in UT-A1 membrane regulation. Using sucrose gradient cell fractionation, we demonstrated that UT-A1 is concentrated in the caveolae-rich fraction both in stably expressing UT-A1 HEK293 cells and in freshly isolated kidney IMCD suspensions. In these gradients, UT-A1 at the cell plasma membrane is codistributed with caveolin-1, a major component of caveolae. The colocalization of UT-A1 in lipid rafts/caveolae was further confirmed in isolated caveolae from UT-A1-HEK293 cells. The direct association of UT-A1 and caveolin-1 was identified by immunoprecipitation and GST pull-down assay. Examination of internalized UT-A1 in pEGFP-UT-A1 transfected HEK293 cells fluorescent overlap with labeled cholera toxin subunit B, a marker of the caveolae-mediated endocytosis pathway. Disruption of lipid rafts by methyl-beta-cyclodextrin or knocking down caveolin-1 by small-interference RNA resulted in UT-A1 cell membrane accumulation. Functionally, overexpression of caveolin-1 in oocytes decreased UT-A1 urea transport activity and UT-A1 cell surface expression. Our results indicate that lipid rafts/caveolae participate in UT-A1 membrane regulation and this effect is mediated via a direct interaction of caveolin-1 with UT-A1.

  9. Metronomic Ceramide Analogs Inhibit Angiogenesis in Pancreatic Cancer through Up-regulation of Caveolin-1 and Thrombospondin-1 and Down-regulation of Cyclin D1

    Directory of Open Access Journals (Sweden)

    Guido Bocci


    Full Text Available AIMS: To evaluate the antitumor and antiangiogenic activity of metronomic ceramide analogs and their relevant molecular mechanisms. METHODS: Human endothelial cells [human dermal microvascular endothelial cells and human umbilical vascular endothelial cell (HUVEC] and pancreatic cancer cells (Capan-1 and MIA PaCa-2 were treated with the ceramide analogs (C2, AL6, C6, and C8, at low concentrations for 144 hours to evaluate any antiproliferative and proapoptotic effects and inhibition of migration and to measure the expression of caveolin-1 (CAV-1 and thrombospondin-1 (TSP-1 mRNAs by real-time reverse transcription-polymerase chain reaction. Assessment of extracellular signal-regulated kinases 1 and 2 (ERK1/2 and Akt phosphorylation and of CAV-1 and cyclin D1 protein expression was performed by ELISA. Maximum tolerated dose (MTD gemcitabine was compared against metronomic doses of the ceramide analogs by evaluating the inhibition of MIA PaCa-2 subcutaneous tumor growth in nude mice. RESULTS: Metronomic ceramide analogs preferentially inhibited cell proliferation and enhanced apoptosis in endothelial cells. Low concentrations of AL6 and C2 caused a significant inhibition of HUVEC migration. ERK1/2 and Akt phosphorylation were significantly decreased after metronomic ceramide analog treatment. Such treatment caused the overexpression of CAV-1 and TSP-1 mRNAs and proteins in endothelial cells, whereas cyclin D1 protein levels were reduced. The antiangiogenic and antitumor impact in vivo of metronomic C2 and AL6 regimens was similar to that caused by MTD gemcitabine. CONCLUSIONS: Metronomic C2 and AL6 analogs have antitumor and antiangiogenic activity, determining the up-regulation of CAV-1 and TSP-1 and the suppression of cyclin D1.

  10. HALO: a reconfigurable image enhancement and multisensor fusion system (United States)

    Wu, F.; Hickman, D. L.; Parker, Steve J.


    Contemporary high definition (HD) cameras and affordable infrared (IR) imagers are set to dramatically improve the effectiveness of security, surveillance and military vision systems. However, the quality of imagery is often compromised by camera shake, or poor scene visibility due to inadequate illumination or bad atmospheric conditions. A versatile vision processing system called HALO™ is presented that can address these issues, by providing flexible image processing functionality on a low size, weight and power (SWaP) platform. Example processing functions include video distortion correction, stabilisation, multi-sensor fusion and image contrast enhancement (ICE). The system is based around an all-programmable system-on-a-chip (SoC), which combines the computational power of a field-programmable gate array (FPGA) with the flexibility of a CPU. The FPGA accelerates computationally intensive real-time processes, whereas the CPU provides management and decision making functions that can automatically reconfigure the platform based on user input and scene content. These capabilities enable a HALO™ equipped reconnaissance or surveillance system to operate in poor visibility, providing potentially critical operational advantages in visually complex and challenging usage scenarios. The choice of an FPGA based SoC is discussed, and the HALO™ architecture and its implementation are described. The capabilities of image distortion correction, stabilisation, fusion and ICE are illustrated using laboratory and trials data.


    Institute of Scientific and Technical Information of China (English)

    Li Jing; Yang Tao; Pan Quan; Cheng Yongmei


    This paper presents a video context enhancement method for night surveillance. The basic idea is to extract and fuse the meaningful information of video sequence captured from a fixed camera under different illuminations. A unique characteristic of the algorithm is to separate the image context into two classes and estimate them in different ways. One class contains basic surrounding scene information and scene model, which is obtained via background modeling and object tracking in daytime video sequence. The other class is extracted from nighttime video, including frequently moving region, high illumination region and high gradient region. The scene model and pixel-wise difference method are used to segment the three regions. A shift-invariant discrete wavelet based image fusion technique is used to integral all those context information in the final result. Experiment results demonstrate that the proposed approach can provide much more details and meaningful information for nighttime video.

  12. Caveolin-1敲除对C57BL/6小鼠繁殖性能及 子代离乳前体质量的影响%Effect of Caveolin-1 knockout on weight and reproductive performance before weaning in C57BL/6 mice

    Institute of Scientific and Technical Information of China (English)

    俞悦; 易健; 蔡光先; 刘柏炎


    目的 探讨小窝蛋白Caveolin-1敲除对C57BL/6小鼠离乳前繁殖性能及体质量的影响.方法 分别对Caveolin-1基因敲除小鼠和同源C57小鼠进行体质量、初产日龄、胎次间隔时间、平均产仔数及离乳存活率的观察及分析.结果 C57BL/6小鼠鼠仔平均体质量均高于Caveolin-1基因敲除鼠,在1、7、14 d时两者比较差异无统计学意义(P>0.05);21 d时,两者差异具有统计学意义(P<0.05);两组初产日龄、胎次间隔时间及平均产仔数差异无统计学意义(P>0.05),但C57BL/6小鼠离乳存活率明显高于基因敲除鼠,两者差异具有统计学意义(P<0.05).结论 Caveolin-1敲除小鼠的体质量下降、繁殖性能下降.%Objective evaluate the effects of Caveolin-1 knockout on weight and reproductive performance before weaning in C57BI76 mice. Methods The growth curves, primiparous age, parity time interval, the average litter sizes and weaning survival were observed and analyzed respectively in caveolin-1 knockout mice and C57 mice homologous. Results The average body weight of C57BL/6 newborn mice were higher than that of Caveolin-1 knockout mice in 1st, 7th and 14th days, but there were no significant differences (P>0.05); in 21st day, the difference was significant (P<0.05); the primiparous age, parity, litter size and the average interval between the two was no significant difference (P>0.05), but the survival rate of C57BL/6 mice was significantly higher than that of knockout mice(P<0.05). Conclusion Caveolin-1 knockout can slow the growth and decrease the reproductive ability of C57BL/6 mice.

  13. Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p RequirementD⃞


    Tedrick, Kelly; Trischuk, Tim; Lehner, Richard; Eitzen, Gary


    Organization of lipids into membrane microdomains is a vital mechanism of protein processing. Here we show that overexpression of ERG6, a gene involved in ergosterol synthesis, elevates sterol levels 1.5-fold on the vacuole membrane and enhances their homotypic fusion. The mechanism of sterol-enhanced fusion is not via more efficient sorting, but instead promotes increased kinetics of fusion subreactions. We initially isolated ERG6 as a suppressor of a vrp1Δ growth defect selective for vacuol...

  14. 弓形虫速殖子入侵对宿主细胞窖蛋白-1的表达变化%Study on the Change of Caveolin-1 During the Invasion of Toxoplasma gondii

    Institute of Scientific and Technical Information of China (English)

    覃珊珊; 汪琦; 朱家勇; 江钢锋; 李娟兰


    Caveolae is a specific invagination mini-district, and caveolin-1 is a marker protein of caveolae. Our work focus on the expression change of caveolin-1 during the invasive process for the further study on the control and treatment of Toxoplasmosis. Based on gene sequence of caveolin-1 in GenBank, we designed primers for RT-PCR and real-time PCR to detect the changes of the expression of caveolin-1 at 10 min, 30 min and 60 min after invasion of Toxoplasma gondii into the host cells. The results showed that the expression of caveolin-1 was positive correlation with the concentration of the parasites. With the increase of the parasites, the expression of caveolin-1 increased, and also with the increase of infection times, it showed an increasing tendency. It was concluded that caveolin 1 may participate the process of T. gondii initiative invasion.%胞膜窖Caveolae,又称细胞膜穴样凹陷,是细胞表面特异性的内陷微区,Caveolin-1是其的标记蛋白.Caveolae结构和caveolin蛋白在多种细胞生理功能方面如细胞信号转导、胆固醇转运、内吞和肿瘤抑制等发挥着重要作用.在动脉硬化、肌营养不良和Alzheimer'S综合征等多种疾病中均发现存在caveolae和caveolin的异常.作者根据GenBank中caveolin-1的基因序列设计引物,RT-PCR和实时荧光定量PCR检测不同数量的弓形虫速殖子入侵Hela细胞10、30和60 min时,caveolin-1的表达变化.结果显示弓形虫入侵宿主细胞后caveolin-1的表达与虫体的浓度呈正相关,即caveolin-1的表达量随虫体浓度的增加而升高,并随着感染时间的延长而呈增加趋势.推测宿主细胞可能参与了弓形虫的主动入侵过程,研究结果将为深入研究弓形虫致病机制奠定基础.

  15. Fusion

    CERN Document Server

    Mahaffey, James A


    As energy problems of the world grow, work toward fusion power continues at a greater pace than ever before. The topic of fusion is one that is often met with the most recognition and interest in the nuclear power arena. Written in clear and jargon-free prose, Fusion explores the big bang of creation to the blackout death of worn-out stars. A brief history of fusion research, beginning with the first tentative theories in the early 20th century, is also discussed, as well as the race for fusion power. This brand-new, full-color resource examines the various programs currently being funded or p

  16. Human melanoma cells express FGFR/Src/Rho signaling that entails an adhesion-independent caveolin-1 membrane association. (United States)

    Fecchi, Katia; Travaglione, Sara; Spadaro, Francesca; Quattrini, Adriano; Parolini, Isabella; Piccaro, Giovanni; Raggi, Carla; Fabbri, Alessia; Felicetti, Federica; Carè, Alessandra; Fiorentini, Carla; Sargiacomo, Massimo


    Caveolae have been indicated as a center of cytoskeleton regulation for Src kinase/Rho GTPase signaling. In addition, Src recruitment on intact cortical actin cytoskeleton appears to be required for bFGF/FGFR signal activation. Recently, we established a relationship between caveolin-1 (Cav-1) expression and cell migration in human malignant melanoma, constitutively activated by a bFGF autoregulatory loop. This work intends to investigate whether caveolae's asset, through bFGF/FGFR/c-Src/Rho signaling, could be related to melanoma cell anchorage. Accordingly, we revealed the existence of a FGFR/Src kinase pathway in Cav-1 enriched detergent-resistant membranes (DRMs) of Me665/1 metastatic melanoma cells, as confirmed by FGFR silencing. Moreover, we determined the expression and phosphorylation levels of Cav-1/Src/Erk signal pathway as a function of FGFR activation and cell density. A sucrose density gradient ultracentrifugation was employed to monitor Cav-1 membrane association and buoyancy in Me665/1 cells treated for actin fragmentation or for altered phosphorylation signals. As a result, melanoma cells show remarkable resistance to Cav-1 disassembly, together with persisting cell signal activity, being Src and Cav-1 crucial modulators of Rho GTPases. In conclusion, our study primarily highlights, in a metastatic melanoma cell line expressing caveolin, the circumstances whereby caveola structural and functional endurance enables the FGFR/Src/Rho GTPases pathway to keep on cell progression.

  17. DJ-1 deficiency impairs glutamate uptake into astrocytes via the regulation of flotillin-1 and caveolin-1 expression (United States)

    Kim, Jin-Mo; Cha, Seon-Heui; Choi, Yu Ree; Jou, Ilo; Joe, Eun-Hye; Park, Sang Myun


    Parkinson’s disease (PD) is a common chronic and progressive neurodegenerative disorder. Although the cause of PD is still poorly understood, mutations in many genes including SNCA, parkin, PINK1, LRRK2, and DJ-1 have been identified in the familial forms of PD. It was recently proposed that alterations in lipid rafts may cause the neurodegeneration shown in PD. Here, we observe that DJ-1 deficiency decreased the expression of flotillin-1 (flot-1) and caveolin-1 (cav-1), the main protein components of lipid rafts, in primary astrocytes and MEF cells. As a mechanism, DJ-1 regulated flot-1 stability by direct interaction, however, decreased cav-1 expression may not be a direct effect of DJ-1, but rather as a result of decreased flot-1 expression. Dysregulation of flot-1 and cav-1 by DJ-1 deficiency caused an alteration in the cellular cholesterol level, membrane fluidity, and alteration in lipid rafts-dependent endocytosis. Moreover, DJ-1 deficiency impaired glutamate uptake into astrocytes, a major function of astrocytes in the maintenance of CNS homeostasis, by altering EAAT2 expression. This study will be helpful to understand the role of DJ-1 in the pathogenesis of PD, and the modulation of lipid rafts through the regulation of flot-1 or cav-1 may be a novel therapeutic target for PD. PMID:27346864

  18. The activity of the epithelial sodium channels is regulated by caveolin-1 via a Nedd4-2-dependent mechanism. (United States)

    Lee, Il-Ha; Campbell, Craig R; Song, Sung-Hee; Day, Margot L; Kumar, Sharad; Cook, David I; Dinudom, Anuwat


    It has recently been shown that the epithelial Na(+) channel (ENaC) is compartmentalized in caveolin-rich lipid rafts and that pharmacological depletion of membrane cholesterol, which disrupts lipid raft formation, decreases the activity of ENaC. Here we show, for the first time, that a signature protein of caveolae, caveolin-1 (Cav-1), down-regulates the activity and membrane surface expression of ENaC. Physical interaction between ENaC and Cav-1 was also confirmed in a coimmunoprecipitation assay. We found that the effect of Cav-1 on ENaC requires the activity of Nedd4-2, a ubiquitin protein ligase of the Nedd4 family, which is known to induce ubiquitination and internalization of ENaC. The effect of Cav-1 on ENaC requires the proline-rich motifs at the C termini of the beta- and gamma-subunits of ENaC, the binding motifs that mediate interaction with Nedd4-2. Taken together, our data suggest that Cav-1 inhibits the activity of ENaC by decreasing expression of ENaC at the cell membrane via a mechanism that involves the promotion of Nedd4-2-dependent internalization of the channel.

  19. Ceramide displaces cholesterol from lipid rafts and decreases the association of the cholesterol binding protein caveolin-1. (United States)

    Yu, Cuijuan; Alterman, Michail; Dobrowsky, Rick T


    Addition of exogenous ceramide causes a significant displacement of cholesterol in lipid raft model membranes. However, whether ceramide-induced cholesterol displacement is sufficient to alter the protein composition of caveolin-enriched lipid raft membranes is unknown. Therefore, we examined whether increasing endogenous ceramide levels with bacterial sphingomyelinase (bSMase) depleted cholesterol and changed the protein composition of caveolin-enriched membranes (CEMs) isolated from immortalized Schwann cells. bSMase increased ceramide levels severalfold and decreased the cholesterol content of detergent-insoluble CEMs by 25-50% within 2 h. To examine the effect of ceramide on the protein composition of the CEMs, we performed a quantitative proteomic analysis using stable isotope labeling of cells in culture and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Although ceramide rapidly depleted lipid raft cholesterol, the levels of the cholesterol binding protein caveolin-1 (Cav-1) decreased by 25% only after 8 h. Importantly, replenishing the cells with cholesterol rapidly reversed the loss of Cav-1 from the CEMs. Ceramide-induced cholesterol depletion increased the association of 5'-nucleotidase and ATP synthase beta-subunit with the CEMs but had a minimal effect on changing the abundance of other lipid raft proteins, such as flotillin-1 and G-proteins. These results suggest that the ceramide-induced loss of cholesterol from CEMs may contribute to altering the lipid raft proteome.

  20. 姜黄素对巨噬细胞源性荷脂细胞胆固醇水平及caveolin-1表达的影响%The Effect of Curcumin on the Cholesterol Metabolism and the Expression of Caveolin-1 in Macrophage-derived Cholesterol-load Cell

    Institute of Scientific and Technical Information of China (English)

    李熠; 匡双玉; 王北冰; 尹凯; 沈元琼; 桂庆军


    目的 观察姜黄素对巨噬细胞源性荷脂细胞胆固醇水平的影响,并初步探讨caveolin-1蛋白表达在其中的作用. 方法实验分组分为正常巨噬细胞组、巨噬细胞源性荷脂细胞组和姜黄素处理组.3组均采用油红O染色检测细胞荷脂情况,高效液相色谱分析法检测细胞内胆固醇含量,Western印迹法检测caveolin-1蛋白的表达. 结果姜黄素作用于巨噬细胞源性荷脂细胞,细胞内总胆固醇、游离胆固醇和胆固醇酯含量均下降;caveolin-1蛋白表达上调. 结论姜黄素引起巨噬细胞源性荷脂细胞胆固醇含量下降的同时,caveolin-1蛋白表达上调.

  1. Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Yan Qiu; Shan Liu; Hong-Tan Chen; Chao-Hui Yu; Xiao-Dong Teng; Hong-Tian Yao and Guo-Qiang Xu


    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver diseases, with markedly increased prevalence. However, its mechanisms are not clear. The present study was undertaken to illustrate the role of caveolin-1 (cav1) and the scavenger receptor class B type 1 (SR-B1) in NAFLD. METHODS: Adult male C57BL/6 mice were fed with a normal diet  or  high  fat  and  cholesterol  (HFC)  diet  for  14  weeks.  The mice  were  sacrificed  to  collect  plasma  and  harvest  the  liver; their  plasma  lipid  concentration  was  measured.  Hepatic  cav1 and SR-B1 mRNA and protein expression were determined by real-time  quantitative  polymerase  chain  reaction  (qPCR)  and Western blotting, respectively. In order to study cav1 and SR-B1 distribution and change in hepatocytes, immunohistochemical analysis was performed. RESULTS: HFC diet increased plasma lipids, induced NAFLD and  increased  the  liver/body  weight  ratio.  Compared  to  the control mice (n=6), the mRNA and protein levels of cav1 and SR-B1  in  liver  tissue  of  the  NAFLD  mice  (n=12)  increased significantly (cav1 mRNA: 1.536±0.226 vs 0.980±0.272, P CONCLUSION: NAFLD  is  associated  with  increased  concen-tration  of  plasma  lipids  and  upregulation  of  hepatic  cav1  and SR-B1 gene and protein expressions, which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.

  2. Effect of TNF-Alpha on Caveolin-1 Expression and Insulin Signaling During Adipocyte Differentiation and in Mature Adipocytes

    Directory of Open Access Journals (Sweden)

    Sara Palacios-Ortega


    Full Text Available Background/Aims: Tumor necrosis factor-α (TNF-α-mediated chronic low-grade inflammation of adipose tissue is associated with obesity and insulin resistance. Caveolin-1 (Cav-1 is the central component of adipocyte caveolae and has an essential role in the regulation of insulin signaling. The effects of TNF-α on Cav-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes were studied. Methods: 3T3-L1 cells were differentiated (21 days in the presence TNF-α (10 ng/mL and mature adipocytes were also treated with TNF-α for 48 hours. Cav-1 and insulin receptor (IR gene methylation were determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake was measured by the 2-[C14]-deoxyglucose uptake assay. Results: TNF-α slowed down the differentiation program, hindering the expression of some insulin signaling intermediates without fully eliminating insulin-mediated glucose uptake. In mature adipocytes, TNF-α did not compromise lipid-storage capacity, but downregulated the expression of the insulin signaling intermediates, totally blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the level of activated phospho-Cav-1 in both situations, strongly suggesting the direct contribution of Cav-1 to the maintenance of this physiological response. Conclusion: Cav-1 activation by phosphorylation seems to be essential for the maintenance of an active and insulin-sensitive glucose uptake.

  3. The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors

    Directory of Open Access Journals (Sweden)

    Duygu Ayaz


    Full Text Available Objectives: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1 and AT-rich interactive domain 1 alpha (ARID-1A which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs. Materials and Methods: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ARID-1A were performed. Results: In this series, there were 10 leiomyosarcomas (LMSs, 10 uterine smooth muscle tumors of uncertain malignant potentials (STUMPs, and 10 leiomyomas (LMs. Cav-1 expression located cytoplasmic or perivascular area. Cytoplasmic Cav-1 expression was determined in 5 LMSs and 2 STUMPs while perivascular Cav-1 expression was determined in 9 LMSs and 2 STUMPs. Statistically, it was determined that if the tumor becomes malignant and more invasive, it gains the perivascular Cav-1 expression (P = 0.029. On the other hand, the mean nuclear staining rate for ARID-1A in LMSs (63 ± 23.4% was higher than both STUMPs (60 ± 18.5% and LMs (34.5 ± 16.5%. Statistically, it was determined that the expression of ARID-1A was significantly downregulated in LMs when compared with STUMPs and LMSs (P = 0.004. Conclusions: Our findings were demonstrated that perivascular Cav-1 expression was seen to be a marker for malignancy of uterine SMTs. Similarly, we found to link of ARID-1A expression and the aggressiveness of SMTs. Therefore, it may be suggested that Cav-1 and ARID-1A may act as predictive biomarkers in uterine SMTs.

  4. Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles. (United States)

    Umesalma, Shaikamjad; Houwen, Frederick Keith; Baumbach, Gary L; Chan, Siu-Lung


    Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1-induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy.

  5. Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60 cells. (United States)

    Ma, Wei; Wang, Di-Di; Li, Li; Feng, Yu-Kuan; Gu, Hong-Mei; Zhu, Gui-Ming; Piao, Jin-Hua; Yang, Yu; Gao, Xu; Zhang, Peng-Xia


    Our previous study found that caveolin-1 (CAV-1) protein expression is upregulated during oleanolic acid (OA)-induced inhibition of proliferation and promotion of apoptosis in HL-60 cells. CAV-1 is the main structural protein component of caveolae, playing important roles in tumorigenesis and tumor development. It has been shown that cav-1 expression is lower in leukemia cancer cell lines SUP-B15, HL-60, THP-1 and K562 and in chronic lymphocytic leukemia primary (CLP) cells when compared with normal white blood cells, with the lowest cav-1 expression level found in HL-60 cells. To study the effects of cav-1 in HL-60 cells and the effects of cav-1 overexpression on OA drug efficacy, cav-1 was overexpressed in HL-60 cells using lentiviral-mediated transfection combined with OA treatment. The results showed that cav-1 overexpression inhibited HL-60 cell proliferation, promoted apoptosis, arrested the cell cycle in the G1 phase and inhibited activation of the PI3K/AKT/mTOR signaling pathway. Overexpression of CAV-1 also increased HL-60 cell sensitivity to OA. To further verify whether OA affects HL-60 cells via the activation of downstream signaling pathways by CAV-1, cav-1 gene expression was silenced using RNAi, and the cells were treated with OA to examine its efficacy. The results showed that after cav-1 silencing, OA had little effect on cell activity, apoptosis, the cell cycle and phosphorylation of HL-60 cells. This study is the first to show that CAV-1 plays a crucial role in the effects of OA on HL-60 cells.

  6. A compensatory mutation provides resistance to disparate HIV fusion inhibitor peptides and enhances membrane fusion.

    Directory of Open Access Journals (Sweden)

    Matthew P Wood

    Full Text Available Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations.

  7. Feature Fusion Approach on Keystroke Dynamics Efficiency Enhancement

    Directory of Open Access Journals (Sweden)

    Pin Shen Teh


    Full Text Available In this paper we study the performance and effect of diverse keystroke feature combinations on keystroke dynamics authentication system by using fusion approach. First of all, four types of keystroke features are acquired from our collected dataset, later then transformed into similarity scores by using Gaussian Probability Density Function (GPD and Direction Similarity Measure (DSM. Next, three fusion approaches are introduced to merge the scores pairing with different combinations of fusion rules. Result shows that the finest performance is obtained by the combination of both dwell time and flight time collectively. Finally, this experiment also investigates the effect of using larger dataset on recognition performance, which turns out to be rather consistent.

  8. Affection of ApoE Gene-deficiency on the Expression of Caveolin-1 in the Wall of Artery%载脂蛋白E基因缺陷对小鼠主动脉壁caveolin-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    许灿新; 王春; 秦旭平; 朱炳阳; 廖端芳



  9. Hybrid Image Fusion for Sharpness Enhancement of Multi-Spectral Lunar Images (United States)

    Awumah, Anna; Mahanti, Prasun; Robinson, Mark


    Image fusion enhances the sharpness of a multi-spectral (MS) image by incorporating spatial details from a higher-resolution panchromatic (Pan) image [1,2]. Known applications of image fusion for planetary images are rare, although image fusion is well-known for its applications to Earth-based remote sensing. In a recent work [3], six different image fusion algorithms were implemented and their performances were verified with images from the Lunar Reconnaissance Orbiter (LRO) Camera. The image fusion procedure obtained a high-resolution multi-spectral (HRMS) product from the LRO Narrow Angle Camera (used as Pan) and LRO Wide Angle Camera (used as MS) images. The results showed that the Intensity-Hue-Saturation (IHS) algorithm results in a high-spatial quality product while the Wavelet-based image fusion algorithm best preserves spectral quality among all the algorithms. In this work we show the results of a hybrid IHS-Wavelet image fusion algorithm when applied to LROC MS images. The hybrid method provides the best HRMS product - both in terms of spatial resolution and preservation of spectral details. Results from hybrid image fusion can enable new science and increase the science return from existing LROC images.[1] Pohl, Cle, and John L. Van Genderen. "Review article multisensor image fusion in remote sensing: concepts, methods and applications." International journal of remote sensing 19.5 (1998): 823-854.[2] Zhang, Yun. "Understanding image fusion." Photogramm. Eng. Remote Sens 70.6 (2004): 657-661.[3] Mahanti, Prasun et al. "Enhancement of spatial resolution of the LROC Wide Angle Camera images." Archives, XXIII ISPRS Congress Archives (2016).

  10. Novel spinal instrumentation to enhance osteogenesis and fusion: a preliminary study. (United States)

    MacEwan, Matthew R; Talcott, Michael R; Moran, Daniel W; Leuthardt, Eric C


    OBJECTIVE Instrumented spinal fusion continues to exhibit high failure rates in patients undergoing multilevel lumbar fusion or pseudarthrosis revision; with Grade II or higher spondylolisthesis; or in those possessing risk factors such as obesity, tobacco use, or metabolic disorders. Direct current (DC) electrical stimulation of bone growth represents a unique surgical adjunct in vertebral fusion procedures, yet existing spinal fusion stimulators are not optimized to enhance interbody fusion. To develop an advanced method of applying DC electrical stimulation to promote interbody fusion, a novel osteogenic spinal system capable of routing DC through rigid instrumentation and into the vertebral bodies was fabricated. A pilot study was designed to assess the feasibility of osteogenic instrumentation and compare the ability of osteogenic instrumentation to promote successful interbody fusion in vivo to standard spinal instrumentation with autograft. METHODS Instrumented, single-level, posterior lumbar interbody fusion (PLIF) with autologous graft was performed at L4-5 in adult Toggenburg/Alpine goats, using both osteogenic spinal instrumentation (plus electrical stimulation) and standard spinal instrumentation (no electrical stimulation). At terminal time points (3 months, 6 months), animals were killed and lumbar spines were explanted for radiographic analysis using a SOMATOM Dual Source Definition CT Scanner and high-resolution Microcat II CT Scanner. Trabecular continuity, radiodensity within the fusion mass, and regional bone formation were examined to determine successful spinal fusion. RESULTS Quantitative analysis of average bone density in pedicle screw beds confirmed that electroactive pedicle screws used in the osteogenic spinal system focally enhanced bone density in instrumented vertebral bodies. Qualitative and quantitative analysis of high-resolution CT scans of explanted lumbar spines further demonstrated that the osteogenic spinal system induced solid

  11. Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide-High Angiotensin II-Induced Cardiovascular Injury. (United States)

    Pojoga, Luminita H; Yao, Tham M; Opsasnick, Lauren A; Siddiqui, Waleed T; Reslan, Ossama M; Adler, Gail K; Williams, Gordon H; Khalil, Raouf A


    Aldosterone interacts with mineralocorticoid receptor (MR) to stimulate sodium reabsorption in renal tubules and may also affect the vasculature. Caveolin-1 (cav-1), an anchoring protein in plasmalemmal caveolae, binds steroid receptors and also endothelial nitric oxide synthase, thus limiting its translocation and activation. To test for potential MR/cav-1 interaction in the vasculature, we investigated if MR blockade in cav-1-replete or -deficient states would alter vascular function in a mouse model of low nitric oxide (NO)-high angiotensin II (AngII)-induced cardiovascular injury. Wild-type (WT) and cav-1 knockout mice (cav-1(-/-)) consuming a high salt diet (4% NaCl) received Nω-nitro-l-arginine methyl ester (L-NAME) (0.1-0.2 mg/ml in drinking water at days 1-11) plus AngII (0.7-2.8 mg/kg per day via an osmotic minipump at days 8-11) ± MR antagonist eplerenone (EPL) 100 mg/kg per day in food. In both genotypes, blood pressure increased with L-NAME + AngII. EPL minimally changed blood pressure, although its dose was sufficient to block MR and reverse cardiac expression of the injury markers cluster of differentiation 68 and plasminogen activator inhibitor-1 in L-NAME+AngII treated mice. In aortic rings, phenylephrine and KCl contraction was enhanced with EPL in L-NAME+AngII treated WT mice, but not cav-1(-/-) mice. AngII-induced contraction was not different, and angiotensin type 1 receptor expression was reduced in L-NAME + AngII treated WT and cav-1(-/-) mice. In WT mice, acetylcholine-induced relaxation was enhanced with L-NAME + AngII treatment and reversed with EPL. Acetylcholine relaxation in cav-1(-/-) mice was greater than in WT mice, not modified by L-NAME + AngII or EPL, and blocked by ex vivo L-NAME, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or endothelium removal, suggesting the role of NO-cGMP. Cardiac endothelial NO synthase was increased in cav-1(-/-) versus WT mice, further increased with L-NAME + AngII, and not affected by EPL

  12. Enhancement of fusion at near and sub-barrier energies for neutron-rich light nuclei

    CERN Document Server

    Singh, Varinderjit; Steinbach, T K; Wiggins, B B; Hudan, S; Lin, R T deSouza Zidu; Horowitz, C J; Baby, L T; Kuvin, S A; Tripathi, Vandana; Wiedenhover, I


    Measurement of the fusion cross-section for neutron-rich light nuclei is crucial in ascertaining if fusion of these nuclei occurs in the outer crust of a neutron star. We have therefore measured the fusion excitation function at near-barrier energies for the 19O + 12C system and compared the experimental results with the fusion excitation function of 18O + 12C and 16O + 12C. In the experiment a beam of 19O, produced via the 18O(d,p) reaction, was incident on a 12C target at energies near the Coulomb barrier. Evaporation residues produced in fusion of 18,19O ions with 12C target nuclei were detected with good geometric efficiency and identified by measuring their energy and time-of-flight. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. The significantly larger cross-sections observed at near barrier energies are not predicted by a static model of fusion for 19O + 12C indicating that dynamics play an important role in the fusion of neutron-...

  13. Data Mining and Data Fusion for Enhanced Decision Support

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Shiraj [ORNL; Ganguly, Auroop R [ORNL; Gupta, Amar [University of Arizona


    The process of Data Mining converts information to knowledge by utilizing tools from the disciplines of computational statistics, database technologies, machine learning, signal processing, nonlinear dynamics, process modeling, simulation, and allied disciplines. Data Mining allows business problems to be analyzed from diverse perspectives, including dimensionality reduction, correlation and co-occurrence, clustering and classification, regression and forecasting, anomaly detection, and change analysis. The predictive insights generated from Data Mining can be further utilized through real-time analysis and decision sciences, as well as through human-driven analysis based on management by exceptions or by objectives, to generate actionable knowledge. The tools that enable the transformation of raw data to actionable predictive insights are collectively referred as Decision Support tools. This chapter presents a new formalization of the decision process, leading to a new Decision Superiority model, partially motivated by the Joint Directors of Laboratories (JDL) Data Fusion Model. In addition, it examines the growing importance of Data Fusion concepts.

  14. Application of Fusion Gyrotrons to Enhanced Geothermal Systems (EGS) (United States)

    Woskov, P.; Einstein, H.; Oglesby, K.


    The potential size of geothermal energy resources is second only to fusion energy. Advances are needed in drilling technology and heat reservoir formation to realize this potential. Millimeter-wave (MMW) gyrotrons and related technologies developed for fusion energy research could contribute to enabling EGS. Directed MMW energy can be used to advance rock penetration capabilities, borehole casing, and fracking. MMWs are ideally suited because they can penetrate through small particulate extraction plumes, can be efficiently guided long distances in borehole dimensions, and continuous megawatt sources are commercially available. Laboratory experiments with a 10 kW, 28 GHz CPI gyrotron have shown that granite rock can be fractured and melted with power intensities of about 1 kW/cm2 and minute exposure times. Observed melted rock MMW emissivity and estimated thermodynamics suggest that penetrating hot, hard crystalline rock formations may be economic with fusion research developed MMW sources. Supported by USDOE, Office of Energy Efficiency and Renewable Energy and Impact Technologies, LLC.

  15. 陷窝蛋白-1与脑缺血后炎性反应%Caveolin-1 and inflammation after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    黄素芬; 易健; 刘柏炎


    As a cavola marker protein, caveolin-1 participates in many pathophysiological processes through its scaffolding domain oligomering many celular signal transduction molecules, and also regulates inflammation after cerebral ischemia through different pathways. This article reviews advances in caveolin-1 and inflammation after ischemic stroke in recent years, mainly focusing on its mechanism in regulating inflammation.%陷窝蛋白-1作为陷窝的标志蛋白,通过其脚手架结构域寡聚许多细胞信号转导分子,参与许多病理生理过程,也通过不同的途径调控脑缺血后炎症反应。文章对近年来陷窝蛋白-1与缺血性卒中后炎性反应相关研究进展进行了回顾,重点讨论其炎症调控机制。

  16. Palmitoylation of cysteine 415 of CB1 receptor affects ligand-stimulated internalization and selective interaction with membrane cholesterol and caveolin 1. (United States)

    Oddi, Sergio; Stepniewski, Tomasz Maciej; Totaro, Antonio; Selent, Jana; Scipioni, Lucia; Dufrusine, Beatrice; Fezza, Filomena; Dainese, Enrico; Maccarrone, Mauro


    We previously demonstrated that CB1 receptor is palmitoylated at cysteine 415, and that such a post-translational modification affects its biological activity. To assess the molecular mechanisms responsible for modulation of CB1 receptor function by S-palmitoylation, in this study biochemical and morphological approaches were paralleled with computational analyses. Molecular dynamics simulations suggested that this acyl chain stabilizes helix 8 as well as the interaction of CB1 receptor with membrane cholesterol. In keeping with these in silico data, experimental results showed that the non-palmitoylated CB1 receptor was unable to interact efficaciously with caveolin 1, independently of its activation state. Moreover, in contrast with the wild-type receptor, the lack of S-palmitoylation in the helix 8 made the mutant CB1 receptor completely irresponsive to agonist-induced effects in terms of both lipid raft partitioning and receptor internalization. Overall, our results support the notion that palmitoylation of cysteine 415 modulates the conformational state of helix 8 and influences the interactions of CB1 receptor with cholesterol and caveolin 1, suggesting that the palmitoyl chain may serve as a functional interface for CB1 receptor localization and function.

  17. CGRP对氧化损伤人脐静脉内皮细胞的保护作用及Caveolin-1表达的影响%Effect of CGRP on Protection of Human Umbilical Vein Endothelial Cells and Caveolin-1 Expression Induced by H2O2

    Institute of Scientific and Technical Information of China (English)

    周孝钱; 许俊; 唐江琼; 秦旭平


    目的 探讨降钙素基因相关肽(CGRP)对过氧化氢(H2O2)诱导离体培养的人脐静脉内皮细胞(hUVECs)损伤的保护作用及其机制.方法 CGRP预孵育hUVECs后,用不同浓度H2O2处理hUVECs,噻唑蓝比色法(MTT)观察hUVECs活性;Western-blot检测Caveolin-1表达.结果 CGRP(0.1~100.0 nmol/L)能呈浓度依赖性提高hUVECs活性.H2O2(0.2~5.0 mmol/L)能呈浓度依赖性降低hUVECs活性.CGRP(10~100 nmol/L)预孵育hUVECs 30 min能明显提高H2O2诱导的hUVECs抗损伤能力(P﹤0.05);与0.1%FBS组比较,100 nmol/L CGRP和0.05 mmol/L H2O2处理组细胞Caveolin-1蛋白水平表达下降(P﹤0.05);0.8 mmol/L H2O2处理组细胞Caveolin-1蛋白表达水平上升(P﹤0.05);与H2O2处理组比较,100 nmol/L CGRP预孵育hUVECs 30 min能显著降低细胞Caveolin-1蛋白水平的表达(P﹤0.05).结论 CGRP对H2O2诱导的hUVECs损伤有一定的保护作用,其机制可能与下调氧化应激导致的hUVECs Caveolin-1的表达有关.

  18. Enhancement display of veins distribution based on binocular vision and image fusion technology (United States)

    Liu, Peng; Di, Si; Jin, Jian; Bai, Liping


    The capture and display of veins distribution is an important issue for some applications, such as medical diagnosis and identification. Therefore, it has become a popular topic in the field of biomedical imaging. Usually, people capture the veins distribution by infrared imaging, but the display result is similar with that of a gray picture and the color and details of skin cannot be remained. To some degree, it is unreal for doctors. In this paper, we develop a binocular vision system to carry out the enhancement display of veins under the condition of keeping actual skin color. The binocular system is consisted of two adjacent cameras. A visible band filter and an infrared band filter are placed in front of the two lenses, respectively. Therefore, the pictures of visible band and infrared band can be captured simultaneously. After that, a new fusion process is applied to the two pictures, which related to histogram mapping, principal component analysis (PCA) and modified bilateral filter fusion. The final results show that both the veins distribution and the actual skin color of the back of the hand can be clearly displayed. Besides, correlation coefficient, average gradient and average distortion are selected as the parameters to evaluate the image quality. By comparing the parameters, it is evident that our novel fusion method is prior to some popular fusion methods such as Gauss filter fusion, Intensity-hue-saturation (HIS) fusion and bilateral filter fusion.

  19. Improving the recognition of fingerprint biometric system using enhanced image fusion (United States)

    Alsharif, Salim; El-Saba, Aed; Stripathi, Reshma


    Fingerprints recognition systems have been widely used by financial institutions, law enforcement, border control, visa issuing, just to mention few. Biometric identifiers can be counterfeited, but considered more reliable and secure compared to traditional ID cards or personal passwords methods. Fingerprint pattern fusion improves the performance of a fingerprint recognition system in terms of accuracy and security. This paper presents digital enhancement and fusion approaches that improve the biometric of the fingerprint recognition system. It is a two-step approach. In the first step raw fingerprint images are enhanced using high-frequency-emphasis filtering (HFEF). The second step is a simple linear fusion process between the raw images and the HFEF ones. It is shown that the proposed approach increases the verification and identification of the fingerprint biometric recognition system, where any improvement is justified using the correlation performance metrics of the matching algorithm.

  20. Effects of acrylonitrile on T lymphocytes' the lipid raft protein Caveolin-1 and the MEK protein in vitro%丙烯腈T淋巴细胞体外染毒对其脂筏Caveolin-1蛋白、MEK蛋白的影响

    Institute of Scientific and Technical Information of China (English)

    李秀菊; 黄简抒; 王朋; 周元陵; 范卫


    目的 丙烯腈染毒T淋巴细胞,分析膜脂筏及Ras/Raf/MEK/ERK信号通路中MEK蛋白变化,探讨丙烯腈免疫毒性的可能作用机制.方法 采取体外细胞培养技术,以T淋巴细胞Jurkat细胞株为研究对象,分为空白对照组、低浓度、中浓度、高浓度丙烯腈(0、20、100和500μmol/l)细胞染毒组,分析膜脂筏Caveolin-1蛋白、MEK蛋白变化.结果 随染毒浓度增加,受检细胞经处理4h后各染毒组与对照组细胞膜胆固醇含量差异有统计学意义(P<0.05),细胞膜胆固醇的含量下降,间接表明脂筏的数量越少;Caveolin-1蛋白定位改变,变构便于信号传递;p-MEK蛋白随浓度增高条带变浅.结论 丙烯腈可能通过破坏脂筏结构,脂筏数量减少,Caveolin-1蛋白位移变构,Ras/Raf/MEK/ERK信号传导过程受到抑制而发挥免疫毒性.

  1. Enhanced Singular Value Decomposition based Fusion for Super Resolution Image Reconstruction

    Directory of Open Access Journals (Sweden)

    K. Joseph Abraham Sundar


    Full Text Available The singular value decomposition (SVD plays a very important role in the field of image processing for applications such as feature extraction, image compression, etc. The main objective is to enhance the resolution of the image based on Singular Value Decomposition. The original image and the subsequent sub-pixel shifted image, subjected to image registration is transferred to SVD domain. An enhanced method of choosing the singular values from the SVD domain images to reconstruct a high resolution image using fusion techniques is proposesed. This technique is called as enhanced SVD based fusion. Significant improvement in the performance is observed by applying enhanced SVD method preceding the various interpolation methods which are incorporated. The technique has high advantage and computationally fast which is most needed for satellite imaging, high definition television broadcasting, medical imaging diagnosis, military surveillance, remote sensing etc.

  2. Internalization of coxsackievirus A9 is mediated by {beta}2-microglobulin, dynamin, and Arf6 but not by caveolin-1 or clathrin. (United States)

    Heikkilä, Outi; Susi, Petri; Tevaluoto, Tuire; Härmä, Heidi; Marjomäki, Varpu; Hyypiä, Timo; Kiljunen, Saija


    Coxsackievirus A9 (CAV9) is a member of the human enterovirus B species within the Enterovirus genus of the family Picornaviridae. It has been shown to utilize alphaV integrins, particularly alphaVbeta6, as its receptors. The endocytic pathway by which CAV9 enters human cells after the initial attachment to the cell surface has so far been unknown. Here, we present a systematic study concerning the internalization mechanism of CAV9 to A549 human lung carcinoma cells. The small interfering RNA (siRNA) silencing of integrin beta6 subunit inhibited virus proliferation, confirming that alphaVbeta6 mediates the CAV9 infection. However, siRNAs against integrin-linked signaling molecules, such as Src, Fyn, RhoA, phosphatidylinositol 3-kinase, and Akt1, did not reduce CAV9 proliferation, suggesting that the internalization of the virus does not involve integrin-linked signaling events. CAV9 endocytosis was independent of clathrin or caveolin-1 but was restrained by dynasore, an inhibitor of dynamin. The RNA interference silencing of beta2-microglobulin efficiently inhibited virus infection and caused CAV9 to accumulate on the cell surface. Furthermore, CAV9 infection was found to depend on Arf6 as both silencing of this molecule by siRNA and the expression of a dominant negative construct resulted in decreased virus infection. In conclusion, the internalization of CAV9 to A549 cells follows an endocytic pathway that is dependent on integrin alphaVbeta6, beta2-microglobulin, dynamin, and Arf6 but independent of clathrin and caveolin-1.

  3. A Framework for Satellite Image Enhancement Using Quantum Genetic and Weighted IHS+Wavelet Fusion Method

    Directory of Open Access Journals (Sweden)

    Amal A. HAMED


    Full Text Available this paper examined the applicability of quantum genetic algorithms to solve optimization problems posed by satellite image enhancement techniques, particularly super-resolution, and fusion. We introduce a framework starting from reconstructing the higher-resolution panchromatic image by using the subpixel-shifts between a set of lower-resolution images (registration, then interpolation, restoration, till using the higher-resolution image in pan-sharpening a multispectral image by weighted IHS+Wavelet fusion technique. For successful super-resolution, accurate image registration should be achieved by optimal estimation of subpixel-shifts. Optimal-parameters blind restoration and interpolation should be performed for the optimal quality higher-resolution image. There is a trade-off between spatial and spectral enhancement in image fusion; it is difficult for the existing methods to do the best in both aspects. The objective here is to achieve all combined requirements with optimal fusion weights, and use the parameters constraints to direct the optimization process. QGA is used to estimate the optimal parameters needed for each mathematic model in this framework “Super-resolution and fusion.” The simulation results show that the QGA-based method can be used successfully to estimate automatically the approaching parameters which need the maximal accuracy, and achieve higher quality and efficient convergence rate more than the corresponding conventional GA-based and the classic computational methods.

  4. An Approach to Optimize the Fusion Coefficients for Land Cover Information Enhancement with Multisensor Data (United States)

    Garg, Akanksha; Brodu, Nicolas; Yahia, Hussein; Singh, Dharmendra


    This paper explores a novel data fusion method with the application of Machine Learning approach for optimal weighted fusion of multisensor data. It will help to get the maximum information of any land cover. Considerable amount of research work has been carried out on multisensor data fusion but getting an optimal fusion for enhancement of land cover information using random weights is still ambiguous. Therefore, there is a need of such land cover monitoring system which can provide the maximum information of the land cover, generally which is not possible with the help of single sensor data. There is a necessity to develop such techniques by which information of multisensor data can be utilized optimally. Machine learning is one of the best way to optimize this type of information. So, in this paper, the weights of each sensor data have been critically analyzed which is required for the fusion, and observed that weights are quite sensitive in fusion. Therefore, different combinations of weights have been tested exhaustively in the direction to develop a relationship between weights and classification accuracy of the fused data. This relationship can be optimized through machine learning techniques like SVM (Support Vector Machine). In the present study, this experiment has been carried out for PALSAR (Phased Array L-Band Synthetic Aperture RADAR) and MODIS (Moderate Resolution Imaging Spectroradiometer) data. PALSAR is a fully polarimetric data with HH, HV and VV polarizations at good spatial resolution (25m), and NDVI (Normalized Difference Vegetation Index) is a good indicator of vegetation, utilizing different bands (Red and NIR) of freely available MODIS data at 250m resolution. First of all, resolution of NDVI has been enhanced from 250m to 25m (10 times) using modified DWT (Modified Discrete Wavelet Transform) to bring it on the same scale as that of PALSAR. Now, different polarized PALSAR data (HH, HV, VV) have been fused with resolution enhanced NDVI

  5. Enhanced protein expression in the baculovirus/insect cell system using engineered SUMO fusions. (United States)

    Liu, Li; Spurrier, Joshua; Butt, Tauseef R; Strickler, James E


    Recombinant protein expression in insect cells varies greatly from protein to protein. A fusion tag that is not only a tool for detection and purification, but also enhances expression and/or solubility would greatly facilitate both structure/function studies and therapeutic protein production. We have shown that fusion of SUMO (small ubiquitin-related modifier) to several test proteins leads to enhanced expression levels in Escherichia coli. In eukaryotic expression systems, however, the SUMO tag could be cleaved by endogenous desumoylase. In order to adapt SUMO-fusion technology to these systems, we have developed an alternative SUMO-derived tag, designated SUMOstar, which is not processed by native SUMO proteases. In the present study, we tested the SUMOstar tag in a baculovirus/insect cell system with several proteins, i.e. mouse UBP43, human tryptase beta II, USP4, USP15, and GFP. Our results demonstrate that fusion to SUMOstar enhanced protein expression levels at least 4-fold compared to either the native or His(6)-tagged proteins. We isolated active SUMOstar tagged UBP43, USP4, USP15, and GFP. Tryptase was active following cleavage with a SUMOstar specific protease. The SUMOstar system will make significant impact in difficult-to-express proteins and especially to those proteins that require the native N-terminal residue for function.

  6. Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

    Directory of Open Access Journals (Sweden)

    Ma YF


    amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion: The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections. Keywords: liposomes, fusion, bacteria, Pseudomonas aeruginosa, lipid composition

  7. A novel fusion partner for enhanced secretion of recombinant proteins in Saccharomyces cerevisiae. (United States)

    Bae, Jung-Hoon; Sung, Bong Hyun; Seo, Jeong-Woo; Kim, Chul Ho; Sohn, Jung-Hoon


    Expressing proteins with fusion partners improves yield and simplifies the purification process. We developed a novel fusion partner to improve the secretion of heterologous proteins that are otherwise poorly excreted in yeast. The VOA1 (YGR106C) gene of Saccharomyces cerevisiae encodes a subunit of vacuolar ATPase. We found that C-terminally truncated Voa1p was highly secreted into the culture medium, even when fused with rarely secreted heterologous proteins such as human interleukin-2 (hIL-2). Deletion mapping of C-terminally truncated Voa1p, identified a hydrophilic 28-amino acid peptide (HL peptide) that was responsible for the enhanced secretion of target protein. A purification tag and a protease cleavage site were added to use HL peptide as a multi-purpose fusion partner. The utility of this system was tested via the expression and purification of various heterologous proteins. In many cases, the yield of target proteins fused with the peptide was significantly increased, and fusion proteins could be directly purified with affinity chromatography. The fusion partner was removed by in vitro processing, and intact proteins were purified by re-application of samples to affinity chromatography.

  8. Fusion of binding domains to Thermobifida cellulosilytica cutinase to tune sorption characteristics and enhancing PET hydrolysis. (United States)

    Ribitsch, Doris; Yebra, Antonio Orcal; Zitzenbacher, Sabine; Wu, Jing; Nowitsch, Susanne; Steinkellner, Georg; Greimel, Katrin; Doliska, Ales; Oberdorfer, Gustav; Gruber, Christian C; Gruber, Karl; Schwab, Helmut; Stana-Kleinschek, Karin; Acero, Enrique Herrero; Guebitz, Georg M


    A cutinase from Thermomyces cellullosylitica (Thc_Cut1), hydrolyzing the synthetic polymer polyethylene terephthalate (PET), was fused with two different binding modules to improve sorption and thereby hydrolysis. The binding modules were from cellobiohydrolase I from Hypocrea jecorina (CBM) and from a polyhydroxyalkanoate depolymerase from Alcaligenes faecalis (PBM). Although both binding modules have a hydrophobic nature, it was possible to express the proteins in E. coli . Both fusion enzymes and the native one had comparable kcat values in the range of 311 to 342 s(-1) on pNP-butyrate, while the catalytic efficiencies kcat/Km decreased from 0.41 s(-1)/ μM (native enzyme) to 0.21 and 0.33 s(-1)/μM for Thc_Cut1+PBM and Thc_Cut1+CBM, respectively. The fusion enzymes were active both on the insoluble PET model substrate bis(benzoyloxyethyl) terephthalate (3PET) and on PET although the hydrolysis pattern was differed when compared to Thc_Cut1. Enhanced adsorption of the fusion enzymes was visible by chemiluminescence after incubation with a 6xHisTag specific horseradish peroxidase (HRP) labeled probe. Increased adsorption to PET by the fusion enzymes was confirmed with Quarz Crystal Microbalance (QCM-D) analysis and indeed resulted in enhanced hydrolysis activity (3.8× for Thc_Cut1+CBM) on PET, as quantified, based on released mono/oligomers.

  9. Enhanced Object Detection via Fusion With Prior Beliefs from Image Classification


    Cao, Yilun; Lee, Hyungtae; Kwon, Heesung


    In this paper, we introduce a novel fusion method that can enhance object detection performance by fusing decisions from two different types of computer vision tasks: object detection and image classification. In the proposed work, the class label of an image obtained from image classification is viewed as prior knowledge about existence or non-existence of certain objects. The prior knowledge is then fused with the decisions of object detection to improve detection accuracy by mitigating fal...

  10. Enhanced Cutinase-Catalyzed Hydrolysis of Polyethylene Terephthalate by Covalent Fusion to Hydrophobins (United States)

    Ribitsch, Doris; Herrero Acero, Enrique; Przylucka, Agnieszka; Zitzenbacher, Sabine; Marold, Annemarie; Gamerith, Caroline; Tscheließnig, Rupert; Jungbauer, Alois; Rennhofer, Harald; Lichtenegger, Helga; Amenitsch, Heinz; Bonazza, Klaus; Kubicek, Christian P.; Guebitz, Georg M.


    Cutinases have shown potential for hydrolysis of the recalcitrant synthetic polymer polyethylene terephthalate (PET). We have shown previously that the rate of this hydrolysis can be enhanced by the addition of hydrophobins, small fungal proteins that can alter the physicochemical properties of surfaces. Here we have investigated whether the PET-hydrolyzing activity of a bacterial cutinase from Thermobifida cellulosilytica (Thc_Cut1) would be further enhanced by fusion to one of three Trichoderma hydrophobins, i.e., the class II hydrophobins HFB4 and HFB7 and the pseudo-class I hydrophobin HFB9b. The fusion enzymes exhibited decreased kcat values on soluble substrates (p-nitrophenyl acetate and p-nitrophenyl butyrate) and strongly decreased the hydrophilicity of glass but caused only small changes in the hydrophobicity of PET. When the enzyme was fused to HFB4 or HFB7, the hydrolysis of PET was enhanced >16-fold over the level with the free enzyme, while a mixture of the enzyme and the hydrophobins led only to a 4-fold increase at most. Fusion with the non-class II hydrophobin HFB9b did not increase the rate of hydrolysis over that of the enzyme-hydrophobin mixture, but HFB9b performed best when PET was preincubated with the hydrophobins before enzyme treatment. The pattern of hydrolysis by the fusion enzymes differed from that of Thc_Cut1 as the concentration of the product mono(2-hydroxyethyl) terephthalate relative to that of the main product, terephthalic acid, increased. Small-angle X-ray scattering (SAXS) analysis revealed an increased scattering contrast of the fusion proteins over that of the free proteins, suggesting a change in conformation or enhanced protein aggregation. Our data show that the level of hydrolysis of PET by cutinase can be significantly increased by fusion to hydrophobins. The data further suggest that this likely involves binding of the hydrophobins to the cutinase and changes in the conformation of its active center. PMID:25795674

  11. Stromal Caveolin-1 Is Associated With Response and Survival in a Phase II Trial of nab-Paclitaxel With Carboplatin for Advanced NSCLC Patients (United States)

    Bertino, Erin M.; Williams, Terence M.; Nana-Sinkam, S. Patrick; Shilo, Konstantin; Chatterjee, Moumita; Mo, Xiaokui; Rahmani, Meliha; Phillips, Gary S.; Villalona-Calero, Miguel A.; Otterson, Gregory A.


    In this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non–small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial. These results suggest Cav-1 might serve as a potential biomarker in this patient population. Background The combination of bevacizumab with platinum-based chemotherapy results in greater response rate (RR) and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC). Bevacizumab is contraindicated in patients with squamous histology or hemoptysis. Nanoparticle albumin-bound (nab)-paclitaxel is a novel formulation of paclitaxel with greater dose tolerance and improved efficacy. We hypothesized that nab-paclitaxel and carboplatin would be superior to alternative doublets in advanced NSCLC patients ineligible for bevacizumab. Patients and Methods We conducted a single-arm phase II trial (NCT00729612) with carboplatin and nab-paclitaxel on day 1 of a 21-day cycle to evaluate RR (primary end point), safety, toxicity, and OS. Eligibility included: squamous histology, hemoptysis, or ongoing anticoagulation. Correlative studies included immunohistochemistry for secreted protein acid rich in cysteine (SPARC) and caveolin-1 (Cav-1). Results Sixty-three patients were enrolled. Most patients had squamous cell carcinoma (n = 48); other reasons for eligibility included hemoptysis (n = 11) and anticoagulation (n = 2). Toxicity Grade ≥ 3/4 included neuropathy, cytopenias, and fatigue. RR was 38% (24 partial response/0 complete response); 20 patients had stable disease (32%). Median progression-free survival was 5 months and median OS was 9.7 months. Immunohistochemistry for SPARC and Cav-1 was performed in 38 and 37 patients respectively. Although no association was found for

  12. Dendritic-tumor fusion cells derived heat shock protein70-peptide complex has enhanced immunogenicity. (United States)

    Zhang, Yunfei; Zhang, Yong; Chen, Jun; Liu, Yunyan; Luo, Wen


    Tumor-derived heat shock protein70-peptide complexes (HSP70.PC-Tu) have shown great promise in tumor immunotherapy due to numerous advantages. However, large-scale phase III clinical trials showed that the limited immunogenicity remained to be enhanced. In previous research, we demonstrated that heat shock protein 70-peptide complexes (HSP70.PC-Fc) derived from dendritic cell (DC)-tumor fusions exhibit enhanced immunogenicity compared with HSP70.PCs from tumor cells. However, the DCs used in our previous research were obtained from healthy donors and not from the patient population. In order to promote the clinical application of these complexes, HSP70.PC-Fc was prepared from patient-derived DC fused directly with patient-derived tumor cells in the current study. Our results showed that compared with HSP70.PC-Tu, HSP70.PC-Fc elicited much more powerful immune responses against the tumor from which the HSP70 was derived, including enhanced T cell activation, and CTL responses that were shown to be antigen specific and HLA restricted. Our results further indicated that the enhanced immunogenicity is related to the activation of CD4+ T cells and increased association with other heat shock proteins, such as HSP90. Therefore, the current study confirms the enhanced immunogenicity of HSP70.PC derived from DC-tumor fusions and may provide direct evidence promoting their future clinical use.

  13. Improving iris recognition performance using segmentation, quality enhancement, match score fusion, and indexing. (United States)

    Vatsa, Mayank; Singh, Richa; Noore, Afzel


    This paper proposes algorithms for iris segmentation, quality enhancement, match score fusion, and indexing to improve both the accuracy and the speed of iris recognition. A curve evolution approach is proposed to effectively segment a nonideal iris image using the modified Mumford-Shah functional. Different enhancement algorithms are concurrently applied on the segmented iris image to produce multiple enhanced versions of the iris image. A support-vector-machine-based learning algorithm selects locally enhanced regions from each globally enhanced image and combines these good-quality regions to create a single high-quality iris image. Two distinct features are extracted from the high-quality iris image. The global textural feature is extracted using the 1-D log polar Gabor transform, and the local topological feature is extracted using Euler numbers. An intelligent fusion algorithm combines the textural and topological matching scores to further improve the iris recognition performance and reduce the false rejection rate, whereas an indexing algorithm enables fast and accurate iris identification. The verification and identification performance of the proposed algorithms is validated and compared with other algorithms using the CASIA Version 3, ICE 2005, and UBIRIS iris databases.

  14. Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver

    Directory of Open Access Journals (Sweden)

    Damian Jozef Flis


    Full Text Available The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1 plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.

  15. Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress (United States)

    Kassan, M.; Vikram, A.; Kim, Y. R.; Li, Q.; Kassan, A.; Patel, H. H.; Kumar, S.; Gabani, M.; Liu, J.; Jacobs, J. S.; Irani, K.


    Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation. All of these effects were reversed by a miR-204 inhibitor (miR-204 I) or with overexpression of Cav1. A miR-204 mimic (miR-204 M) decreased Cav1 in endothelial cells. In addition, high-fat diet (HFD) feeding induced vascular miR-204 and reduced endothelial Cav1. MiR-204-I protected against HFD-induced downregulation of endothelial Cav1. Moreover, pharmacologic induction of ER stress with tunicamycin downregulated endothelial Cav1 and impaired endothelium-dependent vasorelaxation that was rescued by overexpressing Cav1. In conclusion, Sirt1 preserves Cav1-dependent endothelial function by mitigating miR-204-mediated vascular ER stress. PMID:28181559

  16. Involvement of caveolin-1 in low shear stress-induced breast cancer cell motility and adhesion: Roles of FAK/Src and ROCK/p-MLC pathways. (United States)

    Xiong, Niya; Li, Shun; Tang, Kai; Bai, Hongxia; Peng, Yueting; Yang, Hong; Wu, Chunhui; Liu, Yiyao


    Tumor cells translocating to distant sites are subjected to hemodynamic shear forces during their passage in the blood vessels. Low shear stress (LSS) plays a critical role in the regulation of various aspects of tumor cells functions, including motility and adhesion. Beyond its structural role, caveolin-1 (Cav-1), the important component of caveolae, represents a modulator of several cancer-associated functions as tumor progression and metastasis. However, the role of Cav-1 in regulating tumor cells response to shear stress remains poorly explored. Here, we characterized the role of LSS and Cav-1 in mediating cell motility and adhesion on human breast carcinoma MDA-MB-231 cells. We first showed that LSS exposure promoted cell polarity and focal adhesion (FA) dynamics, thus indicating elevated cell migration. Silencing of Cav-1 leaded to a significantly lower formation of stress fibers. However, LSS exposure was able to rescue it via the alteration of actin-associated proteins expression, including ROCK, p-MLC, cofilin and filamin A. Time-lapse migration assay indicated that Cav-1 expression fostered MDA-MB-231 cells motility and LSS triggered cells to rapidly generate new lamellipodia. Furthermore, Cav-1 and LSS significantly influenced cell adhesion. Taken together, our findings provide insights into mechanisms underlying LSS triggered events mediated by downstream Cav-1, including FAK/Src and ROCK/p-MLC pathways, involved in the reorganization of the cytoskeleton, cell motility, FA dynamics and breast cancer cell adhesion.

  17. Advancement of caveolin-1 in lung inflammatory reaction%小窝蛋白-1在肺部炎症反应中的研究进展

    Institute of Scientific and Technical Information of China (English)

    岳扬; 孙耕耘


    Caveolae, a kind of specialized cell membrane structure, is composed of protein and lipidt caveolin is the main structural protein. In the lung inflammatory reaction, many signaling molecules are enriched in caveolae which are the hinge of many signal transduction pathways. Caveolin-1 can regulate the activation of neutrophil, adhesion to endothelial cells, and activity of many signaling molecules such as G protein, protein kinase C, nuclear factor-κB, and thus play an important role in the lung inflammatory reaction.%小窝是一种特化的细胞膜结构,主要由蛋白质和脂类组成,小窝蛋白是其主要的结构蛋白.在肺部炎症反应中,小窝富集多种信号分子,成为信号转导的枢纽.小窝蛋白-1能够调节中性粒细胞的活化及其对内皮细胞的黏附,参与调节多种信号分子如G蛋白、蛋白激酶C、核转录因子κB的活性,因而在肺部炎症反应过程中具有重要的作用.

  18. Evaluation of cell binding peptide (p15) with silk fibre enhanced hydroxyappatite bone substitute for posterolateral spinal fusion in sheep

    DEFF Research Database (Denmark)

    Axelsen, M.; Jespersen, Stig; Overgaard, Søren;


    were assessed with 2D sections and 3D reconstruction images and fusion was defined as intertransverse bridging. Results: Spinal fusion was found in 72 % of levels receiving silk fibre enhanced ABM/P15 graft material. In levels with silk fibre enhanced AMB fusion rate was 41 %. These findings...... on the surface of bone forming cells. The binding initiates natural intra- and extracellular signalling pathways, inducing production of growth factors, bone morphogenic proteins and cytokines. P15 peptide has previously shown to improve osteoinductive properties when coated on graft materials. Purpose...

  19. Fusion of Delayed-enhancement MR Imaging and Contrast-enhanced MR Angiography to Visualize Radiofrequency Ablation Scar on the Pulmonary Vein. (United States)

    Shigenaga, Yutaka; Kiuchi, Kunihiko; Ikeuchi, Kazushi; Ikeda, Takayuki; Okajima, Katsunori; Yasaka, Yoshinori; Kawai, Hiroya


    Delayed-enhancement magnetic resonance imaging (DE-MRI) is reported to detect the radiofrequency (RF) ablation scar of pulmonary vein isolation. However, the precise localization of RF scar is difficult to recognize due to the poor anatomical information of the 3-dimensionally reconstructed DE-MRI. We report 2 cases in which fusion of DE-MRI and contrast-enhanced MR angiography facilitated the identification of RF scar, and we detail our fusion method.

  20. ChimerDB 3.0: an enhanced database for fusion genes from cancer transcriptome and literature data mining (United States)

    Lee, Myunggyo; Lee, Kyubum; Yu, Namhee; Jang, Insu; Choi, Ikjung; Kim, Pora; Jang, Ye Eun; Kim, Byounggun; Kim, Sunkyu; Lee, Byungwook; Kang, Jaewoo; Lee, Sanghyuk


    Fusion gene is an important class of therapeutic targets and prognostic markers in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data and manual curations. In this update, the database coverage was enhanced considerably by adding two new modules of The Cancer Genome Atlas (TCGA) RNA-Seq analysis and PubMed abstract mining. ChimerDB 3.0 is composed of three modules of ChimerKB, ChimerPub and ChimerSeq. ChimerKB represents a knowledgebase including 1066 fusion genes with manual curation that were compiled from public resources of fusion genes with experimental evidences. ChimerPub includes 2767 fusion genes obtained from text mining of PubMed abstracts. ChimerSeq module is designed to archive the fusion candidates from deep sequencing data. Importantly, we have analyzed RNA-Seq data of the TCGA project covering 4569 patients in 23 cancer types using two reliable programs of FusionScan and TopHat-Fusion. The new user interface supports diverse search options and graphic representation of fusion gene structure. ChimerDB 3.0 is available at PMID:27899563

  1. Enhanced charged Higgs production through W -Higgs fusion in W - b scattering (United States)

    Arhrib, Abdesslam; Cheung, Kingman; Lee, Jae Sik; Lu, Chih-Ting


    We study the associated production of a charged Higgs boson with a bottom quark and a light quark at the LHC via pp → H ± b j in the Two Higgs Doublet Models (2HDMs). Using the effective W approximation, we show that there is exact cancellation among various Feynman diagrams in high energy limit. This may imply that the production of charged Higgs can be significantly enhanced in the presence of large mass differences among the neutral Higgs bosons via W ±-Higgs fusion in the pp → H ± b j process. Particularly, we emphasize the potential enhancement due to a light pseudoscalar boson A, which is still allowed by the current data by which we explicitly calculate the allowed regions in ( M A , tan β) plane, and show that the production cross section can be as large as 0.1 pb for large tan β. We also show that the transverse momentum distribution of the b quark can potentially distinguish the W ± - A fusion diagram from the top diagram. Finally, we point out further enhancement when we go beyond the 2HDMs.

  2. SUMO fusion technology for enhanced protein production in prokaryotic and eukaryotic expression systems. (United States)

    Panavas, Tadas; Sanders, Carsten; Butt, Tauseef R


    In eukaryotic cells, the reversible attachment of small ubiquitin-like modifier (SUMO) protein is a post-translational modification that has been demonstrated to play an important role in various cellular processes. Moreover, it has been found that SUMO as an N-terminal fusion partner enhances functional protein production in prokaryotic and eukaryotic expression systems, based upon significantly improved protein stability and solubility. Following the expression and purification of the fusion protein, the SUMO-tag can be cleaved by specific (SUMO) proteases via their endopeptidase activity in vitro to generate the desired N-terminus of the released protein partner. In addition to its physiological relevance in eukaryotes, SUMO can, thus, be used as a powerful biotechnological tool for protein expression in prokaryotic and eukaryotic cell systems.In this chapter, we will describe the construction of a fusion protein with the SUMO-tag, its expression in Escherichia coli, and its purification followed by the removal of the SUMO-tag by a SUMO-specific protease in vitro.

  3. Fast Ignition Thermonuclear Fusion: Enhancement of the Pellet Gain by the Colossal-Magnetic-Field Shells (United States)

    Stefan, V. Alexander


    The fast ignition fusion pellet gain can be enhanced by a laser generated B-field shell. The B-field shell, (similar to Earth's B-field, but with the alternating B-poles), follows the pellet compression in a frozen-in B-field regime. A properly designed laser-pellet coupling can lead to the generation of a B-field shell, (up to 100 MG), which inhibits electron thermal transport and confines the alpha-particles. In principle, a pellet gain of few-100s can be achieved in this manner. Supported in part by Nikola Tesla Labs, Stefan University, 1010 Pearl, La Jolla, CA 92038-1007.

  4. Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method


    Payal Hasmukhlal Patil; Veena Sailendra Belgamwar; Pratibha Ramratan Patil; Sanjay Javerilal Surana


    The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carri...

  5. Regulation of SGLT expression and localization through Epac/PKA-dependent caveolin-1 and F-actin activation in renal proximal tubule cells. (United States)

    Lee, Yu Jin; Kim, Mi Ok; Ryu, Jung Min; Han, Ho Jae


    This study demonstrated that exchange proteins directly activated by cAMP (Epac) and protein kinase A (PKA) by 8-bromo (8-Br)-adenosine 3',5'-cyclic monophosphate (cAMP) stimulated [(14)C]-α-methyl-D-glucopyranoside (α-MG) uptake through increased sodium-glucose cotransporters (SGLTs) expression and translocation to lipid rafts in renal proximal tubule cells (PTCs). In PTCs, SGLTs were colocalized with lipid raft caveolin-1 (cav-1), disrupted by methyl-β-cyclodextrin (MβCD). Selective activators of Epac or PKA, 8-Br-cAMP, and forskolin stimulated expressions of SGLTs and α-MG uptake in PTCs. In addition, 8-Br-cAMP-induced PKA and Epac activation increased phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB), which were involved in expressions of SGLTs. Furthermore, 8-Br-cAMP stimulated SGLTs translocation to lipid rafts via filamentous actin (F-actin) organization, which was blocked by cytochalasin D. In addition, cav-1 and SGLTs stimulated by 8-Br-cAMP were detected in lipid rafts, which were blocked by cytochalasin D. Furthermore, 8-Br-cAMP-induced SGLTs translocation and α-MG uptake were attenuated by inhibition of cav-1 activation with cav-1 small interfering RNA (siRNA) and inhibition of F-actin organization with TRIO and F-actin binding protein (TRIOBP). In conclusion, 8-Br-cAMP stimulated α-MG uptake via Epac and PKA-dependent SGLTs expression and trafficking through cav-1 and F-actin in PTCs.

  6. Relationship with spatial memory in diabetic rats and protein kinase Cγ,caveolin-1 in the hippocampus and neuroprotective effect of catalpol

    Institute of Scientific and Technical Information of China (English)

    Zhou Haicheng; Liu Jing; Ren Liyuan; Liu Wei; Xing Qian; Men Lili; Song Guirong


    Background The mechanisms underlying diabetic encephalopathy are largely unknown,and no effective treatments are available.Catalpol has received much attention due to its numerous biological effects,especially in neuroprotective studies.The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms.Methods A rat model of diabetes was established by streptozotocin injection,followed by intraperitoneal infusion of catalpol after 10 weeks.Two weeks later,the Morris water maze was used to test the spatial learning performance.Nissl staining was performed to evaluate the morphological changes in the hippocampus.Expression of protein kinase Cy (PKCy) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting.Activities of anti-oxidative enzymes such as glutathione (GSH),superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits.Results Significant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes.Moreover,cognitive dysfunction was associated with markedly increased oxidative stress in the brain.Catalpol treatment significantly attenuated cognitive deficits,neuronal damage,and oxidative stress in the brain of diabetic rats.Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats.Conclusions Spatial memory in diabetic rats is associated with the expression of PKCy and Cav-1.Catalpol treatment markedly attenuated oxidative stress,reversed the alteration of PKCy,Cav-1 and spatial memory deficits.

  7. Impact of the loss of caveolin-1 on lung mass and cholesterol metabolism in mice with and without the lysosomal cholesterol transporter, Niemann-Pick type C1. (United States)

    Mundy, Dorothy I; Lopez, Adam M; Posey, Kenneth S; Chuang, Jen-Chieh; Ramirez, Charina M; Scherer, Philipp E; Turley, Stephen D


    Caveolin-1 (Cav-1) is a major structural protein in caveolae in the plasma membranes of many cell types, particularly endothelial cells and adipocytes. Loss of Cav-1 function has been implicated in multiple diseases affecting the cardiopulmonary and central nervous systems, as well as in specific aspects of sterol and lipid metabolism in the liver and intestine. Lungs contain an exceptionally high level of Cav-1. Parameters of cholesterol metabolism in the lung were measured, initially in Cav-1-deficient mice (Cav-1(-/-)), and subsequently in Cav-1(-/-) mice that also lacked the lysosomal cholesterol transporter Niemann-Pick C1 (Npc1) (Cav-1(-/-):Npc1(-/-)). In 50-day-old Cav-1(-/-) mice fed a low- or high-cholesterol chow diet, the total cholesterol concentration (mg/g) in the lungs was marginally lower than in the Cav-1(+/+) controls, but due to an expansion in their lung mass exceeding 30%, whole-lung cholesterol content (mg/organ) was moderately elevated. Lung mass (g) in the Cav-1(-/-):Npc1(-/-) mice (0.356±0.022) markedly exceeded that in their Cav-1(+/+):Npc1(+/+) controls (0.137±0.009), as well as in their Cav-1(-/-):Npc1(+/+) (0.191±0.013) and Cav-1(+/+):Npc1(-/-) (0.213±0.022) littermates. The corresponding lung total cholesterol contents (mg/organ) in mice of these genotypes were 6.74±0.17, 0.71±0.05, 0.96±0.05 and 3.12±0.43, respectively, with the extra cholesterol in the Cav-1(-/-):Npc1(-/-) and Cav-1(+/+):Npc1(-/-) mice being nearly all unesterified (UC). The exacerbation of the Npc1 lung phenotype and increase in the UC level in the Cav-1(-/-):Npc1(-/-) mice imply a regulatory role of Cav-1 in pulmonary cholesterol metabolism when lysosomal sterol transport is disrupted.

  8. Sex-dependent expression of caveolin 1 in response to sex steroid hormones is closely associated with development of obesity in rats.

    Directory of Open Access Journals (Sweden)

    Rajib Mukherjee

    Full Text Available Caveolin-1 (CAV1 is a conserved group of structural membrane proteins that form special cholesterol and sphingolipid-rich compartments, especially in adipocytes. Recently, it has been reported that CAV1 is an important target protein in sex hormone-dependent regulation of various metabolic pathways, particularly in cancer and diabetes. To clarify distinct roles of CAV1 in sex-dependent obesity development, we investigated the effects of high fat diet (HFD and sex steroid hormones on CAV1 expression in adipose tissues of male and female rats. Results of animal experiments revealed that estrogen (17-β-estradiol, E2 and androgen (dihydrotestosterone, DHT had opposite effects on body weight gain as well as on the regulation of CAV1, hormone sensitive lipase (HSL and uncoupling protein 1 (UCP1 in adipose tissues. Furthermore, sex hormone receptors and aromatase were differentially expressed in a sex-dependent manner in response to E2 and DHT treatments. In vivo data were confirmed using 3T3-L1 and HIB1B cell lines, where Cav1 knock down stimulated lipogenesis but suppressed sex hormone receptor signaling proteins. Most importantly, co-immunoprecipitation enabled the identification of previously unrecognized CAV1-interacting mitochondrial or lipid oxidative pathway proteins in adipose tissues. Taken together, current data showed that CAV1 may play important preventive role in the development of obesity, with more prominent effects in females, and proved to be an important target protein for the hormonal regulation of adipose tissue metabolism by manipulating sex hormone receptors and mitochondrial oxidative pathways. Therefore, we can report, for the first time, the molecular mechanism underlying the effects of sex steroid hormones in the sex-dimorphic regulation of CAV1.

  9. Scleroderma-like properties of skin from caveolin-1-deficient mice: implications for new treatment strategies in patients with fibrosis and systemic sclerosis. (United States)

    Castello-Cros, Remedios; Whitaker-Menezes, Diana; Molchansky, Alex; Purkins, George; Soslowsky, Louis J; Beason, David P; Sotgia, Federica; Iozzo, Renato V; Lisanti, Michael P


    Caveolin-1 (Cav-1), the principal structural component of caveolae, participates in the pathogenesis of several fibrotic diseases, including systemic sclerosis (SSc). Interestingly, affected skin and lung samples from patients with SSc show reduced levels of Cav-1, as compared to normal skin. In addition, restoration of Cav-1 function in skin fibroblasts from SSc patients reversed their pro-fibrotic phenotype. Here, we further investigated whether Cav-1 mice are a useful pre-clinical model for studying the pathogenesis of SSc. For this purpose, we performed quantitative transmission electron microscopy, as well as biochemical and immuno-histochemical analysis, of the skin from Cav-1 (-/-) null mice. Using these complementary approaches, we now show that skin from Cav-1 null mice exhibits many of the same characteristics as SSc skin from patients, including a decrease in collagen fiber diameter, increased tensile strength, and stiffness, as well as mononuclear cell infiltration. Furthermore, an increase in autophagy/mitophagy was observed in the stromal cells of the dermis from Cav-1 (-/-) mice. These findings suggest that changes in cellular energy metabolism (e.g., a shift towards aerobic glycolysis) in these stromal cells may be a survival mechanism in this "hostile" or pro-inflammatory microenvironment. Taken together, our results demonstrate that Cav-1 (-/-) null mice are a valuable new pre-clinical model for studying scleroderma. Most importantly, our results suggest that inhibition of autophagy and/or aerobic glycolysis may represent a new promising therapeutic strategy for halting fibrosis in SSc patients. Finally, Cav-1 (-/-) null mice are also a pre-clinical model for a "lethal" tumor micro-environment, possibly explaining the link between fibrosis, tumor progression, and cancer metastasis.

  10. Cross-talk between Dopachrome Tautomerase and Caveolin-1 Is Melanoma Cell Phenotype-specific and Potentially Involved in Tumor Progression. (United States)

    Popa, Ioana L; Milac, Adina L; Sima, Livia E; Alexandru, Petruta R; Pastrama, Florin; Munteanu, Cristian V A; Negroiu, Gabriela


    l-Dopachrome tautomerase (l-DCT), also called tyrosinase-related protein-2 (TRP-2), is a melanoma antigen overexpressed in most chemo-/radiotherapeutic stress-resistant tumor clones, and caveolin-1 (CAV1) is a main regulator of numerous signaling processes. A structural and functional relationship between DCT and CAV1 is first presented here in two human amelanotic melanoma cell lines, derived from vertical growth phase (MelJuSo) and metastatic (SKMel28) melanomas. DCT co-localizes at the plasma membrane with CAV1 and Cavin-1, another molecular marker for caveolae in both cell phenotypes. Our novel structural model proposed for the DCT-CAV1 complex, in addition to co-immunoprecipitation and mass spectrometry data, indicates a possible direct interaction between DCT and CAV1. The CAV1 control on DCT gene expression, DCT post-translational processing, and subcellular distribution is cell phenotype-dependent. DCT is a modulator of CAV1 stability and supramolecular assembly in both cell phenotypes. During autocrine stimulation, the expressions of DCT and CAV1 are oppositely regulated; DCT increases while CAV1 decreases. Sub-confluent MelJuSo clones DCT(high)/CAV1(low) are proliferating and acquire fibroblast-like morphology, forming massive, confluent clusters as demonstrated by immunofluorescent staining and TissueFAXS quantitative image cytometry analysis. CAV1 down-regulation directly contributes to the expansion of MelJuSo DCT(high) subtype. CAV1 involved in the perpetuation of cell phenotype-overexpressing anti-stress DCT molecule supports the concept that CAV1 functions as a tumor suppressor in early stages of melanoma. DCT is a regulator of the CAV1-associated structures and is possibly a new molecular player in CAV1-mediated processes in melanoma.

  11. The Ankrd13 Family of Ubiquitin-interacting Motif-bearing Proteins Regulates Valosin-containing Protein/p97 Protein-mediated Lysosomal Trafficking of Caveolin 1. (United States)

    Burana, Daocharad; Yoshihara, Hidehito; Tanno, Hidetaka; Yamamoto, Akitsugu; Saeki, Yasushi; Tanaka, Keiji; Komada, Masayuki


    Caveolin 1 (Cav-1) is an oligomeric protein that forms flask-shaped, lipid-rich pits, termed caveolae, on the plasma membrane. Cav-1 is targeted for lysosomal degradation in ubiquitination- and valosin-containing protein (VCP)-dependent manners. VCP, an ATPase associated with diverse cellular activities that remodels or segregates ubiquitinated protein complexes, has been proposed to disassemble Cav-1 oligomers on the endosomal membrane, facilitating the trafficking of Cav-1 to the lysosome. Genetic mutations in VCP compromise the lysosomal trafficking of Cav-1, leading to a disease called inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia (IBMPFD). Here we identified the Ankrd13 family of ubiquitin-interacting motif (UIM)-containing proteins as novel VCP-interacting molecules on the endosome. Ankrd13 proteins formed a ternary complex with VCP and Cav-1 and exhibited high binding affinity for ubiquitinated Cav-1 oligomers in an UIM-dependent manner. Mass spectrometric analyses revealed that Cav-1 undergoes Lys-63-linked polyubiquitination, which serves as a lysosomal trafficking signal, and that the UIMs of Ankrd13 proteins bind preferentially to this ubiquitin chain type. The overexpression of Ankrd13 caused enlarged hollow late endosomes, which was reminiscent of the phenotype of the VCP mutations in IBMPFD. Overexpression of Ankrd13 proteins also stabilized ubiquitinated Cav-1 oligomers on the limiting membrane of enlarged endosomes. The interaction with Ankrd13 was abrogated in IMBPFD-associated VCP mutants. Collectively, our results suggest that Ankrd13 proteins cooperate with VCP to regulate the lysosomal trafficking of ubiquitinated Cav-1.

  12. Strategic Targets To induce Neovascularization By Resveratrol In Hypercholesterolemic Rat Myocardium: Role of Caveolin-1, eNOS, HO-1 and VEGF (United States)

    Penumathsa, Suresh Varma; Koneru, Srikanth; Samuel, Samson Mathews; Maulik, Gautam; Bagchi, Debasis; Yet, Shaw-Fang; Menon, Venogopal P.; Maulik, Nilanjana


    Endothelial dysfunction and impaired angiogenesis is a hallmark of hypercholesterolemia (HC). This study was designed to examine the effects of resveratrol (R), an antioxidant with lipid lowering properties like statin, on neovascularization along with caveolar interaction with proangiogenic molecules in hypercholesterolemic (HC) rats. Animals were divided into: control (C), maintained on normal diet; rats maintained on 5% high cholesterol diet for 8 weeks (HC); & HC + R (20mg/kg) orally for 2 weeks (HCR). Myocardial infarction was induced by ligating the left anterior descending artery (LAD). Herein we examined a novel method of stimulating myocardial angiogenesis by pharmacological preconditioning with resveratrol at both capillary and arteriolar levels and the potential role of hemeoxygenase-1 (HO-1), e-NOS and Caveolin-1(Cav-1) in mediating such a response. We also investigated the functional relevance of such treatment by assessing whether the induced neovascularization can help preserve LV–contractile functional reserve in the setting of chronic hypercholesterolemic condition. Four weeks after sham surgery and LAD occlusion, rats underwent echocardiographic evaluation which revealed improvement in ejection fraction and fractional shortening in HCR compared to HC. Left ventricular tissue sections displayed increased capillary and arteriolar density in HCR compared to HC. Western blot analysis displayed downregulation of VEGF, HO-1 and increased association of Cav-1 along with eNOS in HC, preventing availability of eNOS to the system which was reversed with resveratrol treatment in HCR. This study was further validated in cardiac specific HO-1 overexpressed mice assuming molecular cross talk between the targets. Hence, our data identified potential regulators that primarily attenuate and blunt endothelial dysfunction by resveratrol therapy in hypercholesterolemic myocardium. PMID:18694817

  13. Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes. (United States)

    Bitar, Milad S; Abdel-Halim, Samy M; Al-Mulla, Fahd


    A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species, DFs also displayed a significant increase in senescence-associated β-galactosidase activity and phospho-γ-histone H2AX (pH2AX) level. Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes. Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53. This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs. Most of the aforementioned oxidative stress and senescence-based features observed in DFs were recapitulated in a 10-day-old diabetic wound. Intriguingly, we confirmed that the targeted depletion of Cav-1 or PTRF using siRNA- or Vivo-Morpholino antisense-based gene therapy markedly inhibited diabetes/oxidative stress-induced premature senescence and also accelerated tissue repair in this disease state. Overall, our data illuminate Cav-1/PTRF-1 as a key player of a novel signaling pathway that may link a heightened state of oxidative stress to cellular senescence and impaired wound healing in diabetes.

  14. Restoration of caveolin-1 expression suppresses growth, membrane-type-4 metalloproteinase expression and metastasis-associated activities in colon cancer cells. (United States)

    Nimri, Lili; Barak, Hossei; Graeve, Lutz; Schwartz, Betty


    Caveolin-1 (cav-1) and flotillin-1 are two major structural proteins associated with lipid rafts in mammalian cells. The membrane-type matrix metalloproteinases (MT-MMPs) are expressed at the cell surface, hydrolyze extracellular matrix, and play an important role in cancer cell migration and metastasis. Expression of cav-1, flotillin-1, and MT4-MMP in lysates and lipid rafts of LS174T and HM-7 colon cancer cells was determined. The impact of restoration of cav-1 expression on proliferation, adhesion, motility in vitro, and growth of implanted tumors in vivo was characterized. Cav-1 is not expressed in lipid rafts of the highly metastatic colon cancer cell line (HM-7), but expressed in cytosolic fractions of the parental lower metastatic cell line (LS174T). In contrast, MT4-MMP was expressed in lipid rafts of HM-7 cells but not in LS174T cells. Overexpression of cav-1 in HM-7 cells down-regulate proliferation, viability, wound closure, adhesion to laminin, invasion, and development of filopodial and lamellipodial structures in a dose-dependent manner. Cav-1 positive HM-7 clones ceased to express MT4-MMP in their lipid rafts. Comparative proteomic analyses of lipid rafts from cav-1 positive and cav-1 negative cells demonstrated de novo expression of flotillin-1 only on the cells expressing cav-1. Xenografting control cells devoid of cav-1 in nude mice induced development of bigger tumors expressing higher levels of proliferating cell nuclear antigen as compared to mice injected with cells expressing the highest cav-1 levels. We conclude that cav-1 orchestrates and reorganize several proteins in lipid rafts, activities directly associated with reduced tumorigenic and metastatic ability of colon cancer cells.

  15. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression. (United States)

    Ayala, Gustavo; Morello, Matteo; Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Di Vizio, Dolores


    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma.

  16. Enhancement of out-of-focus images using fusion-based PSF estimation and restoration (United States)

    Yoon, Joonshik; Shin, Jeong-Ho; Paik, Joon-Ki


    In this paper, we propose an enhancement algorithm of out-of- focused images using fusion-based Point-spread-function (PSF) estimation and restoration. The proposed algorithm can make in-focused image by using only digital image processing techniques, and it requires neither infrared light/ultrasound nor focusing lens assembly operated by electrically powered movement of focusing lens. In order to increase accuracy in estimating the PSF of the defocus image, the proposed algorithm finds true and linear edges by using Canny edge detector, which is optimal edge detector and has good localization, estimates the step response across the edge for each pixel, computes the one-dimensional step response by averaging the step responses, estimates the two-dimensional PSF from the averaged step response, and then provides in- focused image by image restoration filter based on the estimated PSF. Finally, we execute fusion process, which can enhance the quality of the fused image by fusing restored images. There is a limit of the amount of out-of-focus, which can be recovered by the proposed algorithm. Moreover, the proposed algorithm is operating under assumption that an input image contains at least one piece-wise linear boundary between an object and background. In spite of above-mentioned limitations, the proposed algorithm can make acceptable quality of focused image by using only digital image processing.

  17. Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

    Directory of Open Access Journals (Sweden)

    Payal Hasmukhlal Patil


    Full Text Available The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX, which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV. The optimized ratio for preparing a solid dispersion (SD of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM, differential scanning calorimetry (DSC and powder X-ray diffraction (PXRD studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

  18. Enhancing Throughput of Combinatorial Droplet Devices via Droplet Bifurcation, Parallelized Droplet Fusion, and Parallelized Detection

    Directory of Open Access Journals (Sweden)

    Kuangwen Hsieh


    Full Text Available Combinatorial droplet microfluidic devices with programmable microfluidic valves have recently emerged as a viable approach for performing multiplexed experiments in microfluidic droplets. However, the serial operation in these devices restricts their throughput. To address this limitation, we present a parallelized combinatorial droplet device that enhances device throughput via droplet bifurcation, parallelized droplet fusion, and parallelized droplet detection. In this device, sample droplets split evenly at bifurcating Y-junctions before multiple independent reagent droplets are injected directly into the split sample droplets for robust droplet fusion. Finally, the fused sample and reagent droplets can be imaged in parallel via microscopy. The combination of these approaches enabled us to improve the throughput over traditional, serially-operated combinatorial droplet devices by 16-fold—with ready potential for further enhancement. Given its current performance and prospect for future improvements, we believe the parallelized combinatorial droplet device has the potential to meet the demand as a flexible and cost-effective tool that can perform high throughput screening applications.

  19. Fusion of contrast-enhanced breast MR and mammographic imaging data. (United States)

    Behrenbruch, Christian P; Marias, Kostas; Armitage, Paul A; Yam, Margaret; Moore, Niall; English, Ruth E; Clarke, Jane; Brady, Michael


    Increasing use is being made of Gd-DTPA contrast-enhanced magnetic resonance imaging for breast cancer assessment since it provides 3D functional information via pharmacokinetic interaction between contrast agent and tumour vascularity, and because it is applicable to women of all ages as well as patients with post-operative scarring. Contrast-enhanced MRI (CE-MRI) is complementary to conventional X-ray mammography, since it is a relatively low-resolution functional counterpart of a comparatively high-resolution 2D structural representation. However, despite the additional information provided by MRI, mammography is still an extremely important diagnostic imaging modality, particularly for several common conditions such as ductal carcinoma in situ (DCIS) where it has been shown that there is a strong correlation between microcalcification clusters and malignancy. Pathological indicators such as calcifications and fine spiculations are not visible in CE-MRI and therefore there is clinical and diagnostic value in fusing the high-resolution structural information available from mammography with the functional data acquired from MRI imaging. This paper presents a novel data fusion technique whereby medial-lateral oblique (MLO) and cranial-caudal (CC) mammograms (2D data) are registered to 3D contrast-enhanced MRI volumes. We utilise a combination of pharmacokinetic modelling, projection geometry, wavelet-based landmark detection and thin-plate spline non-rigid 'warping' to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. Of key importance is the use of a flexible wavelet-based feature extraction technique that enables feature correspondences to be robustly determined between the very different image characteristics of X-ray mammography and MRI. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples.

  20. Enhanced exo-inulinase activity and stability by fusion of an inulin-binding module. (United States)

    Zhou, Shun-Hua; Liu, Yuan; Zhao, Yu-Juan; Chi, Zhe; Chi, Zhen-Ming; Liu, Guang-Lei


    In this study, an inulin-binding module from Bacillus macerans was successfully fused to an exo-inulinase from Kluyveromyces marxianus, creating a hybrid functional enzyme. The recombinant exo-inulinase (rINU), the hybrid enzyme (rINUIBM), and the recombinant inulin-binding module (rIBM) were, respectively, heterologously expressed and biochemically characterized. It was found that both the inulinase activity and the catalytic efficiency (k cat/K m(app)) of the rINUIBM were considerably higher than those of rINU. Though the rINU and the rINUIBM shared the same optimum pH of 4.5, the optimum temperature of the rINUIBM (60 °C) was 5 °C higher than that of the rINU. Notably, the fused IBM significantly enhanced both the pH stability and the thermostability of the rINUIBM, suggesting that the rINUIBM obtained would have more extensive potential applications. Furthermore, the fusion of the IBM could substantially improve the inulin-binding capability of the rINUIBM, which was consistent with the determination of the K m(app). This meant that the fused IBM could play a critical role in the recognition of polysaccharides and enhanced the hydrolase activity of the associated inulinase by increasing enzyme-substrate proximity. Besides, the extra supplement of the independent non-catalytic rIBM could also improve the inulinase activity of the rINU. However, this improvement was much better in case of the fusion. Consequently, the IBM could be designated as a multifunctional domain that was responsible for the activity enhancement, the stabilization, and the substrate binding of the rINUIBM. All these features obtained in this study make the rINUIBM become an attractive candidate for an efficient inulin hydrolysis.

  1. Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Meyuhas, Ronit; Noy, Hava; Fishman, Sigal [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Margalit, Alon [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel); Montefiori, David C. [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Gross, Gideon, E-mail: [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel)


    HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immunoligands harboring VH3. Unlike VH3-IgG1 or VH3-CD4-IgG1, CD4-VH3-IgG1 bound gp120 considerably stronger than CD4-IgG1. CD4-VH3-IgG1 exhibited {approx}1.5-2.5-fold increase in neutralization of two T-cell laboratory-adapted strains when compared to CD4-IgG1. CD4-VH3-IgG1 improved neutralization of 7/10 clade B primary isolates or pseudoviruses, exceeding 20-fold for JR-FL and 13-fold for Ba-L. It enhanced neutralization of 4/8 clade C viruses, and had negligible effect on 1/4 clade A pseudoviruses. We attribute this improvement to possible pairing of VH3 with CD4 D1 and stabilization of an Ig Fv-like structure, rather than to superantigen interactions. These novel findings support the current notion that CD4 fusion proteins can act as better HIV-1 entry inhibitors with potential clinical implications.

  2. Why the complete fusion of weakly bond nuclei is enhanced at sub-barrier energies and suppressed above the barrier?

    Energy Technology Data Exchange (ETDEWEB)

    Lubian, J.; Gomes, P.R.S. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Canto, L.F. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Hussein, M.S. [Universidade de Sao Paulo (USP), SP (Brazil)


    Full text: In the last two decades one has asked whether the complete fusion of weakly bound systems is enhanced or suppressed when compared with the situation where there is no break process. Recent systematic results [1] based on the reduction of cross section and the comparison to the Universal Fusion Function have shown that the complete fusion cross section is indeed enhanced at sub-barrier energies and suppressed at energies above the barrier, when compared with calculations which do not take into account the couplings to breakup channels. In this contribution we discuss and propose a method to explain this conclusion. We point out the importance of direct transfer and breakup processes and also the recently observed sequential breakup that follows the transfer. Different behaviors of the dynamic polarization potentials at different energy regions are used to explain the observed fusion excitation functions for several weakly bound systems. While the breakup polarization is the main reaction channel at above the Coulomb barrier energy regime, leading to repulsive polarization, the sequential breakup (transfer followed by breakup) seems to be the main reaction mechanism at below barrier energies. This last mechanism produces attractive polarization and for this reason it enhances the complete fusion cross section. [1] L.F. Canto et al., Nucl. Phys. A 821, 51 (2009); J. of Phys. G 36, 015109 (2009). (author)

  3. Enhanced Computational Infrastructure for Data Analysis at the DIII-D National Fusion Facility

    Energy Technology Data Exchange (ETDEWEB)

    Schissel, D.P.; Peng, Q.; Schachter, J.; Terpstra, T.B.; Casper, T.A.; Freeman, J.; Jong, R.; Keith, K.M.; Meyer, W.H.; Parker, C.T.


    Recently a number of enhancements to the computer hardware infrastructure have been implemented at the DIII-D National Fusion Facility. Utilizing these improvements to the hardware infrastructure, software enhancements are focusing on streamlined analysis, automation, and graphical user interface (GUI) systems to enlarge the user base. The adoption of the load balancing software package LSF Suite by Platform Computing has dramatically increased the availability of CPU cycles and the efficiency of their use. Streamlined analysis has been aided by the adoption of the MDSplus system to provide a unified interface to analyzed DIII-D data. The majority of MDSplus data is made available in between pulses giving the researcher critical information before setting up the next pulse. Work on data viewing and analysis tools focuses on efficient GUI design with object-oriented programming (OOP) for maximum code flexibility. Work to enhance the computational infrastructure at DIII-D has included a significant effort to aid the remote collaborator since the DIII-D National Team consists of scientists from 9 national laboratories, 19 foreign laboratories, 16 universities, and 5 industrial partnerships. As a result of this work, DIII-D data is available on a 24 x 7 basis from a set of viewing and analysis tools that can be run either on the collaborators' or DIII-Ds computer systems. Additionally, a Web based data and code documentation system has been created to aid the novice and expert user alike.

  4. Implication of Culture: User Roles in Information Fusion for Enhanced Situational Understanding (United States)


    IF community has rallied behind the Data Fusion Information Group (DFIG) process model (that replaces the JDL model) with its revisions and...Llinas, C. Bowman, G. Rogova, A. Steinberg, E. Waltz, & F. White, “Revisiting the JDL Data Fusion Model II”, Fusion2004. [39] M. L. Davidson

  5. Subbarrier heavy ion fusion enhanced by nucleon transfer and subbarrier fusion of nuclei far from the line of {beta}-stability

    Energy Technology Data Exchange (ETDEWEB)

    Denisov, V.Yu. [Institute for Nuclear Research, Kiev (Ukraine)]|[Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany)


    We discuss a model for the description of subbarrier fusion of heavy ions which takes into account the coupling to the low-energy surface vibrational states and to the few-nucleon transfer with arbitrary reaction Q-value. The fusion reactions {sup 28,30}Si+{sup 58,62,64}Ni, {sup 40}Ca+{sup 90,96}Zr, {sup 28}S+{sup 94,100}Mo, {sup 16,18,20,22,24}O+{sup 58}Ni and {sup 28}Si+{sup 124,126,128,130,132}Sn are analyzed in detail. The model describes rather well the experimental fusion cross section and mean angular momentum for reactions between nuclei near the {beta}-stability line. It is shown that these quantities are significantly enhanced by few-nucleon transfer with large positive Q-value. A shape independent parameterization of the heavy ion potential at distances smaller then the touching point is proposed. (orig.)

  6. Enhanced efficacy of CTLA-4 fusion anti-caries DNA vaccines in gnotobiotic hamsters

    Institute of Scientific and Technical Information of China (English)

    Feng ZHANG; Yu-hong LI; Ming-wen FAN; Rong JIA; Qing-an XU; Ji-hua GUO; Fei YU; Qi-wei TIAN


    Aim:To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte.associated antigen 4(CTLA-4)fusion anti-caries DNA vaccines pGJA-P/VAX1,pGJA-P,and non-fusion anti-caries DNA construct pGLUA-P in hamsters.In addition,the ability of CTLA-4 to target pGJA-P/VAX1-encoding antigen to dendritic cells was tested in vitro.Methods:All DNA constructs contain genes encoding the A-P regions of a cell surface protein(PAc) and the glucan binding(GLU) domain of glucosyltransferases(GTFs)of cari-ogenic organism Streptococcus mutans.Human dendritic cells were mixed with the CTLA-4-Ig-GLU-A-P protein expressed by pGJA-P/VAX1-transfected cells and analyzed by flow cytometry.Gnotobiotic hamsters were immunized with anti-caries DNA vaccines by intramuscular injection or intranasal administration.Antibody responses to a representative antigen PAc were assayed by ELlSA,and caries protection was evaluated by Keyes caries scores.Results:A flow cytometric analysis demonstrated that CTLA-4-Ig-GLU-A-P protein was capable of bind-ing to human dendritic cells.pGJA-P/VAX1 and pGJA-P induced significantly higher specific salivary and serum anti-PAc antibody responses than pGLUA-R.Significantly fewet caries lesions were alSO observed in hamsters immunized with pGJA-P/VAX1 and pGJA-p There was no significant difference in the anti-PAC antibody level or caries scores between pGJA-P/VAX1 and pGJA-P-immunized groups.Conclusion:Antigen encoded by CTLA-4 fusion anti-caries DNA vac-cine pGJA-P/VAX1 could specifically bind to human dendritic cells through the interaction of CTLA-4 and B7 molecules.Fusing antigen to CTLA-4 has been proven to greatly enhance the immunogenicity and protective efficacy of anti-caries DNA vaccines.

  7. Enhancement of monacolin K production via intergeneric protoplast fusion between Aspergillus terreus and Monascus anka

    Institute of Scientific and Technical Information of China (English)

    Chen Zhi; Lin Wen; Yu Ping; Song Yuan


    Intergenric protoplast fusion between Aspergillus terreus CA99 and Monascus anka M-3, the high and low producers of monacolin K respectively, was performed for enhancement of monacolin K production. The 24-hour-old mycelia of A. terreus CA99 and M. anka M-3 were treated with 0.5 % lywallzyme, 0.3 % snailase and 0.3 % cellulase at 34 ℃ for 5 h and at 30 ℃ for 3.5 h, and their protoplasts formation reached 1.76 × 107/mL and 1.68 × 107/mL respectively. Parental protoplasts were irradiated with a 30 W UVlight away from 30 cm for 3 min and then mixed. The mixture was incubated with 30% PEG 6000 for 15 min. The reviving fusants were isolated on the regeneration plates. Of the 363 fusants isolated, over 100 showed enhanced monacolin K production compared with the parental strain M. anka M-3. Ten of them produced monacolin K about 1.6-fold of that M. anka M-3 does and the monacolin K titer of two fusants (F49 and F104) increased by about 1-fold. The monacolin K yields of F49 and F104 were 460 μg/mL and 457 μg/mL respectively. In optimized fermentation medium, the monacolin K titer of F49 reached 1216 μg/mL.

  8. Creating an Artificial Tail Anchor as a Novel Strategy To Enhance the Potency of Peptide-Based HIV Fusion Inhibitors. (United States)

    Su, Shan; Zhu, Yun; Ye, Sheng; Qi, Qianqian; Xia, Shuai; Ma, Zhenxuan; Yu, Fei; Wang, Qian; Zhang, Rongguang; Jiang, Shibo; Lu, Lu


    20 (enfuvirtide) and other peptides derived from the human immunodeficiency virus type 1 (HIV-1) gp41 C-terminal heptad repeat (CHR) region inhibit HIV fusion by binding to the hydrophobic grooves on the N-terminal heptad repeat (NHR) trimer and blocking six-helix-bundle (6-HB) formation. Several strategies focusing on the binding grooves of the NHR trimer have been adopted to increase the antiviral activity of the CHR peptides. Here, we developed a novel and simple strategy to greatly enhance the potency of the existing peptide-based HIV fusion inhibitors. First, we identified a shallow pocket adjacent to the groove in the N-terminal region of NHR trimer as a new drug target, and then we designed several short artificial peptides to fit this target. After the addition of IDL (Ile-Asp-Leu) to the C terminus of CHR peptide WQ or MT-WQ, the conjugated peptides, WQ-IDL and MT-WQ-IDL, showed much more potent activities than WQ and T20, respectively, in inhibiting HIV-1 IIIB infection. WQ-IDL and MT-WQ-IDL were also more effective than WQ in blocking HIV-1 Env-mediated membrane fusion and had higher levels of binding affinity with NHR peptide N46. We solved the crystal structure of the 6-HB formed by MT-WQ-IDL and N46 and found that, besides the N-terminal MT hook tail, the IDL tail anchor of MT-WQ-IDL also binds with the shallow hydrophobic pocket outside the groove of the NHR trimer, resulting in enhanced inhibition of HIV-1 fusion with the target cell. It is expected that this novel approach can be widely used to improve the potency of peptidic fusion inhibitors against other enveloped viruses with class I fusion proteins.

  9. Enhancement and selective production of avermectin B by recombinants of Streptomyces avermitilis via intraspecific protoplast fusion

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhi; WEN Jia; SONG Yuan; WEN Ying; LI JiLun


    Among eight components of avermectin, B1 fractions have the most effective antiparasitic activities and the lowest level of toxic side-effects and are used widely in veterinary and agricultural fields. Intraspecific protoplast fusion between two strains of Streptomyces avermitilis, one an avermectin high producer (strain 76-05) and the other a genetically engineered strain containing the mutations aveD- and olmA- (strain 73-12) was performed for enhancement and selective production of avermectin B in the absence of oligomycin. Two recombinant strains (F23 and F29) were isolated and characterized with regards to the parental merits. F23 and F29 produced only the four avermectin B components with high yield and produced no oligomycin. The avermectin production of F23 and F29 was about 84.20% and 103.45% of the parental strain 76-05, respectively, and increased about 2.66-fold and 3.50-fold, respectively, compared to that of parental strain 73-12. F23 and F29 were genetically stable prototrophic recombinants and F29 was quite tolerant of fermentation conditions compared to avermectin high producer parental strain 76-05. The ability to produce avermectin B with high yield without the production of other avermectin components and oligomycin will make F23 and F29 useful strains for avermectin production. Strain F29's tolerance of fermentation conditions will also make it suitable for industrial applications.

  10. A Fusion-Loop Antibody Enhances the Infectious Properties of Immature Flavivirus Particles ▿ (United States)

    Rodenhuis-Zybert, Izabela A.; Moesker, Bastiaan; da Silva Voorham, Júlia M.; van der Ende-Metselaar, Heidi; Diamond, Michael S.; Wilschut, Jan; Smit, Jolanda M.


    Flavivirus-infected cells secrete a mixture of mature, partially immature, and fully immature particles into the extracellular space. Although mature virions are highly infectious, prM-containing fully immature virions are noninfectious largely because the prM protein inhibits the cell attachment and fusogenic properties of the virus. If, however, cell attachment and entry are facilitated by anti-prM antibodies, immature flavivirus becomes infectious after efficient processing of the prM protein by the endosomal protease furin. A recent study demonstrated that E53, a cross-reactive monoclonal antibody (MAb) that engages the highly conserved fusion-loop peptide within the flavivirus envelope glycoprotein, preferentially binds to immature flavivirus particles. We investigated here the infectious potential of fully immature West Nile virus (WNV) and dengue virus (DENV) particles opsonized with E53 MAb and observed that, like anti-prM antibodies, this anti-E antibody also has the capacity to render fully immature flaviviruses infectious. E53-mediated enhancement of both immature WNV and DENV depended on efficient cell entry and the enzymatic activity of the endosomal furin. Furthermore, we also observed that E53-opsonized immature DENV particles but not WNV particles required a more acidic pH for efficient cleavage of prM by furin, adding greater complexity to the dynamics of antibody-mediated infection of immature flavivirus virions. PMID:21880758

  11. Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

  12. Chloroquine Increases Glucose Uptake via Enhancing GLUT4 Translocation and Fusion with the Plasma Membrane in L6 Cells

    Directory of Open Access Journals (Sweden)

    Qi Zhou


    Full Text Available Background/Aims: Chloroquine can induce an increase in the cellular uptake of glucose; however, the underlying mechanism is unclear. Methods: In this study, translocation of GLUT4 and intracellular Ca2+ changes were simultaneously observed by confocal microscope in L6 cells stably over-expressing IRAP-mOrange. The GLUT4 fusion with the plasma membrane (PM was traced using HA-GLUT4-GFP. Glucose uptake was measured using a cell-based glucose uptake assay. GLUT4 protein was detected by Western blotting and mRNA level was detected by RT-PCR. Results: We found that chloroquine induced significant increases in glucose uptake, glucose transporter GLUT4 translocation to the plasma membrane (GTPM, GLUT4 fusion with the PM, and intracellular Ca2+ in L6 muscle cells. Chloroquine-induced increases of GTPM and intracellular Ca2+ were inhibited by Gallein (Gβγ inhibitor and U73122 (PLC inhibitor. However, 2-APB (IP3R blocker only blocked the increase in intracellular Ca2+ but did not inhibit GTPM increase. These results indicate that chloroquine, via the Gβγ-PLC-IP3-IP3R pathway, induces elevation of Ca2+, and this Ca2+ increase does not play a role in chloroqui-ne-evoked GTPM increase. However, GLUT4 fusion with the PM and glucose uptake were significantly inhibited with BAPTA-AM. This suggests that Ca2+ enhances GLUT4 fusion with the PM resulting in glucose uptake increase. Conclusion: Our data indicate that chloroquine via Gβγ-PLC-IP3-IP3R induces Ca2+ elevation, which in turn promotes GLUT4 fusion with the PM. Moreover, chloroquine can enhance GLUT4 trafficking to the PM. These mechanisms eventually result in glucose uptake increase in control and insulin-resistant L6 cells. These findings suggest that chloroquine might be a potential drug for improving insulin tolerance in diabetic patients.

  13. The effect of caveolin-1 on the expression of vascular endothelial growth factor receptor-2 in vascular endothelial growth factor-incubated osteosarcoma cells%小窝蛋白-1对血管内皮生长因子孵育的骨肉瘤细胞血管内皮生长因子受体-2表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    何道辉; 赵杰才


    目的:研究小窝蛋白-1(caveolin-1)对血管内皮生长因子(VEGF)孵育的骨肉瘤细胞株(SOSP-9607)血管内皮生长因子受体-2(VEGFR-2)表达的影响,探讨其在骨肉瘤发展中作用的可能机制.方法:实验分为三组,即对照组、VEGF组、VEGF+caveolin-1 小片段干扰核糖核酸(siRNA)组.反转录聚合酶链式反应(RT-PCR)检测VEGF孵育的SOSP-9607细胞中caveolin-1、VEGFR-2信使核糖核酸 (mRNA)的表达;蛋白质印迹(Western Blot)检测caveolin-1、VEGFR-2蛋白的表达.结果:与对照组相比,VEGF组细胞caveolin-1、VEGFR-2 mRNA和蛋白表达明显增加(均P<0.01),VEGF+caveolin-1 siRNA组细胞caveolin-1 mRNA和蛋白表达减少,而VEGFR-2 mRNA表达增加,蛋白水平却表达减少,差异具有统计学意义(P<0.05).结论:caveolin-1能明显减少VEGF刺激下的骨肉瘤细胞中的VEGFR-2蛋白水平的表达,提示caveolin-1在VEGF依赖性信号级联反应中起正调控作用,为临床选择合适的靶点治疗骨肉瘤的血管生成提供实验依据.%Objective: To observe the effect of caveolin-1 on the expression of VEGFR-2 in VEGF-incubated osteosarco-ma cells and to explore the possible mechanism of its role on osteosarcoma development. Methods: There were three groups, control group, VEGF group, VEGF+caveolin-1 siRNA group. The expression of caveolin-1, VEGFR-2 mRNA and protein were detected with RT-PCR and Western Blot. Results: Compared with the control group, the expression of caveolin-1, VEGFR-2 significantly increased in VEGF group (all P<0.01). Compared with the control group, the expressions of mRNA and protein of caveolin-1 decreased, while the expression of mRNA of VEGFR-2 increased, and protein was reduced in VEGF+caveolin-1 siRNA group, there was a significant difference (P<0.05). Conclusion: caveolin-1 can significantly reduce the expression of VEGFR-2 in protein level in VEGF-stimulated osteosarcoma cells, suggesting that cave -olin-1 plays a positive regulatory role in VEGF

  14. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging. (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R


    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  15. An evolved Mxe GyrA intein for enhanced production of fusion proteins. (United States)

    Marshall, Carrie J; Grosskopf, Vanessa A; Moehling, Taylor J; Tillotson, Benjamin J; Wiepz, Gregory J; Abbott, Nicholas L; Raines, Ronald T; Shusta, Eric V


    Expressing antibodies as fusions to the non-self-cleaving Mxe GyrA intein enables site-specific, carboxy-terminal chemical modification of the antibodies by expressed protein ligation (EPL). Bacterial antibody-intein fusion protein expression platforms typically yield insoluble inclusion bodies that require refolding to obtain active antibody-intein fusion proteins. Previously, we demonstrated that it was possible to employ yeast surface display to express properly folded single-chain antibody (scFv)-intein fusions, therefore permitting the direct small-scale chemical functionalization of scFvs. Here, directed evolution of the Mxe GyrA intein was performed to improve both the display and secretion levels of scFv-intein fusion proteins from yeast. The engineered intein was shown to increase the yeast display levels of eight different scFvs by up to 3-fold. Additionally, scFv- and green fluorescent protein (GFP)-intein fusion proteins can be secreted from yeast, and while fusion of the scFvs to the wild-type intein resulted in low expression levels, the engineered intein increased scFv-intein production levels by up to 30-fold. The secreted scFv- and GFP-intein fusion proteins retained their respective binding and fluorescent activities, and upon intein release, EPL resulted in carboxy-terminal azide functionalization of the target proteins. The azide-functionalized scFvs and GFP were subsequently employed in a copper-free, strain-promoted click reaction to site-specifically immobilize the proteins on surfaces, and it was demonstrated that the functionalized, immobilized scFvs retained their antigen binding specificity. Taken together, the evolved yeast intein platform provides a robust alternative to bacterial intein expression systems.

  16. Selective retention of bone marrow-derived cells to enhance spinal fusion. (United States)

    Muschler, George F; Matsukura, Yoichi; Nitto, Hironori; Boehm, Cynthia A; Valdevit, Antonio D; Kambic, Helen E; Davros, William J; Easley, Kirk A; Powell, Kimerly A


    Connective tissue progenitors can be concentrated rapidly from fresh bone marrow aspirates using some porous matrices as a surface for cell attachment and selective retention, and for creating a cellular graft that is enriched with respect to the number of progenitor cells. We evaluated the potential value of this method using demineralized cortical bone powder as the matrix. Matrix alone, matrix plus marrow, and matrix enriched with marrow cells were compared in an established canine spinal fusion model. Fusions were compared based on union score, fusion mass, fusion volume, and by mechanical testing. Enriched matrix grafts delivered a mean of 2.3 times more cells and approximately 5.6 times more progenitors than matrix mixed with bone marrow. The union score with enriched matrix was superior to matrix alone and matrix plus marrow. Fusion volume and fusion area also were greater with the enriched matrix. These data suggest that the strategy of selective retention provides a rapid, simple, and effective method for concentration and delivery of marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting procedures in various clinical settings.

  17. Tumor necrosis factor-{alpha} enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kai; Zhu, Fei; Zhang, Han-zhong [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Shang, Zheng-jun, E-mail: [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); First Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan (China)


    Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events. Our results showed that oral cancer cells can fuse spontaneously with endothelial cells in co-culture and inflammatory cytokine tumor necrosis factor-{alpha} (TNF-{alpha}) increased fusion of human umbilical vein endothelium cells and oral cancer cells by up to 3-fold in vitro. Additionally, human oral squamous cell carcinoma cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA-4, an integrin, previously implicated in fusions between human peripheral blood CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma. Moreover, immunocytochemistry and flow cytometry analysis revealed that expression of VCAM-1 increased obviously in TNF-{alpha}-stimulated endothelial cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer-endothelial adhesion and block such fusion. Collectively, our results suggested that TNF-{alpha} could enhance cancer-endothelial cell adhesion and fusion through VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of cancer-endothelial cell fusion, and has important implications for the development of novel therapeutic strategies for prevention of metastasis. -- Highlights: Black-Right-Pointing-Pointer Spontaneous oral cancer-endothelial cell fusion. Black-Right-Pointing-Pointer TNF-{alpha} enhanced cell fusions. Black-Right-Pointing-Pointer VCAM-1/VLA-4 expressed in oral cancer. Black-Right-Pointing-Pointer TNF-{alpha} increased expression of VCAM-1 on endothelial cells. Black

  18. Caveolin-1 expression in cancer-associated fibroblasts and its correlation with molecular typing of invasive ductal breast carcinoma%Caveolin-1在乳腺浸润性导管癌间质内癌相关成纤维细胞中的表达水平与乳腺癌分子亚型的相关性

    Institute of Scientific and Technical Information of China (English)

    王善伟; 徐侃伦; 赵莉莉; 陈丽荣


    Objective To investigate the expression of caveolin-l (Cav-1) in breast cancer-associated fibroblasts(CAFs) and to indicate its correlation with molecular typing and gene copy number of HER-2/neu in invasive ductal breast carcinoma (IDC). Methods One hundred and forty-five cases of breast cancer molecular subtypes were enrolled in the study. En Vision immunohisto-chemical method was used to detect Cav-1 expression of 168 cases with breast cancer in CAFs situation. Fluorescence in situ hybridization ( FISH) was used to detect HER-2 gene amplification status of breast cancer. HER-2 gene amplification in breast cancer and the correlation with stromal expression of Cav-1 was analyzed. Results Cav-1 expression in CAFs in breast cancer with pathological closely related to molecular typing. The positive rates in HER-2 + type and Luminal B type groups were 83. 3% (35/42) ,83. 3% (20/24), significantly higher than that in Luminal A group(58. 1% ) and Basal-like type group(35. 3% ), the differences were statistically significant (P < 0. 05). Cav-1 expression in CAFs was positively correlated with HER-2 protein expression and HER-2 gene status. HER-2 gene status were detected by FISH, stromal Cav-1 positive rate of HER-2 gene amplification group was 83. 3% (55/66), higher than those without amplification group55. 9% (57/102), the differences were statistically significant (P <0.05). Cav-1 expression in CAFs was positively correlated with molecular typing, HER-2 protein expression and HER-2 gene status. Stromal caveolin-1 expression was significantly associated with prognosis (P = 0. 041). Conclusion Cav-1 expression in CAFs is positively correlated with molecular typing, HER-2 protein expression and HER-2 gene status. The over expression of Cav-1 in stromal CAFs of invasive breast cancer predicts good prognostic outcome.%目的 检测Caveolin-1(Gay-1)在乳腺浸润性导管癌间质内癌相关成纤维细胞(CAFs)中的表达,分析Cav-1与乳腺癌分子亚型、HER-2基

  19. Lensfree Spectral Light-field Fusion Microscopy for Contrast- and Resolution-enhanced Imaging of Biological Specimens

    CERN Document Server

    Kazemzadeh, Farnoud; Molladavoodi, Sara; Mei, Yu; Emelko, Monica B; Gorbet, Maud B; Wong, Alexander


    A lensfree spectral light-field fusion microscopy (LSLFM) system is presented for enabling contrast- and resolution-enhanced imaging of biological specimens. LSLFM consists of a pulsed multispectral lensfree microscope for capturing interferometric light-field encodings at different wavelengths, and Bayesian-based fusion to reconstruct a fused object light-field from the encodings. By fusing unique object detail information captured at different wavelengths, LSLFM can achieve improved resolution, contrast, and signal-to-noise ratio (SNR) over a single-channel lensfree microscopy system. A five-channel LSLFM system was developed and quantitatively evaluated to validate the design. Experimental results demonstrated that the LSLFM system provided SNR improvements of 6.81-16.55 dB, as well as a six-fold improvement in the dispersion index (DI), over that achieved using a single-channel lensfree deconvolution microscopy system at individual wavelengths. Furthermore, the LSLFM system achieved an increase in numeric...

  20. Site-directed antibody immobilization using a protein A-gold binding domain fusion protein for enhanced SPR immunosensing. (United States)

    de Juan-Franco, Elena; Caruz, Antonio; Pedrajas, J R; Lechuga, Laura M


    We have implemented a novel strategy for the oriented immobilization of antibodies onto a gold surface based on the use of a fusion protein, the protein A-gold binding domain (PAG). PAG consists of a gold binding peptide (GBP) coupled to the immunoglobulin-binding domains of staphylococcal protein A. This fusion protein provides an easy and fast oriented immobilization of antibodies preserving its native structure, while leaving the antigen binding sites (Fab) freely exposed. Using this immobilization strategy, we have demonstrated the performance of the immunosensing of the human Growth Hormone by SPR. A limit of detection of 90 ng mL(-1) was obtained with an inter-chip variability lower than 7%. The comparison of this method with other strategies for the direct immobilization of antibodies over gold surfaces has showed the enhanced sensitivity provided by the PAG approach.

  1. Enhanced loss of fusion products during mode conversion heating in TFTR

    Energy Technology Data Exchange (ETDEWEB)

    Darrow, D.S.; Majeski, R.; Fisch, N.J.; Heeter, R.F.; Herrmann, H.W.; Herrmann, M.C.; Zarnstorff, M.C.; Zweben, S.J.


    Ion Bernstein waves (IBWS) have been generated by mode conversion of ion cyclotron range of frequency (ICRF) fast waves in TFTR. The loss rate of fusion products in these discharges can be large, up to 10 times the first orbit loss rate. The losses are observed at the passing/trapped boundary, indicating that passing particles are being moved onto loss orbits either by increase of their v{perpendicular} due to the wave, by outward transport in minor radius, or both. The lost particles appear to be DD fusion produced tritons heated to {approximately}1.5 times their birth energy.

  2. Up-regulation of syncytin-1 contributes to TNF-α-enhanced fusion between OSCC and HUVECs partly via Wnt/β-catenin-dependent pathway (United States)

    Yan, Ting-Lin; Wang, Meng; Xu, Zhi; Huang, Chun-Ming; Zhou, Xiao-Cheng; Jiang, Er-Hui; Zhao, Xiao-Ping; Song, Yong; Song, Kai; Shao, Zhe; Liu, Ke; Shang, Zheng-Jun


    Accumulating evidence implies that cell fusion is one of the driving forces of cancer invasion and metastasis. However, considerably less is still known about the triggering factors and underlying mechanisms associated with cancer-host cell fusion, particularly in inflammatory tumor microenvironment. In this study, we confirmed that inflammatory factor TNF-α could enhance fusion between squamous cell carcinoma cells 9 (SCC-9) and human umbilical vein endothelial cells (HUVEC). Further study revealed that TNF-α could promote up-regulation of syncytin-1 in SCC-9 and its receptor neutral amino acid transporter type 2 (ASCT-2) in HUVEC. Syncytin-1 acted as an important downstream effector in TNF-α-enhanced cancer-endothelial cell fusion. TNF-α treatment also led to the activation of Wnt/β-catenin signal pathway in SCC-9. The activation of Wnt/β-catenin signal pathway was closely associated with the up-regulation of syncytin-1 in SCC-9 and increased fusion between SCC-9 and HUVEC while blocking of Wnt/β-catenin signal pathway resulted in the corresponding down-regulation of syncytin-1 accompanied by sharp decrease of cancer-endothelial cell fusion. Taking together, our results suggest that Wnt/β-catenin signal pathway activation-dependent up-regulation of syncytin-1 contributes to the pro-inflammatory factor TNF-α-enhanced fusion between oral squamous cell carcinoma cells and endothelial cells. PMID:28112190

  3. Enhancement of the multi-channel continuous monitoring system through the use of Xenorhabdus luminescens lux fusions. (United States)

    Lee, Jin Hyung; Mitchell, Robert J; Gu, Man Bock


    The enhancement of the multi-channel continuous toxicity monitoring system developed previously was studied. To achieve better and more stable results from the system, the use of thermo-lux fusion strains that express the luxCDABE genes from Xenorhabdus luminescens was evaluated. A total of six recombinant Escherichia coli strains with the promoters from three oxidative-stress responsive genes, i.e. the katG, sodA and pqi-5 genes, fused to either the lux genes from Vibrio fischeri or X. luminescens were characterized and their responses to different chemicals compared. It was found that the basal level bioluminescence (BL) from the thermo-lux fusion strains was always higher while that of the V. fischeri lux strains were always near or below the lower limit of detection of the system. For example, the katG::V. fischeri lux strain, DPD2511, gave no discernible response due to its low level expression while a fusion of the katG promoter with the X. luminescens lux operon was clearly responsive and capable of detecting hydrogen peroxide down to about 1 ppm. The use of the thermo-lux strains found them to be as sensitive as the V. fischeri lux strains while providing a brighter, more stable basal level bioluminescence, making the analysis and monitoring of water-borne toxicity more reliable.

  4. Enhancing the antimicrobial activity of Sus scrofa lysozyme by N-terminal fusion of a sextuple unique homologous peptide. (United States)

    Zhu, Dewei; Cai, Guolin; Li, Xiaomin; Lu, Jian; Zhang, Liang


    Sus scrofa lysozyme (SSL), an important component of the pig immune system, is a potential candidate to replace antibiotics in feed. However, there is little antimicrobial activity of natural SSL against gram-negative bacteria, which limits its application. In this study, a unique peptide (A-W-V-A-W-K) with antimicrobial activity against gram-negative bacteria was discovered and purified from trypsin hydrolysate of natural SSL. This unique peptide was fused to natural SSL and the recombinant fused SSL exhibited improved activity against gram-negative bacteria. The N-terminal fusion likely increased the membrane penetrability and induced programmed bacterial cell death. The recombinant fused SSL also showed higher activity against some gram-positive bacteria with O-acetylation. By N-terminal fusion of the sextuple peptide, the anti-microbial activity, either to gram-positive or negative bacteria, of the recombinant SSL was higher than the fusion of only one copy of the peptide. This study provides a general, feasible, and highly useful strategy to enhance the antimicrobial activity of lysozyme.

  5. Isotopic dependence of fusion enhancement of various heavy ion systems using energy dependent Woods-Saxon potential (United States)

    Gautam, Manjeet Singh


    In the present work, the fusion of symmetric and asymmetric projectile-target combinations are deeply analyzed within the framework of energy dependent Woods-Saxon potential model (EDWSP model) in conjunction with one dimensional Wong formula and the coupled channel code CCFULL. The neutron transfer channels and the inelastic surface excitations of collision partners are dominating mode of couplings and the coupling of relative motion of colliding nuclei to such relevant internal degrees of freedom produces a significant fusion enhancement at sub-barrier energies. It is quite interesting that the effects of dominant intrinsic degrees of freedom such as multi-phonon vibrational states, neutron transfer channels and proton transfer channels can be simulated by introducing the energy dependence in the nucleus-nucleus potential (EDWSP model). In the EDWSP model calculations, a wide range of diffuseness parameter ranging from a = 0.85 fm to a = 0.97 fm, which is much larger than a value (a = 0.65 fm) extracted from the elastic scattering data, is needed to reproduce sub-barrier fusion data. However, such diffuseness anomaly, which might be an artifact of some dynamical effects, has been resolved by trajectory fluctuation dissipation (TFD) model wherein the resulting nucleus-nucleus potential possesses normal diffuseness parameter.

  6. Isotopic dependence of fusion enhancement of various heavy ion systems using energy dependent Woods–Saxon potential

    Energy Technology Data Exchange (ETDEWEB)

    Gautam, Manjeet Singh, E-mail:


    In the present work, the fusion of symmetric and asymmetric projectile–target combinations are deeply analyzed within the framework of energy dependent Woods–Saxon potential model (EDWSP model) in conjunction with one dimensional Wong formula and the coupled channel code CCFULL. The neutron transfer channels and the inelastic surface excitations of collision partners are dominating mode of couplings and the coupling of relative motion of colliding nuclei to such relevant internal degrees of freedom produces a significant fusion enhancement at sub-barrier energies. It is quite interesting that the effects of dominant intrinsic degrees of freedom such as multi-phonon vibrational states, neutron transfer channels and proton transfer channels can be simulated by introducing the energy dependence in the nucleus–nucleus potential (EDWSP model). In the EDWSP model calculations, a wide range of diffuseness parameter ranging from a=0.85 fm to a=0.97 fm, which is much larger than a value (a=0.65 fm) extracted from the elastic scattering data, is needed to reproduce sub-barrier fusion data. However, such diffuseness anomaly, which might be an artifact of some dynamical effects, has been resolved by trajectory fluctuation dissipation (TFD) model wherein the resulting nucleus–nucleus potential possesses normal diffuseness parameter.

  7. 糖尿病足截肢患者股神经中小窝蛋白1的表达及意义%Expression and significance of caveolin-1 in femoral nerve of diabetic foot amputation patients

    Institute of Scientific and Technical Information of China (English)

    丁敏; 褚月颉; 徐俊; 章鸣放; 赵凤云; 王鹏华


    Objective To investigate the expression and significance of caveolin-1 in femoral nerve of diabetic patients with foot amputation. Methods Forty patients with foot amputation were assigned to 3 groups according to their duration of type 2 diabetes: group A ( <6 years=, group B (6-10 years), and group C ( >10 years). Hematoxylin and eosin (HE) stain and Weil's stain were used to examine the femoral nerve. Silver staining was used to observe the axons and to count the nerve fiber density. The expression of caveolin-1 in Schwann cells of femoral nerve was tested by immunohistochemisty. Results There were evident progressive pathological changes in femoral nerve in the 3 groups. The variance of nerve fiber density in the 3 groups reached statistical significance ( P<0. 05 =, the nerve fiber density showed negative correlation with HbA1C( r =-0. 792, P<0. 01 = and duration ( r=-0.592, P<0. 01 =. The expression of caveolin-1 in Schwann cells of femoral nerve was positive in all the 3 groups and the variance with statistical significance (P<0. 01 ), it was negatively correlated with HbA1C (r=-0. 762, P<0. 01 )and duration (r=-0. 532, P<0. 01 ), and it was positively correlated with nerve fiber density (r=0. 721, P<0.01 ), the partial correlation coefficient of caveolin-1 and HbA1Cwas-0. 505 ( P<0. 01 ).Conclusion In patients with diabetic foot amputation, caveolin-1 may play a role in the development of diabetic peripheral neuropathy and diabetic foot.%目的 探讨糖尿病足截肢患者股神经雪旺氏细胞中小窝蛋白1的表达及意义.方法 40例糖尿病足截肢患者根据2型糖尿病病程分为A(<6年),B(6~10年),C(>10年)3组.HE、Weil氏染色观察股神经病理学改变,银染法进行轴突染色并计数股神经纤维密度.应用免疫组化染色检测雪旺氏细胞中小窝蛋白1的表达.结果 3组股神经均存在明显的病理改变,随着病程延长病变加重.3组间股神经纤维密

  8. A multi-modal fusion scheme for the enhancement of PET/MR viewing

    Energy Technology Data Exchange (ETDEWEB)

    Aiello, Marco [IRCCS SDN, Naples (Italy); Monti, Serena [IRCCS SDN, Naples (Italy); Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano (Italy); Inglese, Marianna; Forte, Ernest; Cavaliere, Carlo [IRCCS SDN, Naples (Italy); Catalano, Onofrio Antonio [IRCCS SDN, Naples (Italy); Università degli studi di Napoli, Parthenope (Italy); Nicolai, Emanuele; Salvatore, Marco [IRCCS SDN, Naples (Italy)


    PET/MR imaging offers the possibility to achieve in one-shot both functional information provided by PET imaging and morpho-functional information with excellent soft tissue contrast provided by MRI. As a result of a typical PET/MR acquisition, each voxel carries a large amount of multivariate information that can be combined into a single image for a synthetic multi-parametric viewing (image fusion). This work is aimed to explore and introduce a reliable fusion scheme able to blend the useful information carried out from each modality into a single meaningful image. The proposed approach consists of a transformation of the source images followed by a blending and a consecutive reconstruction of fused image into the original domain. Following this scheme, three different transformations of source images (wavelet domain, Fourier domain and identity) and two blending procedures (alpha-blending and gamma-blending) were considered. For a comprehensive assessment of the fusion schemes under investigation, the results were evaluated both qualitatively and quantitatively on a dataset of 60 naturally coregistered. FDG-PET/MR studies of different anatomical districts in presence of neurological as well as oncological findings. The quality of fused images was assessed by experts who visually evaluated the loss of useful information with respect to the original modalities. Quantitatively, the information loss was estimated by means of a boundaries-preservation based metric as well as a metric based on mutual information. Preliminary results show that the fusion scheme composed by a wavelet-domain transform and a gamma-blending better depicts useful information of the original modalities. In particular, the proposed approach allows to better unveil the MR signal underlying PET signal in fused images in oncological as well as neurological studies. Furthermore, the use of a gamma-blending procedure ensures the best performances in a fully automated manner.

  9. Ovine Herpesvirus 2 Glycoproteins B, H, and L Are Sufficient for, and Viral Glycoprotein Ov8 Can Enhance, Cell-Cell Membrane Fusion. (United States)

    AlHajri, Salim M; Cunha, Cristina W; Nicola, Anthony V; Aguilar, Hector C; Li, Hong; Taus, Naomi S


    Ovine herpesvirus 2 (OvHV-2) is a gammaherpesvirus in the genus Macavirus that is carried asymptomatically by sheep. Infection of poorly adapted animals with OvHV-2 results in sheep-associated malignant catarrhal fever, a fatal disease characterized by lymphoproliferation and vasculitis. There is no treatment or vaccine for the disease and no cell culture system to propagate the virus. The lack of cell culture has hindered studies of OvHV-2 biology, including its entry mechanism. As an alternative method to study OvHV-2 glycoproteins responsible for membrane fusion as a part of the entry mechanism, we developed a virus-free cell-to-cell membrane fusion assay to identify the minimum required OvHV-2 glycoproteins to induce membrane fusion. OvHV-2 glycoproteins B, H, and L (gB, gH, and gL) were able to induce membrane fusion together but not when expressed individually. Additionally, open reading frame Ov8, unique to OvHV-2, was found to encode a transmembrane glycoprotein that can significantly enhance membrane fusion. Thus, OvHV-2 gB, gH, and gL are sufficient to induce membrane fusion, while glycoprotein Ov8 plays an enhancing role by an unknown mechanism.IMPORTANCE Herpesviruses enter cells via attachment of the virion to the cellular surface and fusion of the viral envelope with cellular membranes. Virus-cell membrane fusion is an important step for a successful viral infection. Elucidating the roles of viral glycoproteins responsible for membrane fusion is critical toward understanding viral entry. Entry of ovine herpesvirus 2 (OvHV-2), the causative agent of sheep associated-malignant catarrhal fever, which is one of the leading causes of death in bison and other ungulates, has not been well studied due to the lack of a cell culture system to propagate the virus. The identification of OvHV-2 glycoproteins that mediate membrane fusion may help identify viral and/or cellular factors involved in OvHV-2 cell tropism and will advance investigation of cellular

  10. Enhanced in vitro refolding of fibroblast growth factor 15 with the assistance of SUMO fusion partner.

    Directory of Open Access Journals (Sweden)

    Bo Kong

    Full Text Available Fibroblast growth factor 15 (Fgf15 is the mouse orthologue of human FGF19. Fgf15 is highly expressed in the ileum and functions as an endocrine signal to regulate liver function, including bile acid synthesis, hepatocyte proliferation and insulin sensitivity. In order to fully understand the function of Fgf15, methods are needed to produce pure Fgf15 protein in the prokaryotic system. However, when expressed in Escherichia coli (E. coli, the recombinant Fgf15 protein was insoluble and found only in inclusion bodies. In the current study, we report a method to produce recombinant Fgf15 protein in E. coli through the use of small ubiquitin-related modifier (SUMO fusion tag. Even though the SUMO has been shown to strongly improve protein solubility and expression levels, our studies suggest that the SUMO does not improve Fgf15 protein solubility. Instead, proper refolding of Fgf15 protein was achieved when Fgf15 was expressed as a partner protein of the fusion tag SUMO, followed by in vitro dialysis refolding. After refolding, the N-terminal SUMO tag was cleaved from the recombinant Fgf15 fusion protein by ScUlp1 (Ubiquitin-Like Protein-Specific Protease 1 from S. cerevisiae. With or without the SUMO tag, the refolded Fgf15 protein was biologically active, as revealed by its ability to reduce hepatic Cyp7a1 mRNA levels in mice. In addition, recombinant Fgf15 protein suppressed Cyp7a1 mRNA levels in a dose-dependent manner. In summary, we have developed a successful method to express functional Fgf15 protein in prokaryotic cells.

  11. 小窝蛋白-1在食管癌患者血清中的表达及其临床意义%The expression of caveolin-1 and its clinic significance in the sera of esophageal cancer patients

    Institute of Scientific and Technical Information of China (English)

    陈素钻; 吴瑞暖; 俞晶; 刘朝晖; 郭光华


    目的:了解小窝蛋白-1( Cav-1)在食管癌患者血清中的表达情况,探讨Cav-1是否可以作为食管癌肿瘤标记物。方法⑴用Western Blot方法检测食管癌细胞EC109、EC9706中Cav-1的表达情况;⑵收集本院43例食管癌患者血清,30例良性食管病变患者血清及50例健康体检者血清,应用ELISA方法检测其Cav-1的表达情况。结果⑴Western Blot 结果显示,Cav-1在食管癌细胞EC109、EC9706中均表达;在低分化的食管癌细胞EC109中表达水平明显高于高分化的食管癌细胞EC9706( t =3.08, P =0.035)。⑵ELISA结果显示,食管癌患者血清Cav-1中位数为0.104 ng/ml;良性食管病变患者血清Cav-1中位数为0.075 ng/ml;健康体检者血清Cav-1中位数为0.081 ng/ml;食管癌患者血清与良性食管病变及健康体检者对比,差异有统计学意义(χ2=23.16, P =0.001)。结论 Cav-1在食管癌患者血清中的表达高于良性食管病变患者及健康体检者,有望成为食管癌肿瘤标志物。%Objective To investigate the expression of caveolin-1 in the sera of esophageal cancer patients , and the possibility of caveolin-1 to be the tumor marker of an esophageal cancer .Methods ⑴Western blot was used to detect the expression of caveolin-1 in esophageal cancer cell EC 109 and EC9706;⑵The sera were collected from 43 esophageal cancer patients , 30 benign esophageal lesions, and 50 healthy control men.Enzyme linked immunosorbent assay (ELISA) was used to detect caveolin-1 in serum.Results⑴Western blot showed that caveolin-1 was detected in two types of esophageal cancer cell lines .The level of caveolin-1 in the poor dif-ferentiated EC109 cell line was mush higher than in the well differentiated EC 9706 cell line ( t =3.08 , P =0.035 ) .⑵ ELISA re-vealed that the median level of serum caveolin-1 in 43 esophageal cancers (0.104 ng/ml) was significantly higher than 30 benign e-sophageal lesions (0

  12. Ischemia Induced Caveolin-1 Moving from Cell Membrane to Lipid Droplets in Type Ⅱ Alveolar Epithelial Cell%缺血引起陷窝蛋白-1在肺泡Ⅱ型上皮细胞定位的改变

    Institute of Scientific and Technical Information of China (English)

    李凌海; 耿万明; 王子彤; 秦林; 张慧娜


    Type Ⅱ alveolar epithelial cells play an important role in ischemia of the lung.In this research,the authors studied the intracellular location of the caveolin-1 in type Ⅱ alveolar epithelial cells under normal and ischemia status.They purified the lipid droplets from type Ⅱ alveolar epithelial cell line A549.The results indicated that caveolin-1 was localized on plasma membrane as well as lipid droplets of alveolar epithelial cell,whereas ischemia stimulus induced caveolin-1 moving from cell membrane to lipid droplets in A549 cell line.In human lung tissue,They also observed the translocation of caveolin-1 from cell membrane to lipid droplets under ischemia status.These findings may promote new directions in future research concerning the mechanism of lung ischemia injury.%肺泡Ⅱ型上皮细胞在肺缺血病理过程中具有重要作用.为研究缺血对陷窝蛋白-1在肺泡Ⅱ型上皮细胞A549脂滴定位的影响,利用已经建立的脂滴纯化方法,纯化得到肺泡Ⅱ型上皮细胞A549的脂滴,并在脂滴上发现了陷窝蛋白-1.在A549细胞缺血模型中发现缺血可以导致陷窝蛋白-1从细胞膜移动到脂滴.人肺组织脂滴纯化实验也证实缺血可以刺激陷窝蛋白-1从细胞膜移动到脂滴.这一发现将为肺缺血机制的研究提供新的思路.


    Directory of Open Access Journals (Sweden)

    K.V. Santhosh


    Full Text Available This paper proposes a technique for measurement of liquid flow using venturi and ultrasonic flow meter(UFM to have following objectives a to design a multi-sensor data fusion (MSDF architecture for using both the sensors, b improve sensitivity and linearity of venturi and ultrasonic flow meter, and c detect and diagnosis of faults in sensor if any. Fuzzy logic algorithm is used to fuse outputs of both the sensor and train the fuzzy block to produces output which has an improved characteristics in terms of both sensitivity and linearity. For identification of sensor faults a comparative test algorithm is designed. Once trained proposed technique is tested in real life, results show successful implementation of proposed objectives.

  14. Screening, mutagenesis and protoplast fusion of Aspergillus niger for the enhancement of extracellular glucose oxidase production. (United States)

    Khattab, A A; Bazaraa, W A


    Various strains of Aspergillus niger were screened for extracellular glucose oxidase (GOD) activity. The most effective producer, strain FS-3 (15.9 U mL(-1)), was mutagenized using UV-irradiation or ethyl methane sulfonate. Of the 400 mutants obtained, 32 were found to be resistant to 2-deoxy D: -glucose, and 17 of these exhibited higher GOD activities (from 114.5 to 332.1%) than the original FS-3 strain. Following determination of antifungal resistance of the highest producing mutants, four mutants were selected and used in protoplast fusions in three different intraspecific crosses. All fusants showed higher activities (from 285.5 to 394.2%) than the original strain. Moreover, of the 30 fusants isolated, 19 showed higher GOD activity than their corresponding higher-producing parent strain.

  15. Enhancement of the influenza A hemagglutinin (HA-mediated cell-cell fusion and virus entry by the viral neuraminidase (NA.

    Directory of Open Access Journals (Sweden)

    Bin Su

    Full Text Available BACKGROUND: The major role of the neuraminidase (NA protein of influenza A virus is related to its sialidase activity, which disrupts the interaction between the envelope hemagglutinin (HA protein and the sialic acid receptors expressed at the surface of infected cells. This enzymatic activity is known to promote the release and spread of progeny viral particles following their production by infected cells, but a potential role of NA in earlier steps of the viral life cycle has never been clearly demonstrated. In this study we have examined the impact of NA expression on influenza HA-mediated viral membrane fusion and virion infectivity. METHODOLOGY/PRINCIPAL FINDINGS: The role of NA in the early stages of influenza virus replication was examined using a cell-cell fusion assay that mimics HA-mediated membrane fusion, and a virion infectivity assay using HIV-based pseudoparticles expressing influenza HA and/or NA proteins. In the cell-cell fusion assay, which bypasses the endocytocytosis step that is characteristic of influenza virus entry, we found that in proper HA maturation conditions, NA clearly enhanced fusion in a dose-dependent manner. Similarly, expression of NA at the surface of pseudoparticles significantly enhanced virion infectivity. Further experiments using exogenous soluble NA revealed that the most likely mechanism for enhancement of fusion and infectivity by NA was related to desialylation of virion-expressed HA. CONCLUSION/SIGNIFICANCE: The NA protein of influenza A virus is not only required for virion release and spread but also plays a critical role in virion infectivity and HA-mediated membrane fusion.

  16. Enhancement of yellow pigment production by intraspecific protoplast fusion of Monascus spp. yellow mutant (ade(-)) and white mutant (prototroph). (United States)

    Klinsupa, Worawan; Phansiri, Salak; Thongpradis, Panida; Yongsmith, Busaba; Pothiratana, Chetsada


    To breed industrially useful strains of a slow-growing, yellow pigment producing strain of Monascus sp., protoplasts of Monascus purpureus yellow mutant (ade(-)) and rapid-growing M. purpureus white mutant (prototroph) were fused and fusants were selected on minimal medium (MM). Preliminary conventional protoplast fusion of the two strains was performed and the result showed that only white colonies were detected on MM. It was not able to differentiate the fusants from the white parental prototroph. To solve this problem, the white parental prototroph was thus pretreated with 20mM iodoacetamide (IOA) for cytoplasm inactivation and subsequently taken into protoplast fusion with slow-growing Monascus yellow mutant. Under this development technique, only the fusants, with viable cytoplasm from Monascus yellow mutant (ade(-)), could thus grow on MM, whereas neither IOA pretreated white parental prototroph nor yellow auxotroph (ade(-)) could survive. Fifty-three fusants isolated from yellow colonies obtained through this developed technique were subsequently inoculated on complete medium (MY agar). Fifteen distinguished yellow colonies from their parental yellow mutant were then selected for biochemical, morphological and fermentative properties in cassava starch and soybean flour (SS) broth. Finally, three most stable fusants (F7, F10 and F43) were then selected and compared in rice solid culture. Enhancement of yellow pigment production over the parental yellow auxotroph was found in F7 and F10, while enhanced glucoamylase activity was found in F43. The formation of fusants was further confirmed by monacolin K content, which was intermediate between the two parents (monacolin K-producing yellow auxotroph and non-monacolin K producing white prototroph).

  17. Uniaxial cyclic strain enhances adipose-derived stem cell fusion with skeletal myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Jens Isak; Juhl, Morten; Nielsen, Thøger; Emmersen, Jeppe; Fink, Trine; Zachar, Vladimir; Pennisi, Cristian Pablo, E-mail:


    Highlights: • Uniaxial cyclic tensile strain (CTS) applied to ASCs alone or in coculture with myogenic precursors. • CTS promoted the formation of a highly ordered array of parallel ASCs. • Without biochemical supplements, CTS did not support advanced myogenic differentiation of ASCs. • Mechanical stimulation of cocultures boosted fusion of ASCs with skeletal myoblasts. - Abstract: Although adult muscle tissue possesses an exceptional capacity for regeneration, in the case of large defects, the restoration to original state is not possible. A well-known source for the de novo regeneration is the adipose-derived stem cells (ASCs), which can be readily isolated and have been shown to have a broad differentiation and regenerative potential. In this work, we employed uniaxial cyclic tensile strain (CTS), to mechanically stimulate human ASCs to participate in the formation skeletal myotubes in an in vitro model of myogenesis. The application of CTS for 48 h resulted in the formation of a highly ordered array of parallel ASCs, but failed to support skeletal muscle terminal differentiation. When the same stimulation paradigm was applied to cocultures with mouse skeletal muscle myoblasts, the percentage of ASCs contributing to the formation of myotubes significantly exceeded the levels reported in the literature hitherto. In perspective, the mechanical strain may be used to increase the efficiency of incorporation of ASCs in the skeletal muscles, which could be found useful in diverse traumatic or pathologic scenarios.

  18. Satellite-based enhancement of archaeological marks through data fusion techniques (United States)

    Lasaponara, Rosa; Masini, Nicola; Aiazzi, Bruno; Alparone, Luciano; Baronti, Stefano


    The application of space technology to archaeological research has been paid great attention worldwide, mainly because the current availability of very high resolution (VHR) satellite imagery, such as, IKONOS (1999) and QuickBird (2001), provide valuable data for searching large areas to find potential archaeological sites. Data from VHR satellite can be very useful for the identification, management and documentation of archaeological resources. Archaeological investigation based on the use of VHR satellite images may take benefits from the integration and synergic use of both panchromatic and multispectral data. This can be achieved by using pansharpening techniques, which allow multispectral and panchromatic images to be merged. The two basic frameworks of pansharpening techniques are Component Substitution (CS), such as Intensity-Hue-Saturation (IHS) Gram-Schmidt (GS), and multiresolution analysis (MRA), such as wavelets and Laplacian pyramids (LP). In this paper, both Gram-Schmidt and Laplacian pyramids with context adaptive (CA) detail injection models were used. QB images were processed for a relevant archaeological area in Southern Italy, the ancient Siris-Heraclea, a very significant test area because it is characterized by the presence of both surface and subsurface ancient remains. Outcomes of different pansharpening techniques have been qualitatively evaluated for both surface and subsurface remains. The visual inspection clearly suggests that the quantitative evaluation of the fusion performance for archaeological applications is a critical issue, and "ad hoc" local (i.e. context-adaptive) indices need to be developed.

  19. Synthetic fusion-protein containing domains of Bt Cry1Ac and Allium sativum lectin (ASAL) conferred enhanced insecticidal activity against major lepidopteran pests. (United States)

    Tajne, Sunita; Boddupally, Dayakar; Sadumpati, Vijayakumar; Vudem, Dashavantha Reddy; Khareedu, Venkateswara Rao


    Different transgenic crop plants, developed with δ-endotoxins of Bacillus thuringiensis (Bt) and mannose-specific plant lectins, exhibited significant protection against chewing and sucking insects. In the present study, a synthetic gene (cry-asal) encoding the fusion-protein having 488 amino acids, comprising DI and DII domains from Bt Cry1Ac and Allium sativum agglutinin (ASAL), was cloned and expressed in Escherichia coli. Ligand blot analysis disclosed that the fusion-protein could bind to more number of receptors of brush border membrane vesicle (BBMV) proteins of Helicoverpa armigera. Artificial diet bioassays revealed that 0.025 μg/g and 0.50 μg/g of fusion-protein were sufficient to cause 100% mortality in Pectinophora gossypiella and H. armigera insects, respectively. As compared to Cry1Ac, the fusion-protein showed enhanced (8-fold and 30-fold) insecticidal activity against two major lepidopteran pests. Binding of fusion-protein to the additional receptors in the midgut cells of insects is attributable to its enhanced entomotoxic effect. The synthetic gene, first of its kind, appears promising and might serve as a potential candidate for engineering crop plants against major insect pests.

  20. Effects of Caveolin-1 in Human Umbilical Vein Endothelial Cell Induced by Serum of Uremia Patients%尿毒症患者血清对内皮细胞小凹蛋白-1的影响及意义

    Institute of Scientific and Technical Information of China (English)

    鲁文辉; 甘华; 杜晓刚; 常晓东; 杨梅; 龚锐


    Objective To detect the level of caveoliri-1 protein expression in the human umbilical vein endothelial cells (HUVECs) induced by the serum of uremia patients before and after hemodialysis in vitro. Methods HUVECs in good condition were divided into 3 groups, healthy control group ( DM EM + serum of healthy control, n =8), before dialysis group ( DMEM + serum of ESRD patients before dialysis, n = 18), after dialysis group (DMEM + serum of ESRD patients after dialysis, n -18). Cell viability was examined by MTT. The levels of caveo-lin-1 protein expression were measured by western blot and iaimunohistochemistry. Results The best time was the twelfth hour and the best concentration of serum was 10% by MTT. Comparing with the healthy control group, the levels of caveolin-l protein expression reduced significantly in before dialysis group (p 0.05). Comparing with the before dialysis group,the levels of caveoiln-1 protein expression improved notably in after dialysis group (p <0.05). Conclusion The expressions of caveolin-] in HUVECs are more in the after dialysis group than in the before dialysis group,and this change can become one of the important reasons why there is an increased incidence of atherosclerosis in the uremia patients on hemodialysis.%目的 体外观察尿毒症患者血液透析前后血清和健康人血清对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVECs)小凹蛋白-1(caveolin-1)表达的影响.方法 取对数生长的HUVECs,分为健康组(DMEM+健康人血清,n=8)、透前组(DMEM+尿毒症患者透前血清,n=18)、透后组(DMEM+尿毒症患者透后血清,n=18).采用MTT法检测细胞活力,免疫组化SABC法和Western blot检测各组细胞内caveolin-1蛋白的分布和含量.结果 MTT法筛选血清最佳干预时间和浓度分别为12小时、10%的血清干预浓度.与健康组比较,透前组细胞内caveolin-1的蛋白表达水平明显下调(p<0.05),透后组改变不明显(p>0.05);而透后组细胞内caveolin

  1. Myxoma virus expressing a fusion protein of interleukin-15 (IL15 and IL15 receptor alpha has enhanced antitumor activity.

    Directory of Open Access Journals (Sweden)

    Vesna Tosic

    Full Text Available Myxoma virus, a rabbit poxvirus, can efficiently infect various types of mouse and human cancer cells. It is a strict rabbit-specific pathogen, and is thought to be safe as a therapeutic agent in all non-rabbit hosts tested including mice and humans. Interleukin-15 (IL15 is an immuno-modulatory cytokine with significant potential for stimulating anti-tumor T lymphocytes and NK cells. Co-expression of IL15 with the α subunit of IL15 receptor (IL15Rα greatly enhances IL15 stability and bioavailability. Therefore, we engineered a new recombinant myxoma virus (vMyx-IL15Rα-tdTr, which expresses an IL15Rα-IL15 fusion protein plus tdTomato red fluorescent reporter protein. Permissive rabbit kidney epithelial (RK-13 cells infected with vMyx-IL15Rα-tdTr expressed and secreted the IL15Rα-IL15 fusion protein. Functional activity was confirmed by demonstrating that the secreted fusion protein stimulated proliferation of cytokine-dependent CTLL-2 cells. Multi-step growth curves showed that murine melanoma (B16-F10 and B16.SIY cell lines were permissive to vMyx-IL15Rα-tdTr infection. In vivo experiments in RAG1-/- mice showed that subcutaneous B16-F10 tumors treated with vMyx-IL15Rα-tdTr exhibited attenuated tumor growth and a significant survival benefit for the treated group compared to the PBS control and the control viruses (vMyx-IL15-tdTr and vMyx-tdTr. Immunohistological analysis of the subcutaneous tumors showed dramatically increased infiltration of NK cells in vMyx-IL15Rα-tdTr treated tumors compared to the controls. In vivo experiments with immunocompetent C57BL/6 mice revealed a strong infiltrate of both NK cells and CD8+ T cells in response to vMyx-IL15Rα-tdTr, and prolonged survival. We conclude that delivery of IL15Rα-IL15 in a myxoma virus vector stimulates both innate and adaptive components of the immune system.

  2. Three-dimensional scaffold-free fusion culture: the way to enhance chondrogenesis of in vitro propagated human articular chondrocytes

    Directory of Open Access Journals (Sweden)

    M. Lehmann


    Full Text Available Cartilage regeneration based on isolated and culture-expanded chondrocytes has been studied in various in vitro models, but the quality varies with respect to the morphology and the physiology of the synthesized tissues. The aim of our study was to promote in vitro chondrogenesis of human articular chondrocytes using a novel three-dimensional (3-D cultivation system in combination with the chondrogenic differentiation factors transforming growth factor beta 2 (TGF-b2 and L-ascorbic acid. Articular chondrocytes isolated from six elderly patients were expanded in monolayer culture. A single-cell suspension of the dedifferentiated chondrocytes was then added to agar-coated dishes without using any scaffold material, in the presence, or absence of TGF-b2 and/or L-ascorbic acid. Three-dimensional cartilage-like constructs, called single spheroids, and microtissues consisting of several spheroids fused together, named as fusions, were formed. Generated tissues were mainly characterized using histological and immunohistochemical techniques. The morphology of the in vitro tissues shared some similarities to native hyaline cartilage in regard to differentiated S100-positive chondrocytes within a cartilaginous matrix, with strong collagen type II expression and increased synthesis of proteoglycans. Finally, our innovative scaffold-free fusion culture technique supported enhanced chondrogenesis of human articular chondrocytes in vitro. These 3-D hyaline cartilage-like microtissues will be useful for in vitro studies of cartilage differentiation and regeneration, enabling optimization of functional tissue engineering and possibly contributing to the development of new approaches to treat traumatic cartilage defects or osteoarthritis.

  3. NSCT-based fusion enhancement for multispectral finger-vein images (United States)

    Wu, Dongdong; Yang, Jinfeng


    Personal identification based on single-spectral finger-vein image has been widely investigated recently. However, in finger-vein imaging, finger-vein image degradation is the main factor causing lower recognition accuracy. So, to improve the finger-vein image quality, in this paper, multispectral finger-vein images (760nm and 850nm) are fused together for contrast enhancement using NSCT transformation. The proposed method can preserve the completeness and sharpness of finger-vein. Experimental results demonstrate that the proposed method is certainly powerful in enhancing finger-vein image contrast and achieves lower equal error rates in finger-vein recognition even if original images have poor contrast.

  4. Effects of Huoxue - rongluo tablets on the expression of Caveolin - 1 in brain tissue of middle cerebral artety occlusion rats%活血荣络片对大脑中动脉缺血模型大鼠脑组织微囊蛋白-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    周德生; 刘利娟; 寇志刚; 陈瑶; 胡华; 钟捷


    Objective To study the effect of Huoxue - rongluo tablets on the expression of Caveolin - 1 in brain tissue of middle cerebral artery occlusion(MCAO)rats,and investigate nerve function recovery mechanism. Methods 96 SD rats were divided into sham operation group(24 cases)and modeling group(72 cases). Rats in modeling group were constructed in MCAO model by suture - occluded method. After successful modeling,rats in modeling group were randomly divided into model group,control group and experimental group,24 rats in each group. Rats in sham operation and model group were received distilled water(2 mL)via gastrogavage. Rats in exper-imental group were received Huoxue - rongluo liquid,and rats in control group were received buflomedil pyridoxal phosphate liquid at 6 h after modeling,twice a day until death. The daily general condition and neurological function defect score was observed. 6 rats in each group were ran-domly selected,sacrificed at 1,3,5,7 d after molding re-spectively. The expressions of Caveolin - 1 in mice brain tis-sue were observed in all groups. Results One day after modeling,there was no statistical difference on neurological function defect score in each group of modeling group(P ﹥ 0. 05). The neurological function defect scores 3,5,7 d after modeling in control and experimental group were high-er than those in model group(P ﹤ 0. 05),and there was no statistical difference between control and experimental group(P ﹥ 0. 05). The expression of Caveolin - 1 1,3,5,7 d after modeling in model control and experimental group was higher than that in sham operation group at same period(P ﹤ 0. 05). There were no statistical differences on Caveolin - 1 expression in experimental and control group at 1,3 and 5 d after modeling(P ﹥ 0. 05). The expres-sion of Caveolin - 1 in experimental group 7 d after modeling was obviously higher than that in control group(P ﹤0. 05). Conclusion Huoxue - rongluo tablets can significantly increased the expression of

  5. ADAM8 enhances osteoclast precursor fusion and osteoclast formation in vitro and in vivo. (United States)

    Ishizuka, Hisako; García-Palacios, Verónica; Lu, Ganwei; Subler, Mark A; Zhang, Heju; Boykin, Christina S; Choi, Sun Jin; Zhao, Liena; Patrene, Kenneth; Galson, Deborah L; Blair, Harry C; Hadi, Tamer M; Windle, Jolene J; Kurihara, Noriyoshi; Roodman, G David


    ADAM8 expression is increased in the interface tissue around a loosened hip prosthesis and in the pannus and synovium of patients with rheumatoid arthritis, but its potential role in these processes is unclear. ADAM8 stimulates osteoclast (OCL) formation, but the effects of overexpression or loss of expression of ADAM8 in vivo and the mechanisms responsible for the effects of ADAM8 on osteoclastogenesis are unknown. Therefore, to determine the effects of modulating ADAM expression, we generated tartrate-resistant acid phosphatase (TRAP)-ADAM8 transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout (ADAM8 KO) mice. TRAP-ADAM8 mice developed osteopenia and had increased numbers of OCL precursors that formed hypermultinucleated OCLs with an increased bone-resorbing capacity per OCL. They also had an enhanced differentiation capacity, increased TRAF6 expression, and increased NF-κB, Erk, and Akt signaling compared with wild-type (WT) littermates. This increased bone-resorbing capacity per OCL was associated with increased levels of p-Pyk2 and p-Src activation. In contrast, ADAM8 KO mice did not display a bone phenotype in vivo, but unlike WT littermates, they did not increase RANKL production, OCL formation, or calvarial fibrosis in response to tumor necrosis factor α (TNF-α) in vivo. Since loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced OCL formation in response to TNF-α, these results suggest that ADAM8 may be an attractive therapeutic target for preventing bone destruction associated with inflammatory disease.

  6. ADAM8 Enhances Osteoclast Precursor Fusion and Osteoclast Formation In Vitro and In Vivo (United States)

    Ishizuka, Hisako; García-Palacios, Verónica; Lu, Ganwei; Subler, Mark A; Zhang, Heju; Boykin, Christina S; Choi, Sun Jin; Zhao, Liena; Patrene, Kenneth; Galson, Deborah L; Blair, Harry C; Hadi, Tamer M; Windle, Jolene J; Kurihara, Noriyoshi; Roodman, G David


    ADAM8 expression is increased in the interface tissue around a loosened hip prosthesis and in the pannus and synovium of patients with rheumatoid arthritis, but its potential role in these processes is unclear. ADAM8 stimulates osteoclast (OCL) formation, but the effects of overexpression or loss of expression of ADAM8 in vivo and the mechanisms responsible for the effects of ADAM8 on osteoclastogenesis are unknown. Therefore, to determine the effects of modulating ADAM expression, we generated tartrate-resistant acid phosphatase (TRAP)–ADAM8 transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout (ADAM8 KO) mice. TRAP-ADAM8 mice developed osteopenia and had increased numbers of OCL precursors that formed hypermultinucleated OCLs with an increased bone-resorbing capacity per OCL. They also had an enhanced differentiation capacity, increased TRAF6 expression, and increased NF-κB, Erk, and Akt signaling compared with wild-type (WT) littermates. This increased bone-resorbing capacity per OCL was associated with increased levels of p-Pyk2 and p-Src activation. In contrast, ADAM8 KO mice did not display a bone phenotype in vivo, but unlike WT littermates, they did not increase RANKL production, OCL formation, or calvarial fibrosis in response to tumor necrosis factor α (TNF-α) in vivo. Since loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced OCL formation in response to TNF-α, these results suggest that ADAM8 may be an attractive therapeutic target for preventing bone destruction associated with inflammatory disease. © 2011 American Society for Bone and Mineral Research. PMID:20683884

  7. Role of caveolin-1 in fibrotic diseases

    NARCIS (Netherlands)

    Gvaramia, D.; Blaauboer, M.E.; Hanemaaijer, R.; Everts, V.


    Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent e

  8. Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.

    Directory of Open Access Journals (Sweden)

    Alexandra J Spencer

    Full Text Available The orthodox role of the invariant chain (CD74; Ii is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA, higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.

  9. Enhanced antitumor immunity of nanoliposome-encapsulated heat shock protein 70 peptide complex derived from dendritic tumor fusion cells. (United States)

    Zhang, Yunfei; Luo, Wen; Wang, Yucai; Chen, Jun; Liu, Yunyan; Zhang, Yong


    Tumor-derived heat shock proteins peptide complex (HSP.PC-Tu) has been regarded as a promising antitumor agent. However, inadequate immunogenicity and low bioavailability limit the clinical uses of this agent. In a previous study, we first produced an improved HSP70.PC-based vaccine purified from dendritic cell (DC)-tumor fusion cells (HSP70.PC-Fc) which had increased immunogenicity due to enhanced antigenic tumor peptides compared to HSP70.PC-Tu. In order to increase the bioavailability of HSP70.PC-Fc, the peptide complex was encapsulated with nanoliposomes (NL-HSP70.PC-Fc) in this study. After encapsulation, the tumor immunogenicity was observed using various assays. It was demonstrated that the NL-HSP70.PC-Fc has acceptable stability. The in vivo antitumor immune response was increased with regard to T-cell activation, CTL response and tumor therapy efficiency compared to that of HSP70.PC-Fc. In addition, it was shown that DC maturation was improved by NL-HSP70.PC-Fc, which added to the antitumor immunity. The results obtained for NL-HSP70.PC-Fc, which improved immunogenicity and increases the bioavailability of HSP70.PC, may represent superior heat shock proteins (HSPs)-based tumor vaccines. Such vaccines deserve further investigation and may provide a preclinical rationale to translate findings into early phase trials for patients with breast tumors.

  10. Genetic interaction between Tmprss2-ERG gene fusion and Nkx3.1-loss does not enhance prostate tumorigenesis in mouse models. (United States)

    Linn, Douglas E; Bronson, Roderick T; Li, Zhe


    Gene fusions involving ETS family transcription factors (mainly TMPRSS2-ERG and TMPRSS2-ETV1 fusions) have been found in ~50% of human prostate cancer cases. Although expression of TMPRSS2-ERG or TMPRSS2-ETV1 fusion alone is insufficient to initiate prostate tumorigenesis, they appear to sensitize prostate epithelial cells for cooperation with additional oncogenic mutations to drive frank prostate adenocarcinoma. To search for such ETS-cooperating oncogenic events, we focused on a well-studied prostate tumor suppressor NKX3.1, as loss of NKX3.1 is another common genetic alteration in human prostate cancer. Previous studies have shown that deletions at 8p21 (harboring NKX3.1) and 21q22 (resulting in TMPRSS2-ERG fusion) were both present in a subtype of prostate cancer cases, and that ERG can lead to epigenetic silencing of NKX3.1 in prostate cancer cells, whereas NKX3.1 can in turn negatively regulate TMPRSS2-ERG fusion expression via suppression of the TMPRSS2 promoter activity. We recently generated knockin mouse models for TMPRSS2-ERG and TMPRSS2-ETV1 fusions, utilizing the endogenous Tmprss2 promoter. We crossed these knockin models to an Nkx3.1 knockout mouse model. In Tmprss2-ERG;Nkx3.1+/- (or -/-) male mice, although we observed a slight but significant upregulation of Tmprss2-ERG fusion expression upon Nkx3.1 loss, we did not detect any significant cooperation between these two genetic events to enhance prostate tumorigenesis in vivo. Furthermore, retrospective analysis of a previously published human prostate cancer dataset revealed that within ERG-overexpressing prostate cancer cases, NKX3.1 loss or deletion did not predict biochemical relapse after radical prostatectomy. Collectively, these data suggest that although TMPRSS2-ERG fusion and loss of NKX3.1 are among the most common mutational events found in prostate cancer, and although each of them can sensitize prostate epithelial cells for cooperating with other oncogenic events, these two events

  11. Multi-Sensor Fusion for Enhanced Contextual Awareness of Everyday Activities with Ubiquitous Devices

    Directory of Open Access Journals (Sweden)

    John J. Guiry


    Full Text Available In this paper, the authors investigate the role that smart devices, including smartphones and smartwatches, can play in identifying activities of daily living. A feasibility study involving N = 10 participants was carried out to evaluate the devices’ ability to differentiate between nine everyday activities. The activities examined include walking, running, cycling, standing, sitting, elevator ascents, elevator descents, stair ascents and stair descents. The authors also evaluated the ability of these devices to differentiate indoors from outdoors, with the aim of enhancing contextual awareness. Data from this study was used to train and test five well known machine learning algorithms: C4.5, CART, Naïve Bayes, Multi-Layer Perceptrons and finally Support Vector Machines. Both single and multi-sensor approaches were examined to better understand the role each sensor in the device can play in unobtrusive activity recognition. The authors found overall results to be promising, with some models correctly classifying up to 100% of all instances.

  12. Multi-Sensor Fusion for Enhanced Contextual Awareness of Everyday Activities with Ubiquitous Devices (United States)

    Guiry, John J.; van de Ven, Pepijn; Nelson, John


    In this paper, the authors investigate the role that smart devices, including smartphones and smartwatches, can play in identifying activities of daily living. A feasibility study involving N = 10 participants was carried out to evaluate the devices' ability to differentiate between nine everyday activities. The activities examined include walking, running, cycling, standing, sitting, elevator ascents, elevator descents, stair ascents and stair descents. The authors also evaluated the ability of these devices to differentiate indoors from outdoors, with the aim of enhancing contextual awareness. Data from this study was used to train and test five well known machine learning algorithms: C4.5, CART, Naïve Bayes, Multi-Layer Perceptrons and finally Support Vector Machines. Both single and multi-sensor approaches were examined to better understand the role each sensor in the device can play in unobtrusive activity recognition. The authors found overall results to be promising, with some models correctly classifying up to 100% of all instances. PMID:24662406

  13. Transgenic plants expressing -ACTX-Hv1a and snowdrop lectin (GNA fusion protein show enhanced resistance to aphids

    Directory of Open Access Journals (Sweden)

    Erich Y.T. Nakasu


    Full Text Available Recombinant fusion proteins containing arthropod toxins have been developed as a new class of biopesticides. The recombinant fusion protein Hv1a/GNA, containing the spider venom toxin w-ACTX-Hv1a linked to snowdrop lectin (GNA was shown to reduce survival of the peach-potato aphid Myzus persicae when delivered in artificial diet, with survival <10% after 8 days exposure to fusion protein at 1 mg/ml. Although the fusion protein was rapidly degraded by proteases in the insect, Hv1a/GNA oral toxicity to M. persicae was significantly greater than GNA alone. A construct encoding the fusion protein, including the GNA leader sequence, under control of the constitutive CaMV 35S promoter was transformed into Arabidopsis; the resulting plants contained intact fusion protein in leaf tissues at an estimated level of 25.6±4.1 ng/mg FW. Transgenic Arabidopsis expressing Hv1a/GNA induced up to 40% mortality of M. persicae after seven days exposure in detached leaf bioassays, demonstrating that transgenic plants can deliver fusion proteins to aphids. Grain aphids (Sitobion avenae were more susceptible than M. persicae to the Hv1a/GNA fusion protein in artificial diet bioassays (LC50=0.73 mg/ml after two days against LC50=1.81 mg/ml for M. persicae, as they were not able to hydrolyze the fusion protein as readily as M. persicae. Expression of this fusion protein in suitable host plants for the grain aphid is likely to confer higher levels of resistance than that shown with the M. persicae/Arabidopsis model system.

  14. Transgenic plants expressing ω-ACTX-Hv1a and snowdrop lectin (GNA) fusion protein show enhanced resistance to aphids. (United States)

    Nakasu, Erich Y T; Edwards, Martin G; Fitches, Elaine; Gatehouse, John A; Gatehouse, Angharad M R


    Recombinant fusion proteins containing arthropod toxins have been developed as a new class of biopesticides. The recombinant fusion protein Hv1a/GNA, containing the spider venom toxin ω-ACTX-Hv1a linked to snowdrop lectin (GNA) was shown to reduce survival of the peach-potato aphid Myzus persicae when delivered in artificial diet, with survival <10% after 8 days exposure to fusion protein at 1 mg/ml. Although the fusion protein was rapidly degraded by proteases in the insect, Hv1a/GNA oral toxicity to M. persicae was significantly greater than GNA alone. A construct encoding the fusion protein, including the GNA leader sequence, under control of the constitutive CaMV 35S promoter was transformed into Arabidopsis; the resulting plants contained intact fusion protein in leaf tissues at an estimated level of 25.6 ± 4.1 ng/mg FW. Transgenic Arabidopsis expressing Hv1a/GNA induced up to 40% mortality of M. persicae after 7 days exposure in detached leaf bioassays, demonstrating that transgenic plants can deliver fusion proteins to aphids. Grain aphids (Sitobion avenae) were more susceptible than M. persicae to the Hv1a/GNA fusion protein in artificial diet bioassays (LC50 = 0.73 mg/ml after 2 days against LC50 = 1.81 mg/ml for M. persicae), as they were not able to hydrolyze the fusion protein as readily as M. persicae. Expression of this fusion protein in suitable host plants for the grain aphid is likely to confer higher levels of resistance than that shown with the M. persicae/Arabidopsis model system.

  15. The self-consistent analysis for sub-barrier fusion enhancement effect in Ca + Ca and Ni + Ni

    CERN Document Server

    Ma, N R; Lin, C J; Yang, L; Xu, X X; Sun, L J; Yang, F; Wu, Z D; Zhang, H Q; Liu, Z H; Wang, D X


    The fusion dynamic mechanism of heavy-ions at energies near the Coulomb barrier is complicated and still not very clear up to now. Accordingly, a self-consistent method based on the CCFULL calculations has been developed and applied for an ingoing study of the effect of the positive Q-value neutron transfer (PQNT) channels in this work. The typical experimental fusion data of Ca + Ca and Ni + Ni is analyzed within the unified calculation scheme. The PQNT effect in near-barrier fusion is further confirmed based on the self-consistent analysis and extracted quantitatively.

  16. A novel thrombopoietin-stem-cell factor fusion protein possesses enhanced potential in stimulating megakaryocyte proliferation and differentiation. (United States)

    Zang, Yuhui; Zhang, Yumin; Peng, Wei; Chen, Bin; Zhu, Jie; Zhang, Chi; Ouyang, Jian; Qin, Junchuan


    TPO (thrombopoietin) and SCF (stem-cell factor) are functionally related cytokines with overlapping but distinct haematopoietic effects. In the present study, a novel TPO-SCF fusion protein that combined the complementary biological effects of TPO and SCF into a single molecule was expressed in, and purified from, Sf9 [Spodoptera frugiperda (fall armyworm)] insect cells. The specific activity of rhTPO (recombinant human TPO)-SCF in megakaryoblastic Mo7e cell proliferation assays was 2.90+/-0.35 x 10(7) units/micromol, approx. 1.7 times as high as that of rhTPO. The specific activity of rhTPO-SCF in TF-1 cells proliferation assays was 7.10+/-0.95 x 10(6) units/micromol, approx. 1.2 times as high as that of rhSCF (recombinant human SCF). In a megakaryocyte-colony-forming assay using human peripheral-blood CD34(+) cells, the SCF moiety of rhTPO-SCF worked in a synergistic way to augment the colony number and exhibited a higher potential to stimulate megakaryocyte colony growth. According to the results of EMSA (electrophoretic mobility-shift assay) and semi-quantitative RT (reverse transcriptase)-PCR, the synergistic effects of the SCF moiety were also reflected in increased STAT5 (signal transducer and activator of transcription 5) DNA binding and enhanced up-regulation of p21 expression in Mo7e cells treated by rhTPO-SCF, suggesting that rhTPO-SCF could be more potent in promoting megakaryocyte proliferation and differentiation.

  17. LETTER: Study of combined NBI and ICRF enhancement of the D-3He fusion yield with a Fokker-Planck code (United States)

    Azoulay, M.; George, M. A.; Burger, A.; Collins, W. E.; Silberman, E.

    A two-dimensional bounce averaged Fokker-Planck code is used to study the fusion yield and the wave absorption by residual hydrogen ions in higher harmonic ICRF heating of D (120 keV) and 3He (80 keV) beams in the JT-60U tokamak. Both for the fourth harmonic resonance of 3He (ω = 4ωc3He(0), which is accompanied by the third harmonic resonance of hydrogen (ω = 3ωcH) at the low field side, and for the third harmonic resonance of 3He (ω = 4ωcD(0) = 3ωc3He(0)) = 2ωcH(0)), a few per cent of hydrogen ions are found to absorb a large fraction of the ICRF power and to degrade the fusion output power. In the latter case, D beam acceleration due to the fourth harmonic resonance in the 3He(D) regime can enhance the fusion yield more effectively. A discussion is given of the effect of D beam acceleration due to the fifth harmonic resonance (ω = 5ωcD) at the high field side in the case of ω = 4ωc3He(0) and of the optimization of the fusion yield in the case of lower electron density and higher electron temperature

  18. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)


    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  19. A fusion tag to fold on: the S-layer protein SgsE confers improved folding kinetics to translationally fused enhanced green fluorescent protein. (United States)

    Ristl, Robin; Kainz, Birgit; Stadlmayr, Gerhard; Schuster, Heinrich; Pum, Dietmar; Messner, Paul; Obinger, Christian; Schaffer, Christina


    Genetic fusion of two proteins frequently induces beneficial effects to the proteins, such as increased solubility, besides the combination of two protein functions. Here, we study the effects of the bacterial surface layer protein SgsE from Geobacillus stearothermophilus NRS 2004/3a on the folding of a C-terminally fused enhanced green fluorescent protein (EGFP) moiety. Although GFPs are generally unable to adopt a functional confirmation in the bacterial periplasm of Escherichia coli cells, we observed periplasmic fluorescence from a chimera of a 150-amino-acid N-terminal truncation of SgsE and EGFP. Based on this finding, unfolding and refolding kinetics of different S-layer-EGFP chimeras, a maltose binding protein-EGFP chimera, and sole EGFP were monitored using green fluorescence as indicator for the folded protein state. Calculated apparent rate constants for unfolding and refolding indicated different folding pathways for EGFP depending on the fusion partner used, and a clearly stabilizing effect was observed for the SgsE_C fusion moiety. Thermal stability, as determined by differential scanning calorimetry, and unfolding equilibria were found to be independent of the fused partner. We conclude that the stabilizing effect SgsE_C exerts on EGFP is due to a reduction of degrees of freedom for folding of EGFP in the fused state.

  20. Fusion of a Short HA2-Derived Peptide Sequence to Cell-Penetrating Peptides Improves Cytosolic Uptake, but Enhances Cytotoxic Activity

    Directory of Open Access Journals (Sweden)

    Igor Kitanovic


    Full Text Available Cell-penetrating peptides (CPP have become a widely used tool for efficient cargo delivery into cells. However, one limiting fact is their uptake by endocytosis causing the enclosure of the CPP-cargo construct within endosomes. One often used method to enhance the outflow into the cytosol is the fusion of endosome-disruptive peptide or protein sequences to CPP. But, until now, no studies exist investigating the effects of the fusion peptide to the cellular distribution, structural arrangements and cytotoxic behaviour of the CPP. In this study, we attached a short modified sequence of hemagglutinin subunit HA2 to different CPP and analysed the biologic activity of the new designed peptides. Interestingly, we observed an increased cytosolic distribution but also highly toxic activities in the micromolar range against several cell lines. Structural analysis revealed that attachment of the fusion peptide had profound implications on the whole conformation of the peptide, which might be responsible for membrane interaction and endosome disruption.

  1. Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats. (United States)

    Zhou, Zhuang; Tian, Fa-Ming; Gou, Yu; Wang, Peng; Zhang, Heng; Song, Hui-Ping; Shen, Yong; Zhang, Ying-Ze; Zhang, Liu


    Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1-34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L4 -L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia.

  2. Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-released microsphere: an experimental study on sheep model. (United States)

    Chen, Liang; Liu, Hai-Long; Gu, Yong; Feng, Yu; Yang, Hui-Lin


    Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P sheep using BCP constructs.

  3. QuantFusion: Novel Unified Methodology for Enhanced Coverage and Precision in Quantifying Global Proteomic Changes in Whole Tissues. (United States)

    Gunawardena, Harsha P; O'Brien, Jonathon; Wrobel, John A; Xie, Ling; Davies, Sherri R; Li, Shunqiang; Ellis, Matthew J; Qaqish, Bahjat F; Chen, Xian


    Single quantitative platforms such as label-based or label-free quantitation (LFQ) present compromises in accuracy, precision, protein sequence coverage, and speed of quantifiable proteomic measurements. To maximize the quantitative precision and the number of quantifiable proteins or the quantifiable coverage of tissue proteomes, we have developed a unified approach, termed QuantFusion, that combines the quantitative ratios of all peptides measured by both LFQ and label-based methodologies. Here, we demonstrate the use of QuantFusion in determining the proteins differentially expressed in a pair of patient-derived tumor xenografts (PDXs) representing two major breast cancer (BC) subtypes, basal and luminal. Label-based in-spectra quantitative peptides derived from amino acid-coded tagging (AACT, also known as SILAC) of a non-malignant mammary cell line were uniformly added to each xenograft with a constant predefined ratio, from which Ratio-of-Ratio estimates were obtained for the label-free peptides paired with AACT peptides in each PDX tumor. A mixed model statistical analysis was used to determine global differential protein expression by combining complementary quantifiable peptide ratios measured by LFQ and Ratio-of-Ratios, respectively. With minimum number of replicates required for obtaining the statistically significant ratios, QuantFusion uses the distinct mechanisms to "rescue" the missing data inherent to both LFQ and label-based quantitation. Combined quantifiable peptide data from both quantitative schemes increased the overall number of peptide level measurements and protein level estimates. In our analysis of the PDX tumor proteomes, QuantFusion increased the number of distinct peptide ratios by 65%, representing differentially expressed proteins between the BC subtypes. This quantifiable coverage improvement, in turn, not only increased the number of measurable protein fold-changes by 8% but also increased the average precision of quantitative

  4. Fusion of 3D models derived from TLS and image-based techniques for CH enhanced documentation (United States)

    Bastonero, P.; Donadio, E.; Chiabrando, F.; Spanò, A.


    Recognizing the various advantages offered by 3D new metric survey technologies in the Cultural Heritage documentation phase, this paper presents some tests of 3D model generation, using different methods, and their possible fusion. With the aim to define potentialities and problems deriving from integration or fusion of metric data acquired with different survey techniques, the elected test case is an outstanding Cultural Heritage item, presenting both widespread and specific complexities connected to the conservation of historical buildings. The site is the Staffarda Abbey, the most relevant evidence of medieval architecture in Piedmont. This application faced one of the most topical architectural issues consisting in the opportunity to study and analyze an object as a whole, from twice location of acquisition sensors, both the terrestrial and the aerial one. In particular, the work consists in the evaluation of chances deriving from a simple union or from the fusion of different 3D cloudmodels of the abbey, achieved by multi-sensor techniques. The aerial survey is based on a photogrammetric RPAS (Remotely piloted aircraft system) flight while the terrestrial acquisition have been fulfilled by laser scanning survey. Both techniques allowed to extract and process different point clouds and to generate consequent 3D continuous models which are characterized by different scale, that is to say different resolutions and diverse contents of details and precisions. Starting from these models, the proposed process, applied to a sample area of the building, aimed to test the generation of a unique 3Dmodel thorough a fusion of different sensor point clouds. Surely, the describing potential and the metric and thematic gains feasible by the final model exceeded those offered by the two detached models.

  5. Osteoclast Fusion

    DEFF Research Database (Denmark)

    Marie Julie Møller, Anaïs; Delaissé, Jean-Marie; Søe, Kent


    suggesting that fusion partners may specifically select each other and that heterogeneity between the partners seems to play a role. Therefore, we set out to directly test the hypothesis that fusion factors have a heterogenic involvement at different stages of nuclearity. Therefore, we have analyzed...... on the nuclearity of fusion partners. While CD47 promotes cell fusions involving mono-nucleated pre-osteoclasts, syncytin-1 promotes fusion of two multi-nucleated osteoclasts, but also reduces the number of fusions between mono-nucleated pre-osteoclasts. Furthermore, CD47 seems to mediate fusion mostly through......Investigations addressing the molecular keys of osteoclast fusion are primarily based on end-point analyses. No matter if investigations are performed in vivo or in vitro the impact of a given factor is predominantly analyzed by counting the number of multi-nucleated cells, the number of nuclei per...

  6. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin


    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  7. Fusion rings and fusion ideals

    DEFF Research Database (Denmark)

    Andersen, Troels Bak

    by the so-called fusion ideals. The fusion rings of Wess-Zumino-Witten models have been widely studied and are well understood in terms of precise combinatorial descriptions and explicit generating sets of the fusion ideals. They also appear in another, more general, setting via tilting modules for quantum...

  8. Fusion of the Mycobacterium tuberculosis antigen 85A to an oligomerization domain enhances its immunogenicity in both mice and non-human primates.

    Directory of Open Access Journals (Sweden)

    Alexandra J Spencer

    Full Text Available To prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species. In mice, the fused antigen 85A showed consistent increases in CD4(+ and CD8(+ T cell responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-γ responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both primary and secondary immunizations. In both animal models, fusion to IMX313 induced a quantitative enhancement in the response without altering its quality: multifunctional cytokines were uniformly increased and differentiation into effector and memory T cell subsets was augmented rather than skewed. An extensive in vivo characterization suggests that IMX313 improves the initiation of immune responses as an increase in antigen 85A specific cells was observed as early as day 3 after vaccination. This report demonstrates that antigen multimerization using IMX313 is a simple and effective cross-species method to improve vaccine immunogenicity with potentially broad applicability.

  9. The ability to enhance the solubility of its fusion partners is an intrinsic property of maltose-binding protein but their folding is either spontaneous or chaperone-mediated.

    Directory of Open Access Journals (Sweden)

    Sreejith Raran-Kurussi

    Full Text Available Escherichia coli maltose binding protein (MBP is commonly used to promote the solubility of its fusion partners. To investigate the mechanism of solubility enhancement by MBP, we compared the properties of MBP fusion proteins refolded in vitro with those of the corresponding fusion proteins purified under native conditions. We fused five aggregation-prone passenger proteins to 3 different N-terminal tags: His₆-MBP, His₆-GST and His₆. After purifying the 15 fusion proteins under denaturing conditions and refolding them by rapid dilution, we recovered far more of the soluble MBP fusion proteins than their GST- or His-tagged counterparts. Hence, we can reproduce the solubilizing activity of MBP in a simple in vitro system, indicating that no additional factors are required to mediate this effect. We assayed both the soluble fusion proteins and their TEV protease digestion products (i.e., with the N-terminal tag removed for biological activity. Little or no activity was detected for some fusion proteins whereas others were quite active. When the MBP fusions proteins were purified from E. coli under native conditions they were all substantially active. These results indicate that the ability of MBP to promote the solubility of its fusion partners in vitro sometimes, but not always, results in their proper folding. We show that the folding of some passenger proteins is mediated by endogenous chaperones in vivo. Hence, MBP serves as a passive participant in the folding process; passenger proteins either fold spontaneously or with the assistance of chaperones.

  10. FN-DFE: Fuzzy-Neural Data Fusion Engine for Enhanced State-Awareness of Resilient Hybrid Energy System

    Energy Technology Data Exchange (ETDEWEB)

    Ondrej Linda; Dumidu Wijayasekara; Milos Manic; Craig Rieger


    Resiliency and improved state-awareness of modern critical infrastructures, such as energy production and industrial systems, is becoming increasingly important. As control systems become increasingly complex, the number of inputs and outputs increase. Therefore, in order to maintain sufficient levels of state-awareness, a robust system state monitoring must be implemented that correctly identifies system behavior even when one or more sensors are faulty. Furthermore, as intelligent cyber adversaries become more capable, incorrect values may be fed to the operators. To address these needs, this paper proposes a Fuzzy-Neural Data Fusion Engine (FN-DFE) for resilient state-awareness of control systems. The designed FN-DFE is composed of a three-layered system consisting of: 1) traditional threshold based alarms, 2) anomalous behavior detector using self-organizing fuzzy logic system, and 3) artificial neural network based system modeling and prediction. The improved control system state-awareness is achieved via fusing input data from multiple sources and combining them into robust anomaly indicators. In addition, the neural network based signal predictions are used to augment the resiliency of the system and provide coherent state-awareness despite temporary unavailability of sensory data. The proposed system was integrated and tested with a model of the Idaho National Laboratory’s (INL) hybrid energy system facility know as HYTEST. Experimental results demonstrate that the proposed FN-DFE provides timely plant performance monitoring and anomaly detection capabilities. It was shown that the system is capable of identifying intrusive behavior significantly earlier than conventional threshold based alarm systems.

  11. Finger-Vein Image Enhancement Using a Fuzzy-Based Fusion Method with Gabor and Retinex Filtering


    Kwang Yong Shin; Young Ho Park; Dat Tien Nguyen; Kang Ryoung Park


    Because of the advantages of finger-vein recognition systems such as live detection and usage as bio-cryptography systems, they can be used to authenticate individual people. However, images of finger-vein patterns are typically unclear because of light scattering by the skin, optical blurring, and motion blurring, which can degrade the performance of finger-vein recognition systems. In response to these issues, a new enhancement method for finger-vein images is proposed. Our method is novel ...

  12. Finger-vein image enhancement using a fuzzy-based fusion method with Gabor and Retinex filtering. (United States)

    Shin, Kwang Yong; Park, Young Ho; Nguyen, Dat Tien; Park, Kang Ryoung


    Because of the advantages of finger-vein recognition systems such as live detection and usage as bio-cryptography systems, they can be used to authenticate individual people. However, images of finger-vein patterns are typically unclear because of light scattering by the skin, optical blurring, and motion blurring, which can degrade the performance of finger-vein recognition systems. In response to these issues, a new enhancement method for finger-vein images is proposed. Our method is novel compared with previous approaches in four respects. First, the local and global features of the vein lines of an input image are amplified using Gabor filters in four directions and Retinex filtering, respectively. Second, the means and standard deviations in the local windows of the images produced after Gabor and Retinex filtering are used as inputs for the fuzzy rule and fuzzy membership function, respectively. Third, the optimal weights required to combine the two Gabor and Retinex filtered images are determined using a defuzzification method. Fourth, the use of a fuzzy-based method means that image enhancement does not require additional training data to determine the optimal weights. Experimental results using two finger-vein databases showed that the proposed method enhanced the accuracy of finger-vein recognition compared with previous methods.

  13. Finger-Vein Image Enhancement Using a Fuzzy-Based Fusion Method with Gabor and Retinex Filtering

    Directory of Open Access Journals (Sweden)

    Kwang Yong Shin


    Full Text Available Because of the advantages of finger-vein recognition systems such as live detection and usage as bio-cryptography systems, they can be used to authenticate individual people. However, images of finger-vein patterns are typically unclear because of light scattering by the skin, optical blurring, and motion blurring, which can degrade the performance of finger-vein recognition systems. In response to these issues, a new enhancement method for finger-vein images is proposed. Our method is novel compared with previous approaches in four respects. First, the local and global features of the vein lines of an input image are amplified using Gabor filters in four directions and Retinex filtering, respectively. Second, the means and standard deviations in the local windows of the images produced after Gabor and Retinex filtering are used as inputs for the fuzzy rule and fuzzy membership function, respectively. Third, the optimal weights required to combine the two Gabor and Retinex filtered images are determined using a defuzzification method. Fourth, the use of a fuzzy-based method means that image enhancement does not require additional training data to determine the optimal weights. Experimental results using two finger-vein databases showed that the proposed method enhanced the accuracy of finger-vein recognition compared with previous methods.

  14. Binding of fusion protein FLSC IgG1 to CCR5 is enhanced by CCR5 antagonist Maraviroc. (United States)

    Latinovic, Olga; Schneider, Kate; Szmacinski, Henryk; Lakowicz, Joseph R; Heredia, Alonso; Redfield, Robert R


    The CCR5 chemokine receptor is crucial for human immunodeficiency virus type 1 (HIV-1) infection, acting as the principal coreceptor for HIV-1 entry and transmission and is thus an attractive target for antiviral therapy. Studies have suggested that CCR5 surface density and its conformational changes subsequent to virion engagement are rate limiting for entry, and consequently, infection. Not all CCR5 antibodies inhibit HIV-1 infection, suggesting a need for more potent reagents. Here we evaluated full length single chain (FLSC) IgG1, a novel IgG-CD4-gp120(BAL) fusion protein with several characteristics that make it an attractive candidate for treatment of HIV-1 infections, including bivalency and a potentially increased serum half-life over FLSC, the parental molecule. FLSC IgG1 binds two domains on CCR5, the N-terminus and the second extracellular loop, lowering the levels of available CCR5 viral attachment sites. Furthermore, FLSC IgG1 synergizes with Maraviroc (MVC), the only licensed CCR5 antagonist. In this study, we used both microscopy and functional assays to address the mechanistic aspects of the interactions of FLSC IgG1 and MVC in the context of CCR5 conformational changes and viral infection. We used a novel stochastic optical reconstruction microscopy (STORM), based on high resolution localization of photoswitchable dyes to visualize direct contacts between FLSC IgG1 and CCR5. We compared viral entry inhibition by FLSC IgG1 with that of other CCR5 blockers and showed FLSC IgG1 to be the most potent. We also showed that lower CCR5 surface densities in HIV-1 infected primary cells result in lower FLSC IgG1 EC50 values. In addition, CCR5 binding by FLSC IgG1, but not CCR5 Ab 2D7, was significantly increased when cells were treated with MVC, suggesting MVC allosterically increases exposure of the FLSC IgG1 binding site. These data have implications for future antiviral therapy development.

  15. Cold fusion

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)


    So called `cold fusion phenomena` are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording {sup 4}He, {sup 3}He, {sup 3}H, which are not rich in quantity basically. An experiment where plenty of {sup 4}He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author).

  16. Spinal Fusion (United States)

    ... results in predictable healing. Autograft is currently the “gold standard” source of bone for a fusion. The ... pump. With this technique, the patient presses a button that delivers a predetermined amount of narcotic pain ...

  17. 利用NSCT实现夜视图像的彩色化增强%A Novel Color Fusion Method for Night Vision Image Enhancement Using NSCT

    Institute of Scientific and Technical Information of China (English)

    何卫华; 郭永彩; 高潮; 周东国


    针对夜视融合图像通常存在细节不够丰富、目标对比度低的问题,为了获得更为理想的图像增强效果,提出一种新颖的基于非下采样轮廓波变换(NSCT)的夜视图像彩色融合方法.构建了基于S函数与子图局部方差信息的可变加权融合策略,在NSCT域内实现可见光及红外源图像的自适应融合;将得到的融合图像与源图像进行组合并映射至YUV颜色空间,生成伪彩色融合图像;再运用颜色传递技术获得重染色的彩色融合图像.实验结果表明,该方法既能丰富彩色融合图像的细节,又能提高其亮度对比度和目标的可探测性,增强了观察者对场景的理解.%Traditional color night vision fusion methods always suffer from the problems of blurry visual effects and the low brightness contrast between the targets and the surroundings. To alleviate above problems, a novel fused image enhancement method for night vision is proposed in this paper. Firstly the nonsubsampled contourlet transform (NSCT) is performed on the infrared and the visible source images, respectively. Then a fused gray level image is obtained according to the self-adaptive fusion rules based on the S function and the local variance values. Subsequently, the source images and the fused image are synthesized together and mapped into the YUV color space, forming a pseudo-color image. Finally, a color transfer technique is employed to transform the pseudo-color image into a new version with natural color appearance. Experimental results demonstrate that the proposed method not only keep abundant details of the background, but also improve the target detectability and notably enhance the situation awareness.

  18. Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA in mice via fusion to recombinant human B lymphocyte stimulator (BLyS

    Directory of Open Access Journals (Sweden)

    Mambula Salamatu S


    Full Text Available Abstract Background B lymphocyte stimulator (BLyS is a member of the tumor necrosis factor superfamily of ligands that mediates its action through three known receptors. BLyS has been shown to enhance the production of antibodies against heterologous antigens when present at elevated concentrations, supporting an immunostimulatory role for BLyS in vivo. Methods We constructed a fusion protein consisting of human BLyS and Pneumococcal Surface Adhesin A (PsaA and used this molecule to immunize mice. The immunostimulatory attributes mediated by BLyS in vivo were evaluated by characterizing immune responses directed against PsaA. Results The PsaA-BLyS fusion protein was able to act as a co-stimulant for murine spleen cell proliferation induced with F(ab'2 fragments of anti-IgM in vitro in a fashion similar to recombinant BLyS, and immunization of mice with the PsaA-BLyS fusion protein resulted in dramatically elevated serum antibodies specific for PsaA. Mice immunized with PsaA admixed with recombinant BLyS exhibited only modest elevations in PsaA-specific responses following two immunizations, while mice immunized twice with PsaA alone exhibited undetectable PsaA-specific serum antibody responses. Sera obtained from PsaA-BLyS immunized mice exhibited high titers of IgG1, IgG2a, IgG2b, and IgG3, but no IgA, while mice immunized with PsaA admixed with BLyS exhibited only elevated titers of IgG1 following two immunizations. Splenocytes from PsaA-BLyS immunized mice exhibited elevated levels of secretion of IL-2, IL-4 and IL-5, and a very modest but consistent elevation of IFN-γ following in vitro stimulation with PsaA. In contrast, mice immunized with either PsaA admixed with BLyS or PsaA alone exhibited modestly elevated to absent PsaA-specific recall responses for the same cytokines. Mice deficient for one of the three receptors for BLyS designated Transmembrane activator, calcium modulator, and cyclophilin ligand [CAML] interactor (TACI exhibited

  19. Multibiometrics Belief Fusion

    CERN Document Server

    Kisku, Dakshina Ranjan; Gupta, Phalguni


    This paper proposes a multimodal biometric system through Gaussian Mixture Model (GMM) for face and ear biometrics with belief fusion of the estimated scores characterized by Gabor responses and the proposed fusion is accomplished by Dempster-Shafer (DS) decision theory. Face and ear images are convolved with Gabor wavelet filters to extracts spatially enhanced Gabor facial features and Gabor ear features. Further, GMM is applied to the high-dimensional Gabor face and Gabor ear responses separately for quantitive measurements. Expectation Maximization (EM) algorithm is used to estimate density parameters in GMM. This produces two sets of feature vectors which are then fused using Dempster-Shafer theory. Experiments are conducted on multimodal database containing face and ear images of 400 individuals. It is found that use of Gabor wavelet filters along with GMM and DS theory can provide robust and efficient multimodal fusion strategy.

  20. Peaceful Uses of Fusion (United States)

    Teller, E.


    Applications of thermonuclear energy for peaceful and constructive purposes are surveyed. Developments and problems in the release and control of fusion energy are reviewed. It is pointed out that the future of thermonuclear power reactors will depend upon the construction of a machine that produces more electric energy than it consumes. The fuel for thermonuclear reactors is cheap and practically inexhaustible. Thermonuclear reactors produce less dangerous radioactive materials than fission reactors and, when once brought under control, are not as likely to be subject to dangerous excursions. The interaction of the hot plasma with magnetic fields opens the way for the direct production of electricity. It is possible that explosive fusion energy released underground may be harnessed for the production of electricity before the same feat is accomplished in controlled fusion processes. Applications of underground detonations of fission devices in mining and for the enhancement of oil flow in large low-specific-yield formations are also suggested.

  1. Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila

    Directory of Open Access Journals (Sweden)

    Belikoff Esther J


    Full Text Available Abstract Background In male Drosophila melanogaster, the male specific lethal (MSL complex is somehow responsible for a two-fold increase in transcription of most X-linked genes, which are enriched for histone H4 acetylated at lysine 16 (H4K16ac. This acetylation requires MOF, a histone acetyltransferase that is a component of the MSL complex. MOF also associates with the non-specific lethal or NSL complex. The MSL complex is bound within active genes on the male X chromosome with a 3' bias. In contrast, the NSL complex is enriched at promoter regions of many autosomal and X-linked genes in both sexes. In this study we have investigated the role of MOF as a transcriptional activator. Results MOF was fused to the DNA binding domain of Gal4 and targeted to the promoter region of UAS-reporter genes in Drosophila. We found that expression of a UAS-red fluorescent protein (DsRed reporter gene was strongly induced by Gal4-MOF. However, DsRed RNA levels were about seven times higher in female than male larvae. Immunostaining of polytene chromosomes showed that Gal4-MOF co-localized with MSL1 to many sites on the X chromosome in male but not female nuclei. However, in female nuclei that express MSL2, Gal4-MOF co-localized with MSL1 to many sites on polytene chromosomes but DsRed expression was reduced. Mutation of conserved active site residues in MOF (Glu714 and Cys680 reduced HAT activity in vitro and UAS-DsRed activation in Drosophila. In the presence of Gal4-MOF, H4K16ac levels were enriched over UAS-lacZ and UAS-arm-lacZ reporter genes. The latter utilizes the constitutive promoter from the arm gene to drive lacZ expression. In contrast to the strong induction of UAS-DsRed expression, UAS-arm-lacZ expression increased by about 2-fold in both sexes. Conclusions Targeting MOF to reporter genes led to transcription enhancement and acetylation of histone H4 at lysine 16. Histone acetyltransferase activity was required for the full transcriptional

  2. The Immunogenicity of the Tumor-Associated Antigen α-Fetoprotein Is Enhanced by a Fusion with a Transmembrane Domain

    Directory of Open Access Journals (Sweden)

    Lucile Tran


    Full Text Available Aim. To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA vector to induce an immune response against a well-tolerated self-antigen. Methods. rMVA vectors expressing different form of α-fetoprotein (AFP were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection. Results. Vaccination with the membrane-associated form of AFP induced a stronger CD8+ T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies. Conclusions. The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

  3. Training Enhances Immune Cells Mitochondrial Biosynthesis, Fission, Fusion, and Their Antioxidant Capabilities Synergistically with Dietary Docosahexaenoic Supplementation (United States)

    Busquets-Cortés, Carla; Capó, Xavier; Tur, Josep A.; Sureda, Antoni


    Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA) supplementation (1.14 g/day) on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs) from sportsmen. Subjects were assigned to an intervention (N = 9) or placebo groups (N = 7) in a randomized double-blind trial. Nutritional intervention significantly increased the DHA content in erythrocyte membranes from the experimental group. No significant differences were reported in terms of circulating PBMCs, Mn-superoxide dismutase protein levels, and their capability to produce reactive oxygen species. The proteins related to mitochondrial dynamics were, in general, increased after an 8-week training and this increase was enhanced by DHA supplementation. The content in mitofusins Mtf-1 and Mtf-2, optic atrophy protein-1 (Opa-1), and mitochondrial transcription factor A (Tfam) were significantly higher in the DHA-supplemented group after intervention. Cytochrome c oxidase (COX-IV) activity and uncoupling proteins UCP-2 and UCP-3 protein levels were increased after training, with higher UCP-3 levels in the supplemented group. In conclusion, training induced mitochondrial adaptations which may contribute to improved mitochondrial function. This mitochondrial response was modulated by DHA supplementation. PMID:27698953

  4. Training Enhances Immune Cells Mitochondrial Biosynthesis, Fission, Fusion, and Their Antioxidant Capabilities Synergistically with Dietary Docosahexaenoic Supplementation

    Directory of Open Access Journals (Sweden)

    Carla Busquets-Cortés


    Full Text Available Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA supplementation (1.14 g/day on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs from sportsmen. Subjects were assigned to an intervention (N=9 or placebo groups (N=7 in a randomized double-blind trial. Nutritional intervention significantly increased the DHA content in erythrocyte membranes from the experimental group. No significant differences were reported in terms of circulating PBMCs, Mn-superoxide dismutase protein levels, and their capability to produce reactive oxygen species. The proteins related to mitochondrial dynamics were, in general, increased after an 8-week training and this increase was enhanced by DHA supplementation. The content in mitofusins Mtf-1 and Mtf-2, optic atrophy protein-1 (Opa-1, and mitochondrial transcription factor A (Tfam were significantly higher in the DHA-supplemented group after intervention. Cytochrome c oxidase (COX-IV activity and uncoupling proteins UCP-2 and UCP-3 protein levels were increased after training, with higher UCP-3 levels in the supplemented group. In conclusion, training induced mitochondrial adaptations which may contribute to improved mitochondrial function. This mitochondrial response was modulated by DHA supplementation.

  5. Construction of a novel fusion protein harboring mouse inter- feron γ and epidermal growth factor receptor binding domain and enhancement of its antitumor activity

    Institute of Scientific and Technical Information of China (English)

    丁炎平; 谭维彦; 胡荣; 陈望秋; 侯云德


    A novel fusion protein harboring mouse interferon γ and epidermal growth factor receptor binding domain was constructed with the method of genetic and protein engineering. The fusion protein kept complete antiviral activity with the titer of 108 IU per liter of culture. The EGF-RBD of the fusion protein exhibited competitive binding activity against 125I-mEGF for mEGF receptors on A431 cells. The fusion protein was shown to be more potent in in-hibiting the growth of cultured mouse breast carcinoma cells than interferon γ. Experimental data on mouse B16 malig-nant melanoma model indicated that the tumor weight of fusion protein-treated group was statistically significantly smaller than that of interferon γ-treated group. The work here provides a necessarily reliable clue for the upcoming clinical employment of a novel class of targeting interferons.

  6. Trophoblast fusion. (United States)

    Huppertz, Berthold; Gauster, Martin


    The villous trophoblast of the human placenta is the epithelial cover of the fetal chorionic villi floating in maternal blood. This epithelial cover is organized in two distinct layers, the multinucleated syncytiotrophoblast directly facing maternal blood and a second layer of mononucleated cytotrophoblasts. During pregnancy single cytotrophoblasts continuously fuse with the overlying syncytiotrophoblast to preserve this end-differentiated layer until delivery. Syncytial fusion continuously supplies the syncytiotrophoblast with compounds of fusing cytotrophoblasts such as proteins, nucleic acids and lipids as well as organelles. At the same time the input of cytotrophoblastic components is counterbalanced by a continuous release of apoptotic material from the syncytiotrophoblast into maternal blood. Fusion is an essential step in maintaining the syncytiotrophoblast. Trophoblast fusion was shown to be dependant on and regulated by multiple factors such as fusion proteins, proteases and cytoskeletal proteins as well as cytokines, hormones and transcription factors. In this chapter we focus on factors that may be involved in the fusion process of trophoblast directly or that may prepare the cytotrophoblast to fuse.

  7. A novel fuzzy sensor fusion algorithm

    Institute of Scientific and Technical Information of China (English)

    FU Hua; YANG Yi-kui; MA Ke; LIU Yu-jia


    A novel fusion algorithm was given based on fuzzy similarity and fuzzy integral theory.First,it calculated the fuzzy similarity among a certain sensor's measurement values and the multiple sensors' objective prediction values to determine the importance weight of each sensor and realize multi-sensor data fusion.Then according to the determined importance weight,an intelligent fusion system based on fuzzy integral theory was given,which can solve FEI-DEO and DEI-DEO fusion problems and realize the decision fusion.Simulation results were proved that fuzzy integral algorithm has enhanced the capability of handling the uncertain information and improved the intelligence degrees.

  8. Fusion Machinery

    DEFF Research Database (Denmark)

    Sørensen, Jakob Balslev; Milosevic, Ira


    the vesicular SNARE VAMP2/synaptobrevin-2 and the target (plasma membrane) SNAREs SNAP25 and syntaxin-1 results in fusion and release of neurotransmitter, synchronized to the electrical activity of the cell by calcium influx and binding to synaptotagmin. Formation of the SNARE complex is tightly regulated...... and appears to start with syntaxin-1 bound to an SM (Sec1/Munc18-like) protein. Proteins of the Munc13-family are responsible for opening up syntaxin and allowing sequential binding of SNAP-25 and VAMP2/synaptobrevin-2. N- to C-terminal “zippering” of the SNARE domains leads to membrane fusion...

  9. Enhancement of HCV polytope DNA vaccine efficacy by fusion to an N-terminal fragment of heat shock protein gp96. (United States)

    Pishraft-Sabet, Leila; Kosinska, Anna D; Rafati, Sima; Bolhassani, Azam; Taheri, Tahereh; Memarnejadian, Arash; Alavian, Seyed-Moayed; Roggendorf, Michael; Samimi-Rad, Katayoun


    Induction of a strong hepatitis C virus (HCV)-specific immune response plays a key role in control and clearance of the virus. A polytope (PT) DNA vaccine containing B- and T-cell epitopes could be a promising vaccination strategy against HCV, but its efficacy needs to be improved. The N-terminal domain of heat shock protein gp96 (NT(gp96)) has been shown to be a potent adjuvant for enhancing immunity. We constructed a PT DNA vaccine encoding four HCV immunodominant cytotoxic T lymphocyte epitopes (two HLA-A2- and two H2-D(d)-specific motifs) from the Core, E2, NS3 and NS5B antigens in addition to a T-helper CD4+ epitope from NS3 and a B-cell epitope from E2. The NT(gp96) was fused to the C- or N-terminal end of the PT DNA (PT-NT(gp96) or NT(gp96)-PT), and their potency was compared. Cellular and humoral immune responses against the expressed peptides were evaluated in CB6F1 mice. Our results showed that immunization of mice with PT DNA vaccine fused to NT(gp96) induced significantly stronger T-cell and antibody responses than PT DNA alone. Furthermore, the adjuvant activity of NT(gp96) was more efficient in the induction of immune responses when fused to the C-terminal end of the HCV DNA polytope. In conclusion, the NT(gp96) improved the efficacy of the DNA vaccine, and this immunomodulatory effect was dependent on the position of the fusion.

  10. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application. (United States)

    Ichiyama, Koji; Gopala Reddy, Sindhoora Bhargavi; Zhang, Li Feng; Chin, Wei Xin; Muschin, Tegshi; Heinig, Lars; Suzuki, Youichi; Nanjundappa, Haraprasad; Yoshinaka, Yoshiyuki; Ryo, Akihide; Nomura, Nobuo; Ooi, Eng Eong; Vasudevan, Subhash G; Yoshida, Takashi; Yamamoto, Naoki


    Curdlan sulfate (CRDS), a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV). CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E) protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion). The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.

  11. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.

    Directory of Open Access Journals (Sweden)

    Koji Ichiyama

    Full Text Available Curdlan sulfate (CRDS, a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV. CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion. The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.

  12. Magnetic fusion; La fusion magnetique

    Energy Technology Data Exchange (ETDEWEB)



    This document is a detailed lecture on thermonuclear fusion. The basic physics principles are recalled and the technological choices that have led to tokamaks or stellarators are exposed. Different aspects concerning thermonuclear reactors such as safety, economy and feasibility are discussed. Tore-supra is described in details as well as the ITER project.

  13. Expression of cholera toxin B subunit-lumbrokinase in edible sunflower seeds-the use of transmucosal carrier to enhance its fusion protein's effect on protection of rats and mice against thrombosis. (United States)

    Guan, Chunfeng; Ji, Jing; Jin, Chao; Wang, Gang; Li, Xiaozhou; Guan, Wenzhu


    Lumbrokinase (LK) is a group of serine proteases with strong fibrinolytic and thrombolytic activities and is useful for treating diseases caused by thrombus. Cholera toxin B subunit (CTB) has been widely used to facilitate antigen delivery by serving as an effective mucosal carrier molecule for the induction of oral tolerance. We investigate here the application of CTB as a transmucosal carrier in enhancing its fusion protein-LKs effect to protect rats against thrombosis. Thus, in this study, CTB-LK fusion gene separated by a furin cleavage site was expressed in seeds of Helianthus annuus L. The activity of recombinant protein in seeds of transgenic sunflower was confirmed by Western blot analysis, fibrin plate assays and GM1 -ganglioside ELISA. The thrombosis model of rats and mice revealed that the oral administration of peeled seeds of sunflower expressing CTB-LK had a more significant anti-thrombotic effect on animals compared with that administration of peeled seeds of sunflower expressing LK. It is possible to conclude that CTB can successfully enhance its fusion protein to be absorbed in rats or mice thrombosis model. The use of CTB as a transmucosal carrier in the delivery of transgenic plant-derived oral therapeutic proteins was supported. In addition, for the purpose of that recombinant CTB-LK was designed for oral administration, thus the expression of CTB-LK in edible sunflower seeds eliminated the need for downstream processing of proteins.

  14. Tame Fusion

    Institute of Scientific and Technical Information of China (English)

    S.D. Scott


    The first section of this paper covers preliminaries. Essentially, the next four cover units. It is shown that a compatible nearring with DCCR is Nnilpotent if and only if every maximal right N-subgroup is a right ideal. The last five sections relate to fusion (I.e., N-groups minimal for being generated by Nsubgroups, where each is N-isomorphic to a given N-group). Right N-subgroups of a tame nearring N with DCCR, minimal for not annihilating a minimal ideal from the left, are self monogenic and N-isomorphic. That this holds for any collection of minimal ideals is significant. Here, the right N-subgroup involved is a 'fusion product' of the 'components'.

  15. Carpal Fusion



    Carpal fusion may be seen in hereditary and nonhereditary conditions such as acrocallosal syndrome,acromegaly, Apert syndrome, arthrogryposis, Carpenter syndrome, chromosomal abnormalities, ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome, the F form of acropectorovertebral dysgenesis or the F syndrome, fetal alcohol syndrome, Holt-Oram syndrome, Leopard syndrome, multiple synostosis syndrome, oligosyndactyly syndrome, Pfeiffer-like syndrome, scleroderma, split hand and foot malformatio...

  16. Fusion rules of equivariantizations of fusion categories



    We determine the fusion rules of the equivariantization of a fusion category $\\mathcal{C}$ under the action of a finite group $G$ in terms of the fusion rules of $\\mathcal{C}$ and group-theoretical data associated to the group action. As an application we obtain a formula for the fusion rules in an equivariantization of a pointed fusion category in terms of group-theoretical data. This entails a description of the fusion rules in any braided group-theoretical fusion category.

  17. Indirect drive targets for fusion power

    Energy Technology Data Exchange (ETDEWEB)

    Amendt, Peter A.; Miles, Robin R.


    A hohlraum for an inertial confinement fusion power plant is disclosed. The hohlraum includes a generally cylindrical exterior surface, and an interior rugby ball-shaped surface. Windows over laser entrance holes at each end of the hohlraum enclose inert gas. Infrared reflectors on opposite sides of the central point reflect fusion chamber heat away from the capsule. P2 shields disposed on the infrared reflectors help assure an enhanced and more uniform x-ray bath for the fusion fuel capsule.

  18. Evaluation of an injectable silk fibroin enhanced calcium phosphate cement loaded with human recombinant bone morphogenetic protein-2 in ovine lumbar interbody fusion. (United States)

    Gu, Yong; Chen, Liang; Yang, Hui-Lin; Luo, Zong-Ping; Tang, Tian-Si


    The objective of this study was to investigate the efficacy of an injectable calcium phosphate cement/silk fibroin/human recombinant bone morphogenetic protein-2 composite (CPC/SF/rhBMP-2) in an ovine interbody fusion model. Twenty-four mature sheep underwent anterior lumbar interbody fusion at the levels of L1/2, L3/4, and L5/6 with random implantation of CPC/SF, CPC/rhBMP-2, CPC/SF/rhBMP-2, or autogenous iliac bone. After the sheep were sacrificed, the fusion segments were evaluated by manual palpation, CT scan, undestructive biomechanical testing, undecalcified histology, and histomorphology. The fusion rates of CPC/SF/rhBMP-2 were 55.56% and 77.78% at 6 and 12 months, respectively. The fusion was superior to all the biomaterial grafts in stiffness, and reached the same stiffness as the autograft at 12 months. The new bone formation was less than autograft at 6 months, but similar with that at 12 months. However, the ceramic residue volume of CPC/SF/rhBMP-2 was significantly decreased compared with CPC/SF and CPC/rhBMP-2 at both times. The results indicated that CPC/SF/rhBMP-2 composite had excellent osteoconduction and osteoinduction, and balanced degradation and osteogenesis.

  19. Information fusion for palmprint authentication (United States)

    Wu, Xiangqian; Wang, Kuanquan; Zhang, David


    A palmprint can be represented using different features and the different representations reflect the different characteristic of a palmprint. Fusion of multiple palmprint features may enhance the performance of a palmprint authentication system. This paper investigates the fusion of two types of palmprint information: the phase (called PalmCode) and the orientation (called OrientationCode). The PalmCode is extracted using the 2-D Gabor filters based algorithm and the OrientationCode is computed using several directional templates. Then several fusion strategies are investigated and compared. The experimental results show that the fusion of the PalmCode and OrientationCode using the Product, Sum and Weighted Sum strategies can greatly improve the accuracy of palmprint authentication, which is up to 99.6%.

  20. On the energy gain enhancement of DT+D3He fuel configuration in nuclear fusion reactor driven by heavy ion beams

    Directory of Open Access Journals (Sweden)

    S Khoshbinfar


    Full Text Available It is expected that advanced fuels be employed in the second generation of nuclear fusion reactors. Theoretical calculations show that in such a fuel, a high plasma temperature about 100 keV is a requisite for reaction rate improvement of nuclear fusion. However, creating such a temporal condition requires a more powerful driver than we have today. Here, introducing an optimal fuel configuration consisting of DT and D-3He layers, suitable for inertial fusion reactors and driven by heavy ion beams, the optimal energy gain conditions have been simulated and derived for 1.3 MJ system. It was found that, in this new fuel configuration, the ideal energy gain, is 22 percent more comparing with energy gain in corresponding single DT fuel layer. Moreover, the inner DT fuel layer contributed as an ignition trigger, while the outer D3He fuel acts as particle and radiation shielding as well as fuel layer.


    Institute of Scientific and Technical Information of China (English)

    Caroline; 黄颖(翻译)


    Fusion World”科技展示体验中心是英国设计公司MET Studio为新加坡科技研究局(A*Star)的科学工程委员会(SERC)所设计的,位于启汇城的办公地点,用于展示该委员会的精选技术作品,以吸引潜在的客户和启汇城内的学生购买群体。

  2. Role of Caveolin-1 in Prostate Cancer Angiogenesis (United States)


    associated with unfavorable clinical prognosis in various adenocarcinomas (reviewed in Bender et al., 2000; Carrion et al., 2003; Davidson et al., 2002...for other malignancies including metastatic colon cancer (Bender et al., 2000; Patlolla et al., 2004), renal cancer (Campbell et al., 2003; Carrion et...formation. Am. J. Pathol. 162, 2029–2039. Carrion , R., et al., 2003. Caveolin expression in adult renal tumors. Urol. Oncol. 21, 191–196. Carver, L.A

  3. Links between CD147 Function, Glycosylation, and Caveolin-1


    Tang, Wei; Chang, Sharon B.; Hemler, Martin E.


    Cell surface CD147 shows remarkable variations in size (31-65 kDa) because of heterogeneous N-glycosylation, with the most highly glycosylated forms functioning to induce matrix metalloproteinase (MMP) production. Here we show that all three CD147 N-glycosylation sites make similar contributions to both high and low glycoforms (HG- and LG-CD147). l-Phytohemagglutinin lectin binding and swainsonine inhibition experiments indicated that HG-CD147 contains N-acetylglucosaminyltransferase V-cataly...

  4. A fusogenic dengue virus-derived peptide enhances antitumor efficacy of an antibody-ribonuclease fusion protein targeting the EGF receptor. (United States)

    Kiesgen, Stefan; Liebers, Nora; Cremer, Martin; Arnold, Ulrich; Weber, Tobias; Keller, Armin; Herold-Mende, Christel; Dyckhoff, Gerhard; Jäger, Dirk; Kontermann, Roland E; Arndt, Michaela A E; Krauss, Jürgen


    Due to its frequent overexpression in a variety of solid tumors the epidermal growth factor receptor (EGFR) is a well-established target for therapeutic interventions in epithelial cancers. In order to target EGFR in head and neck cancer, we have generated a ribonuclease (RNase) fusion protein comprising a humanized anti-EGFR antibody single-chain Fv fragment (scFv) and Ranpirnase, an RNase from Rana pipiens. Fusion of Ranpirnase to the N-terminus of the scFv via a flexible glycine-serine linker (G4S)3 resulted in very poor cytotoxicity of the fusion protein. As endosomal accumulation and lysosomal degradation have been reported to diminish the antitumor efficacy of ribonuclease or toxin-based immunoagents, we explored a fusion peptide from dengue virus that has been reported to be involved in the endosomal escape of the virus. This peptide was introduced as a linker between Ranpirnase and the scFv moiety. The modified immunoRNase exhibited exceptionally high cytotoxicity toward EGFR-expressing head and neck cell lines without affecting specificity. These results indicate that endosomal entrapment needs to be considered for Ranpirnase-based immunoagents and might be overcome by the use of tailored transduction domains from viral proteins.

  5. Carpal Fusion

    Directory of Open Access Journals (Sweden)

    Jalal Jalalshokouhi*


    Full Text Available Carpal fusion may be seen in hereditary and nonhereditary conditions such as acrocallosal syndrome,acromegaly, Apert syndrome, arthrogryposis, Carpenter syndrome, chromosomal abnormalities, ectrodactyly-ectodermal dysplasia-cleft (EEC syndrome, the F form of acropectorovertebral dysgenesis or the F syndrome, fetal alcohol syndrome, Holt-Oram syndrome, Leopard syndrome, multiple synostosis syndrome, oligosyndactyly syndrome, Pfeiffer-like syndrome, scleroderma, split hand and foot malformation, Stickler syndrome, thalidomide embryopathy, Turner syndrome and many other conditions as mentioned in Rubinstein-Taybi's book. Sometimes there is no known causative disease.Diagnosis is usually made by plain X-ray during studying a syndrome or congenital disease or could be an incidental finding like our patients. Hand bone anomalies are more common in syndromes or other congenital or non-hereditary conditions, but polydactyly, syndactyly or oligodactyly and carpal fusions are interesting. X-ray is the modality of choice, but MRI and X-ray CT with multiplanar reconstructions may be used for diagnosis.

  6. The influence of transfer reactions on the sub-barrier fusion enhancement in the systems {sup 58.64}Ni +, {sup 92,100}Mo

    Energy Technology Data Exchange (ETDEWEB)

    Rehm, K.E.; Jiang, C.L.; Esbensen, H. [and others


    High resolution experiments performed during the past few years demonstrated that the various reaction modes occurring in heavy ion collisions can strongly influence each other. This interrelation of the different reaction modes brings a nuclear structure dependence to the fusion and deep-inelastic channels that were previously described in the framework of pure statistical models. In order to fully understand the interrelation between these reaction channels, a complete set of measurements including elastic and inelastic scattering, few-nucleon transfer and fusion is required. In continuation of our earlier measurements of the fusion cross sections in the system {sup 58,64}Ni + {sup 92,100}Mo we finished the studies of the quasielastic process in these systems. The experiments were done in inverse reaction kinematics using the split-pole spectrograph with its hybrid focal-plane detector for particle identification. The experiments with {sup 100}Mo beams were performed previously. First test runs with {sup 92}Mo showed the possible interference with {sup 98}Mo ions which could be eliminated by using the 13{sup +} charge state from the ECR source. The data from these experiments were completely analyzed. The smallest transfer cross sections are observed for the systems {sup 64}Ni + {sup 100}Mo and {sup 58}Ni + {sup 92}Mo, i.e., the most neutron-rich and neutron-deficient systems, respectively. For the other systems, {sup 64}Ni + {sup 92}Mo and {sup 58}Ni + {sup 100}Mo, the transfer cross sections at energies close to the barrier are about of equal magnitude. This observation does not correlate with the deviation of the experimental fusion cross sections from the coupled-channels predictions. While for {sup 58}Ni + {sup 100}Mo discrepancies between the experimental and theoretical fusion cross sections are observed, the system {sup 64}Ni + {sup 92}Mo which shows about the same transfer yields, is quite well described by the coupled-channels calculations.

  7. Enhanced inhibition of tumour growth and metastasis, and induction of antitumour immunity by IL-2-IgG2b fusion protein. (United States)

    Budagian, V; Nanni, P; Lollini, P L; Musiani, P; Di Carlo, E; Bulanova, E; Paus, R; Bulfone-Paus, S


    Cytokine-immunoglobulin (Ig)-fusion proteins have attracted increasing interest as antitumour agents. Here, we have investigated the antimetastatic and antitumour responses elicited in vivo by mammary adenocarcinoma cells (TS/A) engineered to secrete interleukin (IL)-2-IgG fusion proteins. TS/A cells were transfected with DNA coding for IL-2-IgG2b, IgG2b or IL-2, and injected subcutaneously into syngeneic mice. Animals injected with TS/A-IL-2 or TS/A-IL-2-IgG2b both efficiently rejected tumours, whereas treatment with parental cells or TS/A-IgG2b was lethal. Interestingly, only mice vaccinated with IL-2-IgG2b fusion protein-secreting cells showed a long-lasting protective immunity against a later challenge with parental tumour cells. Moreover, the metastatic potential of TS/A-IL-2-IgG2b-transfected cells was dramatically decreased compared with TS/A-IL-2-cells, with a virtual absence of lung metastases after intravenous injection. Adenocarcinomas secreting IL-2-IgG2b exhibited a more prominent, early and persistent infiltration of CD4+, CD8+ and natural killer (NK) cells than TS/A-IL-2 cells. Therefore, upon transfection into adenocarcinoma cells, the IgG2b part of IL-2 fusion protein exerts intriguing added antitumour properties over IL-2 alone, thus contributing to a long-lasting tumour immunity, probably by the recruitment of specific immune effector cells. These findings suggest a promising new oncotherapeutic strategy for poorly immunogenic tumours: vaccination with tumour cells engineered to secrete IL-2-IgG2b fusion protein.

  8. Nuclear Fusion Fuel Cycle Research Perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hongsuk; Koo, Daeseo; Park, Jongcheol; Kim, Yeanjin [KAERI, Daejeon (Korea, Republic of); Yun, Sei-Hun [National Fusion Research Institute, Daejeon (Korea, Republic of)


    As a part of the International Thermonuclear Experimental Reactor (ITER) Project, we at the Korea Atomic Energy Research Institute (KAERI) and our National Fusion Research Institute (NFRI) colleagues are investigating nuclear fusion fuel cycle hardware including a nuclear fusion fuel Storage and Delivery System (SDS). To have a better knowledge of the nuclear fusion fuel cycle, we present our research efforts not only on SDS but also on the Fuel Supply System (FS), Tokamak Exhaust Processing System (TEP), Isotope Separation System (ISS), and Detritiation System (DS). To have better knowledge of the nuclear fusion fuel cycle, we presented our research efforts not only on SDS but also on the Fuel Supply System (FS), Tokamak Exhaust Processing System (TEP), Isotope Separation System (ISS), and Detritiation System (DS). Our efforts to enhance the tritium confinement will be continued for the development of cleaner nuclear fusion power plants.

  9. Catalysed fusion

    CERN Document Server

    Farley, Francis


    A sizzling romance and a romp with subatomic particles at CERN. Love, discovery and adventure in the city where nations meet and beams collide. Life in a large laboratory. As always, the challenges are the same. Who leads? Who follows? Who succeeds? Who gets the credit? Who gets the women or the men? Young Jeremy arrives in CERN and joins the quest for green energy. Coping with baffling jargon and manifold dangers, he is distracted by radioactive rats, lovely ladies and an unscrupulous rival. Full of doubts and hesitations, he falls for a dazzling Danish girl, who leads him astray. His brilliant idea leads to a discovery and a new route to cold fusion. But his personal life is scrambled. Does it bring fame or failure? Tragedy or triumph?

  10. Recent developments concerning the fusion; Developpements recents sur la fusion

    Energy Technology Data Exchange (ETDEWEB)

    Jacquinot, J. [CEA/Cadarache, Dept. de Recherches sur la Fusion Controlee, DRFC, 13 - Saint Paul lez Durance (France); Andre, M. [CEA/DAM Ile de France, 91 - Bruyeres Le Chatel (France); Aymar, R. [ITER Joint Central Team Garching, Muenchen (Germany)] [and others


    Organized the 9 march 2000 by the SFEN, this meeting on the european program concerning the fusion, showed the utility of the exploitation and the enhancement of the actual technology (JET, Tore Supra, ASDEX) and the importance of the Europe engagement in the ITER program. The physical stakes for the magnetic fusion have been developed with a presentation of the progresses in the knowledge of the stability limits. A paper on the inertial fusion was based on the LMJ (Laser MegaJoule) project. The two blanket concepts chosen in the scope of the european program on the tritium blankets, have been discussed. These concepts will be validated by irradiation tests in the ITER-FEAT and adapted for a future reactor. (A.L.B.)

  11. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup


    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

  12. Co-localization of Caveolin-1 and Extracellular Ca2+-sensing Receptor in Caveolae in Human Umbilical Vein Endothelial Cells%小凹蛋白-1和细胞外钙敏感受体在人脐静脉内皮细胞小凹共定位研究

    Institute of Scientific and Technical Information of China (English)

    龚艳; 胡清华; 钟华; 梁霄; 罗小林; 何芳


    前期研究发现小凹蛋白-1(caveolin-1,Cav-1)和细胞外钙敏感受体(extracellular Ca2+-sensing receptor,CaR)在人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)膜上有共定位,且Cav-1下调CaR介导的钙内流.本实验探讨HUVECs中Cav-1与CaR的亚细胞定位,可为进一步机制研究提供理论依据.以3~4代HUVECs随机分为2组:(1)对照组;(2)甲基-β-环糊精(MβCD)处理组,分别采用蔗糖密度梯度离心和Western blot 技术提取含小凹膜碎片和检测Cav-1和CaR蛋白的表达.结果显示,(1) MβCD处理组HUVECs细胞中Cav-1和CaR蛋白的表达与对照组相比无差异(P>0.05).(2)MβCD处理组小凹区Cav-1和CaR蛋白的表达低于对照组(P<0.05).由此可知,Cav-1和CaR蛋白共定位于HUVECs的小凹区,MβCD可抑制两者在小凹的共定位.%Our previous results demonstrated that extracellular Ca2+-sensing receptor (CaR) and caveolin-l(Cav-l) co-localized on the plasma localization of Cav-1 and CaR in HUVECs, which provide a theoretical basis for further functional studies. Methods: The third or fourth passage of HUVECs were randomly divided into two groups:(l) Control groupi (2)methyl-|J-cyelo-dextrin(MpCD) group. We isolated caveolae-enriched membrane fractions from MpCD-treated HUVECs by TritonX-100 sucrose density gradient fractionation and detected the expressions of Cav-1 and CaR protein by Western blot.respectively. Results! (1) The expression of Cav-1 and CaR proteins between control group and MpCD group was no difference (P>0. 05). (2)The expressions of Cav-1 and CaR proteins in caveolae after MpCD treated was significantly reduced(P<0. 05). Conclusion, The present study suggests that CaR and Cav-1 co-localize in caveolae in HUVECS. MpCD reduces the co-localization of Cav-1 and CaR in caveolae.

  13. Fusion Energy from the electric utilities perspective: Fusion Innovation Industry Forum

    Energy Technology Data Exchange (ETDEWEB)

    Tagle, J. A.; Felipe, A.; Gomez, A.; Sanchez-Mayoral, M. L.; Merino, A.


    The paper presents the different future energy scenarios envisaged and the so called Power Generation Fleet Transition in which Fusion Energy could play an important role. A review of the R and D and Innovation main drivers in the electric sector is outline, with a detail description of the main issues and strategic challenges in the medium and short term. The worldwide historical involvement of electric utilities in Fusion is presented and revised under the new USA Utilities technical assessment carried out by the Electric Power Research Institute EPRI. The paper also presents the work done in the last few years by the European Fusion Industry Innovation Forum FIIF-MB in order to to evaluate a wide range of fusion concepts from the utility standpoint, to enhance utilities perspective on fusion, to provide guidance to Government Bodies and national Energy strategies for fusion-utilities and finally to establish a basis for communication and cooperation in fusion for utilities standpoint. Finally the paper comments the utilities challenges pointed out by the Fusion electricity: a road map to the realization of fusion energy report issued this year by the European Fusion Development Agreement EFDA.

  14. Research on an Agricultural Knowledge Fusion Method for Big Data

    Directory of Open Access Journals (Sweden)

    Nengfu Xie


    Full Text Available The object of our research is to develop an ontology-based agricultural knowledge fusion method that can be used as a comprehensive basis on which to solve agricultural information inconsistencies, analyze data, and discover new knowledge. A recent survey has provided a detailed comparison of various fusion methods used with Deep Web data (Li, 2013. In this paper, we propose an effective agricultural ontology-based knowledge fusion method by leveraging recent advances in data fusion, such as the semantic web and big data technologies, that will enhance the identification and fusion of new and existing data sets to make big data analytics more possible. We provide a detailed fusion method that includes agricultural ontology building, fusion rule construction, an evaluation module, etc. Empirical results show that this knowledge fusion method is useful for knowledge discovery.

  15. Effects of entrance channel on fusion probability in hot fusion reactions

    CERN Document Server

    Zhu, Long; Huang, Ching-Yuan; Zhang, Feng-Shou


    Within the framework of the dinuclear system (DNS) model, the fusion reactions leading to the compound nuclei 274Hs and 286Cn are investigated. The fusion probability as a function of DNS excitation energy is studied. The calculated results are in good agreement with the available experimental data. The obtained results show that the fusion probabilities are obviously enhanced for the reactions located at high place in potential energy surface, although these reactions may have small values of mass asymmetry. It is found that the enhancement is due to the large potential energy of the initial DNS.

  16. Combined Sparsifying Transforms for Compressive Image Fusion

    Directory of Open Access Journals (Sweden)

    ZHAO, L.


    Full Text Available In this paper, we present a new compressive image fusion method based on combined sparsifying transforms. First, the framework of compressive image fusion is introduced briefly. Then, combined sparsifying transforms are presented to enhance the sparsity of images. Finally, a reconstruction algorithm based on the nonlinear conjugate gradient is presented to get the fused image. The simulations demonstrate that by using the combined sparsifying transforms better results can be achieved in terms of both the subjective visual effect and the objective evaluation indexes than using only a single sparsifying transform for compressive image fusion.

  17. Transfer reactions as a doorway to fusion

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, P.R.S.; Maciel, A.M.M.; Anjos, R.M.; Moraes, S.B.; Liguori Neto, R.; Cabezas, R.; Muri, C.; Santos, G.M. [Instituto de Fisica, Universidade Federal Fluminense, Av. Litoranea s/n, Gragoata, Niteroi, RJ, 24210-340 (Brazil); Liang, J.F. [Nuclear Physics Laboratory, University of Washington, Seattle, WA 98195 (United States)


    This paper discusses the role played by transfer reactions on the sub-barrier fusion enhancement. A semiclassical formalism is used to derive the transfer form factors, that are used in coupled-channel calculations. It is shown that transfer reactions that take place at small distances may be an important doorway to fusion. The relation between this formalism and the long-range absorptive fusion potential is also discussed. Results of calculations for the {sup 16}O+{sup A}Sm, {sup 32}S+{sup 100}Mo and {sup 16}O+{sup 59}Co systems are presented. (author)

  18. 颜色对比度增强的红外与可见光图像融合方法%One color contrast enhanced infrared and visible image fusion method

    Institute of Scientific and Technical Information of China (English)

    曾祥通; 张玉珍; 孙佳嵩; 喻士领


    针对红外与可见光彩色融合图像中目标与背景间的低对比度的问题,提出一种基于HSI空间颜色对比度增强的红外和可见光图像融合方法。首先对输入的可见光与红外图像进行直方图均衡和中值滤波加强处理,然后对加强的红外图像模糊阈值分割得到红外目标,最后把分割的红外目标图像和加强的可见光和红外图像在HSI空间的三通道线性融合和色彩传递,为了增强目标与背景间的颜色对比度,在色彩传递阶段,H通道的色彩传递方程中引入一个比例因子。实验结果表明:与其他算法相比,该方法得到的彩色融合图像热目标和低温物体与背景间的颜色对比度明显加强,同时背景的细节信息呈现白天类似的自然彩色,更加符合人眼视觉感知。%Focus on color fusion for infrared and visible images with low contrast between target and background issues, a contrast enhancement method for infrared and visible image was presented based on HSI color space. Firstly, the contrast of infrared and visible images was enhanced using local histogram equalization and median filter, then the infrared target was extracted from the enhanced infrared image after fuzzy threshold segmentation. Finally, the two enhanced images and the segmentation infrared target were fused into the three components of a HSI image in terms of a simple linear fusion strategy and color transfer. To enhance the color contrast between the target and the background, a scaling factor was introduced into the transferring equation in the H channel during color transfer process. The experimental results show that, compared with other algorithms, the color fusion images of hot target and color contrast between low temperature object and background abtained by the presented method enhance obviously. At the same time, the details of visible images are endowed with natural color similar to that of the light color images during

  19. Cold fusion research

    Energy Technology Data Exchange (ETDEWEB)



    I am pleased to forward to you the Final Report of the Cold Fusion Panel. This report reviews the current status of cold fusion and includes major chapters on Calorimetry and Excess Heat, Fusion Products and Materials Characterization. In addition, the report makes a number of conclusions and recommendations, as requested by the Secretary of Energy.

  20. Enhanced research in ground-penetrating radar and multisensor fusion with application to the detection and visualization of buried waste. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Devney, A.J.; DiMarzio, C.; Kokar, M.; Miller, E.L.; Rappaport, C.M.; Weedon, W.H.


    Recognizing the difficulty and importance of the landfill remediation problems faced by DOE, and the fact that no one sensor alone can provide complete environmental site characterization, a multidisciplinary team approach was chosen for this project. The authors have developed a multisensor fusion approach that is suitable for the wide variety of sensors available to DOE, that allows separate detection algorithms to be developed and custom-tailored to each sensor. This approach is currently being applied to the Geonics EM-61 and Coleman step-frequency radar data. High-resolution array processing techniques were developed for detecting and localizing buried waste containers. A soil characterization laboratory facility was developed using a HP-8510 network analyzer and near-field coaxial probe. Both internal and external calibration procedures were developed for de-embedding the frequency-dependent soil electrical parameters from the measurements. Dispersive soil propagation modeling algorithms were also developed for simulating wave propagation in dispersive soil media. A study was performed on the application of infrared sensors to the landfill remediation problem, particularly for providing information on volatile organic compounds (VOC`s) in the atmosphere. A dust-emission lidar system is proposed for landfill remediation monitoring. Design specifications are outlined for a system which could be used to monitor dust emissions in a landfill remediation effort. The detailed results of the investigations are contained herein.

  1. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail:


    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  2. Identification of targetable FGFR gene fusions in diverse cancers. (United States)

    Wu, Yi-Mi; Su, Fengyun; Kalyana-Sundaram, Shanker; Khazanov, Nickolay; Ateeq, Bushra; Cao, Xuhong; Lonigro, Robert J; Vats, Pankaj; Wang, Rui; Lin, Su-Fang; Cheng, Ann-Joy; Kunju, Lakshmi P; Siddiqui, Javed; Tomlins, Scott A; Wyngaard, Peter; Sadis, Seth; Roychowdhury, Sameek; Hussain, Maha H; Feng, Felix Y; Zalupski, Mark M; Talpaz, Moshe; Pienta, Kenneth J; Rhodes, Daniel R; Robinson, Dan R; Chinnaiyan, Arul M


    Through a prospective clinical sequencing program for advanced cancers, four index cases were identified which harbor gene rearrangements of FGFR2, including patients with cholangiocarcinoma, breast cancer, and prostate cancer. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, we identified additional FGFR fusions with intact kinase domains in lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins induced cell proliferation. Two bladder cancer cell lines that harbor FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Because of the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts, which incorporate transcriptome analysis for gene fusions, are poised to identify rare, targetable FGFR fusions across diverse cancer types.

  3. Fluorescent visualisation of the hypothalamic oxytocin neurones activated by cholecystokinin-8 in rats expressing c-fos-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 fusion transgenes. (United States)

    Katoh, A; Shoguchi, K; Matsuoka, H; Yoshimura, M; Ohkubo, J-I; Matsuura, T; Maruyama, T; Ishikura, T; Aritomi, T; Fujihara, H; Hashimoto, H; Suzuki, H; Murphy, D; Ueta, Y


    The up-regulation of c-fos gene expression is widely used as a marker of neuronal activation elicited by various stimuli. Anatomically precise observation of c-fos gene products can be achieved at the RNA level by in situ hybridisation or at the protein level by immunocytochemistry. Both of these methods are time and labour intensive. We have developed a novel transgenic rat system that enables the trivial visualisation of c-fos expression using an enhanced green fluorescent protein (eGFP) tag. These rats express a transgene consisting of c-fos gene regulatory sequences that drive the expression of a c-fos-eGFP fusion protein. In c-fos-eGFP transgenic rats, robust nuclear eGFP fluorescence was observed in osmosensitive brain regions 90 min after i.p. administration of hypertonic saline. Nuclear eGFP fluorescence was also observed in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) 90 min after i.p. administration of cholecystokinin (CCK)-8, which selectively activates oxytocin (OXT)-secreting neurones in the hypothalamus. In double transgenic rats that express c-fos-eGFP and an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene, almost all mRFP1-positive neurones in the SON and PVN expressed nuclear eGFP fluorescence 90 min after i.p. administration of CCK-8. It is possible that not only a plane image, but also three-dimensional reconstruction image may identify cytoplasmic vesicles in an activated neurone at the same time.

  4. An Image Enhancement Algrorithm of Foggy Video Surveillance Based on Wavelet Fusion%一种基于小波融合的雾天视频监控图像增强算法

    Institute of Scientific and Technical Information of China (English)

    张恒; 谷丰; 张欣


    针对雾天视频监控系统采集的图像对比度降低、图像模糊的问题,提出一种小波融合算法。该算法在已有的图像增强方法的基础上,应用小波变换、直方图均衡化和非线性增强算子来综合处理雾天降质图像。实验结果表明,该算法对比于传统的方法不但可以明显的提高图像对比度,而且增强图像的边缘细节和纹理特性,取得较好的效果。%In view of problems of low in contrast gradient and fuzzy in imaging quality when video monitoring system acquiring image in fog, propos-es an algorithm based on wavelet fusion. Uses wavelet transform, histogram equalization and non-linear operator to process synthetically fog-degraded image based on the existent image enhancement method. The experiments show that the algorithm compared with conven-tional methods can not only obviously improve image contrast and enhance the image edge details and texture property, and achieve good results.

  5. Study on expression and methylation of caveolin 1 gene in non-small cell lung cancers%非小细胞肺癌中窖蛋白1基因的蛋白表达和甲基化及其意义

    Institute of Scientific and Technical Information of China (English)

    张玉霞; 陈洪雷; 叶波; 杨飞; 喻伦银


    目的 检测窖蛋白1(Car-1)在非小细胞肺癌(NSCLC)中的蛋白表达以及启动子的甲基化状况,探讨Cav-1基因在NSCLC中的作用及其临床意义.方法 应用免疫组织化学(sP法)和量子点Qd600染色检测123例NSCLC组织、17例良性病变肺组织中Cav一1蛋白表达和亚细胞定位.亚硫酸氢钠处理DNA,甲基化特异性PCR(MSP)检测Cav-1基因启动子区域的甲基化水平.结果 Cav-1蛋白在肺支气管黏膜上皮细胞、肺泡上皮细胞、毛细血管内皮细胞、成纤维细胞、平滑肌细胞的胞质和胞膜高表达.癌旁组织(对照)组和肺癌组中Cav-1蛋白的阳性率分别为17/17、43.1%(53/123),两组间差异有统计学意义(P=0.001);Cav-1蛋白在NSCLC不同的组织学类型(P=0.552)和分化程度(P=0.160)中差异均无统计学意义.Cav-1蛋白阳性率与NSCLC的TNM分期(P=0.001)以及淋巴结转移(P=0.001)均相关.在40例Cav-1蛋白表达为阴性的肺癌组织和12例癌旁肺组织,MSP法均未检测到Cav-1因启动子区域的甲基化.结论 Cav-1蛋白失表达的机制可能与启动子区是否甲基化无关.Cav-1蛋白高表达预示NSCLC恶化进展和高侵袭性.%Objective To study the methylation of CpG islands in the promoter region, expression of caveolin 1(Cav-1)gene and their clinical significance in non. small cell lung cancers(NSCLC). Methods Immunohistochemistry and quanta Qd600 staining were used to detect the expression of Cav-1 in tissues from benign lung lesions(n=17)and NSCLC(n=123). DNA was treated with sodium bisulfite and the Cav-1 promoter region was screened using methylation. specmc polymerase chain reaction for the possible methylation sites. Results Cav. 1 protein was highly expressed in cytoplasm and cell membrane of normal bronchial epithelium, alveolar epithelium, endothelial cells. fibroblasts and smooth muscle cells. The expression rates of Cav-1 protein were 100%(17/17)in the control group and 43. 1%(53/123)in the NSCLC group(P=0. 001

  6. Fusion using radioactive ion beams

    Indian Academy of Sciences (India)

    A M Vinodkumar


    The capture-fission cross-section is measured for the collision of the massive nucleus 132Sn with 96Zr at near-barrier energies and compared with the collision of 124Sn with 96Zr. This study gives insight into fusion enhancement and hindrance in systems involving neutron-rich nuclei. The dinuclear system model (DNS) calculations describe the excitation function reasonably well and if we use the barrier heights predicted by this model we can conclude that fusion hindrance (represented by extra push energy) is greater for the more neutron-rich systems. The fusion excitation function for 9Li+70Zn and 9Li+208Pb systems are measured for near-barrier energies using ISAC1 and ISAC2 Facilities at TRIUMF. The -emitting evaporation residues (211−214At) are stopped in the 208Pb target and their decay is measured. The measured excitation function shows evidence for large enhancements in the sub-barrier energies, which is not accounted by current theoretical models. Suppression of the above-barrier cross-section with respect to these theoretical models are also seen.

  7. Data fusion for the detection of buried land mines

    Energy Technology Data Exchange (ETDEWEB)

    Clark, G.A.; Sengupta, S.K.; Schaich, P.C.; Sherwood, R.J.; Buhl, M.R.; Hernandez, J.E.; Kane, R.J.; Barth, M.J.; Fields, D.J.; Carter, M.R.


    The authors conducted experiments to demonstrate the enhanced delectability of buried land mines using sensor fusion techniques. Multiple sensors, including imagery, infrared imagery, and ground penetrating radar, have been used to acquire data on a number of buried mines and mine surrogates. The authors present this data along with a discussion of the application of sensor fusion techniques for this particular detection problem. The authors describe the data fusion architecture and discuss some relevant results of these classification methods.

  8. Elements of Successful and Safe Fusion Experiment Operations

    Energy Technology Data Exchange (ETDEWEB)

    K. Rule, L. Cadwallader, Y. Takase, T. Norimatsu, O. Kaneko, M. Sato, and R. Savercool


    A group of fusion safety professionals contribute to a Joint Working Group (JWG) that performs occupational safety walkthroughs of US and Japanese fusion experiments on a routine basis to enhance the safety of visiting researchers. The most recent walkthrough was completed in Japan in March 2008 by the US Safety Monitor team. This paper gives the general conclusions on fusion facility personnel safety that can be drawn from the series of walkthroughs.

  9. Economics of fusion research

    Energy Technology Data Exchange (ETDEWEB)

    None, None


    This report provides the results of a study of methods of economic analysis applied to the evaluation of fusion research. The study recognizes that a hierarchy of economic analyses of research programs exists: standard benefit-cost analysis, expected value of R and D information, and expected utility analysis. It is shown that standard benefit-cost analysis, as commonly applied to research programs, is inadequate for the evaluation of a high technology research effort such as fusion research. A methodology for performing an expected value analysis is developed and demonstrated and an overview of an approach to perform an expected utility analysis of fusion research is presented. In addition, a potential benefit of fusion research, not previously identified, is discussed and rough estimates of its magnitude are presented. This benefit deals with the effect of a fusion research program on optimal fossil fuel consumption patterns. The results of this study indicate that it is both appropriate and possible to perform an expected value analysis of fusion research in order to assess the economics of a fusion research program. The results indicate further that the major area of benefits of fusion research is likely due to the impact of a fusion research program on optimal fossil fuel consumption patterns and it is recommended that this benefit be included in future assessments of fusion research economics.

  10. Materials research for fusion (United States)

    Knaster, J.; Moeslang, A.; Muroga, T.


    Fusion materials research started in the early 1970s following the observation of the degradation of irradiated materials used in the first commercial fission reactors. The technological challenges of fusion energy are intimately linked with the availability of suitable materials capable of reliably withstanding the extremely severe operational conditions of fusion reactors. Although fission and fusion materials exhibit common features, fusion materials research is broader. The harder mono-energetic spectrum associated with the deuterium-tritium fusion neutrons (14.1 MeV compared to hydrogen and helium as transmutation products that might lead to a (at present undetermined) degradation of structural materials after a few years of operation. Overcoming the historical lack of a fusion-relevant neutron source for materials testing is an essential pending step in fusion roadmaps. Structural materials development, together with research on functional materials capable of sustaining unprecedented power densities during plasma operation in a fusion reactor, have been the subject of decades of worldwide research efforts underpinning the present maturity of the fusion materials research programme.

  11. Enhanced functional expression of aquaporin Z via fusion of in situ cleavable leader peptides in Escherichia coli cell-free system. (United States)

    Zhang, Xu; Lian, Jiazhang; Kai, Lei; Huang, Lei; Cen, Peilin; Xu, Zhinan


    Aquaporin Z (AqpZ) is a water channel protein from Escherichia coli and has attracted many attentions to develop the biomimetic water filtration technology. Cell-free protein synthesis (CFPS) system, one of the most complex multi-enzymatic systems, has the ability of producing the integral membrane protein in vitro. To enhance the synthesis of AqpZ in E. coli cell-free system, several natural leader peptides were respectively fused at the N-terminus and were verified to enhance the expression level significantly. Moreover, the supplementation of detergents or liposome could activate leader peptidase from the cell-free extract and provide hydrophobic environment for proper folding of AqpZ. Thus, the release of mature AqpZ via the in situ removal of leader peptide was achieved, with a specific water transport activity of (2.1 ± 0.1) × 10⁻¹⁴ cm³ s⁻¹ monomer⁻¹. Using this in situ removable leader peptide strategy, the transcription-translation, leader sequence cleavage and membrane protein folding were integrated into a simple process in the cell-free system, providing a convenient approach to enhance the expression of target proteins, especially those membrane proteins difficult to achieve.

  12. Effect of Fuelling Depth on the Fusion Performance and Particle Confinement of a Fusion Reactor (United States)

    Wang, Shijia; Wang, Shaojie


    The fusion performance and particle confinement of an international thermonuclear experimental reactor (ITER)-like fusion device have been modeled by numerically solving the energy transport equation and the particle transport equation. The effect of fuelling depth has been investigated. The plasma is primarily heated by the fusion produced alpha particles and the loss process of particles and energy in the scrape-off layer has been taken into account. To study the effect of fuelling depth on fusion performance, the ITERH-98P(y,2) scaling law has been used to evaluate the transport coefficients. It is shown that the particle confinement and fusion performance are significantly dependent on the fuelling depth. Deviation of 10% of the minor radius on fuelling depth can make the particle confinement change by ∼ 61% and the fusion performance change by ∼ 108%. The enhancement of fusion performance is due to the better particle confinement induced by deeper particle fuelling. supported by National Natural Science Foundation of China (Nos. 11175178 and 11375196) and the National Magnetic Confinement Fusion Science Program of China (No. 2014GB113000)

  13. Muon Catalyzed Fusion (United States)

    Armour, Edward A.G.


    Muon catalyzed fusion is a process in which a negatively charged muon combines with two nuclei of isotopes of hydrogen, e.g, a proton and a deuteron or a deuteron and a triton, to form a muonic molecular ion in which the binding is so tight that nuclear fusion occurs. The muon is normally released after fusion has taken place and so can catalyze further fusions. As the muon has a mean lifetime of 2.2 microseconds, this is the maximum period over which a muon can participate in this process. This article gives an outline of the history of muon catalyzed fusion from 1947, when it was first realised that such a process might occur, to the present day. It includes a description of the contribution that Drachrnan has made to the theory of muon catalyzed fusion and the influence this has had on the author's research.

  14. Magnetic fusion technology

    CERN Document Server

    Dolan, Thomas J


    Magnetic Fusion Technology describes the technologies that are required for successful development of nuclear fusion power plants using strong magnetic fields. These technologies include: ? magnet systems, ? plasma heating systems, ? control systems, ? energy conversion systems, ? advanced materials development, ? vacuum systems, ? cryogenic systems, ? plasma diagnostics, ? safety systems, and ? power plant design studies. Magnetic Fusion Technology will be useful to students and to specialists working in energy research.

  15. Fusion research principles

    CERN Document Server

    Dolan, Thomas James


    Fusion Research, Volume I: Principles provides a general description of the methods and problems of fusion research. The book contains three main parts: Principles, Experiments, and Technology. The Principles part describes the conditions necessary for a fusion reaction, as well as the fundamentals of plasma confinement, heating, and diagnostics. The Experiments part details about forty plasma confinement schemes and experiments. The last part explores various engineering problems associated with reactor design, vacuum and magnet systems, materials, plasma purity, fueling, blankets, neutronics

  16. Paclitaxel-loaded PEG-PE-based micellar nanopreparations targeted with tumor specific landscape phage fusion protein enhance apoptosis and efficiently reduce tumors (United States)

    Wang, Tao; Yang, Shenghong; Mei, Leslie A.; Parmar, Chirag K.; Gillespie, James W.; Praveen, Kulkarni P.; Petrenko, Valery A.; Torchilin, Vladimir P.


    In an effort to improve the therapeutic index of cancer chemotherapy, we developed an advanced nanopreparation based on the combination of landscape phage display to obtain new targeting ligands with micellar nanoparticles for tumor targeting of water insoluble neoplastic agents. With paclitaxel as a drug, this self-assembled nanopreparation composed of MCF-7-specific phage protein and polyethylene glycol phosphatidyl ethanolamine (PEG- PE) micelles showed selective toxicity to target cancer cells rather than non-target, non- cancer cells in vitro. In vivo, the targeted phage-micelles triggered a dramatic tumor reduction and extensive necrosis as a result of improved tumor delivery of paclitaxel. The enhanced anticancer effect was also verified by an enhanced apoptosis and reduced tumor cell proliferation following the treatment with the targeted micellar paclitaxel both in vitro and in vivo. The absence of hepatotoxicity and pathological changes in tissue sections of vital organs, together with maintenance of overall health of mice following the treatment, further support its translational potential as an effective and safe chemotherapy for improved breast cancer treatment. PMID:25239936

  17. Magnetic fusion reactor economics

    Energy Technology Data Exchange (ETDEWEB)

    Krakowski, R.A.


    An almost primordial trend in the conversion and use of energy is an increased complexity and cost of conversion systems designed to utilize cheaper and more-abundant fuels; this trend is exemplified by the progression fossil fission {yields} fusion. The present projections of the latter indicate that capital costs of the fusion ``burner`` far exceed any commensurate savings associated with the cheapest and most-abundant of fuels. These projections suggest competitive fusion power only if internal costs associate with the use of fossil or fission fuels emerge to make them either uneconomic, unacceptable, or both with respect to expensive fusion systems. This ``implementation-by-default`` plan for fusion is re-examined by identifying in general terms fusion power-plant embodiments that might compete favorably under conditions where internal costs (both economic and environmental) of fossil and/or fission are not as great as is needed to justify the contemporary vision for fusion power. Competitive fusion power in this context will require a significant broadening of an overly focused program to explore the physics and simbiotic technologies leading to more compact, simplified, and efficient plasma-confinement configurations that reside at the heart of an attractive fusion power plant.

  18. Magnetic-confinement fusion (United States)

    Ongena, J.; Koch, R.; Wolf, R.; Zohm, H.


    Our modern society requires environmentally friendly solutions for energy production. Energy can be released not only from the fission of heavy nuclei but also from the fusion of light nuclei. Nuclear fusion is an important option for a clean and safe solution for our long-term energy needs. The extremely high temperatures required for the fusion reaction are routinely realized in several magnetic-fusion machines. Since the early 1990s, up to 16 MW of fusion power has been released in pulses of a few seconds, corresponding to a power multiplication close to break-even. Our understanding of the very complex behaviour of a magnetized plasma at temperatures between 150 and 200 million °C surrounded by cold walls has also advanced substantially. This steady progress has resulted in the construction of ITER, a fusion device with a planned fusion power output of 500 MW in pulses of 400 s. ITER should provide answers to remaining important questions on the integration of physics and technology, through a full-size demonstration of a tenfold power multiplication, and on nuclear safety aspects. Here we review the basic physics underlying magnetic fusion: past achievements, present efforts and the prospects for future production of electrical energy. We also discuss questions related to the safety, waste management and decommissioning of a future fusion power plant.

  19. Frontiers in fusion research

    CERN Document Server

    Kikuchi, Mitsuru


    Frontiers in Fusion Research provides a systematic overview of the latest physical principles of fusion and plasma confinement. It is primarily devoted to the principle of magnetic plasma confinement, that has been systematized through 50 years of fusion research. Frontiers in Fusion Research begins with an introduction to the study of plasma, discussing the astronomical birth of hydrogen energy and the beginnings of human attempts to harness the Sun's energy for use on Earth. It moves on to chapters that cover a variety of topics such as: * charged particle motion, * plasma kinetic theory, *

  20. Role of caveolin-1 in down-regulating extracellular Ca2+-sensing receptor-mediated Ca2+ influx in human umbilical vein endothelial cells%小凹蛋白-1下调人脐静脉内皮细胞外钙敏感受体介导的钙内流的作用机制

    Institute of Scientific and Technical Information of China (English)

    钟华; 龚艳; 吴玲玲; 赵慧; 王静; 孙志萍; 邓峰美; 何芳


    AIM: To study the role of caveolin-1 (Cav-1) in down-regulating the extracellular Ca2+-sensing receptor ( CaR)-mediated Ca2+ influx in human umbilical vein endothelial cells (HUVECs) and its mechanisms. METHODS : HUVECs were collected and cultured to the second or third passage. Filipin was used to induce acute caveolae disruption. Methyl-p-cyclodextrin (M[$CD) or shRNA targeting Cav-1 combined with CaR agonist spermine and negative al-losteric modulator Calhex 231 was also used in HUVECs. Intracellular concentration of Ca2+ ([ Ca2+ ] i) was measured by Fura-2/AM loading. The protein expression of Cav-1 and CaR was examined by Western blotting. The interaction and co-localization of Cav-1 and CaR were determined by the method of co-immunoprecipitation (Co-IP). Caveolae-enriched membrane (CEM) fractions were isolated and identified by detergent-free (Na2CO3) sucrose density gradient centrifugation. The protein levels of Cav-1, CaR, flotillin-1,β-coat protein (β-COP) , β-actin and transferrin receptor (TfR) were detec- ted by Western blotting. Noncaveolar fraction I (NCF I) and noncaveolar fraction II (NCF II) in the CEM fractions were separated. RESULTS; Using extracellular buffer with Ca2+ , the increase in [Ca2+ ]i induced by spermine in HUVECs was abolished after inhibition of CaR by its negative allosteric modulator calhex231. Conversely, the effect of spermine on the increased [ Ca 2+], in HUVECs was further augmented after acute caveolae disruption by MβCD. No significant difference of the protein levels of CaR and Cav-1 in HUVECs among treating with different concentrations of MβCD was observed. The results of Co-IP showed that the protein levels of CaR and Cav-1 in every group of HUVECs were not significantly different. Compared with control group, the protein expression of CaR and Cav-1 in CEM was decreased in spermine + Ca2+ group, filipin + spermine + Ca2 + group and MfiCD + spermine + Ca2 + group, and that in NCF I was increased. However, the

  1. Benchmarking of data fusion algorithms in support of earth observation based Antarctic wildlife monitoring (United States)

    Witharana, Chandi; LaRue, Michelle A.; Lynch, Heather J.


    Remote sensing is a rapidly developing tool for mapping the abundance and distribution of Antarctic wildlife. While both panchromatic and multispectral imagery have been used in this context, image fusion techniques have received little attention. We tasked seven widely-used fusion algorithms: Ehlers fusion, hyperspherical color space fusion, high-pass fusion, principal component analysis (PCA) fusion, University of New Brunswick fusion, and wavelet-PCA fusion to resolution enhance a series of single-date QuickBird-2 and Worldview-2 image scenes comprising penguin guano, seals, and vegetation. Fused images were assessed for spectral and spatial fidelity using a variety of quantitative quality indicators and visual inspection methods. Our visual evaluation elected the high-pass fusion algorithm and the University of New Brunswick fusion algorithm as best for manual wildlife detection while the quantitative assessment suggested the Gram-Schmidt fusion algorithm and the University of New Brunswick fusion algorithm as best for automated classification. The hyperspherical color space fusion algorithm exhibited mediocre results in terms of spectral and spatial fidelities. The PCA fusion algorithm showed spatial superiority at the expense of spectral inconsistencies. The Ehlers fusion algorithm and the wavelet-PCA algorithm showed the weakest performances. As remote sensing becomes a more routine method of surveying Antarctic wildlife, these benchmarks will provide guidance for image fusion and pave the way for more standardized products for specific types of wildlife surveys.

  2. Image fusion algorithm using nonsubsampled contourlet transform (United States)

    Xiao, Yang; Cao, Zhiguo; Wang, Kai; Xu, Zhengxiang


    In this paper, a pixel-level image fusion algorithm based on Nonsubsampled Contourlet Transform (NSCT) has been proposed. Compared with Contourlet Transform, NSCT is redundant, shift-invariant and more suitable for image fusion. Each image from different sensors could be decomposed into a low frequency image and a series of high frequency images of different directions by multi-scale NSCT. For low and high frequency images, they are fused based on local-contrast enhancement and definition respectively. Finally, fused image is reconstructed from low and high frequency fused images. Experiment demonstrates that NSCT could preserve edge significantly and the fusion rule based on region segmentation performances well in local-contrast enhancement.

  3. Enhancement of DNA vaccine potency by vaccination with the CTLA-4-based fusion gene%CTLA-4融合基因免疫策略增强DNA疫苗的免疫应答效应

    Institute of Scientific and Technical Information of China (English)

    周承; 陈智


    DNA疫苗具有较大的临床应用前景,但其免疫效力还不够强大,尤其在大动物和人类中.CTLA-4融合基因免疫能同时增强机体的特异性体液和细胞免疫应答,在抗感染、抗肿瘤中显示巨大的应用前景,并且其免疫增强效应已在部分大动物体内得到证实.%DNA vaccine has shown peat prospects in clinical application, but its immune potency is limited, especially in large animals and mankind. Vaccination with the fusion gene encoding the extracellular domain of CTLA-4 fused to the specific antigen is able to enhance both humoral and cellular immune reponses in several kinds of large animals, which represent a promising approach in the treatment of infectious diseases and cancers.

  4. Magnetized Target Fusion (MTF): Principles, Status, and International Collaboration

    Energy Technology Data Exchange (ETDEWEB)

    Kirkpatrick, R.C.


    Magnetized target fusion (MTF) is an approach to thermonuclear fusion that is intermediate between the two extremes of inertial and magnetic confinement. Target plasma preparation is followed by compression to fusion conditions. The use of a magnetic field to reduce electron thermal conduction and potentially enhance DT alpha energy deposition allows the compression rate to be drastically reduced relative to that for inertial confinement fusion. This leads to compact systems with target driver power and intensity requirements that are orders of magnitude lower than for ICF. A liner on plasma experiment has been proposed to provide a firm proof of principle for MTF.

  5. Quantum propagator approach to heavy-ion fusion

    Energy Technology Data Exchange (ETDEWEB)

    Bao, J.D. [Beijing Univ., BJ (China). Dept. of Physics; Boiley, D.; Bao, J.D. [Grand Accelerateur National d' Ions Lourds (GANIL), 14 - Caen (France)


    The real-time path integral propagator approach is used to study the fusion probability of massive nuclei including quantum effect. An analytical expression of the probability to pass over barrier of an inverted harmonic potential is obtained, in which both height and curvature of the barrier are controlled by the neck degree of freedom. The fusion probability of three systems in central collision as a function of the center of mass energy are calculated and compared to experimental results. It is shown that the quantum fluctuation enhances the fusion probability at low energies, and the neck fluctuation makes the slope of the fusion probability curve become flatter. (author)

  6. Cell fusion and nuclear fusion in plants. (United States)

    Maruyama, Daisuke; Ohtsu, Mina; Higashiyama, Tetsuya


    Eukaryotic cells are surrounded by a plasma membrane and have a large nucleus containing the genomic DNA, which is enclosed by a nuclear envelope consisting of the outer and inner nuclear membranes. Although these membranes maintain the identity of cells, they sometimes fuse to each other, such as to produce a zygote during sexual reproduction or to give rise to other characteristically polyploid tissues. Recent studies have demonstrated that the mechanisms of plasma membrane or nuclear membrane fusion in plants are shared to some extent with those of yeasts and animals, despite the unique features of plant cells including thick cell walls and intercellular connections. Here, we summarize the key factors in the fusion of these membranes during plant reproduction, and also focus on "non-gametic cell fusion," which was thought to be rare in plant tissue, in which each cell is separated by a cell wall.

  7. Nuclear fusion inside condense matters

    Institute of Scientific and Technical Information of China (English)

    HE Jing-tang


    This article describes in detail the nuclear fusion inside condense matters--the Fleischmann-Pons effect, the reproducibility of cold fusions, self-consistentcy of cold fusions and the possible applications.

  8. Complementary Advanced Fusion Exploration (United States)


    homographic computer vision image fusion, out-of-sequence measurement and track data handling, Nash bargaining approaches to sensor management... homographic fusion notions are identified together with the Nash approach, the pursuit-evasion approach to threat situation outcome determination, and the

  9. Controlled Nuclear Fusion. (United States)

    Glasstone, Samuel

    This publication is one of a series of information booklets for the general public published by The United States Atomic Energy Commission. Among the topics discussed are: Importance of Fusion Energy; Conditions for Nuclear Fusion; Thermonuclear Reactions in Plasmas; Plasma Confinement by Magnetic Fields; Experiments With Plasmas; High-Temperature…

  10. Fusion helps diversification

    NARCIS (Netherlands)

    S. Liang; Z. Ren; M. de Rijke


    A popular strategy for search result diversification is to first retrieve a set of documents utilizing a standard retrieval method and then rerank the results. We adopt a different perspective on the problem, based on data fusion. Starting from the hypothesis that data fusion can improve performance

  11. Fusion of biological membranes

    Indian Academy of Sciences (India)

    K Katsov; M Müller; M Schick


    The process of membrane fusion has been examined by Monte Carlo simulation, and is found to be very different than the conventional picture. The differences in mechanism lead to several predictions, in particular that fusion is accompanied by transient leakage. This prediction has recently been verified. Self-consistent field theory is applied to examine the free energy barriers in the different scenarios.

  12. Controlled thermonuclear fusion

    CERN Document Server

    Bobin, Jean Louis


    The book is a presentation of the basic principles and main achievements in the field of nuclear fusion. It encompasses both magnetic and inertial confinements plus a few exotic mechanisms for nuclear fusion. The state-of-the-art regarding thermonuclear reactions, hot plasmas, tokamaks, laser-driven compression and future reactors is given.

  13. Data fusion using geographic managed objects

    DEFF Research Database (Denmark)

    Kjems, Erik


    models coming from different systems and vendors representing different professional domains. This paper discusses data exchange and data fusion in general and presents a new development, which gives the possibility to enhance data as intelligent objects opening a whole new paradigm for both data...

  14. Compact fusion reactors

    CERN Document Server

    CERN. Geneva


    Fusion research is currently to a large extent focused on tokamak (ITER) and inertial confinement (NIF) research. In addition to these large international or national efforts there are private companies performing fusion research using much smaller devices than ITER or NIF. The attempt to achieve fusion energy production through relatively small and compact devices compared to tokamaks decreases the costs and building time of the reactors and this has allowed some private companies to enter the field, like EMC2, General Fusion, Helion Energy, Lawrenceville Plasma Physics and Lockheed Martin. Some of these companies are trying to demonstrate net energy production within the next few years. If they are successful their next step is to attempt to commercialize their technology. In this presentation an overview of compact fusion reactor concepts is given.

  15. Geodata fusion study by the Open Geospatial Consortium (United States)

    Percivall, George


    Making new connections in existing data is a powerful method to gain understanding of the world. Data fusion is not a new topic, but new approaches provide opportunities to enhance this ubiquitous process. Interoperability based on open standards is radically changing the classical domains of data fusion while inventing entirely new ways to discern relationships in data with little structure. Associations based on locations and times are of the most primary type. The Open Geospatial Consortium (OGC) conducted a Fusion Standards study with recommendations implemented in testbeds. In the context of this study, Data Fusion was defined as: "the act or process of combining or associating data or information regarding one or more entities considered in an explicit or implicit knowledge framework to improve one's capability (or provide a new capability) for detection, identification, or characterization of that entity". Three categories were used to organize this study: Observation Fusion, Feature fusion, and Decision fusion. The study considered classical fusion as exemplified by the JDL and OODA models as well as how fusion is achieved by new technology such as web-based mash-ups and mobile Internet. The study considers both OGC standards as well open standards from other standards organizations. These technologies and standards aid in bringing structure to unstructured data as well as enabling a major new thrust in Decision Fusion.

  16. Dependence of fusion on isospin dynamics

    CERN Document Server

    Godbey, K; Simenel, C


    We introduce a new microscopic approach to calculate the dependence of fusion barriers and cross-sections on isospin dynamics. The method is based on the time-dependent Hartree-Fock theory and the isoscalar and isovector properties of the energy density functional (EDF). The contribution to the fusion barriers originating from the isoscalar and isovector parts of the EDF is calculated. It is shown that for non-symmetric systems the isovector dynamics influence the sub-barrier fusion cross-sections. For most systems this results in an enhancement of the sub-barrier cross-sections, while for others we observe differing degrees of hindrance. We use this approach to provide an explanation of recently measured fusion cross sections which show a surprising enhancement at low $E_\\mathrm{c.m.}$ energies for the system $^{40}$Ca+$^{132}$Sn as compared to the more neutron-rich system $^{48}$Ca+$^{132}$Sn, and discuss the dependence of sub-barrier fusion cross-sections on transfer.

  17. Color fusion of night vision image based on color transfer and target enhancement%基于颜色传递和目标增强的夜视图像彩色融合

    Institute of Scientific and Technical Information of China (English)

    李成立; 石俊生; 魏利; 徐领章


    Color transfer is a way to get night vision with natural color. For infrared and low-light level image,a color fusion method of night vision image based on color transfer and target enhancement is presented. Firstly,considering the characteristics of infrared and low-light level images,TNO method is used to get a pseudo-color image (target im-age),which preserves the details of the image. Then,a similar reference image is selected,and the target image and reference image are converted to the YCbCr color space,and each of the channel′s mean and standard deviation is matched to complete color transfer. Meanwhile,a contrast enhancement factor is introduced into Cr channel to en-hance the target. The experimental results show that the method can get a night-vision images with a nature color ap-pearance and improve image detail,and the goal is more highlighted,which helps for understanding the scene.%颜色传递是获得夜视图像自然彩色的一种方法,以红外和微光图像为研究对象,提出了一种基于颜色传递和目标增强的夜视图像彩色融合方法。首先结合红外和微光图像各自的特点,采用TN O法生成伪彩色融合图像(目标图像),很好地保留了图像的细节信息,然后选取一幅相近的参考图像,把目标图像和参考图像转换到YCbCr颜色空间进行各个通道一阶(均值)和二阶(标准差)统计量匹配的颜色传递,同时在Cr通道引入一个对比度增强因子来增强图像中的兴趣目标。实验结果表明,文中方法不仅使得夜视图像获得了如白天参考图像般自然、真实的色彩,而且提高了图像的细节,目标也更加突出,更有利于观察者对场景的理解。

  18. Fusion Studies in Japan (United States)

    Ogawa, Yuichi


    A new strategic energy plan decided by the Japanese Cabinet in 2014 strongly supports the steady promotion of nuclear fusion development activities, including the ITER project and the Broader Approach activities from the long-term viewpoint. Atomic Energy Commission (AEC) in Japan formulated the Third Phase Basic Program so as to promote an experimental fusion reactor project. In 2005 AEC has reviewed this Program, and discussed on selection and concentration among many projects of fusion reactor development. In addition to the promotion of ITER project, advanced tokamak research by JT-60SA, helical plasma experiment by LHD, FIREX project in laser fusion research and fusion engineering by IFMIF were highly prioritized. Although the basic concept is quite different between tokamak, helical and laser fusion researches, there exist a lot of common features such as plasma physics on 3-D magnetic geometry, high power heat load on plasma facing component and so on. Therefore, a synergetic scenario on fusion reactor development among various plasma confinement concepts would be important.

  19. Multispectral and panchromatic image fusion based on unsubsampled contourlet transform (United States)

    Liu, Hui; Yuan, Yan; Su, Lijuan; Hu, Liang; Zhang, Siyuan


    In order to achieve the high-resolution multispectral image, we proposed an algorithm for MS image and PAN image fusion based on NSCT and improved fusion rule. This method takes into account two aspects, the spectral similarity between fused image and the original MS image and enhancing the spatial resolution of the fused image. According to local spectral similarity between MS and PAN images, it can help to select high frequency detail coefficients from PAN image, which are injected into MS image then. Thus, spectral distortion is limited; the spatial resolution is enhanced. The experimental results demonstrate that the proposed fusion algorithm perform some improvements in integrating MS and PAN images.

  20. Control of Fusion and Solubility in Fusion Systems

    CERN Document Server

    Craven, David A


    In this article, we consider the control of fusion in fusion systems, proving three previously known, non-trivial results in a new, largely elementary way. We then reprove a result of Aschbacher, that the product of two strongly closed subgroups is strongly closed; to do this, we consolidate the theory of quotients of fusion systems into a consistent theory. We move on considering p-soluble fusion systems, and prove that they are constrained, allowing us to effectively characterize fusion systems of p-soluble groups. This leads us to recast Thompson Factorization for Qd(p)-free fusion systems, and consider Thompson Factorization for more general fusion systems.

  1. Remote sensing image fusion

    CERN Document Server

    Alparone, Luciano; Baronti, Stefano; Garzelli, Andrea


    A synthesis of more than ten years of experience, Remote Sensing Image Fusion covers methods specifically designed for remote sensing imagery. The authors supply a comprehensive classification system and rigorous mathematical description of advanced and state-of-the-art methods for pansharpening of multispectral images, fusion of hyperspectral and panchromatic images, and fusion of data from heterogeneous sensors such as optical and synthetic aperture radar (SAR) images and integration of thermal and visible/near-infrared images. They also explore new trends of signal/image processing, such as

  2. Data Fusion of Barometric Altimeter Enhanced GPS Integrated Navigation System%气压高度表增强GPS组合导航系统数据融合

    Institute of Scientific and Technical Information of China (English)

    杨朝斌; 牛强军; 徐其东


    An integrated navigation system for improving the vertical positioning accuracy of barometric altimeter enhanced GPS was proposed.The state and observation equations were established based on the location error of GPS,height error of BA and their "current" statistic model.The data fusion algorithm was given by iterative Kalman filtering(IKF).The theoretical analysis simulation and test results indicated that the vertical positioning accuracy,performance,reality and availability are improved more efficiently by the IKF algorithm than Kalman filter.The safety and reliability of airplane in the process of near-enter is guaranded by the algorithm which can be used as a guide system for precision approaching and landing.%针对在精密进场着陆阶段GPS信号易受干扰及高度准确性较差,气压高度表对气压及温度敏感的特点,提出了一种提高垂直方向定位精度的组合导航系统。基于GPS定位误差、气压高度表误差以及其"当前"统计模型,建立了系统的状态方程和观测方程,给出了采用迭代Kalman滤波的数据融合算法。理论分析仿真和实验结果表明,迭代Kalman滤波算法提高了垂直方向上的定位精度与实时性,改善可用性,性能优于Kalman滤波,保证了飞机在进近阶段的安全性和可靠性,可以作为精密进近阶段的着陆引导系统。

  3. Cell fusions in mammals

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Bjerregaard, Bolette; Talts, Jan Fredrik


    Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defense system. Additionally, cell fusions participate in tissue repair and may be important to cancer development and progression. A large number of factors appear...... to regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins forming alpha-helical bundles that bring membranes close together. The syncytin family of proteins represent true fusogens and the founding member, syncytin-1......, has been documented to be involved in fusions between placental trophoblasts, between cancer cells and between cancer cells and host ells. We review the literature with emphasis on the syncytin family and propose that syncytins may represent universal fusogens in primates and rodents, which work...

  4. Cold nuclear fusion

    Directory of Open Access Journals (Sweden)

    Huang Zhenqiang Huang Yuxiang


    Full Text Available In normal temperature condition, the nuclear force constraint inertial guidance method, realize the combination of deuterium and tritium, helium and lithium... And with a magnetic moment of light nuclei controlled cold nuclear collide fusion, belongs to the nuclear energy research and development in the field of applied technology "cold nuclear collide fusion". According to the similarity of the nuclear force constraint inertial guidance system, the different velocity and energy of the ion beam mixing control, developed ion speed dc transformer, it is cold nuclear fusion collide, issue of motivation and the nuclear power plant start-up fusion and power transfer system of the important equipment, so the merger to apply for a patent

  5. Fusion Revisits CERN

    CERN Multimedia


    It's going to be a hot summer at CERN. At least in the Main Building, where from 13 July to 20 August an exhibition is being hosted on nuclear fusion, the energy of the Stars. Nuclear fusion is the engine driving the stars but also a potential source of energy for mankind. The exhibition shows the different nuclear fusion techniques and research carried out on the subject in Europe. Inaugurated at CERN in 1993, following collaboration between Lausanne's CRPP-EPFL and CERN, with input from Alessandro Pascolini of Italy's INFN, this exhibition has travelled round Europe before being revamped and returning to CERN. 'Fusion, Energy of the Stars', from 13 July onwards, Main Building

  6. Laser-Driven Fusion. (United States)

    Gibson, A. F.


    Discusses the present status and future prospects of laser-driven fusion. Current research (which is classified under three main headings: laser-matter interaction processes, compression, and laser development) is also presented. (HM)

  7. Fusion plasma physics

    CERN Document Server

    Stacey, Weston M


    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 ...

  8. Optical Fiber Fusion Splicing

    CERN Document Server

    Yablon, Andrew D


    This book is an up-to-date treatment of optical fiber fusion splicing incorporating all the recent innovations in the field. It provides a toolbox of general strategies and specific techniques that the reader can apply when optimizing fusion splices between novel fibers. It specifically addresses considerations important for fusion splicing of contemporary specialty fibers including dispersion compensating fiber, erbium-doped gain fiber, polarization maintaining fiber, and microstructured fiber. Finally, it discusses the future of optical fiber fusion splicing including silica and non-silica based optical fibers as well as the trend toward increasing automation. Whilst serving as a self-contained reference work, abundant citations from the technical literature will enable readers to readily locate primary sources.

  9. Sampling Based Average Classifier Fusion

    Directory of Open Access Journals (Sweden)

    Jian Hou


    fusion algorithms have been proposed in literature, average fusion is almost always selected as the baseline for comparison. Little is done on exploring the potential of average fusion and proposing a better baseline. In this paper we empirically investigate the behavior of soft labels and classifiers in average fusion. As a result, we find that; by proper sampling of soft labels and classifiers, the average fusion performance can be evidently improved. This result presents sampling based average fusion as a better baseline; that is, a newly proposed classifier fusion algorithm should at least perform better than this baseline in order to demonstrate its effectiveness.

  10. Fusion ignition research experiment

    Energy Technology Data Exchange (ETDEWEB)

    Dale Meade


    Understanding the properties of high gain (alpha-dominated) fusion plasmas in an advanced toroidal configuration is the largest remaining open issue that must be addressed to provide the scientific foundation for an attractive magnetic fusion reactor. The critical parts of this science can be obtained in a compact high field tokamak which is also likely to provide the fastest and least expensive path to understanding alpha-dominated plasmas in advanced toroidal systems.

  11. Economically competitive fusion

    Directory of Open Access Journals (Sweden)

    David J. Ward


    Full Text Available Not since the oil crisis of the 1970s has the perception that energy is a crucial and precious resource been as strong as it is today. The need for a new approach to world energy supply, driven by concerns over resources, pollution, and security, is leading to a reappraisal of fusion. Fusion has enormous potential and major safety and environmental advantages, and hence could make a large difference to energy supplies.

  12. Fusion, cold fusion, and space policy

    Energy Technology Data Exchange (ETDEWEB)

    Rotegard, D. (CST Ltd. (United States))


    This paper critiques Americal science policy through a consideration of two examples-cold fusion and asteroid mining. It points out that the failure of central planning in science and technology policy is just as marked as in more mundane activities. It highlights the current low level of debate and points out some technical issues that need to be addressed. It concludes with evidence that the alliance of flawed policy options is further lowering the level of debate. (author).

  13. Observation of incomplete fusion reactions at l < l {sub crit}

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Abhishek, E-mail:; Sharma, Vijay R., E-mail:; Singh, Devendra P., E-mail:; Unnati,; Singh, B. P.; Prasad, R. [Department of Physics, Aligarh Muslim University, Aligarh (UP) - 202 002 (India); Singh, Pushpendra P. [GSI-Helmholtz Centre for Heavy Ion Research GmbH, D-64291 Darmstadt (Germany); Bala, Indu; Kumar, R.; Muralithar, S.; Singh, R. P. [NP-Group: Inter-University Accelerator Center, Aruna Asaf Ali Marg, New Delhi - 110 067 (India); Sharma, M. K. [Department of Physics, S. V. College, Aligarh- 202 001 (India)


    In order to understand the presence of incomplete fusion at low energies i.e. 4-7MeV/nucleon and also to study its dependence on various entrance-channel parameters, the two type of measurements (i) excitation function for {sup 12}C+{sup 159}Tb, and (ii) forward recoil ranges for {sup 12}C+{sup 159}Tb systems have been performed. The experimentally measured excitation functions have been analyzed within the framework of compound nucleus decay using statistical model code PACE4. Analysis of data suggests the production of xn/px)n-channels via complete fusion, as these are found to be well reproduced by PACE4 predictions, while, a significant enhancement in the excitation functions of α-emitting channels has been observed over the theoretical ones, which has been attributed due to the incomplete fusion processes. Further, the incomplete fusion events observed in case of forward recoil range measurements have been explained on the basis of the breakup fusion model, where these events may be attributed to the fusion of {sup 8}Be and/or {sup 4}He from {sup 12}C projectile to the target nucleus. In the present work, the SUMRULE model calculations are found to highly underestimate the observed incomplete fusion cross-sections which indicate that the l-values lower than l {sub crit} (limit of complete fusion) significantly contribute to the incomplete fusion reactions.

  14. Inflammation and proliferation act together to mediate intestinal cell fusion.

    Directory of Open Access Journals (Sweden)

    Paige S Davies

    Full Text Available Cell fusion between circulating bone marrow-derived cells (BMDCs and non-hematopoietic cells is well documented in various tissues and has recently been suggested to occur in response to injury. Here we illustrate that inflammation within the intestine enhanced the level of BMDC fusion with intestinal progenitors. To identify important microenvironmental factors mediating intestinal epithelial cell fusion, we performed bone marrow transplantation into mouse models of inflammation and stimulated epithelial proliferation. Interestingly, in a non-injury model or in instances where inflammation was suppressed, an appreciable baseline level of fusion persisted. This suggests that additional mediators of cell fusion exist. A rigorous temporal analysis of early post-transplantation cellular dynamics revealed that GFP-expressing donor cells first trafficked to the intestine coincident with a striking increase in epithelial proliferation, advocating for a required fusogenic state of the host partner. Directly supporting this hypothesis, induction of augmented epithelial proliferation resulted in a significant increase in intestinal cell fusion. Here we report that intestinal inflammation and epithelial proliferation act together to promote cell fusion. While the physiologic impact of cell fusion is not yet known, the increased incidence in an inflammatory and proliferative microenvironment suggests a potential role for cell fusion in mediating the progression of intestinal inflammatory diseases and cancer.

  15. Effects of entrance channel on fusion probability in hot fusion reactions (United States)

    Zhu, Long; Su, Jun; Huang, Ching-Yuan; Zhang, Feng-Shou


    Within the framework of the dinuclear system (DNS) model, the fusion reactions leading to the compound nuclei 274Hs* and 286Cn* are investigated. The fusion probability as a function of DNS excitation energy is studied. The calculated results are in good agreement with the available experimental data. The obtained results show that the fusion probabilities are obviously enhanced for the reactions located at high place in potential energy surface, although these reactions may have small values of mass asymmetry. It is found that the enhancement is due to the large potential energy of the initial DNS. Supported by Natural Science Foundation of Guangdong Province China (2016A030310208). National Natural Science Foundation of China (11605296, 11405278, 11505150, 11635003), Fundamental Research Funds for the Central Universities (15 lgpy 30) and China Postdoctoral Science Foundation (2015M582730)

  16. Reaction mechanisms in heavy ion fusion

    Directory of Open Access Journals (Sweden)

    Lubian J.


    Full Text Available We discuss the reaction mechanisms involved in heavy ion fusion. We begin with collisions of tightly bound systems, considering three energy regimes: energies above the Coulomb barrier, energies just below the barrier and deep sub-barrier energies. We show that channel coupling effects may influence the fusion process at above-barrier energies, increasing or reducing the cross section predicted by single barrier penetration model. Below the Coulomb barrier, it enhances the cross section, and this effect increases with the system’s size. It is argued that this behavior can be traced back to the increasing importance of Coulomb coupling with the charge of the collision partners. The sharp drop of the fusion cross section observed at deep sub-barrier energies is addressed and the theoretical approaches to this phenomenon are discussed. We then consider the reaction mechanisms involved in fusion reactions of weakly bound systems, paying particular attention to the calculations of complete and incomplete fusion available in the literature.

  17. Slantlet Transform for Multispectral Image Fusion

    Directory of Open Access Journals (Sweden)

    Adnan H.M. Al-Helali


    Full Text Available Problem statement: Image fusion is a process by which multispectral and panchromatic images, or some of their features, are combined together to form a high spatial/high spectral resolutions image. The successful fusion of images acquired from different modalities or instruments is a great importance issue in remote sensing applications. Approach: A new method of image fusion was introduced. It was based on a hybrid transform, which is an extension of Ridgelet transform. It used the slantlet transform instead of wavelet transform in the final steps of Ridgelet transform. The slantlet transform was an orthogonal discrete wavelet transform with two zero moments and with improved time localization. Results: Since edges and noise played fundamental role in image understanding, this hybrid transform was proved to be good way to enhance the edges and reduce the noise. Conclusion: The proposed method of fusion presented richer information in spatial and spectral domains simultaneously as well as it had reached an optimum fusion result.

  18. Fusion Centers and Federalism: Erosion or Enhancement? (United States)


    capabilities, Samuel Clovis also found, but “the inevitable swing of the pendulum of power…moved decidedly toward the central government, with virtually no...Homeland Security (Washington, DC: White House, 2002), 3. 14 federalism…[prior to the] national personal income tax.”21 Clovis , in this work and...strain state capabilities to meet them, is highlighted by Clovis and echoed by Posner as being “less preferable, but…more inevitable.”24 Thus, as the

  19. Estimation of Total Fusion Reactivity and Contribution from Suprathermal Tail using 3-parameter Dagum Ion Speed Distribution

    CERN Document Server

    Majumdar, Rudrodip


    Thermonuclear fusion reactivity is a pivotal quantity in the studies pertaining to fusion energy production, fusion ignition and energy break-even analysis in both inertially and magnetically confined systems. Although nuclear fusion reactivity and thereafter the power density of a magnetic confinement fusion reactor and the fulfillment of the ignition criterion are quantitatively determined by assuming the ion speed distribution to be Maxwellian, a significant population of suprathermal ions,with energy greater than the quasi-Maxwellian background plasma temperature, is generated by the fusion reactions and auxiliary heating in the fusion devices. In the current work 3-parameter Dagum speed distribution has been introduced to include the effect of suprathermal ion population in the calculation of total fusion reactivity. The extent of enhancement in the fusion reactivity, at different back-ground temperatures of the fusion fuel plasma, due to the suprathermal ion population has also been discussed.

  20. Measures of information for multilevel data fusion (United States)

    Oxenham, Martin G.; Kewley, Douglas J.; Nelson, Mark J.


    In many commercial and military activities such as manufacturing, robotics, surveillance, target tracking and military command and control, information may be gathered by a variety of sources. The types of sources which may be used cover a broad spectrum and the data collected may be either numerical or linguistic in nature. Data fusion is the process in which data from multiple sources are combined to provide enhanced information quality and availability over that which is available from any individual source. The question is how to assess these enhancements. Using the U.S. JDL Model, the process of data fusion can be divided into several distinct levels. The first three levels are object refinement, situation refinement and threat refinement. Finally, at the fourth level (process refinement) the performance of the system is monitored to enable product improvement and sensor suite management. This monitoring includes the use of measures of information from the realm of generalized information theory to assess the improvements or degradation due to the fusion processing. The premise is that decreased uncertainty equates to increased information. At each level, the uncertainty may be represented in different ways. In this paper we give an overview of the existing measures of uncertainty and information, and propose some new measures for the various levels of the data fusion process.

  1. Lateral Lumbar Interbody Fusion (United States)

    Hughes, Alexander; Girardi, Federico; Sama, Andrew; Lebl, Darren; Cammisa, Frank


    The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques. PMID:26713134

  2. Myoblast fusion in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Haralalka, Shruti [Stowers Institute for Medical Research, Kansas City, MO 64110 (United States); Abmayr, Susan M., E-mail: [Stowers Institute for Medical Research, Kansas City, MO 64110 (United States); Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, MO 66160 (United States)


    The body wall musculature of a Drosophila larva is composed of an intricate pattern of 30 segmentally repeated muscle fibers in each abdominal hemisegment. Each muscle fiber has unique spatial and behavioral characteristics that include its location, orientation, epidermal attachment, size and pattern of innervation. Many, if not all, of these properties are dictated by founder cells, which determine the muscle pattern and seed the fusion process. Myofibers are then derived from fusion between a specific founder cell and several fusion competent myoblasts (FCMs) fusing with as few as 3-5 FCMs in the small muscles on the most ventral side of the embryo and as many as 30 FCMs in the larger muscles on the dorsal side of the embryo. The focus of the present review is the formation of the larval muscles in the developing embryo, summarizing the major issues and players in this process. We have attempted to emphasize experimentally-validated details of the mechanism of myoblast fusion and distinguish these from the theoretically possible details that have not yet been confirmed experimentally. We also direct the interested reader to other recent reviews that discuss myoblast fusion in Drosophila, each with their own perspective on the process . With apologies, we use gene nomenclature as specified by Flybase ( but provide Table 1 with alternative names and references.

  3. Sensor Data Fusion

    DEFF Research Database (Denmark)

    Plascencia, Alfredo; Stepán, Petr


    The main contribution of this paper is to present a sensor fusion approach to scene environment mapping as part of a Sensor Data Fusion (SDF) architecture. This approach involves combined sonar array with stereo vision readings.  Sonar readings are interpreted using probability density functions...... to the occupied and empty regions. Scale Invariant Feature Transform (SIFT) feature descriptors are interpreted using gaussian probabilistic error models. The use of occupancy grids is proposed for representing the sensor readings. The Bayesian estimation approach is applied to update the sonar array......  and the SIFT descriptors' uncertainty grids. The sensor fusion yields a significant reduction in the uncertainty of the occupancy grid compared to the individual sensor readings....

  4. Fusion research at ORNL

    Energy Technology Data Exchange (ETDEWEB)


    The ORNL Fusion Program includes the experimental and theoretical study of two different classes of magnetic confinement schemes - systems with helical magnetic fields, such as the tokamak and stellarator, and the ELMO Bumpy Torus (EBT) class of toroidally linked mirror systems; the development of technologies, including superconducting magnets, neutral atomic beam and radio frequency (rf) heating systems, fueling systems, materials, and diagnostics; the development of databases for atomic physics and radiation effects; the assessment of the environmental impact of magnetic fusion; and the design of advanced demonstration fusion devices. The program involves wide collaboration, both within ORNL and with other institutions. The elements of this program are shown. This document illustrates the program's scope; and aims by reviewing recent progress.

  5. Medical Image Fusion

    Directory of Open Access Journals (Sweden)

    Mitra Rafizadeh


    Full Text Available Technological advances in medical imaging in the past two decades have enable radiologists to create images of the human body with unprecedented resolution. MRI, PET,... imaging devices can quickly acquire 3D images. Image fusion establishes an anatomical correlation between corresponding images derived from different examination. This fusion is applied either to combine images of different modalities (CT, MRI or single modality (PET-PET."nImage fusion is performed in two steps:"n1 Registration: spatial modification (eg. translation of model image relative to reference image in order to arrive at an ideal matching of both images. Registration methods are feature-based and intensity-based approaches."n2 Visualization: the goal of it is to depict the spatial relationship between the model image and refer-ence image. We can point out its clinical application in nuclear medicine (PET/CT.

  6. Application of the JDL data fusion process model for cyber security (United States)

    Giacobe, Nicklaus A.


    A number of cyber security technologies have proposed the use of data fusion to enhance the defensive capabilities of the network and aid in the development of situational awareness for the security analyst. While there have been advances in fusion technologies and the application of fusion in intrusion detection systems (IDSs), in particular, additional progress can be made by gaining a better understanding of a variety of data fusion processes and applying them to the cyber security application domain. This research explores the underlying processes identified in the Joint Directors of Laboratories (JDL) data fusion process model and further describes them in a cyber security context.

  7. Fusion Propulsion Study (United States)


    of propellant can be millions of times greater than the fuel, only a tiny fraction can completely push out the fuel. If the plasma is moving at a... push -plate for various explosive yields. It appears that the maximum specific impulse for such a system is -4000 to 5000 sec and increasing the base...Energy Agency, 1977, p. 507. Bourque, R.F., "OHTE as a Fusion Reactor," Proc. 4th Topl. Mt,. Tecnology of Controlled NV?4clear Fusion, King of Prussia

  8. Atomic data for fusion

    Energy Technology Data Exchange (ETDEWEB)

    Hunter, H.T.; Kirkpatrick, M.I.; Alvarez, I.; Cisneros, C.; Phaneuf, R.A. (eds.); Barnett, C.F.


    This report provides a handbook of recommended cross-section and rate-coefficient data for inelastic collisions between hydrogen, helium and lithium atoms, molecules and ions, and encompasses more than 400 different reactions of primary interest in fusion research. Published experimental and theoretical data have been collected and evaluated, and the recommended data are presented in tabular, graphical and parametrized form. Processes include excitation and spectral line emission, charge exchange, ionization, stripping, dissociation and particle interchange reactions. The range of collision energies is appropriate to applications in fusion-energy research.

  9. Fusion Welding Research. (United States)


    RD-AlSO 253 FUSION WELDING RESEARCH(U) MASSACHUSETTS INST OF TECH L/I CAMBRIDGE DEPT OF MATERIALS SCIENCE AND ENGINEERING T W EAGAR ET AL. 30 RPR 85...NUMBER 12. GOV’ ACCESSION NO. 3. RECICIE-S CATALOG NUMBER 4. T TL V nd Subtitle) S. P OFRPR PERIOD COVERED 5t h A~nnual Technical Report Fusion Welding ...research S on welding processes. Studies include metal vapors in the arc, development of a high speed infrared temperature monitor, digital signal

  10. Turbulence measurements in fusion plasmas (United States)

    Conway, G. D.


    Turbulence measurements in magnetically confined toroidal plasmas have a long history and relevance due to the detrimental role of turbulence induced transport on particle, energy, impurity and momentum confinement. The turbulence—the microscopic random fluctuations in particle density, temperature, potential and magnetic field—is generally driven by radial gradients in the plasma density and temperature. The correlation between the turbulence properties and global confinement, via enhanced diffusion, convection and direct conduction, is now well documented. Theory, together with recent measurements, also indicates that non-linear interactions within the turbulence generate large scale zonal flows and geodesic oscillations, which can feed back onto the turbulence and equilibrium profiles creating a complex interdependence. An overview of the current status and understanding of plasma turbulence measurements in the closed flux surface region of magnetic confinement fusion devices is presented, highlighting some recent developments and outstanding problems.

  11. Fusion engineering device design description

    Energy Technology Data Exchange (ETDEWEB)

    Flanagan, C.A.; Steiner, D.; Smith, G.E.


    The US Magnetic Fusion Engineering Act of 1980 calls for the operation of a Fusion Engineering Device (FED) by 1990. It is the intent of the Act that the FED, in combination with other testing facilities, will establish the engineering feasibility of magnetic fusion energy. During 1981, the Fusion Engineering Design Center (FEDC), under the guidance of a Technical Management Board (TMB), developed a baseline design for the FED. This design is summarized herein.

  12. Fusion Engineering Device design description

    Energy Technology Data Exchange (ETDEWEB)

    Flanagan, C.A.; Steiner, D.; Smith, G.E.


    The US Magnetic Fusion Engineering Act of 1980 calls for the operation of a Fusion Engineering Device (FED) by 1990. It is the intent of the Act that the FED, in combination with other testing facilities, will establish the engineering feasibility of magnetic fusion energy. During 1981, the Fusion Engineering Design Center (FEDC), under the guidance of a Technical Management Board (TMB), developed a baseline design for the FED. This design is summarized herein.

  13. Synergetic Multisensor Fusion (United States)


    technology have led to increased interest in using DEMs for navigation and other applications. In particular, DEMs are attractive for use in aircraft...Multisensor Fusion for Computer Vision [67]. 30 6. POSI!IONAL zSTIM&TION TECEnIQUzs FOR AN OUTDOOR MOBLE ROBOT The autonomous navigation of mobile robots is

  14. Bouillabaisse sushi fusion power

    CERN Multimedia


    "If avant-garde cuisine is any guide, Japanese-French fusion does not work all that well. And the interminable discussions over the International Thermonuclear Experimental Reactor (ITER) suggest that what is true of cooking is true of physics" (1 page)

  15. International fusion og spaltning

    DEFF Research Database (Denmark)

    Hansen, Lone L.

    Bogen analyserer de nye muligheder fra 2007 i europæisk ret med hensyn til fusion eller spaltning mellem aktieselskaber og anpartsselskaber med hjemsted i forskellige europæiske lande. Bogen gennemgår de nye muligheder for strukturændringer, der herved er opstået mulighed for, og den sætter fokus...

  16. Fusion reactor materials

    Energy Technology Data Exchange (ETDEWEB)



    This paper discuses the following topics on fusion reactor materials: irradiation, facilities, test matrices, and experimental methods; dosimetry, damage parameters, and activation calculations; materials engineering and design requirements; fundamental mechanical behavior; radiation effects; development of structural alloys; solid breeding materials; and ceramics.

  17. Iterative guided image fusion

    Directory of Open Access Journals (Sweden)

    Alexander Toet


    Full Text Available We propose a multi-scale image fusion scheme based on guided filtering. Guided filtering can effectively reduce noise while preserving detail boundaries. When applied in an iterative mode, guided filtering selectively eliminates small scale details while restoring larger scale edges. The proposed multi-scale image fusion scheme achieves spatial consistency by using guided filtering both at the decomposition and at the recombination stage of the multi-scale fusion process. First, size-selective iterative guided filtering is applied to decompose the source images into approximation and residual layers at multiple spatial scales. Then, frequency-tuned filtering is used to compute saliency maps at successive spatial scales. Next, at each spatial scale binary weighting maps are obtained as the pixelwise maximum of corresponding source saliency maps. Guided filtering of the binary weighting maps with their corresponding source images as guidance images serves to reduce noise and to restore spatial consistency. The final fused image is obtained as the weighted recombination of the individual residual layers and the mean of the approximation layers at the coarsest spatial scale. Application to multiband visual (intensified and thermal infrared imagery demonstrates that the proposed method obtains state-of-the-art performance for the fusion of multispectral nightvision images. The method has a simple implementation and is computationally efficient.

  18. Muon catalyzed fusion

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, K. [Advanced Meson Science Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Nagamine, K. [Muon Science Laboratory, IMSS-KEK, 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Matsuzaki, T. [Advanced Meson Science Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kawamura, N. [Muon Science Laboratory, IMSS-KEK, 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan)


    The latest progress of muon catalyzed fusion study at the RIKEN-RAL muon facility (and partly at TRIUMF) is reported. The topics covered are magnetic field effect, muon transfer to {sup 3}He in solid D/T and ortho-para effect in dd{mu} formation.

  19. Fusion at the barrier with light radioactive ion beams

    CERN Document Server

    Signorini, C


    The experimental results recently obtained for fusion reactions at energies close to the Coulomb barrier with light radioactive (loosely bound) beams are reviewed and critically discussed. There have been two conflicting views on the effect of the loose binding of the projectile on the fusion cross section. On the one hand one expects an enhancement of the fusion cross section due to the loose binding while, on the other hand, the easy breakup of the projectile is expected to inhibit the fusion cross section. We critically discuss these two aspects of loose binding by comparing the experimental results for a number of radioactive beams. The data for sup 1 sup 7 F (where the last neutron binding energy S sub n =0.601 MeV), neither show breakup effects nor enhancement when compared with the fusion of the nucleus sup 1 sup 9 F. The data for a sup 6 He beam (S sub 2 sub n =0.975 MeV) show enhancement, very strong in one case, and the strong breakup (BU)+transfer cross section may be related to this. The fusion da...

  20. Hugging fusion and related topics

    Energy Technology Data Exchange (ETDEWEB)

    Iwamoto, Akira [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment


    An important problem related to the synthesis of very heavy nuclides by fusion of two heavy-ions is the extra push effect. To avoid it, we propose a hugging fusion, which is the fusion of two well-deformed heavy-ions. (author)

  1. Data fusion for cylindrical form measurements (United States)

    Liu, Pei; Jusko, Otto; Tutsch, Rainer


    For high-precision form measurements of cylindrical workpieces form profiles such as roundness and straightness profiles are independently acquired via a bird-cage strategy. The 3D point cloud reconstructed by fusing these intersected profiles is meaningful in dimension and form assessment for cylinder, since enhanced accuracy can be achieved by fusion results. Moreover, it plays an important role as the input to other calculations. However, these data cannot be accurately aligned in form reconstruction, due to random absolute offsets in profiles and a lack of absolute positions. Therefore, we propose an approach to data fusion of these profiles to reconstruct cylindrical form. The uncertainties of the fused profile are evaluated, taking an individual contribution of a single profile and a global contribution of all profiles into account. The associated uncertainties are propagated using the Monte Carlo method. Experimental study results indicate that the data fusion procedure improves the accuracy of available datasets. After fusion, all available data points are capable of being used in the form assessment.

  2. Fusion excitation functions involving transitional nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Rehm, K.E.; Jiang, C.L.; Esbensen, H. [and others


    Measurements of fusion excitation functions involving transitional nuclei {sup 78}Kr and {sup 100}Mo showed a different behavior at low energies, if compared to measurements with {sup 86}Kr and {sup 92}Mo. This points to a possible influence of nuclear structure on the fusion process. One way to characterize the structure of vibrational nuclei is via their restoring force parameters C{sub 2} which can be calculated from the energy of the lowest 2{sup +} state and the corresponding B(E2) value. A survey of the even-even nuclei between A = 28-150 shows strong variations in C{sub 2} values spanning two orders of magnitude. The lowest values for C{sub 2} are observed for {sup 78}Kr, {sup 104}Ru and {sup 124}Xe followed by {sup 74,76}Ge, {sup 74,76}Se, {sup 100}Mo and {sup 110}Pd. In order to learn more about the influence of {open_quotes}softness{close_quotes} on the sub-barrier fusion enhancement, we measured cross sections for evaporation residue production for the systems {sup 78}Kr + {sup 104}Ru and {sup 78}Kr + {sup 76}Ge with the gas-filled magnet technique. For both systems, fusion excitation functions involving the closed neutron shell nucleus {sup 86}Kr were measured previously. The data are presently being analyzed.

  3. Approach to multisensor/multilook information fusion (United States)

    Myler, Harley R.; Patton, Ronald


    We are developing a multi-sensor, multi-look Artificial Intelligence Enhanced Information Processor (AIEIP) that combines classification elements of geometric hashing, neural networks and evolutionary algorithms in a synergistic combination. The fusion is coordinated using a piecewise level fusion algorithm that operates on probability data from statistics of the individual classifiers. Further, the AIEIP incorporates a knowledge-based system to aid a user in evaluating target data dynamically. The AIEIP is intended as a semi-autonomous system that not only fuses information from electronic data sources, but also has the capability to include human input derived from battlefield awareness and intelligence sources. The system would be useful in either advanced reconnaissance information fusion tasks where multiple fixed sensors and human observer inputs must be combined or for a dynamic fusion scenario incorporating an unmanned vehicle swarm with dynamic, multiple sensor data inputs. This paper represents our initial results from experiments and data analysis using the individual components of the AIEIP on FLIR target sets of ground vehicles.

  4. Controlled fusion and plasma physics

    CERN Document Server

    Miyamoto, Kenro


    Resulting from ongoing, international research into fusion processes, the International Tokamak Experimental Reactor (ITER) is a major step in the quest for a new energy source.The first graduate-level text to cover the details of ITER, Controlled Fusion and Plasma Physics introduces various aspects and issues of recent fusion research activities through the shortest access path. The distinguished author breaks down the topic by first dealing with fusion and then concentrating on the more complex subject of plasma physics. The book begins with the basics of controlled fusion research, foll

  5. Alphavirus Entry and Membrane Fusion

    Directory of Open Access Journals (Sweden)

    Margaret Kielian


    Full Text Available The study of enveloped animal viruses has greatly advanced our understanding of the general properties of membrane fusion and of the specific pathways that viruses use to infect the host cell. The membrane fusion proteins of the alphaviruses and flaviviruses have many similarities in structure and function. As reviewed here, alphaviruses use receptor-mediated endocytic uptake and low pH-triggered membrane fusion to deliver their RNA genomes into the cytoplasm. Recent advances in understanding the biochemistry and structure of the alphavirus membrane fusion protein provide a clearer picture of this fusion reaction, including the protein’s conformational changes during fusion and the identification of key domains. These insights into the alphavirus fusion mechanism suggest new areas for experimental investigation and potential inhibitor strategies for anti-viral therapy.

  6. Characterization of docking and fusion of synaptic-like microvesicles in PC12 cells using TIRFM

    Institute of Scientific and Technical Information of China (English)


    Neurotransmitters are released by the fusion of synaptic vesicles with presynaptic membrane, which has been extensively studied. The analysis of single vesicle fusion kinetics reveals that there exist fusion modes of "kiss and run" and "kiss and stay" which may be favored by neurons especially during strong firing beside full fusion. Pre-fusion steps of translocation, docking and priming along the exocytotic pathway play important roles in neurotransmitter release and its regulation. In the present report, we used dual-color imaging of VAMP2-pHluorin and VAChT-TDimer2 under total internal reflection fluorescence microscope (TIRFM) to monitor the docking and fusion of synaptic-like microvesicles (SLMVs) in PC12 cells stimulated by high K+. Our results show that "kiss and run" is a dominative fusion mode in PC12 cells under high K+-challenge, and the dwell time of SLMVs is prolonged by the high K+ stimulation that suggests an enhancement of vesicle priming.

  7. Fusion Data Grid Service (United States)

    Shasharina, Svetlana; Wang, Nanbor


    Simulations and experiments in the fusion and plasma physics community generate large datasets at remote sites. Visualization and analysis of these datasets are difficult because of the incompatibility among the various data formats adopted by simulation, experiments, and analysis tools, and the large sizes of analyzed data. Grids and Web Services technologies are capable of providing solutions for such heterogeneous settings, but need to be customized to the field-specific needs and merged with distributed technologies currently used by the community. This paper describes how we are addressing these issues in the Fusion Grid Service under development. We also present performance results of relevant data transfer mechanisms including binary SOAP, DIME, GridFTP and MDSplus and CORBA. We will describe the status of data converters (between HDF5 and MDSplus data types), developed in collaboration with MIT (J. Stillerman). Finally, we will analyze bottlenecks of MDSplus data transfer mechanism (work performed in collaboration with General Atomics (D. Schissel and M. Qian).

  8. Alternate laser fusion drivers

    Energy Technology Data Exchange (ETDEWEB)

    Pleasance, L.D.


    Over the past few years, several laser systems have been considered as possible laser fusion drivers. Recently, there has been an increasing effort to evaluate these systems in terms of a reactor driver application. The specifications for such a system have become firmer and generally more restrictive. Several of the promising candidates such as the group VI laser, the metal vapor excimers and some solid state lasers can be eliminated on the basis of inefficiency. New solid state systems may impact the long range development of a fusion driver. Of the short wavelength gas lasers, the KrF laser used in conjunction with Raman compression and pulse stacking techniques is the most promising approach. Efficiencies approaching 10% may be possible with this system. While technically feasible, these approaches are complex and costly and are unsatisfying in an aethetic sense. A search for new lasers with more compelling features is still needed.

  9. JET: Preparing the future in fusion (United States)

    Mlynár, J.; Ongena, J.; Duran, I.; Hron, M.; Pánek, R.; Petržílka, V.; Žáček, F.


    JET (Joint European Torus) is the largest tokamak in the world and the only fusion facility able to operate with Tritium, the fusion fuel, and Beryllium, the ITER first wall material. JET also features the most complete remote handling equipment for invessel maintenance. As a multinational research center, JET provides logistic experience in preparing for operation of the global facility, tokamak ITER. Experiments on JET are focused on ITER-relevant studies, in particular on detailing the operational scenarios (EL My H-modes and advanced regimes), on enhancing the heating systems, on developing diagnostics for burning plasmas etc. Pioneering real-time control techniques have been implemented that maximize performance and minimize internal disturbances of JET plasmas. In helium plasmas, ion cyclotron heating (ICRH) created fast α-particles, mimicking their populations in future burning plasmas. The recent successful Trace Tritium campaign provided important new data on fuel transport. Current enhancements on JET include a new ITER-like ELM-resilient high power ICRH antenna (7 MW) and over twenty new diagnostics that will further extend the JET scientific capabilities and push the facility even closer to the ITER parameters. A special mention is given to the involvement of the fusion experts from Association EURATOM-IPP.CR, who have been actively participating in the collective use of JET facility for more than three years.

  10. (Fusion energy research)

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, C.A. (ed.)


    This report discusses the following topics: principal parameters achieved in experimental devices (FY88); tokamak fusion test reactor; Princeton beta Experiment-Modification; S-1 Spheromak; current drive experiment; x-ray laser studies; spacecraft glow experiment; plasma deposition and etching of thin films; theoretical plasma; tokamak modeling; compact ignition tokamak; international thermonuclear experimental reactor; Engineering Department; Project Planning and Safety Office; quality assurance and reliability; and technology transfer.

  11. Materials for Fusion Applications

    Directory of Open Access Journals (Sweden)

    Jiří Matějíček


    Full Text Available An overview of materials foreseen for use or already used in fusion devices is given. The operating conditions, material requirements and characteristics of candidate materials in several specific application segments are briefly reviewed. These include: construction materials, electrical insulation, permeation barriers and plasma facing components. Special attention will be paid to the latter and to the issues of plasma-material interaction, materials joining and fuctionally graded interlayers.

  12. Fc-fusion mimetics



    The Fc-fusion mimetic RpR 2 was prepared by disulfide bridging conjugation using a PEG in the place of the Fc. RpR 2 displayed higher affinity for VEGF than aflibercept caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics.

  13. Fusion development and technology

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, D.B.


    This report discusses the following: superconducting magnet technology; high field superconductors; advanced magnetic system and divertor development; poloidal field coils; gyrotron development; commercial reactor studies--aries; ITER physics: alpha physics and alcator R D for ITER; lower hybrid current drive and heating in the ITER device; ITER superconducting PF scenario and magnet analysis; ITER systems studies; and safety, environmental and economic factors in fusion development.

  14. Modular Aneutronic Fusion Engine

    Energy Technology Data Exchange (ETDEWEB)

    Gary Pajer, Yosef Razin, Michael Paluszek, A.H. Glasser and Samuel Cohen


    NASA's JUNO mission will arrive at Jupiter in July 2016, after nearly five years in space. Since operational costs tend to rise with mission time, minimizing such times becomes a top priority. We present the conceptual design for a 10MW aneutronic fusion engine with high exhaust velocities that would reduce transit time for a Jupiter mission to eighteen months and enable more challenging exploration missions in the solar system and beyond. __________________________________________________

  15. Entrance channel effect in the incomplete fusion reactions

    Directory of Open Access Journals (Sweden)

    Singh B.P.


    Full Text Available In the present work the effect of various entrance channel parameters on incomplete fusion strength and the reaction dynamics in 12C+159Tb system at energies ≈ 4-7MeV/A have been investigated by measuring the excitation functions of individual reaction channels. Experimental excitation functions have been analyzed in the framework of compound nucleus decay using statistical model code PACE4. Analysis of data suggests the production of xn/pxn-channels via complete fusion of 12C with 159Tb, as these are found to be well reproduced by PACE4 predictions, while, a significant enhancement in the excitation functions of α-emitting channels has been observed over the theoretical ones. This enhancement has been attributed due to incomplete fusion. For better insight into the underlying dynamics, fraction of incomplete fusion to the total fusion has been deduced and compared with 16O+159Tb and other nearby systems as a function of various entrance channel parameters. The fraction of incomplete fusion has been found to be sensitive to the projectile type, energy and entrance-channel mass-asymmetry.

  16. Theoretical Study of the Effects of Di-Muonic Molecules on Muon-Catalyzed Fusion (United States)


    MOLECULES ON MUON -CATALYZED FUSION DISSERTATION Eugene V. Sheely, Lieutenant Colonel, USA DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY...THEORETICAL STUDY OF THE EFFECTS OF DI-MUONIC MOLECULES ON MUON -CATALYZED FUSION DISSERTATION Presented to the Faculty...potential of enhancing the muon -catalyzed fusion reaction rate. In order to study these di-muonic molecules a method of non-adiabatic quantum mechanics

  17. Contribution of sensor fusion to urban mapping: application to simulated SPOT 5-6 data



    International audience; This communication intends to enhance the contribution of a sensor fusion method to urban mapping using the simulated SPOT 5-6 data. A new scheme is proposed for cartography of urban areas which takes into account the multispectral and the multiresolution nature of the data. This process makes use of classification and segmentation. An application of the sensor fusion method to analyse the simulated SPOT 5-6 data is presented. The benefits of using sensor fusion before...

  18. Bayesian information fusion networks for biosurveillance applications. (United States)

    Mnatsakanyan, Zaruhi R; Burkom, Howard S; Coberly, Jacqueline S; Lombardo, Joseph S


    This study introduces new information fusion algorithms to enhance disease surveillance systems with Bayesian decision support capabilities. A detection system was built and tested using chief complaints from emergency department visits, International Classification of Diseases Revision 9 (ICD-9) codes from records of outpatient visits to civilian and military facilities, and influenza surveillance data from health departments in the National Capital Region (NCR). Data anomalies were identified and distribution of time offsets between events in the multiple data streams were established. The Bayesian Network was built to fuse data from multiple sources and identify influenza-like epidemiologically relevant events. Results showed increased specificity compared with the alerts generated by temporal anomaly detection algorithms currently deployed by NCR health departments. Further research should be done to investigate correlations between data sources for efficient fusion of the collected data.

  19. Plasmonic energy nanofocusing for high-efficiency laser fusion ignition (United States)

    Tanabe, Katsuaki


    We propose an efficient laser fusion ignition system consisting of metal nanoparticles or nanoshells embedded in conventional deuterated polystyrene fuel targets. The incident optical energy of the heating laser is highly concentrated around the metallic particulates randomly dispersed inside imploded targets due to the electromagnetic-field-enhancement effect by surface plasmon resonance, and thus effectively triggers nuclear-fusion chain reactions. Our preliminary calculations exhibit field enhancement factors of around 50 and 1100 for spherical Ag nanoparticles and Ag/SiO2 nanoshells, respectively, in the 1-µm band.

  20. Alpha Heating and Burning Plasmas in Inertial Confinement Fusion (United States)

    Betti, R.; Christopherson, A. R.; Bose, A.; Woo, K. M.


    Assessing the degree to which fusion alpha particles contribute to the fusion yield is essential to understanding the onset of the thermal runaway process of thermonuclear ignition. It is shown that in inertial confinement fusion, the yield enhancement due to alpha particle heating (before ignition occurs) depends on the generalized Lawson parameter that can be inferred from experimental observables. A universal curve valid for arbitrary laser-fusion targets shows the yield amplification due to alpha heating for a given value of the Lawson parameter. The same theory is used to determine the onset of the burning plasma regime when the alpha heating exceeds the compression work. This result can be used to assess the performance of current ignition experiments at the National Ignition Facility.

  1. Application of the JDL data fusion process model to hard/soft information fusion in the condition monitoring of aircraft (United States)

    Bernardo, Joseph T.


    Hard/soft information fusion has been proposed as a way to enhance diagnostic capability for the condition monitoring of machinery. However, there is a limited understanding of where hard/soft information fusion could and should be applied in the condition monitoring of aircraft. Condition-based maintenance refers to the philosophy of performing maintenance when the need arises, based upon indicators of deterioration in the condition of the machinery. The addition of the multisensory capability of human cognition to electronic sensors may create a fuller picture of machinery condition. Since 1988, the Joint Directors of Laboratories (JDL) data fusion process model has served as a framework for information fusion research. Advances are described in the application of hard/soft information fusion in condition monitoring using terms that condition-based maintenance professionals in aviation will recognize. Emerging literature on hard/soft information fusion in condition monitoring is organized into the levels of the JDL data fusion process model. Gaps in the literature are identified, and the author's ongoing research is discussed. Future efforts will focus on building domain-specific frameworks and experimental design, which may provide a foundation for improving flight safety, increasing mission readiness, and reducing the cost of maintenance operations.

  2. Role of caveolin-1 in adult rat CFs proliferation induced by AVP and the intervention of Simvastatin%小窝蛋白-1反义寡核苷酸在AVP诱导大鼠心肌成纤维细胞增殖erk1/2信号转导中的作用及辛伐他汀的干预效应

    Institute of Scientific and Technical Information of China (English)

    何燕萍; 杨军岭; 赵连友; 刘少伟


    Objective To study the effect of caveolin-1 antisense oligonucleotides (cav1-AS ODN) on cardiac fibroblasts (CFs) proliferation induced by arginine vasopressin (AVP) and the involvement of simvastatin (Sim) in the modulation of cholesterol. Methods CFs were isolated from adult SD rats and cultured. Phosphorothioate modified oligonucleotides and AVP were added to the CFs. CFs proliferation was assessed by 3H-TdR incorporation. Protein expressions of cav1 ,erk1/2, p21 and cyclin A were evaluated by western blotting. Results The levels of 3H-TdR incorporation and erk1/2 protein expression were (212 ± 6)% and (7.9 ± 0. 3) relative to control,respectively,in cav1-AS ODN + AVP group, being different from those of ( 172 ± 4) % and (5. 7 ± 0. 2) in AVP group ( both P < 0. 0 1 ). Protein expression of p21 was decreased and cyclin A increased in AS ODN ± AVP group. The presence of β-cyclodextrin or progesterone or Sim decreased cav1 protein expression. The levels of cav1 protein expression were (86 ± 3 )%, (91 ± 4 )% and (94 ± 5 )% relative to control, respectively,in the presence of 10,15 or 20 μg/ml cholesterol,being different from that of Sim group (66 ± 4)% relative to control (P <0. 05,P <0. 01 ). Conclusions cav1-AS ODN potentiates the proliferation-inducing effect of AVP on adult rat CFs,and the intervention of cholesterollowing effect of statins may provide new insights into the anti-fibrosis effect of these drugs.%目的 研究小窝蛋白-1反义寡核苷酸(cav1-AS ODN)在血管加压素(AVP)诱导的成年大鼠心肌成纤维细胞(CFs)增殖erk1/2信号转导中的作用及辛伐他汀(Sim)对cav1表达的干预效应.方法 采用脂质体导入法将cav1-AS ODN导入离体培养的成年大鼠CFs,用3H-TdR掺入法定量观察CFs增殖,蛋白免疫印迹法分析cav1-AS ODN对AVP诱导大鼠CFs增殖后磷酸化erk1/2 (p-erk1/2)、p21和细胞周期蛋白A(cyclin A)表达变化及Sim对cav1表达的影响.结果 cav1-AS ODN与10

  3. Inertial fusion energy; L'energie de fusion inertielle

    Energy Technology Data Exchange (ETDEWEB)

    Decroisette, M.; Andre, M.; Bayer, C.; Juraszek, D. [CEA Bruyeres-le-Chatel, Dir. des Systemes d' Information (CEA/DIF), 91 (France); Le Garrec, B. [CEA Centre d' Etudes Scientifiques et Techniques d' Aquitaine, 33 - Le Barp (France); Deutsch, C. [Paris-11 Univ., 91 - Orsay (France); Migus, A. [Institut d' Optique Centre scientifique, 91 - Orsay (France)


    We first recall the scientific basis of inertial fusion and then describe a generic fusion reactor with the different components: the driver, the fusion chamber, the material treatment unit, the target factory and the turbines. We analyse the options proposed at the present time for the driver and for target irradiation scheme giving the state of art for each approach. We conclude by the presentation of LMJ (laser Megajoule) and NIF (national ignition facility) projects. These facilities aim to demonstrate the feasibility of laboratory DT ignition, first step toward Inertial Fusion Energy. (authors)

  4. High Level Information Fusion (HLIF) with nested fusion loops (United States)

    Woodley, Robert; Gosnell, Michael; Fischer, Amber


    Situation modeling and threat prediction require higher levels of data fusion in order to provide actionable information. Beyond the sensor data and sources the analyst has access to, the use of out-sourced and re-sourced data is becoming common. Through the years, some common frameworks have emerged for dealing with information fusion—perhaps the most ubiquitous being the JDL Data Fusion Group and their initial 4-level data fusion model. Since these initial developments, numerous models of information fusion have emerged, hoping to better capture the human-centric process of data analyses within a machine-centric framework. 21st Century Systems, Inc. has developed Fusion with Uncertainty Reasoning using Nested Assessment Characterizer Elements (FURNACE) to address challenges of high level information fusion and handle bias, ambiguity, and uncertainty (BAU) for Situation Modeling, Threat Modeling, and Threat Prediction. It combines JDL fusion levels with nested fusion loops and state-of-the-art data reasoning. Initial research has shown that FURNACE is able to reduce BAU and improve the fusion process by allowing high level information fusion (HLIF) to affect lower levels without the double counting of information or other biasing issues. The initial FURNACE project was focused on the underlying algorithms to produce a fusion system able to handle BAU and repurposed data in a cohesive manner. FURNACE supports analyst's efforts to develop situation models, threat models, and threat predictions to increase situational awareness of the battlespace. FURNACE will not only revolutionize the military intelligence realm, but also benefit the larger homeland defense, law enforcement, and business intelligence markets.

  5. Fusion Rings for Quantum Groups

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Stroppel, Catharina


    We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from Korff, C., Stroppel, C.: The sl(ˆn)k-WZNW fusion ring: a combinato-rial construction and a realis......We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from Korff, C., Stroppel, C.: The sl(ˆn)k-WZNW fusion ring: a combinato-rial construction...

  6. Report of the Fusion Energy Sciences Advisory Committee. Panel on Integrated Simulation and Optimization of Magnetic Fusion Systems

    Energy Technology Data Exchange (ETDEWEB)

    Dahlburg, Jill [General Atomics, San Diego, CA (United States); Corones, James [Krell Inst., Ames, IA (United States); Batchelor, Donald [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bramley, Randall [Indiana Univ., Bloomington, IN (United States); Greenwald, Martin [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Jardin, Stephen [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Krasheninnikov, Sergei [Univ. of California, San Diego, CA (United States); Laub, Alan [Univ. of California, Davis, CA (United States); Leboeuf, Jean-Noel [Univ. of California, Los Angeles, CA (United States); Lindl, John [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lokke, William [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rosenbluth, Marshall [Univ. of California, San Diego, CA (United States); Ross, David [Univ. of Texas, Austin, TX (United States); Schnack, Dalton [Science Applications International Corporation, Oak Ridge, TN (United States)


    Fusion is potentially an inexhaustible energy source whose exploitation requires a basic understanding of high-temperature plasmas. The development of a science-based predictive capability for fusion-relevant plasmas is a challenge central to fusion energy science, in which numerical modeling has played a vital role for more than four decades. A combination of the very wide range in temporal and spatial scales, extreme anisotropy, the importance of geometric detail, and the requirement of causality which makes it impossible to parallelize over time, makes this problem one of the most challenging in computational physics. Sophisticated computational models are under development for many individual features of magnetically confined plasmas and increases in the scope and reliability of feasible simulations have been enabled by increased scientific understanding and improvements in computer technology. However, full predictive modeling of fusion plasmas will require qualitative improvements and innovations to enable cross coupling of a wider variety of physical processes and to allow solution over a larger range of space and time scales. The exponential growth of computer speed, coupled with the high cost of large-scale experimental facilities, makes an integrated fusion simulation initiative a timely and cost-effective opportunity. Worldwide progress in laboratory fusion experiments provides the basis for a recent FESAC recommendation to proceed with a burning plasma experiment (see FESAC Review of Burning Plasma Physics Report, September 2001). Such an experiment, at the frontier of the physics of complex systems, would be a huge step in establishing the potential of magnetic fusion energy to contribute to the world’s energy security. An integrated simulation capability would dramatically enhance the utilization of such a facility and lead to optimization of toroidal fusion plasmas in general. This science-based predictive capability, which was cited in the FESAC

  7. Effect of neutron transfer in the fusion process near and below the Coulomb barrier

    Energy Technology Data Exchange (ETDEWEB)

    Rachkov, V. A.; Adel, A.; Karpov, A. V.; Denikin, A. S.; Zagrebaev, V. I. [Flerov Laboratory of Nuclear Reactions, JINR, Dubna, 141980, Moscow region (Russian Federation); Physics Department, Faculty of Science, Cairo University, Giza (Egypt); Flerov Laboratory of Nuclear Reactions, JINR, Dubna, 141980, Moscow region (Russian Federation); Flerov Laboratory of Nuclear Reactions, JINR, Dubna, 141980, Moscow region (Russian Federation) and International University ' Dubna' , Dubna, 141980, Moscow region (Russian Federation); Flerov Laboratory of Nuclear Reactions, JINR, Dubna, 141980, Moscow region (Russian Federation)


    Near-barrier and sub-barrier fusion of weakly bound neutron-rich isotopes of lithium is explored within the empirical channel coupling model. Several combinations of colliding nuclei are proposed, for which strong enhancement of the sub-barrier fusion is predicted owing to coupling with neutron transfer channels.

  8. Cold nuclear fusion

    Energy Technology Data Exchange (ETDEWEB)

    Tsyganov, E.N., E-mail: [Cold Fusion Power, International (United States); Bavizhev, M.D. [LLC “Radium”, Moscow (Russian Federation); Buryakov, M.G. [Joint Institute for Nuclear Research (JINR), Dubna (Russian Federation); Dabagov, S.B. [RAS P.N. Lebedev Physical Institute, Leninsky pr. 53, 119991 Moscow (Russian Federation); National Research Nuclear University MEPhI, Kashirskoe shosse 31, 115409 Moscow (Russian Federation); Golovatyuk, V.M.; Lobastov, S.P. [Joint Institute for Nuclear Research (JINR), Dubna (Russian Federation)


    If target deuterium atoms were implanted in a metal crystal in accelerator experiments, a sharp increase in the probability of DD-fusion reaction was clearly observed when compared with the reaction’s theoretical value. The electronic screening potential, which for a collision of free deuterium atoms is about 27 eV, reached 300–700 eV in the case of the DD-fusion in metallic crystals. These data leads to the conclusion that a ban must exist for deuterium atoms to be in the ground state 1s in a niche filled with free conduction electrons. At the same time, the state 2p whose energy level is only 10 eV above that of state 1s is allowed in these conditions. With anisotropy of 2p, 3p or above orbitals, their spatial positions are strictly determined in the lattice coordinate system. When filling out the same potential niches with two deuterium atoms in the states 2p, 3p or higher, the nuclei of these atoms can be permanently positioned without creating much Coulomb repulsion at a very short distance from each other. In this case, the transparency of the potential barrier increases dramatically compared to the ground state 1s for these atoms. The probability of the deuterium nuclei penetrating the Coulomb barrier by zero quantum vibration of the DD-system also increases dramatically. The so-called cold nuclear DD-fusion for a number of years was registered in many experiments, however, was still rejected by mainstream science for allegedly having no consistent scientific explanation. Finally, it received the validation. Below, we outline the concept of this explanation and give the necessary calculations. This paper also considers the further destiny of the formed intermediate state of {sup 4}He{sup ∗}.

  9. Fusion Advanced Design Studies

    Energy Technology Data Exchange (ETDEWEB)

    El-Guebaly, Laila; Henderson, Douglass; Wilson, Paul; Blanchard, Jake


    During the January 1, 2013 – December 31, 2015 contract period, the UW Fusion Technology Institute personnel have actively participated in the ARIES-ACT and FESS-FNSF projects, led the nuclear and thermostructural tasks, attended several project meetings, and participated in all conference calls. The main areas of effort and technical achievements include updating and documenting the nuclear analysis for ARIES-ACT1, performing nuclear analysis for ARIES-ACT2, performing thermostructural analysis for ARIES divertor, performing disruption analysis for ARIES vacuum vessel, and developing blanket testing strategy and Materials Test Module for FNSF.

  10. Core Deuterium Fusion and Radius Inflation in Hot Jupiters (United States)

    Jaikumar, Prashanth; Rachid Ouyed


    Several laboratory-based studies have shown that the Deuterium fusion cross-section is enhanced in a solid deuterated target as compared to a gas target, attributable to enhanced mobility of deuterons in a metal lattice. As an application, we propose that, for core temperatures and compositions characterizing hot Jupiters, screened Deuterium fusion can occur deep in the interior, and show that the amount of radius inflation from this effect can be important if there is sufficient rock-ice in the core. The mechanism of screened Deuterium fusion, operating in the above temperature range, is generally consistent with the trend in radius anomaly with planetary equilibrium temperature. We also explore the trend with planetary mass using a simple analytic model.

  11. A Stable Switch Method Based on Fusion in Uncalibrated Visual Servoing

    Institute of Scientific and Technical Information of China (English)


    Stable switch control between multiple cameras for uncalibrated visual servoing was studied. Switch images based on fusion were presented to get the continuous dynamic image Jacobian matrix among robots and distributed visual sensors. The designed fusion algorithm is suitable to have dynamically adjustable fusion weights,and the fusion structure was analyzed. Simulations and experiments without any knowledge of mobile robots and uncalibrated visual sensors show that the method has higher adaptability than the traditional instant switch control method. The method can enhance the system stability at the switching process.

  12. Review of the mathematical foundations of data fusion techniques in surface metrology (United States)

    Wang, Jian; Leach, Richard K.; Jiang, X.


    The recent proliferation of engineered surfaces, including freeform and structured surfaces, is challenging current metrology techniques. Measurement using multiple sensors has been proposed to achieve enhanced benefits, mainly in terms of spatial frequency bandwidth, which a single sensor cannot provide. When using data from different sensors, a process of data fusion is required and there is much active research in this area. In this paper, current data fusion methods and applications are reviewed, with a focus on the mathematical foundations of the subject. Common research questions in the fusion of surface metrology data are raised and potential fusion algorithms are discussed.

  13. Utility requirements for fusion

    Energy Technology Data Exchange (ETDEWEB)

    Vondrasek, R.J.


    This report describes work done and results obtained during performance of Task 1 of a study of Utility Requirements and Criteria for Fusion Options. The work consisted of developing a list of utility requirements for fusion optics containing definition of the requirements and showing their relative importance to the utility industry. The project team members developed a preliminary list which was refined by discussions and literature searches. The refined list was recast as a questionnaire which was sent to a substantial portion of the utility industry in this country. Forty-three questionnaire recipients responded including thirty-two utilities. A workshop was held to develop a revised requirements list using the survey responses as a major input. The list prepared by the workshop was further refined by a panel consisting of vice presidents of the three project team firms. The results of the study indicate that in addition to considering the cost of energy for a power plant, utilities consider twenty-three other requirements. Four of the requirements were judged to be vital to plant acceptability: Plant Capital Cost, Financial Liability, Plant Safety and Licensability.

  14. JENDL fusion file 99

    Energy Technology Data Exchange (ETDEWEB)

    Chiba, Satoshi; Fukahori, Tokio; Shibata, Keiichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Yu Baosheng [China Institute of Atomic Energy, Beijing (China); Kosako, Kazuaki [Sumitomo Atomic Industries, Tokyo (Japan); Yamamuro, Nobuhiro [Data Engineering Co. Ltd., Yokohama, Kanagawa (Japan)


    The double-differential cross sections (DDXs) of secondary neutrons have been evaluated for 79 isotopes and 13 natural elements ranging from H to Bi to improve the accuracy of predictions for the neutronics calculations in the D-T thermonuclear fusion applications. The data given in JENDL-3.1, which was the newest version of JENDL general purpose file when this project was initiated, was combined with new calculations based on the optical model, DWBA, pre-equilibrium and multi-step statistical models, and the DDX data were generated based on various kinds of systematics for medium-mass nuclei. Different methods were employed for light nuclei to which the above method could not be applied. In addition, the DDXs for emission of charged particles (p, d, t, {sup 3}He and {alpha}-particle) were given for {sup 2}H, {sup 9}Be and elements heavier or equal to F. The present results give an overall good description of the measured DDX data of both the neutron and charged particles emission channels. The data were compiled in ENDF-6 format, and released in 1999 as a special purpose file of JENDL family, namely, JENDL Fusion File 99. (author)

  15. Clean steels for fusion

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S.


    Fusion energy production has an inherent advantage over fission: a fuel supply with reduced long term radioactivity. One of the leading candidate materials for structural applications in a fusion reactor is a tungsten stabilized 9% chromium Martensitic steel. This alloy class is being considered because it offers the opportunity to maintain that advantage in the reactor structure as well as provide good high temperature strength and radiation induced swelling and embrittlement resistance. However, calculations indicate that to obtain acceptable radioactivity levels within 500 years after service, clean steel will be required because the niobium impurity levels must be kept below about 2 appm and nickel, molybdenum, nitrogen, copper, and aluminum must be intentionally restricted. International efforts are addressing the problems of clean steel production. Recently, a 5,000 kg heat was vacuum induction melted in Japan using high purity commercial raw materials giving niobium levels less than 0.7 appm. This paper reviews the need for reduced long term radioactivity, defines the advantageous properties of the tungsten stabilized Martensitic steel class, and describes the international efforts to produce acceptable clean steels.

  16. Fluorescent sensors based on bacterial fusion proteins (United States)

    Prats Mateu, Batirtze; Kainz, Birgit; Pum, Dietmar; Sleytr, Uwe B.; Toca-Herrera, José L.


    Fluorescence proteins are widely used as markers for biomedical and technological purposes. Therefore, the aim of this project was to create a fluorescent sensor, based in the green and cyan fluorescent protein, using bacterial S-layers proteins as scaffold for the fluorescent tag. We report the cloning, expression and purification of three S-layer fluorescent proteins: SgsE-EGFP, SgsE-ECFP and SgsE-13aa-ECFP, this last containing a 13-amino acid rigid linker. The pH dependence of the fluorescence intensity of the S-layer fusion proteins, monitored by fluorescence spectroscopy, showed that the ECFP tag was more stable than EGFP. Furthermore, the fluorescent fusion proteins were reassembled on silica particles modified with cationic and anionic polyelectrolytes. Zeta potential measurements confirmed the particle coatings and indicated their colloidal stability. Flow cytometry and fluorescence microscopy showed that the fluorescence of the fusion proteins was pH dependent and sensitive to the underlying polyelectrolyte coating. This might suggest that the fluorescent tag is not completely exposed to the bulk media as an independent moiety. Finally, it was found out that viscosity enhanced the fluorescence intensity of the three fluorescent S-layer proteins.

  17. 急性胰腺炎肺损伤大鼠肺组织肿瘤坏死因子受体-1与窖蛋白-1的表达及清胰汤的治疗作用%The expression of tumor necrosis factor receptor-1 and caveolin-1 in the lung of acute pancreatitisassociated lung injury rats and the therapeutic role of Qingyitang

    Institute of Scientific and Technical Information of China (English)

    王钢; 陈海龙; 唐颖; 任凤; 李洁; 姜妙娜


    Objective To investigate the expression and function of tumor necrosis factor receptor-1 (TNFR-1) and caveolin-1 (Cav-1) in the lung of acute pancreatitis-associated lung injury rats, and to determine the potential role of Qingyitang. Methods Wistar rats were randomly divided into sham operation (SHAM) group, acute lung injury (ALI) group, dexamethasone (DEX) group and Qingyitang (QYT)group. ALI was induced by retrograde injection of deoxycholate into biliopancreatic duct of rats. Blood and lung tissues were drawn after 24 h. Serum amylase, lung wet/dry (W/D) ratio and pathological section were examined to evaluate the degree of lung injury. Immunoradioassay was used to detect serum tumor necrosis factor-α (TNF-α). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the expression levels of TNFR-1 and Cav-1 mRNA and protein respectively. Results The concentration of serum amylase, the W/D ratio, TNF-α (4.82 ± 0.14 vs 2.96 ± 0. 30, P <0. 01 ) and the degree of pathological lung injury were obviously increased in ALI rats. The expression of TNFR-1 mRNA was increased in ALI rats (1.29 ±0. 15 vs 0.43 ±0.05,P<0.01), but Cav-1 mRNA expression was decreased ( 1.14 ±0. 10 vs 2.00 ±0. 10,P <0.01 ). The expression of TNFR-1 protein in both lipid rafts and non-lipid rafts was increased, but that of Cav-1 in both of the two fractions was decreased. As compared with ALI rats, the concentration of serum amylase, W/D ratio, TNF-αt ( DEX: 3.79 ± 0. 11,QYT: 3.66 ±0. 10, ALI: 4.82 ±0. 14,P <0.01 ) and the degree of pathological lung injury were obviously decreased in DEX and QYT rats. The expression of TNFR-1 mRNA was decreased in both DEX and QYT groups (DEX: 0.48±0.01, QYT: 0.49 ±0.02, ALI: 1.29 ±0. 15,P<0.01), but that of Cav-1 mRNA was up-regulated (DEX: 1.66 ±0.06, QYT: 1.52 ±0.04, ALI: 1.14 ±0. 10,P<0.01). The expression of TNFR-1 protein in both lipid rafts and non-lipid rafts was decreased, but

  18. Hybrid ultrasound imaging techniques (fusion imaging). (United States)

    Sandulescu, Daniela Larisa; Dumitrescu, Daniela; Rogoveanu, Ion; Saftoiu, Adrian


    Visualization of tumor angiogenesis can facilitate non-invasive evaluation of tumor vascular characteristics to supplement the conventional diagnostic imaging goals of depicting tumor location, size, and morphology. Hybrid imaging techniques combine anatomic [ultrasound, computed tomography (CT), and/or magnetic resonance imaging (MRI)] and molecular (single photon emission CT and positron emission tomography) imaging modalities. One example is real-time virtual sonography, which combines ultrasound (grayscale, colour Doppler, or dynamic contrast harmonic imaging) with contrast-enhanced CT/MRI. The benefits of fusion imaging include an increased diagnostic confidence, direct comparison of the lesions using different imaging modalities, more precise monitoring of interventional procedures, and reduced radiation exposure.

  19. Advanced Fusion Reactors for Space Propulsion and Power Systems (United States)

    Chapman, John J.


    In recent years the methodology proposed for conversion of light elements into energy via fusion has made steady progress. Scientific studies and engineering efforts in advanced fusion systems designs have introduced some new concepts with unique aspects including consideration of Aneutronic fuels. The plant parameters for harnessing aneutronic fusion appear more exigent than those required for the conventional fusion fuel cycle. However aneutronic fusion propulsion plants for Space deployment will ultimately offer the possibility of enhanced performance from nuclear gain as compared to existing ionic engines as well as providing a clean solution to Planetary Protection considerations and requirements. Proton triggered 11Boron fuel (p- 11B) will produce abundant ion kinetic energy for In-Space vectored thrust. Thus energetic alpha particles "exhaust" momentum can be used directly to produce high ISP thrust and also offer possibility of power conversion into electricity. p- 11B is an advanced fusion plant fuel with well understood reaction kinematics but will require some new conceptual thinking as to the most effective implementation.

  20. The status of cold fusion (United States)

    Storms, E.

    This report attempts to update the status of the phenomenon of cold fusion. The new field is continuing to grow as a variety of nuclear reactions are discovered to occur in a variety of chemical environments at modest temperatures. However, it must be cautioned that most scientists consider cold fusion as something akin to UFO's, ESP, and numerology.

  1. The quest for fusion power (United States)

    Cowley, Steven C.


    Fusion power is one of a very few sustainable options to replace fossil fuels as the world's primary energy source. Although the conditions for fusion have been reached, much remains to be done to turn scientific success into commercial electrical power.

  2. Fusion Policy Advisory Committee (FPAC)

    Energy Technology Data Exchange (ETDEWEB)


    This document is the final report of the Fusion Policy Advisory Committee. The report conveys the Committee's views on the matters specified by the Secretary in his charge and subsequent letters to the Committee, and also satisfies the provisions of Section 7 of the Magnetic Fusion Energy Engineering Act of 1980, Public Law 96-386, which require a triennial review of the conduct of the national Magnetic Fusion Energy program. Three sub-Committee's were established to address the large number of topics associated with fusion research and development. One considered magnetic fusion energy, a second considered inertial fusion energy, and the third considered issues common to both. For many reasons, the promise of nuclear fusion as a safe, environmentally benign, and affordable source of energy is bright. At the present state of knowledge, however, it is uncertain that this promise will become reality. Only a vigorous, well planned and well executed program of research and development will yield the needed information. The Committee recommends that the US commit to a plan that will resolve this critically important issue. It also outlines the first steps in a development process that will lead to a fusion Demonstration Power Plant by 2025. The recommended program is aggressive, but we believe the goal is reasonable and attainable. International collaboration at a significant level is an important element in the plan.

  3. Fusion research programme in India

    Indian Academy of Sciences (India)

    Shishir Deshpande; Predhiman Kaw


    The fusion energy research program of India is summarized in the context of energy needs and scenario of tokamak advancements on domestic and international fronts. In particular, the various technologies that will lead us to ultimately build a fusion power reactor are identified along with the steps being taken for their indigenous development.

  4. Cellulose binding domain fusion proteins (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.


    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  5. Multi-sensor fusion development (United States)

    Bish, Sheldon; Rohrer, Matthew; Scheffel, Peter; Bennett, Kelly


    The U.S. Army Research Laboratory (ARL) and McQ Inc. are developing a generic sensor fusion architecture that involves several diverse processes working in combination to create a dynamic task-oriented, real-time informational capability. Processes include sensor data collection, persistent and observational data storage, and multimodal and multisensor fusion that includes the flexibility to modify the fusion program rules for each mission. Such a fusion engine lends itself to a diverse set of sensing applications and architectures while using open-source software technologies. In this paper, we describe a fusion engine architecture that combines multimodal and multi-sensor fusion within an Open Standard for Unattended Sensors (OSUS) framework. The modular, plug-and-play architecture of OSUS allows future fusion plugin methodologies to have seamless integration into the fusion architecture at the conceptual and implementation level. Although beyond the scope of this paper, this architecture allows for data and information manipulation and filtering for an array of applications.

  6. Sensor fusion for social robotics


    Duffy, Brian R.; Garcia, C; Rooney, Colm, (Thesis); O'Hare, G.M.P.


    This paper advocates the application of sensor fusion for the visualisation of social robotic behaviour. Experiments with the Virtual Reality Workbench integrate the key elements of Virtual Reality and robotics in a coherent and systematic manner. The deliberative focusing of attention and sensor fusion between vision systems and sonar sensors is implemented on autonomous mobile robots functioning in standard office environments

  7. Membrane fusion during poxvirus entry. (United States)

    Moss, Bernard


    Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. Entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. Whereas many viruses encode one or two proteins for attachment and membrane fusion, vaccinia virus encodes four proteins for attachment and eleven more for membrane fusion and core entry. The entry-fusion proteins are conserved in all poxviruses and form a complex, known as the Entry Fusion Complex (EFC), which is embedded in the membrane of the mature virion. An additional membrane that encloses the mature virion and is discarded prior to entry is present on an extracellular form of the virus. The EFC is held together by multiple interactions that depend on nine of the eleven proteins. The entry process can be divided into attachment, hemifusion and core entry. All eleven EFC proteins are required for core entry and at least eight for hemifusion. To mediate fusion the virus particle is activated by low pH, which removes one or more fusion repressors that interact with EFC components. Additional EFC-interacting fusion repressors insert into cell membranes and prevent secondary infection. The absence of detailed structural information, except for two attachment proteins and one EFC protein, is delaying efforts to determine the fusion mechanism.

  8. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 11: interbody techniques for lumbar fusion. (United States)

    Mummaneni, Praveen V; Dhall, Sanjay S; Eck, Jason C; Groff, Michael W; Ghogawala, Zoher; Watters, William C; Dailey, Andrew T; Resnick, Daniel K; Choudhri, Tanvir F; Sharan, Alok; Wang, Jeffrey C; Kaiser, Michael G


    Interbody fusion techniques have been promoted as an adjunct to lumbar fusion procedures in an effort to enhance fusion rates and potentially improve clinical outcome. The medical evidence continues to suggest that interbody techniques are associated with higher fusion rates compared with posterolateral lumbar fusion (PLF) in patients with degenerative spondylolisthesis who demonstrate preoperative instability. There is no conclusive evidence demonstrating improved clinical or radiographic outcomes based on the different interbody fusion techniques. The addition of a PLF when posterior or anterior interbody lumbar fusion is performed remains an option, although due to increased cost and complications, it is not recommended. No substantial clinical benefit has been demonstrated when a PLF is included with an interbody fusion. For lumbar degenerative disc disease without instability, there is moderate evidence that the standalone anterior lumbar interbody fusion (ALIF) has better clinical outcomes than the ALIF plus instrumented, open PLF. With regard to type of interbody spacer used, frozen allograft is associated with lower pseudarthrosis rates compared with freeze-dried allograft; however, this was not associated with a difference in clinical outcome.

  9. Deployment of membrane fusion protein domains during fusion. (United States)

    Bentz, J; Mittal, A


    It is clear that both viral and intracellular membrane fusion proteins contain a minimal set of domains which must be deployed at the appropriate time during the fusion process. An account of these domains and their functions is given here for the four best-described fusion systems: influenza HA, sendai virus F1, HIV gp120/41 and the neuronal SNARE core composed of synaptobrevin (syn), syntaxin (stx) and the N- and C-termini of SNAP25 (sn25), together with the Ca(2+)binding protein synaptotagmin (syt). Membrane fusion begins with the binding of the virion or vesicle to the target membrane via receptors. The committed step in influenza HA- mediated fusion begins with an aggregate of HAs (at least eight) with some of their HA2 N-termini, a.k.a. fusion peptides, embedded into the viral bilayer (Bentz, 2000 a). The hypothesis presented in Bentz (2000 b) is that the conformational change of HA to the extended coiled coil extracts the fusion peptides from the viral bilayer. When this extraction occurs from the center of the site of restricted lipid flow, it exposes acyl chains and parts of the HA transmembrane domains to the aqueous media, i.e. a hydrophobic defect is formed. This is the 'transition state' of the committed step of fusion. It is stabilized by a 'dam' of HAs, which are inhibited from diffusing away by the rest of the HAs in the aggregate and because that would initially expose more acyl chains to water. Recruitment of lipids from the apposed target membrane can heal this hydrophobic defect, initiating lipid mixing and fusion. The HA transmembrane domains are required to be part of the hydrophobic defect, because the HA aggregate must be closely packed enough to restrict lipid flow. This hypothesis provides a simple and direct coupling between the energy released by the formation of the coiled coil to the energy needed to create and stabilize the high energy intermediates of fusion. Several of these essential domains have been described for the viral fusion

  10. Adjoint affine fusion and tadpoles (United States)

    Urichuk, Andrew; Walton, Mark A.


    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-polytope interpretation follows and allows the straightforward calculation of the genus-1 1-point adjoint Verlinde dimension, the adjoint affine fusion tadpole. Explicit formulas, (piecewise) polynomial in the level, are written for the adjoint tadpoles of all classical Lie algebras. We show that off-diagonal adjoint affine fusion is obtained from the corresponding tensor product by simply dropping non-dominant representations.

  11. Structure information from fusion barriers

    Indian Academy of Sciences (India)

    S V S Sastry; S Santra


    It is shown that the analysis of fusion barrier distributions is not always an unambiguous test or a ‘fingerprint’ of the structure information of the colliding nuclei. Examples are presented with same fusion barrier distributions for nuclei having different structures. The fusion excitation functions for 16O+208Pb, using the coupled reaction channel (CRC) method and correct structure information, have been analysed. The barrier distributions derived from these excitation functions including many of the significant channels are featureless, although these channels have considerable effects on the fusion excitation function. However, a simultaneous analysis of the fusion, elastic and quasi-elastic channels would fix the structure and the reaction unambiguously

  12. Fusion characterization of biomass ash

    DEFF Research Database (Denmark)

    Ma, Teng; Fan, Chuigang; Hao, Lifang;


    The ash fusion characteristics are important parameters for thermochemical utilization of biomass. In this research, a method for measuring the fusion characteristics of biomass ash by Thermo-mechanical Analyzer, TMA, is described. The typical TMA shrinking ratio curve can be divided into two...... stages, which are closely related to ash melting behaviors. Several characteristics temperatures based on the TMA curves are used to assess the ash fusion characteristics. A new characteristics temperature, Tm, is proposed to represent the severe melting temperature of biomass ash. The fusion...... characteristics of six types of biomass ash have been measured by TMA. Compared with standard ash fusibility temperatures (AFT) test, TMA is more suitable for measuring the fusion characteristics of biomass ash. The glassy molten areas of the ash samples are sticky and mainly consist of K-Ca-silicates....

  13. Adjoint affine fusion and tadpoles

    CERN Document Server

    Urichuk, Andrew


    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-polytope interpretation follows, and allows the straightforward calculation of the genus-1 1-point adjoint Verlinde dimension, the adjoint affine fusion tadpole. Explicit formulas, (piecewise) polynomial in the level, are written for the adjoint tadpoles of all classical Lie algebras. We show that off-diagonal adjoint affine fusion is obtained from the corresponding tensor product by simply dropping non-dominant representations.

  14. Fusion - 2050 perspective (in Polish)

    CERN Document Server

    Romaniuk, R S


    The results of strongly exothermic reaction of thermonuclear fusion between nuclei of deuterium and tritium are: helium nuclei and neutrons, plus considerable kinetic energy of neutrons of over 14 MeV. DT nuclides synthesis reaction is probably not the most favorable one for energy production, but is the most advanced technologically. More efficient would be possibly aneutronic fusion. The EU by its EURATOM agenda prepared a Road Map for research and implementation of Fusion as a commercial method of thermonuclear energy generation in the time horizon of 2050.The milestones on this road are tokomak experiments JET, ITER and DEMO, and neutron experiment IFMIF. There is a hope, that by engagement of the national government, and all research and technical fusion communities, part of this Road Map may be realized in Poland. The infrastructure build for fusion experiments may be also used for material engineering research, chemistry, biomedical, associated with environment protection, power engineering, security, ...

  15. Application of optical tweezers and excimer laser to study protoplast fusion (United States)

    Kantawang, Titirat; Samipak, Sompid; Limtrakul, Jumras; Chattham, Nattaporn


    Protoplast fusion is a physical phenomenon that two protoplasts come in contact and fuse together. Doing so, it is possible to combine specific genes from one protoplast to another during fusion such as drought resistance and disease resistance. There are a few possible methods to induce protoplast fusion, for example, electrofusion and chemical fusion. In this study, chemical fusion was performed with laser applied as an external force to enhance rate of fusion and observed under a microscope. Optical tweezers (1064 nm with 100X objective N.A. 1.3) and excimer laser (308 nm LMU-40X-UVB objective) were set with a Nikon Ti-U inverted microscope. Samples were prepared by soaking in hypertonic solution in order to induce cell plasmolysis. Elodea Canadensis and Allium cepa plasmolysed leaves were cut and observed under microscope. Concentration of solution was varied to induce difference turgor pressures on protoplasts pushing at cell wall. Free protoplasts in solution were trapped by optical tweezers to study the effect of Polyethylene glycol (PEG) solution. PEG was diluted by Ca+ solution during the process to induced protoplast cell contact and fusion. Possibility of protoplast fusion by excimer laser was investigated and found possible. Here we report a novel tool for plant cell fusion using excimer laser. Plant growth after cell fusion is currently conducted.

  16. Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit. (United States)

    Wada, Ken-Ichi; Hosokawa, Kazuo; Ito, Yoshihiro; Maeda, Mizuo


    We previously reported a direct cytoplasmic transfer method using a microfluidic device, in which cell fusion was induced through a microslit (slit-through-fusion) by the Sendai virus envelope (HVJ-E) to prevent nuclear mixing. However, the method was impractical due to low efficiency of slit-through-fusion formation and insufficient prevention of nuclear mixing. The purpose of this study was to establish an efficient method for inducing slit-through-fusion without nuclear mixing. We hypothesized that modulation of cytoskeletal component can decrease nuclear migration through the microslit considering its functions. Here we report that supplementation with Y-27632, a specific ROCK inhibitor, significantly enhances cell fusion induction and prevention of nuclear mixing. Supplementation with Y-27632 increased the formation of slit-through-fusion efficiency by more than twofold. Disruption of F-actin by Y-27632 prevented nuclear migration between fused cells through the microslit. These two effects of Y-27632 led to promotion of the slit-through-fusion without nuclear mixing with a 16.5-fold higher frequency compared to our previous method (i.e., cell fusion induction by HVJ-E without supplementation with Y-27632). We also confirmed that mitochondria were successfully transferred to the fusion partner under conditions of Y-27632 supplementation. These findings demonstrate the practicality of our cell fusion system in producing direct cytoplasmic transfer between live cells.

  17. Fusion Guidance in Endovascular Peripheral Artery Interventions: A Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Sailer, Anna M., E-mail:; Haan, Michiel W. de, E-mail:; Graaf, Rick de, E-mail:; Zwam, Willem H. van, E-mail: [Maastricht University Medical Center, Department of Radiology (Netherlands); Schurink, Geert Willem H., E-mail: [Maastricht University Medical Center, Department of Surgery (Netherlands); Nelemans, Patricia J., E-mail: [Maastricht University Medical Centre, Department of Epidemiology (Netherlands); Wildberger, Joachim E., E-mail:; Das, Marco, E-mail: [Maastricht University Medical Center, Department of Radiology (Netherlands)


    PurposeThis study was designed to evaluate the feasibility of endovascular guidance by means of live fluoroscopy fusion with magnetic resonance angiography (MRA) and computed tomography angiography (CTA).MethodsFusion guidance was evaluated in 20 endovascular peripheral artery interventions in 17 patients. Fifteen patients had received preinterventional diagnostic MRA and two patients had undergone CTA. Time for fluoroscopy with MRA/CTA coregistration was recorded. Feasibility of fusion guidance was evaluated according to the following criteria: for every procedure the executing interventional radiologists recorded whether 3D road-mapping provided added value (yes vs. no) and whether PTA and/or stenting could be performed relying on the fusion road-map without need for diagnostic contrast-enhanced angiogram series (CEAS) (yes vs. no). Precision of the fusion road-map was evaluated by recording maximum differences between the position of the vasculature on the virtual CTA/MRA images and conventional angiography.ResultsAverage time needed for image coregistration was 5 ± 2 min. Three-dimensional road-map added value was experienced in 15 procedures in 12 patients. In half of the patients (8/17), intervention was performed relying on the fusion road-map only, without diagnostic CEAS. In two patients, MRA roadmap showed a false-positive lesion. Excluding three patients with inordinate movements, mean difference in position of vasculature on angiography and MRA/CTA road-map was 1.86 ± 0.95 mm, implying that approximately 95 % of differences were between 0 and 3.72 mm (2 ± 1.96 standard deviation).ConclusionsFluoroscopy with MRA/CTA fusion guidance for peripheral artery interventions is feasible. By reducing the number of CEAS, this technology may contribute to enhance procedural safety.

  18. Information integration for data fusion

    Energy Technology Data Exchange (ETDEWEB)

    Bray, O.H.


    Data fusion has been identified by the Department of Defense as a critical technology for the U.S. defense industry. Data fusion requires combining expertise in two areas - sensors and information integration. Although data fusion is a rapidly growing area, there is little synergy and use of common, reusable, and/or tailorable objects and models, especially across different disciplines. The Laboratory-Directed Research and Development project had two purposes: to see if a natural language-based information modeling methodology could be used for data fusion problems, and if so, to determine whether this methodology would help identify commonalities across areas and achieve greater synergy. The project confirmed both of the initial hypotheses: that the natural language-based information modeling methodology could be used effectively in data fusion areas and that commonalities could be found that would allow synergy across various data fusion areas. The project found five common objects that are the basis for all of the data fusion areas examined: targets, behaviors, environments, signatures, and sensors. Many of the objects and the specific facts related to these objects were common across several areas and could easily be reused. In some cases, even the terminology remained the same. In other cases, different areas had their own terminology, but the concepts were the same. This commonality is important with the growing use of multisensor data fusion. Data fusion is much more difficult if each type of sensor uses its own objects and models rather than building on a common set. This report introduces data fusion, discusses how the synergy generated by this LDRD would have benefited an earlier successful project and contains a summary information model from that project, describes a preliminary management information model, and explains how information integration can facilitate cross-treaty synergy for various arms control treaties.

  19. Regulation of HSV glycoprotein induced cascade of events governing cell-cell fusion. (United States)

    Atanasiu, Doina; Saw, Wan Ting; Eisenberg, Roselyn J; Cohen, Gary H


    Receptor dependent HSV-induced fusion requires glycoproteins gD, gH/gL, and gB. Our current model posits that during fusion receptor-activated conformational changes in gD activate gH/gL, which subsequently triggers transformation of the pre-fusion form of gB into a fusogenic state. To examine the role of each glycoprotein in receptor dependent cell-cell fusion we took advantage of our discovery that fusion by wild type HSV-2 glycoproteins occurs twice as fast as that achieved by HSV-1 glycoproteins. By sequentially swapping each glycoprotein between the two serotypes, we established that fusion speed was governed by gH/gL, with gH being the main contributor. While the mutant forms of gB fuse at distinct rates that are dictated by their molecular structure, these restrictions can be overcome by gH2/gL2, thereby enhancing their activity. We also found that deregulated forms of gD1 and gH2/gL2 can alter the fusogenic potential of gB, promoting cell fusion in the absence of a cellular receptor and that deregulated forms of gB can drive the fusion machinery to even higher levels. Low pH enhanced fusion by affecting the structure of both gB and gH/gL mutants. Together, our data highlight the complexity of the fusion machinery, the impact of the activation state of each glycoprotein on the fusion process and the critical role of gH/gL in regulating HSV induced fusion.

  20. Fusion of colour and monochromatic images with edge emphasis

    Directory of Open Access Journals (Sweden)

    Rade M. Pavlović


    Full Text Available We propose a novel method to fuse true colour images with monochromatic non-visible range images that seeks to encode important structural information from monochromatic images efficiently but also preserve the natural appearance of the available true chromacity information. We utilise the β colour opponency channel of the lαβ colour as the domain to fuse information from the monochromatic input into the colour input by the way of robust grayscale fusion. This is followed by an effective gradient structure visualisation step that enhances the visibility of monochromatic information in the final colour fused image. Images fused using this method preserve their natural appearance and chromacity better than conventional methods while at the same time clearly encode structural information from the monochormatic input. This is demonstrated on a number of well-known true colour fusion examples and confirmed by the results of subjective trials on the data from several colour fusion scenarios. Introduction The goal of image fusion can be broadly defined as: the representation of visual information contained in a number of input images into a single fused image without distortion or loss of information. In practice, however, a representation of all available information from multiple inputs in a single image is almost impossible and fusion is generally a data reduction task.  One of the sensors usually provides a true colour image that by definition has all of its data dimensions already populated by the spatial and chromatic information. Fusing such images with information from monochromatic inputs in a conventional manner can severely affect natural appearance of the fused image. This is a difficult problem and partly the reason why colour fusion received only a fraction of the attention than better behaved grayscale fusion even long after colour sensors became widespread. Fusion method Humans tend to see colours as contrasts between opponent

  1. Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention

    Directory of Open Access Journals (Sweden)

    Min Woo Lee


    Full Text Available

    With the technical development of ultrasonography (US, electromagnetic tracking-based fusion imaging of real-time US and computed tomography/magnetic resonance (CT/MR images has been used for percutaneous hepatic intervention such as biopsy and radiofrequency ablation (RFA. Because of the fusion imaging technique, the fused CT or MR images show the same plane and move synchronously while performing real-time US. With this information, fusion imaging can enhance lesion detectability and reduce the false positive detection of focal hepatic lesions with poor sonographic conspicuity. Three-dimensional US can also be fused with realtime US for the percutaneous RFA of liver tumors requiring overlapping ablation. When fusion imaging is not sufficient for identifying small focal hepatic lesions, contrast-enhanced US can be added to fusion imaging.

  2. Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Min Woo [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    With the technical development of ultrasonography (US), electromagnetic tracking-based fusion imaging of real-time US and computed tomography/magnetic resonance (CT/MR) images has been used for percutaneous hepatic intervention such as biopsy and radiofrequency ablation (RFA). Because of the fusion imaging technique, the fused CT or MR images show the same plane and move synchronously while performing real-time US. With this information, fusion imaging can enhance lesion detectability and reduce the false positive detection of focal hepatic lesions with poor sonographic conspicuity. Three-dimensional US can also be fused with realtime US for the percutaneous RFA of liver tumors requiring overlapping ablation. When fusion imaging is not sufficient for identifying small focal hepatic lesions, contrast-enhanced US can be added to fusion imaging.

  3. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma (United States)

    Parker, Brittany C.; Annala, Matti J.; Cogdell, David E.; Granberg, Kirsi J.; Sun, Yan; Ji, Ping; Li, Xia; Gumin, Joy; Zheng, Hong; Hu, Limei; Yli-Harja, Olli; Haapasalo, Hannu; Visakorpi, Tapio; Liu, Xiuping; Liu, Chang-gong; Sawaya, Raymond; Fuller, Gregory N.; Chen, Kexin; Lang, Frederick F.; Nykter, Matti; Zhang, Wei


    Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3′–untranslated region (3′-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3′-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma. PMID:23298836

  4. Prospects for bubble fusion

    Energy Technology Data Exchange (ETDEWEB)

    Nigmatulin, R.I. [Tyumen Institute of Mechanics of Multiphase Systems (TIMMS), Marx (Russian Federation); Lahey, R.T. Jr. [Rensselaer Polytechnic Institute, Troy, NY (United States)


    In this paper a new method for the realization of fusion energy is presented. This method is based on the superhigh compression of a gas bubble (deuterium or deuterium/thritium) in heavy water or another liquid. The superhigh compression of a gas bubble in a liquid is achieved through forced non-linear, non-periodic resonance oscillations using moderate amplitudes of forcing pressure. The key feature of this new method is a coordination of the forced liquid pressure change with the change of bubble volume. The corresponding regime of the bubble oscillation has been called {open_quotes}basketball dribbling (BD) regime{close_quotes}. The analytical solution describing this process for spherically symmetric bubble oscillations, neglecting dissipation and compressibility of the liquid, has been obtained. This solution shown no limitation on the supercompression of the bubble and the corresponding maximum temperature. The various dissipation mechanisms, including viscous, conductive and radiation heat losses have been considered. It is shown that in spite of these losses it is possible to achieve very high gas bubble temperatures. This because the time duration of the gas bubble supercompression becomes very short when increasing the intensity of compression, thus limiting the energy losses. Significantly, the calculated maximum gas temperatures have shown that nuclear fusion may be possible. First estimations of the affect of liquid compressibility have been made to determine possible limitations on gas bubble compression. The next step will be to investigate the role of interfacial instability and breaking down of the bubble, shock wave phenomena around and in the bubble and mutual diffusion of the gas and the liquid.

  5. Circumferential fusion improves outcome in comparison with instrumented posterolateral fusion

    DEFF Research Database (Denmark)

    Videbaek, Tina S; Christensen, Finn B; Soegaard, Rikke;


    with respect to all four DPQ categories: daily activities, work/leisure, anxiety/depression, and social interest. The Oswestry Disability Index supported these results (P physical health (P ...STUDY DESIGN: Prospective randomized clinical study with a 5- to 9-year follow-up period. OBJECTIVE: The aim of the present study was to analyze the long-term outcome with respect to functional disability, pain, and general health of patients treated by means of circumferential lumbar fusion...... fusion (titanium Cotrel-Dubousset) or circumferential lumbar fusion (instrumented posterolateral fusion with anterior intervertebral support by a Brantigan cage). The primary outcome measure was the Dallas Pain Questionnaire (DPQ). The secondary outcome measures were the Oswestry Disability Index, the SF...

  6. Fusion Rings for Quantum Groups

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Stroppel, Catharina


    We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from [12] and give a similar description of the sp2n-fusion ring in terms of noncommutative symmetric...... functions. Moreover we give a presentation of all fusion rings in classical types as quotients of polynomial rings. Finally we also compute the fu- sion rings for type G2....

  7. Controlled fusion and plasma physics

    Energy Technology Data Exchange (ETDEWEB)



    This document presents the several speeches that took place during the 22nd European Physical Society conference on Controlled Fusion and Plasma Physics in Bournemouth, UK, between the 2nd and 7th July 1995. The talks deal with new experiments carried out on several tokamaks, particularly Tore Supra, concerning plasma confinement and fusion. Some information on specific fusion devices or tokamak devices is provided, as well as results of experiments concerning plasma instability. Separate abstracts were prepared for all the 31 papers in this volume. (TEC).

  8. Effect of aniseikonia on fusion. (United States)

    Sharma, P; Prakash, P


    Physiological aniseikonia is the basis of stereopsis but beyond certain limits it becomes an obstacle to fusion. It is not well established as to how much aniseikonia can be tolerated by the fusional mechanism. Different tests under different testing conditions have given a wide range of variation. On the synoptophore we had observed tolerance upto 35% aniseikonia in some cases. Under more physiological conditions on a polaroid dissociation stereoprojector we observed lesser baseline fusional vergences but tolerance in about 70% of the cases upto 30% aniseikonia while 25% could tolerate even 35% aniseikonia. However we realise that these indicate the maximal potential and not the symptom free tolerable limits.

  9. Effect of aniseikonia on fusion

    Directory of Open Access Journals (Sweden)

    Sharma Pradeep


    Full Text Available Physiological aniseikonia is the basis of stereopsis but beyond certain limits it becomes an obstacle to fusion. It is not well established as to how much aniseikonia can be tolerated by the fusional mechanism. Different tests under different testing conditions have given a wide range of variation. On the synoptophore we had observed tolerance upto 35% aniseikonia in some cases. Under more physiological conditions on a polaroid dissociation stereoprojector we observed lesser baseline fusional vergences but tolerance in about 70% of the cases upto 30% aniseikonia while 25% could tolerate even 35% aniseikonia. However we realise that these indicate the maximal potential and not the symptom free tolerable limits.

  10. Advanced fusion concepts: project summaries

    Energy Technology Data Exchange (ETDEWEB)



    This report contains descriptions of the activities of all the projects supported by the Advanced Fusion Concepts Branch of the Office of Fusion Energy, US Department of Energy. These descriptions are project summaries of each of the individual projects, and contain the following: title, principle investigators, funding levels, purpose, approach, progress, plans, milestones, graduate students, graduates, other professional staff, and recent publications. Information is given for each of the following programs: (1) reverse-field pinch, (2) compact toroid, (3) alternate fuel/multipoles, (4) stellarator/torsatron, (5) linear magnetic fusion, (6) liners, and (7) Tormac. (MOW)

  11. Cold nuclear fusion reactor and nuclear fusion rocket

    Directory of Open Access Journals (Sweden)

    Huang Zhenqiang


    Full Text Available "Nuclear restraint inertial guidance directly hit the cold nuclear fusion reactor and ion speed dc transformer" [1], referred to as "cold fusion reactor" invention patents, Chinese Patent Application No. CN: 200910129632.7 [2]. The invention is characterized in that: at room temperature under vacuum conditions, specific combinations of the installation space of the electromagnetic field, based on light nuclei intrinsic magnetic moment and the electric field, the first two strings of the nuclei to be bound fusion on the same line (track of. Re-use nuclear spin angular momentum vector inherent nearly the speed of light to form a super strong spin rotation gyro inertial guidance features, to overcome the Coulomb repulsion strong bias barrier to achieve fusion directly hit. Similar constraints apply nuclear inertial guidance mode for different speeds and energy ion beam mixing speed, the design of ion speed dc transformer is cold fusion reactors, nuclear fusion engines and such nuclear power plants and power delivery systems start important supporting equipment, so apply for a patent merger

  12. Data Fusion Concepts and Ideas

    CERN Document Server

    Mitchell, H B


    “Data Fusion: Concepts and Ideas” provides a comprehensive introduction to the concepts and idea of multisensor data fusion. This textbook is an extensively revised second edition of the author's successful book: "Multi-Sensor Data Fusion: An Introduction". The book is self-contained and no previous knowledge of multi-sensor data fusion is assumed. The reader is made familiar with tools taken from a wide range of diverse subjects including: neural networks, signal processing, statistical estimation, tracking algorithms, computer vision and control theory which are combined by using a common statistical framework. As a consequence, the underlying pattern of relationships that exists between the different methodologies is made evident. The book is illustrated with many real-life examples taken from a diverse range of applications and contains an extensive list of modern references. The new completely revised and updated edition includes nearly 70 pages of new material including a full new chapter as well as...

  13. Aneutronic Fusion Spacecraft Architecture Project (United States)

    National Aeronautics and Space Administration — Description: provide framework to realize fusion propulsion for long-range space travel; analyze “hybrid” schemes with a solar or fission primary energy...

  14. Pulsed Power Driven Fusion Energy

    Energy Technology Data Exchange (ETDEWEB)



    Pulsed power is a robust and inexpensive technology for obtaining high powers. Considerable progress has been made on developing light ion beams as a means of transporting this power to inertial fusion capsules. However, further progress is hampered by the lack of an adequate ion source. Alternatively, z-pinches can efficiently convert pulsed power into thermal radiation, which can be used to drive an inertial fusion capsule. However, a z-pinch driven fusion explosion will destroy a portion of the transmission line that delivers the electrical power to the z-pinch. They investigate several options for providing standoff for z-pinch driven fusion. Recyclable Transmission Lines (RTLs) appear to be the most promising approach.

  15. New trends in fusion research

    CERN Document Server

    CERN. Geneva


    The efforts of the international fusion community aim at demonstrating the scientific feasibility of thermonuclear fusion energy power plants. Understanding the behavior of burning plasmas, i.e. plasmas with strong self-heating, represents a primary scientific challenge for fusion research and a new science frontier. Although integrated studies will only be possible, in new, dedicated experimental facilities, such as the International Tokamak Experimental Reactor (ITER), present devices can address specific issues in regimes relevant to burning plasmas. Among these are an improvement of plasma performance via a reduction of the energy and particle transport, an optimization of the path to ignition or to sustained burn using additional heating and a control of plasma-wall interaction and energy and particle exhaust. These lectures address recent advances in plasma science and technology that are relevant to the development of fusion energy. Mention will be made of the inertial confinement line of research, but...

  16. [On Atomic Nuclear Fusion Processes at Low-Temperatures. An Enhancement of the Probability of Transition through a Potential Barrier Due to the So-Called Barrier Anti-Zeno Effect]. (United States)

    Namiot, V A


    It is known that in quantum mechanics the act of observing the experiment can affect the experimental findings in some cases. In particular, it happens under the so-called Zeno effect. In this work it is shown that in contrast to the "standard" Zeno-effect where the act of observing a process reduces the probability of its reality, an inverse situation when a particle transmits through a potential barrier (a so-called barrier anti-Zeno effect) can be observed, the observation of the particle essentially increases the probability of its transmission through the barrier. The possibility of using the barrier anti-Zeno effect is discussed to explain paradoxical results of experiments on "cold nuclear fusion" observed in various systems including biological ones. (According to the observers who performed the observations, the energy generation, which could not be explained by any chemical processes, as well as the change in the isotope and even element composition of the studied object may occur in these systems.

  17. A preliminary study of a D-T tokamak fusion reactor with advanced blanket using compact fusion advanced Brayton (CFAB) cycle

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, K.; Ohnishi, M.; Yamamoto, Y. [Kyoto Univ. (Japan)] [and others


    Key issues on a D-T Tokamak fusion reactor with advanced blanket concept using CFAB (Compact Fusion Advanced Brayton) cycle are presented. Although the previously proposed and studied compact fusion advanced Rankine cycle using mercury liquid metal has shown, in general, excellent performance characteristics in extracting energy and electricity with high efficiency by the {open_quotes}in-situ{close_quotes} nonequilibrium MHD disk generator, and in enhancing safety potential, there was a fear about uses of hazardous mercury as primary coolant as well as its limited natural resources. To overcome these disadvantages while retaining the advantage features of a ultra-high temperature coolant inherent in the synchrotron energy-enhanced D-T tokamak reactor, a compact fusion advanced Brayton cycle using helium was reexamined which was once considered relatively not superior in the CFAR study, at the expense of high, but acceptable circulation power, lower heat transfer characteristics, and probably of a little bit reduced safety.

  18. Decision-fusion-based automated drill bit toolmark correlator (United States)

    Jones, Brett C.; Press, Michael J.; Guerci, Joseph R.


    This paper describes a recent study conducted to investigate the reproducibility of toolmarks left by drill bits. This paper focuses on the automated analysis aspect of the study, and particularly the advantages of using decision fusion methods in the comparisons. To enable the study to encompass a large number of samples, existing technology was adapted to the task of automatically comparing the test impressions. Advanced forensic pattern recognition algorithms that had been developed for the comparison of ballistic evidence in the DRUGFIRETM system were modified for use in this test. The results of the decision fusion architecture closely matched those obtained by expert visual examination. The study, aided by the improved pattern recognition algorithm, showed that drill bit impressions do contain reproducible marks. In a blind test, the DRUGFIRE pattern recognition algorithm, enhanced with the decision fusion architecture, consistently identified the correct bit as the source of the test impressions.

  19. Multimodality Image Fusion-Guided Procedures: Technique, Accuracy, and Applications

    Energy Technology Data Exchange (ETDEWEB)

    Abi-Jaoudeh, Nadine, E-mail: [National Institutes of Health, Radiology and Imaging Sciences (United States); Kruecker, Jochen, E-mail: [Philips Research North America (United States); Kadoury, Samuel, E-mail: [Ecole Polytechnique de Montreal, Department of Computer and Software Engineering, Institute of Biomedical Engineering (Canada); Kobeiter, Hicham, E-mail: [CHU Henri Mondor, UPEC, Departments of Radiology and d' imagrie medicale (France); Venkatesan, Aradhana M., E-mail:; Levy, Elliot, E-mail:; Wood, Bradford J., E-mail: [National Institutes of Health, Radiology and Imaging Sciences (United States)


    Personalized therapies play an increasingly critical role in cancer care: Image guidance with multimodality image fusion facilitates the targeting of specific tissue for tissue characterization and plays a role in drug discovery and optimization of tailored therapies. Positron-emission tomography (PET), magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CT) may offer additional information not otherwise available to the operator during minimally invasive image-guided procedures, such as biopsy and ablation. With use of multimodality image fusion for image-guided interventions, navigation with advanced modalities does not require the physical presence of the PET, MRI, or CT imaging system. Several commercially available methods of image-fusion and device navigation are reviewed along with an explanation of common tracking hardware and software. An overview of current clinical applications for multimodality navigation is provided.

  20. Multispectral medical image fusion in Contourlet domain for computer based diagnosis of Alzheimer's disease (United States)

    Bhateja, Vikrant; Moin, Aisha; Srivastava, Anuja; Bao, Le Nguyen; Lay-Ekuakille, Aimé; Le, Dac-Nhuong


    Computer based diagnosis of Alzheimer's disease can be performed by dint of the analysis of the functional and structural changes in the brain. Multispectral image fusion deliberates upon fusion of the complementary information while discarding the surplus information to achieve a solitary image which encloses both spatial and spectral details. This paper presents a Non-Sub-sampled Contourlet Transform (NSCT) based multispectral image fusion model for computer-aided diagnosis of Alzheimer's disease. The proposed fusion methodology involves color transformation of the input multispectral image. The multispectral image in YIQ color space is decomposed using NSCT followed by dimensionality reduction using modified Principal Component Analysis algorithm on the low frequency coefficients. Further, the high frequency coefficients are enhanced using non-linear enhancement function. Two different fusion rules are then applied to the low-pass and high-pass sub-bands: Phase congruency is applied to low frequency coefficients and a combination of directive contrast and normalized Shannon entropy is applied to high frequency coefficients. The superiority of the fusion response is depicted by the comparisons made with the other state-of-the-art fusion approaches (in terms of various fusion metrics).

  1. Magnetic fusion 1985: what next

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, T.K.


    Recent budget reductions for magnetic fusion have led to a re-examination of program schedules and objectives. Faced with delays and postponement of major facilities as previously planned, some have called for a near-term focus on science, others have stressed technology. This talk will suggest a different focus as the keynote for this conference, namely, the applications of fusion. There is no doubt that plasma science is by now mature and fusion technology is at the forefront. This has and will continue to benefit many fields of endeavor, both in actual new discoveries and techniques and in attracting and training scientists and engineers who move on to make significant contributions in science, defense and industry. Nonetheless, however superb the science or how challenging the technology, these are means, not ends. To maintain its support, the magnetic fusion program must also offer the promise of power reactors that could be competitive in the future. At this conference, several new reactor designs will be described that claim to be smaller and economically competitive with fission reactors while retaining the environmental and safety characteristics that are the hallmark of fusion. The American Nuclear Society is an appropriate forum in which to examine these new designs critically, and to stimulate better ideas and improvements. As a preview, this talk will include brief discussions of new tokamak, tandem mirror and reversed field pinch reactor designs to be presented in later sessions. Finally, as a preview of the session on fusion breeders, the talk will explore once again the economic implications of a new nuclear age, beginning with improved fission reactors fueled by fusion breeders, then ultimately evolving to reactors based solely on fusion.

  2. Data Fusion and Sensors Model

    Institute of Scientific and Technical Information of China (English)


    In this paper, we take the model of Laser range finder based on synchronized scanner as example, show how to use data fusion method in the process of sensor model designing to get more robust output. Also we provide our idea on the relation of sensor model, data fusion and system structure, and in the paper, there is a solution that transform the parameter space to get linear model for Kalman filter.

  3. Getting started with Clickteam Fusion

    CERN Document Server

    Brunner, Jürgen


    An easy-to-understand, step-by-step guide that shows you how to create 2D video games with Clickteam Fusion. You will learn the magic of game development from scratch without any knowledge of scripting languages.This book is for game enthusiasts who want to create their own 2D video games. No prior knowledge of programming or Multimedia Fusion 2 is necessary.

  4. Effect of aniseikonia on fusion


    Sharma Pradeep; Prakash Prem


    Physiological aniseikonia is the basis of stereopsis but beyond certain limits it becomes an obstacle to fusion. It is not well established as to how much aniseikonia can be tolerated by the fusional mechanism. Different tests under different testing conditions have given a wide range of variation. On the synoptophore we had observed tolerance upto 35% aniseikonia in some cases. Under more physiological conditions on a polaroid dissociation stereoprojector we observed lesser baseline f...

  5. Hydrogen Production in Fusion Reactors


    Sudo, S.; Tomita, Y.; Yamaguchi, S.; Iiyoshi, A.; Momota, H; Motojima, O.; Okamoto, M.; Ohnishi, M.; Onozuka, M; Uenosono, C.


    As one of methods of innovative energy production in fusion reactors without having a conventional turbine-type generator, an efficient use of radiation produced in a fusion reactor with utilizing semiconductor and supplying clean fuel in a form of hydrogen gas are studied. Taking the candidates of reactors such as a toroidal system and an open system for application of the new concepts, the expected efficiency and a concept of plant system are investigated.

  6. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)


    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  7. Data Fusion in Information Retrieval

    CERN Document Server

    Wu, Shengli


    The technique of data fusion has been used extensively in information retrieval due to the complexity and diversity of tasks involved such as web and social networks, legal, enterprise, and many others. This book presents both a theoretical and empirical approach to data fusion. Several typical data fusion algorithms are discussed, analyzed and evaluated. A reader will find answers to the following questions, among others: -          What are the key factors that affect the performance of data fusion algorithms significantly? -          What conditions are favorable to data fusion algorithms? -          CombSum and CombMNZ, which one is better? and why? -          What is the rationale of using the linear combination method? -          How can the best fusion option be found under any given circumstances?


    Energy Technology Data Exchange (ETDEWEB)

    Klein, J. E.; Farmer, D. A.; Moore, M. L.; Tovo, L. L.; Poore, A. S.; Clark, E. A.; Harvel, C. D.


    The US Department of Energy (DOE) has clearly defined requirements for nuclear material control and accountability (MC&A) of tritium whereas the International Atomic Energy Agency (IAEA) does not since tritium is not a fissile material. MC&A requirements are expected for tritium fusion machines and will be dictated by the host country or regulatory body where the machine is operated. Material Balance Areas (MBAs) are defined to aid in the tracking and reporting of nuclear material movements and inventories. Material subaccounts (MSAs) are established along with key measurement points (KMPs) to further subdivide a MBA to localize and minimize uncertainties in the inventory difference (ID) calculations for tritium accountancy. Fusion systems try to minimize tritium inventory which may require continuous movement of material through the MSAs. The ability of making meaningful measurements of these material transfers is described in terms of establishing the MSA structure to perform and reconcile ID calculations. For fusion machines, changes to the traditional ID equation will be discussed which includes breading, burn-up, and retention of tritium in the fusion device. The concept of “net” tritium quantities consumed or lost in fusion devices is described in terms of inventory taking strategies and how it is used to track the accumulation of tritium in components or fusion machines.

  9. Tritium accountancy in fusion systems

    Energy Technology Data Exchange (ETDEWEB)

    Klein, J.E.; Clark, E.A.; Harvel, C.D.; Farmer, D.A.; Tovo, L.L.; Poore, A.S. [Savannah River National Laboratory, Aiken, SC (United States); Moore, M.L. [Savannah River Nuclear Solutions, Aiken, SC (United States)


    The US Department of Energy (DOE) has clearly defined requirements for nuclear material control and accountability (MCA) of tritium whereas the International Atomic Energy Agency (IAEA) does not since tritium is not a fissile material. MCA requirements are expected for tritium fusion machines and will be dictated by the host country or regulatory body where the machine is operated. Material Balance Areas (MBA) are defined to aid in the tracking and reporting of nuclear material movements and inventories. Material sub-accounts (MSA) are established along with key measurement points (KMP) to further subdivide a MBA to localize and minimize uncertainties in the inventory difference (ID) calculations for tritium accountancy. Fusion systems try to minimize tritium inventory which may require continuous movement of material through the MSA. The ability of making meaningful measurements of these material transfers is described in terms of establishing the MSA structure to perform and reconcile ID calculations. For fusion machines, changes to the traditional ID equation will be discussed which includes breeding, burn-up, and retention of tritium in the fusion device. The concept of 'net' tritium quantities consumed or lost in fusion devices is described in terms of inventory taking strategies and how it is used to track the accumulation of tritium in components or fusion machines. (authors)

  10. Information fusion measures of effectiveness (MOE) for decision support (United States)

    Blasch, Erik P.; Breton, Richard; Valin, Pierre


    For decades, there have been discussions on measures of merits (MOM) that include measures of effectiveness (MOE) and measures of performance (MOP) for system-level performance. As the amount of sensed and collected data becomes increasingly large, there is a need to look at the architectures, metrics, and processes that provide the best methods for decision support systems. In this paper, we overview some information fusion methods in decision support and address the capability to measure the effects of the fusion products on user functions. The current standard Information Fusion model is the Data Fusion Information Group (DFIG) model that specifically addresses the needs of the user in an information fusion system. Decision support implies that information methods augment user decision making as opposed to the machine making the decision and displaying it to user. We develop a list of suggested measures of merits that facilitate decision support decision support Measures of Effectiveness (MOE) metrics of quality, information gain, and robustness, from the analysis based on the measures of performance (MOPs) of timeliness, accuracy, confidence, throughput, and cost. We demonstrate in an example with motion imagery to support the MOEs of quality (time/decision confidence plots), information gain (completeness of annotated imagery for situation awareness), and robustness through analysis of imagery over time and repeated looks for enhanced target identification confidence.

  11. Novel Hydrophobin Fusion Tags for Plant-Produced Fusion Proteins (United States)

    Ritala, Anneli; Linder, Markus; Joensuu, Jussi


    Hydrophobin fusion technology has been applied in the expression of several recombinant proteins in plants. Until now, the technology has relied exclusively on the Trichoderma reesei hydrophobin HFBI. We screened eight novel hydrophobin tags, T. reesei HFBII, HFBIII, HFBIV, HFBV, HFBVI and Fusarium verticillioides derived HYD3, HYD4 and HYD5, for production of fusion proteins in plants and purification by two-phase separation. To study the properties of the hydrophobins, we used N-terminal and C-terminal GFP as a fusion partner. Transient expression of the hydrophobin fusions in Nicotiana benthamiana revealed large variability in accumulation levels, which was also reflected in formation of protein bodies. In two-phase separations, only HFBII and HFBIV were able to concentrate GFP into the surfactant phase from a plant extract. The separation efficiency of both tags was comparable to HFBI. When the accumulation was tested side by side, HFBII-GFP gave a better yield than HFBI-GFP, while the yield of HFBIV-GFP remained lower. Thus we present here two alternatives for HFBI as functional fusion tags for plant-based protein production and first step purification. PMID:27706254

  12. Fusion Plasma Theory project summaries

    Energy Technology Data Exchange (ETDEWEB)


    This Project Summary book is a published compilation consisting of short descriptions of each project supported by the Fusion Plasma Theory and Computing Group of the Advanced Physics and Technology Division of the Department of Energy, Office of Fusion Energy. The summaries contained in this volume were written by the individual contractors with minimal editing by the Office of Fusion Energy. Previous summaries were published in February of 1982 and December of 1987. The Plasma Theory program is responsible for the development of concepts and models that describe and predict the behavior of a magnetically confined plasma. Emphasis is given to the modelling and understanding of the processes controlling transport of energy and particles in a toroidal plasma and supporting the design of the International Thermonuclear Experimental Reactor (ITER). A tokamak transport initiative was begun in 1989 to improve understanding of how energy and particles are lost from the plasma by mechanisms that transport them across field lines. The Plasma Theory program has actively-participated in this initiative. Recently, increased attention has been given to issues of importance to the proposed Tokamak Physics Experiment (TPX). Particular attention has been paid to containment and thermalization of fast alpha particles produced in a burning fusion plasma as well as control of sawteeth, current drive, impurity control, and design of improved auxiliary heating. In addition, general models of plasma behavior are developed from physics features common to different confinement geometries. This work uses both analytical and numerical techniques. The Fusion Theory program supports research projects at US government laboratories, universities and industrial contractors. Its support of theoretical work at universities contributes to the office of Fusion Energy mission of training scientific manpower for the US Fusion Energy Program.

  13. The elementary fusion modalities of osteoclasts

    DEFF Research Database (Denmark)

    Søe, Kent; Hobolt-Pedersen, Anne-Sofie; Delaisse, Jean-Marie


    , are not known for the osteoclast. Here we show that osteoclast fusion partners are characterized by differences in mobility, nuclearity, and differentiation level. Our demonstration was based on time-laps videos of human osteoclast preparations from three donors where 656 fusion events were analyzed. Fusions......The last step of the osteoclast differentiation process is cell fusion. Most efforts to understand the fusion mechanism have focused on the identification of molecules involved in the fusion process. Surprisingly, the basic fusion modalities, which are well known for fusion of other cell types...... between a mobile and an immobile partner were most frequent (62%), while fusion between two mobile (26%) or two immobile partners (12%) was less frequent (pfusion partner contained more nuclei than the mobile one (p

  14. Nuclear Fusion with Polarized Nucleons & PolFusion

    CERN Document Server

    Engels, Ralf; Büscher, Markus; Vasilyev, Alexander


    This book offers a detailed examination of the latest work on the potential of polarized fuel to realize the vision of energy production by nuclear fusion. It brings together contributions from nuclear physicists and fusion physicists with the aims of fostering exchange of information between the two communities, describing the current status in the field, and examining new ideas and projects under development. It is evident that polarized fuel can offer huge improvements for the first generation of fusion reactors and open new technological possibilities for future generations, including neutron lean reactors, which could be the most popular and sustainable energy production option to avoid environmental problems. Nevertheless, many questions must be resolved before polarized fuel can be used for energy production in the different reactor types. Readers will find this book to be a stimulating source of information on the key issues. It is based on contributions from leading scientists delivered at the meetin...

  15. Accelerators for Fusion Materials Testing (United States)

    Knaster, Juan; Okumura, Yoshikazu

    Fusion materials research is a worldwide endeavor as old as the parallel one working toward the long term stable confinement of ignited plasma. In a fusion reactor, the preservation of the required minimum thermomechanical properties of the in-vessel components exposed to the severe irradiation and heat flux conditions is an indispensable factor for safe operation; it is also an essential goal for the economic viability of fusion. Energy from fusion power will be extracted from the 14 MeV neutron freed as a product of the deuterium-tritium fusion reactions; thus, this kinetic energy must be absorbed and efficiently evacuated and electricity eventually generated by the conventional methods of a thermal power plant. Worldwide technological efforts to understand the degradation of materials exposed to 14 MeV neutron fluxes >1018 m-2s-1, as expected in future fusion power plants, have been intense over the last four decades. Existing neutron sources can reach suitable dpa (“displacement-per-atom”, the figure of merit to assess materials degradation from being exposed to neutron irradiation), but the differences in the neutron spectrum of fission reactors and spallation sources do not allow one to unravel the physics and to anticipate the degradation of materials exposed to fusion neutrons. Fusion irradiation conditions can be achieved through Li (d, xn) nuclear reactions with suitable deuteron beam current and energy, and an adequate flowing lithium screen. This idea triggered in the late 1970s at Los Alamos National Laboratory (LANL) a campaign working toward the feasibility of continuous wave (CW) high current linacs framed by the Fusion Materials Irradiation Test (FMIT) project. These efforts continued with the Low Energy Demonstrating Accelerator (LEDA) (a validating prototype of the canceled Accelerator Production of Tritium (APT) project), which was proposed in 2002 to the fusion community as a 6.7MeV, 100mA CW beam injector for a Li (d, xn) source to bridge

  16. A Model for Membrane Fusion (United States)

    Ngatchou, Annita


    Pheochromocytoma is a tumor of the adrenal gland which originates from chromaffin cells and is characterized by the secretion of excessive amounts of neurotransmitter which lead to high blood pressure and palpitations. Pheochromocytoma contain membrane bound granules that store neurotransmitter. The release of these stored molecules into the extracellular space occurs by fusion of the granule membrane with the cell plasma membrane, a process called exocytosis. The molecular mechanism of this membrane fusion is not well understood. It is proposed that the so called SNARE proteins [1] are the pillar of vesicle fusion as their cleavage by clostridial toxin notably, Botulinum neurotoxin and Tetanus toxin abrogate the secretion of neurotransmitter [2]. Here, I describe how physical principles are applied to a biological cell to explore the role of the vesicle SNARE protein synaptobrevin-2 in easing granule fusion. The data presented here suggest a paradigm according to which the movement of the C-terminal of synaptobrevin-2 disrupts the lipid bilayer to form a fusion pore through which molecules can exit.

  17. Linear Minimum variance estimation fusion

    Institute of Scientific and Technical Information of China (English)

    ZHU Yunmin; LI Xianrong; ZHAO Juan


    This paper shows that a general mulitisensor unbiased linearly weighted estimation fusion essentially is the linear minimum variance (LMV) estimation with linear equality constraint, and the general estimation fusion formula is developed by extending the Gauss-Markov estimation to the random paramem of distributed estimation fusion in the LMV setting.In this setting ,the fused estimator is a weighted sum of local estimatess with a matrix quadratic optimization problem subject to a convex linear equality constraint. Second, we present a unique solution to the above optimization problem, which depends only on the covariance matrixCK. Third, if a priori information, the expectation and covariance, of the estimated quantity is unknown, a necessary and sufficient condition for the above LMV fusion becoming the best unbiased LMV estimation with dnown prior information as the above is presented. We also discuss the generality and usefulness of the LMV fusion formulas developed. Finally, we provied and off-line recursion of Ck for a class of multisensor linear systems with coupled measurement noises.

  18. Geophysical data fusion for subsurface imaging (United States)

    Hoekstra, P.; Vandergraft, J.; Blohm, M.; Porter, D.


    A geophysical data fusion methodology is under development to combine data from complementary geophysical sensors and incorporate geophysical understanding to obtain three dimensional images of the subsurface. The research reported here is the first phase of a three phase project. The project focuses on the characterization of thin clay lenses (aquitards) in a highly stratified sand and clay coastal geology to depths of up to 300 feet. The sensor suite used in this work includes time-domain electromagnetic induction (TDEM) and near surface seismic techniques. During this first phase of the project, enhancements to the acquisition and processing of TDEM data were studied, by use of simulated data, to assess improvements for the detection of thin clay layers. Secondly, studies were made of the use of compressional wave and shear wave seismic reflection data by using state-of-the-art high frequency vibrator technology. Finally, a newly developed processing technique, called 'data fusion' was implemented to process the geophysical data, and to incorporate a mathematical model of the subsurface strata. Examples are given of the results when applied to real seismic data collected at Hanford, WA, and for simulated data based on the geology of the Savannah River Site.

  19. Overview of the Heavy Ion Fusion Program

    CERN Document Server

    Celata, C M


    The world Heavy Ion Fusion (HIF) Program for inertial fusion energy is looking toward the development and commissioning of several new experiments. Recent and planned upgrades of the facilities at GSI, in Russia, and in Japan greatly enhance the ability to study energy deposition in hot dense matter. Worldwide target design developments have focused on non-ignition targets for nearterm experiments and designs which, while lowering the energy required for ignition, tighten accelerator requirements. The U.S program is transitioning between scaled beam dynamics experiments and high current experiments with power-plant-driver-scale beams. Current effort is aimed at preparation for the next-step large facility, the Integrated Research Experiment (IRE)-- an induction linac accelerating multiple beams to a few hundred MeV, then focusing to deliver tens of kilojoules to a target. The goal is to study heavy ion energy deposition, and to test all of the components and physics needed for an engineering test of a power p...

  20. Nuclear Fusion prize laudation Nuclear Fusion prize laudation (United States)

    Burkart, W.


    Clean energy in abundance will be of critical importance to the pursuit of world peace and development. As part of the IAEA's activities to facilitate the dissemination of fusion related science and technology, the journal Nuclear Fusion is intended to contribute to the realization of such energy from fusion. In 2010, we celebrated the 50th anniversary of the IAEA journal. The excellence of research published in the journal is attested to by its high citation index. The IAEA recognizes excellence by means of an annual prize awarded to the authors of papers judged to have made the greatest impact. On the occasion of the 2010 IAEA Fusion Energy Conference in Daejeon, Republic of Korea at the welcome dinner hosted by the city of Daejeon, we celebrated the achievements of the 2009 and 2010 Nuclear Fusion prize winners. Steve Sabbagh, from the Department of Applied Physics and Applied Mathematics, Columbia University, New York is the winner of the 2009 award for his paper: 'Resistive wall stabilized operation in rotating high beta NSTX plasmas' [1]. This is a landmark paper which reports record parameters of beta in a large spherical torus plasma and presents a thorough investigation of the physics of resistive wall mode (RWM) instability. The paper makes a significant contribution to the critical topic of RWM stabilization. John Rice, from the Plasma Science and Fusion Center, MIT, Cambridge is the winner of the 2010 award for his paper: 'Inter-machine comparison of intrinsic toroidal rotation in tokamaks' [2]. The 2010 award is for a seminal paper that analyzes results across a range of machines in order to develop a universal scaling that can be used to predict intrinsic rotation. This paper has already triggered a wealth of experimental and theoretical work. I congratulate both authors and their colleagues on these exceptional papers. W. Burkart Deputy Director General Department of Nuclear Sciences and Applications International Atomic Energy Agency, Vienna

  1. 丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究%Experimental study on lumbar interbody fusion with silk fibroin enhanced calcium phosphate cement composite loaded with recombinant human bone morphogenetic protein-2 in sheep

    Institute of Scientific and Technical Information of China (English)

    陈亮; 顾勇; 陈晓庆; 干旻峰; 朱雪松; 杨惠林; 唐天驷


    Objective To evaluate the osteogenic characteristics of an injectable silk fibroin (SF) enhanced calcium phosphate cement (CPC) composite loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar interbody fusion in sheep. Methods Twenty-four mature sheep were randomly divided into two groups. Each sheep underwent L1.2, L3.4 and L5.6 lumber interbody fusion, and the three disc spaces were randomly implanted with three of the following materials: SF/CPC, CPC/rhBMP-2, SF/CPC/rhBMP2 and autogenous iliac crest bone. One group was killed at 6 months and the other at 12 months. The fusion segments were observed and analyzed by manual palpation, CT scan, undestructive biomechanical testing, undecalcified histology, and histomorphology. Results The fusion rates of SF/CPC, CPC/rhBMP-2, SF/CPC/rhBMP-2 and autogenous bone assessed by manual palpation were 0, 33.33%, 55.56% and 77.78% respectively at 6 months. At 12 months, the fusion rates improved to 11.11%, 44.44%, 77.78% and 77.78%, respectively.The biomechanical results showed that fusion stiffness was significantly greater in autograft compared with SF/CPC/rhBMP-2, CPC/rhBMP-2, and SF/CPC in 4 degrees of freedom (flexion, extension, right bending, and left bending) at 6 months. The SF/CPC/rhBMP-2 composite showed similar stiffness as autograft, which was significantly greater than CPC/rhBMP-2 and SF/CPC at 12 nonths. Both CPC/rhBMP-2 and SF/CPC/rhBMP-2 showed significantly greater stiffness at 12 months compared with that of at 6 months. The results showed that bone volume was significantly greater in autograft compared with SF/CPC/rhBMP-2, CPC/rhBMP-2, and SF/CPC at 6 months. There was significant difference among ceramic residue among SF/CPC, CPC/rhBMP-2 and SF/CPC/rhBMP-2, with SF/CPC the greatest and SF/CPC/thBMP-2 the least. At 12 months, the bone volume of SF/CPC/rhBMP-2 composite was comparable with autograft, and greater than that of CPC/rhBMP-2 and SF/CPC. The bone volume of SF/CPC, CPC

  2. Data fusion mathematics theory and practice

    CERN Document Server

    Raol, Jitendra R


    Fills the Existing Gap of Mathematics for Data FusionData fusion (DF) combines large amounts of information from a variety of sources and fuses this data algorithmically, logically and, if required intelligently, using artificial intelligence (AI). Also, known as sensor data fusion (SDF), the DF fusion system is an important component for use in various applications that include the monitoring of vehicles, aerospace systems, large-scale structures, and large industrial automation plants. Data Fusion Mathematics: Theory and Practice offers a comprehensive overview of data fusion, and provides a

  3. Plasma physics for controlled fusion

    CERN Document Server

    Miyamoto, Kenro


    This new edition presents the essential theoretical and analytical methods needed to understand the recent fusion research of tokamak and alternate approaches. The author describes magnetohydrodynamic and kinetic theories of cold and hot plasmas in detail. The book covers new important topics for fusion studies such as plasma transport by drift turbulence, which depend on the magnetic configuration and zonal flows. These are universal phenomena of microturbulence. They can modify the onset criterion for turbulent transport, instabilities driven by energetic particles as well as alpha particle generation and typical plasma models for computer simulation. The fusion research of tokamaks with various new versions of H modes are explained. The design concept of ITER, the international tokamak experimental reactor, is described for inductively driven operations as well as steady-state operations using non-inductive drives.