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Sample records for affecting intracellular fuel

  1. Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets

    Energy Technology Data Exchange (ETDEWEB)

    Alquier, Thierry; Peyot, Marie-Line; Latour, M. G.; Kebede, Melkam; Sorensen, Christina M.; Gesta, Stephane; Kahn, C. R.; Smith, Richard D.; Jetton, Thomas L.; Metz, Thomas O.; Prentki, Marc; Poitout, Vincent J.

    2009-11-01

    The G protein-coupled receptor GPR40 mediates fatty-acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. We observed that glucose- and arginine-stimulated insulin secretion, assessed by hyperglycemic clamps, was decreased by approximately 60% in GPR40 knock-out (KO) fasted and fed mice, without changes in insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps. Glucose and palmitate metabolism were not affected by GPR40 deletion. Lipid profiling revealed a similar increase in triglyceride and decrease in lysophosphatidylethanolamine species in WT and KO islets in response to palmitate. These results demonstrate that GPR40 regulates insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism.

  2. Issues affecting the acceptance of hydrogen fuel

    International Nuclear Information System (INIS)

    Schulte, I.; Hart, D.; Vorst, R. van der

    2004-01-01

    While the topic of hydrogen as an alternative vehicle fuel is gaining increasing attention internationally, one significant aspect of its introduction has been given less attention than others: the public acceptance of such a new technology and fuel. After reviewing the existing literature on acceptance, risk perception and customer satisfaction, this paper describes the development of a model that illustrates important aspects in influencing a person's attitude towards a new product. 'Values', 'wants' and 'perception' are the three components found to influence acceptance, they themselves are affected by 'social background' and 'experience'. Suggestions are then given on how to use marketing methods, education projects and product exposure in order to maximise the likelihood of a successful introduction of hydrogen as an alternative fuel. (author)

  3. Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

    Science.gov (United States)

    das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2012-06-01

    To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

  4. Blockade of intracellular Zn2+ signaling in the basolateral amygdala affects object recognition memory via attenuation of dentate gyrus LTP.

    Science.gov (United States)

    Fujise, Yuki; Kubota, Mitsuyasu; Suzuki, Miki; Tamano, Haruna; Takeda, Atsushi

    2017-09-01

    Hippocampus-dependent memory is modulated by the amygdala. However, it is unknown whether intracellular Zn 2+ signaling in the amygdala is involved in hippocampus-dependent memory. On the basis of the evidence that intracellular Zn 2+ signaling in dentate granule cells (DGC) is necessary for object recognition memory via LTP at medial perforant pathway (PP)-DGC synapses, the present study examined whether intracellular Zn 2+ signaling in the amygdala influences object recognition memory via modulation of LTP at medial PP-DGC synapses. When ZnAF-2DA (100 μM, 2 μl) was injected into the basolateral amygdala (BLA), intracellular ZnAF-2 locally chelated intracellular Zn 2+ in the amygdala. Recognition memory was affected when training of object recognition test was performed 20 min after ZnAF-2DA injection into the BLA. Twenty minutes after injection of ZnAF-2DA into the BLA, LTP induction at medial PP-DGC synapses was attenuated, while LTP induction at PP-BLA synapses was potentiated and LTP induction at BLA-DGC synapses was attenuated. These results suggest that intracellular Zn 2+ signaling in the BLA is involved in BLA-associated LTP and modulates LTP at medial PP-DGC synapses, followed by modulation of object recognition memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Expression of Bax in yeast affects not only the mitochondria but also vacuolar integrity and intracellular protein traffic

    DEFF Research Database (Denmark)

    Dimitrova, Irina; Toby, Garabet G; Tili, Esmerina

    2004-01-01

    -transferase (BI-GST) leads to aggregation, but not fusion of the mitochondria. In addition, Bax affects the integrity of yeast vacuoles, resulting in the disintegration and eventual loss of the organelles, and the disruption of intracellular protein traffic. While Bcl-2 coexpression only partially corrects...

  6. SLC30A9 mutation affecting intracellular zinc homeostasis causes a novel cerebro-renal syndrome.

    Science.gov (United States)

    Perez, Yonatan; Shorer, Zamir; Liani-Leibson, Keren; Chabosseau, Pauline; Kadir, Rotem; Volodarsky, Michael; Halperin, Daniel; Barber-Zucker, Shiran; Shalev, Hanna; Schreiber, Ruth; Gradstein, Libe; Gurevich, Evgenia; Zarivach, Raz; Rutter, Guy A; Landau, Daniel; Birk, Ohad S

    2017-04-01

    A novel autosomal recessive cerebro-renal syndrome was identified in consanguineous Bedouin kindred: neurological deterioration was evident as of early age, progressing into severe intellectual disability, profound ataxia, camptocormia and oculomotor apraxia. Brain MRI was normal. Four of the six affected individuals also had early-onset nephropathy with features of tubulo-interstitial nephritis, hypertension and tendency for hyperkalemia, though none had rapid deterioration of renal function. Genome wide linkage analysis identified an ∼18 Mb disease-associated locus on chromosome 4 (maximal logarithm of odds score 4.4 at D4S2971; θ = 0). Whole exome sequencing identified a single mutation in SLC30A9 within this locus, segregating as expected within the kindred and not found in a homozygous state in 300 Bedouin controls. We showed that SLC30A9 (solute carrier family 30 member 9; also known as ZnT-9) is ubiquitously expressed with high levels in cerebellum, skeletal muscle, thymus and kidney. Confocal analysis of SH-SY5Y cells overexpressing SLC30A9 fused to enhanced green fluorescent protein demonstrated vesicular cytosolic localization associated with the endoplasmic reticulum, not co-localizing with endosomal or Golgi markers. SLC30A9 encodes a putative zinc transporter (by similarity) previously associated with Wnt signalling. However, using dual-luciferase reporter assay in SH-SY5Y cells we showed that Wnt signalling was not affected by the mutation. Based on protein modelling, the identified mutation is expected to affect SLC30A9's highly conserved cation efflux domain, putatively disrupting its transmembrane helix structure. Cytosolic Zn2+ measurements in HEK293 cells overexpressing wild-type and mutant SLC30A9 showed lower zinc concentration within mutant rather than wild-type SLC30A9 cells. This suggests that SLC30A9 has zinc transport properties affecting intracellular zinc homeostasis, and that the molecular mechanism of the disease is through

  7. Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by modulating critical intracellular pathways.

    Science.gov (United States)

    Bezerra, Fábio; Ferreira, Marcel R; Fontes, Giselle N; da Costa Fernandes, Célio Jr; Andia, Denise C; Cruz, Nilson C; da Silva, Rodrigo A; Zambuzzi, Willian F

    2017-08-01

    Although, intracellular signaling pathways are proposed to predict the quality of cell-surface relationship, this study addressed pre-osteoblast behavior in response to nano hydroxyapatite (HA)-blasted titanium (Ti) surface by exploring critical intracellular pathways and pre-osteoblast morphological change. Physicochemical properties were evaluated by atomic force microscopy (AFM) and wettability considering water contact angle of three differently texturized Ti surfaces: Machined (Mac), Dual acid-etching (DAE), and nano hydroxyapatite-blasted (nHA). The results revealed critical differences in surface topography, impacting the water contact angle and later the osteoblast performance. In order to evaluate the effect of those topographical characteristics on biological responses, we have seeded pre-osteoblast cells on the Ti discs for up to 4 h and subjected the cultures to biological analysis. First, we have observed pre-osteoblasts morphological changes resulting from the interaction with the Ti texturized surfaces whereas the cells cultured on nHA presented a more advanced spreading process when compared with the cells cultured on the other surfaces. These results argued us for analyzing the molecular machinery and thus, we have shown that nHA promoted a lower Bax/Bcl2 ratio, suggesting an interesting anti-apoptotic effect, maybe explained by the fact that HA is a natural element present in bone composition. Thereafter, we investigated the potential effect of those surfaces on promoting pre-osteoblast adhesion and survival signaling by performing crystal violet and immunoblotting approaches, respectively. Our results showed that nHA promoted a higher pre-osteoblast adhesion supported by up-modulating FAK and Src activations, both signaling transducers involved during eukaryotic cell adhesion. Also, we have shown Ras-Erk stimulation by the all evaluated surfaces. Finally, we showed that all Ti-texturing surfaces were able to promote osteoblast differentiation

  8. Calcium influx affects intracellular transport and membrane repair following nanosecond pulsed electric field exposure.

    Science.gov (United States)

    Thompson, Gary Lee; Roth, Caleb C; Dalzell, Danielle R; Kuipers, Marjorie; Ibey, Bennett L

    2014-05-01

    The cellular response to subtle membrane damage following exposure to nanosecond pulsed electric fields (nsPEF) is not well understood. Recent work has shown that when cells are exposed to nsPEF, ion permeable nanopores (2  nm) created by longer micro- and millisecond duration pulses. Nanoporation of the plasma membrane by nsPEF has been shown to cause a transient increase in intracellular calcium concentration within milliseconds after exposure. Our research objective is to determine the impact of nsPEF on calcium-dependent structural and repair systems in mammalian cells. Chinese hamster ovary (CHO-K1) cells were exposed in the presence and absence of calcium ions in the outside buffer to either 1 or 20, 600-ns duration electrical pulses at 16.2  kV/cm, and pore size was determined using propidium iodide and calcium green. Membrane organization was observed with morphological changes and increases in FM1-43 fluorescence. Migration of lysosomes, implicated in membrane repair, was followed using confocal microscopy of red fluorescent protein-tagged LAMP1. Microtubule structure was imaged using mEmerald-tubulin. We found that at high 600-ns PEF dosage, calcium-induced membrane restructuring and microtubule depolymerization coincide with interruption of membrane repair via lysosomal exocytosis.

  9. Increase of Intracellular Cyclic AMP by PDE4 Inhibitors Affects HepG2 Cell Cycle Progression and Survival.

    Science.gov (United States)

    Massimi, Mara; Cardarelli, Silvia; Galli, Francesca; Giardi, Maria Federica; Ragusa, Federica; Panera, Nadia; Cinque, Benedetta; Cifone, Maria Grazia; Biagioni, Stefano; Giorgi, Mauro

    2017-06-01

    Type 4 cyclic nucleotide phosphodiesterases (PDE4) are major members of a superfamily of enzymes (PDE) involved in modulation of intracellular signaling mediated by cAMP. Broadly expressed in most human tissues and present in large amounts in the liver, PDEs have in the last decade been key therapeutic targets for several inflammatory diseases. Recently, a significant body of work has underscored their involvement in different kinds of cancer, but with no attention paid to liver cancer. The present study investigated the effects of two PDE4 inhibitors, rolipram and DC-TA-46, on the growth of human hepatoma HepG2 cells. Treatment with these inhibitors caused a marked increase of intracellular cAMP level and a dose- and time-dependent effect on cell growth. The concentrations of inhibitors that halved cell proliferation to about 50% were used for cell cycle experiments. Rolipram (10 μM) and DC-TA-46 (0.5 μM) produced a decrease of cyclin expression, in particular of cyclin A, as well as an increase in p21, p27 and p53, as evaluated by Western blot analysis. Changes in the intracellular localization of cyclin D1 were also observed after treatments. In addition, both inhibitors caused apoptosis, as demonstrated by an Annexin-V cytofluorimetric assay and analysis of caspase-3/7 activity. Results demonstrated that treatment with PDE4 inhibitors affected HepG2 cell cycle and survival, suggesting that they might be useful as potential adjuvant, chemotherapeutic or chemopreventive agents in hepatocellular carcinoma. J. Cell. Biochem. 118: 1401-1411, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.

    Science.gov (United States)

    Hussain, Rashida; Shahror, Rami; Karpati, Ferenc; Roomans, Godfried M

    2015-01-01

    Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

  11. Intracellular calcium chelation and pharmacological SERCA inhibition of Ca2+ pump in the insular cortex differentially affect taste aversive memory formation and retrieval.

    Science.gov (United States)

    Miranda, María Isabel; González-Cedillo, Francisco J; Díaz-Muñoz, Mauricio

    2011-09-01

    Variation in intracellular calcium concentration regulates the induction of long-term synaptic plasticity and is associated with a variety of memory/retrieval and learning paradigms. Accordingly, impaired calcium mobilization from internal deposits affects synaptic plasticity and cognition in the aged brain. During taste memory formation several proteins are modulated directly or indirectly by calcium, and recent evidence suggests the importance of calcium buffering and the role of intracellular calcium deposits during cognitive processes. Thus, the main goal of this research was to study the consequence of hampering changes in cytoplasmic calcium and inhibiting SERCA activity by BAPTA-AM and thapsigargin treatments, respectively, in the insular cortex during different stages of taste memory formation. Using conditioned taste aversion (CTA), we found differential effects of BAPTA-AM and thapsigargin infusions before and after gustatory stimulation, as well as during taste aversive memory consolidation; BAPTA-AM, but not thapsigargin, attenuates acquisition and/or consolidation of CTA, but neither compound affects taste aversive memory retrieval. These results point to the importance of intracellular calcium dynamics in the insular cortex during different stages of taste aversive memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Parameters affecting level measurement interpretation of nuclear fuel solutions

    International Nuclear Information System (INIS)

    Hunt, B.A.; Landat, D.A.

    1999-01-01

    This paper describes a level measurement technique commonly used in the measurement of radioactive liquids and equipment utilised by the inspectors for safeguards purposes. Some of the influencing parameters affecting the measurement results by this technique are characterised. An essential requisite for successful process operations in chemical facilities involving liquids generally require some physical measurements to be made in-line for both process and quality control in order to achieve the necessary final product specifications . In nuclear fuel reprocessing facilities, the same objectives apply coupled however with an additional requirement of achieving nuclear material accountancy and control. In view of the strategic importance of some of the process vessels in nuclear facilities, accountancy has to be supported by volume and density measurements of low uncertainty. Inspectors therefore require instruments which are at the very least as good as or better than operator's equipment. The classical measurement technique and most widely applied for process liquids in nuclear installations is the bubbler probe or dip-tube technique. Here a regulated flow of air passes through tubes inserted to various depths into the vessel and pressure readings are measured which are a function of the presence of liquid height and density of solution in the tank. These readings, taken together with a pre-determined calibration curve are sufficient for the volume and amount of liquor in a tank to be quantified. All measurement equipment and instrumentation are long distances from the tank environment. The key physical parameter to measure at this location is therefore pressure. Equipment designed developed, commissioned and tested in the tank measurement facilities at Ispra and in nuclear installations in Europe, Japan and the USA, house digital pressure transducer modules with manufacture's declared features of better than 0.01% accuracy and long term stability of 0.01% full

  13. Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

    Science.gov (United States)

    Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

  14. Memantine, an antagonist of the NMDA glutamate receptor, affects cell proliferation, differentiation and the intracellular cycle and induces apoptosis in Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Flávia Silva Damasceno

    2014-02-01

    Full Text Available Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and affects approximately 10 million people in endemic areas of Mexico and Central and South America. Currently available chemotherapies are limited to two compounds: Nifurtimox and Benznidazole. Both drugs reduce the symptoms of the disease and mortality among infected individuals when used during the acute phase, but their efficacy during the chronic phase (during which the majority of cases are diagnosed remains controversial. Moreover, these drugs have several side effects. The aim of this study was to evaluate the effect of Memantine, an antagonist of the glutamate receptor in the CNS of mammals, on the life cycle of T. cruzi. Memantine exhibited a trypanocidal effect, inhibiting the proliferation of epimastigotes (IC50 172.6 µM. Furthermore, this compound interfered with metacyclogenesis (approximately 30% reduction and affected the energy metabolism of the parasite. In addition, Memantine triggered mechanisms that led to the apoptosis-like cell death of epimastigotes, with extracellular exposure of phosphatidylserine, increased production of reactive oxygen species, decreased ATP levels, increased intracellular Ca(2+ and morphological changes. Moreover, Memantine interfered with the intracellular cycle of the parasite, specifically the amastigote stage (IC50 31 µM. Interestingly, the stages of the parasite life cycle that require more energy (epimastigote and amastigote were more affected as were the processes of differentiation and cell invasion.

  15. Factors affecting diesel fuel degradation using a bespoke high-pressure fuel system rig

    OpenAIRE

    Gopalan, Kesavan; Smith, Christopher; Pickering, Simon; Chuck, Christopher; Bannister, Christopher

    2018-01-01

    Recently, there has been automotive industry-wide impetus to reduce overall diesel vehicle emissions and fuel consumption by increasing fuel injection pressures within common rail systems. Many production fuel injection systems are now capable of delivering rail pressures of 1800-2000 bar with those able to achieve 3000 bar under development. In addition, there has been a gradual increase in the permitted FAME content in EN590 diesel from 5% to 7% with further increases to 10% proposed. With ...

  16. Cell wall assembly and intracellular trafficking in plant cells are directly affected by changes in the magnitude of gravitational acceleration.

    Directory of Open Access Journals (Sweden)

    Youssef Chebli

    Full Text Available Plants are able to sense the magnitude and direction of gravity. This capacity is thought to reside in selected cell types within the plant body that are equipped with specialized organelles called statoliths. However, most plant cells do not possess statoliths, yet they respond to changes in gravitational acceleration. To understand the effect of gravity on the metabolism and cellular functioning of non-specialized plant cells, we investigated a rapidly growing plant cell devoid of known statoliths and without gravitropic behavior, the pollen tube. The effects of hyper-gravity and omnidirectional exposure to gravity on intracellular trafficking and on cell wall assembly were assessed in Camellia pollen tubes, a model system with highly reproducible growth behavior in vitro. Using an epi-fluorescence microscope mounted on the Large Diameter Centrifuge at the European Space Agency, we were able to demonstrate that vesicular trafficking is reduced under hyper-gravity conditions. Immuno-cytochemistry confirmed that both in hyper and omnidirectional gravity conditions, the characteristic spatial profiles of cellulose and callose distribution in the pollen tube wall were altered, in accordance with a dose-dependent effect on pollen tube diameter. Our findings suggest that in response to gravity induced stress, the pollen tube responds by modifying cell wall assembly to compensate for the altered mechanical load. The effect was reversible within few minutes demonstrating that the pollen tube is able to quickly adapt to changing stress conditions.

  17. Macrophage ABCA2 deletion modulates intracellular cholesterol deposition, affects macrophage apoptosis, and decreases early atherosclerosis in LDL receptor knockout mice.

    Science.gov (United States)

    Calpe-Berdiel, Laura; Zhao, Ying; de Graauw, Marjo; Ye, Dan; van Santbrink, Peter J; Mommaas, A Mieke; Foks, Amanda; Bot, Martine; Meurs, Illiana; Kuiper, Johan; Mack, Jody T; Van Eck, Miranda; Tew, Kenneth D; van Berkel, Theo J C

    2012-08-01

    The ABCA2 transporter shares high structural homology to ABCA1, which is crucial for the removal of excess cholesterol from macrophages and, by extension, in atherosclerosis. It has been suggested that ABCA2 sequesters cholesterol inside the lysosomes, however, little is known of the macrophage-specific role of ABCA2 in regulating lipid homeostasis in vivo and in modulating susceptibility to atherosclerosis. Chimeras with dysfunctional macrophage ABCA2 were generated by transplantation of bone marrow from ABCA2 knockout (KO) mice into irradiated LDL receptor (LDLr) KO mice. Interestingly, lack of ABCA2 in macrophages resulted in a diminished lesion size in the aortic root (-24.5%) and descending thoracic aorta (-36.6%) associated with a 3-fold increase in apoptotic cells, as measured by both caspase 3 and TUNEL. Upon oxidized LDL exposure, macrophages from wildtype (WT) transplanted animals developed filipin-positive droplets in lysosomal-like compartments, corresponding to free cholesterol (FC) accumulation. In contrast, ABCA2-deficient macrophages displayed an abnormal diffuse distribution of FC over peripheral regions. The accumulation of neutral sterols in lipid droplets was increased in ABCA2-deficient macrophages, but primarily in cytoplasmic clusters and not in lysosomes. Importantly, apoptosis of oxLDL loaded macrophages lacking ABCA2 was increased 2.7-fold, probably as a consequence of the broad cellular distribution of FC. Lack of functional ABCA2 generates abnormalities in intracellular lipid distribution/trafficking in macrophages consistent with its lysosomal sequestering role, leading to an increased susceptibility to apoptosis in response to oxidized lipids and reduced atherosclerotic lesion development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. AMP affects intracellular Ca2+ signaling, migration, cytokine secretion and T cell priming capacity of dendritic cells.

    Directory of Open Access Journals (Sweden)

    Elisabeth Panther

    Full Text Available The nucleotide adenosine-5'-monophosphate (AMP can be released by various cell types and has been shown to elicit different cellular responses. In the extracellular space AMP is dephosphorylated to the nucleoside adenosine which can then bind to adenosine receptors. However, it has been shown that AMP can also activate A(1 and A(2a receptors directly. Here we show that AMP is a potent modulator of mouse and human dendritic cell (DC function. AMP increased intracellular Ca(2+ concentration in a time and dose dependent manner. Furthermore, AMP stimulated actin-polymerization in human DCs and induced migration of immature human and bone marrow derived mouse DCs, both via direct activation of A(1 receptors. AMP strongly inhibited secretion of TNF-α and IL-12p70, while it enhanced production of IL-10 both via activation of A(2a receptors. Consequently, DCs matured in the presence of AMP and co-cultivated with naive CD4(+CD45RA(+ T cells inhibited IFN-γ production whereas secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune response could also be observed when OVA-pulsed murine DCs were pretreated with AMP prior to co-culture with OVA-transgenic naïve OTII T cells. An effect due to the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still elicited migration and changes in cytokine secretion in bone-marrow derived DCs generated from CD73-deficient animals and in human DCs pretreated with the ecto-nucleotidase inhibitor 5'-(alpha,beta-methylene diphosphate (APCP. Finally, the influence of contaminating adenosine could be excluded, as AMP admixed with adenosine desaminase (ADA was still able to influence DC function. In summary our data show that AMP when present during maturation is a potent regulator of dendritic cell function and point out the role for AMP in the pathogenesis of inflammatory disorders.

  19. Amastin Knockdown in Leishmania braziliensis Affects Parasite-Macrophage Interaction and Results in Impaired Viability of Intracellular Amastigotes.

    Directory of Open Access Journals (Sweden)

    Rita Marcia Cardoso de Paiva

    2015-12-01

    Full Text Available Leishmaniasis, a human parasitic disease with manifestations ranging from cutaneous ulcerations to fatal visceral infection, is caused by several Leishmania species. These protozoan parasites replicate as extracellular, flagellated promastigotes in the gut of a sandfly vector and as amastigotes inside the parasitophorous vacuole of vertebrate host macrophages. Amastins are surface glycoproteins encoded by large gene families present in the genomes of several trypanosomatids and highly expressed in the intracellular amastigote stages of Trypanosoma cruzi and Leishmania spp. Here, we showed that the genome of L. braziliensis contains 52 amastin genes belonging to all four previously described amastin subfamilies and that the expression of members of all subfamilies is upregulated in L. braziliensis amastigotes. Although primary sequence alignments showed no homology to any known protein sequence, homology searches based on secondary structure predictions indicate that amastins are related to claudins, a group of proteins that are components of eukaryotic tight junction complexes. By knocking-down the expression of δ-amastins in L. braziliensis, their essential role during infection became evident. δ-amastin knockdown parasites showed impaired growth after in vitro infection of mouse macrophages and completely failed to produce infection when inoculated in BALB/c mice, an attenuated phenotype that was reverted by the re-expression of an RNAi-resistant amastin gene. Further highlighting their essential role in host-parasite interactions, electron microscopy analyses of macrophages infected with amastin knockdown parasites showed significant alterations in the tight contact that is normally observed between the surface of wild type amastigotes and the membrane of the parasitophorous vacuole.

  20. Expression of intracellular interferon-alpha confers antiviral properties in transfected bovine fetal fibroblasts and does not affect the full development of SCNT embryos.

    Directory of Open Access Journals (Sweden)

    Dawei Yu

    Full Text Available Foot-and-mouth disease, one of the most significant diseases of dairy herds, has substantial effects on farm economics, and currently, disease control measures are limited. In this study, we constructed a vector with a human interferon-α (hIFN-α (without secretory signal sequence gene cassette containing the immediate early promoter of human cytomegalovirus. Stably transfected bovine fetal fibroblasts were obtained by G418 selection, and hIFN-α transgenic embryos were produced by somatic cell nuclear transfer (SCNT. Forty-six transgenic embryos were transplanted into surrogate cows, and five cows (10.9% became pregnant. Two male cloned calves were born. Expression of hIFN-α was detected in transfected bovine fetal fibroblasts, transgenic SCNT embryos, and different tissues from a transgenic SCNT calf at two days old. In transfected bovine fetal fibroblasts, expression of intracellular IFN-α induced resistance to vesicular stomatitis virus infection, increased apoptosis, and induced the expression of double-stranded RNA-activated protein kinase gene (PKR and the 2'-5'-oligoadenylate synthetase gene (2'-5' OAS, which are IFN-inducible genes with antiviral activity. Analysis by qRT-PCR showed that the mRNA expression levels of PKR, 2'-5' OAS, and P53 were significantly increased in wild-type bovine fetal fibroblasts stimulated with extracellular recombinant human IFN-α-2b, showing that intracellular IFN-α induces biological functions similar to extracellular IFN-α. In conclusion, expression of intracellular hIFN-α conferred antiviral properties in transfected bovine fetal fibroblasts and did not significantly affect the full development of SCNT embryos. Thus, IFN-α transgenic technology may provide a revolutionary way to achieve elite breeding of livestock.

  1. Investigation and proposal of the system to affect nuclear fuel type authorization and analysis code certification

    International Nuclear Information System (INIS)

    2006-03-01

    In order to develop the system to affect more advanced and rational regulations of nuclear fuels and earlier introduction of new technologies in nuclear power plants, domestic and overseas safety regulation systems and state of their implementation for water cooled reactor fuel and safety analysis code had been investigated and new regulation system to affect nuclear fuel type authorization and analysis code certification was proposed. Topical report system for common parts related with nuclear fuel type authorization and analysis code certification was firstly proposed for knowledge base. Maintaining consistent safety examination supported by experts, introduction of domestic efficient system for lead irradiation test fuel, and analysis code certification and quality assurance were also proposed. (T. Tanaka)

  2. AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

    Science.gov (United States)

    Panther, Elisabeth; Dürk, Thorsten; Ferrari, Davide; Di Virgilio, Francesco; Grimm, Melanie; Sorichter, Stephan; Cicko, Sanja; Herouy, Yared; Norgauer, Johannes; Idzko, Marco; Müller, Tobias

    2012-01-01

    The nucleotide adenosine-5′-monophosphate (AMP) can be released by various cell types and has been shown to elicit different cellular responses. In the extracellular space AMP is dephosphorylated to the nucleoside adenosine which can then bind to adenosine receptors. However, it has been shown that AMP can also activate A1 and A2a receptors directly. Here we show that AMP is a potent modulator of mouse and human dendritic cell (DC) function. AMP increased intracellular Ca2+ concentration in a time and dose dependent manner. Furthermore, AMP stimulated actin-polymerization in human DCs and induced migration of immature human and bone marrow derived mouse DCs, both via direct activation of A1 receptors. AMP strongly inhibited secretion of TNF-α and IL-12p70, while it enhanced production of IL-10 both via activation of A2a receptors. Consequently, DCs matured in the presence of AMP and co-cultivated with naive CD4+CD45RA+ T cells inhibited IFN-γ production whereas secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune response could also be observed when OVA-pulsed murine DCs were pretreated with AMP prior to co-culture with OVA-transgenic naïve OTII T cells. An effect due to the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still elicited migration and changes in cytokine secretion in bone-marrow derived DCs generated from CD73-deficient animals and in human DCs pretreated with the ecto-nucleotidase inhibitor 5′-(alpha,beta-methylene) diphosphate (APCP). Finally, the influence of contaminating adenosine could be excluded, as AMP admixed with adenosine desaminase (ADA) was still able to influence DC function. In summary our data show that AMP when present during maturation is a potent regulator of dendritic cell function and point out the role for AMP in the pathogenesis of inflammatory disorders. PMID:22624049

  3. Does habitual behavior affect the choice of alternative fuel vehicles?

    DEFF Research Database (Denmark)

    Valeri, Eva; Cherchi, Elisabetta

    2016-01-01

    Because of the recent improvements in the electrification process of cars, several types of alternative fuel vehicles are appearing in the car market. However, these new engine technologies are not easily penetrating the market around the world and the conventional ones are still the leaders....... A vast literature has explored the reasons for such low market penetration, due mainly to car's features. Using a hybrid choice model approach, in this research we study if, and to which extent, habitual car use influences individual propensity to buy a specific type of engine technology. We found...... of a conventional one. The importance of taking into account this latent construct is demonstrated also with the results of the simulated elasticity measures. In fact, the exclusion of latent habitual effect significantly underestimates the elasticity of diesel and hybrid cars and overestimates the elasticity...

  4. Copper anode corrosion affects power generation in microbial fuel cells

    KAUST Repository

    Zhu, Xiuping; Logan, Bruce E.

    2013-01-01

    Non-corrosive, carbon-based materials are usually used as anodes in microbial fuel cells (MFCs). In some cases, however, metals have been used that can corrode (e.g. copper) or that are corrosion resistant (e.g. stainless steel, SS). Corrosion could increase current through galvanic (abiotic) current production or by increasing exposed surface area, or decrease current due to generation of toxic products from corrosion. In order to directly examine the effects of using corrodible metal anodes, MFCs with Cu were compared with reactors using SS and carbon cloth anodes. MFCs with Cu anodes initially showed high current generation similar to abiotic controls, but subsequently they produced little power (2 mW m-2). Higher power was produced with microbes using SS (12 mW m-2) or carbon cloth (880 mW m-2) anodes, with no power generated by abiotic controls. These results demonstrate that copper is an unsuitable anode material, due to corrosion and likely copper toxicity to microorganisms. © 2013 Society of Chemical Industry.

  5. Copper anode corrosion affects power generation in microbial fuel cells

    KAUST Repository

    Zhu, Xiuping

    2013-07-16

    Non-corrosive, carbon-based materials are usually used as anodes in microbial fuel cells (MFCs). In some cases, however, metals have been used that can corrode (e.g. copper) or that are corrosion resistant (e.g. stainless steel, SS). Corrosion could increase current through galvanic (abiotic) current production or by increasing exposed surface area, or decrease current due to generation of toxic products from corrosion. In order to directly examine the effects of using corrodible metal anodes, MFCs with Cu were compared with reactors using SS and carbon cloth anodes. MFCs with Cu anodes initially showed high current generation similar to abiotic controls, but subsequently they produced little power (2 mW m-2). Higher power was produced with microbes using SS (12 mW m-2) or carbon cloth (880 mW m-2) anodes, with no power generated by abiotic controls. These results demonstrate that copper is an unsuitable anode material, due to corrosion and likely copper toxicity to microorganisms. © 2013 Society of Chemical Industry.

  6. Brucella suis vaccine strain 2 induces endoplasmic reticulum stress that affects intracellular replication in goat trophoblast cells in vitro

    Directory of Open Access Journals (Sweden)

    Xiangguo eWang

    2016-02-01

    Full Text Available Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER, and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2 in goat trophoblast cells (GTCs and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm, a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA, a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1α and IRE1α proteins with Irestatin 9389 (IRE1 antagonist in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection.

  7. Factors affecting actinide solubility in a repository for spent fuel, 1

    International Nuclear Information System (INIS)

    Snellman, Margit

    1986-07-01

    The main tasks in the study were to get information on the chemical conditions in a repository for spent fuel and information on factors affecting releases of actinides from spent fuel and solubility of actinides in a repository for spent fuel. The work in this field started at the Reactor Laboratory of the Technical Research Centre of Finland (VTT) in 1982. This is a report on the effects on the main parameters, Eh, pH, carbonate, organic compounds, colloids, microbes and radiation on the actinide solubility in the nearfield of the repository. Another task has been to identify available models and reported experience from actinide solubility calculations with different codes. 167 refs

  8. Analysis of factors affecting the implementation of back-end nuclear fuel cycle policy in Korea

    International Nuclear Information System (INIS)

    Choi, Yung Myung; Yang, Maeng Ho; Kim, Hyun Joon; Chung, Hwan Sam; Oh, Keun Bae; Lee, Byung OoK; Ko, Han Suk; Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Lee, Han Myung

    1994-01-01

    In this study, the back-end nuclear fuel cycle acceptability is surveyed and analyzed in the following three aspects. To begin with, the future political situation and energy-environmental issues are analyzed as part of the socio-economic aspect. Secondly, the domestic situation of nuclear industries and the fuel cycle policy of foreign countries are surveyed as the technical aspect. Finally, NPT, IAEA safeguards and nuclear export control regimes are analyzed as the institutional aspect. The unification period of South and North Korea also will greatly affect the implementation of back-end fuel cycle policy, and public attitudes will affect the acquisition of site, construction, and operation of nuclear facilities. An effort to release international restrictions on the back-end fuel cycle is also required to accelerate the implementation of the policy. In this regard, the back-end fuel cycle policy should be clear-cut to avoid misunderstanding with respect to nuclear proliferation. Importantly, agreements with foreign countries should be amended at a mutual equivalent level. (Author) 30 refs., 5 figs., 25 tabs

  9. Analysis of factors affecting the implementation of back-end nuclear fuel cycle policy in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yung Myung; Yang, Maeng Ho; Kim, Hyun Joon; Chung, Hwan Sam; Oh, Keun Bae; Lee, Byung OoK; Ko, Han Suk; Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Lee, Han Myung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-01-01

    In this study, the back-end nuclear fuel cycle acceptability is surveyed and analyzed in the following three aspects. To begin with, the future political situation and energy-environmental issues are analyzed as part of the socio-economic aspect. Secondly, the domestic situation of nuclear industries and the fuel cycle policy of foreign countries are surveyed as the technical aspect. Finally, NPT, IAEA safeguards and nuclear export control regimes are analyzed as the institutional aspect. The unification period of South and North Korea also will greatly affect the implementation of back-end fuel cycle policy, and public attitudes will affect the acquisition of site, construction, and operation of nuclear facilities. An effort to release international restrictions on the back-end fuel cycle is also required to accelerate the implementation of the policy. In this regard, the back-end fuel cycle policy should be clear-cut to avoid misunderstanding with respect to nuclear proliferation. Importantly, agreements with foreign countries should be amended at a mutual equivalent level. (Author) 30 refs., 5 figs., 25 tabs.

  10. Intracellular ice and cell survival in cryo-exposed embryonic axes of recalcitrant seeds of Acer saccharinum: an ultrastructural study of factors affecting cell and ice structures

    CSIR Research Space (South Africa)

    Wesley-Smith, J

    2014-03-01

    Full Text Available Cryopreservation is the only long-term conservation strategy available for germplasm of recalcitrant-seeded species. Efforts to cryopreserve this form of germplasm are hampered by potentially lethal intracellular freezing events; thus...

  11. Factors affecting the amounts of emissions arising from fluidized bed combustion of solid fuels

    International Nuclear Information System (INIS)

    Horbaj, P.

    1996-01-01

    The factors affecting the amounts of nitrogen oxides (NO x ) and sulfur oxides (SO x , i.e. SO 2 + SO 3 ) formed during fluidized bed combustion of fossil fuels are analyzed using both theoretical concepts and experimental data. The factors treated include temperature, excess air, fuel parameters, pressure, degree of combustion gas recycling, combustion distribution along the combustion chamber height, and sulfur trapping processes for NO x , and the Ca/S ratio, fluidized layer height and fluidization rate, granulometry and absorbent type, fluidized layer temperature, and pressure during combustion for SO x . It is concluded that fluidized bed boilers are promising power generating facilities, mitigating the environmental burden arising from fossil fuel combustion. (P.A.). 12 figs., 9 refs

  12. Factors affecting the differences in reactivity and dissolution rates between UO2 and spent nuclear fuel

    International Nuclear Information System (INIS)

    Shoesmith, D.W.; Tait, J.C.; Sunder, S.; Steward, S.; Russo, R.E.; Rudnicki, J.D.

    1996-08-01

    Strategies for the permanent disposal of spent nuclear fuel are being investigated by the U.S. Department of Energy at the Yucca Mountain site and by Atomic Energy of Canada Limited (AECL) in plutonic rock formations in the Canadian Shield. Uranium dioxide is the primary constituent of spent nuclear fuel and dissolution of the matrix is regarded as a necessary step for the release of radionuclides to repository groundwaters. In order to develop models to describe the dissolution of the U0 2 fuel matrix and subsequent release of radionuclides, it is necessary to understand both chemical and oxidative dissolution processes and how they can be affected by parameters such as groundwater composition, pH, temperature, surface area, radiolysis and redox potential. This report summarizes both published and on-going dissolution studies of U0 2 and both LWR and CANDU spent fuels being conducted at the Pacific Northwest Laboratory, Lawrence Livermore National Laboratory and Lawrence Berkeley Laboratory in the U.S. and at AECL's Whiteshell Laboratories in Canada. The studies include both dissolution tests and electrochemical experiments to measure uranium dissolution rates. The report focuses on identifying differences in reactivity towards aqueous dissolution between U0 2 and spent fuel samples as well as estimating bounding values for uranium dissolution rates. This review also outlines the basic tenets for the development of a dissolution model that is based on electrochemical principles. (author). 49 refs., 2 tabs., 11 figs

  13. Factors affecting criticality for spent-fuel materials in a geologic setting

    International Nuclear Information System (INIS)

    Gore, B.F.; Jenquin, U.P.; Serne, R.J.

    1981-04-01

    Following closure of a geologic repository for spent fuel, geologic process may change geometries and spacings, and water may enter the repository. In this study the conditions required for the criticality of spent fuel constituents are determined. Many factors affect criticality, and the effects of various possible post-closure changes are investigated. Factors having the greatest effect on criticality are identified to provide guidance for research programs and for design and evaluation studies. Section II describes the calculational methods and computer codes used to determine critical conditions. Section III of this document addresses effects of the fissile content of spent fuel on criticality. Calculations have been performed to determine the minimum critical mass of spent fuel actinides as a function of the duration of in-reactor fuel exposure for a variety of possible conditions. Section IV addresses the conditions required for criticality under a scenario believed to be highly unlikely but having a unique possibility. Pu quantities and concentrations required for criticality without water were determined for various conditions of Pu separation, rock moderation and reflection, rock impurities and isotopic content of the Pu. Section V addresses the possibility of geochemical processes separating Pu from other spent fuel constituents. Solubilities of U and Pu are calculated for groundwaters characteristic of basalt, tuff, granite, bedded and dome salt. Maximum concentrations which could be adsorbed on geologic media in contact with these groundwaters are then calculated. Comparison of these maximum adsorbed concentrations with the results presented in Section IV yields the conclusion that criticality cannot occur in sorbed deposits of Pu in geologic media due to the low Pu concentrations achievable. The possibility of selective Pu precipitation, however, is not ruled out by these arguments

  14. Intracellular ice and cell survival in cryo-exposed embryonic axes of recalcitrant seeds of Acer saccharinum: an ultrastructural study of factors affecting cell and ice structures.

    Science.gov (United States)

    Wesley-Smith, James; Berjak, Patricia; Pammenter, N W; Walters, Christina

    2014-03-01

    Cryopreservation is the only long-term conservation strategy available for germplasm of recalcitrant-seeded species. Efforts to cryopreserve this form of germplasm are hampered by potentially lethal intracellular freezing events; thus, it is important to understand the relationships among cryo-exposure techniques, water content, structure and survival. Undried embryonic axes of Acer saccharinum and those rapidly dried to two different water contents were cooled at three rates and re-warmed at two rates. Ultrastructural observations were carried out on radicle and shoot tips prepared by freeze-fracture and freeze-substitution to assess immediate (i.e. pre-thaw) responses to cooling treatments. Survival of axes was assessed in vitro. Intracellular ice formation was not necessarily lethal. Embryo cells survived when crystal diameter was between 0·2 and 0·4 µm and fewer than 20 crystals were distributed per μm(2) in the cytoplasm. Ice was not uniformly distributed within the cells. In fully hydrated axes cooled at an intermediate rate, the interiors of many organelles were apparently ice-free; this may have prevented the disruption of vital intracellular machinery. Intracytoplasmic ice formation did not apparently impact the integrity of the plasmalemma. The maximum number of ice crystals was far greater in shoot apices, which were more sensitive than radicles to cryo-exposure. The findings challenge the accepted paradigm that intracellular ice formation is always lethal, as the results show that cells can survive intracellular ice if crystals are small and localized in the cytoplasm. Further understanding of the interactions among water content, cooling rate, cell structure and ice structure is required to optimize cryopreservation treatments without undue reliance on empirical approaches.

  15. Numerical Simulation for Flow Distribution in ACE7 Fuel Assemblies affected by a Spacer Grid Deformation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jongpil; Jeong, Ji Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    In spite of various efforts to understand hydraulic phenomena in a rod bundle containing deformed rods due to swelling and/or ballooning of clad, the studies for flow blockage due to spacer grid deformation have been limited. In the present work, 3D CFD analysis for flow blockage was performed to evaluate coolant flow within ACE7 fuel assemblies (FAs) containing a FA affected by a spacer grid deformation. The real geometry except for inner grids was used in the simulation and the region including inner grid was replaced by porous media. In the present work, the numerical simulation was performed to predict coolant flow within ACE7 FAs affected by a Mid grid deformation. The 3D CFD result shows that approximately 60 subchannel hydraulic diameter is required to fully recover coolant flow under normal operating condition.

  16. Factors affecting fuel break effectiveness in the control of large fires on the Los Padres National Forest, California

    Science.gov (United States)

    Syphard, Alexandra D.; Keeley, Jon E.; Brennan, Teresa J.

    2011-01-01

    As wildfires have increased in frequency and extent, so have the number of homes developed in the wildland-urban interface. In California, the predominant approach to mitigating fire risk is construction of fuel breaks, but there has been little empirical study of their role in controlling large fires.We constructed a spatial database of fuel breaks on the Los Padres National Forest in southern California to better understand characteristics of fuel breaks that affect the behaviour of large fires and to map where fires and fuel breaks most commonly intersect. We evaluated whether fires stopped or crossed over fuel breaks over a 28-year period and compared the outcomes with physical characteristics of the sites, weather and firefighting activities during the fire event. Many fuel breaks never intersected fires, but others intersected several, primarily in historically fire-prone areas. Fires stopped at fuel breaks 46% of the time, almost invariably owing to fire suppression activities. Firefighter access to treatments, smaller fires and longer fuel breaks were significant direct influences, and younger vegetation and fuel break maintenance indirectly improved the outcome by facilitating firefighter access. This study illustrates the importance of strategic location of fuel breaks because they have been most effective where they provided access for firefighting activities.

  17. Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX-Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model.

    Science.gov (United States)

    Zareba, Ilona; Surazynski, Arkadiusz; Chrusciel, Marcin; Miltyk, Wojciech; Doroszko, Milena; Rahman, Nafis; Palka, Jerzy

    2017-01-01

    The effect of impaired intracellular proline availability for proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis was studied. We generated a constitutively knocked-down PRODH/POX MCF-7 breast cancer cell line (MCF-7shPRODH/POX) as a model to analyze the functional consequences of impaired intracellular proline levels. We have used inhibitor of proline utilization in collagen biosynthesis, 2-metoxyestradiol (MOE), inhibitor of prolidase that generate proline, rapamycin (Rap) and glycyl-proline (GlyPro), substrate for prolidase. Collagen and DNA biosynthesis were evaluated by radiometric assays. Cell viability was determined using Nucleo-Counter NC-3000. The activity of prolidase was determined by colorimetric assay. Expression of proteins was assessed by Western blot and immunofluorescence bioimaging. Concentration of proline was analyzed by liquid chromatography with mass spectrometry. PRODH/POX knockdown decreased DNA and collagen biosynthesis, whereas increased prolidase activity and intracellular proline level in MCF-7shPRODH/POX cells. All studied compounds decreased cell viability in MCF-7 and MCF-7shPRODH/POX cells. DNA biosynthesis was similarly inhibited by Rap and MOE in both cell lines, but GlyPro inhibited the process only in MCF-7shPRODH/POX and MOE+GlyPro only in MCF-7 cells. All the compounds inhibited collagen biosynthesis, increased prolidase activity and cytoplasmic proline level in MCF-7shPRODH/POX cells and contributed to the induction of pro-survival mode only in MCF-7shPRODH/POX cells. In contrast, all studied compounds upregulated expression of pro-apoptotic protein only in MCF-7 cells. PRODH/POX was confirmed as a driver of apoptosis and proved the eligibility of MCF-7shPRODH/POX cell line as a highly effective model to elucidate the different mechanisms underlying proline utilization or generation in PRODH/POX-dependent pro-apoptotic pathways. © 2017 The Author(s). Published by S. Karger AG, Basel.

  18. Difference between Extra- and Intracellular T1 Values of Carboxylic Acids Affects the Quantitative Analysis of Cellular Kinetics by Hyperpolarized NMR

    DEFF Research Database (Denmark)

    Karlsson, Magnus; Jensen, Pernille Rose; Ardenkjær-Larsen, Jan Henrik

    2016-01-01

    on the quantification of intracellular metabolicactivity. It is expected that the significantly shorter T1valueof the carboxylic moieties inside cells is a result of macro-molecular crowding. An artificial cytosol has been preparedand applied to predict the T1of other carboxylic acids. Wedemonstrate the value......Incomplete knowledge of the longitudinal relaxationtime constant (T1) leads to incorrect assumptions in quantita-tive kinetic models of cellular systems, studied by hyper-polarized real-time NMR. Using an assay that measures theintracellular signal of small carboxylic acids in living cells...

  19. Growth media simulating ileal and colonic environments affect the intracellular proteome and carbon fluxes of enterohemorrhagic Escherichia coli O157:H7 strain EDL933.

    Science.gov (United States)

    Polzin, Sabrina; Huber, Claudia; Eylert, Eva; Elsenhans, Ines; Eisenreich, Wolfgang; Schmidt, Herbert

    2013-06-01

    In this study, the intracellular proteome of Escherichia coli O157:H7 strain EDL933 was analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) spectrometry after growth in simulated ileal environment media (SIEM) and simulated colonic environment media (SCEM) under aerobic and microaerobic conditions. Differentially expressed intracellular proteins were identified and allocated to functional protein groups. Moreover, metabolic fluxes were analyzed by isotopologue profiling with [U-(13)C(6)]glucose as a tracer. The results of this study show that EDL933 responds with differential expression of a complex network of proteins and metabolic pathways, reflecting the high metabolic adaptability of the strain. Growth in SIEM and SCEM is obviously facilitated by the upregulation of nucleotide biosynthesis pathway proteins and could be impaired by exposition to 50 µM 6-mercaptopurine under aerobic conditions. Notably, various stress and virulence factors, including Shiga toxin, were expressed without having contact with a human host.

  20. Rates of fuel discharge as affected by the design of fuel-injection systems for internal-combustion engines

    Science.gov (United States)

    Gelalles, A G; Marsh, E T

    1933-01-01

    Using the method of weighing fuel collected in a receiver during a definite interval of the injection period, rates of discharge were determined, and the effects noted, when various changes were made in a fuel-injection system. The injection system consisted primarily of a by-pass controlled fuel pump and an automatic injection valve. The variables of the system studied were the pump speed, pump-throttle setting, discharge-orifice diameter, injection-valve opening and closing pressures, and injection-tube length and diameter.

  1. Factors affecting defective fraction of biso-coated HTGR fuel particles during in-block carbonization

    International Nuclear Information System (INIS)

    Caputo, A.J.; Johnson, D.R.; Bayne, C.K.

    1977-01-01

    The performance of Biso-coated thoria fuel particles during the in-block processing step of HTGR fuel element refabrication was evaluated. The effect of various process variables (heating rate, particle crushing strength, horizontal and/or vertical position in the fuel element blocks, and fuel hole permeability) on pitch coke yield, defective fraction of fuel particles, matrix structure, and matrix porosity was evaluated. Of the variables tested, only heating rate had a significant effect on pitch coke yield while both heating rate and particle crushing strength had a significant effect on defective fraction of fuel particles

  2. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free

  3. Fuels planning: science synthesis and integration; social issues fact sheet 18: Issues affecting social acceptability of fuels treatments

    Science.gov (United States)

    Christine Esposito

    2006-01-01

    Researchers have tried to understand how information about forest management can influence a person's landscape preferences and aesthetic appreciation. These findings are relevant for fuels management projects, since these projects are often characterized by conflicts between aesthetic and ecological objectives. This fact sheet discusses different aspects and ways...

  4. Microwave induced plasma for solid fuels and waste processing: A review on affecting factors and performance criteria.

    Science.gov (United States)

    Ho, Guan Sem; Faizal, Hasan Mohd; Ani, Farid Nasir

    2017-11-01

    High temperature thermal plasma has a major drawback which consumes high energy. Therefore, non-thermal plasma which uses comparatively lower energy, for instance, microwave plasma is more attractive to be applied in gasification process. Microwave-induced plasma gasification also carries the advantages in terms of simplicity, compactness, lightweight, uniform heating and the ability to operate under atmospheric pressure that gains attention from researchers. The present paper synthesizes the current knowledge available for microwave plasma gasification on solid fuels and waste, specifically on affecting parameters and their performance. The review starts with a brief outline on microwave plasma setup in general, and followed by the effect of various operating parameters on resulting output. Operating parameters including fuel characteristics, fuel injection position, microwave power, addition of steam, oxygen/fuel ratio and plasma working gas flow rate are discussed along with several performance criteria such as resulting syngas composition, efficiency, carbon conversion, and hydrogen production rate. Based on the present review, fuel retention time is found to be the key parameter that influences the gasification performance. Therefore, emphasis on retention time is necessary in order to improve the performance of microwave plasma gasification of solid fuels and wastes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Denitrifying bacterial communities affect current production and nitrous oxide accumulation in a microbial fuel cell.

    Science.gov (United States)

    Vilar-Sanz, Ariadna; Puig, Sebastià; García-Lledó, Arantzazu; Trias, Rosalia; Balaguer, M Dolors; Colprim, Jesús; Bañeras, Lluís

    2013-01-01

    The biocathodic reduction of nitrate in Microbial Fuel Cells (MFCs) is an alternative to remove nitrogen in low carbon to nitrogen wastewater and relies entirely on microbial activity. In this paper the community composition of denitrifiers in the cathode of a MFC is analysed in relation to added electron acceptors (nitrate and nitrite) and organic matter in the cathode. Nitrate reducers and nitrite reducers were highly affected by the operational conditions and displayed high diversity. The number of retrieved species-level Operational Taxonomic Units (OTUs) for narG, napA, nirS and nirK genes was 11, 10, 31 and 22, respectively. In contrast, nitrous oxide reducers remained virtually unchanged at all conditions. About 90% of the retrieved nosZ sequences grouped in a single OTU with a high similarity with Oligotropha carboxidovorans nosZ gene. nirS-containing denitrifiers were dominant at all conditions and accounted for a significant amount of the total bacterial density. Current production decreased from 15.0 A · m(-3) NCC (Net Cathodic Compartment), when nitrate was used as an electron acceptor, to 14.1 A · m(-3) NCC in the case of nitrite. Contrarily, nitrous oxide (N2O) accumulation in the MFC was higher when nitrite was used as the main electron acceptor and accounted for 70% of gaseous nitrogen. Relative abundance of nitrite to nitrous oxide reducers, calculated as (qnirS+qnirK)/qnosZ, correlated positively with N2O emissions. Collectively, data indicate that bacteria catalysing the initial denitrification steps in a MFC are highly influenced by main electron acceptors and have a major influence on current production and N2O accumulation.

  6. Sirt3 deficiency does not affect venous thrombosis or NETosis despite mild elevation of intracellular ROS in platelets and neutrophils in mice.

    Directory of Open Access Journals (Sweden)

    Hideki Hayashi

    Full Text Available Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets. Using Sirt3-/- mice as a model of accelerated aging, we investigated the effects of Sirt3 deficiency on NETosis and platelet function, aiming to detect enhancement of thrombosis. More mitochondrial reactive oxygen species (ROS were generated in neutrophils and platelets of Sirt3-/- mice compared to WT, when stimulated with a low concentration of phorbol 12-myristate 13-acetate (PMA and a high concentration of thrombin, respectively. There were no differences in in vitro NETosis, with or without stimulation. Platelet aggregation was mildly augmented in Sirt3-/- mice compared to WT mice, when stimulated with a low concentration of collagen. The effect of Sirt3 deficiency on platelet and neutrophil activation in vivo was examined by the venous thrombosis model of inferior vena cava stenosis. Elevation of plasma DNA concentration was observed after stenosis in both genotypes, but no difference was shown between the two genotypes. The systemic response to thrombosis was enhanced in Sirt3-/- mice with significantly elevated neutrophil count and reduced platelet count. However, no differences were observed in incidence of thrombus formation, thrombus weight and thrombin-antithrombin complex generation between WT and Sirt3-/- mice. We conclude that Sirt3 does not considerably impact NET formation, platelet function, or venous

  7. Investigation of Factors Affecting Fuel Consumption of Rural Households in Central District of Zahedan County

    Directory of Open Access Journals (Sweden)

    Maryam Sharifzadeh

    2014-08-01

    Full Text Available Domestic fuel forms a significant part of the total energy demand and providing adequate and sustainable fuel is considered as a pivotal foundation for development. This survey study aims at investigating domestic fuel consumption patterns of rural areas in central district of Zahedan County, Eastern Iran. The sample was consisted of 250 household heads resided in rural areas with more than 25 households. The validity of questionnaire was confirmed by a panel of experts and its reliability was measured by using a pilot study. Findings revealed that, only 43 percent (n=102 household revealed an efficient energy use behavior. The efficient energy consumers were significantly different with respect to their education level, age, income, and the other household characteristics. Results from the structural equation modeling which was used to confirm adequacy of the reasoned action model of fuel consumption behavior, showed that 0.24 percent of fuel consumption behavior was determined by attitude, intention and subjective norms towards fuel consumption. The paper presented applied suggestions regarding fuel consumption with special consideration on health and ecosystem and indoor sanitation issues.

  8. Diagrammatic representation of economic factors affecting the nuclear fuel cycle strategy within the European Community

    International Nuclear Information System (INIS)

    1979-05-01

    This paper, which also appears as an Appendix to the Final Working Group 4 Report, forms part of the overall economic evaluation of reprocessing. The indicative position and illustrative ''phase diagram'' for the Commission of the European Communities (CEC) is presented. The European Community has to import 80% or more of the uranium needed to fuel its nuclear power capacity. Nuclear fuel reprocessing together with recycle of the recovered uranium and plutonium has the potential to reduce the uranium needs of the Community some 20 to 25% during the near term period 1990-2000 and in the longer term (after 2000) with the gradual introduction of fast breeder reactors to decrease sharply the need to import uranium. This illustrates the high economic value assigned to fuel reprocessing within the European Community

  9. 14 CFR 26.35 - Changes to type certificates affecting fuel tank flammability.

    Science.gov (United States)

    2010-01-01

    ... assessment of the fuel tank system, as modified by their design change. The assessment must identify any... and applicants subject to paragraph (a)(1) or (a)(3)(iii) of this section, if the assessment required... tanks. (c) Impact Assessment. By the times specified in paragraphs (c)(1) and (c)(2) of this section...

  10. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.

    2017-01-01

    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  11. Homo- and heterofermentative lactobacilli differently affect sugarcane-based fuel ethanol fermentation.

    Science.gov (United States)

    Basso, Thiago Olitta; Gomes, Fernanda Sgarbosa; Lopes, Mario Lucio; de Amorim, Henrique Vianna; Eggleston, Gillian; Basso, Luiz Carlos

    2014-01-01

    Bacterial contamination during industrial yeast fermentation has serious economic consequences for fuel ethanol producers. In addition to deviating carbon away from ethanol formation, bacterial cells and their metabolites often have a detrimental effect on yeast fermentative performance. The bacterial contaminants are commonly lactic acid bacteria (LAB), comprising both homo- and heterofermentative strains. We have studied the effects of these two different types of bacteria upon yeast fermentative performance, particularly in connection with sugarcane-based fuel ethanol fermentation process. Homofermentative Lactobacillus plantarum was found to be more detrimental to an industrial yeast strain (Saccharomyces cerevisiae CAT-1), when compared with heterofermentative Lactobacillus fermentum, in terms of reduced yeast viability and ethanol formation, presumably due to the higher titres of lactic acid in the growth medium. These effects were only noticed when bacteria and yeast were inoculated in equal cell numbers. However, when simulating industrial fuel ethanol conditions, as conducted in Brazil where high yeast cell densities and short fermentation time prevail, the heterofermentative strain was more deleterious than the homofermentative type, causing lower ethanol yield and out competing yeast cells during cell recycle. Yeast overproduction of glycerol was noticed only in the presence of the heterofermentative bacterium. Since the heterofermentative bacterium was shown to be more deleterious to yeast cells than the homofermentative strain, we believe our findings could stimulate the search for more strain-specific antimicrobial agents to treat bacterial contaminations during industrial ethanol fermentation.

  12. Performance of PEM fuel cells stack as affected by number of cell and gas flow-rate

    Science.gov (United States)

    Syampurwadi, A.; Onggo, H.; Indriyati; Yudianti, R.

    2017-03-01

    The proton exchange membrane fuel cell (PEMFC) is a promising technology as an alternative green energy due to its high power density, low operating temperatures, low local emissions, quiet operation and fast start up-shutdown. In order to apply fuel cell as portable power supply, the performance investigation of small number of cells is needed. In this study, PEMFC stacks consisting of 1, 3, 5 and 7-cells with an active area of 25 cm2 per cell have been designed and developed. Their was evaluated in variation of gas flow rate. The membrane electrode assembly (MEA) was prepared by hot-pressing commercial gas diffusion electrodes (Pt loading 0.5 mg/cm2) on pre-treated Nafion 117 membrane. The stacks were constructed using bipolar plates in serpentine pattern and Z-type gas flow configuration. The experimental results were presented as polarization and power output curves which show the effects of varying number of cells and H2/O2 flow-rates on the PEMFC performance. The experimental results showed that not only number of cells and gas flow-rates affected the fuel cells performance, but also the operating temperature as a result of electrochemistry reaction inside the cell.

  13. Alternative materials for solid oxide fuel cells: Factors affecting air-sintering of chromite interconnections

    International Nuclear Information System (INIS)

    Chick, L.A.; Bates, J.L.

    1992-01-01

    The purpose of this research is to develop alternative materials for solid oxide fuel cell (SOFC) interconnections and electrodes with improved electrical, thermal and electrochemical properties. Another objective is to develop synthesis and fabrication processes for these materials whereby they can be consolidated in air into SOFC's. The approach is to (1) develop modifications of the current, state-of-the-art materials used in SOFC's, (2) minimize the number of cations used in the SOFC materials to reduce potential deleterious interactions, (3) improve thermal, electrical, and electrochemical properties, (4) develop methods to synthesize both state-of-the-art and alternative materials for the simultaneous fabrication and consolidation in air of the interconnections and electrodes with the solid electrolyte, and (5) understand electrochemical reactions at materials interfaces and the effects of component compositions and processing on those reactions

  14. Factors affecting radiation doses from dedicated rail transport of spent reactor fuel

    International Nuclear Information System (INIS)

    Martin, J.E.

    1988-01-01

    This paper reports there are two exposure control concerns associated with the shipment of spent reactor fuel in dedicated trains -- compliance with transportation regulations for maximum allowable radiation levels, and minimizing the dose received by the general public. This article examines the methods used to calculate the dose equivalent rates alongside stationary (transport regulations) and moving trains (public exposure) of various lengths. The factors examined include the source term, the effect of overlapping radiation fields, the speed of the train, and the location of the population relative to the train. Trains made up of series of cars that individually meet transport regulations can, as a whole, exceed transport vehicle dose equivalent rate limits by up to 23% due to overlapping radiation fields. For moving trains and the worst case analyzed -- a person located 20 feet from the tracks and a train speed of 5 mph --- 141 rail cars would have to pass by to deliver a dose equivalent of 1 mrem

  15. Factors affecting the silver corrosion performance of jet fuel from the Merox process

    Energy Technology Data Exchange (ETDEWEB)

    Viljoen, C.L. [Sasol Oil R& D (South Africa); Hietkamp, S. [CSIR, Pretoria (South Africa); Marais, B.; Venter, J.J. [National Petroleum Refineries of South Africa, Sasolburg (South Africa)

    1995-05-01

    The Natref refinery at Sasolburg, South Africa, which is 63,6% owned by Sasol and 36,5% by Total, is producing Jet A-1 fuel at a rate of 80 m{sup 3}/h by means of a UOP Merox process. A substantial part of the crude oil slate is made up from crudes which have been stored for considerable times in underground mines. Since the 1970`s, Natref has experienced sporadic non-conformance of its treated jet fuel to the silver corrosion (IP 227) test. Various causes and explanations for the sporadic silver corrosion occurrence have been put forward but a direct causal link has remained obscure. The paper addresses these possible causes for silver corrosion and some of the process changes which have been made to alleviate the problem. Emphasis is placed on the most recent approaches which were taken to identify the origin of the sporadic silver corrosion. An inventory of all the potential causes was made, such a bacterial action, elemental sulphur formation in storage, etc. and experiments designed to test the validity of these causes, are discussed. A statistical evaluation which was done of the historical process data over a 2 year period, failed to link the use of mine crudes directly to Ag-corrosion occurrence. However, a correlation between elemental sulphur and H{sub 2}S levels in the feed to the Merox reactor and Ag-corrosion was observed. Finally, the outcome of the experiments are discussed, as well as the conclusions which were reached from the observed results.

  16. Away-from-reactor storage of spent nuclear fuel: factors affecting demand

    International Nuclear Information System (INIS)

    Dinneen, P.M.; Solomon, K.A.; Triplett, M.B.

    1980-10-01

    This report analyzes factors that affect the magnitude and timing of demand for government AFRs, relative to the demand for other storage options, to assist policymakers in predicting this demand. Past predictions of AFT demand range widely and often appear to conflict. This report helps to explain the apparent conflicts among existing demand predictions by demonstrating their sensitivity to changes in key assumptions. Specifically, the report analyzes factors affecting the demand for government AFR storage facilities; illustrates why demand estimates may vary; and identifies actions that may be undertaken by groups, within and outside the government, to influence the level and timing of demands

  17. Monitored natural attenuation (MNA) and risk management applied to an active industrial site affected by fuel spill in groundwater

    International Nuclear Information System (INIS)

    De Pablo, J.; Marti, V.; Rovira, M.; Vinolas, C.; Navarro, O.

    2005-01-01

    Monitored Natural Attenuation (MNA) applied to sites were groundwater have been affected by a fuel spill from an Industrial Underground Storage Tank (UST) is economically viable and a reliable methodology to achieve remediation goals. MNA process consists in the control of naturally occurring physical, chemical , and biological processes and is based in the knowledge of the processes that take place and reduce the charge of compounds derived from fuel in the site of study. Because the risk for Human Health and Ecosystem define the concept of contaminant, during MNA special attention has to be taken on concentration diminution of that are or could become contaminants and in this way is possible to perform Risk-Based Land Management (RBLM) by measuring both, the primary lines of evidence (shrinking or stable plume of contaminants) and secondary lines of evidence (given by geochemical indicators in the plume). Once, evidences have been gathered, is possible to calculate the rate of attenuation of contaminants and evaluate if admissible risk is reached an in a reasonable time framework, in order to propose MNA as a unique remediation or combined with other procedures to apply to an affected site. The objective of the present study is to evaluate the application of MNA to an active industrial site in order to develop a RBLM able to assess that the risk for Human Health and ecosystem are acceptable. The added attractive of this methodology is the non-intrusiveness that allows not to stop the industrial activity. The site considered in our study is in an active company located about 15 Km to NW from Barcelona, Spain.The company has a buried UST containing heavy fuel oil for energetic use. During 2002 a general soil impact study revealed that subsoil and groundwater close to the UST were affected by hydrocarbon losses from the tank and in January 2003 the fuel of the tank was emptied by pumping. The free phase of fuel floating on groundwater remained on the aquifer. As a

  18. Design of experiment study of the parameters that affect performance of three flow plate configurations of a proton exchange membrane fuel cell

    International Nuclear Information System (INIS)

    Carton, J.G.; Olabi, A.G.

    2010-01-01

    Low temperature hydrogen fuel cells are electrochemical devices which offer a promising alternative to traditional power sources. Fuel cells produce electricity with a reaction of the fuel (hydrogen) and air. Fuel cells have the advantage of being clean; only producing water and heat as by products. The efficiency of a fuel cell varies depending on the type; SOFC with CHP for example, can have a system efficiency of up to 65%. What the Authors present here is a comparison between three different configurations of flow plates of a proton exchange membrane fuel cell, the manufacturer's serpentine flow plate and two new configurations; the maze flow plate and the parallel flow plate. A study of the input parameters affecting output responses of voltage, current, power and efficiency of a fuel cell is performed through experimentation. The results were taken from direct readings of the fuel cell and from polarisation curves produced. This information was then analysed through a design of experiment to investigate the effects of the changing parameters on different configurations of the fuel cell's flow plates. The results indicate that, in relation to current and voltage response of the polarisation curve and the corresponding graphs produced from the DOE, the serpentine flow plate design is a much more effective design than the maze or parallel flow plate design. It was noted that the parallel flow plate performed reasonably well at higher pressures but over all statically the serpentine flow plate performed better.

  19. Uncertainties in criticality analysis which affect the storage and transportation of LWR fuel

    International Nuclear Information System (INIS)

    Napolitani, D.G.

    1989-01-01

    Satisfying the design criteria for subcriticality with uncertainties affects: the capacity of LWR storage arrays, maximum allowable enrichment, minimum allowable burnup and economics of various storage options. There are uncertainties due to: calculational method, data libraries, geometric limitations, modelling bias, the number and quality of benchmarks performed and mechanical uncertainties in the array. Yankee Atomic Electric Co. (YAEC) has developed and benchmarked methods to handle: high density storage rack designs, pin consolidation, low density moderation and burnup credit. The uncertainties associated with such criticality analysis are quantified on the basis of clean criticals, power reactor criticals and intercomparison of independent analysis methods

  20. The food, fuel, and financial crises affect the urban and rural poor disproportionately: a review of the evidence.

    Science.gov (United States)

    Ruel, Marie T; Garrett, James L; Hawkes, Corinna; Cohen, Marc J

    2010-01-01

    The vulnerability of the urban poor to the recent food and fuel price crisis has been widely acknowledged. The unfolding global financial crisis, which brings higher unemployment and underemployment, is likely to further intensify this vulnerability. This paper reviews the evidence concerning the disproportionate vulnerability of the urban compared with the rural poor to these types of shocks. It reviews some of the unique characteristics of urban life that could make the urban poor particularly susceptible to price and financial shocks and summarizes the evidence regarding the disproportionate vulnerability of the urban poor. The focus is on impacts on poverty, food insecurity, and malnutrition. The review shows that although the urban poor are clearly one of the population groups most affected by the current (and previous) crises, the rural poor, landless, and net buyers are in no better position to confront the crisis without significant suffering. The poorest of the poor are the ones who will be most affected, irrespective of the continent, country, or urban or rural area where they live. The magnitude and severity of their suffering depends on their ability to adapt and on the specific nature, extent, and duration of the coping strategies they adopt. A better understanding of how these coping strategies are used and staggered is critical to help design triggers for action that can prevent households from moving to more desperate measures. Using these early coping strategies as early warning indicators could help prevent dramatic losses in welfare.

  1. Viscoelastic response of HTPB based solid fuel to horizontal and vertical storage slumping conditions and it's affect on service life

    International Nuclear Information System (INIS)

    Nawaz, Q.; Nizam, F.

    2011-01-01

    Frequent use of solid fuels as thrust generating energy source in modern day space vehicle systems has created a need to assess their serviceability for long term storage under various conditions. Solid fuel grain, the most important part of any solid fuel system, responds visco elastically to any loading condition. For the assessment of the service life of any solid fuel system, the solid fuel grain has to be structurally evaluated in applied storage conditions. Structural integrity of the grain is exceptionally significant to guarantee the successful operation of the solid fuel system. In this work, numerical simulations have been performed to assess the mechanical stresses and strains induced in an HTPB based solid fuel grain during service life employing ABAQUS standard FEA software using 4-node bilinear quadrilateral elements. For finite element analysis (FEA), typical 2-D and p/nth axisymmetric section of 5-point (n) star grain geometry is considered. Mechanical loads include the horizontal or vertical 1-g (solid fuel weight) storage condition. The simulation results are compared with the analytical results for the same grain geometry. Analytically measured slump deflections in grain segment at various storage times have been found in good relation with the FEA based simulation results. This proves the validity of the procedure adopted and is helpful in assessment of the service life of solid fuel systems. (author)

  2. [Fire behavior of Mongolian oak leaves fuel bed under no-wind and zero-slope conditions. II. Analysis of the factors affecting flame length and residence time and related prediction models].

    Science.gov (United States)

    Zhang, Ji-Li; Liu, Bo-Fei; Di, Xue-Ying; Chu, Teng-Fei; Jin, Sen

    2012-11-01

    Taking fuel moisture content, fuel loading, and fuel bed depth as controlling factors, the fuel beds of Mongolian oak leaves in Maoershan region of Northeast China in field were simulated, and a total of one hundred experimental burnings under no-wind and zero-slope conditions were conducted in laboratory, with the effects of the fuel moisture content, fuel loading, and fuel bed depth on the flame length and its residence time analyzed and the multivariate linear prediction models constructed. The results indicated that fuel moisture content had a significant negative liner correlation with flame length, but less correlation with flame residence time. Both the fuel loading and the fuel bed depth were significantly positively correlated with flame length and its residence time. The interactions of fuel bed depth with fuel moisture content and fuel loading had significant effects on the flame length, while the interactions of fuel moisture content with fuel loading and fuel bed depth affected the flame residence time significantly. The prediction model of flame length had better prediction effect, which could explain 83.3% of variance, with a mean absolute error of 7.8 cm and a mean relative error of 16.2%, while the prediction model of flame residence time was not good enough, which could only explain 54% of variance, with a mean absolute error of 9.2 s and a mean relative error of 18.6%.

  3. Intracellular calcium homeostasis and signaling.

    Science.gov (United States)

    Brini, Marisa; Calì, Tito; Ottolini, Denis; Carafoli, Ernesto

    2013-01-01

    Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.

  4. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Science.gov (United States)

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  5. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

    Directory of Open Access Journals (Sweden)

    Farhana R. Pinu

    2017-10-01

    Full Text Available Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  6. Stochastic models of intracellular transport

    KAUST Repository

    Bressloff, Paul C.; Newby, Jay M.

    2013-01-01

    mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually

  7. Epithelial Cell Gene Expression Induced by Intracellular Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Xianglu Li

    2009-01-01

    Full Text Available HEp-2 cell monolayers were cocultured with intracellular Staphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. Intracellular S. aureus affected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes including atf3, sgk, map2k1, map2k3, arhb, and arhe was increased. In addition, elevated transcription of proinflammatory genes was observed for tnfa, il1b, il6, il8, cxcl1, ccl20, cox2, and pai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellular S. aureus. Notably, intracellular S. aureus induced strong transcriptional down-regulation of several cholesterol biosynthesis genes. These results suggest that epithelial cells respond to intracellular S. aureus by inducing genes affecting immunity and in repairing damage caused by the organism, and are consistent with the possibility that the organism exploits an intracellular environment to subvert host immunity and promote colonization.

  8. Commuters' exposure to particulate matter air pollution is affected by mode of transport, fuel type, and route.

    Science.gov (United States)

    Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Lenters, Virissa; Meliefste, Kees; van den Hazel, Peter; Brunekreef, Bert

    2010-06-01

    Commuters are exposed to high concentrations of air pollutants, but little quantitative information is currently available on differences in exposure between different modes of transport, routes, and fuel types. The aim of our study was to assess differences in commuters' exposure to traffic-related air pollution related to transport mode, route, and fuel type. We measured particle number counts (PNCs) and concentrations of PM2.5 (particulate matter bus passengers, we calculated that the inhaled air pollution doses were highest for cyclists. With the exception of PM10, we found that inhaled air pollution doses were lowest for electric bus passengers. Commuters' rush hour exposures were significantly influenced by mode of transport, route, and fuel type.

  9. Insecticide resistance and intracellular proteases.

    Science.gov (United States)

    Wilkins, Richard M

    2017-12-01

    Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide-resistant insects have constitutively elevated intracellular protease activity compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods. Upregulation and expression of proteases have been characterised in resistant strains of some insect species, including mosquitoes. This increase in proteolysis results in more degradation products (amino acids) of intracellular proteins. These may be utilised in the resistant strain to better protect the cell from stress. There are changes in insect intracellular proteases shortly after insecticide exposure, suggesting a role in stress response. The use of protease and proteasome inhibitors or peptide mimetics as synergists with improved application techniques and through protease gene knockdown using RNA interference (possibly expressed in crop plants) may be potential pest management strategies, in situations where elevated intracellular proteases are relevant. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  10. Commuters’ Exposure to Particulate Matter Air Pollution Is Affected by Mode of Transport, Fuel Type, and Route

    Science.gov (United States)

    Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Lenters, Virissa; Meliefste, Kees; van den Hazel, Peter; Brunekreef, Bert

    2010-01-01

    Background Commuters are exposed to high concentrations of air pollutants, but little quantitative information is currently available on differences in exposure between different modes of transport, routes, and fuel types. Objectives The aim of our study was to assess differences in commuters’ exposure to traffic-related air pollution related to transport mode, route, and fuel type. Methods We measured particle number counts (PNCs) and concentrations of PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter), PM10, and soot between June 2007 and June 2008 on 47 weekdays, from 0800 to 1000 hours, in diesel and electric buses, gasoline- and diesel-fueled cars, and along two bicycle routes with different traffic intensities in Arnhem, the Netherlands. In addition, each-day measurements were taken at an urban background location. Results We found that median PNC exposures were highest in diesel buses (38,500 particles/cm3) and for cyclists along the high-traffic intensity route (46,600 particles/cm3) and lowest in electric buses (29,200 particles/cm3). Median PM10 exposure was highest from diesel buses (47 μg/m3) and lowest along the high- and low-traffic bicycle routes (39 and 37 μg/m3). The median soot exposure was highest in gasoline-fueled cars (9.0 × 10−5/m), diesel cars (7.9 × 10−5/m), and diesel buses (7.4 × 10−5/m) and lowest along the low-traffic bicycle route (4.9 × 10−5/m). Because the minute ventilation (volume of air per minute) of cyclists, which we estimated from measured heart rates, was twice the minute ventilation of car and bus passengers, we calculated that the inhaled air pollution doses were highest for cyclists. With the exception of PM10, we found that inhaled air pollution doses were lowest for electric bus passengers. Conclusions Commuters’ rush hour exposures were significantly influenced by mode of transport, route, and fuel type. PMID:20185385

  11. DOCUMENTATION OF NATIONAL WEATHER CONDITIONS AFFECTING LONG-TERM DEGRADATION OF COMMERCIAL SPENT NUCLEAR FUEL AND DOE SPENT NUCLEAR FUEL AND HIGH-LEVEL WASTE

    International Nuclear Information System (INIS)

    W. L. Poe, Jr.; P.F. Wise

    1998-01-01

    The U.S. Department of Energy (DOE) is preparing a proposal to construct, operate 2nd monitor, and eventually close a repository at Yucca Mountain in Nye County, Nevada, for the geologic disposal of spent nuclear fuel (SNF) and high-level radioactive waste (HLW). As part of this effort, DOE has prepared a viability assessment and an assessment of potential consequences that may exist if the repository is not constructed. The assessment of potential consequences if the repository is not constructed assumes that all SNF and HLW would be left at the generator sites. These include 72 commercial generator sites (three commercial facility pairs--Salem and Hope Creek, Fitzpatrick and Nine Mile Point, and Dresden and Morris--would share common storage due to their close proximity to each other) and five DOE sites across the country. DOE analyzed the environmental consequences of the effects of the continued storage of these materials at these sites in a report titled Continued Storage Analysis Report (CSAR; Reference 1 ) . The CSAR analysis includes a discussion of the degradation of these materials when exposed to the environment. This document describes the environmental parameters that influence the degradation analyzed in the CSAR. These include temperature, relative humidity, precipitation chemistry (pH and chemical composition), annual precipitation rates, annual number of rain-days, and annual freeze/thaw cycles. The document also tabulates weather conditions for each storage site, evaluates the degradation of concrete storage modules and vaults in different regions of the country, and provides a thermal analysis of commercial SNF in storage

  12. Uptake and intracellular activity of AM-1155 in phagocytic cells.

    Science.gov (United States)

    Yamamoto, T; Kusajima, H; Hosaka, M; Fukuda, H; Oomori, Y; Shinoda, H

    1996-01-01

    The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity. PMID:9124835

  13. Considerations affecting deep-well disposal of tritium-bearing low-level aqueous waste from nuclear fuel reprocessing plants

    International Nuclear Information System (INIS)

    Trevorrow, L.E.; Warner, D.L.; Steindler, M.J.

    1977-03-01

    Present concepts of disposal of low-level aqueous wastes (LLAW) that contain much of the fission-product tritium from light water reactors involve dispersal to the atmosphere or to surface streams at fuel reprocessing plants. These concepts have been challenged in recent years. Deep-well injection of low-level aqueous wastes, an alternative to biospheric dispersal, is the subject of this presentation. Many factors must be considered in assessing its feasibility, including technology, costs, environmental impact, legal and regulatory constraints, and siting. Examination of these factors indicates that the technology of deep-well injection, extensively developed for other industrial wastes, would require little innovation before application to low-level aqueous wastes. Costs would be low, of the order of magnitude of 10 -4 mill/kWh. The environmental impact of normal deep-well disposal would be small, compared with dispersal to the atmosphere or to surface streams; abnormal operation would not be expected to produce catastrophic results. Geologically suitable sites are abundant in the U.S., but a well would best be co-located with the fuel-reprocessing plant where the LLAW is produced. Legal and regulatory constraints now being developed will be the most important determinants of the feasibility of applying the method

  14. Factors affecting the performance of a single-chamber microbial fuel cell-type biological oxygen demand sensor.

    Science.gov (United States)

    Yang, Gai-Xiu; Sun, Yong-Ming; Kong, Xiao-Ying; Zhen, Feng; Li, Ying; Li, Lian-Hua; Lei, Ting-Zhou; Yuan, Zhen-Hong; Chen, Guan-Yi

    2013-01-01

    Microbial fuel cells (MFCs) are devices that exploit microorganisms as biocatalysts to degrade organic matter or sludge present in wastewater (WW), and thereby generate electricity. We developed a simple, low-cost single-chamber microbial fuel cell (SCMFC)-type biochemical oxygen demand (BOD) sensor using carbon felt (anode) and activated sludge, and demonstrated its feasibility in the construction of a real-time BOD measurement system. Further, the effects of anodic pH and organic concentration on SCMFC performance were examined, and the correlation between BOD concentration and its response time was analyzed. Our results demonstrated that the SCMFC exhibited a stable voltage after 132 min following the addition of synthetic WW (BOD concentration: 200 mg/L). Notably, the response signal increased with an increase in BOD concentration (range: 5-200 mg/L) and was found to be directly proportional to the substrate concentration. However, at higher BOD concentrations (>120 mg/L) the response signal remained unaltered. Furthermore, we optimized the SCMFC using synthetic WW, and tested it with real WW. Upon feeding real WW, the BOD values exhibited a standard deviation from 2.08 to 8.3% when compared to the standard BOD5 method, thus demonstrating the practical applicability of the developed system to real treatment effluents.

  15. Variation in tree mortality and regeneration affect forest carbon recovery following fuel treatments and wildfire in the Lake Tahoe Basin, California, USA

    Directory of Open Access Journals (Sweden)

    Carlson Chris H

    2012-06-01

    Full Text Available Abstract Background Forest fuel treatments have been proposed as tools to stabilize carbon stocks in fire-prone forests in the Western U.S.A. Although fuel treatments such as thinning and burning are known to immediately reduce forest carbon stocks, there are suggestions that these losses may be paid back over the long-term if treatments sufficiently reduce future wildfire severity, or prevent deforestation. Although fire severity and post-fire tree regeneration have been indicated as important influences on long-term carbon dynamics, it remains unclear how natural variability in these processes might affect the ability of fuel treatments to protect forest carbon resources. We surveyed a wildfire where fuel treatments were put in place before fire and estimated the short-term impact of treatment and wildfire on aboveground carbon stocks at our study site. We then used a common vegetation growth simulator in conjunction with sensitivity analysis techniques to assess how predicted timescales of carbon recovery after fire are sensitive to variation in rates of fire-related tree mortality, and post-fire tree regeneration. Results We found that fuel reduction treatments were successful at ameliorating fire severity at our study site by removing an estimated 36% of aboveground biomass. Treated and untreated stands stored similar amounts of carbon three years after wildfire, but differences in fire severity were such that untreated stands maintained only 7% of aboveground carbon as live trees, versus 51% in treated stands. Over the long-term, our simulations suggest that treated stands in our study area will recover baseline carbon storage 10–35 years more quickly than untreated stands. Our sensitivity analysis found that rates of fire-related tree mortality strongly influence estimates of post-fire carbon recovery. Rates of regeneration were less influential on recovery timing, except when fire severity was high. Conclusions Our ability to predict

  16. Variation in tree mortality and regeneration affect forest carbon recovery following fuel treatments and wildfire in the Lake Tahoe Basin, California, USA.

    Science.gov (United States)

    Carlson, Chris H; Dobrowski, Solomon Z; Safford, Hugh D

    2012-06-28

    Forest fuel treatments have been proposed as tools to stabilize carbon stocks in fire-prone forests in the Western U.S.A. Although fuel treatments such as thinning and burning are known to immediately reduce forest carbon stocks, there are suggestions that these losses may be paid back over the long-term if treatments sufficiently reduce future wildfire severity, or prevent deforestation. Although fire severity and post-fire tree regeneration have been indicated as important influences on long-term carbon dynamics, it remains unclear how natural variability in these processes might affect the ability of fuel treatments to protect forest carbon resources. We surveyed a wildfire where fuel treatments were put in place before fire and estimated the short-term impact of treatment and wildfire on aboveground carbon stocks at our study site. We then used a common vegetation growth simulator in conjunction with sensitivity analysis techniques to assess how predicted timescales of carbon recovery after fire are sensitive to variation in rates of fire-related tree mortality, and post-fire tree regeneration. We found that fuel reduction treatments were successful at ameliorating fire severity at our study site by removing an estimated 36% of aboveground biomass. Treated and untreated stands stored similar amounts of carbon three years after wildfire, but differences in fire severity were such that untreated stands maintained only 7% of aboveground carbon as live trees, versus 51% in treated stands. Over the long-term, our simulations suggest that treated stands in our study area will recover baseline carbon storage 10-35 years more quickly than untreated stands. Our sensitivity analysis found that rates of fire-related tree mortality strongly influence estimates of post-fire carbon recovery. Rates of regeneration were less influential on recovery timing, except when fire severity was high. Our ability to predict the response of forest carbon resources to anthropogenic and

  17. Factors affecting microbial activity in compacted clay-based sealing materials proposed for use in a deep geologic repository for used nuclear fuel

    International Nuclear Information System (INIS)

    Stroes-Gascoyne, S.; Hamon, C.J.; Dixon, D.A.; Kjartanson, B.K.

    2006-01-01

    Microbial activity in clay-based barriers immediately adjacent to metal used-fuel containers in a repository could affect the longevity of such containers. The current emphasis is, therefore, on reducing or minimizing microbial activity in such clay-based barriers through material composition design. Factors affecting microbial activity in clay-based materials were studied in large-scale and smaller-scale experiments. Results suggested that keeping water activity (a w ) values below ∼0.95 may minimize microbial activity in clay-based barrier materials. A considerably higher effective montmorillonite dry density (EMDD), which partially controls a w , is achievable for 100% bentonite than for previously proposed reference buffer materials, which contain only 50% bentonite. (author)

  18. Fuels processing for transportation fuel cell systems

    Science.gov (United States)

    Kumar, R.; Ahmed, S.

    Fuel cells primarily use hydrogen as the fuel. This hydrogen must be produced from other fuels such as natural gas or methanol. The fuel processor requirements are affected by the fuel to be converted, the type of fuel cell to be supplied, and the fuel cell application. The conventional fuel processing technology has been reexamined to determine how it must be adapted for use in demanding applications such as transportation. The two major fuel conversion processes are steam reforming and partial oxidation reforming. The former is established practice for stationary applications; the latter offers certain advantages for mobile systems and is presently in various stages of development. This paper discusses these fuel processing technologies and the more recent developments for fuel cell systems used in transportation. The need for new materials in fuels processing, particularly in the area of reforming catalysis and hydrogen purification, is discussed.

  19. Stochastic models of intracellular transport

    KAUST Repository

    Bressloff, Paul C.

    2013-01-09

    The interior of a living cell is a crowded, heterogenuous, fluctuating environment. Hence, a major challenge in modeling intracellular transport is to analyze stochastic processes within complex environments. Broadly speaking, there are two basic mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually in the form of adenosine triphosphate hydrolysis, and can be direction specific, allowing biomolecules to be transported long distances; this is particularly important in neurons due to their complex geometry. In this review a wide range of analytical methods and models of intracellular transport is presented. In the case of diffusive transport, narrow escape problems, diffusion to a small target, confined and single-file diffusion, homogenization theory, and fractional diffusion are considered. In the case of active transport, Brownian ratchets, random walk models, exclusion processes, random intermittent search processes, quasi-steady-state reduction methods, and mean-field approximations are considered. Applications include receptor trafficking, axonal transport, membrane diffusion, nuclear transport, protein-DNA interactions, virus trafficking, and the self-organization of subcellular structures. © 2013 American Physical Society.

  20. Mechanisms of cellular invasion by intracellular parasites.

    Science.gov (United States)

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  1. [Intracellular signaling mechanisms in thyroid cancer].

    Science.gov (United States)

    Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

    2016-01-01

    Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  2. Characterization of Leptin Intracellular Trafficking

    Directory of Open Access Journals (Sweden)

    E Walum

    2009-12-01

    Full Text Available Leptin is produced by adipose tissue, and its concentration in plasma is related to the amount of fat in the body. The leptin receptor (OBR is a member of the class I cytokine receptor family and several different isoforms, produced by alternative mRNA splicing are found in many tissues, including the hypothalamus. The two predominant isoforms includes a long form (OBRl with an intracellular domain of 303 amino acids and a shorter form (OBRs with an intracellular domain of 34 amino acids. Since OBRl is mainly expressed in the hypotalamus, it has been suggested to be the main signalling form. The peripheral production of leptin by adipocyte tissue and its effects as a signal of satiety in the central nervous system imply that leptin gains access to regions of the brain regulating in energy balance by crossing the blood-brain barrier. In an attempt to characterize the intracellular transport of leptin, we have followed binding internalization and degradation of leptin in HEK293 cells. We have also monitored the intracellular transport pathway of fluorescent conjugated leptin in HEK293 cells. Phenylarsine oxide, a general inhibitor of endocytosis, as well as incubation at mild hypertonic conditions, prevented the uptake of leptin, confirming a receptor-mediated internalization process. When internalized, 125I-leptin was rapidly accumulated inside the cells and reached a maximum after 10 min. After 70 minutes about 40-50% of total counts in each time point were found in the medium as TCA-soluble material. Leptin sorting, at the level of early endosomes, did not seem to involve recycling endosomes, since FITC-leptin was sorted from Cy3- transferrin containing compartments at 37°C. At 45 minutes of continuos internalization, FITC-leptin appeared mainly accumulated in late endocytic structures colocalizing with internalized rhodamine coupled epidermial growth factor (EGF and the lysosomal marker protein lamp-1. The transport of leptin was also shown

  3. Electrochemically active microorganisms from an acid mine drainage-affected site promote cathode oxidation in microbial fuel cells

    KAUST Repository

    Rojas, Claudia; Vargas, Ignacio T.; Bruns, Mary Ann; Regan, John M.

    2017-01-01

    The limited database of acidophilic or acidotolerant electrochemically active microorganisms prevents advancements on microbial fuel cells (MFCs) operated under low pH. In this study, three MFCs were used to enrich cathodic biofilms using acid mine drainage (AMD) sediments as inoculum. Linear sweep voltammetry showed cathodic current plateaus of 5.5 (± 0.7) mA at about − 170 mV vs Ag/AgCl and 8.5 (± 0.9) mA between − 500 mV to − 450 mV vs Ag/AgCl for biofilms developed on small graphite fiber brushes. After gamma irradiation, biocathodes exhibited a decrease in current density approaching that of abiotic controls. Electrochemical impedance spectroscopy showed six-fold lower charge transfer resistance with viable biofilm. Pyrosequencing data showed that Proteobacteria and Firmicutes dominated the biofilms. Acidithiobacillus representatives were enriched in some biocathodes, supporting the potential importance of these known iron and sulfur oxidizers as cathodic biocatalysts. Other acidophilic chemolithoautotrophs identified included Sulfobacillus and Leptospirillum species. The presence of chemoautotrophs was consistent with functional capabilities predicted by PICRUSt related to carbon fixation pathways in prokaryotic microorganisms. Acidophilic or acidotolerant heterotrophs were also abundant; however, their contribution to cathodic performance is unknown. This study directs subsequent research efforts to particular groups of AMD-associated bacteria that are electrochemically active on cathodes.

  4. Electrochemically active microorganisms from an acid mine drainage-affected site promote cathode oxidation in microbial fuel cells

    KAUST Repository

    Rojas, Claudia

    2017-08-03

    The limited database of acidophilic or acidotolerant electrochemically active microorganisms prevents advancements on microbial fuel cells (MFCs) operated under low pH. In this study, three MFCs were used to enrich cathodic biofilms using acid mine drainage (AMD) sediments as inoculum. Linear sweep voltammetry showed cathodic current plateaus of 5.5 (± 0.7) mA at about − 170 mV vs Ag/AgCl and 8.5 (± 0.9) mA between − 500 mV to − 450 mV vs Ag/AgCl for biofilms developed on small graphite fiber brushes. After gamma irradiation, biocathodes exhibited a decrease in current density approaching that of abiotic controls. Electrochemical impedance spectroscopy showed six-fold lower charge transfer resistance with viable biofilm. Pyrosequencing data showed that Proteobacteria and Firmicutes dominated the biofilms. Acidithiobacillus representatives were enriched in some biocathodes, supporting the potential importance of these known iron and sulfur oxidizers as cathodic biocatalysts. Other acidophilic chemolithoautotrophs identified included Sulfobacillus and Leptospirillum species. The presence of chemoautotrophs was consistent with functional capabilities predicted by PICRUSt related to carbon fixation pathways in prokaryotic microorganisms. Acidophilic or acidotolerant heterotrophs were also abundant; however, their contribution to cathodic performance is unknown. This study directs subsequent research efforts to particular groups of AMD-associated bacteria that are electrochemically active on cathodes.

  5. Drosophila VAMP7 regulates Wingless intracellular trafficking.

    Science.gov (United States)

    Gao, Han; He, Fang; Lin, Xinhua; Wu, Yihui

    2017-01-01

    Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in Rab4-dependent recycling endosomes might affect Wg signaling.

  6. Exploring anti-bacterial compounds against intracellular Legionella.

    Directory of Open Access Journals (Sweden)

    Christopher F Harrison

    Full Text Available Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an 'accidental' human pathogen and cause a severe pneumonia known as Legionnaires' disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target.

  7. Exploring Anti-Bacterial Compounds against Intracellular Legionella

    Science.gov (United States)

    Harrison, Christopher F.; Kicka, Sébastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

    2013-01-01

    Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoeba castellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

  8. Electron Microscopy of Intracellular Protozoa

    Science.gov (United States)

    1988-12-20

    Classification) " ELECTRON MICROSCOPY OF INTRACELLULAR PROTOZOA 12. PERSONAL AUTHOR(S) Aikawa, Masamichi 13a. TYPE OF REPORT I13b. TIME COVERED 114...authors suggest that anti-CS protein antibody is important in reducing the prevalence of malaria with increasing age among persons in such areas and... Hygine 33, 220-226. 0Giudice, G.D., Engers, H.D., Tougne, C., Biro, S.S., Weiss, N., Verdini, A.S., Pessi, A., Degremont, A.A., Freyvogel, T.A., Lambert

  9. Pathogenic mechanisms of intracellular bacteria.

    Science.gov (United States)

    Niller, Hans Helmut; Masa, Roland; Venkei, Annamária; Mészáros, Sándor; Minarovits, Janos

    2017-06-01

    We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread. DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host cell DNA and altered the pattern of gene expression. Gene silencing by CpG methylation and histone deacetylation, mediated by cellular enzymes, also occurred in M. tuberculosis-infected macrophages. M. tuberculosis elicited cell type-specific epigenetic changes: it caused increased DNA methylation in macrophages, but induced demethylation, deposition of euchromatic histone marks and activation of immune-related genes in dendritic cells. A secreted transposase of Acinetobacter baumannii silenced a cellular gene, whereas Mycobacterium leprae altered the epigenotype, phenotype, and fate of infected Schwann cells. The 'keystone pathogen' oral bacterium Porphyromonas gingivalis induced local DNA methylation and increased the level of histone acetylation in host cells. These epigenetic changes at the biofilm-gingiva interface may contribute to the development of periodontitis. Epigenetic regulators produced by intracellular bacteria alter the epigenotype and gene expression pattern of host cells and play an important role in pathogenesis.

  10. MR imaging of intracellular and extracellular deoxyhemoglobin

    International Nuclear Information System (INIS)

    Janick, P.A.; Grossman, R.I.; Asakura, T.

    1989-01-01

    MR imaging was performed on varying concentrations of intracellular and extracellular deoxyhemoglobin as well as varying proportions of deoxyhemoglobin and oxyhemoglobin in vitro at 1.5T with use of standard spin-echo and gradient-refocused spin sequences. This study indicates that susceptibility-induced T2 shortening occurs over a broad range of intracellular deoxyhemoglobin concentrations (maximal at hematocrits between 20% and 45%), reflecting diffusional effects at the cellular level. T2* gradient-echo imaging enhances the observed hypointensity in images of intracellular deoxyhemoglobin. The characteristic MR appearance of acute hemotomas can be modeled by the behavior of intracellular and extracellular deoxyhemoglobin and oxyhemoglobin

  11. Dynamics of intracellular information decoding

    International Nuclear Information System (INIS)

    Kobayashi, Tetsuya J; Kamimura, Atsushi

    2011-01-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity

  12. Dynamics of intracellular information decoding.

    Science.gov (United States)

    Kobayashi, Tetsuya J; Kamimura, Atsushi

    2011-10-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity.

  13. Secretome of obligate intracellular Rickettsia

    Science.gov (United States)

    Gillespie, Joseph J.; Kaur, Simran J.; Rahman, M. Sayeedur; Rennoll-Bankert, Kristen; Sears, Khandra T.; Beier-Sexton, Magda; Azad, Abdu F.

    2014-01-01

    The genus Rickettsia (Alphaproteobacteria, Rickettsiales, Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently, there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, although others (e.g. josamycin, ciprofloxacin, chloramphenicol, and azithromycin) are also effective. Much of the recent research geared toward understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial ‘life on the inside’. PMID:25168200

  14. Identification and understanding the factors affecting the public and political acceptance of long term storage of spent fuel and high-level radioactive wastes

    International Nuclear Information System (INIS)

    Gorea, Valica

    2006-01-01

    , during the storage. There is a powerful scientific and technical consensus according to which a well placed final repository must be provided with some barriers, including the geological and engineered ones. The wide-spread and accepted concept of final repository for spent fuel and high level waste is the so-called geological disposal which means the solid radioactive waste storage in underground repositories in a stable geological structure (ordinary at some hundreds of meters deep) so ensuring the isolation of radionuclides from biosphere on long term. The types of radioactive waste (high level and long life waste) which will be placed in geological repository are established by the national strategy and politics for the safe management of the radioactive waste. The development and implementation process of a repository can be achieved in the next non compulsory steps: - Developing the national politics in the field of safe management of the radioactive waste - Developing the legislative and institutional framework - Developing the technical concept of geological repository - Initiation of underground and surface investigations for the characterization of the host rock - Selecting the suitable site for an underground repository - Design, licensing for construction (which takes into account the environmental impact, nuclear safety and so on), operation and shut down. The decision to construct a geological repository must be taken by the Government or by the producers of waste. The steps for the establishing the legal framework, regulation and licensing are prerogatives of the Government, all the others steps could be achieved by non governmental organizations. The achievement of a geological repository, from the technical concept to the operation may last even more than 50 years and its operation some hundreds years. The paper contains the following sections: 1. Introduction; 2. Public and political acceptance; 3. Factors which affect the public and political

  15. Intracellular localization of Arabidopsis sulfurtransferases.

    Science.gov (United States)

    Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D; Papenbrock, Jutta

    2004-06-01

    Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism.

  16. Intracellular Nitrate of Marine Diatoms as a Driver of Anaerobic Nitrogen Cycling in Sinking Aggregates

    Directory of Open Access Journals (Sweden)

    Anja Kamp

    2016-11-01

    Full Text Available Diatom-bacteria aggregates are key for the vertical transport of organic carbon in the ocean. Sinking aggregates also represent pelagic microniches with intensified microbial activity, oxygen depletion in the center, and anaerobic nitrogen cycling. Since some of the aggregate-forming diatom species store nitrate intracellularly, we explored the fate of intracellular nitrate and its availability for microbial metabolism within anoxic diatom-bacteria aggregates. The ubiquitous nitrate-storing diatom Skeletonema marinoi was studied as both axenic cultures and laboratory-produced diatom-bacteria aggregates. Stable 15N isotope incubations under dark and anoxic conditions revealed that axenic S. marinoi is able to reduce intracellular nitrate to ammonium that is immediately excreted by the cells. When exposed to a light:dark cycle and oxic conditions, S. marinoi stored nitrate intracellularly in concentrations > 60 mmol L-1 both as free-living cells and associated to aggregates. Intracellular nitrate concentrations exceeded extracellular concentrations by three orders of magnitude. Intracellular nitrate was used up within 2-3 days after shifting diatom-bacteria aggregates to dark and anoxic conditions. Thirty-one percent of the diatom-derived nitrate was converted to nitrogen gas, indicating that a substantial fraction of the intracellular nitrate pool of S. marinoi becomes available to the aggregate-associated bacterial community. Only 5% of the intracellular nitrate was reduced to ammonium, while 59% was recovered as nitrite. Hence, aggregate-associated diatoms accumulate nitrate from the surrounding water and sustain complex nitrogen transformations, including loss of fixed nitrogen, in anoxic, pelagic microniches. Additionally, it may be expected that intracellular nitrate not converted before the aggregates have settled onto the seafloor could fuel benthic nitrogen transformations.

  17. An Analysis of Environmental Dimensions Affected in Adoption of Hydrogen Fuel Cell Vehicles: A Study in Shah ALAM Industrial AREA, Selangor

    Directory of Open Access Journals (Sweden)

    Siron Rusinah

    2016-01-01

    Full Text Available The aim of the study is to identify the perceptions of respondents on environmental dimensions hat affected in adoption of hydrogen fuel cell vehicles. The study was conducted at Shah Alam industrial areas of Selangor, Malaysia, with the number of respondents are 120 respondents with various job positions that related with engineering and automobiles industry. The findings of the research shows that the dimensions of HFCV Internal Environmental total score of the items statement is 3.40 with the percentage of agreement in implementation is 3.72 percent, HFCV Environmental Information Systems shows that the total score of the items statement is 3.63 with the percentage of agreement on use to great extend is 42.5 percent, HFCV Cooperation with Customers shows that the total score of the items statement is 3.81 with the percentage of agreement on implementation is 44.2 percent. The findings on HFCV Eco Design shows that the total score of items statement is 4.02 with the percentage of agreement on implementation is 42.3 percent, HFCV Environmental Organizational Culture shows that the total score of the items statement is 3.37 with the percentage of agreement is 34.2 percent, HFCV Environmental Leadership shows that the total score of the items statement is 3.34 with the percentage of agreement is 48.2 percent. HFCV Proactive Green Innovation shows that the total score of items statement is 4.10 ahead of automobile got the highest mean score of 4.32 with the percentage of agreement is 41 percent. HFCV Environmental performance shows that the total score of the items statement is 3.87 with the percentage of agreement is 39 percent and the last environmental dimensions was HFCV Environmental Risks shows that the total score of the item statement is 4.00 with the percentage of agreement is 40 percent

  18. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

    Science.gov (United States)

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-23

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

  19. WWER identification and analysis of dominant factors affecting the fuel failure rates in WWER-1000 units in Czech Republic, Bulgaria, Ukraine and Russia

    International Nuclear Information System (INIS)

    Evdokimov, I.; Likhanskii, V.; Afanasieva, E.; Kanukova, V.; Kozhakin, A.; Maslova, L.; Chernetskiy, M.; Zborovskii, V.; Sorokin, A.

    2015-01-01

    The paper reviews the major findings of the study in the frame of the “Zero Failure Rate” project for WWER. The study included analysis and systematization of available data on leaking fuel assemblies found in 2003 through 2014 in WWER-1000 nuclear units in Russia, Ukraine, Czech Republic and Bulgaria. The study was intended to be used in preparation of recommendations and elaboration of corrective measures for enhancement of reliability and decrease of the failure rates for the WWER-1000 fuel. One of the key areas in successful implementation of the industry ‘zero failure’ goal is a challenge of significant increase of inspections of WWER-1000 fuel assemblies. It may be reasonable (with account taken for international experience) to think of development of more effective equipment for prompt fuel inspections & repair in WWER-1000 spent fuel pool. Another challenge is the elaboration of unified fuel inspection guidelines to ensure that limited industry resources are spent in the most productive way. In the frame of this work it may be helpful to implement in practice the criteria for safe removal of defective fuel rods from the leaking FA under repair

  20. Does a Change in Price of Fuel Affect GDP Growth? An Examination of the U.S. Data from 1950–2013

    Directory of Open Access Journals (Sweden)

    Michael Aucott

    2014-10-01

    Full Text Available We examined data on fuel consumption and costs for the years 1950 through 2013, along with economic and population data, to determine the percent of U.S. gross domestic product (GDP spent each year on fuels, including fossil fuels and nuclear ore, and the growth of the economy. We found that these variables are inversely correlated. This suggests that the availability and cost of energy is a significant determinant of economic performance. We believe this relation is consistent with analyses based on the energy return on investment (EROI concept in that increasingly scarce, and hence expensive, fuels are a drag on economic growth. The best-fitting linear equation relating the percent of GDP (energy cost share and year-over-year (YoY GDP change variables suggests that a threshold exists in the vicinity of 4%; if the percent of GDP spent on fuels is greater than this, poorer economic performance has been likely. Currently, about 5% of GDP is spent on fuels; most of this is for liquids. Continued weak economic performance appears likely unless improvements in energy efficiency, on the order of a factor of 3 for liquid fuels, and/or a more rapid adoption of renewable or nuclear energy sources can be achieved, provided that the EROI of these new sources proves to be sufficiently high.

  1. Chelation of intracellular calcium blocks insulin action in the adipocyte

    International Nuclear Information System (INIS)

    Pershadsingh, H.A.; Shade, D.L.; Delfert, D.M.; McDonald, J.M.

    1987-01-01

    The hypothesis that intracellular Ca 2+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca 2+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl 2 and the Ca 2+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl 2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 μM quin-2 or quin-2 AM had no effect on intracellular ATP concentration or the specific binding of 125 I=labeled insulin to adipocytes. These findings suggest that intracellular Ca 2+ is an essential component in the coupling of the insulin-activated receptor complex to cellular physiological/metabolic machinery. Furthermore, differing quin-2 AM dose-response profiles suggest the presence of dual Ca 2+ -dependent pathways in the adipocyte. One involves insulin stimulation of glucose transport and oxidation, whereas the other involves the antilipolytic action of insulin

  2. Nanoparticles for intracellular-targeted drug delivery

    International Nuclear Information System (INIS)

    Paulo, Cristiana S O; Pires das Neves, Ricardo; Ferreira, Lino S

    2011-01-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  3. Biological synthesis and characterization of intracellular gold ...

    Indian Academy of Sciences (India)

    thods of reduction of metal ions using plants or microorganisms are often ... have several advantages over bacteria, they are often pre- ferred. ... in static condition for a period of 7 days. ... work was focused on the production of intracellular gold.

  4. Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

    DEFF Research Database (Denmark)

    Krabbe, Simon; Engelhart, Merete; Thybo, Sören

    2017-01-01

    This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal......, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma....

  5. An evaluation of the policy and techno-economic factors affecting the potential for biogas upgrading for transport fuel use in the UK

    International Nuclear Information System (INIS)

    Patterson, Tim; Esteves, Sandra; Dinsdale, Richard; Guwy, Alan

    2011-01-01

    Gaseous biofuels including biomethane, which has been shown to be more environmentally beneficial than liquid biofuels, should contribute to meeting the challenging UK targets set for the supplying of biofuels to the road transport fuel market. Under the Renewable Transport Fuel Obligations the financial incentives for the supply of biofuels have been volatile, e.g. 2008/2009 saw Renewable Transport Fuel Certificate values fall to zero. Any shortfall from the maximum value has significant implications for all biofuels. It is demonstrated that biomethane can be produced at a cost which is competitive with liquid biofuels and fossil fuels within the UK. Technologies such as water scrubbing, pressure swing adsorption and physical and chemical absorption are available to upgrade biogas generated by anaerobic digestion of organic wastes to transport fuel quality, and technologies such as membrane separation and cryogenic distillation are being modified for such an application. The manufacture and sale of biomethane as a transport fuel is also financially competitive with Combined Heat and Power. One limiting factor may be the additional cost of purchasing and maintaining biomethane fuelled vehicles. Support in this area could lead to the rapid expansion of biomethane transport fuel infrastructure and bring significant long term environmental and economic advantages. - Research highlights: → A technical summary of commercially available biogas upgrading technologies is made. → An assessment of energetic, environmental and economic performance is included. → Proposed financial subsidies for biomethane transport fuel are investigated. → Biomethane can be financially competitive with liquid biofuels. → The enhanced environmental performance of biomethane should be reflected by the level of subsidy.

  6. Extracellular and Intracellular Mechanisms Mediating Metastatic Activity of Exogenous Osteopontin

    Science.gov (United States)

    Mandelin, Jami; Lin, Emme C. K.; Hu, Dana D.; Knowles, Susan K.; Do, Kim-Anh; Wang, Xuemei; Sage, E. Helene; Smith, Jeffrey W.; Arap, Wadih; Pasqualini, Renata

    2009-01-01

    BACKGROUND Osteopontin affects several steps of the metastatic cascade. Despite direct correlation with metastasis in experimental systems and in patient studies, the extracellular and intracellular basis for these observations remains unsolved. We used human melanoma and sarcoma cell lines to evaluate the effects of soluble osteopontin on metastasis. METHODS Exogenous osteopontin or negative controls, including a site-directed mutant osteopontin, were used in functional assays in vitro, ex vivo, and in vivo designed to test extracellular and intracellular mechanisms involved in experimental metastasis. RESULTS In the extracellular environment, we confirm that soluble osteopontin is required for its pro-metastatic effects; this phenomenon is specific, RGD-dependent, and evident in experimental models of metastasis. In the intracellular environment, osteopontin initially induces rapid Tyr-418 dephosphorylation of c-Src, with decreases in actin stress fibers and increased binding to the vascular endothelium. This heretofore undescribed Tyr dephosphorylation is followed by a tandem c-Src phosphorylation after tumor cell attachment to the metastatic site. CONCLUSION Our results reveal a complex molecular interaction as well as a dual role for osteopontin in metastasis that is dependent on whether tumor cells are in circulation or attached. Such context-dependent functional insights may contribute to anti-metastasis strategies. PMID:19224553

  7. Minimum Specific Fuel Consumption of a Liquid-Cooled Multicylinder Aircraft Engine as Affected by Compression Ratio and Engine Operating Conditions

    Science.gov (United States)

    Brun, Rinaldo J.; Feder, Melvin S.; Harries, Myron L.

    1947-01-01

    An investigation was conducted on a 12-cylinder V-type liquid-cooled aircraft engine of 1710-cubic-inch displacement to determine the minimum specific fuel consumption at constant cruising engine speed and compression ratios of 6.65, 7.93, and 9.68. At each compression ratio, the effect.of the following variables was investigated at manifold pressures of 28, 34, 40, and 50 inches of mercury absolute: temperature of the inlet-air to the auxiliary-stage supercharger, fuel-air ratio, and spark advance. Standard sea-level atmospheric pressure was maintained at the auxiliary-stage supercharger inlet and the exhaust pressure was atmospheric. Advancing the spark timing from 34 deg and 28 deg B.T.C. (exhaust and intake, respectively) to 42 deg and 36 deg B.T.C. at a compression ratio of 6.65 resulted in a decrease of approximately 3 percent in brake specific fuel consumption. Further decreases in brake specific fuel consumption of 10.5 to 14.1 percent (depending on power level) were observed as the compression ratio was increased from 6.65 to 9.68, maintaining at each compression ratio the spark advance required for maximum torque at a fuel-air ratio of 0.06. This increase in compression ratio with a power output of 0.585 horsepower per cubic inch required a change from . a fuel- lend of 6-percent triptane with 94-percent 68--R fuel at a compression ratio of 6.65 to a fuel blend of 58-percent, triptane with 42-percent 28-R fuel at a compression ratio of 9.68 to provide for knock-free engine operation. As an aid in the evaluation of engine mechanical endurance, peak cylinder pressures were measured on a single-cylinder engine at several operating conditions. Peak cylinder pressures of 1900 pounds per square inch can be expected at a compression ratio of 9.68 and an indicated mean effective pressure of 320 pounds per square inch. The engine durability was considerably reduced at these conditions.

  8. Fuel Exhaling Fuel Cell.

    Science.gov (United States)

    Manzoor Bhat, Zahid; Thimmappa, Ravikumar; Devendrachari, Mruthyunjayachari Chattanahalli; Kottaichamy, Alagar Raja; Shafi, Shahid Pottachola; Varhade, Swapnil; Gautam, Manu; Thotiyl, Musthafa Ottakam

    2018-01-18

    State-of-the-art proton exchange membrane fuel cells (PEMFCs) anodically inhale H 2 fuel and cathodically expel water molecules. We show an unprecedented fuel cell concept exhibiting cathodic fuel exhalation capability of anodically inhaled fuel, driven by the neutralization energy on decoupling the direct acid-base chemistry. The fuel exhaling fuel cell delivered a peak power density of 70 mW/cm 2 at a peak current density of 160 mA/cm 2 with a cathodic H 2 output of ∼80 mL in 1 h. We illustrate that the energy benefits from the same fuel stream can at least be doubled by directing it through proposed neutralization electrochemical cell prior to PEMFC in a tandem configuration.

  9. Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout

    Directory of Open Access Journals (Sweden)

    Birkedal Rikke

    2009-12-01

    Full Text Available Abstract Background Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss, which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes. Previous studies suggest that trout permeabilized cardiac fibers also have diffusion restrictions. However, results from fibers may be affected by incomplete separation of the cells. This is avoided when studying permeabilized, isolated cardiomyocytes. The aim of this study was to verify the existence of diffusion restrictions in trout cardiomyocytes by comparing ADP-kinetics of mitochondrial respiration in permeabilized fibers, permeabilized cardiomyocytes and isolated mitochondria from rainbow trout heart. Experiments were performed at 10, 15 and 20°C in the absence and presence of creatine. Results Trout cardiomyocytes hypercontracted in the solutions used for mammalian cardiomyocytes. We developed a new solution in which they retained their shape and showed stable steady state respiration rates throughout an experiment. The apparent ADP-affinity of permeabilized cardiomyocytes was different from that of fibers. It was higher, independent of temperature and not increased by creatine. However, it was still about ten times lower than in isolated mitochondria. Conclusions The differences between fibers and cardiomyocytes suggest that results from trout heart fibers were affected by incomplete separation of the cells. However, the lower ADP-affinity of cardiomyocytes compared to isolated mitochondria indicate that intracellular diffusion restrictions are still present in trout cardiomyocytes despite their lower density of intracellular membrane structures. The lack of a creatine effect indicates that

  10. Intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Ogawa, Taisuke; Takada, Shunsuke; Nakamura, Masatoshi; Fujii, Hiroaki; Ando, Masaki

    2014-11-01

    The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) levels were decreased by injection of clioquinol and N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression. Copyright © 2014 Wiley Periodicals, Inc.

  11. The effect of high pressure on the intracellular trehalose synthase activity of Thermus aquaticus.

    Science.gov (United States)

    Dong, Yongsheng; Ma, Lei; Duan, Yuanliang

    2016-01-01

    To understand the effect of high pressure on the intracellular trehalose synthase activity, Thermus aquaticus (T. aquaticus) in the logarithmic growth phase was treated with high-pressure air, and its intracellular trehalose synthase (TSase) activity was determined. Our results indicated that pressure is a factor strongly affecting the cell growth. High pressure significantly attenuated the growth rate of T. aquaticus and shortened the duration of stationary phase. However, after 2 h of culture under 1.0 MPa pressure, the activity of intracellular TSase in T. aquaticus reached its maximum value, indicating that pressure can significantly increase the activity of intracellular TSase in T. aquaticus. Thus the present study provides an important guide for the enzymatic production of trehalose.

  12. Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

    Science.gov (United States)

    Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

    2015-06-21

    High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

  13. Knock-Limited Performance of Triptane and 28-R Fuel Blends as Affected by Changes in Compression Ratio and in Engine Operating Variables

    Science.gov (United States)

    Brun, Rinaldo J.; Feder, Melvin S.; Fisher, William F.

    1947-01-01

    A knock-limited performance investigation was conducted on blends of triptane and 28-P fuel with a 12-cylinder, V-type, liquid-cooled aircraft engine of 1710-cubic-inch displacement at three compression ratios: 6.65, 7.93, and 9.68. At each compression ratio, the effect of changes in temperature of the inlet air to the auxiliary-stage supercharger and in fuel-air ratio were investigated at engine speeds of 2280 and. 3000 rpm. The results show that knock-limited engine performance, as improved by the use of triptane, allowed operation at both take-off and cruising power at a compression ratio of 9.68. At an inlet-air temperature of 60 deg F, an engine speed of 3000 rpm ; and a fuel-air ratio of 0,095 (approximately take-off conditions), a knock-limited engine output of 1500 brake horsepower was possible with 100-percent 28-R fuel at a compression ratio of 6.65; 20-percent triptane was required for the same power output at a compression ratio of 7.93, and 75 percent at a compression ratio of 9.68 allowed an output of 1480 brake horsepower. Knock-limited power output was more sensitive to changes in fuel-air ratio as the engine speed was increased from 2280 to 3000 rpm, as the compression ratio is raised from 6.65 to 9.68, or as the inlet-air temperature is raised from 0 deg to 120 deg F.

  14. Investigating Internalization and Intracellular Trafficking of GPCRs

    DEFF Research Database (Denmark)

    Foster, Simon R; Bräuner-Osborne, Hans

    2017-01-01

    for signal transduction. One of the major mechanisms for GPCR regulation involves their endocytic trafficking, which serves to internalize the receptors from the plasma membrane and thereby attenuate G protein-dependent signaling. However, there is accumulating evidence to suggest that GPCRs can signal...... independently of G proteins, as well as from intracellular compartments including endosomes. It is in this context that receptor internalization and intracellular trafficking have attracted renewed interest within the GPCR field. In this chapter, we will review the current understanding and methodologies...

  15. Detection of ubiquitinated huntingtin species in intracellular aggregates

    Directory of Open Access Journals (Sweden)

    Katrin eJuenemann

    2015-01-01

    Full Text Available Protein conformation diseases, including polyglutamine diseases, result from the accumulation and aggregation of misfolded proteins. Huntington’s disease is one of nine diseases caused by an expanded polyglutamine repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin fragments and other sequestered proteins. Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated huntingtin such as ubiquitination. Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. Studying the ubiquitination pattern of aggregated huntingtin fragments offers an important possibility to understand huntingtin degradation and aggregation processes within the cell. For the identification of aggregated huntingtin and its ubiquitinated species, solubilization of the cellular aggregates is mandatory. Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant huntingtin. This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate.

  16. Cationic polymers for intracellular delivery of proteins

    NARCIS (Netherlands)

    Coué, G.M.J.P.C.; Engbersen, Johannes F.J.; Samal, Sangram; Dubruel, Peter

    2015-01-01

    Many therapeutic proteins exert their pharmaceutical action inside the cytoplasm or onto individual organelles inside the cell. Intracellular protein delivery is considered to be the most direct, fastest and safest approach for curing gene-deficiency diseases, enhancing vaccination and triggering

  17. Molecular detection and characterization of sustainable intracellular ...

    African Journals Online (AJOL)

    3Centre for Biopolymer and Bio-Molecular Research, Athlone College of Technology, Republic of Ireland. ... cells was associated with the elongation of micro-villar extension that ... Keywords: Intracellular contaminants, cell cultures, bacteria culture, pre-clinical studies. ... production work involving culture technology.

  18. Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport

    Science.gov (United States)

    Hafner, Anne E.; Rieger, Heiko

    2018-03-01

    The efficiency of intracellular cargo transport from specific source to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance realizes a spatially inhomogeneous intermittent search strategy. In order to analyze the efficiency of such intracellular search strategies we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.

  19. Biological synthesis and characterization of intracellular gold ...

    Indian Academy of Sciences (India)

    In the present study, Aspergillus fumigatus was used for the intracellular synthesis of gold nanoparticles. Stable nanoparticles were produced when an aqueous solution of chloroauric acid (HAuCl4) was reduced by A. fumigatus biomass as the reducing agent. Production of nanoparticles was confirmed by the colour ...

  20. Fuel cycles for the 80's

    International Nuclear Information System (INIS)

    1980-01-01

    Papers presented at the American Nuclear Society's topical meeting on the fuel cycle are summarized. Present progress and goals in the areas of fuel fabrication, fuel reprocessing, spent fuel storage, accountability, and safeguards are reported. Present governmental policies which affect the fuel cycle are also discussed. Individual presentations are processed for inclusion in the Energy Data Base

  1. Optimizing Nanoelectrode Arrays for Scalable Intracellular Electrophysiology.

    Science.gov (United States)

    Abbott, Jeffrey; Ye, Tianyang; Ham, Donhee; Park, Hongkun

    2018-03-20

    Electrode technology for electrophysiology has a long history of innovation, with some decisive steps including the development of the voltage-clamp measurement technique by Hodgkin and Huxley in the 1940s and the invention of the patch clamp electrode by Neher and Sakmann in the 1970s. The high-precision intracellular recording enabled by the patch clamp electrode has since been a gold standard in studying the fundamental cellular processes underlying the electrical activities of neurons and other excitable cells. One logical next step would then be to parallelize these intracellular electrodes, since simultaneous intracellular recording from a large number of cells will benefit the study of complex neuronal networks and will increase the throughput of electrophysiological screening from basic neurobiology laboratories to the pharmaceutical industry. Patch clamp electrodes, however, are not built for parallelization; as for now, only ∼10 patch measurements in parallel are possible. It has long been envisioned that nanoscale electrodes may help meet this challenge. First, nanoscale electrodes were shown to enable intracellular access. Second, because their size scale is within the normal reach of the standard top-down fabrication, the nanoelectrodes can be scaled into a large array for parallelization. Third, such a nanoelectrode array can be monolithically integrated with complementary metal-oxide semiconductor (CMOS) electronics to facilitate the large array operation and the recording of the signals from a massive number of cells. These are some of the central ideas that have motivated the research activity into nanoelectrode electrophysiology, and these past years have seen fruitful developments. This Account aims to synthesize these findings so as to provide a useful reference. Summing up from the recent studies, we will first elucidate the morphology and associated electrical properties of the interface between a nanoelectrode and a cellular membrane

  2. Intracellular Bacterial Infections: A Challenge for Developing Cellular Mediated Immunity Vaccines for Farmed Fish

    Directory of Open Access Journals (Sweden)

    Hetron Mweemba Munang’andu

    2018-04-01

    Full Text Available Aquaculture is one of the most rapidly expanding farming systems in the world. Its rapid expansion has brought with it several pathogens infecting different fish species. As a result, there has been a corresponding expansion in vaccine development to cope with the increasing number of infectious diseases in aquaculture. The success of vaccine development for bacterial diseases in aquaculture is largely attributed to empirical vaccine designs based on inactivation of whole cell (WCI bacteria vaccines. However, an upcoming challenge in vaccine design is the increase of intracellular bacterial pathogens that are not responsive to WCI vaccines. Intracellular bacterial vaccines evoke cellular mediated immune (CMI responses that “kill” and eliminate infected cells, unlike WCI vaccines that induce humoral immune responses whose protective mechanism is neutralization of extracellular replicating pathogens by antibodies. In this synopsis, I provide an overview of the intracellular bacterial pathogens infecting different fish species in aquaculture, outlining their mechanisms of invasion, replication, and survival intracellularly based on existing data. I also bring into perspective the current state of CMI understanding in fish together with its potential application in vaccine development. Further, I highlight the immunological pitfalls that have derailed our ability to produce protective vaccines against intracellular pathogens for finfish. Overall, the synopsis put forth herein advocates for a shift in vaccine design to include CMI-based vaccines against intracellular pathogens currently adversely affecting the aquaculture industry.

  3. Fuel assemblies

    International Nuclear Information System (INIS)

    Mukai, Hideyuki

    1987-01-01

    Purpose: To prevent bending of fuel rods caused by the difference of irradiation growth between coupling fuel rods and standards fuel rods thereby maintain the fuel rod integrity. Constitution: The f value for a fuel can (the ratio of pole of zirconium crystals in the entire crystals along the axial direction of the fuel can) of a coupling fuel rod secured by upper and lower tie plates is made smaller than the f value for the fuel can of a standard fuel rod not secured by the upper and the lower tie plates. This can make the irradiation growth of the fuel can of the coupling fuel rod greater than the irradiation growth of the fuel can of the standard fuel rod and, accordingly, since the elongation of the standard fuel rod can always by made greater, bending of the standard fuel rod can be prevented. (Yoshihara, M.)

  4. Nuclear fuel waste disposal

    International Nuclear Information System (INIS)

    Merrett, G.J.; Gillespie, P.A.

    1983-07-01

    This report discusses events and processes that could adversely affect the long-term stability of a nuclear fuel waste disposal vault or the regions of the geosphere and the biosphere to which radionuclides might migrate from such a vault

  5. Sodium transport and intracellular sodium activity in cultured human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

     human nasal epithelium (HNE). Under control conditions, intracellular Na+ activity (acNa) was 23 +/- 1 mM (n = 44 preparations, 393 impalements).Amiloride (10(-4) M) hyperpolarized the apical membrane and increased the fractional apical membrane resistance but did not affect acNa. Exposure to...

  6. Intracellular pH Response to Weak Acid Stress in Individual Vegetative Bacillus subtilis Cells

    NARCIS (Netherlands)

    Pandey, R.; Vischer, N.O.E.; Smelt, J.P.P.M.; van Beilen, J.W.A.; Ter Beek, A.; De Vos, W.H.; Brul, S.; Manders, E.M.M.

    2016-01-01

    Intracellular pH (pHi) critically affects bacterial cell physiology. Hence, a variety of food preservation strategies are aimed at perturbing pHi homeostasis. Unfortunately, accurate pHi quantification with existing methods is suboptimal, since measurements are averages across populations of cells,

  7. Dynamics of gradient formation by intracellular shuttling

    Energy Technology Data Exchange (ETDEWEB)

    Berezhkovskii, Alexander M. [Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892 (United States); Shvartsman, Stanislav Y. [Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544 (United States)

    2015-08-21

    A number of important cellular functions rely on the formation of intracellular protein concentration gradients. Experimental studies discovered a number of mechanisms for the formation of such gradients. One of the mechanisms relies on the intracellular shuttling of a protein that interconverts between the two states with different diffusivities, under the action of two enzymes, one of which is localized to the plasma membrane, whereas the second is uniformly distributed in the cytoplasm. Recent work reported an analytical solution for the steady state gradient in this mechanism, obtained in the framework of a one-dimensional reaction-diffusion model. Here, we study the dynamics in this model and derive analytical expressions for the Laplace transforms of the time-dependent concentration profiles in terms of elementary transcendental functions. Inverting these transforms numerically, one can obtain time-dependent concentration profiles of the two forms of the protein.

  8. Leishmania hijacking of the macrophage intracellular compartments.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa; Loiseau, Philippe M

    2016-02-01

    Leishmania spp., transmitted to humans by the bite of the sandfly vector, are responsible for the three major forms of leishmaniasis, cutaneous, diffuse mucocutaneous and visceral. Leishmania spp. interact with membrane receptors of neutrophils and macrophages. In macrophages, the parasite is internalized within a parasitophorous vacuole and engages in a particular intracellular lifestyle in which the flagellated, motile Leishmania promastigote metacyclic form differentiates into non-motile, metacyclic amastigote form. This phenomenon is induced by Leishmania-triggered events leading to the fusion of the parasitophorous vacuole with vesicular members of the host cell endocytic pathway including recycling endosomes, late endosomes and the endoplasmic reticulum. Maturation of the parasitophorous vacuole leads to the intracellular proliferation of the Leishmania amastigote forms by acquisition of host cell nutrients while escaping host defense responses. © 2015 FEBS.

  9. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-05-01

    The intracellular glutathione (GSH) content in HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulfoximine (BSO) or diethyl maleate (DEM). Clonogenicity, single strand DNA breaks (ssb) and double strand DNA breaks (dsb) were used as criteria for radiation induced damage after X- or γ irradiation. In survival experiments DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the OER was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (Auth.)

  10. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-01-01

    The intracellular glutathione (GSH) content of HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulphoximine or diethyl maleate (DEM). Clonogenicity, single-strand DNA breaks (ssb) and double-strand DNA breaks (dsb) were used as criteria for radiation-induced damage after X- or γ-irradiation. In survival experiments, DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the o.e.r. was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (author)

  11. Intracellular mechanisms of solar water disinfection

    Science.gov (United States)

    Castro-Alférez, María; Polo-López, María Inmaculada; Fernández-Ibáñez, Pilar

    2016-12-01

    Solar water disinfection (SODIS) is a zero-cost intervention measure to disinfect drinking water in areas of poor access to improved water sources, used by more than 6 million people in the world. The bactericidal action of solar radiation in water has been widely proven, nevertheless the causes for this remain still unclear. Scientific literature points out that generation of reactive oxygen species (ROS) inside microorganisms promoted by solar light absorption is the main reason. For the first time, this work reports on the experimental measurement of accumulated intracellular ROS in E. coli during solar irradiation. For this experimental achievement, a modified protocol based on the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA), widely used for oxidative stress in eukaryotic cells, has been tested and validated for E. coli. Our results demonstrate that ROS and their accumulated oxidative damages at intracellular level are key in solar water disinfection.

  12. Behaviour of defective CANDU fuel: fuel oxidation kinetic and thermodynamic modelling

    International Nuclear Information System (INIS)

    Higgs, J.

    2005-01-01

    The thermal performance of operating CANDU fuel under defect conditions is affected by the ingress of heavy water into the fuel element. A mechanistic model has been developed to predict the extent of fuel oxidation in defective fuel and its affect on fuel thermal performance. A thermodynamic treatment of such oxidized fuel has been performed as a basis for the boundary conditions in the kinetic model. Both the kinetic and thermodynamic models have been benchmarked against recent experimental work. (author)

  13. Intracellular serpins, firewalls and tissue necrosis.

    Science.gov (United States)

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.

  14. Fluorescent nanoparticles for intracellular sensing: A review

    International Nuclear Information System (INIS)

    Ruedas-Rama, Maria J.; Walters, Jamie D.; Orte, Angel; Hall, Elizabeth A.H.

    2012-01-01

    Highlights: ► Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. ► Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. ► Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  15. Fluorescent nanoparticles for intracellular sensing: A review

    Energy Technology Data Exchange (ETDEWEB)

    Ruedas-Rama, Maria J., E-mail: mjruedas@ugr.esmailto [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Walters, Jamie D. [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QT (United Kingdom); Orte, Angel [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Hall, Elizabeth A.H., E-mail: lisa.hall@biotech.cam.ac.uk [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT (United Kingdom)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. Black-Right-Pointing-Pointer Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. Black-Right-Pointing-Pointer Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  16. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  17. A bacteriophage endolysin that eliminates intracellular streptococci

    Science.gov (United States)

    Shen, Yang; Barros, Marilia; Vennemann, Tarek; Gallagher, D Travis; Yin, Yizhou; Linden, Sara B; Heselpoth, Ryan D; Spencer, Dennis J; Donovan, David M; Moult, John; Fischetti, Vincent A; Heinrich, Frank; Lösche, Mathias; Nelson, Daniel C

    2016-01-01

    PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB–PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities. DOI: http://dx.doi.org/10.7554/eLife.13152.001 PMID:26978792

  18. Light irradiation helps magnetotactic bacteria eliminate intracellular reactive oxygen species.

    Science.gov (United States)

    Li, Kefeng; Wang, Pingping; Chen, Chuanfang; Chen, Changyou; Li, Lulu; Song, Tao

    2017-09-01

    Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known about the biological significance of this behaviour. Magnetosomes exhibit peroxidase-like activity and can scavenge reactive oxygen species (ROS). Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show enhanced peroxidase-like activity under illumination. The present study investigated the effects of light irradiation on nonmagnetic (without magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that light irradiation did not affect the growth of nonmagnetic and magnetic cells but significantly increased magnetosome synthesis and reduced intracellular ROS level in magnetic cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyse the expression level of magnetosome formation-associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA, oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation upregulated the expression of mms6, mms13 and mmsF. Furthermore, light irradiation upregulated the expression of stress-related genes in nonmagnetic cells but downregulated them in magnetic cells. Additionally, magnetic cells exhibited stronger phototactic behaviour than nonmagnetic ones. These results suggested that light irradiation could heighten the ability of MTB to eliminate intracellular ROS and help them adapt to lighted environments. This phenomenon may be related to the enhanced peroxidase-like activity of magnetosomes under light irradiation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  19. Horizontal Transmission of Intracellular Insect Symbionts via Plants

    Directory of Open Access Journals (Sweden)

    Ewa Chrostek

    2017-11-01

    Full Text Available Experimental evidence is accumulating that endosymbionts of phytophagous insects may transmit horizontally via plants. Intracellular symbionts known for manipulating insect reproduction and altering fitness (Rickettsia, Cardinium, Wolbachia, and bacterial parasite of the leafhopper Euscelidius variegatus have been found to travel from infected insects into plants. Other insects, either of the same or different species can acquire the symbiont from the plant through feeding, and in some cases transfer it to their progeny. These reports prompt many questions regarding how intracellular insect symbionts are delivered to plants and how they affect them. Are symbionts passively transported along the insect-plant-insect path, or do they actively participate in the process? How widespread are these interactions? How does symbiont presence influence the plant? And what conditions are required for the new infection to establish in an insect? From an ecological, evolutionary, and applied perspective, this mode of horizontal transmission could have profound implications if occurring frequently enough or if new stable symbiont infections are established. Transmission of symbionts through plants likely represents an underappreciated means of infection, both in terms of symbiont epidemiology and the movement of symbionts to new host species.

  20. Data feature: Fuel procurement

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    This document is a review of the effect of fuel costs on the procurement strategies of a utility and a conjecture that the same strategies may have an effect on the price of fuel. Factors affecting fuel costs are reviewed, and a number of procurement strategies taken to trim fuel costs are reviewed. The major trend is away from long-term enrichment contracts and into such strategies as: (1) Spot market purchases, (2) Inventory reduction, (3) Purchase of CIS material, and (4) Market-related contracts instead of base-escalated contracts

  1. Preparation method of Ni@Pt/C nanocatalyst affects the performance of direct borohydride-hydrogen peroxide fuel cell: Improved power density and increased catalytic oxidation of borohydride.

    Science.gov (United States)

    Hosseini, Mir Ghasem; Mahmoodi, Raana

    2017-08-15

    The Ni@Pt/C electrocatalysts were synthesized using two different methods: with sodium dodecyl sulfate (SDS) and without SDS. The metal loading in synthesized nanocatalysts was 20wt% and the molar ratio of Ni: Pt was 1:1. The structural characterizations of Ni@Pt/C electrocatalysts were investigated by field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The electrocatalytic activity of Ni@Pt/C electrocatalysts toward BH 4 - oxidation in alkaline medium was studied by means of cyclic voltammetry (CV), chronopotentiometry (CP), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS). The results showed that Ni@Pt/C electrocatalyst synthesized without SDS has superior catalytic activity toward borohydride oxidation (22016.92Ag Pt -1 ) in comparison with a catalyst prepared in the presence of SDS (17766.15Ag Pt -1 ) in NaBH 4 0.1M at 25°C. The Membrane Electrode Assembly (MEA) used in fuel cell set-up was fabricated with catalyst-coated membrane (CCM) technique. The effect of Ni@Pt/C catalysts prepared with two methods as anode catalyst on the performance of direct borohydride-hydrogen peroxide fuel cell was studied. The maximum power density was obtained using Ni@Pt/C catalyst synthesized without SDS at 60°C, 1M NaBH 4 and 2M H 2 O 2 (133.38mWcm -2 ). Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Tight Coupling of Metabolic Oscillations and Intracellular Water Dynamics in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Thoke, Henrik Seir; Tobiesen, Asger; Brewer, Jonathan R.

    2015-01-01

    We detected very strong coupling between the oscillating concentration of ATP and the dynamics of intracellular water during glycolysis in Saccharomyces cerevisiae. Our results indicate that: i) dipolar relaxation of intracellular water is heterogeneous within the cell and different from dilute...... conditions, ii) water dipolar relaxation oscillates with glycolysis and in phase with ATP concentration, iii) this phenomenon is scale-invariant from the subcellular to the ensemble of synchronized cells and, iv) the periodicity of both glycolytic oscillations and dipolar relaxation are equally affected by D...

  3. Handbook of fuel cell performance

    Energy Technology Data Exchange (ETDEWEB)

    Benjamin, T.G.; Camara, E.H.; Marianowski, L.G.

    1980-05-01

    The intent of this document is to provide a description of fuel cells, their performances and operating conditions, and the relationship between fuel processors and fuel cells. This information will enable fuel cell engineers to know which fuel processing schemes are most compatible with which fuel cells and to predict the performance of a fuel cell integrated with any fuel processor. The data and estimates presented are for the phosphoric acid and molten carbonate fuel cells because they are closer to commercialization than other types of fuel cells. Performance of the cells is shown as a function of operating temperature, pressure, fuel conversion (utilization), and oxidant utilization. The effect of oxidant composition (for example, air versus O/sub 2/) as well as fuel composition is examined because fuels provided by some of the more advanced fuel processing schemes such as coal conversion will contain varying amounts of H/sub 2/, CO, CO/sub 2/, CH/sub 4/, H/sub 2/O, and sulfur and nitrogen compounds. A brief description of fuel cells and their application to industrial, commercial, and residential power generation is given. The electrochemical aspects of fuel cells are reviewed. The phosphoric acid fuel cell is discussed, including how it is affected by operating conditions; and the molten carbonate fuel cell is discussed. The equations developed will help systems engineers to evaluate the application of the phosphoric acid and molten carbonate fuel cells to commercial, utility, and industrial power generation and waste heat utilization. A detailed discussion of fuel cell efficiency, and examples of fuel cell systems are given.

  4. Alternative Fuels

    Science.gov (United States)

    Alternative fuels include gaseous fuels such as hydrogen, natural gas, and propane; alcohols such as ethanol, methanol, and butanol; vegetable and waste-derived oils; and electricity. Overview of alternative fuels is here.

  5. Factors controlling metal fuel lifetime

    International Nuclear Information System (INIS)

    Porter, D.L.; Hofman, G.L.; Seidel, B.R.; Walters, L.C.

    1986-01-01

    The reliability of metal fuel elements is determined by a fuel burnup at which a statistically predicted number of fuel breaches would occur, the number of breaches determined by the amount of free fission gas which a particular reactor design can tolerate. The reliability is therefore measured using experimentally determined breach statistics, or by modelling fuel element behavior and those factors which contribute to cladding breach. The factors are fuel/cladding mechanical and chemical interactions, fission gas pressure, fuel phase transformations involving volume changes, and fission product effects on cladding integrity. Experimental data for EBR-II fuel elements has shown that the primary, and perhaps the only significant factor affecting metal fuel reliability, is the pressure-induced stresses caused by fission gas release. Other metal fuel/cladding systems may perform similarly

  6. Azithromycin effectiveness against intracellular infections of Francisella

    Directory of Open Access Journals (Sweden)

    Mann Barbara J

    2010-04-01

    Full Text Available Abstract Background Macrolide antibiotics are commonly administered for bacterial respiratory illnesses. Azithromycin (Az is especially noted for extremely high intracellular concentrations achieved within macrophages which is far greater than the serum concentration. Clinical strains of Type B Francisella (F. tularensis have been reported to be resistant to Az, however our laboratory Francisella strains were found to be sensitive. We hypothesized that different strains/species of Francisella (including Type A may have different susceptibilities to Az, a widely used and well-tolerated antibiotic. Results In vitro susceptibility testing of Az confirmed that F. tularensis subsp. holarctica Live Vaccine Strain (LVS (Type B was not sensitive while F. philomiragia, F. novicida, and Type A F. tularensis (NIH B38 and Schu S4 strain were susceptible. In J774A.1 mouse macrophage cells infected with F. philomiragia, F. novicida, and F. tularensis LVS, 5 μg/ml Az applied extracellularly eliminated intracellular Francisella infections. A concentration of 25 μg/ml Az was required for Francisella-infected A549 human lung epithelial cells, suggesting that macrophages are more effective at concentrating Az than epithelial cells. Mutants of RND efflux components (tolC and ftlC in F. novicida demonstrated less sensitivity to Az by MIC than the parental strain, but the tolC disc-inhibition assay demonstrated increased sensitivity, indicating a complex role for the outer-membrane transporter. Mutants of acrA and acrB mutants were less sensitive to Az than the parental strain, suggesting that AcrAB is not critical for the efflux of Az in F. novicida. In contrast, F. tularensis Schu S4 mutants ΔacrB and ΔacrA were more sensitive than the parental strain, indicating that the AcrAB may be important for Az efflux in F. tularensis Schu S4. F. novicida LPS O-antigen mutants (wbtN, wbtE, wbtQ and wbtA were found to be less sensitive in vitro to Az compared to the wild

  7. Fuel assembly

    International Nuclear Information System (INIS)

    Chaki, Masao; Nishida, Koji; Karasawa, Hidetoshi; Kanazawa, Toru; Orii, Akihito; Nagayoshi, Takuji; Kashiwai, Shin-ichi; Masuhara, Yasuhiro

    1998-01-01

    The present invention concerns a fuel assembly, for a BWR type nuclear reactor, comprising fuel rods in 9 x 9 matrix. The inner width of the channel box is about 132mm and the length of the fuel rods which are not short fuel rods is about 4m. Two water rods having a circular cross section are arranged on a diagonal line in a portion of 3 x 3 matrix at the center of the fuel assembly, and two fuel rods are disposed at vacant spaces, and the number of fuel rods is 74. Eight fuel rods are determined as short fuel rods among 74 fuel rods. Assuming the fuel inventory in the short fuel rod as X(kg), and the fuel inventory in the fuel rods other than the short fuel rods as Y(kg), X and Y satisfy the relation: X + Y ≥ 173m, Y ≤ - 9.7X + 292, Y ≤ - 0.3X + 203 and X > 0. Then, even when the short fuel rods are used, the fuel inventory is increased and fuel economy can be improved. (I.N.)

  8. Fuel assembly

    International Nuclear Information System (INIS)

    Yamazaki, Hajime.

    1995-01-01

    In a fuel assembly having fuel rods of different length, fuel pellets of mixed oxides of uranium and plutonium are loaded to a short fuel rod. The volume ratio of a pellet-loaded portion to a plenum portion of the short fuel rod is made greater than the volume ratio of a fuel rod to which uranium fuel pellets are loaded. In addition, the volume of the plenum portion of the short fuel rod is set greater depending on the plutonium content in the loaded fuel pellets. MOX fuel pellets are loaded on the short fuel rods having a greater degree of freedom relevant to the setting for the volume of the plenum portion compared with that of a long rod fuel, and the volume of the plenum portion is ensured greater depending on the plutonium content. Even if a large amount of FP gas and He gas are discharged from the MOX fuels compared with that from the uranium fuels, the internal pressure of the MOX fuel rod during operation is maintained substantially identical with that of the uranium fuel rod, so that a risk of generating excess stresses applied to the fuel cladding tubes and rupture of fuels are greatly reduced. (N.H.)

  9. Intracellular bacteria: the origin of dinoflagellate toxicity.

    Science.gov (United States)

    Silva, E S

    1990-01-01

    Dinoflagellate blooms of the same species have been registered either as toxic or nontoxic and, in the latter case, toxicity may be of different types. A hypothesis has been formulated according to which the bacteria having in some way taken part in the toxin formation are either inside the dinoflagellate cell or in the nutritive liquid. The presence of intracellular bacteria in those microorganisms has been studied mainly in material from cultures, a few from the sea, and several strains were isolated from different species. Experiments with crossed inoculations have shown that the bacterial strain from Gonyaulax tamarensis caused the cells of some other species to become toxic. From nontoxic clonal cultures of Prorocentrum balticum, Glenodinium foliaceum, and Gyrodinium instriatum, after inoculation of that bacterial strain, cultures were obtained whose cell extracts showed the same kind of toxicity as G. tamarensis. No toxic action could be found in the extracts of the bacterial cells form the assayed strains. The interference of intracellular bacteria in the metabolism of dinoflagellates must be the main cause of their toxicity.

  10. Fluorescent nanoparticles for intracellular sensing: a review.

    Science.gov (United States)

    Ruedas-Rama, Maria J; Walters, Jamie D; Orte, Angel; Hall, Elizabeth A H

    2012-11-02

    Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Nuclear fuels

    International Nuclear Information System (INIS)

    Gangwani, Saloni; Chakrabortty, Sumita

    2011-01-01

    Nuclear fuel is a material that can be consumed to derive nuclear energy, by analogy to chemical fuel that is burned for energy. Nuclear fuels are the most dense sources of energy available. Nuclear fuel in a nuclear fuel cycle can refer to the fuel itself, or to physical objects (for example bundles composed of fuel rods) composed of the fuel material, mixed with structural, neutron moderating, or neutron reflecting materials. Long-lived radioactive waste from the back end of the fuel cycle is especially relevant when designing a complete waste management plan for SNF. When looking at long-term radioactive decay, the actinides in the SNF have a significant influence due to their characteristically long half-lives. Depending on what a nuclear reactor is fueled with, the actinide composition in the SNF will be different. The following paper will also include the uses. advancements, advantages, disadvantages, various processes and behavior of nuclear fuels

  12. Fuel and nuclear fuel cycle

    International Nuclear Information System (INIS)

    Prunier, C.

    1998-01-01

    The nuclear fuel is studied in detail, the best choice and why in relation with the type of reactor, the properties of the fuel cans, the choice of fuel materials. An important part is granted to the fuel assembly of PWR type reactor and the performances of nuclear fuels are tackled. The different subjects for research and development are discussed and this article ends with the particular situation of mixed oxide fuels ( materials, behavior, efficiency). (N.C.)

  13. Identification of lactoferricin B intracellular targets using an Escherichia coli proteome chip.

    Science.gov (United States)

    Tu, Yu-Hsuan; Ho, Yu-Hsuan; Chuang, Ying-Chih; Chen, Po-Chung; Chen, Chien-Sheng

    2011-01-01

    Lactoferricin B (LfcinB) is a well-known antimicrobial peptide. Several studies have indicated that it can inhibit bacteria by affecting intracellular activities, but the intracellular targets of this antimicrobial peptide have not been identified. Therefore, we used E. coli proteome chips to identify the intracellular target proteins of LfcinB in a high-throughput manner. We probed LfcinB with E. coli proteome chips and further conducted normalization and Gene Ontology (GO) analyses. The results of the GO analyses showed that the identified proteins were associated with metabolic processes. Moreover, we validated the interactions between LfcinB and chip assay-identified proteins with fluorescence polarization (FP) assays. Sixteen proteins were identified, and an E. coli interaction database (EcID) analysis revealed that the majority of the proteins that interact with these 16 proteins affected the tricarboxylic acid (TCA) cycle. Knockout assays were conducted to further validate the FP assay results. These results showed that phosphoenolpyruvate carboxylase was a target of LfcinB, indicating that one of its mechanisms of action may be associated with pyruvate metabolism. Thus, we used pyruvate assays to conduct an in vivo validation of the relationship between LfcinB and pyruvate level in E. coli. These results showed that E. coli exposed to LfcinB had abnormal pyruvate amounts, indicating that LfcinB caused an accumulation of pyruvate. In conclusion, this study successfully revealed the intracellular targets of LfcinB using an E. coli proteome chip approach.

  14. Fuel assembly

    International Nuclear Information System (INIS)

    Sakuyama, Tadashi; Mukai, Hideyuki.

    1988-01-01

    Purpose: To prevent the bending of a fuel rod caused by the difference in the elongation between a joined fuel rod and a standard fuel rod thereby maintain the fuel rod integrity. Constitution: A joined fuel rod is in a thread engagement at its lower end plug thereof with a lower plate, while passed through at its upper end plug into an upper tie plate and secured with a nut. Further, a standard fuel rod is engaged at its upper end plug and lower end plug with the upper tie plate and the lower tie plate respectively. Expansion springs are mounted to the upper end plugs of these bonded fuel rods and the standard fuel rods for preventing this lifting. Each of the fuel rods comprises a plurality of sintered pellets of nuclear fuel materials laminated in a zircaloy fuel can. The content of the alloy ingredient in the fuel can of the bonded fuel rod is made greater than that of the alloy ingredient of the standard fuel rod. this can increase the elongation for the bonded fuel rod, and the spring of the standard fuel rod is tightly bonded to prevent the bending. (Yoshino, Y.)

  15. Brucella abortus Induces a Warburg Shift in Host Metabolism That Is Linked to Enhanced Intracellular Survival of the Pathogen.

    Science.gov (United States)

    Czyż, Daniel M; Willett, Jonathan W; Crosson, Sean

    2017-08-01

    Intracellular bacterial pathogens exploit host cell resources to replicate and survive inside the host. Targeting these host systems is one promising approach to developing novel antimicrobials to treat intracellular infections. We show that human macrophage-like cells infected with Brucella abortus undergo a metabolic shift characterized by attenuated tricarboxylic acid cycle metabolism, reduced amino acid consumption, altered mitochondrial localization, and increased lactate production. This shift to an aerobic glycolytic state resembles the Warburg effect, a change in energy production that is well described in cancer cells and also occurs in activated inflammatory cells. B. abortus efficiently uses lactic acid as its sole carbon and energy source and requires the ability to metabolize lactate for normal survival in human macrophage-like cells. We demonstrate that chemical inhibitors of host glycolysis and lactate production do not affect in vitro growth of B. abortus in axenic culture but decrease its survival in the intracellular niche. Our data support a model in which infection shifts host metabolism to a Warburg-like state, and B. abortus uses this change in metabolism to promote intracellular survival. Pharmacological perturbation of these features of host cell metabolism may be a useful strategy to inhibit infection by intracellular pathogens. IMPORTANCE Brucella spp. are intracellular bacterial pathogens that cause disease in a range of mammals, including livestock. Transmission from livestock to humans is common and can lead to chronic human disease. Human macrophage-like cells infected with Brucella abortus undergo a Warburg-like metabolic shift to an aerobic glycolytic state where the host cells produce lactic acid and have reduced amino acid catabolism. We provide evidence that the pathogen can exploit this change in host metabolism to support growth and survival in the intracellular niche. Drugs that inhibit this shift in host cell metabolism

  16. Affects and Affect Consciousness

    Science.gov (United States)

    MONSEN, JON T.; EILERTSEN, DAG ERIK; MELGÅRD, TROND; ØDEGÅRD, PÅL

    1996-01-01

    Affect consciousness (AC) was operationalized as degrees of awareness, tolerance, nonverbal expression, and conceptual expression of nine specific affects. A semistructured interview (ACI) and separate scales were developed to assess these aspects of affect integration. Their psychometric properties were preliminarily explored by having 20 former psychiatric outpatients complete the interview. Concurrent validity was assessed by using DSM-III-R Axis I and II diagnoses, the Health-Sickness Rating Scale, SCL-90-R, and several indexes from the Minnesota Multiphasic Personality Inventory. Satisfactory interrater reliability and high levels of internal consistency supported the construct validity of the measure. Results suggest the most meaningful use of this instrument is in measuring specific affect and overall AC. Clinically, the ACI has provided highly specific and relevant qualitative data for use in planning psychotherapeutic interventions. PMID:22700292

  17. Fuel processing

    International Nuclear Information System (INIS)

    Allardice, R.H.

    1990-01-01

    The technical and economic viability of the fast breeder reactor as an electricity generating system depends not only upon the reactor performance but also on a capability to recycle plutonium efficiently, reliably and economically through the reactor and fuel cycle facilities. Thus the fuel cycle is an integral and essential part of the system. Fuel cycle research and development has focused on demonstrating that the challenging technical requirements of processing plutonium fuel could be met and that the sometimes conflicting requirements of the fuel developer, fuel fabricator and fuel reprocessor could be reconciled. Pilot plant operation and development and design studies have established both the technical and economic feasibility of the fuel cycle but scope for further improvement exists through process intensification and flowsheet optimization. These objectives and the increasing processing demands made by the continuing improvement to fuel design and irradiation performance provide an incentive for continuing fuel cycle development work. (author)

  18. Liposome-based Formulation for Intracellular Delivery of Functional Proteins

    Directory of Open Access Journals (Sweden)

    Benoît Chatin

    2015-01-01

    Full Text Available The intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the β-galactosidase (β-gal enzyme and the anti-cytokeratin8 (K8 antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium-tren-cholesterol (BGTC (bis (guanidinium-tren-cholesterol combined to the colipid dioleoyl phosphatidylethanolamine (DOPE (dioleoyl phosphatidylethanolamine was shown to efficiently deliver the β-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC:DOPE/β-gal and DOSP:MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP:MM27/K8 rescues the cyclic adenosine monophosphate (cAMP-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.

  19. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications

    Science.gov (United States)

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F. L.; Leonhardt, Heinrich

    2018-01-01

    Abstract Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. PMID:28913971

  20. Intracellular pH in sperm physiology.

    Science.gov (United States)

    Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

    2014-08-01

    Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications.

    Science.gov (United States)

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F L; Leonhardt, Heinrich; Hackenberger, Christian P R

    2018-02-23

    Nanobodies can be seen as next-generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site-specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  2. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  3. Intracellular sphingosine releases calcium from lysosomes.

    Science.gov (United States)

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-11-27

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

  4. [Limbic encephalitis with antibodies against intracellular antigens].

    Science.gov (United States)

    Morita, Akihiko; Kamei, Satoshi

    2010-04-01

    Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

  5. Single-cell intracellular nano-pH probes†

    OpenAIRE

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2015-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular p...

  6. Intracellular delivery of poly(I:C) induces apoptosis of fibroblast-like synoviocytes via an unknown dsRNA sensor

    Energy Technology Data Exchange (ETDEWEB)

    Karpus, Olga N.; Hsiao, Cheng-Chih; Kort, Hanneke de; Tak, Paul P.; Hamann, Jörg, E-mail: j.hamann@amc.uva.nl

    2016-08-26

    Fibroblast-like synoviocytes (FLS) express functional membranous and cytoplasmic sensors for double-stranded (ds)RNA. Notably, FLS undergo apoptosis upon transfection with the synthetic dsRNA analog poly(I:C). We here studied the mechanism of intracellular poly(I:C) recognition and subsequent cell death in FLS. FLS responded similarly to poly(I:C) or 3pRNA transfection; however, only intracellular delivery of poly(I:C) induced significant cell death, accompanied by upregulation of pro-apoptotic proteins Puma and Noxa, caspase 3 cleavage, and nuclear segregation. Knockdown of the DExD/H-box helicase MDA5 did not affect the response to intracellular poly(I:C); in contrast, knockdown of RIG-I abrogated the response to 3pRNA. Knockdown of the downstream adaptor proteins IPS, STING, and TRIF or inhibition of TBK1 did not affect the response to intracellular poly(I:C), while knockdown of IFNAR blocked intracellular poly(I:C)-mediated signaling and cell death. We conclude that a so far unknown intracellular sensor recognizes linear dsRNA and induces apoptosis in FLS. - Highlights: • Intracellular poly(I:C) and 3pRNA evoke immune responses in FLS. • Only intracellular delivery of poly(I:C) induces FLS apoptosis. • FLS do not require MDA5 for their response to intracellular poly(I:C). • FLS respond to intracellular poly(I:C) independent of IPS and STING. • An unknown intracellular sensor recognizes linear dsRNA in FLS.

  7. Quality assurance of nuclear fuel

    International Nuclear Information System (INIS)

    1994-01-01

    The guide presents the quality assurance requirements to be completed with in the procurement, design, manufacture, transport, handling and operation of the nuclear fuel. The guide also applies to the procurement of the control rods and the shield elements to be placed in the reactor. The guide is mainly aimed for the licensee responsible for the procurement and operation of fuel, for the fuel designer and manufacturer and for other organizations whose activities affect fuel quality, the safety of fuel transport, storage and operation. (2 refs.)

  8. Nuclear fuels

    International Nuclear Information System (INIS)

    Beauvy, M.; Berthoud, G.; Defranceschi, M.; Ducros, G.; Guerin, Y.; Limoge, Y.; Madic, Ch.; Santarini, G.; Seiler, J.M.; Sollogoub, P.; Vernaz, E.; Guillet, J.L.; Ballagny, A.; Bechade, J.L.; Bonin, B.; Brachet, J.Ch.; Delpech, M.; Dubois, S.; Ferry, C.; Freyss, M.; Gilbon, D.; Grouiller, J.P.; Iracane, D.; Lansiart, S.; Lemoine, P.; Lenain, R.; Marsault, Ph.; Michel, B.; Noirot, J.; Parrat, D.; Pelletier, M.; Perrais, Ch.; Phelip, M.; Pillon, S.; Poinssot, Ch.; Vallory, J.; Valot, C.; Pradel, Ph.; Bonin, B.; Bouquin, B.; Dozol, M.; Lecomte, M.; Vallee, A.; Bazile, F.; Parisot, J.F.; Finot, P.; Roberts, J.F.

    2009-01-01

    Fuel is one of the essential components in a reactor. It is within that fuel that nuclear reactions take place, i.e. fission of heavy atoms, uranium and plutonium. Fuel is at the core of the reactor, but equally at the core of the nuclear system as a whole. Fuel design and properties influence reactor behavior, performance, and safety. Even though it only accounts for a small part of the cost per kilowatt-hour of power provided by current nuclear power plants, good utilization of fuel is a major economic issue. Major advances have yet to be achieved, to ensure longer in-reactor dwell-time, thus enabling fuel to yield more energy; and improve ruggedness. Aside from economics, and safety, such strategic issues as use of plutonium, conservation of resources, and nuclear waste management have to be addressed, and true technological challenges arise. This Monograph surveys current knowledge regarding in-reactor behavior, operating limits, and avenues for R and D. It also provides illustrations of ongoing research work, setting out a few noteworthy results recently achieved. Content: 1 - Introduction; 2 - Water reactor fuel: What are the features of water reactor fuel? 9 (What is the purpose of a nuclear fuel?, Ceramic fuel, Fuel rods, PWR fuel assemblies, BWR fuel assemblies); Fabrication of water reactor fuels (Fabrication of UO 2 pellets, Fabrication of MOX (mixed uranium-plutonium oxide) pellets, Fabrication of claddings); In-reactor behavior of UO 2 and MOX fuels (Irradiation conditions during nominal operation, Heat generation, and removal, The processes involved at the start of irradiation, Fission gas behavior, Microstructural changes); Water reactor fuel behavior in loss of tightness conditions (Cladding, the first containment barrier, Causes of failure, Consequences of a failure); Microscopic morphology of fuel ceramic and its evolution under irradiation; Migration and localization of fission products in UOX and MOX matrices (The ceramic under irradiation

  9. Nuclear fuels

    Energy Technology Data Exchange (ETDEWEB)

    Beauvy, M.; Berthoud, G.; Defranceschi, M.; Ducros, G.; Guerin, Y.; Limoge, Y.; Madic, Ch.; Santarini, G.; Seiler, J.M.; Sollogoub, P.; Vernaz, E.; Guillet, J.L.; Ballagny, A.; Bechade, J.L.; Bonin, B.; Brachet, J.Ch.; Delpech, M.; Dubois, S.; Ferry, C.; Freyss, M.; Gilbon, D.; Grouiller, J.P.; Iracane, D.; Lansiart, S.; Lemoine, P.; Lenain, R.; Marsault, Ph.; Michel, B.; Noirot, J.; Parrat, D.; Pelletier, M.; Perrais, Ch.; Phelip, M.; Pillon, S.; Poinssot, Ch.; Vallory, J.; Valot, C.; Pradel, Ph.; Bonin, B.; Bouquin, B.; Dozol, M.; Lecomte, M.; Vallee, A.; Bazile, F.; Parisot, J.F.; Finot, P.; Roberts, J.F

    2009-07-01

    Fuel is one of the essential components in a reactor. It is within that fuel that nuclear reactions take place, i.e. fission of heavy atoms, uranium and plutonium. Fuel is at the core of the reactor, but equally at the core of the nuclear system as a whole. Fuel design and properties influence reactor behavior, performance, and safety. Even though it only accounts for a small part of the cost per kilowatt-hour of power provided by current nuclear power plants, good utilization of fuel is a major economic issue. Major advances have yet to be achieved, to ensure longer in-reactor dwell-time, thus enabling fuel to yield more energy; and improve ruggedness. Aside from economics, and safety, such strategic issues as use of plutonium, conservation of resources, and nuclear waste management have to be addressed, and true technological challenges arise. This Monograph surveys current knowledge regarding in-reactor behavior, operating limits, and avenues for R and D. It also provides illustrations of ongoing research work, setting out a few noteworthy results recently achieved. Content: 1 - Introduction; 2 - Water reactor fuel: What are the features of water reactor fuel? 9 (What is the purpose of a nuclear fuel?, Ceramic fuel, Fuel rods, PWR fuel assemblies, BWR fuel assemblies); Fabrication of water reactor fuels (Fabrication of UO{sub 2} pellets, Fabrication of MOX (mixed uranium-plutonium oxide) pellets, Fabrication of claddings); In-reactor behavior of UO{sub 2} and MOX fuels (Irradiation conditions during nominal operation, Heat generation, and removal, The processes involved at the start of irradiation, Fission gas behavior, Microstructural changes); Water reactor fuel behavior in loss of tightness conditions (Cladding, the first containment barrier, Causes of failure, Consequences of a failure); Microscopic morphology of fuel ceramic and its evolution under irradiation; Migration and localization of fission products in UOX and MOX matrices (The ceramic under

  10. Fuel assembly

    International Nuclear Information System (INIS)

    Fujibayashi, Toru.

    1970-01-01

    Herein disclosed is a fuel assembly in which a fuel rod bundle is easily detachable by rotating a fuel rod fastener rotatably mounted to the upper surface of an upper tie-plate supporting a fuel bundle therebelow. A locking portion at the leading end of each fuel rod protrudes through the upper tie-plate and is engaged with or separated from the tie-plate by the rotation of the fastener. The removal of a desired fuel rod can therefore be remotely accomplished without the necessity of handling pawls, locking washers and nuts. (Owens, K.J.)

  11. Nuclear fuel

    International Nuclear Information System (INIS)

    D Hondt, P.

    1998-01-01

    The research and development programme on nuclear fuel at the Belgian Nuclear Research Centre SCK/CEN is described. The objective of this programme is to enhance the quantitative prediction of the operational limits of nuclear fuel and to assess the behaviour of fuel under incidental and accidental conditions. Progress is described in different domains including the modelling of fission gas release in LWR fuel, thermal conductivity, basic physical phenomena, post-irradiation examination for fuel performance assessment, and conceptual studies of incidental and accidental fuel experiments

  12. Nuclear fuel quality assurance

    International Nuclear Information System (INIS)

    1976-01-01

    Full text: Quality assurance is used extensively in the design, construction and operation of nuclear power plants. This methodology is applied to all activities affecting the quality of a nuclear power plant in order to obtain confidence that an item or a facility will perform satisfactorily in service. Although the achievement of quality is the responsibility of all parties participating in a nuclear power project, establishment and implementation of the quality assurance programme for the whole plant is a main responsibility of the plant owner. For the plant owner, the main concern is to achieve control over the quality of purchased products or services through contractual arrangements with the vendors. In the case of purchase of nuclear fuel, the application of quality assurance might be faced with several difficulties because of the lack of standardization in nuclear fuel and the proprietary information of the fuel manufacturers on fuel design specifications and fuel manufacturing procedures. The problems of quality assurance for purchase of nuclear fuel were discussed in detail during the seminar. Due to the lack of generally acceptable standards, the successful application of the quality assurance concept to the procurement of fuel depends on how much information can be provided by the fuel manufacturer to the utility which is purchasing fuel, and in what form and how early this information can be provided. The extent of information transfer is basically set out in the individual vendor-utility contracts, with some indirect influence from the requirements of regulatory bodies. Any conflict that exists appears to come from utilities which desire more extensive control over the product they are buying. There is a reluctance on the part of vendors to permit close insight of the purchasers into their design and manufacturing procedures, but there nevertheless seems to be an increasing trend towards release of more information to the purchasers. It appears that

  13. Effect of bauhinia bauhinioides kallikrein inhibitor on endothelial proliferation and intracellular calcium concentration.

    Science.gov (United States)

    Bilgin, M; Burgazli, K M; Rafiq, A; Mericliler, M; Neuhof, C; Oliva, M L; Parahuleva, M; Soydan, N; Doerr, O; Abdallah, Y; Erdogan, A

    2014-01-01

    Proteinase inhibitors act as a defensive system against predators e.g. insects, in plants. Bauhinia bauhinioides kallikrein inhibitor (BbKI) is a serine proteinase inhibitor, isolated from seeds of Bauhinia bauhinioides and is structurally similar to plant Kunitz-type inhibitors but lacks disulfide bridges. In this study we evaluated the antiproliferative effect of BbKI on endothelial cells and its impact on changes in membrane potential and intracellular calcium. HUVEC proliferation was significantly reduced by incubation with BbKI 50 and 100 µM 12% and 13%. Furthermore, BbKI (100 µM) exposure caused a significant increase in intracellular Ca2+ concentration by 35% as compared to untreated control. The intracellular rise in calcium was not affected by the absence of extracellular calcium. BBKI also caused a significant change in the cell membrane potential but the antiproliferative effect was independent of changes in membrane potential. BBKI has an antiproliferative effect on HUVEC, which is independent of the changes in membrane potential, and it causes an increase in intracellular Ca2+.

  14. MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb.

    Science.gov (United States)

    Wang, Jinli; Yang, Kun; Zhou, Lin; Minhaowu; Wu, Yongjian; Zhu, Min; Lai, Xiaomin; Chen, Tao; Feng, Lianqiang; Li, Meiyu; Huang, Chunyu; Zhong, Qiu; Huang, Xi

    2013-01-01

    Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment.

  15. MicroRNA-155 promotes autophagy to eliminate intracellular mycobacteria by targeting Rheb.

    Directory of Open Access Journals (Sweden)

    Jinli Wang

    Full Text Available Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7 reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3'-untranslated region of Ras homologue enriched in brain (Rheb, a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment.

  16. Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery

    International Nuclear Information System (INIS)

    Majumdar, S.; Basu, S.K.

    1991-01-01

    p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections

  17. Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification

    Directory of Open Access Journals (Sweden)

    Bush Ashley I

    2009-01-01

    Full Text Available Abstract Background The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Aβ aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results In the present work, we found that intracellular Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic and V18A (NIC. Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism.

  18. Fuel management

    International Nuclear Information System (INIS)

    Schwarz, E.R.

    1975-01-01

    Description of the operation of power plants and the respective procurement of fuel to fulfil the needs of the grid. The operation of the plants shall be optimised with respect to the fuel cost. (orig./RW) [de

  19. Fuel gases

    International Nuclear Information System (INIS)

    Anon.

    1996-01-01

    This paper gives a brief presentation of the context, perspectives of production, specificities, and the conditions required for the development of NGV (Natural Gas for Vehicle) and LPG-f (Liquefied Petroleum Gas fuel) alternative fuels. After an historical presentation of 80 years of LPG evolution in vehicle fuels, a first part describes the economical and environmental advantages of gaseous alternative fuels (cleaner combustion, longer engines life, reduced noise pollution, greater natural gas reserves, lower political-economical petroleum dependence..). The second part gives a comparative cost and environmental evaluation between the available alternative fuels: bio-fuels, electric power and fuel gases, taking into account the processes and constraints involved in the production of these fuels. (J.S.)

  20. Fuel cycles

    International Nuclear Information System (INIS)

    Hawley, N.J.

    1983-05-01

    AECL publications, from the open literature, on fuels and fuel cycles used in CANDU reactors are listed in this bibliography. The accompanying index is by subject. The bibliography will be brought up to date periodically

  1. Implications and control of fuel-cladding chemical interaction for LMFBR fuel pin design

    International Nuclear Information System (INIS)

    Roake, W.E.

    1977-01-01

    Fuel-cladding-chemical-interaction (FCCI) is typically incorporated into the design of an LMFBR fuel pin as a wastage allowance. Several interrelated factors are considered during the evolution of an LMFBR fuel pin design. Those which are indirectly affected by FCCI include: allowable pin power, fuel restructuring, fission gas migration and release from the fuel, fuel cracking, fuel swelling, in-reactor cladding creep, cladding swelling, and the cladding mechanical strain. Chemical activity of oxygen is the most readily controlled factor in FCCI. Two methods are being investigated: control of total oxygen inventory by limiting fuel O/M, and control of oxygen activity with buffer metals

  2. Implications and control of fuel-cladding chemical interaction for LMFBR fuel pin design

    Energy Technology Data Exchange (ETDEWEB)

    Roake, W E [Westinghouse-Hanford Co., Richland, WA (United States)

    1977-04-01

    Fuel-cladding-chemical-interaction (FCCI) is typically incorporated into the design of an LMFBR fuel pin as a wastage allowance. Several interrelated factors are considered during the evolution of an LMFBR fuel pin design. Those which are indirectly affected by FCCI include: allowable pin power, fuel restructuring, fission gas migration and release from the fuel, fuel cracking, fuel swelling, in-reactor cladding creep, cladding swelling, and the cladding mechanical strain. Chemical activity of oxygen is the most readily controlled factor in FCCI. Two methods are being investigated: control of total oxygen inventory by limiting fuel O/M, and control of oxygen activity with buffer metals.

  3. LIPID SYNTHESIS, INTRACELLULAR TRANSPORT, AND SECRETION

    Science.gov (United States)

    Stein, Olga; Stein, Yechezkiel

    1967-01-01

    In the mammary glands of lactating albino mice injected intravenously with 9, 10-oleic acid-3H or 9, 10-palmitic acid-3H, it has been shown that the labeled fatty acids are incorporated into mammary gland glycerides. The labeled lipid in the mammary gland 1 min after injection was in esterified form (> 95%), and the radioautographic reaction was seen over the rough endoplasmic reticulum and over lipid droplets, both intracellular and intraluminal. At 10–60 min after injection, the silver grains were concentrated predominantly over lipid droplets. There was no concentration of radioactivity over the granules in the Golgi apparatus, at any time interval studied. These findings were interpreted to indicate that after esterification of the fatty acid into glycerides in the rough endoplasmic reticulum an in situ aggregation of lipid occurs, with acquisition of droplet form. The release of the lipid into the lumen proceeds directly and not through the Golgi apparatus, in contradistinction to the mode of secretion of casein in the mammary gland or of lipoprotein in the liver. The presence of strands of endoplasmic reticulum attached to intraluminal lipid droplets provides a structural counterpart to the milk microsomes described in ruminant milk. PMID:6033535

  4. Endothelial remodelling and intracellular calcium machinery.

    Science.gov (United States)

    Moccia, F; Tanzi, F; Munaron, L

    2014-05-01

    Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

  5. Intracellular events regulating cross-presentation

    Directory of Open Access Journals (Sweden)

    Peter eCresswell

    2012-06-01

    Full Text Available Cross-presentation plays a fundamental role in the induction of CD8-T cell immunity. However, although more than three decades have passed since its discovery, surprisingly little is known about the exact mechanisms involved. Here we give an overview of the components involved at different stages of this process. First, antigens must be internalized into the cross-presenting cell. The involvement of different receptors, method of antigen uptake, and nature of the antigen can influence intracellular trafficking and access to the cross-presentation pathway. Once antigens access the endocytic system, different requirements for endosomal/phagosomal processing arise, such as proteolysis and reduction of disulfide bonds. The majority of cross-presented peptides are generated by proteasomal degradation. Therefore, antigens must cross a membrane barrier in a manner analogous to the fate of misfolded proteins in the endoplasmic reticulum (ER that are retrotranslocated into the cytosol for degradation. Indeed, some components of the ER-associated degradation (ERAD machinery have been implicated in cross-presentation. Further complicating the matter, endosomal and phagosomal compartments have been suggested as alternative sites to the ER for loading of peptides on MHC class I molecules. Finally, the antigen presenting cells involved, particularly dendritic cell subsets and their state of maturation, influence the efficiency of cross-presentation.

  6. Intracellular recording from a spider vibration receptor.

    Science.gov (United States)

    Gingl, Ewald; Burger, Anna-M; Barth, Friedrich G

    2006-05-01

    The present study introduces a new preparation of a spider vibration receptor that allows intracellular recording of responses to natural mechanical or electrical stimulation of the associated mechanoreceptor cells. The spider vibration receptor is a lyriform slit sense organ made up of 21 cuticular slits located on the distal end of the metatarsus of each walking leg. The organ is stimulated when the tarsus receives substrate vibrations, which it transmits to the organ's cuticular structures, reducing the displacement to about one tenth due to geometrical reasons. Current clamp recording was used to record action potentials generated by electrical or mechanical stimuli. Square pulse stimulation identified two groups of sensory cells, the first being single-spike cells which generated only one or two action potentials and the second being multi-spike cells which produced bursts of action potentials. When the more natural mechanical sinusoidal stimulation was applied, differences in adaptation rate between the two cell types remained. In agreement with prior extracellular recordings, both cell types showed a decrease in the threshold tarsus deflection with increasing stimulus frequency. Off-responses to mechanical stimuli have also been seen in the metatarsal organ for the first time.

  7. On the Computing Potential of Intracellular Vesicles.

    Science.gov (United States)

    Mayne, Richard; Adamatzky, Andrew

    2015-01-01

    Collision-based computing (CBC) is a form of unconventional computing in which travelling localisations represent data and conditional routing of signals determines the output state; collisions between localisations represent logical operations. We investigated patterns of Ca2+-containing vesicle distribution within a live organism, slime mould Physarum polycephalum, with confocal microscopy and observed them colliding regularly. Vesicles travel down cytoskeletal 'circuitry' and their collisions may result in reflection, fusion or annihilation. We demonstrate through experimental observations that naturally-occurring vesicle dynamics may be characterised as a computationally-universal set of Boolean logical operations and present a 'vesicle modification' of the archetypal CBC 'billiard ball model' of computation. We proceed to discuss the viability of intracellular vesicles as an unconventional computing substrate in which we delineate practical considerations for reliable vesicle 'programming' in both in vivo and in vitro vesicle computing architectures and present optimised designs for both single logical gates and combinatorial logic circuits based on cytoskeletal network conformations. The results presented here demonstrate the first characterisation of intracelluar phenomena as collision-based computing and hence the viability of biological substrates for computing.

  8. Nuclear fuels

    International Nuclear Information System (INIS)

    2008-01-01

    The nuclear fuel is one of the key component of a nuclear reactor. Inside it, the fission reactions of heavy atoms, uranium and plutonium, take place. It is located in the core of the reactor, but also in the core of the whole nuclear system. Its design and properties influence the behaviour, the efficiency and the safety of the reactor. Even if it represents a weak share of the generated electricity cost, its proper use represents an important economic stake. Important improvements remain to be made to increase its residence time inside the reactor, to supply more energy, and to improve its robustness. Beyond the economical and safety considerations, strategical questions have to find an answer, like the use of plutonium, the management of resources and the management of nuclear wastes and real technological challenges have to be taken up. This monograph summarizes the existing knowledge about the nuclear fuel, its behaviour inside the reactor, its limits of use, and its R and D tracks. It illustrates also the researches in progress and presents some key results obtained recently. Content: 1 - Introduction; 2 - The fuel of water-cooled reactors: aspect, fabrication, behaviour of UO 2 and MOX fuels inside the reactor, behaviour in loss of tightness situation, microscopic morphology of fuel ceramics and evolution under irradiation - migration and localisation of fission products in UOX and MOX matrices, modeling of fuels behaviour - modeling of defects and fission products in the UO 2 ceramics by ab initio calculations, cladding and assembly materials, pellet-cladding interaction, advanced UO 2 and MOX ceramics, mechanical behaviour of the fuel assembly, fuel during a loss of coolant accident, fuel during a reactivity accident, fuel during a serious accident, fuel management inside reactor cores, fuel cycle materials balance, long-term behaviour of the spent fuel, fuel of boiling water reactors; 3 - the fuel of liquid metal fast reactors: fast neutrons radiation

  9. Modeling HIV-1 intracellular replication: two simulation approaches

    NARCIS (Netherlands)

    Zarrabi, N.; Mancini, E.; Tay, J.; Shahand, S.; Sloot, P.M.A.

    2010-01-01

    Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular

  10. Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

    Science.gov (United States)

    Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

    2018-06-04

    Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

  11. Fuel pellet

    International Nuclear Information System (INIS)

    Hayashi, K.

    1980-01-01

    Fuel pellet for insertion into a cladding tube in order to form a fuel element or a fuel rod. The fuel pellet has got a belt-like projection around its essentially cylindrical lateral circumferential surface. The upper and lower edges in vertical direction of this belt-like projection are wave-shaped. The projection is made of the same material as the bulk pellet. Both are made in one piece. (orig.) [de

  12. Fossil Fuels.

    Science.gov (United States)

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with fossil fuels. Some topics covered are historic facts, development of fuels, history of oil production, current and future trends of the oil industry, refining fossil fuels, and environmental problems. Material in each unit may…

  13. Fuel element

    International Nuclear Information System (INIS)

    1974-01-01

    A new fuel can with a loose bottom and head is described. The fuel bar is attached to the loose bottom and head with two grid poles keeping the distance between bottom and head. A bow-shaped handle is attached to the head so that the fuel bar can be lifted from the can

  14. Fuel reprocessing and waste management

    International Nuclear Information System (INIS)

    Philippone, R.L.; Kaiser, R.A.

    1989-01-01

    Because of different economic, social and political factors, there has been a tendency to compartmentalize the commercial nuclear power industry into separate power and fuel cycle operations to a greater degree in some countries compared to other countries. The purpose of this paper is to describe how actions in one part of the industry can affect the other parts and recommend an overall systems engineering approach which incorporates more cooperation and coordination between individual parts of the fuel cycle. Descriptions are given of the fuel cycle segments and examples are presented of how a systems engineering approach has benefitted the fuel cycle. Descriptions of fuel reprocessing methods and the waste forms generated are given. Illustrations are presented describing how reprocessing options affect waste management operations and how waste management decisions affect reprocessing

  15. TACO: fuel pin performance analysis

    International Nuclear Information System (INIS)

    Stoudt, R.H.; Buchanan, D.T.; Buescher, B.J.; Losh, L.L.; Wilson, H.W.; Henningson, P.J.

    1977-08-01

    The thermal performance of fuel in an LWR during its operational lifetime must be described for LOCA analysis as well as for other safety analyses. The determination of stored energy in the LOCA analysis, for example, requires a conservative fuel pin thermal performance model that is capable of calculating fuel and cladding behavior, including the gap conductance between the fuel and cladding, as a function of burnup. The determination of parameters that affect the fuel and cladding performance, such as fuel densification, fission gas release, cladding dimensional changes, fuel relocation, and thermal expansion, should be accounted for in the model. Babcock and Wilcox (B and W) has submitted a topical report, BAW-10087P, December 1975, which describes their thermal performance model TACO. A summary of the elements that comprise the TACO model and an evaluation are presented

  16. Quality management of nuclear fuel

    International Nuclear Information System (INIS)

    2006-01-01

    The Guide presents the quality management requirements to be complied with in the procurement, design, manufacture, transport, receipt, storage, handling and operation of nuclear fuel. The Guide also applies to control rods and shield elements to be placed in the reactor. The Guide is mainly aimed for the licensee responsible for the procurement and operation of fuel, for the fuel designer and manufacturer and for other organisations, whose activities affect fuel quality and the safety of fuel transport, storage and operation. General requirements for nuclear fuel are presented in Section 114 of the Finnish Nuclear Energy Decree and in Section 15 of the Government Decision (395/1991). Regulatory control of the safety of fuel is described in Guides YVL6.1, YVL6.2 and YVL6.3. An overview of the regulatory control of nuclear power plants carried out by STUK (Radiation and Nuclear Safety Authority, Finland) is clarified in Guide YVL1.1

  17. The Fuel Performance Analysis of LWR Fuel containing High Thermal Conductivity Reinforcements

    International Nuclear Information System (INIS)

    Kim, Seung Su; Ryu, Ho Jin

    2015-01-01

    The thermal conductivity of fuel affects many performance parameters including the fuel centerline temperature, fission gas release and internal pressure. In addition, enhanced safety margin of fuel might be expected when the thermal conductivity of fuel is improved by the addition of high thermal conductivity reinforcements. Therefore, the effects of thermal conductivity enhancement on the fuel performance of reinforced UO2 fuel with high thermal conductivity compounds should be analyzed. In this study, we analyzed the fuel performance of modified UO2 fuel with high thermal conductivity reinforcements by using the FRAPCON-3.5 code. The fissile density and mechanical properties of the modified fuel are considered the same with the standard UO2 fuel. The fuel performance of modified UO2 with high thermal conductivity reinforcements were analyzed by using the FRAPCON-3.5 code. The thermal conductivity enhancement factors of the modified fuels were obtained from the Maxwell model considering the volume fraction of reinforcements

  18. Imaging and controlling intracellular reactions: Lysosome transport as a function of diameter and the intracellular synthesis of conducting polymers

    Science.gov (United States)

    Payne, Christine

    2014-03-01

    Eukaryotic cells are the ultimate complex environment with intracellular chemical reactions regulated by the local cellular environment. For example, reactants are sequestered into specific organelles to control local concentration and pH, motor proteins transport reactants within the cell, and intracellular vesicles undergo fusion to bring reactants together. Current research in the Payne Lab in the School of Chemistry and Biochemistry at Georgia Tech is aimed at understanding and utilizing this complex environment to control intracellular chemical reactions. This will be illustrated using two examples, intracellular transport as a function of organelle diameter and the intracellular synthesis of conducting polymers. Using single particle tracking fluorescence microscopy, we measured the intracellular transport of lysosomes, membrane-bound organelles, as a function of diameter as they underwent transport in living cells. Both ATP-dependent active transport and diffusion were examined. As expected, diffusion scales with the diameter of the lysosome. However, active transport is unaffected suggesting that motor proteins are insensitive to cytosolic drag. In a second example, we utilize intracellular complexity, specifically the distinct micro-environments of different organelles, to carry out chemical reactions. We show that catalase, found in the peroxisomes of cells, can be used to catalyze the polymerization of the conducting polymer PEDOT:PSS. More importantly, we have found that a range of iron-containing biomolecules are suitable catalysts with different iron-containing biomolecules leading to different polymer properties. These experiments illustrate the advantage of intracellular complexity for the synthesis of novel materials.

  19. LPG fuel

    International Nuclear Information System (INIS)

    Dagnas, F.X.; Jeuland, N.; Fouquet, J.P.; Lauraire, S.; Coroller, P.

    2005-01-01

    LPG fuel has become frequently used through a distribution network with 2 000 service stations over the French territory. LPG fuel ranks number 3 world-wide given that it can be used on individual vehicles, professional fleets, or public transport. What is the environmental benefit of LPG fuel? What is the technology used for these engines? What is the current regulation? Government commitment and dedication on support to promote LPG fuel? Car makers projects? Actions to favour the use of LPG fuel? This article gathers 5 presentations about this topic given at the gas conference

  20. [Hyperosmolarity: Intracellular effects and implication in dry eye disease].

    Science.gov (United States)

    Warcoin, E; Clouzeau, C; Brignole-Baudouin, F; Baudouin, C

    2016-09-01

    Dry eye disease is a multifactorial disease affecting the lacrimal functional unit and which has a significant impact on the quality of life of patients. This pathology works as a vicious circle at the ocular surface in which hyperosmolarity of the tear film plays a key role. This review intends to describe the different reported intracellular effects induced by hyperosmolarity in cells: alteration of cytoskeleton, cell cycle slowdown, adaptation mechanisms triggered as restoration of cell volume and accumulation of compatible osmolytes, the crucial role of the osmoprotectant factor Nuclear Factor of the Activated T cells-5 (NFAT5), apoptosis, as well as oxidative stress and inflammatory responses caused by this particular condition. Reported effects of hyperosmolarity in the experimental studies specific of dry eye disease concerning ocular surface cells will be described in parallel. Indeed, these data allow to understand a part of the pathophysiology of the disease, and specially the links between tear hyperosmolarity and inflammation of the ocular surface, the second key of the pathology phenomenon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Collective Dynamics of Intracellular Water in Living Cells

    International Nuclear Information System (INIS)

    Orecchini, A; Sebastiani, F; Paciaroni, A; Petrillo, C; Sacchetti, F; Jasnin, M; Francesco, A De; Zaccai, G; Moulin, M; Haertlein, M

    2012-01-01

    Water dynamics plays a fundamental role for the fulfillment of biological functions in living organisms. Decades of hydrated protein powder studies have revealed the peculiar dynamical properties of hydration water with respect to pure water, due to close coupling interactions with the macromolecule. In such a framework, we have studied coherent collective dynamics in protein and DNA hydration water. State-of-the-art neutron instrumentation has allowed us to observe the propagation of coherent density fluctuations within the hydration shell of the biomolecules. The corresponding dispersion curves resulted to be only slightly affected by the coupling with the macromolecules. Nevertheless, the effects of the interaction appeared as a marked increase of the mode damping factors, which suggested a destructuring of the water hydrogen-bond network. Such results were interpreted as the signature of a 'glassy' dynamical character of macromolecule hydration water, in agreement with indications from measurements of the density of vibrational states. Extending the investigations to living organisms at physiological conditions, we present here an in-vivo study of collective dynamics of intracellular water in Escherichia coli cells. The cells and water were fully deuterated to minimise the incoherent neutron scattering background. The water dynamics observed in the living cells is discussed in terms of the dynamics of pure bulk water and that of hydration water measured in powder samples.

  2. Intracellular Localization of Arabidopsis Sulfurtransferases1

    Science.gov (United States)

    Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D.; Papenbrock, Jutta

    2004-01-01

    Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism. PMID:15181206

  3. Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells?

    DEFF Research Database (Denmark)

    Vestergaard, Christian L.; Flyvbjerg, Henrik; Møller, Ian Max

    2012-01-01

    of the physical and biochemical conditions in plant cells. As model system, we use a H(2)O(2) signal originating at the plasma membrane (PM) and spreading through the cytosol. We consider two maximally simple types of signals, isolated pulses and harmonic oscillations. First we consider the basic limits......Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view...

  4. Fuel assembly

    International Nuclear Information System (INIS)

    Ueda, Makoto; Ogiya, Shunsuke.

    1989-01-01

    For improving the economy of a BWR type reactor by making the operation cycle longer, the fuel enrichment degree has to be increased further. However, this makes the subcriticality shallower in the upper portion of the reactor core, to bring about a possibility that the reactor shutdown becomes impossible. In the present invention, a portion of fuel rod is constituted as partial length fuel rods (P-fuel rods) in which the entire stack length in the effective portion is made shorter by reducing the concentration of fissionable materials in the axial portion. A plurality of moderator rods are disposed at least on one diagonal line of a fuel assembly and P-fuel rods are arranged at a position put between the moderator rods. This makes it possible to reactor shutdown and makes the axial power distribution satisfactory even if the fuel enrichment degree is increased. (T.M.)

  5. Fuel Services

    International Nuclear Information System (INIS)

    Silberstein, A.

    1982-09-01

    FRAGEMA has developed most types of inspection equipments to work on irradiated fuel assemblies and on single fuel rods during reactor outages with an efficiency compatible with the utilities operating priorities. In order to illustrate this statement, two specific examples of inspection equipments are shortly described: the on-site removable fuel rod assembly examination stand, and the fuel assembly multiple examination device. FRAGEMA has developed techniques for the identifiction of the leaking fuel rods in the fuel assembly and the tooling necessary to perform the replacement of the faulted element. These examples of methods, techniques and equipments described and the experience accumulated through their use allow FRAGEMA to qualify for offering the supply of the corresponding software, hardware or both whenever an accurate understanding of the fuel behaviour is necessary and whenever direct intervention on the assembly and associated components is necessary due to safety, operating or economical reasons

  6. Fuel assembly

    International Nuclear Information System (INIS)

    Watanabe, Shoichi; Hirano, Yasushi.

    1998-01-01

    A one-half or more of entire fuel rods in a fuel assembly comprises MOX fuel rods containing less than 1wt% of burnable poisons, and at least a portion of the burnable poisons comprises gadolinium. Then, surplus reactivity at an initial stage of operation cycle is controlled to eliminate burnable poisons remained unburnt at a final stage, as well as increase thermal reactivity. In addition, the content of fission plutonium is determined to greater than the content of uranium 235, and fuel rods at corner portions are made not to incorporate burnable poisons. Fuel rods not containing burnable poisons are disposed at positions in adjacent with fuel rods facing to a water rod at one or two directions. Local power at radial center of the fuel assembly is increased to flatten the distortion of radial power distribution. (N.H.)

  7. Pulsed electromagnetic fields promote the proliferation and differentiation of osteoblasts by reinforcing intracellular calcium transients.

    Science.gov (United States)

    Tong, Jie; Sun, Lijun; Zhu, Bin; Fan, Yun; Ma, Xingfeng; Yu, Liyin; Zhang, Jianbao

    2017-10-01

    Pulsed electromagnetic fields (PEMF) can be used to treat bone-related diseases, but the underlying mechanism remains unclear, especially the process by which PEMFs initiate biological effects. In this study, we demonstrated the effects of PEMF on proliferation and differentiation of osteoblasts using the model of calcium transients induced by high extracellular calcium. Our results showed that PEMF can increase both the percentage of responding cells and amplitude of intracellular calcium transients induced by high extracellular calcium stimulation. Compared with corresponding extracellular calcium levels, PEMF stimulation increased proliferation and differentiation of osteoblasts and related gene expressions, such as insulin-like growth factor 1 (IGF-1), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), which can be completely abolished by BAPTA-AM. Moreover, PEMF did not affect proliferation and differentiation of osteoblasts if no intracellular calcium transient was present in osteoblasts during PEMF exposure. Our results revealed that PEMF affects osteoblast proliferation and differentiation through enhanced intracellular calcium transients, which provided a cue to treat bone-related diseases with PEMF. Bioelectromagnetics. 38:541-549, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. New perspective in the assessment of total intracellular magnesium

    Directory of Open Access Journals (Sweden)

    Azzurra Sargenti

    2014-01-01

    Full Text Available Magnesium (Mg is essential for biological processes, but its cellular homeostasis has not been thoroughly elucidated, mainly because of the inadequacy of the available techniques to map intracellular Mg distribution. Recently, particular interest has been raised by a new family of fluorescent probes, diaza-18-crown-hydroxyquinoline (DCHQ, that shows remarkably high affinity and specificity for Mg, thus permitting the detection of the total intracellular Mg. The data obtained by fluori- metric and cytofluorimetric assays performed with DCHQ5 are in good agreement with atomic absorption spectroscopy, confirming that DCHQ5 probe allows both qualitative and quantitative determination of total intracellular Mg.

  9. Imaging Intracellular pH in Live Cells with a Genetically-Encoded Red Fluorescent Protein Sensor

    OpenAIRE

    Tantama, Mathew; Hung, Yin Pun; Yellen, Gary

    2011-01-01

    Intracellular pH affects protein structure and function, and proton gradients underlie the function of organelles such as lysosomes and mitochondria. We engineered a genetically-encoded pH sensor by mutagenesis of the red fluorescent protein mKeima, providing a new tool to image intracellular pH in live cells. This sensor, named pHRed, is the first ratiometric, single-protein red fluorescent sensor of pH. Fluorescence emission of pHRed peaks at 610 nm while exhibiting dual excitation peaks at...

  10. Identification of lactoferricin B intracellular targets using an Escherichia coli proteome chip.

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Tu

    Full Text Available Lactoferricin B (LfcinB is a well-known antimicrobial peptide. Several studies have indicated that it can inhibit bacteria by affecting intracellular activities, but the intracellular targets of this antimicrobial peptide have not been identified. Therefore, we used E. coli proteome chips to identify the intracellular target proteins of LfcinB in a high-throughput manner. We probed LfcinB with E. coli proteome chips and further conducted normalization and Gene Ontology (GO analyses. The results of the GO analyses showed that the identified proteins were associated with metabolic processes. Moreover, we validated the interactions between LfcinB and chip assay-identified proteins with fluorescence polarization (FP assays. Sixteen proteins were identified, and an E. coli interaction database (EcID analysis revealed that the majority of the proteins that interact with these 16 proteins affected the tricarboxylic acid (TCA cycle. Knockout assays were conducted to further validate the FP assay results. These results showed that phosphoenolpyruvate carboxylase was a target of LfcinB, indicating that one of its mechanisms of action may be associated with pyruvate metabolism. Thus, we used pyruvate assays to conduct an in vivo validation of the relationship between LfcinB and pyruvate level in E. coli. These results showed that E. coli exposed to LfcinB had abnormal pyruvate amounts, indicating that LfcinB caused an accumulation of pyruvate. In conclusion, this study successfully revealed the intracellular targets of LfcinB using an E. coli proteome chip approach.

  11. Intracellular transport of ions in mineralizing tissues

    International Nuclear Information System (INIS)

    Matthews, J.L.

    This study resulted in the development of a new model for bone cell physiology and has provided the means for studying the mechanism and site of action of bone affecting hormones and vitamin metabolites and has provided new information on mechanisms of mineralization and mineralization defects

  12. Fuel assembly

    International Nuclear Information System (INIS)

    Nakatsuka, Masafumi; Matsuzuka, Ryuji.

    1976-01-01

    Object: To provide a fuel assembly which can decrease pressure loss of coolant to uniform temperature. Structure: A sectional area of a flow passage in the vicinity of an inner peripheral surface of a wrapper tube is limited over the entire length to prevent the temperature of a fuel element in the outermost peripheral portion from being excessively decreased to thereby flatten temperature distribution. To this end, a plurality of pincture-frame-like sheet metals constituting a spacer for supporting a fuel assembly, which has a plurality of fuel elements planted lengthwise and in given spaced relation within the wrapper tube, is disposed in longitudinal grooves and in stacked fashion to form a substantially honeycomb-like space in cross section. The fuel elements are inserted and supported in the space to form a fuel assembly. (Kamimura, M.)

  13. Fuel assemblies

    International Nuclear Information System (INIS)

    Nagano, Mamoru; Yoshioka, Ritsuo

    1983-01-01

    Purpose: To effectively utilize nuclear fuels by increasing the reactivity of a fuel assembly and reduce the concentration at the central region thereof upon completion of the burning. Constitution: A fuel assembly is bisected into a central region and a peripheral region by disposing an inner channel box within a channel box. The flow rate of coolants passing through the central region is made greater than that in the peripheral region. The concentration of uranium 235 of the fuel rods in the central region is made higher. In such a structure, since the moderating effect in the central region is improved, the reactivity of the fuel assembly is increased and the uranium concentration in the central region upon completion of the burning can be reduced, fuel economy and effective utilization of uranium can be attained. (Kamimura, M.)

  14. Fuel assembly

    International Nuclear Information System (INIS)

    Bando, Masaru.

    1993-01-01

    As neutron irradiation progresses on a fuel assembly of an FBR type reactor, a strong force is exerted to cause ruptures if the arrangement of fuel elements is not displaced, whereas the fuel elements may be brought into direct contact with each other not by way of spacers to cause burning damages if the arrangement is displaced. In the present invention, the circumference of fuel elements arranged in a normal triangle lattice is surrounded by a wrapper tube having a hexagonal cross section, wire spacers are wound therearound, and deformable spacers are distributed to optional positions for fuel elements in the wrapper tube. Interaction between the fuel elements caused by irradiation is effectively absorbed, thereby enabling to delay the occurrence of the rupture and burning damages of the elements. (N.H.)

  15. Fuel assembly

    International Nuclear Information System (INIS)

    Yokota, Tokunobu.

    1990-01-01

    A fuel assembly used in a FBR type nuclear reactor comprises a plurality of fuel rods and a moderator guide member (water rod). A moderator exit opening/closing mechanism is formed at the upper portion of the moderator guide member for opening and closing a moderator exit. In the initial fuel charging operation cycle to the reactor, the moderator exit is closed by the moderator exit opening/closing mechanism. Then, voids are accumulated at the inner upper portion of the moderator guide member to harden spectrum and a great amount of plutonium is generated and accumulated in the fuel assembly. Further, in the fuel re-charging operation cycle, the moderator guide member is used having the moderator exit opened. In this case, voids are discharged from the moderator guide member to decrease the ratio, and the plutonium accumulated in the initial charging operation cycle is burnt. In this way, the fuel economy can be improved. (I.N.)

  16. Fuel spacer

    International Nuclear Information System (INIS)

    Nishida, Koji; Yokomizo, Osamu; Kanazawa, Toru; Kashiwai, Shin-ichi; Orii, Akihito.

    1992-01-01

    The present invention concerns a fuel spacer for a fuel assembly of a BWR type reactor and a PTR type reactor. Springs each having a vane are disposed on the side surface of a circular cell which supports a fuel rods. A vortex streams having a vertical component are formed by the vanes in the flowing direction of a flowing channel between adjacent cylindrical cells. Liquid droplets carried by streams are deposited on liquid membrane streams flowing along the fuel rod at the downstream of the spacer by the vortex streams. In view of the above, the liquid droplets can be deposited to the fuel rod without increasing the amount of metal of the spacer. Accordingly, the thermal margin of the fuel assembly can be improved without losing neutron economy. (I.N.)

  17. Checklist for transition to new highway fuel(s).

    Energy Technology Data Exchange (ETDEWEB)

    Risch, C.; Santini, D.J. (Energy Systems)

    2011-12-15

    Transportation is vital to the U.S. economy and society. As such, U.S. Presidents have repeatedly stated that the nation needs to reduce dependence on petroleum, especially for the highway transportation sector. Throughout history, highway transportation fuel transitions have been completed successfully both in United States and abroad. Other attempts have failed, as described in Appendix A: Historical Highway Fuel Transitions. Planning for a transition is critical because the changes can affect our nation's ability to compete in the world market. A transition will take many years to complete. While it is tempting to make quick decisions about the new fuel(s) of choice, it is preferable and necessary to analyze all the pertinent criteria to ensure that correct decisions are made. Doing so will reduce the number of changes in highway fuel(s). Obviously, changes may become necessary because of occurrences such as significant technology breakthroughs or major world events. With any and all of the possible transitions to new fuel(s), the total replacement of gasoline and diesel fuels is not expected. These conventional fuels are envisioned to coexist with the new fuel(s) for decades, while the revised fuel and vehicle infrastructures are implemented. The transition process must analyze the needs of the primary 'players,' which consist of the customers, the government, the fuel industry, and the automotive industry. To maximize the probability of future successes, the prime considerations of these groups must be addressed. Section 2 presents a succinct outline of the Checklist. Section 3 provides a brief discussion about the groupings on the Checklist.

  18. Sipping fuel and saving lives: increasing fuel economy withoutsacrificing safety

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Deborah; Greene, David L.; Ross, Marc H.; Wenzel, Tom P.

    2007-06-11

    The public, automakers, and policymakers have long worried about trade-offs between increased fuel economy in motor vehicles and reduced safety. The conclusion of a broad group of experts on safety and fuel economy in the auto sector is that no trade-off is required. There are a wide variety of technologies and approaches available to advance vehicle fuel economy that have no effect on vehicle safety. Conversely, there are many technologies and approaches available to advance vehicle safety that are not detrimental to vehicle fuel economy. Congress is considering new policies to increase the fuel economy of new automobiles in order to reduce oil dependence and reduce greenhouse gas emissions. The findings reported here offer reassurance on an important dimension of that work: It is possible to significantly increase the fuel economy of motor vehicles without compromising their safety. Automobiles on the road today demonstrate that higher fuel economy and greater safety can co-exist. Some of the safest vehicles have higher fuel economy, while some of the least safe vehicles driven today--heavy, large trucks and SUVs--have the lowest fuel economy. At an October 3, 2006 workshop, leading researchers from national laboratories, academia, auto manufacturers, insurance research industry, consumer and environmental groups, material supply industries, and the federal government agreed that vehicles could be designed to simultaneously improve safety and fuel economy. The real question is not whether we can realize this goal, but the best path to get there. The experts' studies reveal important new conclusions about fuel economy and safety, including: (1) Vehicle fuel economy can be increased without affecting safety, and vice versa; (2) Reducing the weight and height of the heaviest SUVs and pickup trucks will simultaneously increase both their fuel economy and overall safety; and (3) Advanced materials can decouple size from mass, creating important new possibilities

  19. Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans.

    Science.gov (United States)

    Blondin, Denis P; Frisch, Frédérique; Phoenix, Serge; Guérin, Brigitte; Turcotte, Éric E; Haman, François; Richard, Denis; Carpentier, André C

    2017-02-07

    Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11 C-acetate and 18 F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Fuel Cells

    DEFF Research Database (Denmark)

    Smith, Anders; Pedersen, Allan Schrøder

    2014-01-01

    Fuel cells have been the subject of intense research and development efforts for the past decades. Even so, the technology has not had its commercial breakthrough yet. This entry gives an overview of the technological challenges and status of fuel cells and discusses the most promising applications...... of the different types of fuel cells. Finally, their role in a future energy supply with a large share of fluctuating sustainable power sources, e.g., solar or wind, is surveyed....

  1. Fuel cycle

    International Nuclear Information System (INIS)

    Bahm, W.

    1989-01-01

    The situation of the nuclear fuel cycle for LWR type reactors in France and in the Federal Republic of Germany was presented in 14 lectures with the aim to compare the state-of-the-art in both countries. In addition to the momentarily changing fuilds of fuel element development and fueling strategies, the situation of reprocessing, made interesting by some recent developmnts, was portrayed and differences in ultimate waste disposal elucidated. (orig.) [de

  2. Nuclear fuel

    International Nuclear Information System (INIS)

    Azevedo, J.B.L. de.

    1980-01-01

    All stages of nuclear fuel cycle are analysed with respect to the present situation and future perspectives of supply and demand of services; the prices and the unitary cost estimation of these stages for the international fuel market are also mentioned. From the world resources and projections of uranium consumption, medium-and long term analyses are made of fuel availability for several strategies of use of different reactor types. Finally, the cost of nuclear fuel in the generation of electric energy is calculated to be used in the energetic planning of the electric sector. (M.A.) [pt

  3. Fuel assembly

    International Nuclear Information System (INIS)

    Nomata, Terumitsu.

    1993-01-01

    Among fuel pellets to be loaded to fuel cans of a fuel assembly, fuel pellets having a small thermal power are charged in a region from the end of each of spacers up to about 50mm on the upstream of coolants that flow vertically at the periphery of fuel rods. Coolants at the periphery of fuel rods are heated by the heat generation, to result in voids. However, since cooling effect on the upstream of the spacers is low due to influences of the spacers. Further, since the fuel pellets disposed in the upstream region have small thermal power, a void coefficient is not increased. Even if a thermal power exceeding cooling performance should be generated, there is no worry of causing burnout in the upstream region. Even if burnout should be caused, safety margin and reliability relative to burnout are improved, to increase an allowable thermal power, thereby enabling to improve integrity and reliability of fuel rods and fuel assemblies. (N.H.)

  4. Fuel assembly

    International Nuclear Information System (INIS)

    Gjertsen, R.K.; Bassler, E.A.; Huckestein, E.A.; Salton, R.B.; Tower, S.N.

    1988-01-01

    A fuel assembly adapted for use with a pressurized water nuclear reactor having capabilities for fluid moderator spectral shift control is described comprising: parallel arranged elongated nuclear fuel elements; means for providing for axial support of the fuel elements and for arranging the fuel elements in a spaced array; thimbles interspersed among the fuel elements adapted for insertion of a rod control cluster therewithin; means for structurally joining the fuel elements and the guide thimbles; fluid moderator control means for providing a volume of low neutron absorbing fluid within the fuel assembly and for removing a substantially equivalent volume of reactor coolant water therefrom, a first flow manifold at one end of the fuel assembly sealingly connected to a first end of the moderator control tubes whereby the first ends are commonly flow connected; and a second flow manifold, having an inlet passage and an outlet passage therein, sealingly connected to a second end of the moderator control tubes at a second end of the fuel assembly

  5. Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs. PMID:28814834

  6. Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

  7. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    Science.gov (United States)

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  8. Data for automated, high-throughput microscopy analysis of intracellular bacterial colonies using spot detection

    DEFF Research Database (Denmark)

    Ernstsen, Christina Lundgaard; Login, Frédéric H.; Jensen, Helene Halkjær

    2017-01-01

    Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacteria...

  9. Proceedings of fuel strategies for conventional and unconventional fuels

    International Nuclear Information System (INIS)

    Mahr, D.; Nechvatal, T.T.

    1991-01-01

    Fuel selection is a major decision for a power engineer. It is the single largest item in the power plant operating budget and has a major effect on power plant economics. Fuel determines plant design requirements and the types of systems that are provided. As a result, it affects capital budgets and financing requirements. In the last few decades, we have seen different fuels of choice at any one time. Coal has always been a staple for power generation. During the 1950s and 1960s, oil became an attractive alternative. Nuclear fuel became a popular choice due to its very low energy cost. After Three-Mile-Island, however, capital budgets went through the roof, resulting in severe financial constraints. Natural gas, which was rationed in some regions a few years ago, is now a popular choice. Some sources predict that its cost will increase faster than other fuels. To mitigate the relative variations in energy cost for different fuels, a balanced energy plan is required. A balanced power generation plan with fuel options provides the flexibility to react to unpredictable changes. The papers in this book are a continuation of the Fuel Strategies theme. Three technical topics are covered: Converting to Orimulsion, A Replacement Fuel for Heavy Oil; Innovations in Handling Conventional and Unconventional Fuels for Power Plants; and Pacific Rim Experience With Coal

  10. Hydrogen fuel - Universal energy

    Science.gov (United States)

    Prince, A. G.; Burg, J. A.

    The technology for the production, storage, transmission, and consumption of hydrogen as a fuel is surveyed, with the physical and chemical properties of hydrogen examined as they affect its use as a fuel. Sources of hydrogen production are described including synthesis from coal or natural gas, biomass conversion, thermochemical decomposition of water, and electrolysis of water, of these only electrolysis is considered economicially and technologically feasible in the near future. Methods of production of the large quantities of electricity required for the electrolysis of sea water are explored: fossil fuels, hydroelectric plants, nuclear fission, solar energy, wind power, geothermal energy, tidal power, wave motion, electrochemical concentration cells, and finally ocean thermal energy conversion (OTEC). The wind power and OTEC are considered in detail as the most feasible approaches. Techniques for transmission (by railcar or pipeline), storage (as liquid in underwater or underground tanks, as granular metal hydride, or as cryogenic liquid), and consumption (in fuel cells in conventional power plants, for home usage, for industrial furnaces, and for cars and aircraft) are analyzed. The safety problems of hydrogen as a universal fuel are discussed, noting that they are no greater than those for conventional fuels.

  11. Hydroxyhydroquinone, a by-product of coffee bean roasting, increases intracellular Ca2+ concentration in rat thymic lymphocytes.

    Science.gov (United States)

    Kamae, Risa; Nojima, Shoko; Akiyoshi, Kenji; Setsu, Shoki; Honda, Sari; Masuda, Toshiya; Oyama, Yasuo

    2017-04-01

    Hydroxyhydroquinone (HHQ) is generated during coffee bean roasting. A cup of coffee contains 0.1-1.7 mg of HHQ. The actions of HHQ on mammalian DNA were examined because HHQ is a metabolite of benzene, which causes leukemia. Currently, information on the cellular actions of HHQ is limited. We examined the effects of sublethal levels of HHQ on the concentration of intracellular Ca 2+ in rat thymic lymphocytes by using a flow cytometric technique with fluorescent probes. HHQ at 10 μM or more significantly elevated intracellular Ca 2+ levels by increasing the membrane permeability of divalent cations, resulting in hyperpolarization via the activation of Ca 2+ -dependent K + channels. HHQ-induced changes in the intracellular Ca 2+ concentration and membrane potential may affect the cell functions of lymphocytes. HHQ-reduced coffee may be preferable in order to avoid the possible adverse effects of HHQ. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection.

    Science.gov (United States)

    Mentzer, Robert M; Lasley, Robert D; Jessel, Andreas; Karmazyn, Morris

    2003-02-01

    Although the mechanisms underlying ischemia/reperfusion injury remain elusive, evidence supports the etiologic role of intracellular calcium overload and oxidative stress induced by reactive oxygen species. Activation of the sodium hydrogen exchanger (NHE) is associated with intracellular calcium accumulation. Inhibition of the NHE-1 isoform may attenuate the consequences of this injury. Although there is strong preclinical and early clinical evidence that NHE inhibitors may be cardioprotective, definitive proof of this concept in humans awaits the results of ongoing clinical trials.

  13. Fuel alcohol opportunities for Indiana

    Energy Technology Data Exchange (ETDEWEB)

    Greenglass, Bert

    1980-08-01

    Prepared at the request of US Senator Birch Bayh, Chairman of the National Alcohol Fuels Commission, this study may be best utilized as a guidebook and resource manual to foster the development of a statewide fuel alcohol plan. It examines sectors in Indiana which will impact or be impacted upon by the fuel alcohol industry. The study describes fuel alcohol technologies that could be pertinent to Indiana and also looks closely at how such a fuel alcohol industry may affect the economic and policy development of the State. Finally, the study presents options for Indiana, taking into account the national context of the developing fuel alcohol industry which, unlike many others, will be highly decentralized and more under the control of the lifeblood of our society - the agricultural community.

  14. Fuel cracking in relation to fuel oxidation in support of an out-reactor instrumented defected fuel experiment

    Energy Technology Data Exchange (ETDEWEB)

    Quastel, A.; Thiriet, C. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Lewis, B., E-mail: brent.lewis@uoit.ca [Univ. of Ontario Inst. of Tech., Oshawa, ON (Canada); Corcoran, E., E-mail: emily.corcoran@rmc.ca [Royal Military College of Canada, Kingston, ON (Canada)

    2014-07-01

    An experimental program funded by the CANDU Owners Group (COG) is studying an out-reactor instrumented defected fuel experiment in Stern Laboratories (Hamilton, Ontario) with guidance from Atomic Energy of Canada Limited (AECL). The objective of this test is to provide experimental data for validation of a mechanistic fuel oxidation model. In this experiment a defected fuel element with UO{sub 2} pellets will be internally heated with an electrical heater element, causing the fuel to crack. By defecting the sheath in-situ the fuel will be exposed to light water coolant near normal reactor operating conditions (pressure 10 MPa and temperature 265-310{sup o}C) causing fuel oxidation, especially near the hotter regions of the fuel in the cracks. The fuel thermal conductivity will change, resulting in a change in the temperature distribution of the fuel element. This paper provides 2D r-θ plane strain solid mechanics models to simulate fuel thermal expansion, where conditions for fuel crack propagation are investigated with the thermal J integral to predict fuel crack stress intensity factors. Finally since fuel crack geometry can affect fuel oxidation this paper shows that the solid mechanics model with pre-set radial cracks can be coupled to a 2D r-θ fuel oxidation model. (author)

  15. Fuel element

    International Nuclear Information System (INIS)

    Kennedy, S.T.

    1982-01-01

    A nuclear reactor fuel element wherein a stack of nuclear fuel is prevented from displacement within its sheath by a retainer comprising a tube member which is radially expanded into frictional contact with the sheath by means of a captive ball within a tapered bore. (author)

  16. Nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, H [Power Reactor and Nuclear Fuel Development Corp., Tokyo (Japan)

    1976-10-01

    It is expected that nuclear power generation will reach 49 million kW in 1985 and 129 million kW in 1995, and the nuclear fuel having to be supplied and processed will increase in proportion to these values. The technical problems concerning nuclear fuel are presented on the basis of the balance between the benefit for human beings and the burden on the human beings. Recently, especially the downstream of nuclear fuel attracts public attention. Enriched uranium as the raw material for light water reactor fuel is almost monopolized by the U.S., and the technical information has not been published for fear of the diversion to nuclear weapons. In this paper, the present situations of uranium enrichment, fuel fabrication, transportation, reprocessing and waste disposal and the future problems are described according to the path of nuclear fuel cycle. The demand and supply of enriched uranium in Japan will be balanced up to about 1988, but afterwards, the supply must rely upon the early establishment of the domestic technology by centrifugal separation method. No problem remains in the fabrication of light water reactor fuel, but for the fabrication of mixed oxide fuel, the mechanization of the production facility and labor saving are necessary. The solution of the capital risk for the construction of the second reprocessing plant is the main problem. Japan must develop waste disposal techniques with all-out efforts.

  17. Fuel cells

    NARCIS (Netherlands)

    Veen, van J.A.R.; Janssen, F.J.J.G.; Santen, van R.A.

    1999-01-01

    The principles and present-day embodiments of fuel cells are discussed. Nearly all cells are hydrogen/oxygen ones, where the hydrogen fuel is usually obtained on-site from the reforming of methane or methanol. There exists a tension between the promise of high efficiency in the conversion of

  18. Fuel assembly

    International Nuclear Information System (INIS)

    Nakajima, Akiyoshi; Bessho, Yasunori; Aoyama, Motoo; Koyama, Jun-ichi; Hirakawa, Hiromasa; Yamashita, Jun-ichi; Hayashi, Tatsuo

    1998-01-01

    In a fuel assembly of a BWR type reactor in which a water rod of a large diameter is disposed at the central portion, the cross sectional area perpendicular to the axial direction comprises a region a of a fuel rod group facing to a wide gap water region to which a control rod is inserted, a region b of a fuel rod group disposed on the side of the wide gap water region other than the region a, a region d of a fuel rod group facing to a narrow gap water region and a region c of a fuel rod group disposed on the side of the narrow gap water region other than the region d. When comparing an amount of fission products contained in the four regions relative to that in the entire regions and average enrichment degrees of fuel rods for the four regions, the relative amount and the average enrichment degree of the fuel rod group of the region a is minimized, and the relative amount and the average enrichment degree of the fuel rod group in the region b is maximized. Then, reactor shut down margin during cold operation can be improved while flattening the power in the cross section perpendicular to the axial direction. (N.H.)

  19. Nuclear fuel

    International Nuclear Information System (INIS)

    Quinauk, J.P.

    1990-01-01

    Since 1985, Fragema has been marketing and selling the Advanced Fuel Assemby AFA whose main features are its zircaloy grids and removable top and bottom nozzles. It is this product, which exists for several different fuel assembly arrays and heights, that will be employed in the reactors at Daya Bay. Fragema employs gadolinium as the consumable poison to enable highperformance fuel management. More recently, the company has supplied fuel assemblies of the mixed-oxide(MOX) and enriched reprocessed uranium type. The reliability level of the fuel sold by Fragema is one of the highest in the world, thanks in particular to the excellence of the quality assurance and quality control programs that have been implemented at all stages of its design and manufacture

  20. Fuel assemblies

    International Nuclear Information System (INIS)

    Echigoya, Hironori; Nomata, Terumitsu.

    1983-01-01

    Purpose: To render the axial distribution relatively flat. Constitution: First nuclear element comprises a fuel can made of zircalloy i.e., the metal with less neutron absorption, which is filled with a plurality of UO 2 pellets and sealed by using a lower end plug, a plenum spring and an upper end plug by means of welding. Second fuel element is formed by substituting a part of the UO 2 pellets with a water tube which is sealed with water and has a space for allowing the heat expansion. The nuclear fuel assembly is constituted by using the first and second fuel elements together. In such a structure, since water reflects neutrons and decrease their leakage to increase the temperature, reactivity is added at the upper portion of the fuel assembly to thereby flatten the axial power distribution. Accordingly, stable operation is possible only by means of deep control rods while requiring no shallow control rods. (Sekiya, K.)

  1. Imaging intracellular pH in live cells with a genetically encoded red fluorescent protein sensor.

    Science.gov (United States)

    Tantama, Mathew; Hung, Yin Pun; Yellen, Gary

    2011-07-06

    Intracellular pH affects protein structure and function, and proton gradients underlie the function of organelles such as lysosomes and mitochondria. We engineered a genetically encoded pH sensor by mutagenesis of the red fluorescent protein mKeima, providing a new tool to image intracellular pH in live cells. This sensor, named pHRed, is the first ratiometric, single-protein red fluorescent sensor of pH. Fluorescence emission of pHRed peaks at 610 nm while exhibiting dual excitation peaks at 440 and 585 nm that can be used for ratiometric imaging. The intensity ratio responds with an apparent pK(a) of 6.6 and a >10-fold dynamic range. Furthermore, pHRed has a pH-responsive fluorescence lifetime that changes by ~0.4 ns over physiological pH values and can be monitored with single-wavelength two-photon excitation. After characterizing the sensor, we tested pHRed's ability to monitor intracellular pH by imaging energy-dependent changes in cytosolic and mitochondrial pH.

  2. Effect of serum proteins on polystyrene nanoparticle uptake and intracellular trafficking in endothelial cells

    International Nuclear Information System (INIS)

    Guarnieri, Daniela; Guaccio, Angela; Fusco, Sabato; Netti, Paolo A.

    2011-01-01

    The physico-chemical properties of nanoparticles (NPs), such as small dimensions, surface charge and surface functionalization, control their capability to interact with cells and, in particular, with sub-cellular components. This interaction can be also influenced by the adsorption of molecules present in biological fluids, like blood, on NP surface. Here, we analysed the effect of serum proteins on 49 and 100 nm red fluorescent polystyrene NP uptake in porcine aortic endothelial (PAE) cells, as a model for vascular transport. To this aim, NP uptake kinetic, endocytic pathway and intracellular trafficking were studied by monitoring NPs inside cells through confocal microscopy and multiple particle tracking (MPT). We demonstrated that NPs are rapidly internalized by cells in serum-free (SF) medium, according to a saturation kinetic. Conversely, in 10% foetal bovine serum-enriched (SE) medium, NP uptake rate results drastically reduced. Moreover, NP internalization depends on an active endocytic mechanism that does not involve clathrin- and caveolae-mediated vesicular transport, in both SE and SF media. Furthermore, MPT data indicate that NP intracellular trafficking is unaffected by protein presence. Indeed, approximately 50–60% of internalized NPs is characterized by a sub-diffusive behaviour, whereas the remaining fraction shows an active motion. These findings demonstrate that the unspecific protein adsorption on NP surface can affect cellular uptake in terms of internalization kinetics, but it is not effective in controlling active and cellular-mediated uptake mechanisms of NPs and their intracellular routes.

  3. Intracellular localisation of proteins to specific cellular areas by nanocapsule mediated delivery.

    Science.gov (United States)

    Wang, Huabin; Chen, Ligang; Sun, Xianchao; Fu, Ailing

    2017-09-01

    Nanocapsules are promising carriers with great potential for intracellular protein transport. Although many studies have intended to improve cell uptake efficacy, there is an increasing interest in understanding of subcellular distribution of cargoes inside cells, which is essential for purposeful delivery of biomolecules into specific sites within cells. Herein, we interrogate the intracellular localisation of exogenous proteins, including fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) and green fluorescent protein (GFP), mediated by specially designed nanocapsules. The results show that the designed nanocapsules can deliver the two types of fluorescent proteins into different cellular destinations (cytosol, nucleus or the whole cell), depending on the composition of nanocapsules. Meanwhile, several impact factors that influence the distribution of proteins in cells have also been investigated, and the results suggest that the localisation of capsule-mediated proteins in cells is strongly affected by the surface properties of nanocapsules, the types of stabilisers and proteins, and environmental temperatures. The rational control of intracellular localised delivery of exogenous proteins as we demonstrated in this study might open new avenues to obtain desired magnitude of drug effects for modulating cell activity.

  4. Optical fuel spray measurements

    Energy Technology Data Exchange (ETDEWEB)

    Hillamo, H.

    2011-07-01

    Diesel fuel sprays, including fuel/air mixing and the physics of two-phase jet formation, are discussed in the thesis. The fuel/air mixing strongly affects emissions formation in spray combustion processes where the local combustion conditions dictate the emission formation. This study comprises optical measurements both in pressurized spray test rigs and in a running engine.The studied fuel injection was arranged with a common rail injection system and the injectors were operated with a solenoid-based injection valve. Both marine and heavy-duty diesel engine injectors were used in the study. Optical fuel spray measurements were carried out with a laser-based double-framing camera system. This kind of equipments is usually used for flow field measurements with Particle Image Velocimetry technique (PIV) as well as for backlight imaging. Fundamental fuel spray properties and spray formation were studied in spray test rigs. These measurements involved studies of mixing, atomization, and the flow field. Test rig measurements were used to study the effect of individual injection parameters and component designs. Measurements of the fuel spray flow field, spray penetration, spray tip velocity, spray angle, spray structure, droplet accumulation, and droplet size estimates are shown. Measurement campaign in a running optically accessible large-bore medium-speed engine was also carried out. The results from engine tests were compared with equivalent test rig measurements, as well as computational results, to evaluate the level of understanding of sprays. It was shown that transient spray has an acceleration and a deceleration phase. Successive flow field measurements (PIV) in optically dense diesel spray resulted in local and average velocity data of diesel sprays. Processing fuel spray generates a flow field to surrounding gas and entrainment of surrounding gas into fuel jet was also seen at the sides of the spray. Laser sheet imaging revealed the inner structure of diesel

  5. Reforming options for hydrogen production from fossil fuels for PEM fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ersoz, Atilla; Olgun, Hayati [TUBITAK Marmara Research Center, Institute of Energy, Gebze, 41470 Kocaeli (Turkey); Ozdogan, Sibel [Marmara University Faculty of Engineering, Goztepe, 81040 Istanbul (Turkey)

    2006-03-09

    PEM fuel cell systems are considered as a sustainable option for the future transport sector in the future. There is great interest in converting current hydrocarbon based transportation fuels into hydrogen rich gases acceptable by PEM fuel cells on-board of vehicles. In this paper, we compare the results of our simulation studies for 100kW PEM fuel cell systems utilizing three different major reforming technologies, namely steam reforming (SREF), partial oxidation (POX) and autothermal reforming (ATR). Natural gas, gasoline and diesel are the selected hydrocarbon fuels. It is desired to investigate the effect of the selected fuel reforming options on the overall fuel cell system efficiency, which depends on the fuel processing, PEM fuel cell and auxiliary system efficiencies. The Aspen-HYSYS 3.1 code has been used for simulation purposes. Process parameters of fuel preparation steps have been determined considering the limitations set by the catalysts and hydrocarbons involved. Results indicate that fuel properties, fuel processing system and its operation parameters, and PEM fuel cell characteristics all affect the overall system efficiencies. Steam reforming appears as the most efficient fuel preparation option for all investigated fuels. Natural gas with steam reforming shows the highest fuel cell system efficiency. Good heat integration within the fuel cell system is absolutely necessary to achieve acceptable overall system efficiencies. (author)

  6. Reforming options for hydrogen production from fossil fuels for PEM fuel cells

    Science.gov (United States)

    Ersoz, Atilla; Olgun, Hayati; Ozdogan, Sibel

    PEM fuel cell systems are considered as a sustainable option for the future transport sector in the future. There is great interest in converting current hydrocarbon based transportation fuels into hydrogen rich gases acceptable by PEM fuel cells on-board of vehicles. In this paper, we compare the results of our simulation studies for 100 kW PEM fuel cell systems utilizing three different major reforming technologies, namely steam reforming (SREF), partial oxidation (POX) and autothermal reforming (ATR). Natural gas, gasoline and diesel are the selected hydrocarbon fuels. It is desired to investigate the effect of the selected fuel reforming options on the overall fuel cell system efficiency, which depends on the fuel processing, PEM fuel cell and auxiliary system efficiencies. The Aspen-HYSYS 3.1 code has been used for simulation purposes. Process parameters of fuel preparation steps have been determined considering the limitations set by the catalysts and hydrocarbons involved. Results indicate that fuel properties, fuel processing system and its operation parameters, and PEM fuel cell characteristics all affect the overall system efficiencies. Steam reforming appears as the most efficient fuel preparation option for all investigated fuels. Natural gas with steam reforming shows the highest fuel cell system efficiency. Good heat integration within the fuel cell system is absolutely necessary to achieve acceptable overall system efficiencies.

  7. Nuclear fuel cladding material

    International Nuclear Information System (INIS)

    Nakahigashi, Shigeo.

    1982-01-01

    Purpose: To largely improve the durability and the safety of fuel cladding material. Constitution: Diffusion preventive layers, e.g., aluminum or the like are covered on both sides of a zirconium alloy base layer of thin material, and corrosion resistant layers, e.g., copper or the like are covered thereon. This thin plate material is intimately wound in a circularly tubular shape in a plurality of layers to form a fuel cladding tube. With such construction, corrosion of the tube due to fuel and impurity can be prevented by the corrosion resistant layers, and the diffusion of the corrosion resistant material to the zirconium alloy can be prevented by the diffusion preventive layers. Since a plurality of layers are cladded, even if the corrosion resistant layers are damaged or cracked due to stress corrosion, only one layer is damaged or cracked, but the other layers are not affected. (Sekiya, K.)

  8. Optimal fuel inventory strategies

    International Nuclear Information System (INIS)

    Caspary, P.J.; Hollibaugh, J.B.; Licklider, P.L.; Patel, K.P.

    1990-01-01

    In an effort to maintain their competitive edge, most utilities are reevaluating many of their conventional practices and policies in an effort to further minimize customer revenue requirements without sacrificing system reliability. Over the past several years, Illinois Power has been rethinking its traditional fuel inventory strategies, recognizing that coal supplies are competitive and plentiful and that carrying charges on inventory are expensive. To help the Company achieve one of its strategic corporate goals, an optimal fuel inventory study was performed for its five major coal-fired generating stations. The purpose of this paper is to briefly describe Illinois Power's system and past practices concerning coal inventories, highlight the analytical process behind the optimal fuel inventory study, and discuss some of the recent experiences affecting coal deliveries and economic dispatch

  9. Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

    Science.gov (United States)

    Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

    2018-01-01

    Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

  10. Factors influencing intracellular uptake and radiosensitization by 2-nitroimidazoles in vitro

    International Nuclear Information System (INIS)

    Brown, D.M.; Gonzalez-Mendez, R.; Brown, J.M.

    1983-01-01

    In this study it is shown that the radiosensitization of hypoxic Chinese hamster ovary (HA-1) cells in vitro by misonidazole (MIS) and other 1-substituted 2-nitroimidazoles depends on the rate and extent of intracellular uptake of these radiosensitizers, which in turn is governed by their lipophilicity [expressed as the octanol:water partition coefficient (P)]. As the lipophilicity of the compounds decreased, the rate of drug entry into the cells was slower, and below P values of approximately 0.05, peak intracellular drug concentrations were found to be lower than that of MIS (P=0.43). In addition, the number of hydroxyl groups on the side chain of the nitroimidazole molecule influenced the uptake of drug into the cells. For compounds of similar P, but differing in the number of side-chain hydroxyl groups, the addition of a single hydroxyl group to the molecule decreased the amount of drug entering the cell by a factor of approximately 2. These compounds enter the cell by nonmediated passive diffusion since altering the energy (ATP) capacity of the cell by 2-deoxyglucose did not affect uptake. It is also shown that increases in temperature or decreases in pH can increase the intracellular uptake of MIS. For example, equal intracellular and extracellular concentrations (100% uptake) of MIS were obtained if cells were heated to 44-45 0 C for 15 min compared to 20-40% uptake at 37 0 C. Increases in MIS uptake by factors of 2 to 3 could be demonstrated within 30 min when cells were incubated in Hanks' balanced salt solution at pH between 6.0 and 6.3 without loss of cell viability. In addition, MIS uptake in aerobic cultured cells varied from 15 to 60% depending on the cell line and culure conditions used

  11. Type IV pili in Francisella – A virulence trait in an intracellular pathogen

    Directory of Open Access Journals (Sweden)

    Emelie eNäslund Salomonsson

    2011-02-01

    Full Text Available Francisella tularensis is a highly virulent intracellular human pathogen that is capable of rapid proliferation in the infected host. Mutants affected in intracellular survival and growth are highly attenuated which highlights the importance of the intracellular phase of the infection. Genomic analysis has revealed that Francisella encodes all genes required for expression of functional type IV pili (Tfp, and in this focused review we summarise recent findings regarding this system in the pathogenesis of tularemia. Tfp are dynamic adhesive structures that have been identified as major virulence determinants in several human pathogens, but it is not obvious what role these structures could have in an intracellular pathogen like Francisella. In the human pathogenic strains, genes required for secretion and assembly of Tfp and one pilin, PilA, have shown to be required for full virulence. Importantly, specific genetic differences have been identified between the different Francisella subspecies where in the most pathogenic type A variants all genes are intact while several Tfp genes are pseudogenes in the less pathogenic type B strains. This suggests that there has been a selection for expression of Tfp with different properties in the different subspecies. There is also a possibility that the genetic differences reflect adaption to different environmental niches of the subspecies and plays a role in transmission of tularemia. This is also in line with recent findings where Tfp pilins are found to be glycosylated which could reflect a role for Tfp in the environment to promote survival and transmission. We are still far from understanding the role of Tfp in virulence and transmission of tularemia, but with the genomic information and genetic tools available we are in a good position to address these issues in the future.

  12. Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

    Directory of Open Access Journals (Sweden)

    Jiang LQ

    2017-08-01

    Full Text Available Li Qun Jiang,1 Ting Yu Wang,1 Thomas J Webster,2 Hua-Jian Duan,1 Jing Ying Qiu,1 Zi Ming Zhao,1 Xiao Xing Yin,1,* Chun Li Zheng3,* 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs in macrophages, a primary cell of the mononuclear phagocyte system (MPS. Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm were prepared, and a murine macrophage cell line (RAW 264.7 was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition

  13. Fuel cells:

    DEFF Research Database (Denmark)

    Sørensen, Bent

    2013-01-01

    A brief overview of the progress in fuel cell applications and basic technology development is presented, as a backdrop for discussing readiness for penetration into the marketplace as a solution to problems of depletion, safety, climate or environmental impact from currently used fossil and nucl......A brief overview of the progress in fuel cell applications and basic technology development is presented, as a backdrop for discussing readiness for penetration into the marketplace as a solution to problems of depletion, safety, climate or environmental impact from currently used fossil...... and nuclear fuel-based energy technologies....

  14. Fuel assemblies

    International Nuclear Information System (INIS)

    Nakatsuka, Masafumi.

    1979-01-01

    Purpose: To prevent scattering of gaseous fission products released from fuel assemblies stored in an fbr type reactor. Constitution; A cap provided with means capable of storing gas is adapted to amount to the assembly handling head, for example, by way of threading in a storage rack of spent fuel assemblies consisting of a bottom plate, a top plate and an assembly support mechanism. By previously eliminating the gas inside of the assembly and the cap in the storage rack, gaseous fission products upon loading, if released from fuel rods during storage, are stored in the cap and do not scatter in the storage rack. (Horiuchi, T.)

  15. Model analysis of the relationship between intracellular Po2 and energy demand in skeletal muscle

    OpenAIRE

    Spires, Jessica; Gladden, L. Bruce; Grassi, Bruno; Saidel, Gerald M.; Lai, Nicola

    2012-01-01

    On the basis of experimental studies, the intracellular O2 (iPo2)-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPo2 reached a plateau at 60% of maximal WR, while another found that iPo2 decreased linearly at higher WR, inferring capillary permeability-surface area (PS) and blood-tissue O2 gradient, respectively, as alternative dominant factors for determining O2 diffusion changes during exercise. This relationship is affected by several factors, including...

  16. Relevance of intracellular polarity to accuracy of eukaryotic chemotaxis

    International Nuclear Information System (INIS)

    Hiraiwa, Tetsuya; Nishikawa, Masatoshi; Shibata, Tatsuo; Nagamatsu, Akihiro; Akuzawa, Naohiro

    2014-01-01

    Eukaryotic chemotaxis is usually mediated by intracellular signals that tend to localize at the front or back of the cell. Such intracellular polarities frequently require no extracellular guidance cues, indicating that spontaneous polarization occurs in the signal network. Spontaneous polarization activity is considered relevant to the persistent motions in random cell migrations and chemotaxis. In this study, we propose a theoretical model that connects spontaneous intracellular polarity and motile ability in a chemoattractant solution. We demonstrate that the intracellular polarity can enhance the accuracy of chemotaxis. Chemotactic accuracy should also depend on chemoattractant concentration through the concentration-dependent correlation time in the polarity direction. Both the polarity correlation time and the chemotactic accuracy depend on the degree of responsiveness to the chemical gradient. We show that optimally accurate chemotaxis occurs at an intermediate responsiveness of intracellular polarity. Experimentally, we find that the persistence time of randomly migrating Dictyostelium cells depends on the chemoattractant concentration, as predicted by our theory. At the optimum responsiveness, this ameboid cell can enhance its chemotactic accuracy tenfold. (paper)

  17. Intracellular calcium levels can regulate Importin-dependent nuclear import

    International Nuclear Information System (INIS)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A.

    2014-01-01

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca 2+ on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery

  18. Intracellular transport of fat-soluble vitamins A and E.

    Science.gov (United States)

    Kono, Nozomu; Arai, Hiroyuki

    2015-01-01

    Vitamins are compounds that are essential for the normal growth, reproduction and functioning of the human body. Of the 13 known vitamins, vitamins A, D, E and K are lipophilic compounds and are therefore called fat-soluble vitamins. Because of their lipophilicity, fat-soluble vitamins are solubilized and transported by intracellular carrier proteins to exert their actions and to be metabolized properly. Vitamin A and its derivatives, collectively called retinoids, are solubilized by intracellular retinoid-binding proteins such as cellular retinol-binding protein (CRBP), cellular retinoic acid-binding protein (CRABP) and cellular retinal-binding protein (CRALBP). These proteins act as chaperones that regulate the metabolism, signaling and transport of retinoids. CRALBP-mediated intracellular retinoid transport is essential for vision in human. α-Tocopherol, the main form of vitamin E found in the body, is transported by α-tocopherol transfer protein (α-TTP) in hepatic cells. Defects of α-TTP cause vitamin E deficiency and neurological disorders in humans. Recently, it has been shown that the interaction of α-TTP with phosphoinositides plays a critical role in the intracellular transport of α-tocopherol and is associated with familial vitamin E deficiency. In this review, we summarize the mechanisms and biological significance of the intracellular transport of vitamins A and E. © 2014 The Authors. Traffic published by John Wiley & Sons Ltd.

  19. Surveillance for Intracellular Antibody by Cytosolic Fc Receptor TRIM21

    Directory of Open Access Journals (Sweden)

    William A. McEwan

    2016-11-01

    Full Text Available TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY domain. Following binding of intracellular antibody, TRIM21 acts as both antiviral effector and sensor for innate immune signalling. These activities serve to reduce viral replication by orders of magnitude in vitro and contribute to host survival during in vivo infection. Neutralization occurs rapidly after detection and requires the activity of the ubiquitin-proteasome system. The microbial targets of this arm of intracellular immunity are still being identified: TRIM21 activity has been reported following infection by several non-enveloped viruses and intracellular bacteria. These findings extend the sphere of influence of antibodies to the intracellular domain and have broad implications for immunity. TRIM21 has been implicated in the chronic auto-immune condition systemic lupus erythematosus and is itself an auto-antigen in Sjögren’s syndrome. This review summarises our current understanding of TRIM21’s role as a cytosolic Fc receptor and briefly discusses pathological circumstances where intracellular antibodies have been described, or are hypothesized to occur, and may benefit from further investigations of the role of TRIM21.

  20. Advances in genetic manipulation of obligate intracellular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Paul eBeare

    2011-05-01

    Full Text Available Infections by obligate intracellular bacterial pathogens result in significant morbidity and mortality worldwide. These bacteria include Chlamydia spp., which causes millions of cases of sexually transmitted disease and blinding trachoma annually, and members of the α-proteobacterial genera Anaplasma, Ehrlichia, Orientia and Rickettsia, agents of serious human illnesses including epidemic typhus. Coxiella burnetii, the agent of human Q fever, has also been considered a prototypical obligate intracellular bacterium, but recent host cell-free (axenic growth has rescued it from obligatism. The historic genetic intractability of obligate intracellular bacteria has severely limited molecular dissection of their unique lifestyles and virulence factors involved in pathogenesis. Host cell restricted growth is a significant barrier to genetic transformation that can make simple procedures for free-living bacteria, such as cloning, exceedingly difficult. Low transformation efficiency requiring long term culture in host cells to expand small transformant populations is another obstacle. Despite numerous technical limitations, the last decade has witnessed significant gains in genetic manipulation of obligate intracellular bacteria including allelic exchange. Continued development of genetic tools should soon enable routine mutation and complementation strategies for virulence factor discovery and stimulate renewed interest in these refractory pathogens. In this review, we discuss the technical challenges associated with genetic transformation of obligate intracellular bacteria and highlight advances made with individual genera.

  1. Intracellular calcium levels can regulate Importin-dependent nuclear import

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

    2014-07-18

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.

  2. Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implications

    Directory of Open Access Journals (Sweden)

    Walmor eDe Mello

    2015-01-01

    Full Text Available The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; 1 under normal conditions, Lucifer Yellow flows from cell-to-cell through gap junctions; 2 the intracellular dialysis of renin (100nM disrupts chemical communication-an effect enhanced by simultaneous administration of angiotensinogen (100nM; 3 enalaprilat (10-9M administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; 4 aliskiren (10-8M inhibited the effect of renin on chemical communication;5 the possible role of intracellular renin independently of angiotensin II (Ang II was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; 6 the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed;7 the present results indicate that intracellular renin due to internalization or in situ synthesis, causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.

  3. Self-organization of intracellular gradients during mitosis

    Directory of Open Access Journals (Sweden)

    Fuller Brian G

    2010-01-01

    Full Text Available Abstract Gradients are used in a number of biological systems to transmit spatial information over a range of distances. The best studied are morphogen gradients where information is transmitted over many cell lengths. Smaller mitotic gradients reflect the need to organize several distinct events along the length of the mitotic spindle. The intracellular gradients that characterize mitosis are emerging as important regulatory paradigms. Intracellular gradients utilize intrinsic auto-regulatory feedback loops and diffusion to establish stable regions of activity within the mitotic cytosol. We review three recently described intracellular mitotic gradients. The Ran GTP gradient with its elaborate cascade of nuclear transport receptors and cargoes is the best characterized, yet the dynamics underlying the robust gradient of Ran-GTP have received little attention. Gradients of phosphorylation have been observed on Aurora B kinase substrates both before and after anaphase onset. In both instances the phosphorylation gradient appears to result from a soluble gradient of Aurora B kinase activity. Regulatory properties that support gradient formation are highlighted. Intracellular activity gradients that regulate localized mitotic events bare several hallmarks of self-organizing biologic systems that designate spatial information during pattern formation. Intracellular pattern formation represents a new paradigm in mitotic regulation.

  4. Acute effects of nitroglycerin depend on both plasma and intracellular sulfhydryl compound levels in vivo. Effect of agents with different sulfhydryl-modulating properties

    DEFF Research Database (Denmark)

    Boesgaard, S; Poulsen, H E; Aldershvile, J

    1993-01-01

    in SH group concentrations (cysteine and glutathione [GSH]) affect the responsiveness to NTG in vivo. METHODS AND RESULTS: GSH and cysteine levels in plasma, vena cava, and aorta were measured after administration of N-acetylserine (placebo, n = 6), N-acetylcysteine (NAC, extracellular and intracellular......BACKGROUND: Changes in sulfhydryl (SH) compound availability may alter the hemodynamic effect of nitroglycerin (NTG). Data on the relation between NTG effect and thiol levels are, however, limited to in vitro experiments. The present study investigates how intracellular and extracellular changes...... SH donor, n = 6), oxothiazolidine (OXO, intracellular SH donor, n = 6), buthionine sulfoximine (BSO, intracellular GSH-depleting agent, n = 6), BSO+NAC (n = 6), and BSO+OXO (n = 6) in chronically catheterized conscious rats. In addition, the effect of 2.5 mg NTG/kg i.v. on mean arterial pressure (MAP...

  5. ABC transporters affect the detection of intracellular oxidants by fluorescent probes

    Czech Academy of Sciences Publication Activity Database

    Procházková, J.; Kubala, Lukáš; Kotasová, H.; Gudernová, I.; Šrámková, Z.; Pekarová, Michaela; Sarkadi, B.; Pachernik, J.

    2011-01-01

    Roč. 45, č. 7 (2011), s. 779-787 ISSN 1071-5762 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : Fluorescence * redox status * mitochondria Subject RIV: BO - Biophysics Impact factor: 2.878, year: 2011

  6. Cathelicidin LL-37 Affects Surface and Intracellular Toll-Like Receptor Expression in Tissue Mast Cells

    Directory of Open Access Journals (Sweden)

    Justyna Agier

    2018-01-01

    Full Text Available Undoubtedly, mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, they release many proinflammatory and antimicrobial mediators, and they express pattern recognition receptors, such as TLRs. These receptors play a key role in recognition and binding molecules associated with microorganisms and molecules associated with damage. Cathelicidins exhibit direct antimicrobial activities against a broad spectrum of microbes by perturbing their cell membranes. Accumulating evidence suggests a role for these molecules in supporting cell activation. We examined the impact of human cathelicidin LL-37 on tissue mast cell TLR expression and distribution. Depending on context, we show that LL-37 stimulation resulted in minor to major effects on TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9 expression. Confocal microscopy analysis showed that, upon stimulation, TLRs may translocate from the cell interior to the surface and conversely. FPR2 and EGFR inhibitors reduced the increase in expression of selected receptors. We also established that LL-37 acts as a powerful inducer of CCL3 and ROS generation. These results showed that in response to LL-37, mast cells enhance the capability to detect invading pathogens by modulation of TLR expression in what may be involved FPR2 or EGFR molecules.

  7. Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene Affecting Human Bone Formation

    DEFF Research Database (Denmark)

    Brum, A M; Leije, M; J, Schreuders-Koedam

    2017-01-01

    is diminished and more adipocytes are seen in the bone marrow, suggesting a shift in MSC lineage commitment. Identification of specific factors that stimulate osteoblast differentiation from human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this study was to identify novel genes...... an in vivo human bone formation model in which hMSCs lentivirally transduced with the CLIC3 overexpression construct were loaded onto a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD-SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression led to a 15...

  8. Fuel behaviour

    International Nuclear Information System (INIS)

    Fodor, M.; Matus, L.; Vigassy, J.

    1987-11-01

    A short summary of the main critical points in fuel performance of nuclear power reactors from chemical and mechanical point of view is given. A schedule for a limited research program is included. (author) 17 refs

  9. Fuel cells

    International Nuclear Information System (INIS)

    Niederdoeckl, J.

    2001-01-01

    Europe has at present big hopes on the fuel cells technology, in comparison with other energy conversion technologies, this technology has important advantages, for example: high efficiency, very low pollution and parallel use of electric and thermal energy. Preliminary works for fuel cells developing and its commercial exploitation are at full speed; until now the European Union has invested approx. 1.7 billion Schillings, 60 relevant projects are being executed. The Austrian industry is interested in applying this technique to drives, thermal power stations and the miniature fuel cells as replacement of batteries in electronic products (Notebooks, mobile telephones, etc.). A general description of the historic development of fuel cells including the main types is given as well as what is the situation in Austria. (nevyjel)

  10. Fuel assembly

    International Nuclear Information System (INIS)

    Ishibashi, Yoko; Aoyama, Motoo; Oyama, Jun-ichi.

    1995-01-01

    Burnable poison-incorporating fuel rods of a first group are disposed in a region in adjacent with a water rod having a large diameter (neutron moderator rod) disposed to the central portion of a fuel assembly. Burnable poison-incorporating fuel rods of a second group are disposed to a region other than peripheral zone in adjacent with a channel box and corners positioned at an inner zone, in adjacent with the channel box. The average concentration of burnable poisons of the burnable poison-incorporating fuel rods of the first group is made greater than that of the second group. With such a constitution, when the burnable poisons of the first group are burnt out, the burnable poisons of the second group are also burnt out at the same time. Accordingly, an amount of burnable poisons left unburnt at the final stage of the operation cycle is reduced, to improve the reactivity. This can improve the economical property. (I.N.)

  11. A comparative analysis of in vitro toxicity of diesel exhaust particles from combustion of 1st- and 2nd-generation biodiesel fuels in relation to their physicochemical properties-the FuelHealth project.

    Science.gov (United States)

    Lankoff, Anna; Brzoska, Kamil; Czarnocka, Joanna; Kowalska, Magdalena; Lisowska, Halina; Mruk, Remigiusz; Øvrevik, Johan; Wegierek-Ciuk, Aneta; Zuberek, Mariusz; Kruszewski, Marcin

    2017-08-01

    Biodiesels represent more carbon-neutral fuels and are introduced at an increasing extent to reduce emission of greenhouse gases. However, the potential impact of different types and blend concentrations of biodiesel on the toxicity of diesel engine emissions are still relatively scarce and to some extent contradictory. The objective of the present work was to compare the toxicity of diesel exhaust particles (DEP) from combustion of two 1st-generation fuels: 7% fatty acid methyl esters (FAME; B7) and 20% FAME (B20) and a 2nd-generation 20% FAME/HVO (synthetic hydrocarbon biofuel (SHB)) fuel. Our findings indicate that particulate emissions of each type of biodiesel fuel induce cytotoxic effects in BEAS-2B and A549 cells, manifested as cell death (apoptosis or necrosis), decreased protein concentrations, intracellular ROS production, as well as increased expression of antioxidant genes and genes coding for DNA damage-response proteins. The different biodiesel blend percentages and biodiesel feedstocks led to marked differences in chemical composition of the emitted DEP. The different DEPs also displayed statistically significant differences in cytotoxicity in A549 and BEAS-2B cells, but the magnitude of these variations was limited. Overall, it seems that increasing biodiesel blend concentrations from the current 7 to 20% FAME, or substituting 1st-generation FAME biodiesel with 2nd-generation HVO biodiesel (at least below 20% blends), affects the in vitro toxicity of the emitted DEP to some extent, but the biological significance of this may be moderate.

  12. Fuel element

    International Nuclear Information System (INIS)

    Armijo, J.S.

    1976-01-01

    A fuel element for nuclear reactors is proposed which has a higher corrosion resisting quality in reactor operations. The zirconium alloy coating around the fuel element (uranium or plutonium compound) has on its inside a protection layer of metal which is metallurgically bound to the substance of the coating. As materials are namned: Alluminium, copper, niobium, stainless steel, and iron. This protective metallic layer has another inner layer, also metallurgically bound to its surface, which consists usually of a zirconium alloy. (UWI) [de

  13. Quantifying intracellular hydrogen peroxide perturbations in terms of concentration

    Directory of Open Access Journals (Sweden)

    Beijing K. Huang

    2014-01-01

    Full Text Available Molecular level, mechanistic understanding of the roles of reactive oxygen species (ROS in a variety of pathological conditions is hindered by the difficulties associated with determining the concentration of various ROS species. Here, we present an approach that converts fold-change in the signal from an intracellular sensor of hydrogen peroxide into changes in absolute concentration. The method uses extracellular additions of peroxide and an improved biochemical measurement of the gradient between extracellular and intracellular peroxide concentrations to calibrate the intracellular sensor. By measuring peroxiredoxin activity, we found that this gradient is 650-fold rather than the 7–10-fold that is widely cited. The resulting calibration is important for understanding the mass-action kinetics of complex networks of redox reactions, and it enables meaningful characterization and comparison of outputs from endogenous peroxide generating tools and therapeutics across studies.

  14. Simple Recovery of Intracellular Gold Nanoparticles from Peanut Seedling Roots.

    Science.gov (United States)

    Raju, D; Mehta, Urmil J; Ahmad, Absar

    2015-02-01

    Fabrication of inorganic nanomaterials via a biological route witnesses the formation either extracellularly, intracellulary or both. Whereas extracellular formation of these nanomaterials is cherished owing to their easy and economical extraction and purification processes; the intracellular formation of nanomaterials, due to the lack of a proper recovery protocol has always been dreaded, as the extraction processes used so far were tedious, costly, time consuming and often resulting in very low recovery. The aim of the present study was to overcome the problems related with the extraction and recovery of intracellularly synthesized inorganic nanoparticles, and to devise a method to increasing the output, the shape, size, composition and dispersal of nanoparticles is not altered. Water proved to be much better system as it provided well dispersed, stable gold nanoparticles and higher recovery. This is the first report, where intracellular nanoparticles have been recovered using a very cost-effective and eco-friendly approach.

  15. Non-recessive Bt toxin resistance conferred by an intracellular cadherin mutation in field-selected populations of cotton bollworm.

    Directory of Open Access Journals (Sweden)

    Haonan Zhang

    Full Text Available Transgenic crops producing Bacillus thuringiensis (Bt toxins have been planted widely to control insect pests, yet evolution of resistance by the pests can reduce the benefits of this approach. Recessive mutations in the extracellular domain of toxin-binding cadherin proteins that confer resistance to Bt toxin Cry1Ac by disrupting toxin binding have been reported previously in three major lepidopteran pests, including the cotton bollworm, Helicoverpa armigera. Here we report a novel allele from cotton bollworm with a deletion in the intracellular domain of cadherin that is genetically linked with non-recessive resistance to Cry1Ac. We discovered this allele in each of three field-selected populations we screened from northern China where Bt cotton producing Cry1Ac has been grown intensively. We expressed four types of cadherin alleles in heterologous cell cultures: susceptible, resistant with the intracellular domain mutation, and two complementary chimeric alleles with and without the mutation. Cells transfected with each of the four cadherin alleles bound Cry1Ac and were killed by Cry1Ac. However, relative to cells transfected with either the susceptible allele or the chimeric allele lacking the intracellular domain mutation, cells transfected with the resistant allele or the chimeric allele containing the intracellular domain mutation were less susceptible to Cry1Ac. These results suggest that the intracellular domain of cadherin is involved in post-binding events that affect toxicity of Cry1Ac. This evidence is consistent with the vital role of the intracellular region of cadherin proposed by the cell signaling model of the mode of action of Bt toxins. Considered together with previously reported data, the results suggest that both pore formation and cell signaling pathways contribute to the efficacy of Bt toxins.

  16. Fuel assembly

    International Nuclear Information System (INIS)

    Ueda, Sei; Ando, Ryohei; Mitsutake, Toru.

    1995-01-01

    The present invention concerns a fuel assembly suitable to a BWR-type reactor and improved especially with the nuclear characteristic, heat performance, hydraulic performance, dismantling or assembling performance and economical property. A part of poison rods are formed as a large-diameter/multi-region poison rods having a larger diameter than a fuel rod. A large number of fuel rods are disposed surrounding a large diameter water rod and a group of the large-diameter/multi-region poison rods in adjacent with the water rod. The large-diameter water rod has a burnable poison at the tube wall portion. At least a portion of the large-diameter poison rods has a coolant circulation portion allowing coolants to circulate therethrough. Since the large-diameter poison rods are disposed at a position of high neutron fluxes, a large neutron multiplication factor suppression effect can be provided, thereby enabling to reduce the number of burnable poison rods relative to fuels. As a result, power peaking in the fuel assembly is moderated and a greater amount of plutonium can be loaded. In addition the flow of cooling water which tends to gather around the large diameter water rod can be controlled to improve cooling performance of fuels. (N.H.)

  17. Cracking and relocation of UO2 fuel during nuclear operation

    International Nuclear Information System (INIS)

    Appelhans, A.D.; Dagbjartsson, S.J.

    1981-01-01

    Cracking and relocation of light water reactor (LWR) fuel pellets affect the axial gas flow path within nuclear reactor fuel rods and the thermal performance of the fuel. As part of the Nuclear Regulatory Commission's Water Reactor Safety Research Fuel Behavior Program, the Thermal Fuels Behavior Program of EG and G Idaho, Inc., is conducting fuel rod behavior studies in the Heavy Boiling Water Reactor in Halden, Norway. The Instrumental Fuel Assembly-430 (IFA-430) operated in that facility is a multipurpose assembly designed to provide information on fuel cracking and relocation, the long-term thermal response of LWR fuel rods subjected to various internal pressures and gas compositions, and the release of fission gases. This report presents the results of an analysis of fuel cracking and relocation phenomena as deduced from fuel rod axial gas flow and fuel temperature data from the first 6.5 GWd/tUO 2 burnup of the IFA-430

  18. Temperature Calculation of Annular Fuel Pellet by Finite Difference Method

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yong Sik; Bang, Je Geon; Kim, Dae Ho; Kim, Sun Ki; Lim, Ik Sung; Song, Kun Woo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-10-15

    KAERI has started an innovative fuel development project for applying dual-cooled annular fuel to existing PWR reactor. In fuel design, fuel temperature is the most important factor which can affect nuclear fuel integrity and safety. Many models and methodologies, which can calculate temperature distribution in a fuel pellet have been proposed. However, due to the geometrical characteristics and cooling condition differences between existing solid type fuel and dual-cooled annular fuel, current fuel temperature calculation models can not be applied directly. Therefore, the new heat conduction model of fuel pellet was established. In general, fuel pellet temperature is calculated by FDM(Finite Difference Method) or FEM(Finite Element Method), because, temperature dependency of fuel thermal conductivity and spatial dependency heat generation in the pellet due to the self-shielding should be considered. In our study, FDM is adopted due to high exactness and short calculation time.

  19. Tethering factors as organizers of intracellular vesicular traffic.

    Science.gov (United States)

    Yu, I-Mei; Hughson, Frederick M

    2010-01-01

    Intracellular trafficking entails the budding, transport, tethering, and fusion of transport vesicles and other membrane carriers. Here we review recent progress toward a mechanistic understanding of vesicle tethering. The known tethering factors are large complexes important for one or more intracellular trafficking pathways and are capable of interacting directly with many of the other principal components of the cellular trafficking machinery. Our review emphasizes recent developments in the in vitro reconstitution of vesicle tethering and the structural characterization of multisubunit tethering factors. The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work.

  20. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

    Science.gov (United States)

    Pareja, Maria Eugenia Mansilla; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

  1. Overexpression of the transcription factor Yap1 modifies intracellular redox conditions and enhances recombinant protein secretion

    Directory of Open Access Journals (Sweden)

    Marizela Delic

    2014-10-01

    Full Text Available Oxidative folding of secretory proteins in the endoplasmic reticulum (ER is a redox active process, which also impacts the redox conditions in the cytosol. As the transcription factor Yap1 is involved in the transcriptional response to oxidative stress, we investigate its role upon the production of secretory proteins, using the yeast Pichia pastoris as model, and report a novel important role of Yap1 during oxidative protein folding. Yap1 is needed for the detoxification of reactive oxygen species (ROS caused by increased oxidative protein folding. Constitutive co-overexpression of PpYAP1 leads to increased levels of secreted recombinant protein, while a lowered Yap1 function leads to accumulation of ROS and strong flocculation. Transcriptional analysis revealed that more than 150 genes were affected by overexpression of YAP1, in particular genes coding for antioxidant enzymes or involved in oxidation-reduction processes. By monitoring intracellular redox conditions within the cytosol and the ER using redox-sensitive roGFP1 variants, we could show that overexpression of YAP1 restores cellular redox conditions of protein-secreting P. pastoris by reoxidizing the cytosolic redox state to the levels of the wild type. These alterations are also reflected by increased levels of oxidized intracellular glutathione (GSSG in the YAP1 co-overexpressing strain. Taken together, these data indicate a strong impact of intracellular redox balance on the secretion of (recombinant proteins without affecting protein folding per se. Re-establishing suitable redox conditions by tuning the antioxidant capacity of the cell reduces metabolic load and cell stress caused by high oxidative protein folding load, thereby increasing the secretion capacity.

  2. Sulphur release from alternative fuel firing

    DEFF Research Database (Denmark)

    Cortada Mut, Maria del Mar; Nørskov, Linda Kaare; Glarborg, Peter

    2014-01-01

    The cement industry has long been dependent on the use of fossil fuels, although a recent trend in replacing fossil fuels with alternative fuels has arisen. 1, 2 However, when unconverted or partly converted alternative fuels are admitted directly in the rotary kiln inlet, the volatiles released...... from the fuels may react with sulphates present in the hot meal to form SO 2 . Here Maria del Mar Cortada Mut and associates describe pilot and industrial scale experiments focusing on the factors that affect SO 2 release in the cement kiln inlet....

  3. The epithelial cell cytoskeleton and intracellular trafficking. I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more.

    Science.gov (United States)

    Johannes, Ludger

    2002-07-01

    Many intracellular transport routes are still little explored. This is particularly true for retrograde transport between the plasma membrane and the endoplasmic reticulum. Shiga toxin B subunit has become a powerful tool to study this pathway, and recent advances on the molecular mechanisms of transport in the retrograde route and on its physiological function(s) are summarized. Furthermore, it is discussed how the study of retrograde transport of Shiga toxin B subunit allows one to design new methods for the intracellular delivery of therapeutic compounds.

  4. Fuel rods

    International Nuclear Information System (INIS)

    Adachi, Hajime; Ueda, Makoto

    1985-01-01

    Purpose: To provide a structure capable of measuring, in a non-destructive manner, the releasing amount of nuclear gaseous fission products from spent fuels easily and at a high accuracy. Constitution: In order to confirm the integrity and the design feasibility of a nuclear fuel rod, it is important to accurately determine the amount of gaseous nuclear fission products released from nuclear pellets. In a structure where a plurality of fuel pellets are charged in a fuel cladding tube and retained by an inconel spring, a hollow and no-sealed type spacer tube made of zirconium or the alloy thereof, for example, not containing iron, cobalt, nickel or manganese is formed between the spring and the upper end plug. In the fuel rod of such a structure, by disposing a gamma ray collimator and a gamma ray detector on the extension of the spacer pipe, the gamma rays from the gaseous nuclear fission products accumulated in the spacer pipe can be detected while avoiding the interference with the induction radioactivity from inconel. (Kamimura, M.)

  5. Fuel rods

    International Nuclear Information System (INIS)

    Hattori, Shinji; Kajiwara, Koichi.

    1980-01-01

    Purpose: To ensure the safety for the fuel rod failures by adapting plenum springs to function when small forces such as during transportation of fuel rods is exerted and not to function the resilient force when a relatively great force is exerted. Constitution: Between an upper end plug and a plenum spring in a fuel rod, is disposed an insertion member to the lower portion of which is mounted a pin. This pin is kept upright and causes the plenum spring to function resiliently to the pellets against the loads due to accelerations and mechanical vibrations exerted during transportation of the fuel rods. While on the other hand, if a compression force of a relatively high level is exerted to the plenum spring during reactor operation, the pin of the insertion member is buckled and the insertion member is inserted to the inside of the plenum spring, whereby the pellets are allowed to expand freely and the failures in the fuel elements can be prevented. (Moriyama, K.)

  6. Fuel assembly

    International Nuclear Information System (INIS)

    Abe, Hideaki; Sakai, Takao; Ishida, Tomio; Yokota, Norikatsu.

    1992-01-01

    The lower ends of a plurality of plate-like shape memory alloys are secured at the periphery of the upper inside of the handling head of a fuel assembly. As the shape memory alloy, a Cu-Zn alloy, a Ti-Pd alloy or a Fe-Ni alloy is used. When high temperature coolants flow out to the handling head, the shape memory alloy deforms by warping to the outer side more greatly toward the upper portion thereof with the temperature increase of the coolants. As the result, the shape of the flow channel of the coolants is changed so as to enlarge at the exit of the upper end of the fuel assembly. Then, the pressure loss of the coolants in the fuel assembly is decreased by the enlargement. Accordingly, the flow rate of the coolants in the fuel assembly is increased to lower the temperature of the coolants. Further, high temperature coolants and low temperature coolants are mixed sufficiently just above the fuel assembly. This can suppress the temperature fluctuation of the mixed coolants in the upper portion of the reactor core, thereby enabling to decrease a fatigue and failures of the structural components in the upper portion of the reactor core. (I.N.)

  7. Fuel assembly

    International Nuclear Information System (INIS)

    Sano, Hiroki; Fushimi, Atsushi; Tominaga, Kenji; Aoyama, Motoo; Ishii, Kazuya.

    1997-01-01

    In burnable poison-incorporated uranium fuels of a BWR type reactor, the compositional ratio of isotopes of the burnable poisons is changed so as to increase the amount of those having a large neutron absorbing cross sectional area. For example, if the ratio of Gd-157 at the same burnable poison enrichment degree is made greater than the natural ratio, this gives the same effect as the increase of the enrichment degree per one fuel rod, thereby providing an effect of reducing a surplus reactivity. Gadolinium, hafnium and europium as burnable poisons have an absorbing cross sectional area being greater in odd numbered nuclei than in even numbered nuclei, on the contrary, boron has a cross section being greater in even numbered nucleus than odd numbered nuclei. Accordingly, if the ratio of isotopes having greater cross section at the same burnable poison enrichment degree is made greater than the natural ratio, surplus reactivity at the initial stage of the burning can be reduced without greatly increasing the amount of burnable poison-incorporated uranium fuels, fuel loading amount is not reduced and the fuel economy is not worsened. (N.H.)

  8. Transepithelial SCFA fluxes link intracellular and extracellular pH regulation of mouse colonocytes.

    Science.gov (United States)

    Chu, S; Montrose, M H

    1997-10-01

    We have studied pH regulation in both intracellular and extracellular compartments of mouse colonic crypts, using distal colonic mucosa with intact epithelial architecture. In this work, we question how transepithelial SCFA gradients affect intracellular pH (pHi) and examine interactions between extracellular pH (pHo) and pHi regulation in crypts of distal colonic epithelium from mouse. We studied pH regulation in three adjacent compartments of distal colonic epithelium (crypt lumen, crypt epithelial cell cytosol, and lamina propria) with SNARF-1 (a pH sensitive fluorescent dye), digital imaging microscopy (for pHi), and confocal microscopy (for pHo). Combining results from the three compartments allows us to find how pHi and pHo are regulated and related under the influence of physiological transepithelial SCFA gradients, and develop a better understanding of pH regulation mechanisms in colonic crypts. Results suggest a complex interdependency between SCFA fluxes and pHo values, which can directly affect how strongly SCFAs acidify colonocytes.

  9. Tyrosine phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

    Science.gov (United States)

    Zhong, Li; Li, Baozheng; Jayandharan, Giridhararao; Mah, Cathryn S.; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Herzog, Roland W.; Weigel-Van Aken, Kirsten A.; Hobbs, Jacqueline A.; Zolotukhin, Sergei; Muzyczka, Nicholas; Srivastava, Arun

    2008-01-01

    We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV capsids can indeed be phosphorylated at tyrosine residues by EGFR-PTK in in vitro phosphorylation assays and that phosphorylated AAV capsids retain their structural integrity. However, although phosphorylated AAV vectors enter cells as efficiently as their unphosphorylated counterparts, their transduction efficiency is significantly reduced. This reduction is not due to impaired viral second-strand DNA synthesis since transduction efficiency of both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors is decreased by ~68% and ~74%, respectively. We also observed that intracellular trafficking of tyrosine-phosphorylated AAV vectors from cytoplasm to nucleus is significantly decreased, which leads to ubiquitination of AAV capsids followed by proteasome-mediated degradation, although downstream consequences of capsid ubiquitination may also be affected by tyrosine-phosphorylation. These studies provide new insights into the role of tyrosine-phosphorylation of AAV capsids in various steps in the virus life cycle, which has implications in the optimal use of recombinant AAV vectors in human gene therapy. PMID:18834608

  10. Canadian power reactor fuel

    International Nuclear Information System (INIS)

    Page, R.D.

    1976-03-01

    The following subjects are covered: the basic CANDU fuel design, the history of the bundle design, the significant differences between CANDU and LWR fuel, bundle manufacture, fissile and structural materials and coolants used in the CANDU fuel program, fuel and material behaviour, and performance under irradiation, fuel physics and management, booster rods and reactivity mechanisms, fuel procurement, organization and industry, and fuel costs. (author)

  11. Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

    OpenAIRE

    Zhong, Li; Li, Baozheng; Jayandharan, Giridhararao; Mah, Cathryn S.; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Herzog, Roland W.; Weigel-Van Aken, Kirsten A.; Hobbs, Jacqueline A.; Zolotukhin, Sergei; Muzyczka, Nicholas; Srivastava, Arun

    2008-01-01

    We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV cap...

  12. Progress and recent trends in biodiesel fuels

    International Nuclear Information System (INIS)

    Demirbas, Ayhan

    2009-01-01

    Fossil fuel resources are decreasing daily. Biodiesel fuels are attracting increasing attention worldwide as blending components or direct replacements for diesel fuel in vehicle engines. Biodiesel fuel typically comprises lower alkyl fatty acid (chain length C 14 -C 22 ), esters of short-chain alcohols, primarily, methanol or ethanol. Various methods have been reported for the production of biodiesel from vegetable oil, such as direct use and blending, microemulsification, pyrolysis, and transesterification. Among these, transesterification is an attractive and widely accepted technique. The purpose of the transesterification process is to lower the viscosity of the oil. The most important variables affecting methyl ester yield during the transesterification reaction are the molar ratio of alcohol to vegetable oil and the reaction temperature. Methanol is the commonly used alcohol in this process, due in part to its low cost. Methyl esters of vegetable oils have several outstanding advantages over other new-renewable and clean engine fuel alternatives. Biodiesel fuel is a renewable substitute fuel for petroleum diesel or petrodiesel fuel made from vegetable or animal fats; it can be used in any mixture with petrodiesel fuel, as it has very similar characteristics, but it has lower exhaust emissions. Biodiesel fuel has better properties than petrodiesel fuel; it is renewable, biodegradable, non-toxic, and essentially free of sulfur and aromatics. Biodiesel seems to be a realistic fuel for future; it has become more attractive recently because of its environmental benefits. Biodiesel is an environmentally friendly fuel that can be used in any diesel engine without modification

  13. Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

    Science.gov (United States)

    There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...

  14. FLIPR assays of intracellular calcium in GPCR drug discovery

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Bräuner-Osborne, Hans

    2009-01-01

    Fluorescent dyes sensitive to changes in intracellular calcium have become increasingly popular in G protein-coupled receptor (GPCR) drug discovery for several reasons. First of all, the assays using the dyes are easy to perform and are of low cost compared to other assays. Second, most non...

  15. Intracellular localization of Na + /H + antiporter from Malus zumi ...

    African Journals Online (AJOL)

    In this study, we examined the intracellular localization of the product of Na+/H+ antiporter gene (MzNHX1) cloned from Malus zumi. Analysis using yeast cells expressing a fusion protein of MzNHX1 and green fluorescent protein confirmed the localization of MzNHX1 on the tonoplast.

  16. Intracellular pH gradients in migrating cells

    DEFF Research Database (Denmark)

    Martin, Christine; Pedersen, Stine Helene Falsig; Schwab, Albrecht

    2011-01-01

    might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of p...

  17. Structural rearrangement of the intracellular domains during AMPA receptor activation

    DEFF Research Database (Denmark)

    Zachariassen, Linda Grønborg; Katchan, Ljudmila; Jensen, Anna Guldvang

    2016-01-01

    -clamp fluorometry of the double- and single-insert constructs showed that both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane. Our time-resolved measurements revealed unexpectedly complex fluorescence...

  18. The interferon response to intracellular DNA: why so many receptors?

    Science.gov (United States)

    Unterholzner, Leonie

    2013-11-01

    The detection of intracellular DNA has emerged to be a key event in the innate immune response to viruses and intracellular bacteria, and during conditions of sterile inflammation and autoimmunity. One of the consequences of the detection of DNA as a 'stranger' and a 'danger' signal is the production of type I interferons and pro-inflammatory cytokines. Much work has been dedicated to the elucidation of the signalling cascades that activate this DNA-induced gene expression programme. However, while many proteins have been proposed to act as sensors for intracellular DNA in recent years, none has been met with universal acceptance, and a theory linking all the recent observations is, as yet, lacking. This review presents the evidence for the various interferon-inducing DNA receptors proposed to date, and examines the hypotheses that might explain why so many different receptors appear to be involved in the innate immune recognition of intracellular DNA. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Manipulation of Host Cholesterol by Obligate Intracellular Bacteria

    Directory of Open Access Journals (Sweden)

    Dhritiman Samanta

    2017-05-01

    Full Text Available Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol metabolism, uptake, efflux, and storage. In this review, we examine the strategies obligate intracellular bacterial pathogens employ to manipulate cholesterol during host cell colonization. Understanding how obligate intracellular pathogens target and use host cholesterol provides critical insight into the host-pathogen relationship.

  20. Engineering of obligate intracellular bacteria: progress, challenges and paradigms

    Science.gov (United States)

    Over twenty years have passed since the first report of genetic manipulation of an obligate intracellular bacterium. Through progress interspersed by bouts of stagnation, microbiologists and geneticists have developed approaches to genetically manipulate obligates. A brief overview of the current ge...

  1. Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

    DEFF Research Database (Denmark)

    Carlsson, Carl Michael; Bengtson, Per; Cucak, Helena

    2013-01-01

    these transferrin glycoforms differently after preloading with exogenously added galectin-3. In all, this study provides the first evidence of a functional role for transferrin glycans, in intracellular trafficking after uptake. Moreover, the galectin-3 bound glycoform increased in cancer, suggesting...

  2. Dihydroceramide biology - Structure-specific metabolism and intracellular localization

    NARCIS (Netherlands)

    Kok, JW; NikolovaKarakashian, M; Klappe, K; Alexander, C; Merrill, AH

    1997-01-01

    This study utilized fluorescent analogs to characterize the intracellular transport and metabolism of dihydroceramide (DN-Cer), an intermediate in de novo sphingolipid biosynthesis, When 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoyl-DH-Cer (C-6-NBD-DH-Cer) was incubated with HT29, NRK, BHK,

  3. CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

    Directory of Open Access Journals (Sweden)

    Samuel eGoodchild

    2012-06-01

    Full Text Available Voltage sensing domains of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K+ ions to flow. Conformational transitions within the voltage sensing domain caused by changes in the applied voltage across the membrane field are coupled to the conducting pore region and the gating of ionic conductance. However, several other factors not directly linked to the voltage dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

  4. Biomineralization Patterns of Intracellular Carbonatogenesis in Cyanobacteria: Molecular Hypotheses

    Directory of Open Access Journals (Sweden)

    Jinhua Li

    2016-02-01

    Full Text Available The recent discovery of intracellular carbonatogenesis in several cyanobacteria species has challenged the traditional view that this process was extracellular and not controlled. However, a detailed analysis of the size distribution, chemical composition and 3-D-arrangement of carbonates in these cyanobacteria is lacking. Here, we characterized these features in Candidatus Gloeomargarita lithophora C7 and Candidatus Synechococcus calcipolaris G9 by conventional transmission electron microscopy, tomography, ultramicrotomy, and scanning transmission X-ray microscopy (STXM. Both Ca. G. lithophora C7 and Ca. S. calcipolaris G9 formed numerous polyphosphate granules adjacent or engulfing Ca-carbonate inclusions when grown in phosphate-rich solutions. Ca-carbonates were scattered within Ca. G. lithophora C7 cells under these conditions, but sometimes arranged in one or several chains. In contrast, Ca-carbonates formed at cell septa in Ca. S. calcipolaris G9 and were segregated equally between daughter cells after cell division, arranging as distorted disks at cell poles. The size distribution of carbonates evolved from a positively to a negatively skewed distribution as particles grew. Conventional ultramicrotomy did not preserve Ca-carbonates explaining partly why intracellular calcification has been overlooked in the past. All these new observations allow discussing with unprecedented insight some nucleation and growth processes occurring in intracellularly calcifying cyanobacteria with a particular emphasis on the possible involvement of intracellular compartments and cytoskeleton.

  5. Antibody- and TRIM21-dependent intracellular restriction of Salmonella enterica.

    Science.gov (United States)

    Rakebrandt, Nikolas; Lentes, Sabine; Neumann, Heinz; James, Leo C; Neumann-Staubitz, Petra

    2014-11-01

    TRIM21 ('tripartite motif-containing protein 21', Ro52) is a ubiquitously expressed cytosolic Fc receptor, which has a potent role in protective immunity against nonenveloped viruses. TRIM21 mediates intracellular neutralisation of antibody-coated viruses, a process called ADIN (antibody-dependent intracellular neutralisation). Our results reveal a similar mechanism to fight bacterial infections. TRIM21 is recruited to the intracellular pathogen Salmonella enterica in epithelial cells early in infection. TRIM21 does not bind directly to S. enterica, but to antibodies opsonising it. Most importantly, bacterial restriction is dependent on TRIM21 as well as on the opsonisation state of the bacteria. Finally, Salmonella and TRIM21 colocalise with the autophagosomal marker LC3, and intracellular defence is enhanced in starved cells suggesting an involvement of the autophagocytic pathway. Our data extend the protective role of TRIM21 from viruses to bacteria and thereby strengthening the general role of ADIN in cellular immunity. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  6. Cytoplasmic tail of coronavirus spike protein has intracellular

    Indian Academy of Sciences (India)

    https://www.ias.ac.in/article/fulltext/jbsc/042/02/0231-0244. Keywords. Coronavirus spike protein trafficking; cytoplasmic tail signal; endoplasmic reticulum–Golgi intermediate complex; lysosome. Abstract. Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spikeprotein is ...

  7. Facilitating Intracellular Drug Delivery by Ultrasound-Activated Microbubbles

    NARCIS (Netherlands)

    Lammertink, BHA

    2017-01-01

    The goal of this thesis was to investigate the combination of ultrasound and microbubbles (USMB) for intracellular delivery of (model) drugs in vitro. We have focused on clinically approved drugs, i.e. cisplatin, and microbubbles, i.e. SonoVue™, to facilitate clinical translation. In addition, model

  8. Fuel performance analysis code 'FAIR'

    International Nuclear Information System (INIS)

    Swami Prasad, P.; Dutta, B.K.; Kushwaha, H.S.; Mahajan, S.C.; Kakodkar, A.

    1994-01-01

    For modelling nuclear reactor fuel rod behaviour of water cooled reactors under severe power maneuvering and high burnups, a mechanistic fuel performance analysis code FAIR has been developed. The code incorporates finite element based thermomechanical module, physically based fission gas release module and relevant models for modelling fuel related phenomena, such as, pellet cracking, densification and swelling, radial flux redistribution across the pellet due to the build up of plutonium near the pellet surface, pellet clad mechanical interaction/stress corrosion cracking (PCMI/SSC) failure of sheath etc. The code follows the established principles of fuel rod analysis programmes, such as coupling of thermal and mechanical solutions along with the fission gas release calculations, analysing different axial segments of fuel rod simultaneously, providing means for performing local analysis such as clad ridging analysis etc. The modular nature of the code offers flexibility in affecting modifications easily to the code for modelling MOX fuels and thorium based fuels. For performing analysis of fuel rods subjected to very long power histories within a reasonable amount of time, the code has been parallelised and is commissioned on the ANUPAM parallel processing system developed at Bhabha Atomic Research Centre (BARC). (author). 37 refs

  9. Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes

    Science.gov (United States)

    Ericson, Megan E.; Frank, Matthew W.

    2016-01-01

    Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogen Listeria monocytogenes encode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype of Escherichia coli strain JP1111 [fabI(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate of L. monocytogenes in laboratory medium. Robust exogenous fatty acid incorporation was not detected in L. monocytogenes unless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth of L. monocytogenes, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth of L. monocytogenes. Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth of L. monocytogenes. PMID:27736774

  10. Single-cell intracellular nano-pH probes†

    Science.gov (United States)

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2016-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution. PMID:27708772

  11. Single-cell intracellular nano-pH probes.

    Science.gov (United States)

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2015-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

  12. Legionella pneumophila transcriptome during intracellular multiplication in human macrophages

    Directory of Open Access Journals (Sweden)

    Sebastien P Faucher

    2011-04-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires’ disease, an acute pulmonary infection. L. pneumophila is able to infect and multiply in both phagocytic protozoa, such as Acanthamoeba castellanii, and mammalian professional phagocytes. The best-known L. pneumophila virulence determinant is the Icm/Dot Type IVB secretion system (TFBSS, which is used to translocate more than 150 effector proteins to host cells. While the transcriptional response of Legionella to the intracellular environment of A. castellanii has been investigated, much less is known about the Legionella transcriptional response inside human macrophages. In this study, the transcriptome of L. pneumophila was monitored during exponential and post-exponential phase in rich AYE broth as well as during infection of human cultured macrophages. This was accomplished with microarrays and an RNA amplification procedure called SCOTS to detect small amounts of mRNA from low numbers of intracellular bacteria. Among the genes induced intracellularly are those involved in amino acid biosynthetic pathways leading to L-arginine, L-histidine and L-proline as well as many transport systems involved in amino acid and iron uptake. Gene involved in catabolism of glycerol is also induced during intracellular growth and could be used as a carbon source. The genes encoding the Icm/Dot system are not differentially expressed inside cells compared to control bacteria grown in rich broth, but the genes encoding several translocated effectors are strongly induced. Moreover, we used the transcriptome data to predict previously unrecognized Icm/Dot effector genes based on their expression pattern and confirmed translocation for three candidates. This study provides a comprehensive view of how L. pneumophila responds to the human macrophage intracellular environment.

  13. Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Troemel, Emily R; Félix, Marie-Anne; Whiteman, Noah K; Barrière, Antoine; Ausubel, Frederick M

    2008-12-09

    For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF) signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wild-caught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes.

  14. Depletion of intracellular calcium stores facilitates the influx of extracellular calcium in platelet derived growth factor stimulated A172 glioblastoma cells.

    Science.gov (United States)

    Vereb, G; Szöllösi, J; Mátyus, L; Balázs, M; Hyun, W C; Feuerstein, B G

    1996-05-01

    Calcium signaling in non-excitable cells is the consequence of calcium release from intracellular stores, at times followed by entry of extracellular calcium through the plasma membrane. To study whether entry of calcium depends upon the level of saturation of intracellular stores, we measured calcium channel opening in the plasma membrane of single confluent A172 glioblastoma cells stimulated with platelet derived growth factor (PDGF) and/or bradykinin (BK). We monitored the entry of extracellular calcium by measuring manganese quenching of Indo-1 fluorescence. PDGF raised intracellular calcium concentration ([Ca2+]i) after a dose-dependent delay (tdel) and then opened calcium channels after a dose-independent delay (tch). At higher doses (> 3 nM), BK increased [Ca2+]i after a tdel approximately 0 s, and tch decreased inversely with both dose and peak [Ca2+]i. Experiments with thapsigargin (TG), BK, and PDGF indicated that BK and PDGF share intracellular Ca2+ pools that are sensitive to TG. When these stores were depleted by treatment with BK and intracellular BAPTA, tdel did not change, but tch fell to almost 0 s in PDGF stimulated cells, indicating that depletion of calcium stores affects calcium channel opening in the plasma membrane. Our data support the capacitative model for calcium channel opening and the steady-state model describing quantal Ca2+ release from intracellular stores.

  15. Inhibition of IgE-induced mast cell activation by ethyl tertiary-butyl ether, a bioethanol-derived fuel oxygenate.

    Science.gov (United States)

    Yamaki, Kouya; Yoshino, Shin

    2009-09-01

    The effect of ethyl tertiary-butyl ether (ETBE), which is widely used as a fuel oxygenate commonly produced from bioethanol, on immunoglobulin (Ig)E-dependent mast cell activation was investigated. The rat mast cell line RBL2H3 sensitised with monoclonal anti-ovalbumin IgE was challenged with ovalbumin in the presence or absence of ETBE, tert-butanol (TBA), which is the main metabolite of ETBE in humans, and ethanol. Degranulation of RBL2H3 was examined by the release of beta-hexosaminidase. To understand the mechanisms responsible for regulating mast cell function, the effects of ETBE, TBA and ethanol on the levels of intracellular calcium, phosphorylation of Akt (as a marker of phosphatidylinositol 3-kinase) and global tyrosine phosphorylation were also measured as indicators of mast cell activation. In the presence of ETBE, TBA or ethanol, IgE-induced release of beta-hexosaminidase was decreased. These compounds also attenuated the IgE-mediated increase in the levels of intracellular Ca(2+), phosphorylation of Akt and global tyrosine phosphorylation in RBL2H3 cells. ETBE, TBA and ethanol inhibited mast cell degranulation by inhibiting the increase in intracellular calcium ion concentration and activation of phosphatidylinositol 3-kinase and protein tyrosine kinase activation, suggesting that exposure to ETBE might affect immune responses, particularly in allergic diseases.

  16. CANDU fuel

    International Nuclear Information System (INIS)

    MacEwan, J.R.; Notley, M.J.F.; Wood, J.C.; Gacesa, M.

    1982-09-01

    The direction of CANDU fuel development was set in 1957 with the decision to build pressure tube reactors. Short - 50 cm long - rodded bundles of natural UO 2 clad in Zircaloy were adopted to facilitate on-power fuelling to improve uranium utilization. Progressive improvements were made during 25 years of development, involving 650 man years and 180 million dollars. Today's CANDU bundle is based on the knowledge gained from extensive irradiation testing and experience in power reactors. The main thrust of future development is to demonstrate that the present bundle is suitable, with minor modifications, for thorium fuels

  17. Nuclear fuels and development of nuclear fuel elements

    International Nuclear Information System (INIS)

    Sundaram, C.V.; Mannan, S.L.

    1989-01-01

    Safe, reliable and economic operation of nuclear fission reactors, the source of nuclear power at present, requires judicious choice, careful preparation and specialised fabrication procedures for fuels and fuel element structural materials. These aspects of nuclear fuels (uranium, plutonium and their oxides and carbides), fuel element technology and structural materials (aluminium, zircaloy, stainless steel etc.) are discussed with particular reference to research and power reactors in India, e.g. the DHRUVA research reactor at BARC, Trombay, the pressurised heavy water reactors (PHWR) at Rajasthan and Kalpakkam, and the Fast Breeder Test Reactor (FBTR) at Kalpakkam. Other reactors like the gas-cooled reactors operating in UK are also mentioned. Because of the limited uranium resources, India has opted for a three-stage nuclear power programme aimed at the ultimate utilization of her abundant thorium resources. The first phase consists of natural uranium dioxide-fuelled, heavy water-moderated and cooled PHWR. The second phase was initiated with the attainment of criticality in the FBTR at Kalpakkam. Fast Breeder Reactors (FBR) utilize the plutonium and uranium by-products of phase 1. Moreover, FBR can convert thorium into fissile 233 U. They produce more fuel than is consumed - hence, the name breeders. The fuel parameters of some of the operating or proposed fast reactors in the world are compared. FBTR is unique in the choice of mixed carbides of plutonium and uranium as fuel. Factors affecting the fuel element performance and life in various reactors e.g. hydriding of zircaloys, fuel pellet-cladding interaction etc. in PHWR and void swelling; irradiation creep and helium embrittlement of fuel element structural materials in FBR are discussed along with measures to overcome some of these problems. (author). 15 refs., 9 tabs., 23 figs

  18. Fuels characterization studies. [jet fuels

    Science.gov (United States)

    Seng, G. T.; Antoine, A. C.; Flores, F. J.

    1980-01-01

    Current analytical techniques used in the characterization of broadened properties fuels are briefly described. Included are liquid chromatography, gas chromatography, and nuclear magnetic resonance spectroscopy. High performance liquid chromatographic ground-type methods development is being approached from several directions, including aromatic fraction standards development and the elimination of standards through removal or partial removal of the alkene and aromatic fractions or through the use of whole fuel refractive index values. More sensitive methods for alkene determinations using an ultraviolet-visible detector are also being pursued. Some of the more successful gas chromatographic physical property determinations for petroleum derived fuels are the distillation curve (simulated distillation), heat of combustion, hydrogen content, API gravity, viscosity, flash point, and (to a lesser extent) freezing point.

  19. Alternative Fuels Data Center: Ethanol Fueling Stations

    Science.gov (United States)

    ... More in this section... Ethanol Basics Benefits & Considerations Stations Locations Infrastructure fueling stations by location or along a route. Infrastructure Development Learn about ethanol fueling infrastructure; codes, standards, and safety; and ethanol equipment options. Maps & Data E85 Fueling Station

  20. Alternative Fuels Data Center: Biodiesel Fueling Stations

    Science.gov (United States)

    Locations Infrastructure Development Vehicles Laws & Incentives Biodiesel Fueling Stations Photo of a location or along a route. Infrastructure Development Learn about biodiesel fueling infrastructure codes Case Studies California Ramps Up Biofuels Infrastructure Green Fueling Station Powers Fleets in Upstate

  1. The LP-FP-2 severe fuel damage scenario and discussion of the relative influence of the transient and reflood phases in affecting the final condition of the bundle

    International Nuclear Information System (INIS)

    Modro, S.M.; Carboneau, M.L.

    1990-01-01

    The purpose of this paper is to review the evidence from the OECD LP-FP-2 experiment that a high temperature excursion occurred within the center fuel module (CFM) during the reflood portion of the test, was caused by rapid metal-water reaction. It is shown that this reflood scenario explains many perplexing observations from the experiment, in particular, the small amount of fission products and hydrogen transported to the blowdown suppression tank (BST) as compared with the larger quantities trapped within the primary coolant system (PCS). The timing and destruction of the CFM upper tie plate, as well as the transport of fuel debris to the top of this plate, are also explained. In general, all measurements, observations, and analyses of the LP-FP-2 data indicate that most of the CFM damage occurred during a relatively short period of time coincident with the reflood portion of the experiment. 4 refs., 6 figs

  2. Fuel assembly

    International Nuclear Information System (INIS)

    Kurihara, Kunitoshi; Azekura, Kazuo.

    1992-01-01

    In a reactor core of a heavy water moderated light water cooled pressure tube type reactor, no sufficient effects have been obtained for the transfer width to a negative side of void reactivity change in a region of a great void coefficient. Then, a moderation region divided into upper and lower two regions is disposed at the central portion of a fuel assembly. Coolants flown into the lower region can be discharged to the cooling region from an opening disposed at the upper end portion of the lower region. Light water flows from the lower region of the moderator region to the cooling region of the reactor core upper portion, to lower the void coefficient. As a result, the reactivity performance at low void coefficient, i.e., a void reaction rate is transferred to the negative side. Thus, this flattens the power distribution in the fuel assembly, increases the thermal margin and enables rapid operaiton and control of the reactor core, as well as contributes to the increase of fuel burnup ratio and reduction of the fuel cycle cost. (N.H.)

  3. Fuel assembly

    International Nuclear Information System (INIS)

    Fushimi, Atsushi; Shimada, Hidemitsu; Aoyama, Motoo; Nakajima, Junjiro

    1998-01-01

    In a fuel assembly for an n x n lattice-like BWR type reactor, n is determined to 9 or greater, and the enrichment degree of plutonium is determined to 4.4% by weight or less. Alternatively, n is determined to 10 or greater, and the enrichment degree of plutonium is determined to 5.2% by weight or less. An average take-out burnup degree is determined to 39GWd/t or less, and the matrix is determined to 9 x 9 or more, or the average take-out burnup degree is determined to 51GWd/t, and the matrix is determined to 10 x 10 or more and the increase of the margin of the maximum power density obtained thereby is utilized for the compensation of the increase of distortion of power distribution due to decrease of the kinds of plutonium enrichment degree, thereby enabling to reduce the kind of the enrichment degree of MOX fuel rods to one. As a result, the manufacturing step for fuel pellets can be simplified to reduce the manufacturing cost for MOX fuel assemblies. (N.H.)

  4. Fuel rods

    International Nuclear Information System (INIS)

    Fukushima, Kimichika.

    1984-01-01

    Purpose: To reduce the size of the reactor core upper mechanisms and the reactor container, as well as decrease the nuclear power plant construction costs in reactors using liquid metals as the coolants. Constitution: Isotope capturing devices comprising a plurality of pipes are disposed to the gas plenum portion of a nuclear fuel rod main body at the most downstream end in the flowing direction of the coolants. Each of the capturing devices is made of nickel, nickel alloys, stainless steel applied with nickel plating on the surface, nickel alloys applied with nickel plating on the surface or the like. Thus, radioactive nuclides incorporated in the coolants are surely captured by the capturing devices disposed at the most downstream end of the nuclear fuel main body as the coolants flow along the nuclear fuel main body. Accordingly, since discharging of radioactive nuclides to the intermediate fuel exchange system can be prevented, the maintenance or reparing work for the system can be facilitated. (Moriyama, K.)

  5. Transport fuel

    DEFF Research Database (Denmark)

    Ronsse, Frederik; Jørgensen, Henning; Schüßler, Ingmar

    2014-01-01

    Worldwide, the use of transport fuel derived from biomass increased four-fold between 2003 and 2012. Mainly based on food resources, these conventional biofuels did not achieve the expected emission savings and contributed to higher prices for food commod - ities, especially maize and oilseeds...

  6. Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.

    Science.gov (United States)

    Wang, Yi-Chi; Yang, Jyh-Jeen; Huang, Rong-Chi

    2012-10-01

    Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+)-sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.

  7. Additional danger of arsenic exposure through inhalation from burning of cow dung cakes laced with arsenic as a fuel in arsenic affected villages in Ganga-Meghna-Brahmaputra plain.

    Science.gov (United States)

    Pal, Arup; Nayak, Bishwajit; Das, Bhaskar; Hossain, M Amir; Ahamed, Sad; Chakraborti, Dipankar

    2007-10-01

    In arsenic contaminated areas of the Ganga-Meghna-Brahmaputra (GMB) plain (area 569,749 sq. km; population over 500 million) where traditionally cow dung cake is used as a fuel in unventilated ovens for cooking purposes, people are simply exposed to 1859.2 ng arsenic per day through direct inhalation, of which 464.8 ng could be absorbed in respiratory tract.

  8. A geographical analysis of the Swedish wood fuel market

    International Nuclear Information System (INIS)

    Roos, Anders; Bohlin, Folke; Hektor, Bo; Hillring, Bengt; Parikka, Matti

    2000-01-01

    The geographical variation in Swedish wood fuel market characteristics for the district heating sector has been studied using Geographical Information Systems (GIS) and cross-sectional Tobit analysis. The results indicate that local availability and competition for wood fuels influence the wood fuel consumption at inland heating plants. The factors affecting the decision to use wood fuel at heating plants close to seaports, however, were not captured by the model, suggesting that coastal location reduces dependency on the local wood fuel market. The effects of changes in local wood fuel availability on wood fuel use by an inland heating plant are presented and discussed

  9. Fuel economy and life-cycle cost analysis of a fuel cell hybrid vehicle

    Science.gov (United States)

    Jeong, Kwi Seong; Oh, Byeong Soo

    The most promising vehicle engine that can overcome the problem of present internal combustion is the hydrogen fuel cell. Fuel cells are devices that change chemical energy directly into electrical energy without combustion. Pure fuel cell vehicles and fuel cell hybrid vehicles (i.e. a combination of fuel cell and battery) as energy sources are studied. Considerations of efficiency, fuel economy, and the characteristics of power output in hybridization of fuel cell vehicle are necessary. In the case of Federal Urban Driving Schedule (FUDS) cycle simulation, hybridization is more efficient than a pure fuel cell vehicle. The reason is that it is possible to capture regenerative braking energy and to operate the fuel cell system within a more efficient range by using battery. Life-cycle cost is largely affected by the fuel cell size, fuel cell cost, and hydrogen cost. When the cost of fuel cell is high, hybridization is profitable, but when the cost of fuel cell is less than 400 US$/kW, a pure fuel cell vehicle is more profitable.

  10. Excitation contraction uncoupling by high intracellular [Ca2+] in frog skeletal muscle: a voltage clamp study.

    Science.gov (United States)

    Olivera, J Fernando; Pizarro, Gonzalo

    2016-10-01

    Raising the intracellular [Ca 2+ ] ([Ca 2+ ] i ) was previously found to produce uncoupling between the electrical depolarization of the transverse tubules and contraction in skinned muscle fibers. Here we study the effect of elevated [Ca 2+ ] i in voltage clamped cut fibers of frog skeletal muscle to establish how the charge movement, a measure of the activation of the dihydropyridine receptors (DHPR)-voltage sensors, and Ca 2+ release, a consequence of the opening of the ryanodine receptor (RyR)-release channels, were affected. [Ca 2+ ] i was raised by various procedures (pharmacological release from the sarcoplasmic reticulum, application of high [Ca 2+ ] i intracellular solution, permeabilization of the plasma membrane by a Ca 2+ ionophore) all of which produced impairment of excitation-contraction coupling. The charge movement was reduced from 20.2 ± 1.24 to 9.9 ± 0.94 nC/μF meanwhile the Ca 2+ release flux was reduced from 13.5 + 0.7 to 2.2 ± 0.3 μM/ms (n = 33). This suggests that a significant fraction of the DHPRs that remained functional, could not activate RyRs, and were therefore presumably disconnected. These results are broadly consistent with the original reports in skinned fibers. Uncoupling was prevented by the addition to the intracellular solution of the protease inhibitor leupeptin. In approximately 40 % of the uncoupled cells we observed that the [Ca 2+ ] i transient continued to rise after the voltage clamp pulse was turned off. This loss of control by membrane voltage suggests that the uncoupled release channels might have another mechanism of activation, likely by Ca 2+ .

  11. Thorium fuel cycle management

    International Nuclear Information System (INIS)

    Zajac, R.; Darilek, P.; Breza, J.; Necas, V.

    2010-01-01

    In this presentation author deals with the thorium fuel cycle management. Description of the thorium fuels and thorium fuel cycle benefits and challenges as well as thorium fuel calculations performed by the computer code HELIOS are presented.

  12. Criticality impacts on LWR fuel storage efficiency

    International Nuclear Information System (INIS)

    Napolitano, D.

    1992-01-01

    This presentation discusses the criticality impacts throughout storage of fuel onsite including new fuel storage, spent fuel storage, consolidation, and dry storage. The general principles for criticality safety are also be discussed. There is first an introduction which explains today's situation for criticality safety concerns. This is followed by a discussion of criticality safety Regulatory Guides, safety limits and fundamental principles. Design objectives for criticality safety in the 1990's include higher burnups, longer cycles, and higher enrichments which impact the criticality safety design. Criticality safety for new fuel storage, spent fuel storage, fuel consolidation, and dry storage are followed by conclusions. Today's situation is one in which the US does not reprocess, and does not have an operating MRS facility or repository. High density fuel storage rack designs of the 1980s, are filling up. Dry cask storage systems for spent fuel storage are being utilized. Enrichments continue to increase PWR fuel assemblies with enrichments of 4.5 to 5.0 weight percent U-235 and BWR fuel assemblies with enrichments of 3.25 to 3.5 weight percent U-235 are common. Criticality concerns affect the capacity and the economics of light water reactor (LWR) fuel storage arrays by dictating the spacing of fuel assemblies in a storage system, or the use of poisons or exotic materials in the storage system design

  13. Repairing fuel for reinsertion

    International Nuclear Information System (INIS)

    Krukshenk, A.

    1986-01-01

    Eqiupment for nuclear reactor fuel assembly repairing produced by Westinghouse and Brawn Bovery companies is described. Repair of failed fuel assemblies replacement of defect fuel elements gives a noticeable economical effect. Thus if the cost of a new fuel assembly is 450-500 thousand dollars, the replacement of one fuel element in it costs approximately 40-60 thousand dollars. In simple cases repairing includes either removal of failed fuel elements from a fuel assembly and its reinsertion with the rest of fuel elements into the reactor core (reactor refueling), or replacement of unfailed fuel elements from one fuel assembly to a new one (fuel assembly overhaul and reconditioning)

  14. Cesium migration in LMFBR fuel pins

    International Nuclear Information System (INIS)

    Karnesky, R.A.; Jost, J.W.; Stone, I.Z.

    1978-10-01

    The factors affecting the axial migration of cesium in mixed oxide fuel pins and the effects of cesium migration on fuel pin performance are examined. The development and application of a correlated model which will predict the occurrence of cesium migration in a mixed oxide (75 w/o UO 2 + 25 w/o PuO 2 ) fuel pins over a wide range of fabrication and irradiation conditions are described

  15. Nuclear power fuel cycle

    International Nuclear Information System (INIS)

    Havelka, S.; Jakesova, L.

    1982-01-01

    Economic problems are discussed of the fuel cycle (cost of the individual parts of the fuel cycle and the share of the fuel cycle in the price of 1 kWh), the technological problems of the fuel cycle (uranium ore mining and processing, uranium isotope enrichment, the manufacture of fuel elements, the building of long-term storage sites for spent fuel, spent fuel reprocessing, liquid and gaseous waste processing), and the ecologic aspects of the fuel cycle. (H.S.)

  16. Intracellular pH regulation in unstimulated Calliphora salivary glands is Na+ dependent and requires V-ATPase activity.

    Science.gov (United States)

    Schewe, Bettina; Blenau, Wolfgang; Walz, Bernd

    2012-04-15

    Salivary gland cells of the blowfly Calliphora vicina have a vacuolar-type H(+)-ATPase (V-ATPase) that lies in their apical membrane and energizes the secretion of a KCl-rich primary saliva upon stimulation with serotonin (5-hydroxytryptamine). Whether and to what extent V-ATPase contributes to intracellular pH (pH(i)) regulation in unstimulated gland cells is unknown. We used the fluorescent dye BCECF to study intracellular pH(i) regulation microfluorometrically and show that: (1) under resting conditions, the application of Na(+)-free physiological saline induces an intracellular alkalinization attributable to the inhibition of the activity of a Na(+)-dependent glutamate transporter; (2) the maintenance of resting pH(i) is Na(+), Cl(-), concanamycin A and DIDS sensitive; (3) recovery from an intracellular acid load is Na(+) sensitive and requires V-ATPase activity; (4) the Na(+)/H(+) antiporter is not involved in pH(i) recovery after a NH(4)Cl prepulse; and (5) at least one Na(+)-dependent transporter and the V-ATPase maintain recovery from an intracellular acid load. Thus, under resting conditions, the V-ATPase and at least one Na(+)-dependent transporter maintain normal pH(i) values of pH 7.5. We have also detected the presence of a Na(+)-dependent glutamate transporter, which seems to act as an acid loader. Despite this not being a common pH(i)-regulating transporter, its activity affects steady-state pH(i) in C. vicina salivary gland cells.

  17. Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system

    International Nuclear Information System (INIS)

    Matsumae, Yoshiharu; Takahashi, Yasufumi; Ino, Kosuke; Shiku, Hitoshi; Matsue, Tomokazu

    2014-01-01

    Graphical abstract: NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells were evaluated by using the menadione–ferrocyanide double mediator system combined with scanning electrochemical microscopy (SECM). - Highlights: • NAD(P)H:quinone oxidoreductase activity of single cells were evaluated with SECM. • Fe(CN) 6 3− /menadione concentrations were optimized for long-term SECM monitoring. • Menadione affect the intracellular levels of reactive oxygen species and GSH. • At 100 μM menadione, the Fe(CN) 6 3− generation rate decreased rapidly within 30 min. - Abstract: We evaluated the intracellular NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells by using the menadione–ferrocyanide double-mediator system combined with scanning electrochemical microscopy (SECM). The double-mediator system was used to amplify the current response from the intracellular NQO activity and to reduce menadione-induced cell damage. The electron shuttle between the electrode and menadione was mediated by the ferrocyanide/ferricyanide redox couple. Generation of ferrocyanide was observed immediately after the addition of a lower concentration (10 μM) of menadione. The ferrocyanide generation rate was constant for 120 min. At a higher menadione concentration (100 μM), the ferrocyanide generation rate decreased within 30 min because of the cytotoxic effect of menadione. We also investigated the relationship between intracellular reactive oxygen species or glutathione levels and exposure to different menadione concentrations to determine the optimal condition for SECM with minimal invasiveness. The present study clearly demonstrates that SECM is useful for the analysis of intracellular enzymatic activities in single cells with a double-mediator system

  18. Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system

    Energy Technology Data Exchange (ETDEWEB)

    Matsumae, Yoshiharu [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Takahashi, Yasufumi [Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba, Sendai 980-8577 (Japan); Ino, Kosuke [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Shiku, Hitoshi, E-mail: shiku@bioinfo.che.tohoku.ac.jp [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Matsue, Tomokazu, E-mail: matsue@bioinfo.che.tohoku.ac.jp [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba, Sendai 980-8577 (Japan)

    2014-09-09

    Graphical abstract: NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells were evaluated by using the menadione–ferrocyanide double mediator system combined with scanning electrochemical microscopy (SECM). - Highlights: • NAD(P)H:quinone oxidoreductase activity of single cells were evaluated with SECM. • Fe(CN){sub 6}{sup 3−}/menadione concentrations were optimized for long-term SECM monitoring. • Menadione affect the intracellular levels of reactive oxygen species and GSH. • At 100 μM menadione, the Fe(CN){sub 6}{sup 3−} generation rate decreased rapidly within 30 min. - Abstract: We evaluated the intracellular NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells by using the menadione–ferrocyanide double-mediator system combined with scanning electrochemical microscopy (SECM). The double-mediator system was used to amplify the current response from the intracellular NQO activity and to reduce menadione-induced cell damage. The electron shuttle between the electrode and menadione was mediated by the ferrocyanide/ferricyanide redox couple. Generation of ferrocyanide was observed immediately after the addition of a lower concentration (10 μM) of menadione. The ferrocyanide generation rate was constant for 120 min. At a higher menadione concentration (100 μM), the ferrocyanide generation rate decreased within 30 min because of the cytotoxic effect of menadione. We also investigated the relationship between intracellular reactive oxygen species or glutathione levels and exposure to different menadione concentrations to determine the optimal condition for SECM with minimal invasiveness. The present study clearly demonstrates that SECM is useful for the analysis of intracellular enzymatic activities in single cells with a double-mediator system.

  19. Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

    Science.gov (United States)

    Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

    2016-08-26

    An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Leucocins 4010 from Leuconostoc carnosum cause a matrix related decrease in intracellular pH of Listeria monocytogenes

    DEFF Research Database (Denmark)

    Fang, Weihuan; Budde, Birgitte Bjørn; Siegumfeldt, Henrik

    2006-01-01

    A mixed culture of single cells of Listeria monocytogenes and the bacteriocin producing Leuconostoc carnosum 4010 showed growth inhibition of L. monocytogenes, although the intracellular pH (pHi) of L. monocytogenes followed by fluorescence ratio imaging microscopy was not affected. Furthermore, L...

  1. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

    Kahlig, Kristopher M; Lute, Brandon J; Wei, Yuqiang

    2006-01-01

    -induced cell surface DAT redistribution may result in long-lasting changes in DA homeostasis. The molecular mechanism by which AMPH induces trafficking is not clear. Because AMPH is a substrate, we do not know whether extracellular AMPH stimulates trafficking through its interaction with DAT and subsequent...... alteration in DAT function, thereby triggering intracellular signaling or whether AMPH must be transported and then act intracellularly. In agreement with our previous studies, extracellular AMPH caused cytosolic redistribution of the wild-type human DAT (WT-hDAT). However, AMPH did not induce cytosolic...... redistribution in an uptake-impaired hDAT (Y335A-hDAT) that still binds AMPH. The divalent cation zinc (Zn(2+)) inhibits WT-hDAT activity, but it restores Y335A-hDAT uptake. Coadministration of Zn(2+) and AMPH consistently reduced WT-hDAT trafficking but stimulated cytosolic redistribution of Y335A...

  2. Pico gauges for minimally invasive intracellular hydrostatic pressure measurements

    DEFF Research Database (Denmark)

    Knoblauch, Jan; Mullendore, Daniel L.; Jensen, Kaare Hartvig

    2014-01-01

    Intracellular pressure has a multitude of functions in cells surrounded by a cell wall or similar matrix in all kingdoms of life. The functions include cell growth, nastic movements, and penetration of tissue by parasites. The precise measurement of intracellular pressure in the majority of cells......, however, remains difficult or impossible due to their small size and/or sensitivity to manipulation. Here, we report on a method that allows precise measurements in basically any cell type over all ranges of pressure. It is based on the compression of nanoliter and picoliter volumes of oil entrapped...... in the tip of microcapillaries, which we call pico gauges. The production of pico gauges can be accomplished with standard laboratory equipment, and measurements are comparably easy to conduct. Example pressure measurements are performed on cells that are difficult or impossible to measure with other methods....

  3. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  4. Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems.

    Science.gov (United States)

    Ngo, Anh H; Bose, Sohini; Do, Loi H

    2018-03-23

    This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small-molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small-molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition, allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation. Other promising targets for new biocompatible reaction discovery will also be discussed, with a special emphasis on how such innovations could lead to the development of novel technologies and chemical tools. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Behavior of fission products released from severely damaged fuel during the PBF severe fuel damage tests

    International Nuclear Information System (INIS)

    Osetek, D.J.; Cronenberg, A.W.; Hagrman, D.L.; Broughton, J.M.; Rest, J.

    1984-01-01

    The results of fission product release behavior during the first two Power Burst Facility Severe Fuel Damage tests are presented. Measured fission product release is compared with calculated release using temperature dependent release rate correlations and FASTGRASS analysis. The test results indicate that release from fuel of the high volatility fission products (Xe, Kr, I, Cs, and Te) is strongly influenced by parameters other than fuel temperature; namely fuel/fission product morphology, fuel and cladding oxidation state, extent of fuel liquefaction, and quench induced fuel shattering. Fission product transport from the test fuel through the sample system was strongly influenced by chemical effects. Holdup of I and Cs was affected by fission product chemistry, and transport time while Te release was primarily influenced by the extent of zircaloy oxidation. Analysis demonstrates that such integral test data can be used to confirm physical, chemical, and mechanistic models of fission product behavior for severe accident conditions

  6. Safety issues on advanced fuel

    International Nuclear Information System (INIS)

    Gross, H.; Krebs, W.D.

    1998-01-01

    In the recent years a general discussion has started whether unsolved safety issues are related to advanced fuel. Advanced fuel is in this context a summary of features like high burnup, improved clad materials, low leakage loading pattern with high peaking factors etc. The design basis accidents RIA and Loca are of special interest for this discussion. From the Siemens point of view RIA is not a safety issue. There are sufficient margins between the enthalpy rise calculated by modern 3D methods and the fuel failures which occurred in RIA simulation tests when the effect of pulse width is taken into account. The evaluation of possible uncertainties for the established Loca criteria (17% equivalent corrosion, 1200 C clad temperature) for high burnup makes sense. But fuel with high burnup has significantly lower peaking factors than fuel with lower burnup. This gives sufficient margin counterbalancing possible uncertainties. In contrast to the above incomplete control rod insertion at higher burnup is potentially a real safety issue. Although Siemens fuel was not affected by the reported incidents they addressed the problem and checked that they have sufficient design margin for their fuel. (orig.) [de

  7. Intracellular Detection of Viral Transcription and Replication Using RNA FISH

    Science.gov (United States)

    2016-05-26

    Chapter 14. Intracellular detection of viral transcription and replication using RNA FISH i. Summary/Abstract Many hemorrhagic fever viruses...only allow entirely new investigations into the replication of these viruses, but also how this method can be applied to any virus with a known...localization, TurboFISH, hemorrhagic fever virus replication 1. Introduction RNA FISH was developed as a method to visualize cellular RNA by binding a

  8. Mycobacterium avium-intracellulare: a rare cause of subacromial bursitis.

    Science.gov (United States)

    Sinha, Raj; Tuckett, John; Hide, Geoff; Dildey, Petra; Karsandas, Alvin

    2015-01-01

    Septic subacromial bursitis is an uncommon disorder with only a few reported cases in the literature. The most common causative organism is Staphylococcus aureus. We report the case of a 61-year-old female with a septic subacromial bursitis where the causative organism was found to be Mycobacterium avium-intracellulare (MAI). The diagnosis was only made following a biopsy, and we use this case to highlight the importance of recognising the need to consider a biopsy and aspiration in atypical situations.

  9. Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes

    DEFF Research Database (Denmark)

    Westgate, G E; Weaver, A C; Couchman, J R

    1985-01-01

    immunofluorescent staining for BPA is linear at the basement membrane zone (BMZ) of skin and many other epithelial tissues. At higher magnification however, we observed a punctate staining pattern for BPA which was regular in appearance and suggested localization of BPA to discrete structures at the BMZ. Subsequent...... intracellularly both in vivo and in vitro. We suggest that BPA is not normally a lamina lucida component, but that it may form part of a linkage between the cytoskeleton and the basement membrane....

  10. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Onkar Sharma

    2016-03-01

    Full Text Available A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase. When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO, and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells.

  11. Molecular evolution, intracellular organization, and the quinary structure of proteins.

    OpenAIRE

    McConkey, E H

    1982-01-01

    High-resolution two-dimensional polyacrylamide gel electrophoresis shows that at least half of 370 denatured polypeptides from hamster cells and human cells are indistinguishable in terms of isoelectric points and molecular weights. Molecular evolution may have been more conservative for this set of proteins than sequence studies on soluble proteins have implied. This may be a consequence of complexities of intracellular organization and the numerous macromolecular interactions in which most ...

  12. Control of intracellular heme levels: Heme transporters and heme oxygenases

    OpenAIRE

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number...

  13. Evaluation of Intracellular Signaling Downstream Chimeric Antigen Receptors.

    Directory of Open Access Journals (Sweden)

    Hannah Karlsson

    Full Text Available CD19-targeting CAR T cells have shown potency in clinical trials targeting B cell leukemia. Although mainly second generation (2G CARs carrying CD28 or 4-1BB have been investigated in patients, preclinical studies suggest that third generation (3G CARs with both CD28 and 4-1BB have enhanced capacity. However, little is known about the intracellular signaling pathways downstream of CARs. In the present work, we have analyzed the signaling capacity post antigen stimulation in both 2G and 3G CARs. 3G CAR T cells expanded better than 2G CAR T cells upon repeated stimulation with IL-2 and autologous B cells. An antigen-driven accumulation of CAR+ cells was evident post antigen stimulation. The cytotoxicity of both 2G and 3G CAR T cells was maintained by repeated stimulation. The phosphorylation status of intracellular signaling proteins post antigen stimulation showed that 3G CAR T cells had a higher activation status than 2G. Several proteins involved in signaling downstream the TCR were activated, as were proteins involved in the cell cycle, cell adhesion and exocytosis. In conclusion, 3G CAR T cells had a higher degree of intracellular signaling activity than 2G CARs which may explain the increased proliferative capacity seen in 3G CAR T cells. The study also indicates that there may be other signaling pathways to consider when designing or evaluating new generations of CARs.

  14. Fatty Acid Signaling: The New Function of Intracellular Lipases

    Directory of Open Access Journals (Sweden)

    Zuzana Papackova

    2015-02-01

    Full Text Available Until recently, intracellular triacylglycerols (TAG stored in the form of cytoplasmic lipid droplets have been considered to be only passive “energy conserves”. Nevertheless, degradation of TAG gives rise to a pleiotropic spectrum of bioactive intermediates, which may function as potent co-factors of transcription factors or enzymes and contribute to the regulation of numerous cellular processes. From this point of view, the process of lipolysis not only provides energy-rich equivalents but also acquires a new regulatory function. In this review, we will concentrate on the role that fatty acids liberated from intracellular TAG stores play as signaling molecules. The first part provides an overview of the transcription factors, which are regulated by fatty acids derived from intracellular stores. The second part is devoted to the role of fatty acid signaling in different organs/tissues. The specific contribution of free fatty acids released by particular lipases, hormone-sensitive lipase, adipose triacylglycerol lipase and lysosomal lipase will also be discussed.

  15. Estimating the biophysical properties of neurons with intracellular calcium dynamics.

    Science.gov (United States)

    Ye, Jingxin; Rozdeba, Paul J; Morone, Uriel I; Daou, Arij; Abarbanel, Henry D I

    2014-06-01

    We investigate the dynamics of a conductance-based neuron model coupled to a model of intracellular calcium uptake and release by the endoplasmic reticulum. The intracellular calcium dynamics occur on a time scale that is orders of magnitude slower than voltage spiking behavior. Coupling these mechanisms sets the stage for the appearance of chaotic dynamics, which we observe within certain ranges of model parameter values. We then explore the question of whether one can, using observed voltage data alone, estimate the states and parameters of the voltage plus calcium (V+Ca) dynamics model. We find the answer is negative. Indeed, we show that voltage plus another observed quantity must be known to allow the estimation to be accurate. We show that observing both the voltage time course V(t) and the intracellular Ca time course will permit accurate estimation, and from the estimated model state, accurate prediction after observations are completed. This sets the stage for how one will be able to use a more detailed model of V+Ca dynamics in neuron activity in the analysis of experimental data on individual neurons as well as functional networks in which the nodes (neurons) have these biophysical properties.

  16. New intracellular activities of matrix metalloproteinases shine in the moonlight.

    Science.gov (United States)

    Jobin, Parker G; Butler, Georgina S; Overall, Christopher M

    2017-11-01

    Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders. However, growing evidence has convincingly identified select MMPs in intracellular compartments with unexpected physiological and pathological roles. Intracellular MMPs have both proteolytic and non-proteolytic functions, including signal transduction and transcription factor activity thereby challenging their traditional designation as extracellular proteases. This review highlights current knowledge of subcellular location and activity of these "moonlighting" MMPs. Intracellular roles herald a new era of MMP research, rejuvenating interest in targeting these proteases in therapeutic strategies. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Intracellular Hg(0) Oxidation in Desulfovibrio desulfuricans ND132.

    Science.gov (United States)

    Wang, Yuwei; Schaefer, Jeffra K; Mishra, Bhoopesh; Yee, Nathan

    2016-10-03

    The disposal of elemental mercury (Hg(0)) wastes in mining and manufacturing areas has caused serious soil and groundwater contamination issues. Under anoxic conditions, certain anaerobic bacteria can oxidize dissolved elemental mercury and convert the oxidized Hg to neurotoxic methylmercury. In this study, we conducted experiments with the Hg-methylating bacterium Desulfovibrio desulfuricans ND132 to elucidate the role of cellular thiols in anaerobic Hg(0) oxidation. The concentrations of cell-surface and intracellular thiols were measured, and specific fractions of D. desulfuricans ND132 were examined for Hg(0) oxidation activity and analyzed with extended X-ray absorption fine structure (EXAFS) spectroscopy. The experimental data indicate that intracellular thiol concentrations are approximately six times higher than those of the cell wall. Cells reacted with a thiol-blocking reagent were severely impaired in Hg(0) oxidation activity. Spheroplasts lacking cell walls rapidly oxidized Hg(0) to Hg(II), while cell wall fragments exhibited low reactivity toward Hg(0). EXAFS analysis of spheroplast samples revealed that multiple different forms of Hg-thiols are produced by the Hg(0) oxidation reaction and that the local coordination environment of the oxidized Hg changes with reaction time. The results of this study indicate that Hg(0) oxidation in D. desulfuricans ND132 is an intracellular process that occurs by reaction with thiol-containing molecules.

  18. Identification of intracellular proteins and signaling pathways in human endothelial cells regulated by angiotensin-(1-7).

    Science.gov (United States)

    Meinert, Christian; Gembardt, Florian; Böhme, Ilka; Tetzner, Anja; Wieland, Thomas; Greenberg, Barry; Walther, Thomas

    2016-01-01

    The study aimed to identify proteins regulated by the cardiovascular protective peptide angiotensin-(1-7) and to determine potential intracellular signaling cascades. Human endothelial cells were stimulated with Ang-(1-7) for 1 h, 3 h, 6 h, and 9 h. Peptide effects on intracellular signaling were assessed via antibody microarray, containing antibodies against 725 proteins. Bioinformatics software was used to identify affected intracellular signaling pathways. Microarray data was verified exemplarily by Western blot, Real-Time RT-PCR, and immunohistochemical studies. The microarray identified 110 regulated proteins after 1 h, 119 after 3 h, 31 after 6 h, and 86 after 9 h Ang-(1-7) stimulation. Regulated proteins were associated with high significance to several metabolic pathways like “Molecular Mechanism of Cancer” and “p53 signaling” in a time dependent manner. Exemplarily, Western blots for the E3-type small ubiquitin-like modifier ligase PIAS2 confirmed the microarray data and displayed a decrease by more than 50% after Ang-(1-7) stimulation at 1 h and 3 h without affecting its mRNA. Immunohistochemical studies with PIAS2 in human endothelial cells showed a decrease in cytoplasmic PIAS2 after Ang-(1-7) treatment. The Ang-(1-7) mediated decrease of PIAS2 was reproduced in other endothelial cell types. The results suggest that angiotensin-(1-7) plays a role in metabolic pathways related to cell death and cell survival in human endothelial cells.

  19. Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells

    Directory of Open Access Journals (Sweden)

    Kira G. Slepchenko

    2012-01-01

    Full Text Available Zinc (Zn2+ appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

  20. Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

    Science.gov (United States)

    Slepchenko, Kira G; Li, Yang V

    2012-01-01

    Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

  1. Business environment in the wood fuels field

    International Nuclear Information System (INIS)

    Laitinen, H.; Ranta, T.

    1995-01-01

    In this publication the business environment in the wood fuels sector and the internal and external factors affecting it are studied. It has been considered important to describe both the present situation and future possibilities of the business in order to develop it so that the planned increase in the use of wood fuels can be achieved

  2. Fuel trading

    International Nuclear Information System (INIS)

    2015-01-01

    A first part of this report proposes an overview of trends and predictions. After a synthesis on the sector changes and trends, it indicates and comments the most recent predictions for the consumption of refined oil products and for the turnover of the fuel wholesale market, reports the main highlights concerning the sector's life, and gives a dashboard of the sector activity. The second part proposes the annual report on trends and competition. It presents the main operator profiles and fuel categories, the main determining factors of the activity, the evolution of the sector context between 2005 and 2015 (consumptions, prices, temperature evolution). It analyses the evolution of the sector activity and indicators (sales, turnovers, prices, imports). Financial performances of enterprises are presented. The economic structure of the sector is described (evolution of the economic fabric, structural characteristics, French foreign trade). Actors are then presented and ranked in terms of turnover, of added value, and of result

  3. Fuel assembly

    International Nuclear Information System (INIS)

    Ueda, Makoto.

    1991-01-01

    In a fuel assembly in which spectral shift type moderator guide members are arranged, the moderator guide member has a flow channel resistance member, that provides flow resistance against the moderators, in the upstream of a moderator flowing channel, by which the ratio of removing coolants is set greater at the upstream than downstream. With such a constitution, the void distribution increasing upward in the channel box except for the portion of the moderator guide member is moderated by the increase of the area of the void region that expands downward in the guide member. Accordingly, the axial power distribution is flattened throughout the operation cycle and excess distortion is eliminated to improve the fuel integrity. (T.M.)

  4. Fuel element

    International Nuclear Information System (INIS)

    Hirose, Yasuo.

    1982-01-01

    Purpose: To increase the plenum space in a fuel element used for a liquid metal cooled reactor. Constitution: A fuel pellet is secured at one end with an end plug and at the other with a coil spring in a tubular container. A mechanism for fixing the coil spring composed of a tubular unit is mounted by friction with the inner surface of the tubular container. Accordingly, the recoiling force of the coil spring can be retained by fixing mechanism with a small volume, and since a large amount of plenum space can be obtained, the internal pressure rise in the cladding tube can be suppressed even if large quantities of fission products are discharged. (Kamimura, M.)

  5. Fuel assembly

    International Nuclear Information System (INIS)

    Kawai, Mitsuo.

    1988-01-01

    Purpose: To reduce the corrosion rate and suppress the increase of radioactive corrosion products in reactor water of nuclear fuel assemblies for use in BWR type reactors having spacer springs made of nickel based deposition reinforced type alloys. Constitution: Spacer rings made of nickel based deposition reinforced type alloy are incorporated and used as fuel assemblies after applying treatment of dipping and maintaining at high temperature water followed by heating in steams. Since this can remove the nickel leaching into reactor water at the initial stage, Co-58 as the radioactive corrosion products in the reactor water can be reduced, and the operation at in-service inspection or repairement can be facilitated to improve the working efficiency of the nuclear power plant. The dipping time is desirably more than 10 hours and more desirably more than 30 hours. (Horiuchi, T. )

  6. Fuel assemblies

    International Nuclear Information System (INIS)

    Yoshioka, Ritsuo.

    1983-01-01

    Purpose: To improve the operation performance of a BWR type reactor by improving the distribution of the uranium enrichment and the incorporation amount of burnable poisons in fuel assemblies. Constitution: The average enrichment of uranium 235 is increased in the upper portion as compared with that in the lower portion, while the incorporation amount of burnable poisons is increased in an upper portion as compared with that in the lower portion. The difference in the incorporation amount of the burnable poisons between the upper and lower portions is attained by charging two kinds of fuel rods; the ones incorporated with the burnable poisons over the entire length and the others incorporated with the burnable poisons only in the upper portions. (Seki, T.)

  7. Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores.

    Science.gov (United States)

    Kim, Hee Jung; Yum, Keun Sang; Sung, Jong-Ho; Rhie, Duck-Joo; Kim, Myung-Jun; Min, Do Sik; Hahn, Sang June; Kim, Myung-Suk; Jo, Yang-Hyeok; Yoon, Shin Hee

    2004-02-01

    Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.

  8. Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

    International Nuclear Information System (INIS)

    Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

    1987-01-01

    The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size

  9. Involvement of intracellular free Ca2+ in enhanced release of herpes simplex virus by hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Ogawa Yuzo

    2006-08-01

    Full Text Available Abstract Background It was reported that elevation of the intracellular concentration of free Ca2+ ([Ca2+]i by a calcium ionophore increased the release of herpes simplex virus type 1 (HSV-1. Freely diffusible hydrogen peroxide (H2O2 is implied to alter Ca2+ homeostasis, which further enhances abnormal cellular activity, causing changes in signal transduction, and cellular dysfunction. Whether H2O2 could affect [Ca2+]i in HSV-1-infected cells had not been investigated. Results H2O2 treatment increased the amount of cell-free virus and decreased the proportion of viable cells. After the treatment, an elevation in [Ca2+]i was observed and the increase in [Ca2+]i was suppressed when intracellular and cytosolic Ca2+ were buffered by Ca2+ chelators. In the presence of Ca2+ chelators, H2O2-mediated increases of cell-free virus and cell death were also diminished. Electron microscopic analysis revealed enlarged cell junctions and a focal disintegration of the plasma membrane in H2O2-treated cells. Conclusion These results indicate that H2O2 can elevate [Ca2+]i and induces non-apoptotic cell death with membrane lesions, which is responsible for the increased release of HSV-1 from epithelial cells.

  10. Clinical Concentrations of Thioridazine Kill Intracellular Multidrug-Resistant Mycobacterium tuberculosis

    Science.gov (United States)

    Ordway, Diane; Viveiros, Miguel; Leandro, Clara; Bettencourt, Rosário; Almeida, Josefina; Martins, Marta; Kristiansen, Jette E.; Molnar, Joseph; Amaral, Leonard

    2003-01-01

    The phenothiazines chlorpromazine (CPZ) and thioridazine (TZ) have equal in vitro activities against antibiotic-sensitive and -resistant Mycobacterium tuberculosis. These compounds have not been used as anti-M. tuberculosis agents because their in vitro activities take place at concentrations which are beyond those that are clinically achievable. In addition, chronic administration of CPZ produces frequent severe side effects. Because CPZ has been shown to enhance the killing of intracellular M. tuberculosis at concentrations in the medium that are clinically relevant, we have investigated whether TZ, a phenothiazine whose negative side effects are less frequent and serious than those associated with CPZ, kills M. tuberculosis organisms that have been phagocytosed by human macrophages, which have nominal killing activities against these bacteria. Both CPZ and TZ killed intracellular antibiotic-sensitive and -resistant M. tuberculosis organisms when they were used at concentrations in the medium well below those present in the plasma of patients treated with these agents. These concentrations in vitro were not toxic to the macrophage, nor did they affect in vitro cellular immune processes. TZ thus appears to be a serious candidate for the management of a freshly diagnosed infection of pulmonary tuberculosis or as an adjunct to conventional antituberculosis therapy if the patient originates from an area known to have a high prevalence of multidrug-resistant M. tuberculosis isolates. Nevertheless, we must await the outcomes of clinical trials to determine whether TZ itself may be safely and effectively used as an antituberculosis agent. PMID:12604522

  11. The Intracellular Destiny of the Protein Corona: A Study on its Cellular Internalization and Evolution.

    Science.gov (United States)

    Bertoli, Filippo; Garry, David; Monopoli, Marco P; Salvati, Anna; Dawson, Kenneth A

    2016-11-22

    It has been well established that the early stages of nanoparticle-cell interactions are governed, at least in part, by the layer of proteins and other biomolecules adsorbed and slowly exchanged with the surrounding biological media (biomolecular corona). Subsequent to membrane interactions, nanoparticles are typically internalized into the cell and trafficked along defined pathways such as, in many cases, the endolysosomal pathway. Indeed, if the original corona is partially retained on the nanoparticle surface, the biomolecules in this layer may play an important role in determining subsequent cellular processing. In this work, using a combination of organelle separation and fluorescence labeling of the initial extracellular corona, we clarify its intracellular evolution as nanoparticles travel within the cell. We show that specific proteins present in the original protein corona are retained on the nanoparticles until they accumulate in lysosomes, and, once there, they are degraded. We also report on how different bare surfaces (amino and carboxyl modified) affect the details of this evolution. One overarching discovery is that the same serum proteins can exhibit different intracellular processing when carried inside cells by nanoparticles, as components of their corona, compared to what is observed when they are transported freely from the extracellular medium.

  12. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments.

    Science.gov (United States)

    Wu, Yu; Pons, Valérie; Goudet, Amélie; Panigai, Laetitia; Fischer, Annette; Herweg, Jo-Ana; Kali, Sabrina; Davey, Robert A; Laporte, Jérôme; Bouclier, Céline; Yousfi, Rahima; Aubenque, Céline; Merer, Goulven; Gobbo, Emilie; Lopez, Roman; Gillet, Cynthia; Cojean, Sandrine; Popoff, Michel R; Clayette, Pascal; Le Grand, Roger; Boulogne, Claire; Tordo, Noël; Lemichez, Emmanuel; Loiseau, Philippe M; Rudel, Thomas; Sauvaire, Didier; Cintrat, Jean-Christophe; Gillet, Daniel; Barbier, Julien

    2017-11-14

    Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

  13. Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes.

    Science.gov (United States)

    Petri e Silva, Simone Carolina Soares; Palace-Berl, Fanny; Tavares, Leoberto Costa; Soares, Sandra Regina Castro; Lindoso, José Angelo Lauletta

    2016-04-01

    Leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries. Clinical manifestation depends on the interaction between Leishmania and the host's immune response. Currently available treatment options for leishmaniasis are limited and induce severe side effects. In this research, we tested nitro-heterocyclic compounds (BSF series) as a new alternative against Leishmania. Its activity was measured in Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes using MTT colorimetric assay. Additionally, we assessed the phosphatidylserine exposure by promastigotes, measured by flow cytometry, as well as nitric oxide production, measured by Griess' method. The nitro-heterocyclic compounds (BSF series) showed activity against L. (L.) infantum promastigotes, inducting the phosphatidylserine exposition by promastigotes, decreasing intracellular amastigotes and increasing oxide nitric production. The selectivity index was more prominent to Leishmania than to macrophages. Compared to amphotericin b, our compounds presented higher IC50, however the selectivity index was more specific to parasite than to amphotericin b. In conclusion, these nitro-heterocyclic compounds showed to be promising as an anti-Leishmania drug, in in vitro studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. INTRACELLULAR COPPER ACCUMULATION ENHANCES THE GROWTH OF KINEOCOCCUS RADIOTOLERANS DURING CHRONIC IRRADIATION

    International Nuclear Information System (INIS)

    Bagwell, C; Charles Milliken, C

    2007-01-01

    The actinobacteria Kineococcus radiotolerans is highly resistant to ionizing radiation, desiccation, and oxidative stress; though the underlying biochemical mechanisms are unknown. The purpose of this study was to explore a possible linkage between the uptake of transition metals and extreme resistance to ionizing radiation and oxidative stress. The effects of 6 different divalent cationic metals on growth were examined in the absence of ionizing radiation. None of the metals tested were stimulatory, though cobalt was inhibitory to growth. In contrast, copper supplementation dramatically increased cell growth during chronic irradiation. K. radiotolerans exhibited specific uptake and intracellular accumulation of copper compared to only a weak response to both iron and manganese supplementation. Copper accumulation sensitized cells to hydrogen peroxide. Acute irradiation induced DNA damage was similar between the copper-loaded culture as the age-synchronized no copper control culture, though low molecular weight DNA was more persistent during post-irradiation recovery in the Cu-loaded culture. Still, the estimated times for genome restoration differed by only 1 hr between treatments. While we cannot discount the possibility that copper fulfills an unexpectedly important biochemical role in a radioactive environment; K. radiotolerans has a high capacity for intracellular copper sequestration, and presumably efficiently coordinated oxidative stress defenses and detoxification systems, which confers cross-protection from the damaging affects ionizing radiation

  15. 31P MR spectroscopic measurement of intracellular pH in normal human hearts

    International Nuclear Information System (INIS)

    Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min

    2002-01-01

    To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of γ-ATP after performing MRS with ECG-gated two-dimensional 31 P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled 31 P CSI was performed on a 1.5-T scanner using a 1 H 31 P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of α-, β-, γ-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and γ-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm (γ-ATP), -7.8 ppm (α-ATP), and -16.3 ppm (β-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/β-ATP ratio was 2.20±0.17 and the PDE/β-ATP ratio, 1.04±0.09 pHi readings were 7.31±0.23 (calculated by the shift of Pi) and 6.81±0.20 (calculated by the shift of γ-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method

  16. {sup 31}P MR spectroscopic measurement of intracellular pH in normal human hearts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min [Kyungpook National Univ., Taegu (Korea, Republic of)] [and others

    2002-05-01

    To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of {gamma}-ATP after performing MRS with ECG-gated two-dimensional {sup 31}P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled {sup 31}P CSI was performed on a 1.5-T scanner using a {sup 1}H{sup 31}P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of {alpha}-, {beta}-, {gamma}-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and {gamma}-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm ({gamma}-ATP), -7.8 ppm ({alpha}-ATP), and -16.3 ppm ({beta}-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/{beta}-ATP ratio was 2.20{+-}0.17 and the PDE/{beta}-ATP ratio, 1.04{+-}0.09 pHi readings were 7.31{+-}0.23 (calculated by the shift of Pi) and 6.81{+-}0.20 (calculated by the shift of {gamma}-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method.

  17. Fuel assembly

    International Nuclear Information System (INIS)

    Hirukawa, Koji; Sakurada, Koichi.

    1992-01-01

    In a fuel assembly for a BWR type reactor, water rods or water crosses are disposed between fuel rods, and a value with a spring is disposed at the top of the coolant flow channel thereof, which opens a discharge port when pressure is increased to greater than a predetermined value. Further, a control element for the amount of coolant flow rate is inserted retractable to a control element guide tube formed at the lower portion of the water rod or the water cross. When the amount of control elements inserted to the control element guide tube is small and the inflown coolant flow rate is great, the void coefficient at the inside of the water rod is less than 5%. On the other hand, when the control elements are inserted, the flow resistance is increased, so that the void coefficient in the water rod is greater than 80%. When the pressure in the water rod is increased, the valve with the spring is raised to escape water or steams. Then, since the variation range of the change of the void coefficient can be controlled reliably by the amount of the control elements inserted, and nuclear fuel materials can be utilized effectively. (N.H.)

  18. Immunotoxicology of JP-8 Jet Fuel

    National Research Council Canada - National Science Library

    Harris, David

    2000-01-01

    ... of infectious disease and cancer. Chronic exposure to jet fuel has been shown to adversely affect human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans...

  19. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play......, experience and consumption are all strategic design tools applied by planners and architects. Whereas urban design in former modernist planning served merely functional or political means, urban design has increasingly become an aesthetical mediator of ideologies embedded in the urban field of life forces....... Under these circumstances affective aesthetics operate strategically within the urban field of interests, capital flows and desires of the social. This ‘affective urbanism’ (Anderson & Holden 2008) is linked to a society influenced by new kinds of information flows, where culture is mediated and enacted...

  20. Solid TRU fuels and fuel cycle technology

    International Nuclear Information System (INIS)

    Ogawa, Toru; Suzuki, Yasufumi

    1997-01-01

    Alloys and nitrides are candidate solid fuels for transmutation. However, the nitride fuels are preferred to the alloys because they have more favorable thermal properties which allows to apply a cold-fuel concept. The nitride fuel cycle technology is briefly presented

  1. Used fuel packing plant for CANDU fuel

    Energy Technology Data Exchange (ETDEWEB)

    Menzies, I.; Thayer, B.; Bains, N., E-mail: imenzies@atsautomation.com [ATS Automation, Cambridge, ON (Canada); Murchison, A., E-mail: amurchison@nwmo.ca [NWMO, Toronto, ON (Canada)

    2015-07-01

    Large forgings have been selected to containerize Light Water Reactor used nuclear fuel. CANDU fuel, which is significantly smaller in size, allows novel approaches for containerization. For example, by utilizing commercially available extruded ASME pipe a conceptual design of a Used Fuel Packing Plant for containerization of used CANDU fuel in a long lived metallic container has been developed. The design adopts a modular approach with multiple independent work cells to transfer and containerize the used fuel. Based on current technologies and concepts from proven industrial systems, the Used Fuel Packing Plant can assemble twelve used fuel containers per day considering conservative levels of process availability. (author)

  2. Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells.

    Science.gov (United States)

    Rimpelä, Anna-Kaisa; Hagström, Marja; Kidron, Heidi; Urtti, Arto

    2018-05-31

    Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, F ic , were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity. Copyright © 2017. Published by Elsevier B.V.

  3. Safeguards aspects for future fuel management alternatives

    International Nuclear Information System (INIS)

    Richter, B.; Stein, G.; Gerstler, R.

    1987-01-01

    In the future, more flexible fuel management strategies will be realized in light-water reactor power stations. The incentives for this development are based on considerations related to safe and economic plant operation, e.g. improved fuel strategies can save fuel resources and waste management efforts. A further important aspect of the nuclear fuel cycle deals with recycling strategies. At the back-end of the fuel cycle, the direct final disposal of spent fuel will have to be assessed as an alternative to recycling strategies. These major development fields will also have consequences for international safeguards. In particular, reactor fuel strategies may involve higher burn-up, conditioning of spent fuel directly in the power plant, gadolinium-poisoned fuel and different levels of enrichment. These strategies will have an impact on inspection activities, especially on the applicability of NDA techniques. The inspection frequency could also be affected in recycling strategies using MOX fuel. There may be problems with NDA methods if reprocessed feed is used in enrichment plants. On the other hand, the direct final disposal of spent fuel will raise safeguards problems regarding design verification, long-term safeguarding and the very feasibility of inaccessible nuclear material

  4. Economic comparison of fusion fuel cycles

    International Nuclear Information System (INIS)

    Brereton, S.J.; Kazimi, M.S.

    1987-01-01

    The economics of the DT, DD, and DHe fusion fuel cycles are evaluated by comparison on a consistent basis. The designs for the comparison employ HT-9 structure and helium coolant; liquid lithium is used as the tritium breeding material for the DT fuel cycle. The reactors are pulsed, superconducting tokamaks, producing 1200 MW of electric power. The DT and DD designs scan a range of values of plasma beta, assuming first stability scaling laws. The results indicate that on a purely economic basis, the DT fuel cycle is superior to both of the advanced fuel cycles. Geometric factors, materials limitations, and plasma beta were seen to have an impact on the Cost of Electricity (COE). The economics for the DD fuel cycle are more strongly affected by these parameters than is the DT fuel cycle. Fuel costs are a major factor in determining the COE for the DHe fuel cycle. Based on costs directly attributable to the fuel cycle, the DT fuel cycle appears most attractive. Technological advances, improved understanding of physics, or strides in advanced energy conversion schemes may result in altering the economic ranking of the fuel cycles indicated here. 7 refs., 6 figs., 2 tabs

  5. DMPD: Intracellular DNA sensors in immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18573338 Intracellular DNA sensors in immunity. Takeshita F, Ishii KJ. Curr Opin Im...munol. 2008 Aug;20(4):383-8. Epub 2008 Jun 23. (.png) (.svg) (.html) (.csml) Show Intracellular DNA sensors ...in immunity. PubmedID 18573338 Title Intracellular DNA sensors in immunity. Authors Takeshita F, Ishii KJ. P

  6. DMPD: NOD-like receptors (NLRs): bona fide intracellular microbial sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18585455 NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Shaw...tml) (.csml) Show NOD-like receptors (NLRs): bona fide intracellular microbial sensors. PubmedID 18585455 Ti...tle NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Authors

  7. An economic analysis of transportation fuel policies in Brazil: Fuel choice, land use, and environmental impacts

    International Nuclear Information System (INIS)

    Nuñez, Hector M.; Önal, Hayri

    2016-01-01

    Brazil uses taxes, subsidies, and blending mandates as policy instruments to manage and stabilize its transportation fuel markets. The fuel sector has been very dynamic in recent years due to frequent policy adjustments and variable market conditions. In this paper, we use a price endogenous economic simulation model to analyze the impacts of such policy adjustments under various challenging conditions in the global ethanol and sugar markets. Our analysis specifically focuses on Brazilian producers' supply responses, consumers' driving demand and fuel choice, ethanol trade, land use, greenhouse gas emissions, and social welfare. The model results show that (i) under a low ethanol blending rate, conventional vehicles would be driven significantly less while flex-fuel and ethanol-dedicated vehicles would not be affected significantly; (ii) lowering the fuel taxes adversely affects the competitiveness of sugarcane ethanol against gasoline blends, thus lowering producers' surplus; and (iii) while a reduction in fuel taxes is advantageous in terms of overall social welfare, it has serious environmental impacts by increasing the GHG emissions from transportation fuels consumed in Brazil. - Highlights: • We examine the economic and environmental impacts of Brazilian fuel policies. • We also analyze impacts under different sugar and ethanol markets conditions. • Lowering blending rate reduces distance driven by conventional cars. • Lowering fuel tax rates affects competitiveness of ethanol against gasoline blend. • Reducing fuel tax rates has dramatic environmental impacts by increasing emissions.

  8. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  9. Nuclear fuel preheating system

    International Nuclear Information System (INIS)

    Andrea, C.

    1975-01-01

    A nuclear reactor new fuel handling system which conveys new fuel from a fuel preparation room into the reactor containment boundary is described. The handling system is provided with a fuel preheating station which is adaptd to heat the new fuel to reactor refueling temperatures in such a way that the fuel is heated from the top down so that fuel element cladding failure due to thermal expansions is avoided. (U.S.)

  10. Fuel element loading system

    International Nuclear Information System (INIS)

    Arya, S.P; s.

    1978-01-01

    A nuclear fuel element loading system is described which conveys a plurality of fuel rods to longitudinal passages in fuel elements. Conveyor means successively position the fuel rods above the longitudinal passages in axial alignment therewith and adapter means guide the fuel rods from the conveyor means into the longitudinal passages. The fuel elements are vibrated to cause the fuel rods to fall into the longitudinal passages through the adapter means

  11. Transmutation Fuel Fabrication-Fiscal Year 2016

    Energy Technology Data Exchange (ETDEWEB)

    Fielding, Randall Sidney [Idaho National Lab. (INL), Idaho Falls, ID (United States); Grover, Blair Kenneth [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-12-01

    ABSTRACT Nearly all of the metallic fuel that has been irradiated and characterized by the Advanced Fuel Campaign, and its earlier predecessors, has been arc cast. Arc casting is a very flexible method of casting lab scale quantities of materials. Although the method offers flexibility, it is an operator dependent process. Small changes in parameter space or alloy composition may affect how the material is cast. This report provides a historical insight in how the casting process has been modified over the history of the advanced fuels campaign as well as the physical parameters of the fuels cast in fiscal year 2016.

  12. Cold exposure affects carbohydrates and lipid metabolism, and induces Hog1p phosphorylation in Dekkera bruxellensis strain CBS 2499.

    Science.gov (United States)

    Galafassi, Silvia; Toscano, Marco; Vigentini, Ileana; Zambelli, Paolo; Simonetti, Paolo; Foschino, Roberto; Compagno, Concetta

    2015-05-01

    Dekkera bruxellensis is a yeast known to affect the quality of wine and beer. This species, due to its high ethanol and acid tolerance, has been reported also to compete with Saccharomyces cerevisiae in distilleries producing fuel ethanol. In order to understand how this species responds when exposed to low temperatures, some mechanisms like synthesis and accumulation of intracellular metabolites, changes in lipid composition and activation of the HOG-MAPK pathway were investigated in the genome sequenced strain CBS 2499. We show that cold stress caused intracellular accumulation of glycogen, but did not induce accumulation of trehalose and glycerol. The cellular fatty acid composition changed after the temperature downshift, and a significant increase of palmitoleic acid was observed. RT-PCR analysis revealed that OLE1 encoding for Δ9-fatty acid desaturase was up-regulated, whereas TPS1 and INO1 didn't show changes in their expression. In D. bruxellensis Hog1p was activated by phosphorylation, as described in S. cerevisiae, highlighting a conserved role of the HOG-MAP kinase signaling pathway in cold stress response.

  13. Back-end of the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Choi, J.S.

    2002-01-01

    Current strategies of the back-end nuclear fuel cycles are: (1) direct-disposal of spent fuel (Open Cycle), and (2) reprocessing of the spent fuel and recycling of the recovered nuclear materials (Closed Cycle). The selection of these strategies is country-specific, and factors affecting selection of strategy are identified and discussed in this paper. (author)

  14. Artificial fuel

    Energy Technology Data Exchange (ETDEWEB)

    Hamon, L L.W.

    1918-08-20

    Lignite, peat, sud, leaf-mold, or shale, or two or more of these raw carbonaceous materials are mixed with cellulose material, such as sawdust, silica, alkali, and tar or pitch, or residues from tar or pitch, or residues from the distillation of oils, and the mixture is molded into blocks. Other carbonaceous materials, such as graphite, anthracite, or coal-dust, coke, breeze, or culm, and mineral substances, such as iron and manganese ores, may be added. A smokeless fuel can be obtained by coking the blocks in the usual way in retorts.

  15. Transient fluctuations of intracellular zinc ions in cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Maret, Wolfgang, E-mail: womaret@utmb.edu [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2009-08-15

    Zinc is essential for cell proliferation, differentiation, and viability. When zinc becomes limited for cultured cells, DNA synthesis ceases and the cell cycle is arrested. The molecular mechanisms of actions of zinc are believed to involve changes in the availability of zinc(II) ions (Zn{sup 2+}). By employing a fluorescent Zn{sup 2+} probe, FluoZin-3 acetoxymethyl ester, intracellular Zn{sup 2+} concentrations were measured in undifferentiated and in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Intracellular Zn{sup 2+} concentrations are pico- to nanomolar in PC12 cells and are higher in the differentiated than in the undifferentiated cells. When following cellular Zn{sup 2+} concentrations for 48 h after the removal of serum, a condition that is known to cause cell cycle arrest, Zn{sup 2+} concentrations decrease after 30 min but, remarkably, increase after 1 h, and then decrease again to about one half of the initial concentration. Cell proliferation, measured by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, decreases after both serum starvation and zinc chelation. Two peaks of Zn{sup 2+} concentrations occur within one cell cycle: one early in the G1 phase and the other in the late G1/S phase. Thus, fluctuations of intracellular Zn{sup 2+} concentrations and established modulation of phosphorylation signaling, via an inhibition of protein tyrosine phosphatases at commensurately low Zn{sup 2+} concentrations, suggest a role for Zn{sup 2+} in the control of the cell cycle. Interventions targeted at these picomolar Zn{sup 2+} fluctuations may be a way of controlling cell growth in hyperplasia, neoplasia, and diseases associated with aberrant differentiation.

  16. Nuclear Fuel elements

    International Nuclear Information System (INIS)

    Hirakawa, Hiromasa.

    1979-01-01

    Purpose: To reduce the stress gradient resulted in the fuel can in fuel rods adapted to control the axial power distribution by the combination of fuel pellets having different linear power densities. Constitution: In a fuel rod comprising a first fuel pellet of a relatively low linear power density and a second fuel pellet of a relatively high linear power density, the second fuel pellet is cut at its both end faces by an amount corresponding to the heat expansion of the pellet due to the difference in the linear power density to the adjacent first fuel pellet. Thus, the second fuel pellet takes a smaller space than the first fuel pellet in the fuel can. This can reduce the stress produced in the portion of the fuel can corresponding to the boundary between the adjacent fuel pellets. (Kawakami, Y.)

  17. Polymeric gel nanoparticle pH sensors for intracellular measurements

    OpenAIRE

    Almdal, Kristoffer; Andresen, Thomas Lars; Benjaminsen, Rikke Vicki; Christensen, Nynne Meyn; Henriksen, Jonas Rosager; Sun, Honghao

    2011-01-01

    Precise measurements of pH in cells and intracellular compartments are of importance to both the fundamental understanding of metabolism and to the development of drugs that are released from the endosomes-lysome pathway. We have developed polymer gel nanoparticles as carriers of covalently bound fluorophores for ratiometric measurements of pH. One pH insensitive fluorophore serves as a reference while one or more pH sensitive fluorophores serve to give the desired pH dependence of the output...

  18. Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    Science.gov (United States)

    Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

    2015-09-01

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

  19. Dependence of cerebral arterial contractions on intracellularly stored Ca++.

    Science.gov (United States)

    Sasaki, T; Kassell, N F; Zuccarello, M

    1986-01-01

    The purpose of the present study was to evaluate the dependence of the arterial contractions induced by different vasoactive agents upon intracellularly stored calcium in canine versus monkey cerebral arteries. The potency for inducing contractions in Ca++-free media was in the order of 9,11-epithio-11,12-metano-thromboxane A2 (STXA2) greater than prostaglandin F2 alpha (PGF2 alpha) much greater than serotonin greater than K+ in canine basilar arteries, and STXA2 greater than PGF2 alpha much greater than serotonin = K+ in monkey basilar arteries.

  20. Oxygen effect and intracellular oxygen content (adaptation hypothesis)

    Energy Technology Data Exchange (ETDEWEB)

    Yarmonenko, S P; Ehpshtejn, I M [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Tsentr

    1977-01-01

    Experimental data indicating that a radiomodifying action of hypoxia is dependent on the ''prehistory'' of the irradiated object are considered. This dependence manifests itself in a decreased protective action of acute hypoxia on the hypoxia-adapted objects. To explain this a hypothesis is proposed connecting a degree of cell radiosensitivity modification, determined by the oxygen effect, with the intracellular oxygen content. The latter, in accord with current ideas, is regulated by variations in the diffusion resistance to oxygen shown by the cytoplasmic membranes depending on the energy level of the cell and the degree of its oxygenation.

  1. Oxygen effect and intracellular oxygen content (adaptation hypothesis)

    International Nuclear Information System (INIS)

    Yarmonenko, S.P.; Ehpshtejn, I.M.

    1977-01-01

    Experimental data indicating that a radiomodifying action of hypoxia is dependent on the ''prehistory'' of the irradiated object are considered. This dependence manifests itself in a decreased protective action of acute hypoxia on the hypoxia-adapted objects. To explain this a hypothesis is proposed connecting a degree of cell radiosensitivity modification, determined by the oxygen effect, with the intracellular oxygen content. The latter, in accord with current ideas, is regulated by variations in the diffusion resistance to oxygen shown by the cytoplasmic membranes depending on the energy level of the cell and the degree of its oxygenation

  2. Subcellular site and nature of intracellular cadmium in plants

    International Nuclear Information System (INIS)

    Wagner, G.J.

    1979-01-01

    The mechanisms underlying heavy metal accumulation, toxicity, and tolerance in higher plants are poorly understood. Since subcellular processes are undoubtedly involved in all these phenomena, it is of interest to study the extent, subcellular site and nature of intracellularly accumulated cadmium in higher plants. Whole plants supplied 109 CdCl 2 or 112 CdSO 4 accumulated Cd into roots and aerial tissues. Preparation of protoplasts from aerial tissues followed by subcellular fractionation of the protoplasts to obtain intact vacuoles, chloroplasts and cytosol revealed the presence of Cd in the cytosol but not in vacuoles or chloroplasts. No evidence was obtained for the production of volatile Cd complexes in tobacco

  3. Fuel pin transfer tool

    International Nuclear Information System (INIS)

    Patenaude, R. S.

    1985-01-01

    A fuel pin transfer tool has a latching device of the collet type attached to a first member movable vertically through a long work stroke enabling a fuel pin in an under water assembly to be engaged and withdrawn therefrom or placed therein and released. The latching device has a collet provided with a plurality of resilient fingers having cam portions normally spaced apart to receive the upper end of a fuel pin between them and a second member, movable vertically through a short stroke relative to the first member is provided with cam portions engageable with those of the fingers and is yieldably and resiliently held in a raised position in which its cam portions engage those of the fingers and force the fingers into their pin-gripping positions. When a predetermined force is applied to the second member, it is so moved that its cam portions are disengaged from the cam portions of the fingers permitting the latter to move into their normal relationship in which a gripped pin is released or another pin received but with their pin-gripping relationship positively re-established and maintained once the force on the tubular member is lessened. Movement of the first member in either direction and movement of the second member into its raised position is attended by forces inadequate to affect the integrity of fuel pin cladding. That force is applied in the preferred embodiment, by a power operated actuator which is within the upper portion of a housing and, in the preferred embodiment, carried by the long stroke member but always in the upper housing portion which is of a material sufficiently translucent to enable the actuator to be observed throughout the work stroke and is sufficiently light in weight to prevent the tool from being top heavy

  4. Fuel assembly

    International Nuclear Information System (INIS)

    Hiraiwa, Koji; Ueda, Makoto

    1989-01-01

    In a fuel assembly used for a light water cooled reactor such as a BWR type reactor, a water rod is divided axially into an upper outer tube and a lower outer tube by means of a plug disposed from the lower end of a water rod to a position 1/4 - 1/2 of the entire length for the water rod. Inlet apertures and exit apertures for moderators are respectively perforated for the divided outer tube and upper and lower portions. Further, an upper inner tube with less neutron irradiation growing amount than the outer tube is perforated on the plug in the outer tube, while a lower inner tube with greater neutron irradiation growing amount than the outer tube is suspended from the lower surface of the plug in the outer tube. Then, the opening area for the exit apertures disposed to the upper outer tube and the lower outer tube is controlled depending on the difference of the neutron irradiation growing amount between the upper inner tube and the upper outer tube, and the difference of the neutron irradiation growing amount between the lower inner tube and the lower outer tube. This enables effective spectral shift operation and improve the fuel economy. (T.M.)

  5. Fuel Burn Estimation Model

    Science.gov (United States)

    Chatterji, Gano

    2011-01-01

    Conclusions: Validated the fuel estimation procedure using flight test data. A good fuel model can be created if weight and fuel data are available. Error in assumed takeoff weight results in similar amount of error in the fuel estimate. Fuel estimation error bounds can be determined.

  6. CANDU type fuel activities in Argentina

    International Nuclear Information System (INIS)

    Lavarez, L.; Casario, J.A.; Moreno, C.

    2003-01-01

    Domestic fuel performance in Embalse NPP during the last two years has been excellent without a significant occurrence of fuel failures. The defect rate level was reasonably low with a lowest value of 0.02 % in 2002. The implementation of fuel design optimizations to increase uranium content was fully completed by the end of year 2000. The in-reactor performance was not affected and shows the high degree of maturity reached for both the design and the manufacturing procedures and capabilities. A feasibility study for the utilization of SEU in Embalse NPP mainly conducted by NA-SA and AECL is almost completed. Some fuel related activities are still in progress. As part of them fuel behavior simulations using simplified power histories were performed to assess the influence of SEU fuel burnup extension. (author)

  7. Assessment of bio-fuel options for solid oxide fuel cell applications

    Science.gov (United States)

    Lin, Jiefeng

    Rising concerns of inadequate petroleum supply, volatile crude oil price, and adverse environmental impacts from using fossil fuels have spurred the United States to promote bio-fuel domestic production and develop advanced energy systems such as fuel cells. The present dissertation analyzed the bio-fuel applications in a solid oxide fuel cell-based auxiliary power unit from environmental, economic, and technological perspectives. Life cycle assessment integrated with thermodynamics was applied to evaluate the environmental impacts (e.g., greenhouse gas emission, fossil energy consumption) of producing bio-fuels from waste biomass. Landfill gas from municipal solid wastes and biodiesel from waste cooking oil are both suggested as the promising bio-fuel options. A nonlinear optimization model was developed with a multi-objective optimization technique to analyze the economic aspect of biodiesel-ethanol-diesel ternary blends used in transportation sectors and capture the dynamic variables affecting bio-fuel productions and applications (e.g., market disturbances, bio-fuel tax credit, policy changes, fuel specification, and technological innovation). A single-tube catalytic reformer with rhodium/ceria-zirconia catalyst was used for autothermal reformation of various heavy hydrocarbon fuels (e.g., diesel, biodiesel, biodiesel-diesel, and biodiesel-ethanol-diesel) to produce a hydrogen-rich stream reformates suitable for use in solid oxide fuel cell systems. A customized mixing chamber was designed and integrated with the reformer to overcome the technical challenges of heavy hydrocarbon reformation. A thermodynamic analysis, based on total Gibbs free energy minimization, was implemented to optimize the operating environment for the reformations of various fuels. This was complimented by experimental investigations of fuel autothermal reformation. 25% biodiesel blended with 10% ethanol and 65% diesel was determined to be viable fuel for use on a truck travelling with

  8. Fuel compliance model for pellet-cladding mechanical interaction

    International Nuclear Information System (INIS)

    Shah, V.N.; Carlson, E.R.

    1985-01-01

    This paper describes two aspects of fuel pellet deformation that play significant roles in determining maximum cladding hoop strains during pellet-cladding mechanical interaction: compliance of fragmented fuel pellets and influence of the pellet end-face design on the transmission of axial compressive force in the fuel stack. The latter aspect affects cladding ridge formation and explains several related observations that cannot be explained by the hourglassing model. An empirical model, called the fuel compliance model and representing the above aspects of fuel deformation, has been developed using the results from two Halden experiments and incorporated into the FRAP-T6 fuel performance code

  9. Effect of broadened-specification fuels on aircraft engines and fuel systems

    Science.gov (United States)

    Rudey, R. A.

    1979-01-01

    A wide variety of studies on the potential effects of broadened-specification fuels on future aircraft engines and fuel systems are summarized. The compositions and characteristics of aircraft fuels that may be derived from current and future crude-oil sources are described, and the most critical properties that may affect aircraft engines and fuel systems are identified and discussed. The problems that are most likely to be encountered because of changes in selected fuel properties are described; and the related effects on engine performance, component durability and maintenance, and aircraft fuel-system performance are discussed. The ability of current technology to accept possible future fuel-specification changes is discussed, and selected technological advances that can reduce the severity of the potential problems are illustrated.

  10. Constant strength fuel-fuel cell

    International Nuclear Information System (INIS)

    Vaseen, V.A.

    1980-01-01

    A fuel cell is an electrochemical apparatus composed of both a nonconsumable anode and cathode; and electrolyte, fuel oxidant and controls. This invention guarantees the constant transfer of hydrogen atoms and their respective electrons, thus a constant flow of power by submergence of the negative electrode in a constant strength hydrogen furnishing fuel; when said fuel is an aqueous absorbed hydrocarbon, such as and similar to ethanol or methnol. The objective is accomplished by recirculation of the liquid fuel, as depleted in the cell through specific type membranes which pass water molecules and reject the fuel molecules; thus concentrating them for recycle use

  11. Highly durable, coking and sulfur tolerant, fuel-flexible protonic ceramic fuel cells.

    Science.gov (United States)

    Duan, Chuancheng; Kee, Robert J; Zhu, Huayang; Karakaya, Canan; Chen, Yachao; Ricote, Sandrine; Jarry, Angelique; Crumlin, Ethan J; Hook, David; Braun, Robert; Sullivan, Neal P; O'Hayre, Ryan

    2018-05-01

    Protonic ceramic fuel cells, like their higher-temperature solid-oxide fuel cell counterparts, can directly use both hydrogen and hydrocarbon fuels to produce electricity at potentially more than 50 per cent efficiency 1,2 . Most previous direct-hydrocarbon fuel cell research has focused on solid-oxide fuel cells based on oxygen-ion-conducting electrolytes, but carbon deposition (coking) and sulfur poisoning typically occur when such fuel cells are directly operated on hydrocarbon- and/or sulfur-containing fuels, resulting in severe performance degradation over time 3-6 . Despite studies suggesting good performance and anti-coking resistance in hydrocarbon-fuelled protonic ceramic fuel cells 2,7,8 , there have been no systematic studies of long-term durability. Here we present results from long-term testing of protonic ceramic fuel cells using a total of 11 different fuels (hydrogen, methane, domestic natural gas (with and without hydrogen sulfide), propane, n-butane, i-butane, iso-octane, methanol, ethanol and ammonia) at temperatures between 500 and 600 degrees Celsius. Several cells have been tested for over 6,000 hours, and we demonstrate excellent performance and exceptional durability (less than 1.5 per cent degradation per 1,000 hours in most cases) across all fuels without any modifications in the cell composition or architecture. Large fluctuations in temperature are tolerated, and coking is not observed even after thousands of hours of continuous operation. Finally, sulfur, a notorious poison for both low-temperature and high-temperature fuel cells, does not seem to affect the performance of protonic ceramic fuel cells when supplied at levels consistent with commercial fuels. The fuel flexibility and long-term durability demonstrated by the protonic ceramic fuel cell devices highlight the promise of this technology and its potential for commercial application.

  12. Objective and subjective measures of fuel poverty

    International Nuclear Information System (INIS)

    Waddams Price, Catherine; Brazier, Karl; Wang, Wenjia

    2012-01-01

    As energy prices continue to rise to reflect the real cost of carbon, the numbers of households in fuel poverty is increasing rapidly. This paper uses a unique data set to explore one alternative measure of fuel poverty based on whether consumers feel able to afford their energy, similar to one introduced by the government a few years ago. We explore the links between an expenditure based and our subjective measure of fuel poverty and compare these differences with those between official measures. Amongst low income households, 28% spent more than a tenth of their income on energy in the home, and so would be likely to qualify as fuel poor under the most usual definition; but only 16% felt unable to afford sufficient energy to keep their homes warm. Amongst this group who felt they had difficulty in affording sufficient energy, less than half were ‘expenditure’ fuel poor. The paper argues that reintroduction of a self-reported measure by the government would be a valuable aid to policy development. - Highlights: ► Defines a subjective measure of fuel poverty (unable to afford heating). ► Fewer households feel fuel poor than meet the official definition of fuel poverty. ► Though they are positively related, different factors affect the two measures. ► Those on standard and prepayment metres more likely to feel fuel poor. ► Large families spend a higher proportion of income on energy but are no more likely to feel fuel poor.

  13. Metabolic Characterization of Intact Cells Reveals Intracellular Amyloid Beta but Not Its Precursor Protein to Reduce Mitochondrial Respiration

    Science.gov (United States)

    Schaefer, Patrick M.; von Einem, Bjoern; Walther, Paul; Calzia, Enrico; von Arnim, Christine A. F.

    2016-01-01

    One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization. We performed an overexpression of APP or beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), increasing APP and Aβ levels or Aβ alone, respectively. Conducting a comprehensive metabolic characterization we demonstrate that only APP overexpression reduced mitochondrial respiration, despite lower extracellular Aβ levels compared to BACE overexpression. Surprisingly, this could be rescued by a gamma secretase inhibitor, oppositionally indicating an Aβ-mediated mitochondrial toxicity. Analyzing Aβ localization revealed that intracellular levels of Aβ and an increased spatial association of APP/Aβ with mitochondria are associated with reduced mitochondrial respiration. Thus, our data provide marked evidence for a prominent role of intracellular Aβ accumulation in Alzheimer´s disease associated mitochondrial dysfunction. Thereby it highlights the importance of the localization of APP processing and intracellular transport as a decisive factor for mitochondrial function, linking two prominent hallmarks of neurodegenerative diseases. PMID:28005987

  14. Intracellular crowding effects on the self-association of the bacterial cell division protein FtsZ.

    Science.gov (United States)

    Naddaf, Lamis; Sayyed-Ahmad, Abdallah

    2014-12-15

    The dimerization rate of the bacterial cell division protein FtsZ is strongly affected by the intracellular crowding. Yet the complexity of the intracellular environment makes it difficult to investigate via all-atom molecular dynamics or other detailed theoretical methods. We study the crowding effect on FtsZ dimerization which is the first step of an oligomerization process that results in more elaborate supramolecular structures. In particular, we consider the effect of intracellular crowding on the reaction rates, and their dependence on the different concentrations of crowding agents. We achieved this goal by using Brownian dynamics (BD) simulation techniques and a modified post-processing approach in which we decompose the rate constant in crowded media as a product of the rate constant in the dilute solution times a factor that incorporates the crowding effect. The latter factor accounts for the diffusion reduction and crowder induced energy. In addition we include the crowding effects on water viscosity in the BD simulations of crowded media. We finally show that biomolecular crowding has a considerable effect on the FtsZ dimerization by increasing the dimerization rate constant from 2.6×10(7)M(-1)s(-1) in the absence of crowders to 1.0×10(8)M(-1)s(-1) at crowding level of 0.30. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cell internalizable and intracellularly degradable cationic polyurethane micelles as a potential platform for efficient imaging and drug delivery.

    Science.gov (United States)

    Ding, Mingming; Zeng, Xin; He, Xueling; Li, Jiehua; Tan, Hong; Fu, Qiang

    2014-08-11

    A cell internalizable and intracellularly degradable micellar system, assembled from multiblock polyurethanes bearing cell-penetrating gemini quaternary ammonium pendent groups in the side chain and redox-responsive disulfide linkages throughout the backbone, was developed for potential magnetic resonance imaging (MRI) and drug delivery. The nanocarrier is featured as a typical "cleavable core-internalizable shell-protective corona" architecture, which exhibits small size, positive surface charge, high loading capacity, and reduction-triggered destabilization. Furthermore, it can rapidly enter tumor cells and release its cargo in response to an intracellular level of glutathione, resulting in enhanced drug efficacy in vitro. The magnetic micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles demonstrate excellent MRI contrast enhancement, with T2 relaxivity found to be affected by the morphology of SPIO-clustering inside the micelle core. The multifunctional carrier with good cytocompatibility and nontoxic degradation products can serve as a promising theranostic candidate for efficient intracellular delivery of anticancer drugs and real-time monitoring of therapeutic effect.

  16. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... of digital cartographies has been highlighted as the ‘processual turn’ in critical cartography, whereas in related computational journalism it can be seen as an interactive and iterative process of mapping complex and fragile ecological developments. This paper looks at computer-assisted cartography as part...

  17. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

    International Nuclear Information System (INIS)

    Sanson, Benoît; Wang, Tao; Sun, Jing; Wang, Liqun; Kaczocha, Martin; Ojima, Iwao; Deutsch, Dale; Li, Huilin

    2014-01-01

    FABP5 was recently found to intracellularly transport endocannabinoid signaling lipids. The structures of FABP5 complexed with two endocannabinoids and an inhibitor were solved. Human FABP5 was found to dimerize via a domain-swapping mechanism. This work will help in the development of inhibitors to raise endocannabinoid levels. In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels

  18. Imaging the intracellular degradation of biodegradable polymer nanoparticles

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Barthel

    2014-10-01

    Full Text Available In recent years, the development of smart drug delivery systems based on biodegradable polymeric nanoparticles has become of great interest. Drug-loaded nanoparticles can be introduced into the cell interior via endocytotic processes followed by the slow release of the drug due to degradation of the nanoparticle. In this work, poly(L-lactic acid (PLLA was chosen as the biodegradable polymer. Although common degradation of PLLA has been studied in various biological environments, intracellular degradation processes have been examined only to a very limited extent. PLLA nanoparticles with an average diameter of approximately 120 nm were decorated with magnetite nanocrystals and introduced into mesenchymal stem cells (MSCs. The release of the magnetite particles from the surface of the PLLA nanoparticles during the intracellular residence was monitored by transmission electron microscopy (TEM over a period of 14 days. It was demonstrated by the release of the magnetite nanocrystals from the PLLA surface that the PLLA nanoparticles do in fact undergo degradation within the cell. Furthermore, even after 14 days of residence, the PLLA nanoparticles were found in the MSCs. Additionally, the ultrastructural TEM examinations yield insight into the long term intercellular fate of these nanoparticles. From the statistical analysis of ultrastructural details (e.g., number of detached magnetite crystals, and the number of nanoparticles in one endosome, we demonstrate the importance of TEM studies for such applications in addition to fluorescence studies (flow cytometry and confocal laser scanning microscopy.

  19. Fluorescent nanosensors for intracellular measurements: synthesis, characterisation, calibration and measurement

    Directory of Open Access Journals (Sweden)

    Arpan Shailesh Desai

    2014-01-01

    Full Text Available Measurement of intracellular acidification is important for understanding fundamental biological pathways as well as developing effective therapeutic strategies. Fluorescent pH nanosensors are an enabling technology for real-time monitoring of intracellular acidification. The physicochemical characteristics of nanosensors can be engineered to target specific cellular compartments and respond to external stimuli. Therefore nanosensors represent a versatile approach for probing biological pathways inside cells. The fundamental components of nanosensors comprise a pH-sensitive fluorophore (signal transducer and a pH-insensitive reference fluorophore (internal standard immobilised in an inert non-toxic matrix. The inert matrix prevents interference of cellular components with the sensing elements as well as minimizing potentially harmful effects of some fluorophores on cell function. Fluorescent nanosensors are synthesised using standard laboratory equipment and are detectable by non-invasive widely accessibly imaging techniques. The outcomes of studies employing this technology are dependent on reliable methodology for performing measurements. In particular special consideration must be given to conditions for sensor calibration, uptake conditions and parameters for image analysis. We describe procedures for: 1 synthesis and characterisation of polyacrylamide and silica based nanosensors 2 nanosensor calibration and 3 performing measurements using fluorescence microscopy.

  20. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Energy Technology Data Exchange (ETDEWEB)

    Dobay, M. P. D., E-mail: maria.pamela.david@physik.uni-muenchen.de; Alberola, A. Piera; Mendoza, E. R.; Raedler, J. O., E-mail: joachim.raedler@physik.uni-muenchen.de [Ludwig-Maximilians University, Faculty of Physics, Center for NanoScience (Germany)

    2012-03-15

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  1. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    International Nuclear Information System (INIS)

    Dobay, M. P. D.; Alberola, A. Piera; Mendoza, E. R.; Rädler, J. O.

    2012-01-01

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  2. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Science.gov (United States)

    Dobay, M. P. D.; Alberola, A. Piera; Mendoza, E. R.; Rädler, J. O.

    2012-03-01

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  3. Molecular characterization of a novel intracellular ADP-ribosyl cyclase.

    Directory of Open Access Journals (Sweden)

    Dev Churamani

    2007-08-01

    Full Text Available ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates.Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1 is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained.Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized.

  4. Cell fate reprogramming by control of intracellular network dynamics

    Science.gov (United States)

    Zanudo, Jorge G. T.; Albert, Reka

    Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

  5. Transient light-induced intracellular oxidation revealed by redox biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Kolossov, Vladimir L., E-mail: viadimer@illinois.edu [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Beaudoin, Jessica N. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Hanafin, William P. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); DiLiberto, Stephen J. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Kenis, Paul J.A. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801 (United States); Rex Gaskins, H. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Avenue, Urbana, IL 61801 (United States); Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, Urbana, IL 61801 (United States)

    2013-10-04

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition.

  6. Downregulation of transferrin receptor surface expression by intracellular antibody

    International Nuclear Information System (INIS)

    Peng Jilin; Wu Sha; Zhao Xiaoping; Wang Min; Li Wenhan; Shen Xin; Liu Jing; Lei Ping; Zhu Huifen; Shen Guanxin

    2007-01-01

    To deplete cellular iron uptake, and consequently inhibit the proliferation of tumor cells, we attempt to block surface expression of transferrin receptor (TfR) by intracellular antibody technology. We constructed two expression plasmids (scFv-HAK and scFv-HA) coding for intracellular single-chain antibody against TfR with or without endoplasmic reticulum (ER) retention signal, respectively. Then they were transfected tumor cells MCF-7 by liposome. Applying RT-PCR, Western blotting, immunofluorescence microscopy and immunoelectron microscope experiments, we insure that scFv-HAK intrabody was successfully expressed and retained in ER contrasted to the secreted expression of scFv-HA. Flow cytometric analysis confirmed that the TfR surface expression was markedly decreased approximately 83.4 ± 2.5% in scFv-HAK transfected cells, while there was not significantly decrease in scFv-HA transfected cells. Further cell growth and apoptosis characteristics were evaluated by cell cycle analysis, nuclei staining and MTT assay. Results indicated that expression of scFv-HAK can dramatically induce cell cycle G1 phase arrest and apoptosis of tumor cells, and consequently significantly suppress proliferation of tumor cells compared with other control groups. For First time this study demonstrates the potential usage of anti-TfR scFv-intrabody as a growth inhibitor of TfR overexpressing tumors

  7. Cyanobacteria perceive nitrogen status by sensing intracellular 2-oxoglutarate levels.

    Science.gov (United States)

    Muro-Pastor, M I; Reyes, J C; Florencio, F J

    2001-10-12

    The regulatory circuits that control nitrogen metabolism are relatively well known in several bacterial model groups. However, much less is understood about how the nitrogen status of the cell is perceived in vivo. In cyanobacteria, the transcription factor NtcA is required for regulation (activation or repression) of an extensive number of genes involved in nitrogen metabolism. In contrast, how NtcA activity is regulated is largely unknown. Assimilation of ammonium by most microorganisms occurs through the sequential action of two enzymes: glutamine synthetase (GS) and glutamate synthase. Interestingly, regulation of the expression of NtcA-dependent genes in the cyanobacterium Synechocystis sp. PCC 6803 is altered in mutants with modified levels of GS activity. Two types of mutants were analyzed: glnA null mutants that lack GS type I and gif mutants unable to inactivate GS in the presence of ammonium. Changes in the intracellular pools of 19 different amino acids and the keto acid 2-oxoglutarate were recorded in wild-type and mutant strains under different nitrogen conditions. Our data strongly indicate that the nitrogen status in cyanobacteria is perceived as changes in the intracellular 2-oxoglutarate pool.

  8. Optochemokine Tandem for Light-Control of Intracellular Ca2.

    Directory of Open Access Journals (Sweden)

    Katrin Feldbauer

    Full Text Available An optochemokine tandem was developed to control the release of calcium from endosomes into the cytosol by light and to analyze the internalization kinetics of G-protein coupled receptors (GPCRs by electrophysiology. A previously constructed rhodopsin tandem was re-engineered to combine the light-gated Ca2+-permeable cation channel Channelrhodopsin-2(L132C, CatCh, with the chemokine receptor CXCR4 in a functional tandem protein tCXCR4/CatCh. The GPCR was used as a shuttle protein to displace CatCh from the plasma membrane into intracellular areas. As shown by patch-clamp measurements and confocal laser scanning microscopy, heterologously expressed tCXCR4/CatCh was internalized via the endocytic SDF1/CXCR4 signaling pathway. The kinetics of internalization could be followed electrophysiologically via the amplitude of the CatCh signal. The light-induced release of Ca2+ by tandem endosomes into the cytosol via CatCh was visualized using the Ca2+-sensitive dyes rhod2 and rhod2-AM showing an increase of intracellular Ca2+ in response to light.

  9. Transient light-induced intracellular oxidation revealed by redox biosensor

    International Nuclear Information System (INIS)

    Kolossov, Vladimir L.; Beaudoin, Jessica N.; Hanafin, William P.; DiLiberto, Stephen J.; Kenis, Paul J.A.; Rex Gaskins, H.

    2013-01-01

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition

  10. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

    Energy Technology Data Exchange (ETDEWEB)

    Sanson, Benoît; Wang, Tao [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Sun, Jing; Wang, Liqun; Kaczocha, Martin [Stony Brook University, Stony Brook, NY 11794-5213 (United States); Ojima, Iwao [Stony Brook University, Stony Brook, NY 1794-3400 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States); Deutsch, Dale, E-mail: dale.deutsch@stonybrook.edu [Stony Brook University, Stony Brook, NY 11794-5213 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States); Li, Huilin, E-mail: dale.deutsch@stonybrook.edu [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Stony Brook University, Stony Brook, NY 11794-5213 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States)

    2014-02-01

    FABP5 was recently found to intracellularly transport endocannabinoid signaling lipids. The structures of FABP5 complexed with two endocannabinoids and an inhibitor were solved. Human FABP5 was found to dimerize via a domain-swapping mechanism. This work will help in the development of inhibitors to raise endocannabinoid levels. In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels.

  11. CIRRHOSIS INDUCES APOPTOSIS IN RENAL TISSUE THROUGH INTRACELLULAR OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Keli Cristina Simões da SILVEIRA

    2015-03-01

    Full Text Available Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

  12. Spent fuel and fuel pool component integrity. Annual report, FY 1979

    International Nuclear Information System (INIS)

    Johnson, A.B. Jr.; Bailey, W.J.; Schreiber, R.E.; Kustas, F.M.

    1980-05-01

    International meetings under the BEFAST program and under INFCE Working Group No. 6 during 1978 and 1979 continue to indicate that no cases of fuel cladding degradation have developed on pool-stored fuel from water reactors. A section from a spent fuel rack stand, exposed for 1.5 y in the Yankee Rowe (PWR) pool had 0.001- to 0.003-in.-deep (25- to 75-μm) intergranular corrosion in weld heat-affected zones but no evidence of stress corrosion cracking. A section of a 304 stainless steel spent fuel storage rack exposed 6.67 y in the Point Beach reactor (PWR) spent fuel pool showed no significant corrosion. A section of 304 stainless steel 8-in.-dia pipe from the Three Mile Island No. 1 (PWR) spent fuel pool heat exchanger plumbing developed a through-wall crack. The crack was intergranular, initiating from the inside surface in a weld heat-affected zone. The zone where the crack occurred was severely sensitized during field welding. The Kraftwerk Union (Erlangen, GFR) disassembled a stainless-steel fuel-handling machine that operated for 12 y in a PWR (boric acid) spent fuel pool. There was no evidence of deterioration, and the fuel-handling machine was reassembled for further use. A spent fuel pool at a Swedish PWR was decontaminated. The procedure is outlined in this report

  13. KMRR fuel design

    International Nuclear Information System (INIS)

    Son, D.S.; Sim, B.S.; Kim, T.R.; Hwang, W.; Kim, B.G.; Ku, Y.H.; Lee, C.B.; Lim, I.C.

    1992-06-01

    KMRR fuel rod design criteria on fuel swelling, blistering and oxide spallation have been reexamined. Fuel centerline temperature limit of 250deg C in normal operation condition and fuel swelling limit of 12 % at the end of life have been proposed to prevent fuel failure due to excessive fuel swelling. Fuel temperature limit of 485deg C has been proposed to exclude the possibility of fuel failures during transients or under accident condition. Further analyses are needed to decide the fuel cladding temperature limit to preclude the oxide spallation. Design changes in fuel assembly structure and their effects on related systems have been reviewed from a structural integrity viewpoint. The remained works in fuel mechanical design area have been identified and further efforts of fuel design group will be focused on these aspects. (Author)

  14. Fuel Property Blend Model

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, William J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Mehl, Marco [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wagnon, Scott J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zhang, Kuiwen [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kukkadapu, Goutham [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Westbrook, Charles K. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-01-12

    The object of this project is to develop chemical models and associated correlations to predict the blending behavior of bio-derived fuels when mixed with conventional fuels like gasoline and diesel fuels.

  15. Logistic Fuel Processor Development

    National Research Council Canada - National Science Library

    Salavani, Reza

    2004-01-01

    The Air Base Technologies Division of the Air Force Research Laboratory has developed a logistic fuel processor that removes the sulfur content of the fuel and in the process converts logistic fuel...

  16. Fuel pellet loading apparatus

    International Nuclear Information System (INIS)

    1980-01-01

    Apparatus is described for loading a predetermined amount of nuclear fuel pellets into nuclear fuel elements and particularly for the automatic loading of fuel pellets from within a sealed compartment. (author)

  17. Economic feasibility prediction of the commercial fuel cells

    International Nuclear Information System (INIS)

    Ma Yan; Karady, George G.; Winston, Anthony; Gilbert, Palomino; Hess, Robert; Pelley, Don

    2009-01-01

    This paper presents a prediction method and corresponding Visual Basic program to evaluate the economic feasibility of the commercial fuel cells in utility systems. The economic feasibility of a fuel cell is defined as having a net present value (NPV) greater than zero. The basic process of the method is to combine fuel cell specifications and real energy market data to calculate yearly earning and cost for obtaining the NPV of fuel cells. The Fuel Cell Analysis Software was developed using Visual Basic based on the proposed method. The investigation of a 250 kW molten carbonate fuel cell (FuelCell Energy DFC300A) predicted that, for application specifically in Arizona, United States, no profit would result from the installation of this fuel cell. The analysis results indicated that the efficiency, investment cost, and operation cost are three key factors affecting potential feasibility of the commercial fuel cells

  18. Fuel assembly

    International Nuclear Information System (INIS)

    Wataumi, Kazutoshi; Tajiri, Hiroshi.

    1992-01-01

    In a fuel assembly of a BWR type reactor, a pellet to be loaded comprises an external layer of fissile materials containing burnable poisons and an internal layer of fissile materials not containing burnable poison. For example, there is provided a dual type pellet comprising an external layer made of UO 2 incorporated with Gd 2 O 3 at a predetermined concentration as the burnable poisons and an internal layer made of UO 2 not containing Gd 2 O 3 . The amount of the burnable poisons required for predetermined places is controlled by the thickness of the ring of the external layer. This can dissipate an unnecessary poisoning effect at the final stage of the combustion cycle. Further, since only one or a few kinds of powder mixture of the burnable poisons and the fissile materials is necessary, production and product control can be facilitated. (I.N.)

  19. Alternative Fuel Reduction Treatments in the Gunflint Corridor of the Superior National Forest: Second year results and sampling recommendations

    Science.gov (United States)

    Daniel W. Gilmore; Douglas N. Kastendick; John C. Zasada; Paula J. Anderson

    2003-01-01

    Fuel loadings need to be considered in two ways: 1) the total fuel loadings of various size classes and 2) their distribution across a site. Fuel treatments in this study affected both. We conclude that 1) mechanical treatments of machine piling and salvage logging reduced fine and heavy fuel loadings and 2) prescribed fire was successful in reducing fine fuel...

  20. Fuel storage

    International Nuclear Information System (INIS)

    Palacios, C.; Alvarez-Miranda, A.

    2009-01-01

    ENSA is a well known manufacturer of multi-system primary components for the nuclear industry and is totally prepared to satisfy future market requirements in this industry. At the same time that ENSA has been gaining a reputation world wider for the supply of primary components, has been strengthening its commitment and experience in supplying spent fuel components, either pool racks or storage and transportation casks, and offers not only fabrication but also design capabilities for its products. ENSA has supplied Spent Fuel Pool Racks, in spain, Finland, Taiwan, Korea, China, and currently it is in the process of licensing its own rack design in the United States of America for the ESBWR along with Ge-Hitachi. ENSA has supplied racks for 20 pools and 22 different reactors and it has also manufactured racks under all available technologies and developed a design known as Interlock Cell Matrix whose main features are outlined in this article. Another ENSA achievement in rack technology is the use of remote control for re-racking activities instead of using divers, which improves the ALARA requirements. Regarding casks for storage and transportation, ENSA also has al leading worldwide position, with exports prevailing over the Spanish market where ENSA has supplied 16 storage and transportation casks to the Spanish nuclear power Trillo. In some cases, ENSA acts as subcontractor for other clients. Foreign markets are still a major challenge for ENSA. ENSA-is well known for its manufacturing capabilities in the nuclear industry, but has been always involved in design activities through its engineering division, which carries out different tasks: components Design; Tooling Design; Engineering and Documentation; Project Engineering; Calculations, Design and Development Engineering. (Author)

  1. Development of analytical model for condensation of vapor mixture of nitric acid and water affected volatilized ruthenium behavior in accident of evaporation to dryness by boiling of reprocessed high level liquid waste at fuel reprocessing facilities

    International Nuclear Information System (INIS)

    Yoshida, Kazuo

    2016-08-01

    An accident of evaporation to dryness by boiling of high level liquid waste is postulated as one of the severe accidents caused by the loss of cooling function at a fuel reprocessing plant. In this case, continuous vaporing of nitric acid and water leads to increase Ru volatilization in liquid waste temperature over 120degC at later boiling and dry out phases. It has been observed at the experiments with actual and synthetic liquid waste that some amount of Ru volatilizes and transfers into condensed nitric acid solution at those phases. The nitric acid and water vapor flowing from waste tank are expected to condense at compartments of actual facilities building. The volatilized Ru could transfer into condensed liquid. It is key issues for quantifying the amount of transferred Ru through the facility building to simulate these thermodynamic and chemical behaviors. An analytical model has been proposed in this report based on the condensation mechanisms of nitric acid and water in vapor-liquid equilibria. It has been also carried out for the proposed model being feasible to formulate the activity coefficients and to review the thermodynamic properties of nitric acid solution. Practicability of the proposed analytical model has been shown successfully through the feasibility study with simulation of an experiment result. (author)

  2. Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Anjali Kumari

    Full Text Available Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl ethylenediamine (TPEN and Zinc Sulfate (ZnSO4. Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death

  3. Regulation of intracellular pH in LLC-PK1 cells by Na+/H+ exchange.

    Science.gov (United States)

    Montrose, M H; Murer, H

    1986-01-01

    Suspensions of LLC-PK1 cells (a continuous epitheliod cell line with renal characteristics) are examined for mechanisms of intracellular pH regulation using the fluorescent probe BCECF. Initial experiments determine suitable calibration procedures for use of the BCECF fluorescent signal. They also determine that the cell suspension contains cells which (after 4 hr in suspension) have Na+ and K+ gradients comparable to those of cells in monolayer culture. The steady-state intracellular pH (7.05 +/- 0.01, n = 5) of cells which have recovered in (pH 7.4) Na+-containing medium is not affected over several minutes by addition of 100 microM amiloride or removal of extracellular Na+ (Na+o less than 1 mM). In contrast, when the cells recover from an acid load (caused by NH4 preincubation and removal), the recovery is largely Na+ dependent and is sensitive to 100 microM amiloride. These results suggest that with resting pH near neutrality, both Na+o/H+i and Na+i/H+o exchange reactions are functionally inactive (compared to cellular buffering capacity). In contrast, Na+o/H+i exchange is activated by an increased cellular acid load. This activation may be observed directly either as a stimulation of net H+ efflux or net Na+ influx with decreasing intracellular pH. The extrapolation of this latter data suggests a "set point" of Na+/H+ exchange of approximately pH 7.0, consistent with the observed resting intracellular pH of approximately 7.05.

  4. Nuclear fuel replacement device

    International Nuclear Information System (INIS)

    Ritz, W.C.; Robey, R.M.; Wett, J.F.

    1984-01-01

    A fuel handling arrangement for a liquid metal cooled nuclear reactor having a single rotating plug eccentric to the fuel core and a fuel handling machine radially movable along a slot in the plug with a transfer station disposed outside the fuel core but covered by the eccentric plug and within range of movement of said fuel handling machine to permit transfer of fuel assemblies between the core and the transfer station. (author)

  5. CANDU fuel performance

    International Nuclear Information System (INIS)

    Ivanoff, N.V.; Bazeley, E.G.; Hastings, I.J.

    1982-01-01

    CANDU fuel has operated successfully in Ontario Hydro's power reactors since 1962. In the 19 years of experience, about 99.9% of all fuel bundles have performed as designed. Most defects occurred before 1979 and subsequent changes in fuel design, fuel management, reactor control, and manufacturing quality control have reduced the current defect rate to near zero. Loss of power production due to defective fuel has been negligible. The outstanding performance continues while maintaining a low unit energy cost for fuel

  6. Fuels Combustion Research: Supercritical Fuel Pyrolysis

    National Research Council Canada - National Science Library

    Glassman, Irvin

    2001-01-01

    .... The focus during the subject period was directed to understanding the pyrolysis and combustion of endothermic fuels under subcritical conditions and the pyrolysis of these fuels under supercritical conditions...

  7. Fuels Combustion Research: Supercritical Fuel Pyrolysis

    National Research Council Canada - National Science Library

    Glassman, Irvin

    2000-01-01

    .... The focus during the subject period was directed to understanding the pyrolysis and combustion of endothermic fuels under subcritical conditions and the pyrolysis of these fuels under supercritical conditions...

  8. Progress in Chemical Kinetic Modeling for Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Westbrook, C K; Herbinet, O; Silke, E J

    2008-06-06

    Gasoline, diesel, and other alternative transportation fuels contain hundreds to thousands of compounds. It is currently not possible to represent all these compounds in detailed chemical kinetic models. Instead, these fuels are represented by surrogate fuel models which contain a limited number of representative compounds. We have been extending the list of compounds for detailed chemical models that are available for use in fuel surrogate models. Detailed models for components with larger and more complicated fuel molecular structures are now available. These advancements are allowing a more accurate representation of practical and alternative fuels. We have developed detailed chemical kinetic models for fuels with higher molecular weight fuel molecules such as n-hexadecane (C16). Also, we can consider more complicated fuel molecular structures like cyclic alkanes and aromatics that are found in practical fuels. For alternative fuels, the capability to model large biodiesel fuels that have ester structures is becoming available. These newly addressed cyclic and ester structures in fuels profoundly affect the reaction rate of the fuel predicted by the model. Finally, these surrogate fuel models contain large numbers of species and reactions and must be reduced for use in multi-dimensional models for spark-ignition, HCCI and diesel engines.

  9. Performance Evaluation of Metallic Dispersion Fuel for Advanced Research Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Ho Jin; Park, Jong Man; Kim, Chang Kyu; Chae, Hee Taek; Song, Kee Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Yeon Soo [Argonne National Laboratory, New York (United States)

    2007-07-01

    Uranium alloys with a high uranium density has been developed for high power research reactor fuel using low-enriched uranium (LEU). U-Mo alloys have been developed as candidate fuel material because of excellent irradiation behavior. Irradiation behavior of U-Mo/Al dispersion fuel has been investigated to develop high performance research reactor fuel as RERTR international research program. While plate-type and rod-type dispersion fuel elements are used for research reactors, HANARO uses rod-type dispersion fuel elements. PLATE code is developed by Argonne National Laboratory for the performance evaluation of plate-type dispersion fuel, but there is no counterpart for rod-type dispersion fuel. Especially, thermal conductivity of fuel meat decreases during the irradiation mainly because of interaction layer formation at the interface between the U-Mo fuel particle and Al matrix. The thermal conductivity of the interaction layer is not as high as the Al matrix. The growth of interaction layer is interactively affected by the temperature of fuel because it is associated with a diffusion reaction which is a thermally activated process. It is difficult to estimate the temperature profile during irradiation test due to the interdependency of fuel temperature and thermal conductivity changed by interaction layer growth. In this study, fuel performance of rod-type U-Mo/Al dispersion fuels during irradiation tests were estimated by considering the effect of interaction layer growth on the thermal conductivity of fuel meat.

  10. Performance Evaluation of Metallic Dispersion Fuel for Advanced Research Reactors

    International Nuclear Information System (INIS)

    Ryu, Ho Jin; Park, Jong Man; Kim, Chang Kyu; Chae, Hee Taek; Song, Kee Chan; Kim, Yeon Soo

    2007-01-01

    Uranium alloys with a high uranium density has been developed for high power research reactor fuel using low-enriched uranium (LEU). U-Mo alloys have been developed as candidate fuel material because of excellent irradiation behavior. Irradiation behavior of U-Mo/Al dispersion fuel has been investigated to develop high performance research reactor fuel as RERTR international research program. While plate-type and rod-type dispersion fuel elements are used for research reactors, HANARO uses rod-type dispersion fuel elements. PLATE code is developed by Argonne National Laboratory for the performance evaluation of plate-type dispersion fuel, but there is no counterpart for rod-type dispersion fuel. Especially, thermal conductivity of fuel meat decreases during the irradiation mainly because of interaction layer formation at the interface between the U-Mo fuel particle and Al matrix. The thermal conductivity of the interaction layer is not as high as the Al matrix. The growth of interaction layer is interactively affected by the temperature of fuel because it is associated with a diffusion reaction which is a thermally activated process. It is difficult to estimate the temperature profile during irradiation test due to the interdependency of fuel temperature and thermal conductivity changed by interaction layer growth. In this study, fuel performance of rod-type U-Mo/Al dispersion fuels during irradiation tests were estimated by considering the effect of interaction layer growth on the thermal conductivity of fuel meat

  11. GSPEL - Fuel Cell Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Fuel Cell Lab (FCL)Established to investigate, integrate, testand verifyperformance and technology readiness offuel cell systems and fuel reformers for use with...

  12. Fuel performance experience

    International Nuclear Information System (INIS)

    Sofer, G.A.

    1986-01-01

    The history of LWR fuel supply has been characterized by a wide range of design developments and fuel cycle cost improvements. Exxon Nuclear Company, Inc. has pursued an aggressive fuel research and development program aimed at improved fuel performance. Exxon Nuclear has introduced many design innovations which have improved fuel cycle economics and operating flexibility while fuel failures remain at very low levels. The removable upper tie plate feature of Exxon Nuclear assemblies has helped accelerate this development, enabling repeated inspections during successive plant outages. Also, this design feature has made it possible to repair damaged fuel assemblies during refueling outages, thereby minimizing the economic impact of fuel failure from all causes

  13. Catalytic Fuel Conversion Facility

    Data.gov (United States)

    Federal Laboratory Consortium — This facility enables unique catalysis research related to power and energy applications using military jet fuels and alternative fuels. It is equipped with research...

  14. HTGR fuel reprocessing technology

    International Nuclear Information System (INIS)

    Brooks, L.H.; Heath, C.A.; Shefcik, J.J.

    1976-01-01

    The following aspects of HTGR reprocessing technology are discussed: characteristics of HTGR fuels, criteria for a fuel reprocessing flowsheet; selection of a reference reprocessing flowsheet, and waste treatment

  15. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  16. The Effect of Curcumin on Intracellular pH (pHi), Membrane Hyperpolarization and Sperm Motility.

    Science.gov (United States)

    Naz, Rajesh K

    2014-04-01

    Curcumin has shown to affect sperm motility and function in vitro and fertility in vivo. The molecular mechanism(s) by which curcumin affects sperm motility has not been delineated. Since modulation of intracellular pH (pHi) and plasma membrane polarization is involved in sperm motility, the present study was conducted to investigate the effect of curcumin on these sperm (human and murine) parameters. The effect of curcumin on sperm forward motility was examined by counting percentages of forward moving sperm. The effect of curcumin on intracellular pH (pHi) was measured by the fluorescent pH indicator 2,7-bicarboxyethyl-5,6-carboxyfluorescein-acetoxymethyl ester (BCECF-AM). The effect of curcumin on plasma membrane polarization was examined using the fluorescence sensitive dye bis (1,3-dibarbituric acid)-trimethine oxanol [DiBAC4(3)]. Curcumin caused a concentration-dependent (ppHi) in both human and mouse sperm. Curcumin induced significant (ppHi and membrane polarization that affect sperm forward motility. These exciting findings will have application in deciphering the signal transduction pathway involved in sperm motility and function and in development of a novel non-steroidal contraceptive for infertility.

  17. Intracellular Trafficking Modulation by Ginsenoside Rg3 Inhibits Brucella abortus Uptake and Intracellular Survival within RAW 264.7 Cells.

    Science.gov (United States)

    Huy, Tran Xuan Ngoc; Reyes, Alisha Wehdnesday Bernardo; Hop, Huynh Tan; Arayan, Lauren Togonon; Min, WonGi; Lee, Hu Jang; Rhee, Man Hee; Chang, Hong Hee; Kim, Suk

    2017-03-28

    Ginsenoside Rg3, a saponin extracted from ginseng, has various pharmacological and biological activities; however, its effects against Brucella infection are still unclear. Herein, the inhibitory effects of ginsenoside Rg3 against intracellular parasitic Brucella infection were evaluated through bacterial infection, adherence assays, and LAMP-1 colocalization, as well as immunoblotting and FACS for detecting MAPK signaling proteins and F-actin polymerization, respectively. The internalization, intracellular growth, and adherence of Brucella abortus in Rg3-treated RAW 264.7 cells were significantly decreased compared with the Rg3-untreated control. Furthermore, an apparent reduction of F-actin content and intensity of F-actin fluorescence in Rg3-treated cells was observed compared with B. abortus -infected cells without treatment by flow cytometry analysis and confocal microscopy, respectively. In addition, treating cells with Rg3 decreased the phosphorylation of MAPK signaling proteins such as ERK 1/2 and p38 compared with untreated cells. Moreover, the colocalization of B. abortus -containing phagosomes with LAMP-1 was markedly increased in Rg3-treated cells. These findings suggest that ginsenoside Rg3 inhibits B. abortus infection in mammalian cells and can be used as an alternative approach in the treatment of brucellosis.

  18. Costing of spent nuclear fuel storage

    International Nuclear Information System (INIS)

    2009-01-01

    This report deals with economic analysis and cost estimation, based on exploration of relevant issues, including a survey of analytical tools for assessment and updated information on the market and financial issues associated with spent fuel storage. The development of new storage technologies and changes in some of the circumstances affecting the costs of spent fuel storage are also incorporated. This report aims to provide comprehensive information on spent fuel storage costs to engineers and nuclear professionals as well as other stakeholders in the nuclear industry. This report is meant to provide informative guidance on economic aspects involved in selecting a spent fuel storage system, including basic methods of analysis and cost data for project evaluation and comparison of storage options, together with financial and business aspects associated with spent fuel storage. After the review of technical options for spent fuel storage in Section 2, cost categories and components involved in the lifecycle of a storage facility are identified in Section 3 and factors affecting costs of spent fuel storage are then reviewed in the Section 4. Methods for cost estimation and analysis are introduced in Section 5, and other financial and business aspects associated with spent fuel storage are discussed in Section 6.

  19. Effect of aviation fuel type and fuel injection conditions on the spray characteristics of pressure swirl and hybrid air blast fuel injectors

    Science.gov (United States)

    Feddema, Rick

    Feddema, Rick T. M.S.M.E., Purdue University, December 2013. Effect of Aviation Fuel Type and Fuel Injection Conditions on the Spray Characteristics of Pressure Swirl and Hybrid Air Blast Fuel Injectors. Major Professor: Dr. Paul E. Sojka, School of Mechanical Engineering Spray performance of pressure swirl and hybrid air blast fuel injectors are central to combustion stability, combustor heat management, and pollutant formation in aviation gas turbine engines. Next generation aviation gas turbine engines will optimize spray atomization characteristics of the fuel injector in order to achieve engine efficiency and emissions requirements. Fuel injector spray atomization performance is affected by the type of fuel injector, fuel liquid properties, fuel injection pressure, fuel injection temperature, and ambient pressure. Performance of pressure swirl atomizer and hybrid air blast nozzle type fuel injectors are compared in this study. Aviation jet fuels, JP-8, Jet A, JP-5, and JP-10 and their effect on fuel injector performance is investigated. Fuel injector set conditions involving fuel injector pressure, fuel temperature and ambient pressure are varied in order to compare each fuel type. One objective of this thesis is to contribute spray patternation measurements to the body of existing drop size data in the literature. Fuel droplet size tends to increase with decreasing fuel injection pressure, decreasing fuel injection temperature and increasing ambient injection pressure. The differences between fuel types at particular set conditions occur due to differences in liquid properties between fuels. Liquid viscosity and surface tension are identified to be fuel-specific properties that affect the drop size of the fuel. An open aspect of current research that this paper addresses is how much the type of aviation jet fuel affects spray atomization characteristics. Conventional aviation fuel specifications are becoming more important with new interest in alternative

  20. Simulation of a 250 kW diesel fuel processor/PEM fuel cell system

    Science.gov (United States)

    Amphlett, J. C.; Mann, R. F.; Peppley, B. A.; Roberge, P. R.; Rodrigues, A.; Salvador, J. P.

    Polymer-electrolyte membrane (PEM) fuel cell systems offer a potential power source for utility and mobile applications. Practical fuel cell systems use fuel processors for the production of hydrogen-rich gas. Liquid fuels, such as diesel or other related fuels, are attractive options as feeds to a fuel processor. The generation of hydrogen gas for fuel cells, in most cases, becomes the crucial design issue with respect to weight and volume in these applications. Furthermore, these systems will require a gas clean-up system to insure that the fuel quality meets the demands of the cell anode. The endothermic nature of the reformer will have a significant affect on the overall system efficiency. The gas clean-up system may also significantly effect the overall heat balance. To optimize the performance of this integrated system, therefore, waste heat must be used effectively. Previously, we have concentrated on catalytic methanol-steam reforming. A model of a methanol steam reformer has been previously developed and has been used as the basis for a new, higher temperature model for liquid hydrocarbon fuels. Similarly, our fuel cell evaluation program previously led to the development of a steady-state electrochemical fuel cell model (SSEM). The hydrocarbon fuel processor model and the SSEM have now been incorporated in the development of a process simulation of a 250 kW diesel-fueled reformer/fuel cell system using a process simulator. The performance of this system has been investigated for a variety of operating conditions and a preliminary assessment of thermal integration issues has been carried out. This study demonstrates the application of a process simulation model as a design analysis tool for the development of a 250 kW fuel cell system.

  1. Mechanism of H. pylori intracellular entry: an in vitro study

    Directory of Open Access Journals (Sweden)

    Hui eLiu

    2012-03-01

    Full Text Available The majority of H. pylori reside on gastric epithelial cell surfaces and in the overlying mucus, but a small fraction of H. pylori enter host epithelial and immune cells. To explore the role of the nudA invasin in host cell entry, a ΔnudA deletion derivative of strain J99 was constructed and transformants were verified by PCR and by fluorescence in situ hybridization. AGS cells were inoculated with either wild type (WT strain J99 or its ΔnudA mutant to determine the fraction of bacteria that were bound to the cells and inside these cells using the gentamicin protection assay. We observed no significant difference between either the density of H. pylori bound to AGS cell membranes or the density of intracellular H. pylori. To further explore this finding, separate chambers of each culture were fixed in glutaraldehyde for transmission electron microscopy (TEM and immunogold TEM. This addition to the classical gentamicin assay demonstrated that there were significantly more intracellular, and fewer membrane-bound, H. pylori in WT-infected AGS cells than in ΔnudA allele infected cells. Thus, the sum of intracellular and membrane-bound H. pylori was similar in the two groups. Since no other similar TEM study has been performed, it is at present unknown whether our observations can be reproduced by others Taken together however, our observations suggest that the classical gentamicin protection assay is not sufficiently sensitive to analyze H. pylori cell entry and that the addition of TEM to the test demonstrate that nudA plays a role in H. pylori entry into AGS cells in vitro. In addition, deletion of the invasin gene appears to limit H. pylori to the AGS cell surface, where it may be partly protected against gentamicin. In contrast, this specific environment may render H. pylori more vulnerable to host defense and therapeutic intervention, and less prone to trigger normal immune, carcinogenic, and other developmental response pathways.

  2. Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging

    Directory of Open Access Journals (Sweden)

    Tamarand Lee Darling

    2017-09-01

    Full Text Available Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein–protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV and Ebolavirus (EBOV. Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X- for crosslinking. Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking

  3. LDL Receptors as Gateways for Intracellular Porphyrin Uptake

    International Nuclear Information System (INIS)

    Novick, S.; Laster, B.; Quastel, M.

    2004-01-01

    Boronated compounds are currently being studied for possible use in Boron Neutron Capture Therapy (BNCT). We found that one of these agents, BOPP (tetrakis-carborane-carboxylate, esters of 2,4-bis (a,b- dihydroxyethyl) deuteroporphyrin IX), could also be labeled with indium (In-BOPP) and, therefore, could also be used potentially to transport high Z atoms into tumor cell DNA for AET (Auger Electron Therapy). In order to assess the uptake of these agents into cells, the role of the LDL receptor in the intracellular accumulation of BOPP and In-BOPP was investigated. Pre-incubation of V-79 Chinese hamster cells in medium containing delipidized fetal bovine serum (FBS) markedly increased the subsequent uptake of intracellular boron transported by both BOPP and In-BOPP when compared with cells that had been pre-incubated with medium containing 10% normal FBS (lipidized). The increased uptake was characterized by elevated levels of receptor, and greater affinity was shown for both BOPP and In-BOPP, although less marked with the latter. Positive cooperativity was demonstrated by sigmoid saturation curves, Scatchard analysis and Hill plots. Increasing the amount of LDL in the incubation medium had a relatively small effect on the total accumulation of either indium or boron atoms inside the cell. Furthermore, chemical acetylation of LDL did not decrease the intracellular uptake of either boron or indium transported by BOPP or In-BOPP. It is thus concluded that BOPP and In-BOPP preferentially enter the cells directly by way of the LDL receptor and that only a small fraction of these molecules are transported into the cells indirectly using serum LDLs as their carriers. These data suggest a novel way of bringing greater amounts of boron and indium (and perhaps other agents) into tissues. Porphyrins can be used to transport different agents into tumor cells because they are tumor affinic molecules. Tumors express a higher number of LDL receptors than do most normal tissues

  4. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

    Science.gov (United States)

    Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

    2018-01-01

    Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Nuclear fuel production

    International Nuclear Information System (INIS)

    Randol, A.G.

    1985-01-01

    The production of new fuel for a power plant reactor and its disposition following discharge from the power plant is usually referred to as the ''nuclear fuel cycle.'' The processing of fuel is cyclic in nature since sometime during a power plant's operation old or ''depleted'' fuel must be removed and new fuel inserted. For light water reactors this step typically occurs once every 12-18 months. Since the time required for mining of the raw ore to recovery of reusable fuel materials from discharged materials can span up to 8 years, the management of fuel to assure continuous power plant operation requires simultaneous handling of various aspects of several fuel cycles, for example, material is being mined for fuel to be inserted in a power plant 2 years into the future at the same time fuel is being reprocessed from a discharge 5 years prior. Important aspects of each step in the fuel production process are discussed

  6. Cost of the external MTR-fuel cycle. (Uranium , reprocessing and related services)

    International Nuclear Information System (INIS)

    Mueller, H.; Gruber, G.

    1991-01-01

    This paper points out how the RERTR program has affected NUKEM's fuel supplies for MTRs and how the prices in the External MTR Fuel Cycle have developed during this period. In addition other potential fuel sources and services on the External MTR Fuel Cycle are given. (orig.)

  7. Fuel manufacturing and utilization

    International Nuclear Information System (INIS)

    2005-01-01

    The efficient utilisation of nuclear fuel requires manufacturing facilities capable of making advanced fuel types, with appropriate quality control. Once made, the use of such fuels requires a proper understanding of their behaviour in the reactor environment, so that safe operation for the design life can be achieved. The International Atomic Energy Agency supports Member States to improve in-pile fuel performance and management of materials; and to develop advanced fuel technologies for ensuring reliability and economic efficiency of the nuclear fuel cycle. It provides assistance to Member States to support fuel-manufacturing capability, including quality assurance techniques, optimization of manufacturing parameters and radiation protection. The IAEA supports the development fuel modelling expertise in Member States, covering both normal operation and postulated and severe accident conditions. It provides information and support for the operation of Nuclear Power Plant to ensure that the environment and water chemistry is appropriate for fuel operation. The IAEA supports fuel failure investigations, including equipment for failed fuel detection and for post-irradiation examination and inspection, as well as fuel repair, it provides information and support research into the basic properties of fuel materials, including UO 2 , MOX and zirconium alloys. It further offers guidance on the relationship with back-end requirement (interim storage, transport, reprocessing, disposal), fuel utilization and management, MOX fuels, alternative fuels and advanced fuel technology

  8. Instrumentation of fuel elements and fuel plates

    International Nuclear Information System (INIS)

    Durand, J.P.; Fanjas, Y.

    1993-01-01

    When controlling the behaviour of a reactor or developing a new fuel concept, it is of utmost interest to have the possibility to confirm the thermohydraulic calculations by actual measurements in the fuel elements or in the fuel plates. For years, CERCA has developed the technology and supplied its customers with fuel elements equipped with pressure or temperature measuring devices according to the requirements. Recent customer projects have led to the development of a new method to introduce thermocouples directly into the fuel plate meat instead of the cladding. The purpose of this paper is to review the various instrumentation possibilities available at CERCA. (author)

  9. Instrumentation of fuel elements and fuel plates

    International Nuclear Information System (INIS)

    Durand, J.P.; Fanjas, Y.

    1994-01-01

    When controlling the behaviour of a reactor or developing a new fuel concept, it is of utmost interest to have the possibility to confirm the thermohydraulic calculations by actual measurements in the fuel elements or in the fuel plates. For years, CERCA has developed the technology and supplied its customers with fuel elements equipped with pressure or temperature measuring devices according to the requirements. Recent customer projects have lead to the development of a new method to introduce thermocouples directly into the fuel plate meat instead of the cladding. The purpose of this paper is to review the various instrumentation possibilities available at CERCA. (author)

  10. Poking cells for efficient vector-free intracellular delivery

    Science.gov (United States)

    Wang, Ying; Yang, Yang; Yan, Li; Kwok, So Ying; Li, Wei; Wang, Zhigang; Zhu, Xiaoyue; Zhu, Guangyu; Zhang, Wenjun; Chen, Xianfeng; Shi, Peng

    2014-07-01

    Techniques for introducing foreign molecules and materials into living cells are of great value in cell biology research. A major barrier for intracellular delivery is to cross the cell membrane. Here we demonstrate a novel platform utilizing diamond nanoneedle arrays to facilitate efficient vector-free cytosolic delivery. Using our technique, cellular membrane is deformed by an array of nanoneedles with a force on the order of a few nanonewtons. We show that this technique is applicable to deliver a broad range of molecules and materials into different types of cells, including primary neurons in adherent culture. Especially, for delivering plasmid DNAs into neurons, our technique produces at least eightfold improvement (~45% versus ~1-5%) in transfection efficiency with a dramatically shorter experimental protocol, when compared with the commonly used lipofection approach. It is anticipated that our technique will greatly benefit basic research in cell biology and also a wide variety of clinical applications.

  11. Subcellular site and nature of intracellular cadmium in plants

    International Nuclear Information System (INIS)

    Wagner, G.J.

    1979-01-01

    The mechanisms underlying heavy metal accumulation, toxicity and tolerance in higher plants are poorly understood. Since subcellular processes are undoubtedly involved in all these phenomena, it is of interest to study the extent of, subcellular site of and nature of intracellularly accumulated cadmium in higher plants. Whole plants supplied 109 CdCl 2 or 112 CdSO 4 accumulated Cd into roots and aerial tissues. Preparation of protoplasts from aerial tissue followed by subcellular fractionation of the protoplasts to obtain intact vacuoles, chloroplasts and cytosol revealed the presence of Cd in the cytosol but not in vacuoles or chloroplasts. Particulate materials containing other cell components were also labeled. Of the 109 Cd supplied to plants, 2 to 10% was recovered in both cytosol preparations and in particulate materials. Cytosol contained proteinaceous--Cd complexes, free metal and low molecular weight Cd complexes. Labeling of protoplasts gave similar results. No evidence was obtained for the production of volatile Cd complexes in tobacco

  12. The intracellular cholesterol landscape: dynamic integrator of the immune response

    Science.gov (United States)

    Fessler, Michael B.

    2016-01-01

    Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, ‘professional’ role for sterols and oxysterols in macrophage and T cell immunity. Host defense may have been the original selection pressure behind the development of mechanisms for intracellular cholesterol homeostasis. Functional coupling between sterol metabolism and immunity has fundamental implications for health and disease. PMID:27692616

  13. Extraction of intracellular protein from Glaciozyma antarctica for proteomics analysis

    Science.gov (United States)

    Faizura, S. Nor; Farahayu, K.; Faizal, A. B. Mohd; Asmahani, A. A. S.; Amir, R.; Nazalan, N.; Diba, A. B. Farah; Muhammad, M. Nor; Munir, A. M. Abdul

    2013-11-01

    Two preparation methods of crude extracts of psychrophilic yeast Glaciozyma antarctica were compared in order to obtain a good recovery of intracellular proteins. Extraction with mechanical procedures using sonication was found to be more effective for obtaining good yield compare to alkaline treatment method. The procedure is simple, rapid, and produce better yield. A total of 52 proteins were identified by combining both extraction methods. Most of the proteins identified in this study involves in the metabolic process including glycolysis pathway, pentose phosphate pathway, pyruyate decarboxylation and also urea cyle. Several chaperons were identified including probable cpr1-cyclophilin (peptidylprolyl isomerase), macrolide-binding protein fkbp12 and heat shock proteins which were postulate to accelerate proper protein folding. Characteristic of the fundamental cellular processes inferred from the expressed-proteome highlight the evolutionary and functional complexity existing in this domain of life.

  14. Intracellular pH in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Hug, M; Greger, R

    1997-01-01

    In order to study the mechanism of H+ and HCO3- transport in a HCO3- secreting epithelium, pancreatic ducts, we have measured the intracellular pH (pHi) in this tissue using the pH sensitive probe BCECF. We found that exposures of ducts to solutions containing acetate/acetic acid or NH4+/NH3...... buffers (20 mmol/l) led to pHi changes in accordance with entry of lipid-soluble forms of the buffers, followed by back-regulation of pHi by duct cells. In another type of experiment, changes in extracellular pH of solutions containing HEPES or HCO3-/CO2 buffers led to significant changes in pHi that did....... Under some conditions, these exchangers can be invoked to regulate cell pH....

  15. Intracellular Signaling Mediators in the Circulatory and Ventilatory Systems

    CERN Document Server

    Thiriet, Marc

    2013-01-01

    The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors.  Activation of...

  16. Intracellular mediators of potassium-induced aldosterone secretion

    International Nuclear Information System (INIS)

    Ganguly, A.; Chiou, S.; Davis, J.S.

    1990-01-01

    We have investigated the intracellular messengers of potassium in eliciting aldosterone secretion in calf adrenal glomerulosa cells since there were unresolved issues relating to the role of phosphoinositides, cAMP and protein kinases. We observed no evidence of hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) in 3 H-inositol labeled alf adrenal cells or increase of cAMP in response to potassium. Addition of calcium channel blocker, nitrendipine after stimulating adrenal glomerulosa cells with potassium, markedly inhibited aldosterone secretion. A calmodulin inhibitor (W-7) produced greater reduction of aldosterone secretion than an inhibitor of protein kinase C (H-7). These results suggest that a rise in cytosolic free calcium concentration through voltage-dependent calcium channel and calmodulin are the critical determinants of aldosterone secretion stimulated by potassium

  17. ATPase and GTPase Tangos Drive Intracellular Protein Transport.

    Science.gov (United States)

    Shan, Shu-Ou

    2016-12-01

    The GTPase superfamily of proteins provides molecular switches to regulate numerous cellular processes. The 'GTPase switch' paradigm, in which external regulatory factors control the switch of a GTPase between 'on' and 'off' states, has been used to interpret the regulatory mechanism of many GTPases. However, recent work unveiled a class of nucleotide hydrolases that do not adhere to this classical paradigm. Instead, they use nucleotide-dependent dimerization cycles to regulate key cellular processes. In this review article, recent studies of dimeric GTPases and ATPases involved in intracellular protein targeting are summarized. It is suggested that these proteins can use the conformational plasticity at their dimer interface to generate multiple points of regulation, thereby providing the driving force and spatiotemporal coordination of complex cellular pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Evaluating Nanoparticle Sensor Design for Intracellular pH Measurements

    DEFF Research Database (Denmark)

    Benjaminsen, Rikke Vicki; Sun, Honghao; Henriksen, Jonas Rosager

    2011-01-01

    Particle-based nanosensors have over the last decade been designed for optical fluorescent-based ratiometric measurements of pH in living cells. However, quantitative and time-resolved intracellular measurements of pH in endosomes and lysosomes using particle nanosensors is challenging...... and there is a need to improve measurement methodology. In the present paper, we have successfully carried out time resolved pH measurements in endosomes and lyosomes in living cells using nanoparticle sensors and show the importance of sensor choice for successful quantification. We have studied two nanoparticle...... quantification of pH is an unfortunate result when measuring pH too close to the limit of the sensitive range of the sensors. Triple-labeled nanosensors with a pH measurement range of 3.2-7.0, which was synthesized by adding two pH-sensitive fluorophores with different pKa to each sensor, seem to be a solution...

  19. Intracellular Events and Cell Fate in Filovirus Infection

    Directory of Open Access Journals (Sweden)

    Elena Ryabchikova

    2011-08-01

    Full Text Available Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.

  20. Intracellular Transport and Kinesin Superfamily Proteins: Structure, Function and Dynamics

    Science.gov (United States)

    Hirokawa, N.; Takemura, R.

    Using various molecular cell biological and molecular genetic approaches, we identified kinesin superfamily proteins (KIFs) and characterized their significant functions in intracellular transport, which is fundamental for cellular morphogenesis, functioning, and survival. We showed that KIFs not only transport various membranous organelles, proteins complexes and mRNAs fundamental for cellular functions but also play significant roles in higher brain functions such as memory and learning, determination of important developmental processes such as left-right asymmetry formation and brain wiring. We also elucidated that KIFs recognize and bind to their specific cargoes using scaffolding or adaptor protein complexes. Concerning the mechanism of motility, we discovered the simplest unique monomeric motor KIF1A and determined by molecular biophysics, cryoelectron microscopy and X-ray crystallography that KIF1A can move on a microtubule processively as a monomer by biased Brownian motion and by hydolyzing ATP.

  1. Purification and characterization of an intracellular peroxidase from Streptomyces cyaneus.

    OpenAIRE

    Mliki, A; Zimmermann, W

    1992-01-01

    An intracellular peroxidase (EC 1.11.1.7) from Streptomyces cyaneus was purified to homogeneity. The enzyme had a molecular weight of 185,000 and was composed of two subunits of equal size. It had an isoelectric point of 6.1. The enzyme had a peroxidase activity toward o-dianisidine with a Km of 17.8 microM and a pH optimum of 5.0. It also showed catalase activity with a Km of 2.07 mM H2O2 and a pH optimum of 8.0. The purified enzyme did not catalyze C alpha-C beta bond cleavage of 1,3-dihydr...

  2. Measuring intracellular redox conditions using GFP-based sensors

    DEFF Research Database (Denmark)

    Björnberg, Olof; Ostergaard, Henrik; Winther, Jakob R

    2006-01-01

    Recent years have seen the development of methods for analyzing the redox conditions in specific compartments in living cells. These methods are based on genetically encoded sensors comprising variants of Green Fluorescent Protein in which vicinal cysteine residues have been introduced at solvent......-exposed positions. Several mutant forms have been identified in which formation of a disulfide bond between these cysteine residues results in changes of their fluorescence properties. The redox sensors have been characterized biochemically and found to behave differently, both spectroscopically and in terms...... of redox properties. As genetically encoded sensors they can be expressed in living cells and used for analysis of intracellular redox conditions; however, which parameters are measured depends on how the sensors interact with various cellular redox components. Results of both biochemical and cell...

  3. 2011 Rita Schaffer lecture: nanoparticles for intracellular nucleic acid delivery.

    Science.gov (United States)

    Green, Jordan J

    2012-07-01

    Nanoparticles are a promising technology for delivery of new types of therapeutics. A polymer library approach has allowed engineering of polymeric particles that are particularly effective for the delivery of DNA and siRNA to human cells. Certain chemical structural motifs, degradable linkages, hydrophobicity, and biophysical properties are key for successful intracellular delivery. Small differences to biomaterial structure, and especially the type of degradable linkage in the polymers, can be critical for successful delivery of siRNA vs. DNA. Furthermore, subtle changes to biomaterial structure can facilitate cell-type gene delivery specificity between human brain cancer cells and healthy cells as well as between human retinal endothelial cells and epithelial cells. These polymeric nanoparticles are effective for nucleic acid delivery in a broad range of human cell types and have applications to regenerative medicine, ophthalmology, and cancer among many other biomedical research areas.

  4. Control of intracellular heme levels: Heme transporters and Heme oxygenases

    Science.gov (United States)

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number of transporters of heme and heme synthesis intermediates have been described. Here we review aspects of heme metabolism and discuss our current understanding of heme transporters, with emphasis on the function of the cell-surface heme exporter, FLVCR. Knockdown of Flvcr in mice leads to both defective erythropoiesis and disturbed systemic iron homeostasis, underscoring the critical role of heme transporters in mammalian physiology. PMID:21238504

  5. An active matter analysis of intracellular Active Transport

    Science.gov (United States)

    Wang, Bo; Chen, Kejia; Bae, Sung Chul; Granick, Steve

    2012-02-01

    Tens of thousands of fluorescence-based trajectories at nm resolution have been analyzed, regarding active transport along microtubules in living cells. The following picture emerges. Directed motion to pre-determined locations is certainly an attractive idea, but cannot be pre-programmed as to do so would sacrifice adaptability. The polarity of microtubules is inadequate to identify these directions in cells, and no other mechanism is currently known. We conclude that molecular motors carry cargo through disordered intracellular microtubule networks in a statistical way, with loud cellular ``noise'' both in directionality and speed. Programmed random walks describe how local 1D active transport traverses crowded cellular space efficiently, rapidly, minimizing the energy waste that would result from redundant activity. The mechanism of statistical regulation is not yet understood, however.

  6. Variety in intracellular diffusion during the cell cycle

    DEFF Research Database (Denmark)

    Selhuber-Unkel, C.; Yde, P.; Berg-Sørensen, Kirstine

    2009-01-01

    During the cell cycle, the organization of the cytoskeletal network undergoes dramatic changes. In order to reveal possible changes of the viscoelastic properties in the intracellular space during the cell cycle we investigated the diffusion of endogenous lipid granules within the fission yeast...... Schizosaccharomyces Pombe using optical tweezers. The cell cycle was divided into interphase and mitotic cell division, and the mitotic cell division was further subdivided in its stages. During all stages of the cell cycle, the granules predominantly underwent subdiffusive motion, characterized by an exponent...... a that is also linked to the viscoelastic moduli of the cytoplasm. The exponent a was significantly smaller during interphase than during any stage of the mitotic cell division, signifying that the cytoplasm was more elastic during interphase than during division. We found no significant differences...

  7. Vector-free intracellular delivery by reversible permeabilization.

    Directory of Open Access Journals (Sweden)

    Shirley O'Dea

    Full Text Available Despite advances in intracellular delivery technologies, efficient methods are still required that are vector-free, can address a wide range of cargo types and can be applied to cells that are difficult to transfect whilst maintaining cell viability. We have developed a novel vector-free method that uses reversible permeabilization to achieve rapid intracellular delivery of cargos with varying composition, properties and size. A permeabilizing delivery solution was developed that contains a low level of ethanol as the permeabilizing agent. Reversal of cell permeabilization is achieved by temporally and volumetrically controlling the contact of the target cells with this solution. Cells are seeded in conventional multi-well plates. Following removal of the supernatant, the cargo is mixed with the delivery solution and applied directly to the cells using an atomizer. After a short incubation period, permeabilization is halted by incubating the cells in a phosphate buffer saline solution that dilutes the ethanol and is non-toxic to the permeabilized cells. Normal culture medium is then added. The procedure lasts less than 5 min. With this method, proteins, mRNA, plasmid DNA and other molecules have been delivered to a variety of cell types, including primary cells, with low toxicity and cargo functionality has been confirmed in proof-of-principle studies. Co-delivery of different cargo types has also been demonstrated. Importantly, delivery occurs by diffusion directly into the cytoplasm in an endocytic-independent manner. Unlike some other vector-free methods, adherent cells are addressed in situ without the need for detachment from their substratum. The method has also been adapted to address suspension cells. This delivery method is gentle yet highly reproducible, compatible with high throughput and automated cell-based assays and has the potential to enable a broad range of research, drug discovery and clinical applications.

  8. Bioreducible Lipid-like Nanoparticles for Intracellular Protein Delivery

    Science.gov (United States)

    Arellano, Carlos Luis

    Protein-based therapy is one of the most direct ways to manipulate cell function and treat human disease. Although protein therapeutics has made its way to clinical practice, with five of the top fifteen global pharmaceuticals being peptide or protein-based drugs, one common limitation is that the effects of protein therapy are only achieved through the targeting of cell surface receptors and intracellular domains. Due to the impermeability of the cell membrane to most foreign materials, entire classes of potentially therapeutic proteins cannot thoroughly be studied without a safe and efficient method of transporting proteins into the cytosol. We report the use of a combinatorially-designed bioreducible lipid-like material (termed "lipidoid") - based protein delivery platform for the transfection of human cancer cell lines. Lipidoid nanoparticles are synthesized through a thin film dispersion method. The degradation of the bioreducible nanoparticles was observed when exposed to glutathione, a highly reductive compound present in the cytosol. We demonstrate that the nanoparticles are capable of transfecting a dose-dependent concentration of our model protein, beta-galactosidase into HeLa cells. Furthermore, formulations of the lipidoid containing the cytotoxic proteins saporin and RNase-A are both capable of inhibiting tumor cell proliferation as observed in in vitro treatment of different human cancer cell lines. There was no observed loss in protein activity after lyophilization and long--term storage, indicating the potential of pre-clinical applications. Overall, we demonstrate an effective approach to protein formulation and intracellular delivery. We believe that our formulations will lead to the study of a whole class of previously untapped therapeutics that may generate new solutions for previously untreatable diseases.

  9. Loperamide Restricts Intracellular Growth of Mycobacterium tuberculosis in Lung Macrophages.

    Science.gov (United States)

    Juárez, Esmeralda; Carranza, Claudia; Sánchez, Guadalupe; González, Mitzi; Chávez, Jaime; Sarabia, Carmen; Torres, Martha; Sada, Eduardo

    2016-12-01

    New approaches for improving tuberculosis (TB) control using adjunct host-directed cellular and repurposed drug therapies are needed. Autophagy plays a crucial role in the response to TB, and a variety of autophagy-inducing drugs that are currently available for various medical conditions may serve as an adjunct treatment in pulmonary TB. Here, we evaluated the potential of loperamide, carbamazepine, valproic acid, verapamil, and rapamycin to enhance the antimicrobial immune response to Mycobacterium tuberculosis (Mtb). Human monocyte-derived macrophages (MDMs) and murine alveolar cells (MACs) were infected with Mtb and treated with loperamide, carbamazepine, valproic acid, verapamil, and rapamycin in vitro. Balb/c mice were intraperitoneally administered loperamide, valproic acid, and verapamil, and MACs were infected in vitro with Mtb. The induction of autophagy, the containment of Mtb within autophagosomes and the intracellular Mtb burden were determined. Autophagy was induced by all of the drugs in human and mouse macrophages, and loperamide significantly increased the colocalization of microtubule-associated protein 1 light chain 3 with Mtb in MDMs. Carbamazepine, loperamide, and valproic acid induced microtubule-associated protein 1 light chain 3 and autophagy related 16- like protein 1 gene expression in MDMs and in MACs. Loperamide also induced a reduction in TNF-α production. Loperamide and verapamil induced autophagy, which was associated with a significant reduction in the intracellular growth of Mtb in MACs and alveolar macrophages. The intraperitoneal administration of loperamide and valproic acid induced autophagy in freshly isolated MACs. The antimycobacterial activity in MACs was higher after loperamide treatment and was associated with the degradation of p62. In conclusion, loperamide shows potential as an adjunctive therapy for the treatment of TB.

  10. Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes.

    Science.gov (United States)

    Mato, Susana; Victoria Sánchez-Gómez, María; Matute, Carlos

    2010-11-01

    Heavy marijuana use has been linked to white matter histological alterations. However, the impact of cannabis constituents on oligodendroglial pathophysiology remains poorly understood. Here, we investigated the in vitro effects of cannabidiol, the main nonpsychoactive marijuana component, on oligodendrocytes. Exposure to cannabidiol induced an intracellular Ca(2+) rise in optic nerve oligodendrocytes that was not primarily mediated by entry from the extracellular space, nor by interactions with ryanodine or IP(3) receptors. Application of the mitochondrial protonophore carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP; 1 μM) completely prevented subsequent cannabidiol-induced Ca(2+) responses. Conversely, the increase in cytosolic Ca(2+) levels elicited by FCCP was reduced after previous exposure to cannabidiol, further suggesting that the mitochondria acts as the source of cannabidiol-evoked Ca(2+) rise in oligodendrocytes. n addition, brief exposure to cannabidiol (100 nM-10 μM) led to a concentration-dependent decrease of oligodendroglial viability that was not prevented by antagonists of CB(1), CB(2), vanilloid, A(2A) or PPARγ receptors, but was instead reduced in the absence of extracellular Ca(2+). The oligodendrotoxic effect of cannabidiol was partially blocked by inhibitors of caspase-3, -8 and -9, PARP-1 and calpains, suggesting the activation of caspase-dependent and -independent death pathways. Cannabidiol also elicited a concentration-dependent alteration of mitochondrial membrane potential, and an increase in reactive oxygen species (ROS) that was reduced in the absence of extracellular Ca(2+). Finally, cannabidiol-induced cytotoxicity was partially prevented by the ROS scavenger trolox. Together, these results suggest that cannabidiol causes intracellular Ca(2+) dysregulation which can lead to oligodendrocytes demise.

  11. Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2007-11-01

    Full Text Available Abstract Background Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132 in neuroblastoma cells and primary cortical neurons. Results Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1 and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2 and cyclo-oxygenase-1 (COX-1, enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. Conclusion As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.

  12. Alternate-Fueled Combustor-Sector Performance

    Science.gov (United States)

    Thomas, Anna E.; Saxena, Nikita T.; Shouse, Dale T.; Neuroth, Craig; Hendricks, Robert C.; Lynch, Amy; Frayne, Charles W.; Stutrud, Jeffrey S.; Corporan, Edwin; Hankins, Terry

    2013-01-01

    In order to realize alternative fueling for military and commercial use, the industry has set forth guidelines that must be met by each fuel. These aviation fueling requirements are outlined in MIL-DTL-83133F(2008) or ASTM D 7566 Annex (2011) standards, and are classified as "drop-in" fuel replacements. This report provides combustor performance data for synthetic-paraffinic-kerosene- (SPK-) type (Fischer-Tropsch (FT)) fuel and blends with JP-8+100, relative to JP-8+100 as baseline fueling. Data were taken at various nominal inlet conditions: 75 psia (0.52 MPa) at 500 degF (533 K), 125 psia (0.86 MPa) at 625 degF (603 K), 175 psia (1.21 MPa) at 725 degF (658 K), and 225 psia (1.55 MPa) at 790 degF (694 K). Combustor performance analysis assessments were made for the change in flame temperatures, combustor efficiency, wall temperatures, and exhaust plane temperatures at 3, 4, and 5 percent combustor pressure drop (DP) for fuel:air ratios (F/A) ranging from 0.010 to 0.025. Significant general trends show lower liner temperatures and higher flame and combustor outlet temperatures with increases in FT fueling relative to JP-8+100 fueling. The latter affects both turbine efficiency and blade and vane lives.

  13. Nuclear magnetic resonance studies of intracellular ions in perfused from heart

    International Nuclear Information System (INIS)

    Burnstein, D.; Fossel, E.T.

    1987-01-01

    Intracellular sodium, potassium, and lithium were observed in a perfused frog heart by nuclear magnetic resonance (NMR) spectroscopy. A perfusate buffer containing the shift reagent, dysprosium tripolyphosphate, was used in combination with mathematical filtering or presaturation of the extracellular resonance to separate the intra- and extracellular sodium NMR signals. Addition of 10 μM ouabain to the perfusate, perfusion with a zero potassium, low-calcium buffer, and replacement of 66% of the perfusate sodium with lithium resulted in changes in the intracellular sodium levels. An increase of 45% in the intracellular sodium was observed when changing the pacing rate from 0 to 60 beats/min (with proportional changes for intermediate pacing rates). The ratio of intracellular potassium to sodium concentration was determined to be 2.3 by NMR, indicating that a substantial amount of the intracellular potassium is undetectable with these NMR method. In addition, intracellular lithium was observed during perfusion with a lithium-containing perfusate

  14. The Role of Membrane Curvature in Nanoscale Topography-Induced Intracellular Signaling.

    Science.gov (United States)

    Lou, Hsin-Ya; Zhao, Wenting; Zeng, Yongpeng; Cui, Bianxiao

    2018-05-15

    Over the past decade, there has been growing interest in developing biosensors and devices with nanoscale and vertical topography. Vertical nanostructures induce spontaneous cell engulfment, which enhances the cell-probe coupling efficiency and the sensitivity of biosensors. Although local membranes in contact with the nanostructures are found to be fully fluidic for lipid and membrane protein diffusions, cells appear to actively sense and respond to the surface topography presented by vertical nanostructures. For future development of biodevices, it is important to understand how cells interact with these nanostructures and how their presence modulates cellular function and activities. How cells recognize nanoscale surface topography has been an area of active research for two decades before the recent biosensor works. Extensive studies show that surface topographies in the range of tens to hundreds of nanometers can significantly affect cell functions, behaviors, and ultimately the cell fate. For example, titanium implants having rough surfaces are better for osteoblast attachment and host-implant integration than those with smooth surfaces. At the cellular level, nanoscale surface topography has been shown by a large number of studies to modulate cell attachment, activity, and differentiation. However, a mechanistic understanding of how cells interact and respond to nanoscale topographic features is still lacking. In this Account, we focus on some recent studies that support a new mechanism that local membrane curvature induced by nanoscale topography directly acts as a biochemical signal to induce intracellular signaling, which we refer to as the curvature hypothesis. The curvature hypothesis proposes that some intracellular proteins can recognize membrane curvatures of a certain range at the cell-to-material interface. These proteins then recruit and activate downstream components to modulate cell signaling and behavior. We discuss current technologies

  15. HTGR fuel and fuel cycle technology

    International Nuclear Information System (INIS)

    Lotts, A.L.; Coobs, J.H.

    1976-08-01

    The status of fuel and fuel cycle technology for high-temperature gas-cooled reactors (HTGRs) is reviewed. The all-ceramic core of the HTGRs permits high temperatures compared with other reactors. Core outlet temperatures of 740 0 C are now available for the steam cycle. For advanced HTGRs such as are required for direct-cycle power generation and for high-temperature process heat, coolant temperatures as high as 1000 0 C may be expected. The paper discusses the variations of HTGR fuel designs that meet the performance requirements and the requirements of the isotopes to be used in the fuel cycle. Also discussed are the fuel cycle possibilities, which include the low-enrichment cycle, the Th- 233 U cycle, and plutonium utilization in either cycle. The status of fuel and fuel cycle development is summarized

  16. Fuel lattice design using heuristics and new strategies

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz S, J. J.; Castillo M, J. A.; Torres V, M.; Perusquia del Cueto, R. [ININ, Carretera Mexico-Toluca s/n, Ocoyoacac 52750, Estado de Mexico (Mexico); Pelta, D. A. [ETS Ingenieria Informatica y Telecomunicaciones, Universidad de Granada, Daniel Saucedo Aranda s/n, 18071 Granada (Spain); Campos S, Y., E-mail: juanjose.ortiz@inin.gob.m [IPN, Escuela Superior de Fisica y Matematicas, Unidad Profesional Adolfo Lopez Mateos, Edif. 9, 07738 Mexico D. F. (Mexico)

    2010-10-15

    This work show some results of the fuel lattice design in BWRs when some allocation pin rod rules are not taking into account. Heuristics techniques like Path Re linking and Greedy to design fuel lattices were used. The scope of this work is to search about how do classical rules in design fuel lattices affect the heuristics techniques results and the fuel lattice quality. The fuel lattices quality is measured by Power Peaking Factor and Infinite Multiplication Factor at the beginning of the fuel lattice life. CASMO-4 code to calculate these parameters was used. The analyzed rules are the following: pin rods with lowest uranium enrichment are only allocated in the fuel lattice corner, and pin rods with gadolinium cannot allocated in the fuel lattice edge. Fuel lattices with and without gadolinium in the main diagonal were studied. Some fuel lattices were simulated in an equilibrium cycle fuel reload, using Simulate-3 to verify their performance. So, the effective multiplication factor and thermal limits can be verified. The obtained results show a good performance in some fuel lattices designed, even thought, the knowing rules were not implemented. A fuel lattice performance and fuel lattice design characteristics analysis was made. To the realized tests, a dell workstation was used, under Li nux platform. (Author)

  17. Fuel lattice design using heuristics and new strategies

    International Nuclear Information System (INIS)

    Ortiz S, J. J.; Castillo M, J. A.; Torres V, M.; Perusquia del Cueto, R.; Pelta, D. A.; Campos S, Y.

    2010-10-01

    This work show some results of the fuel lattice design in BWRs when some allocation pin rod rules are not taking into account. Heuristics techniques like Path Re linking and Greedy to design fuel lattices were used. The scope of this work is to search about how do classical rules in design fuel lattices affect the heuristics techniques results and the fuel lattice quality. The fuel lattices quality is measured by Power Peaking Factor and Infinite Multiplication Factor at the beginning of the fuel lattice life. CASMO-4 code to calculate these parameters was used. The analyzed rules are the following: pin rods with lowest uranium enrichment are only allocated in the fuel lattice corner, and pin rods with gadolinium cannot allocated in the fuel lattice edge. Fuel lattices with and without gadolinium in the main diagonal were studied. Some fuel lattices were simulated in an equilibrium cycle fuel reload, using Simulate-3 to verify their performance. So, the effective multiplication factor and thermal limits can be verified. The obtained results show a good performance in some fuel lattices designed, even thought, the knowing rules were not implemented. A fuel lattice performance and fuel lattice design characteristics analysis was made. To the realized tests, a dell workstation was used, under Li nux platform. (Author)

  18. A Thapsigargin-Resistant Intracellular Calcium Sequestering Compartment in Rat Brain

    Science.gov (United States)

    2000-03-31

    have a major impact on neuronal intracellular signaling. Most of the ER in neurons and glia appears to accumulate calcium by energy driven ion pumps...secretion of exocrine, endocrine, and neurocrine products, regulation of glycogenolysis and gluconeogenesis , intracellular transport, secretion of fluids...the RyRs [140]. Furthermore, the intracellular expression of these receptor-channels in neuronal ER is also reciprocal with RyRs located primarily in

  19. HTGR fuel and fuel cycle technology

    International Nuclear Information System (INIS)

    Lotts, A.L.; Homan, F.J.; Balthesen, E.; Turner, R.F.

    1977-01-01

    Significant advances have occurred in the development of HTGR fuel and fuel cycle. These accomplishments permit a wide choice of fuel designs, reactor concepts, and fuel cycles. Fuels capable of providing helium outlet temperatures of 750 0 C are available, and fuels capable of 1000 0 C outlet temperatures may be expected from extension of present technology. Fuels have been developed for two basic HTGR designs, one using a spherical (pebble bed) element and the other a prismatic element. Within each concept a number of variations of geometry, fuel composition, and structural materials are permitted. Potential fuel cycles include both low-enriched and high-enriched Th- 235 U, recycle Th- 233 U, and Th-Pu or U-Pu cycles. This flexibility offered by the HTGR is of great practical benefit considering the rapidly changing economics of power production. The inflation of ore prices has increased optimum conversion ratios, and increased the necessity of fuel recycle at an early date. Fuel element makeup is very similar for prismatic and spherical designs. Both use spherical fissile and fertile particles coated with combinations of pyrolytic carbon and silicon carbide. Both use carbonaceous binder materials, and graphite as the structural material. Weak-acid resin (WAR) UO 2 -UC 2 fissile fuels and sol-gel-derived ThO 2 fertile fuels have been selected for the Th- 233 U cycle in the prismatic design. Sol-gel-derived UO 2 UC 2 is the reference fissile fuel for the low-enriched pebble bed design. Both the United States and Federal Republic of Germany are developing technology for fuel cycle operations including fabrication, reprocessing, refabrication, and waste handling. Feasibility of basic processes has been established and designs developed for full-scale equipment. Fuel and fuel cycle technology provide the basis for a broad range of applications of the HTGR. Extension of the fuels to higher operating temperatures and development and commercial demonstration of fuel

  20. Impact of future fuel properties on aircraft engines and fuel systems

    Science.gov (United States)

    Rudey, R. A.; Grobman, J. S.

    1978-01-01

    From current projections of the availability of high-quality petroleum crude oils, it is becoming increasingly apparent that the specifications for hydrocarbon jet fuels may have to be modified. The problems that are most likely to be encountered as a result of these modifications relate to engine performance, component durability and maintenance, and aircraft fuel-system performance. The effect on engine performance will be associated with changes in specific fuel consumption, ignition at relight limits, at exhaust emissions. Durability and maintenance will be affected by increases in combustor liner temperatures, carbon deposition, gum formation in fuel nozzles, and erosion and corrosion of turbine blades and vanes. Aircraft fuel-system performance will be affected by increased deposits in fuel-system heat exchangers and changes in the pumpability and flowability of the fuel. The severity of the potential problems is described in terms of the fuel characteristics most likely to change in the future. Recent data that evaluate the ability of current-technology aircraft to accept fuel specification changes are presented, and selected technological advances that can reduce the severity of the problems are described and discussed.