Binding Mode and Induced Fit Predictions for Prospective Computational Drug Design.

Science.gov (United States)

Grebner, Christoph; Iegre, Jessica; Ulander, Johan; Edman, Karl; Hogner, Anders; Tyrchan, Christian

2016-04-25

Computer-aided drug design plays an important role in medicinal chemistry to obtain insights into molecular mechanisms and to prioritize design strategies. Although significant improvement has been made in structure based design, it still remains a key challenge to accurately model and predict induced fit mechanisms. Most of the current available techniques either do not provide sufficient protein conformational sampling or are too computationally demanding to fit an industrial setting. The current study presents a systematic and exhaustive investigation of predicting binding modes for a range of systems using PELE (Protein Energy Landscape Exploration), an efficient and fast protein-ligand sampling algorithm. The systems analyzed (cytochrome P, kinase, protease, and nuclear hormone receptor) exhibit different complexities of ligand induced fit mechanisms and protein dynamics. The results are compared with results from classical molecular dynamics simulations and (induced fit) docking. This study shows that ligand induced side chain rearrangements and smaller to medium backbone movements are captured well in PELE. Large secondary structure rearrangements, however, remain challenging for all employed techniques. Relevant binding modes (ligand heavy atom RMSD PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles.

Induced prismatic effects due to poorly fitting spectacle frames

Directory of Open Access Journals (Sweden)

V. R. Moodley

2011-12-01

toms were reported by 50% of subjects experiencing base-out, 0% base-in and 47% vertical induced prismatic effects.  However, no correlation existed between those subjects experiencing induced prism and symptoms reported.  Prism adaptation may account for some participants being asymptomatic.  Sixty three percent of subjects were not aware of the importance of properly fitted spectacle frames.  Proper optical dispensing with associated patient education is necessary to achieve optimal optical benefits of spectacles and careful attention should be given to this aspect by practitioners.  It is recommended that patients return periodically to their optometrists to have the frame alignment assessed and the fit modified if necessary. (S Afr Optom 2011 70(4 168-174

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

Science.gov (United States)

Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

2017-12-01

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

Control of phospholipid flip-flop by transmembrane peptides

International Nuclear Information System (INIS)

Kaihara, Masanori; Nakao, Hiroyuki; Yokoyama, Hirokazu; Endo, Hitoshi; Ishihama, Yasushi; Handa, Tetsurou; Nakano, Minoru

2013-01-01

Highlights: ► Phospholipid flip-flop in transmembrane peptide-containing vesicles was investigated. ► Peptides that contained polar residues in the center of the transmembrane region promoted phospholipid flip-flop. ► A bioinformatics approach revealed the presence of polar residues in the transmembrane region of ER membrane proteins. ► Polar residues in ER membrane proteins possibly provide flippase-like activity. - Abstract: We designed three types of transmembrane model peptides whose sequence originates from a frequently used model peptide KALP23, and we investigated their effects on phospholipid flip-flop. Time-resolved small-angle neutron scattering and a dithionite fluorescent quenching assay demonstrated that TMP-L, which has a fully hydrophobic transmembrane region, did not enhance phospholipid flip-flop, whereas TMP-K and TMP-E, which have Lys and Glu, respectively, in the center of their transmembrane regions, enhanced phospholipid flip-flop. Introduction of polar residues in the membrane-spanning helices is considered to produce a locally polar region and enable the lipid head group to interact with the polar side-chain inside the bilayers, thereby reducing the activation energy for the flip-flop. A bioinformatics approach revealed that acidic and basic residues account for 4.5% of the central region of the transmembrane domain in human ER membrane proteins. Therefore, polar residues in ER membrane proteins are considered to provide flippase-like activity

Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

Directory of Open Access Journals (Sweden)

Douglas Blackiston

2011-01-01

Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.

Multiplexed image storage by electromagnetically induced transparency in a solid

Science.gov (United States)

Heinze, G.; Rentzsch, N.; Halfmann, T.

2012-11-01

We report on frequency- and angle-multiplexed image storage by electromagnetically induced transparency (EIT) in a Pr3+:Y2SiO5 crystal. Frequency multiplexing by EIT relies on simultaneous storage of light pulses in atomic coherences, driven in different frequency ensembles of the inhomogeneously broadened solid medium. Angular multiplexing by EIT relies on phase matching of the driving laser beams, which permits simultaneous storage of light pulses propagating under different angles into the crystal. We apply the multiplexing techniques to increase the storage capacity of the EIT-driven optical memory, in particular to implement multiplexed storage of larger two-dimensional amounts of data (images). We demonstrate selective storage and readout of images by frequency-multiplexed EIT and angular-multiplexed EIT, as well as the potential to combine both multiplexing approaches towards further enhanced storage capacities.

Environmentally induced development costs underlie fitness tradeoffs.

Science.gov (United States)

Walter, Greg M; Wilkinson, Melanie J; Aguirre, J David; Blows, Mark W; Ortiz-Barrientos, Daniel

2018-06-01

environmentally dependent changes in development rate suggest that foreign environments induce organisms to develop at a rate different from their native habitat, incurring consequences for lifetime fitness and population divergence. © 2018 by the Ecological Society of America.

Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity

DEFF Research Database (Denmark)

Rosenkilde, Mette M; Benned-Jensen, Tau; Holst, Peter J

2006-01-01

Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor...

Hidden markov model for the prediction of transmembrane proteins using MATLAB.

Science.gov (United States)

Chaturvedi, Navaneet; Shanker, Sudhanshu; Singh, Vinay Kumar; Sinha, Dhiraj; Pandey, Paras Nath

2011-01-01

Since membranous proteins play a key role in drug targeting therefore transmembrane proteins prediction is active and challenging area of biological sciences. Location based prediction of transmembrane proteins are significant for functional annotation of protein sequences. Hidden markov model based method was widely applied for transmembrane topology prediction. Here we have presented a revised and a better understanding model than an existing one for transmembrane protein prediction. Scripting on MATLAB was built and compiled for parameter estimation of model and applied this model on amino acid sequence to know the transmembrane and its adjacent locations. Estimated model of transmembrane topology was based on TMHMM model architecture. Only 7 super states are defined in the given dataset, which were converted to 96 states on the basis of their length in sequence. Accuracy of the prediction of model was observed about 74 %, is a good enough in the area of transmembrane topology prediction. Therefore we have concluded the hidden markov model plays crucial role in transmembrane helices prediction on MATLAB platform and it could also be useful for drug discovery strategy. The database is available for free at bioinfonavneet@gmail.comvinaysingh@bhu.ac.in.

Topology of transmembrane channel-like gene 1 protein.

Science.gov (United States)

Labay, Valentina; Weichert, Rachel M; Makishima, Tomoko; Griffith, Andrew J

2010-10-05

Mutations of transmembrane channel-like gene 1 (TMC1) cause hearing loss in humans and mice. TMC1 is the founding member of a family of genes encoding proteins of unknown function that are predicted to contain multiple transmembrane domains. The goal of our study was to define the topology of mouse TMC1 expressed heterologously in tissue culture cells. TMC1 was retained in the endoplasmic reticulum (ER) membrane of five tissue culture cell lines that we tested. We used anti-TMC1 and anti-HA antibodies to probe the topologic orientation of three native epitopes and seven HA epitope tags along full-length TMC1 after selective or complete permeabilization of transfected cells with digitonin or Triton X-100, respectively. TMC1 was present within the ER as an integral membrane protein containing six transmembrane domains and cytosolic N- and C-termini. There is a large cytoplasmic loop, between the fourth and fifth transmembrane domains, with two highly conserved hydrophobic regions that might associate with or penetrate, but do not span, the plasma membrane. Our study is the first to demonstrate that TMC1 is a transmembrane protein. The topologic organization revealed by this study shares some features with that of the shaker-TRP superfamily of ion channels.

Adaptive self-assembly and induced-fit transformations of anion-binding metal-organic macrocycles

Science.gov (United States)

Zhang, Ting; Zhou, Li-Peng; Guo, Xiao-Qing; Cai, Li-Xuan; Sun, Qing-Fu

2017-06-01

Container-molecules are attractive to chemists due to their unique structural characteristics comparable to enzymes and receptors in nature. We report here a family of artificial self-assembled macrocyclic containers that feature induced-fit transformations in response to different anionic guests. Five metal-organic macrocycles with empirical formula of MnL2n (M=Metal L=Ligand n=3, 4, 5, 6, 7) are selectively obtained starting from one simple benzimidazole-based ligand and square-planar palladium(II) ions, either by direct anion-adaptive self-assembly or induced-fit transformations. Hydrogen-bonding interactions between the inner surface of the macrocycles and the anionic guests dictate the shape and size of the product. A comprehensive induced-fit transformation map across all the MnL2n species is drawn, with a representative reconstitution process from Pd7L14 to Pd3L6 traced in detail, revealing a gradual ring-shrinking mechanism. We envisage that these macrocyclic molecules with adjustable well-defined hydrogen-bonding pockets will find wide applications in molecular sensing or catalysis.

Sensitivity of molecular docking to induced fit effects in influenza virus neuraminidase

Science.gov (United States)

Birch, Louise; Murray, Christopher W.; Hartshorn, Michael J.; Tickle, Ian J.; Verdonk, Marcel L.

2002-12-01

Many proteins undergo small side chain or even backbone movements on binding of different ligands into the same protein structure. This is known as induced fit and is potentially problematic for virtual screening of databases against protein targets. In this report we investigate the limits of the rigid protein approximation used by the docking program, GOLD, through cross-docking using protein structures of influenza neuraminidase. Neuraminidase is known to exhibit small but significant induced fit effects on ligand binding. Some neuraminidase crystal structures caused concern due to the bound ligand conformation and GOLD performed poorly on these complexes. A `clean' set, which contained unique, unambiguous complexes, was defined. For this set, the lowest energy structure was correctly docked (i.e. RMSD < 1.5 Å away from the crystal reference structure) in 84% of proteins, and the most promiscuous protein (1mwe) was able to dock all 15 ligands accurately including those that normally required an induced fit movement. This is considerably better than the 70% success rate seen with GOLD against general validation sets. Inclusion of specific water molecules involved in water-mediated hydrogen bonds did not significantly improve the docking performance for ligands that formed water-mediated contacts but it did prevent docking of ligands that displaced these waters. Our data supports the use of a single protein structure for virtual screening with GOLD in some applications involving induced fit effects, although care must be taken to identify the protein structure that performs best against a wide variety of ligands. The performance of GOLD was significantly better than the GOLD implementation of ChemScore and the reasons for this are discussed. Overall, GOLD has shown itself to be an extremely good, robust docking program for this system.

Role of ATP binding and hydrolysis in the gating of the cystic fibrosis transmembrane conductance regulator

Directory of Open Access Journals (Sweden)

Taras Gout

2012-01-01

Full Text Available The CFTR gene is unique within the ATP-binding cassette (ABC protein family, predominantly of transporters, by coding a chloride channel. The gating mechanism of ABC proteins has been characterized by the ATP Switch model in terms cycles of dimer formation and dissociation linked to ATP binding and hydrolysis, respectively. It would be of interest to assess the extent that Cystic Fibrosis Transmembrane Conductance Regulator (CFTR, a functional channel, fits the ATP Switch model for ABC transporters. Additional transporter mechanisms, namely those of Pgp and HlyB, are discussed for perspective. Literature search of databases selected key references in comparing and contrasting the gating mechanism. CFTR is a functional chloride channel facilitating transmembrane anion flow down electrochemical gradients. A dysfunctional CFTR protein results in cystic fibrosis, a fatal pleiotropic disease currently managed symptomatically. Understanding the gating mechanism will help target drug development aimed at alleviating and curing the disease.

Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors

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Dongjun Lee

2014-11-01

Full Text Available Central to cellular proliferative, survival, and metabolic responses is the serine/threonine kinase mTOR, which is activated in many human cancers. mTOR is present in distinct complexes that are either modulated by AKT (mTORC1 or are upstream and regulatory of it (mTORC2. Governance of mTORC2 activity is poorly understood. Here, we report a transmembrane molecule in hematopoietic progenitor cells that physically interacts with and inhibits RICTOR, an essential component of mTORC2. Upstream of mTORC2 (UT2 negatively regulates mTORC2 enzymatic activity, reducing AKTS473, PKCα, and NDRG1 phosphorylation and increasing FOXO transcriptional activity in an mTORC2-dependent manner. Modulating UT2 levels altered animal survival in a T cell acute lymphoid leukemia (T-ALL model that is known to be mTORC2 sensitive. These studies identify an inhibitory component upstream of mTORC2 in hematopoietic cells that can reduce mortality from NOTCH-induced T-ALL. A transmembrane inhibitor of mTORC2 may provide an attractive target to affect this critical cell regulatory pathway.

Magnox waste storage complex

International Nuclear Information System (INIS)

Anon.

1990-01-01

This article looks at the design and construction of British Nuclear Fuel Limited's (BNFL) Magnox waste storage complex by Costain Engineering Limited. Magnox swarf from fuel decanning is stored underwater in specially designed silos. Gas processing capabilities from Costain Engineering Limited and the experience of BNFL combined in this project to provide the necessary problem-solving skills necessary for this waste storage upgrading and extension project. A retrofitted inerting facility was fitted to an existing building and a new storage extension was fitted, both without interrupting reprocessing operations at Sellafield. (UK)

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

Science.gov (United States)

Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

2003-08-01

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

Czech Academy of Sciences Publication Activity Database

Falkovich, S. G.; Martinez-Seara, Hector; Nesterenko, A. M.; Vattulainen, I.; Gurtovenko, A. A.

2016-01-01

Roč. 7, č. 22 (2016), s. 4585-4590 ISSN 1948-7185 Institutional support: RVO:61388963 Keywords : membrane * cholesterol * membrane asymmetry * membrane dipole potential * transmembrane distribution Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 9.353, year: 2016

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

Science.gov (United States)

Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

Directory of Open Access Journals (Sweden)

Xin Wang

Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

The first transmembrane domain (TM1) of β2-subunit binds to the transmembrane domain S1 of α-subunit in BK potassium channels

Science.gov (United States)

Morera, Francisco J.; Alioua, Abderrahmane; Kundu, Pallob; Salazar, Marcelo; Gonzalez, Carlos; Martinez, Agustin D.; Stefani, Enrico; Toro, Ligia; Latorre, Ramon

2012-01-01

The BK channel is one of the most broadly expressed ion channels in mammals. In many tissues, the BK channel pore-forming α-subunit is associated to an auxiliary β-subunit that modulates the voltage- and Ca2+-dependent activation of the channel. Structural components present in β-subunits that are important for the physical association with the α-subunit are yet unknown. Here, we show through co-immunoprecipitation that the intracellular C-terminus, the second transmembrane domain (TM2) and the extracellular loop of the β2-subunit are dispensable for association with the α-subunit pointing transmembrane domain 1 (TM1) as responsible for the interaction. Indeed, the TOXCAT assay for transmembrane protein–protein interactions demonstrated for the first time that TM1 of the β2-subunit physically binds to the transmembrane S1 domain of the α-subunit. PMID:22710124

Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations.

Science.gov (United States)

Paul, Fabian; Noé, Frank; Weikl, Thomas R

2018-03-27

Unstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25-109 Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering.

What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

DEFF Research Database (Denmark)

Falkovich, Stanislav G.; Martinez-Seara, Hector; Nesterenko, Alexey M.

2016-01-01

Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations ...

Pyridoxal phosphate as a probe of the cytoplasmic domains of transmembrane proteins: Application to the nicotinic acetylcholine receptor

International Nuclear Information System (INIS)

Perez-Ramirez, B.; Martinez-Carrion, M.

1989-01-01

A novel procedure has been developed to specifically label the cytoplasmic domains of transmembrane proteins with the aldehyde pyridoxal 5-phosphate (PLP). Torpedo californica acetylcholine receptor (AcChR) vesicles were loaded with [ 3 H]pyridoxine 5-phosphate ([ 3 H]PNP) and pyridoxine-5-phosphate oxidase, followed by intravesicular enzymatic oxidation of [ 3 H]PNP at 37 degree C in the presence of externally added cytochrome c as a scavenger of possible leaking PLP product. The four receptor subunits were labeled whether the reaction was carried out on the internal surface or separately designed to mark the external one. On the other hand, the relative pyridoxylation of the subunits differed in both cases, reflecting differences in accessible lysyl residues in each side of the membrane. Even though there are no large differences in the total lysine content among the subunits and there are two copies of the α-subunit, internal surface labeling by PLP was greatest for the highest molecular weight (δ) subunit, reinforcing the concept that the four receptor subunits are transmembranous and may protrude into the cytoplasmic face in a fashion that is proportional to their subunit molecular weight. Yet, the labeling data do not fit well to any of the models proposed for AcChR subunit folding. The method described can be used for selective labeling of the cytoplasmic domains of transmembrane proteins in sealed membrane vesicles

New concept for energy storage: Microwave-induced carbon gasification with CO2

International Nuclear Information System (INIS)

Bermúdez, J.M.; Ruisánchez, E.; Arenillas, A.; Moreno, A.H.; Menéndez, J.A.

2014-01-01

Highlights: • A new system for energy storage based in microwave-induced gasification is proposed. • From the carbonaceous materials tested, charcoal yielded the best results. • The systems achieved energy efficiencies of about 45% without any optimization. • The system is competitive in terms of efficiency with some conventional systems. - Abstract: Energy storage is a topic of great importance for the development of renewable energy, since it appears to be the only solution to the problem of intermittency of production, inherent to such technologies. In this paper, a new technology for energy storage, based on microwave-induced CO 2 gasification of carbon materials is proposed. The tests carried out in this study on different carbon materials showed that charcoal consumes the least amount of energy. Two microwave heating mechanisms, a single-mode oven and a multimode device, were evaluated with the latter proving itself to be the more efficient in terms of energy consumption and recovery. The initial results obtained showed that this technology is able to achieve energy efficiencies of 45% at laboratory scale with every indication that these results can be improved upon to make this approach highly competitive against other energy storage technologies

PDBTM: Protein Data Bank of transmembrane proteins after 8 years.

Science.gov (United States)

Kozma, Dániel; Simon, István; Tusnády, Gábor E

2013-01-01

The PDBTM database (available at http://pdbtm.enzim.hu), the first comprehensive and up-to-date transmembrane protein selection of the Protein Data Bank, was launched in 2004. The database was created and has been continuously updated by the TMDET algorithm that is able to distinguish between transmembrane and non-transmembrane proteins using their 3D atomic coordinates only. The TMDET algorithm can locate the spatial positions of transmembrane proteins in lipid bilayer as well. During the last 8 years not only the size of the PDBTM database has been steadily growing from ∼400 to 1700 entries but also new structural elements have been identified, in addition to the well-known α-helical bundle and β-barrel structures. Numerous 'exotic' transmembrane protein structures have been solved since the first release, which has made it necessary to define these new structural elements, such as membrane loops or interfacial helices in the database. This article reports the new features of the PDBTM database that have been added since its first release, and our current efforts to keep the database up-to-date and easy to use so that it may continue to serve as a fundamental resource for the scientific community.

Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function.

Science.gov (United States)

Wee, Yin Shen; Roundy, Kirstin M; Weis, Janis J; Weis, John H

2012-12-01

The innate response interferon-inducible transmembrane (Ifitm) proteins have been characterized as influencing proliferation, signaling complexes and restricting virus infections. Treatment of cells lacking these proteins (IfitmDel) with IFN-β resulted in the loss of clathrin from membrane compartments and the inhibition of clathrin-mediated phagocytosis, suggesting a molecular interaction between clathrin and Ifitm proteins. The pH of endosomes of IfitmDel cells, with or without IFN activation, was neutralized, suggesting the function of the vacular ATPase proton pumps in such cells was compromised. Co-immunoprecipitation of Ifitm3 with Atp6v0b demonstrated a direct interaction between the Ifitm proteins and the v-ATPase. These data suggest that the Ifitm proteins help stabilize v-ATPase complexes in cellular membranes which, in turn, facilitates the appropriate subcellular localization of clathrin.

Glycine Perturbs Local and Global Conformational Flexibility of a Transmembrane Helix

DEFF Research Database (Denmark)

Högel, Philipp; Götz, Alexander; Kuhne, Felix

2018-01-01

Flexible transmembrane helices frequently support the conformational transitions between different functional states of membrane proteins. While proline is well known to distort and destabilize transmembrane helices, the role of glycine is still debated. Here, we systematically investigated the e...

Intrinsic potential of cell membranes: opposite effects of lipid transmembrane asymmetry and asymmetric salt ion distribution

DEFF Research Database (Denmark)

Gurtovenko, Andrey A; Vattulainen, Ilpo

2009-01-01

Using atomic-scale molecular dynamics simulations, we consider the intrinsic cell membrane potential that is found to originate from a subtle interplay between lipid transmembrane asymmetry and the asymmetric distribution of monovalent salt ions on the two sides of the cell membrane. It turns out......Cl saline solution and the PE leaflet is exposed to KCl, the outcome is that the effects of asymmetric lipid and salt ion distributions essentially cancel one another almost completely. Overall, our study highlights the complex nature of the intrinsic potential of cell membranes under physiological...... that both the asymmetric distribution of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids across a membrane and the asymmetric distribution of NaCl and KCl induce nonzero drops in the transmembrane potential. However, these potential drops are opposite in sign. As the PC leaflet faces a Na...

A monocyte chemotaxis inhibiting factor in serum of HIV infected men shares epitopes with the HIV transmembrane protein gp41

NARCIS (Netherlands)

Tas, M.; Drexhage, H. A.; Goudsmit, J.

1988-01-01

This report describes that gp41, the transmembranous envelope protein of HIV, is able to inhibit monocyte chemotaxis (measured as FMLP-induced polarization). To study the presence of such immunosuppressive HIV env proteins in the circulation of HIV-infected men, fractions were prepared from serum

Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74

DEFF Research Database (Denmark)

Rosenkilde, M M; Kledal, T N; Holst, Peter Johannes

2000-01-01

Open reading frame 74 (ORF74) encoded by human herpesvirus 8 is a highly constitutively active seven transmembrane (7TM) receptor stimulated by angiogenic chemokines, e.g. growth-related oncogene-alpha, and inhibited by angiostatic chemokines e.g. interferon-gamma-inducible protein. Transgenic mice...

Two Cases of CrossFit®-Induced Rhabdomyolysis: A Rising Concern

Directory of Open Access Journals (Sweden)

Madhur Rathi

2015-10-01

Full Text Available ackground: The author reports the cases of two adult males who presented with severe rhabdomyolysis following identical CrossFit® workouts performed on the same day, at the same time and at the same location. Results: For both cases, symptoms of rhabdomyolysis disappeared upon discontinuation of the regime and within three days of aggressive hydration and rest. Patients made a complete recovery upon discharge. Conclusion: The rhabdomyolysis was attributed to the same excruciating workout both men underwent. Exertional rhabdomyolysis exemplified by the cases presented highlights a rising concern over the health consequences of the popular training program. CrossFit®-induced rhabdomyolysis is underrecognized and should be considered in patients presenting with signs and symptoms of rhabdomyolysis.

Biological amine transport in chromaffin ghosts. Coupling to the transmembrane proton and potential gradients.

Science.gov (United States)

Johnson, R G; Pfister, D; Carty, S E; Scarpa, A

1979-11-10

The effect of the transmembrane proton gradient (delta pH) and potential gradient (delta psi) upon the rate and extent of amine accumulation was investigated in chromaffin ghosts. The chromaffin ghosts were formed by hypo-osmotic lysis of isolated bovine chromaffin granules and extensive dialysis in order to remove intragranular binding components and dissipate the endogenous electrochemical gradients. Upon ATP addition to suspensions of chromaffin ghosts, a transmembrane proton gradient alone, a transmembrane gradient alone, or both, could be established, depending upon the compositions of the media in which the ghosts were formed and resuspended. When chloride was present in the medium, addition of ATP resulted in the generation of a transmembrane proton gradient, acidic inside of 1 pH unit (measured by [14C]methylamine distribution), and no transmembrane potential (measured by [14C]-thiocyanate distribution). When ATP was added to chromaffin ghosts suspended in a medium in which chloride was substituted by isethionate, a transmembrane potential, inside positive, of 45 mV and no transmembrane proton gradient, was measured. In each medium, the addition of agents known to affect proton or potential gradients, respectively, exerted a predictable mechanism of action. Accumulation of [14C]epinephrine or [14C]5-hydroxytryptamine was over 1 order of magnitude greater in the presence of the transmembrane proton gradient or the transmembrane potential than in the absence of any gradient and, moreover, was related to the magnitude of the proton or potential gradient in a dose-dependent manner. When ghosts were added to a medium containing chloride and isethionate, both a delta pH and delta psi could be generated upon addition of ATP. In this preparation, the maximal rate of amine accumulation was observed. The results indicate that amine accumulation into chromaffin ghosts can occur in the presence of either a transmembrane proton gradient, or a transmembrane potential

Single molecule insights on conformational selection and induced fit mechanism

DEFF Research Database (Denmark)

Hatzakis, Nikos

2014-01-01

. To describe the molecular basis of this behavior, two main mechanisms have been advanced: 'induced fit' and 'conformational selection'. Our understanding of these models relies primarily on NMR, computational studies and kinetic measurements. These techniques report the average behavior of a large ensemble...... of unsynchronized molecules, often masking intrinsic dynamic behavior of proteins and biologically significant transient intermediates. Single molecule measurements are emerging as a powerful tool for characterizing protein function. They offer the direct observation and quantification of the activity, abundance...

Proteomic and Functional Analyses of the Virion Transmembrane Proteome of Cyprinid Herpesvirus 3.

Science.gov (United States)

Vancsok, Catherine; Peñaranda, M Michelle D; Raj, V Stalin; Leroy, Baptiste; Jazowiecka-Rakus, Joanna; Boutier, Maxime; Gao, Yuan; Wilkie, Gavin S; Suárez, Nicolás M; Wattiez, Ruddy; Gillet, Laurent; Davison, Andrew J; Vanderplasschen, Alain F C

2017-11-01

major findings were: (i) the FL strain encodes 16 virion transmembrane proteins; (ii) eight of these proteins are essential for viral growth in vitro ; (iii) seven of the nonessential proteins affect viral growth in vitro , and two affect virulence in vivo ; and (iv) a mutant lacking ORF25 is highly attenuated but induces moderate immune protection. This study represents a major breakthrough in understanding the biology of CyHV-3 and will contribute to the development of prophylactic methods. It also provides a firm basis for the further research on alloherpesvirus virion transmembrane proteins. Copyright © 2017 Vancsok et al.

Transmembrane-sequence-dependent overexpression and secretion of glycoproteins in Saccharomyces cerevisiae.

Science.gov (United States)

Schuster, M; Wasserbauer, E; Aversa, G; Jungbauer, A

2001-02-01

Protein expression using the secretory pathway in Saccharomyces cerevisiae can lead to high amounts of overexpressed and secreted proteins in culture supernatants in a short period of time. These post-translational modified expression products can be purified up to >90% in a single step. The overexpression and secretion of the transmembrane glycoprotein signaling lymphocytic activation molecule (SLAM) was studied. SLAM belongs to the immunoglobulin superfamily and its engagement results in T-cell expansion and INF-gamma production. The molecule is composed of an extracellular, a single-span transmembrane and a cytoplasmatic domain. The extracellular part may be relevant for stimulation studies in vitro since SLAM is a high-affinity self-ligand. Therefore several fragments of this region have been expressed as Flag-fusions in S. cerevisiae: a full-length fragment containing the transmembrane region and the autologous signal sequence, another without the transmembrane region, and two fragments without the autologous signal sequence with and without the transmembrane region. By molecular cloning, the different deletion mutants of the cDNA encoding the full-length construct have been inserted in a yeast episomal plasmid. Upstream of the cDNA, the alpha-leader sequence of a yeast mating pheromone has been cloned to direct the fusion proteins into the secretory protein maturation pathway. All four fragments were expressed but yield, location, and maturation were highly influenced by the transmembrane domain and the autologous signal sequence. Only the fragment without autologous signal sequence and transmembrane domain could be efficiently secreted. High-mannose glycosylation was analyzed by lectin mapping and digestion with specific glycosidases. After enzyme treatment, a single band product with the theoretical size could be detected and identified as SLAM by a specific monoclonal antibody. The fusion protein concentration in the supernatant was 30 microg/ml. The

Sexual harassment induces a temporary fitness cost but does not constrain the acquisition of environmental information in fruit flies.

Science.gov (United States)

Teseo, Serafino; Veerus, Liisa; Moreno, Céline; Mery, Frédéric

2016-01-01

Across animals, sexual harassment induces fitness costs for females and males. However, little is known about the cognitive costs involved, i.e. whether it constrains learning processes, which could ultimately affect an individual's fitness. Here we evaluate the acquisition of environmental information in groups of fruit flies challenged with various levels of male sexual harassment. We show that, although high sexual harassment induces a temporary fitness cost for females, all fly groups of both sexes exhibit similar levels of learning. This suggests that, in fruit flies, the fitness benefits of acquiring environmental information are not affected by the fitness costs of sexual harassment, and that selection may favour cognition even in unfavourable social contexts. Our study provides novel insights into the relationship between sexual conflicts and cognition and the evolution of female counterstrategies against male sexual harassment. © 2016 The Author(s).

Analysis of decay of radicals induced in irradiated foods during long storage

International Nuclear Information System (INIS)

Kishita, Keigo; Kawamura, Shoei; Nakamura, Hideo; Ukai, Mitsuko; Kikuchi, Masahiro; Kobayashi, Yasuhiko

2013-01-01

By electron spin resonance (ESR) spectroscopy, we revealed free radicals in γ-ray irradiated foods ; black pepper, green coffee bean, cereal flour and ginseng. We also analyzed the decay behavior of radiation induced free radicals during long storage. The ESR spectrum of experimental irradiated foods consists of a sextet signal centered at g=2.0 and a singlet signal at the same g-value position and a singlet signal at g=4.0. The ESR spectrum of the cereal flour sample showed only singlet signal at g=2.0. The singlet signal at g=2.0 is originated from organic free radicals and its peak intensity showed the dependence of γ-ray radiation dose levels. But the signal intensity was decreased during storage. Only after 3 hours of radiation treatment the peak intensity was decreased fast and after that the intensity was decreased slowly. The analysis of radical decay process using the simulation methods based on the theory of reaction speed, the three decay behavior was showed. It is considered that at least three or more kinds of radicals were induced in irradiated foods and in decay during long time storage. (author)

Induced seismicity and carbon storage: Risk assessment and mitigation strategies

Energy Technology Data Exchange (ETDEWEB)

White, Joshua A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Foxall, William [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Bachmann, Corinne [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chiaramonte, Laura [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Daley, Thomas M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2016-01-28

Geologic carbon storage (GCS) is widely recognized as an important strategy to reduce atmospheric carbon dioxide (CO₂) emissions. Like all technologies, however, sequestration projects create a number of potential environmental and safety hazards that must be addressed. These include earthquakes—from microseismicity to large, damaging events—that can be triggered by altering pore-pressure conditions in the subsurface. To date, measured seismicity due to CO₂ injection has been limited to a few modest events, but the hazard exists and must be considered. There are important similarities between CO₂ injection and fluid injection from other applications that have induced significant events—e.g. geothermal systems, waste-fluid injection, hydrocarbon extraction, and others. There are also important distinctions among these technologies that should be considered in a discussion of seismic hazard. This report focuses on strategies for assessing and mitigating risk during each phase of a CO₂ storage project. Four key risks related to fault reactivation and induced seismicity were considered. Induced slip on faults could potentially lead to: (1) infrastructure damage, (2) a public nuisance, (3) brine-contaminated drinking water, and (4) CO₂-contaminated drinking water. These scenarios lead to different types of damage—to property, to drinking water quality, or to the public welfare. Given these four risks, this report focuses on strategies for assessing (and altering) their likelihoods of occurrence and the damage that may result. This report begins with an overview of the basic physical mechanisms behind induced seismicity. This science basis—and its gaps—is crucial because it forms the foundation for risk assessment and mitigation. Available techniques for characterizing and monitoring seismic behavior are also described. Again, this technical basis—and its limitations—must be factored into the risk

Membrane shape modulates transmembrane protein distribution.

Science.gov (United States)

Aimon, Sophie; Callan-Jones, Andrew; Berthaud, Alice; Pinot, Mathieu; Toombes, Gilman E S; Bassereau, Patricia

2014-01-27

Although membrane shape varies greatly throughout the cell, the contribution of membrane curvature to transmembrane protein targeting is unknown because of the numerous sorting mechanisms that take place concurrently in cells. To isolate the effect of membrane shape, we used cell-sized giant unilamellar vesicles (GUVs) containing either the potassium channel KvAP or the water channel AQP0 to form membrane nanotubes with controlled radii. Whereas the AQP0 concentrations in flat and curved membranes were indistinguishable, KvAP was enriched in the tubes, with greater enrichment in more highly curved membranes. Fluorescence recovery after photobleaching measurements showed that both proteins could freely diffuse through the neck between the tube and GUV, and the effect of each protein on membrane shape and stiffness was characterized using a thermodynamic sorting model. This study establishes the importance of membrane shape for targeting transmembrane proteins and provides a method for determining the effective shape and flexibility of membrane proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo.

Science.gov (United States)

Xu, Jinfang; Qian, Ping; Wu, Qunfeng; Liu, Shasha; Fan, Wenchun; Zhang, Keshan; Wang, Rong; Zhang, Huawei; Chen, Huanchun; Li, Xiangmin

2014-09-01

The interferon-induced transmembrane protein 3 (IFITM3) is a widely expressed potent antiviral effector of the host innate immune system. It restricts a diverse group of pathogenic, enveloped viruses, by interfering with endosomal fusion. In this report, the swine IFITM3 (sIFITM3) gene was cloned. It shares the functionally conserved CD225 domain and multiple critical amino acid residues (Y19, F74, F77, R86 and Y98) with its human ortholog, which are essential for antiviral activity. Ectopic expression of sIFITM3 significantly inhibited non-enveloped foot-and-mouth disease virus (FMDV) infection in BHK-21 cells. Furthermore, sIFITM3 blocked FMDV infection at early steps in the virus life cycle by disrupting viral attachment to the host cell surface. Importantly, inoculation of 2-day-old suckling mice with a plasmid expressing sIFITM3 conferred protection against lethal challenge with FMDV. These results suggest that sIFITM3 is a promising antiviral agent and that can safeguard the host from infection with FMDV. Copyright © 2014 Elsevier B.V. All rights reserved.

Transmission of integrin β7 transmembrane domain topology enables gut lymphoid tissue development.

Science.gov (United States)

Sun, Hao; Lagarrigue, Frederic; Gingras, Alexandre R; Fan, Zhichao; Ley, Klaus; Ginsberg, Mark H

2018-04-02

Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration. Furthermore, the α4β7(L721P) mutation blocks lymphocyte homing to and development of the GALT. These studies show that impairing the ability of an integrin β TMD to transmit talin-induced TMD topology inhibits agonist-induced physiological integrin activation and biological function in development. © 2018 Sun et al.

In vivo evidence for a functional role of both tumor necrosis factor (TNF) receptors and transmembrane TNF in experimental hepatitis.

Science.gov (United States)

Küsters, S; Tiegs, G; Alexopoulou, L; Pasparakis, M; Douni, E; Künstle, G; Bluethmann, H; Wendel, A; Pfizenmaier, K; Kollias, G; Grell, M

1997-11-01

The significance of tumor necrosis factor receptor 1 (TNFR1) for TNF function in vivo is well documented, whereas the role of TNFR2 so far remains obscure. In a model of concanavalin A (Con A)-induced, CD4+ T cell-dependent experimental hepatitis in mice, in which TNF is a central mediator of apoptotic and necrotic liver damage, we now provide evidence for an essential in vivo function of TNFR2 in this pathophysiological process. We demonstrate that a cooperation of TNFR1 and TNFR2 is required for hepatotoxicity as mice deficient of either receptor were resistant against Con A. A significant role of TNFR2 for Con A-induced hepatitis is also shown by the enhanced sensitivity of transgenic mice overexpressing the human TNFR2. The ligand for cytotoxic signaling via both TNF receptors is the precursor of soluble TNF, i.e. transmembrane TNF. Indeed, transmembrane TNF is sufficient to mediate hepatic damage, as transgenic mice deficient in wild-type soluble TNF but expressing a mutated nonsecretable form of TNF developed inflammatory liver disease.

Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1

KAUST Repository

Rashid, Fahad

2017-02-23

Human flap endonuclease 1 (FEN1) and related structure-specific 5\\'nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5\\'nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually \\'locks\\' protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never misses cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability.

Low rate doses effects of gamma radiation on glycoproteins of transmembrane junctions in fibroblasts

International Nuclear Information System (INIS)

Bringas, J.E.; Caceres, J.L.

1996-01-01

Glycoproteins of trans-membrane junctions are molecules that help to bind cells with the extracellular matrix. Integrins are the most important trans-membrane molecules among others. The damage of gamma radiation on those proteins could be an important early event that causes membrane abnormalities which may lead to cell malfunction and cancer induced by radiation due to cell dissociation. Randomized blocks with 3 repetitions of mouse embryo fibroblast cultures, were irradiated with Cobalt-60 gamma rays, during 20 days. Biological damage to glycoproteins and integrins was evaluated by cellular growth and fibroblast proliferative capacity. Integrins damage was studied by isolation by column immunoaffinity chromatography migrated on SDS-Page under reducing and non reducing conditions, and inhibition of integrins extracellular matrix adhesion by monoclonal antibodies effect. The dose/rate (0.05 Gy/day-0.2 Gy/day) of gamma given to cells did not show damage evidence on glycoproteins and integrins. If damage happened, it was repaired by cells very soon, was delayed by continuous cellular division or by glycoproteins characteristic of being multiple extracellular ligatures. Bio effects became more evident with an irradiation time greater than 20 days or a high dose/rate. (authors). 6 refs

The Role of Water Distribution Controlled by Transmembrane Potentials in the Cytochrome c-Cardiolipin Interaction: Revealing from Surface-Enhanced Infrared Absorption Spectroscopy.

Science.gov (United States)

Zeng, Li; Wu, Lie; Liu, Li; Jiang, Xiue

2017-11-02

The interaction of cytochrome c (cyt c) with cardiolipin (CL) plays a crucial role in apoptotic functions, however, the changes of the transmembrane potential in governing the protein behavior at the membrane-water interface have not been studied due to the difficulties in simultaneously monitoring the interaction and regulating the electric field. Herein, surface-enhanced infrared absorption (SEIRA) spectroelectrochemistry is employed to study the mechanism of how the transmembrane potentials control the interaction of cyt c with CL membranes by regulating the electrode potentials of an Au film. When the transmembrane potential decreases, the water content at the interface of the membranes can be increased to slow down protein adsorption through decreasing the hydrogen-bond and hydrophobic interactions, but regulates the redox behavior of CL-bound cyt c through a possible water-facilitated proton-coupled electron transfer process. Our results suggest that the potential drop-induced restructure of the CL conformation and the hydration state could modify the structure and function of CL-bound cyt c on the lipid membrane. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improvements in fitness are not obligatory for exercise training-induced improvements in CV risk factors.

Science.gov (United States)

Hartman, Yvonne A W; Hopman, Maria T E; Schreuder, Tim H; Verheggen, Rebecca J H M; Scholten, Ralph R; Oudegeest-Sander, Madelijn H; Poelkens, Fleur; Maiorana, Andrew J; Naylor, Louise H; Willems, Peter H; Tack, Cees J; Thijssen, Dick H J; Green, Daniel J

2018-02-01

The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center-based and supervised exercise training programs in subjects with increased cardiovascular risk. We pooled data from exercise training studies of subjects with increased cardiovascular risk (n = 166) who underwent 8-52 weeks endurance training. We determined fitness (i.e., peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with nonresponder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol, and 49% for high-density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P > 0.05). Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, while improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training-induced improvements in cardiovascular risk factors. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Transmembrane signalling at the epidermal growth factor receptor. Positive regulation by the C-terminal phosphotyrosine residues

DEFF Research Database (Denmark)

Magni, M; Pandiella, A; Helin, K

1991-01-01

a positive role in the regulation of transmembrane signalling at the EGF receptor. The stepwise decrease in signal generation observed in single, double and triple point mutants suggest that the role of phosphotyrosine residues is not in the participation in specific amino acid sequences, but rather...... in the double and the triple mutants. In the latter mutant, expression of the EGF-receptor-activated lipolytic enzyme phospholipase C gamma was unchanged, whereas its tyrosine phosphorylation induced by the growth factor was lowered to approx. 25% of that in the controls. In all of the cell clones employed......, the accumulation of inositol phosphates induced by treatment with fetal calf serum varied only slightly, whereas the same effect induced by EGF was consistently lowered in those lines expressing mutated receptors. This decrease was moderate for those receptors missing only the distal tyrosine (point and deletion...

Hollow optical fiber induced solar cells with optical energy storage and conversion.

Science.gov (United States)

Ding, Jie; Zhao, Yuanyuan; Duan, Jialong; Duan, Yanyan; Tang, Qunwei

2017-11-09

Hollow optical fiber induced dye-sensitized solar cells are made by twisting Ti wire/N719-TiO 2 nanotube photoanodes and Ti wire/Pt (CoSe, Pt 3 Ni) counter electrodes, yielding a maximized efficiency of 0.7% and good stability. Arising from optical energy storage ability, the solar cells can generate electricity without laser illumination.

[Bacterial synthesis, purification, and solubilization of transmembrane segments of ErbB family members].

Science.gov (United States)

Goncharuk, M V; Shul'ga, A A; Ermoliuk, Ia S; Tkach, E N; Goncharuk, S A; Pustovalova, Iu E; Mineev, K S; Bocharov, É V; Maslennikov, I V; Arsen'ev, A S; Kirpichnikov, M P

2011-01-01

A family of epidermal growth factor receptors, ErbB, represents an important class of receptor tyrosine kinases, playing a leading role in cellular growth, development and differentiation. Transmembrane domains of these receptors transduce biochemical signals across plasma membrane via lateral homo- and heterodimerization. Relatively small size of complexes of ErbB transmembrane domains with detergents or lipids allows one to study their detailed spatial structure using three-dimensional heteronuclear high-resolution NMR spectroscopy. Here, we describe the effective expression system and purification procedure for preparative-scale production of transmembrane peptides from four representatives of ErbB family, ErbB1, ErbB2, ErbB3, ErbB4, for structural studies. The recombinant peptides were produced in Escherichia coli BL21(DE3)pLysS as C-terminal extensions of thioredoxin A. The fusion protein cleavage was accomplished with the light subunit of human enterokinase. Several (10-30) milligrams of purified isotope-labeled transmembrane peptides were isolated with the use of a simple and convenient procedure, which consists of consecutive steps of immobilized metal affinity chromatography and cation-exchange chromatography. The purified peptides were reconstituted in lipid/detergent environment (micelles or bicelles) and characterized using dynamic light scattering, CD and NMR spectroscopy. The data obtained indicate that the purified ErbB transmembrane peptides are suitable for structural and dynamic studies of their homo- and heterodimer complexes using high resolution NMR spectroscopy.

The soluble loop BC region guides, but not dictates, the assembly of the transmembrane cytochrome b6.

Directory of Open Access Journals (Sweden)

Lydia Tome-Stangl

Full Text Available Studying folding and assembly of naturally occurring α-helical transmembrane proteins can inspire the design of membrane proteins with defined functions. Thus far, most studies have focused on the role of membrane-integrated protein regions. However, to fully understand folding pathways and stabilization of α-helical membrane proteins, it is vital to also include the role of soluble loops. We have analyzed the impact of interhelical loops on folding, assembly and stability of the heme-containing four-helix bundle transmembrane protein cytochrome b6 that is involved in charge transfer across biomembranes. Cytochrome b6 consists of two transmembrane helical hairpins that sandwich two heme molecules. Our analyses strongly suggest that the loop connecting the helical hairpins is not crucial for positioning the two protein "halves" for proper folding and assembly of the holo-protein. Furthermore, proteolytic removal of any of the remaining two loops, which connect the two transmembrane helices of a hairpin structure, appears to also not crucially effect folding and assembly. Overall, the transmembrane four-helix bundle appears to be mainly stabilized via interhelical interactions in the transmembrane regions, while the soluble loop regions guide assembly and stabilize the holo-protein. The results of this study might steer future strategies aiming at designing heme-binding four-helix bundle structures, involved in transmembrane charge transfer reactions.

Two Predicted Transmembrane Domains Exclude Very Long Chain Fatty acyl-CoAs from the Active Site of Mouse Wax Synthase.

Directory of Open Access Journals (Sweden)

Steffen Kawelke

Full Text Available Wax esters are used as coatings or storage lipids in all kingdoms of life. They are synthesized from a fatty alcohol and an acyl-CoA by wax synthases. In order to get insights into the structure-function relationships of a wax synthase from Mus musculus, a domain swap experiment between the mouse acyl-CoA:wax alcohol acyltransferase (AWAT2 and the homologous mouse acyl-CoA:diacylglycerol O-acyltransferase 2 (DGAT2 was performed. This showed that the substrate specificity of AWAT2 is partially determined by two predicted transmembrane domains near the amino terminus of AWAT2. Upon exchange of the two domains for the respective part of DGAT2, the resulting chimeric enzyme was capable of incorporating up to 20% of very long acyl chains in the wax esters upon expression in S. cerevisiae strain H1246. The amount of very long acyl chains in wax esters synthesized by wild type AWAT2 was negligible. The effect was narrowed down to a single amino acid position within one of the predicted membrane domains, the AWAT2 N36R variant. Taken together, we provide first evidence that two predicted transmembrane domains in AWAT2 are involved in determining its acyl chain length specificity.

Transmembrane Tumor Necrosis Factor Controls Myeloid-Derived Suppressor Cell Activity via TNF Receptor 2 and Protects from Excessive Inflammation during BCG-Induced Pleurisy

Directory of Open Access Journals (Sweden)

Leslie Chavez-Galan

2017-08-01

Full Text Available Pleural tuberculosis (TB is a form of extra-pulmonary TB observed in patients infected with Mycobacterium tuberculosis. Accumulation of myeloid-derived suppressor cells (MDSC has been observed in animal models of TB and in human patients but their role remains to be fully elucidated. In this study, we analyzed the role of transmembrane TNF (tmTNF in the accumulation and function of MDSC in the pleural cavity during an acute mycobacterial infection. Mycobacterium bovis BCG-induced pleurisy was resolved in mice expressing tmTNF, but lethal in the absence of tumor necrosis factor. Pleural infection induced MDSC accumulation in the pleural cavity and functional MDSC required tmTNF to suppress T cells as did pleural wild-type MDSC. Interaction of MDSC expressing tmTNF with CD4 T cells bearing TNF receptor 2 (TNFR2, but not TNFR1, was required for MDSC suppressive activity on CD4 T cells. Expression of tmTNF attenuated Th1 cell-mediated inflammatory responses generated by the acute pleural mycobacterial infection in association with effective MDSC expressing tmTNF and interacting with CD4 T cells expressing TNFR2. In conclusion, this study provides new insights into the crucial role played by the tmTNF/TNFR2 pathway in MDSC suppressive activity required during acute pleural infection to attenuate excessive inflammation generated by the infection.

TMS-induced neural noise in sensory cortex interferes with short-term memory storage

Directory of Open Access Journals (Sweden)

Tyler D Bancroft

2014-03-01

Full Text Available In a previous study, Harris et al. (2002 found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation to primary somatosensory cortex (SI early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.’s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature.

Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase.

Science.gov (United States)

Wang, Hong; Brautigan, David L

2006-11-01

Human lemur (Lmr) kinases are predicted to be Tyr kinases based on sequences and are related to neurotrophin receptor Trk kinases. This study used homogeneous recombinant KPI-2 (Lmr2, LMTK2, Cprk, brain-enriched protein kinase) kinase domain and a library of 1,154 peptides on a microarray to analyze substrate specificity. We found that KPI-2 is strictly a Ser/Thr kinase that reacts with Ser either preceded by or followed by Pro residues but unlike other Pro-directed kinases does not strictly require an adjacent Pro residue. The most reactive peptide in the library corresponds to Ser-737 of cystic fibrosis transmembrane conductance regulator, and the recombinant R domain of cystic fibrosis transmembrane conductance regulator was a preferred substrate. Furthermore the KPI-2 kinase phosphorylated peptides corresponding to the single site in phosphorylase and purified phosphorylase b, making this only the second known phosphorylase b kinase. Phosphorylase was used as a specific substrate to show that KPI-2 is inhibited in living cells by addition of nerve growth factor or serum. The results demonstrate the utility of the peptide library to probe specificity and discover kinase substrates and offer a specific assay that reveals hormonal regulation of the activity of this unusual transmembrane kinase.

Pumped storage system model and experimental investigations on S-induced issues during transients

Science.gov (United States)

Zeng, Wei; Yang, Jiandong; Hu, Jinhong

2017-06-01

Because of the important role of pumped storage stations in the peak regulation and frequency control of a power grid, pump turbines must rapidly switch between different operating modes, such as fast startup and load rejection. However, pump turbines go through the unstable S region in these transition processes, threatening the security and stability of the pumped storage station. This issue has mainly been investigated through numerical simulations, while field experiments generally involve high risks and are difficult to perform. Therefore, in this work, the model test method was employed to study S-induced security and stability issues for a pumped storage station in transition processes. First, a pumped storage system model was set up, including the piping system, model units, electrical control systems and measurement system. In this model, two pump turbines with different S-shaped characteristics were installed to determine the influence of S-shaped characteristics on transition processes. The model platform can be applied to simulate any hydraulic transition process that occurs in real power stations, such as load rejection, startup, and grid connection. On the experimental platform, the S-shaped characteristic curves were measured to be the basis of other experiments. Runaway experiments were performed to verify the impact of the S-shaped characteristics on the pump turbine runaway stability. Full load rejection tests were performed to validate the effect of the S-shaped characteristics on the water-hammer pressure. The condition of one pump turbine rejecting its load after another defined as one-after-another (OAA) load rejection was performed to validate the possibility of S-induced extreme draft tube pressure. Load rejection experiments with different guide vane closing schemes were performed to determine a suitable scheme to adapt the S-shaped characteristics. Through these experiments, the threats existing in the station were verified, the

Correlation of Aquaporins and Transmembrane Solute Transporters Revealed by Genome-Wide Analysis in Developing Maize Leaf

Directory of Open Access Journals (Sweden)

Xun Yue

2012-01-01

Full Text Available Aquaporins are multifunctional membrane channels that facilitate the transmembrane transport of water and solutes. When transmembrane mineral nutrient transporters exhibit the same expression patterns as aquaporins under diverse temporal and physiological conditions, there is a greater probability that they interact. In this study, genome-wide temporal profiling of transcripts analysis and coexpression network-based approaches are used to examine the significant specificity correlation of aquaporins and transmembrane solute transporters in developing maize leaf. The results indicate that specific maize aquaporins are related to specific transmembrane solute transporters. The analysis demonstrates a systems-level correlation between aquaporins, nutrient transporters, and the homeostasis of mineral nutrients in developing maize leaf. Our results provide a resource for further studies into the physiological function of these aquaporins.

30 CFR 77.1103 - Flammable liquids; storage.

Science.gov (United States)

2010-07-01

... storage tanks shall be mounted securely on firm foundations. Outlet piping shall be provided with flexible connections or other special fittings to prevent adverse effects from tank settling. (c) Fuel lines shall be... hazards. (d) Areas surrounding flammable-liquid storage tanks and electric substations and transformers...

Long-term effects of inducible mutagenic DNA repair on relative fitness and phenotypic diversification in Pseudomonas cichorii 302959.

Science.gov (United States)

Weigand, Michael R; Sundin, George W

2009-01-01

Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for approximately 500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of "round" and "fuzzy" colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.

Alternatives for water basin spent fuel storage using pin storage

International Nuclear Information System (INIS)

Viebrock, J.M.; Carlson, R.W.

1979-09-01

The densest tolerable form for storing spent nuclear fuel is storage of only the fuel rods. This eliminates the space between the fuel rods and frees the hardware to be treated as non-fuel waste. The storage density can be as much as 1.07 MTU/ft 2 when racks are used that just satisfy the criticality and thermal limitations. One of the major advantages of pin storage is that it is compatible with existing racks; however, this reduces the storage density to 0.69 MTU/ft 2 . Even this is a substantial increase over the 0.39 MTU/ft 2 that is achievable with current high capacity stainless steel racks which have been selected as the bases for comparison. Disassembly requires extensive operation on the fuel assembly to remove the upper end fitting and to extract the fuel rods from the assembly skeleton. These operations will be performed with the aid of an elevator to raise the assembly where each fuel rod is grappled. Lowering the elevator will free the fuel rod for transfer to the storage canister. A storage savings of $1510 per MTU can be realized if the pin storage concept is incorporated at a new away-from-reactor facility. The storage cost ranges from $3340 to $7820 per MTU of fuel stored with the lower cost applying to storage at an existing away-from-reactor storage facility and the higher cost applying to at-reactor storage

Coarse Grained Molecular Dynamics Simulations of Transmembrane Protein-Lipid Systems

Directory of Open Access Journals (Sweden)

Peter Spijker

2010-06-01

Full Text Available Many biological cellular processes occur at the micro- or millisecond time scale. With traditional all-atom molecular modeling techniques it is difficult to investigate the dynamics of long time scales or large systems, such as protein aggregation or activation. Coarse graining (CG can be used to reduce the number of degrees of freedom in such a system, and reduce the computational complexity. In this paper the first version of a coarse grained model for transmembrane proteins is presented. This model differs from other coarse grained protein models due to the introduction of a novel angle potential as well as a hydrogen bonding potential. These new potentials are used to stabilize the backbone. The model has been validated by investigating the adaptation of the hydrophobic mismatch induced by the insertion of WALP-peptides into a lipid membrane, showing that the first step in the adaptation is an increase in the membrane thickness, followed by a tilting of the peptide.

Induction of IL-1 during hemodialysis: Transmembrane passage of intact endotoxins (LPS)

Energy Technology Data Exchange (ETDEWEB)

Laude-Sharp, M.; Caroff, M.; Simard, L.; Pusineri, C.; Kazatchkine, M.D.; Haeffner-Cavaillon, N. (INSERM U 28, Hopital Broussais, Paris (France))

1990-12-01

Circulating monocytes of patients undergoing chronic hemodialysis are triggered to produce interleukin-1 (IL-1) in vivo. Intradialytic induction of IL-1 is associated with complement activation in patients dialyzed with first-use cellulose membranes. Chronic stimulation of IL-1 production occurs because of an yet unidentified mechanism in patients dialyzed with high permeability membranes. The present study demonstrates that intact bacterial lipopolysaccharide (LPS) molecules may cross cuprophan, AN69 and polysulfone membranes under in vitro conditions simulating in vivo hemodialysis. The experiments used purified LPS from Neisseria meningitidis and LPS from Pseudomonas testosteroni, a bacterial strain grown out from a clinically used dialysate. LPS were purified to homogeneity and radiolabeled. Transmembrane passage of 3H-labeled LPS was observed within the first five minutes of dialysis. A total of 0.1 to 1% of 3H-labeled LPS were recovered in the dialysate compartment after one hour of dialysis. High amounts of LPS, representing 40 to 70% of the amount originally present in the dialysate, were absorbed onto high permeability membranes. Low amounts of LPS were absorbed onto cuprophan membranes. The amount of LPS absorbed decreased with the concentration of LPS in the dialysate. LPS recovered from the blood compartment exhibited the same molecular weight as that used to contaminate the dialysate. Biochemically detectable transmembrane passage of LPS was not associated with that of material detectable using the limulus amebocyte lysate (LAL) assay. An IL-1-inducing activity was, however, detected in the blood compartment upon dialysis with high permeability membranes, as previously found by others with cuprophan membranes.

Induction of IL-1 during hemodialysis: Transmembrane passage of intact endotoxins (LPS)

International Nuclear Information System (INIS)

Laude-Sharp, M.; Caroff, M.; Simard, L.; Pusineri, C.; Kazatchkine, M.D.; Haeffner-Cavaillon, N.

1990-01-01

Circulating monocytes of patients undergoing chronic hemodialysis are triggered to produce interleukin-1 (IL-1) in vivo. Intradialytic induction of IL-1 is associated with complement activation in patients dialyzed with first-use cellulose membranes. Chronic stimulation of IL-1 production occurs because of an yet unidentified mechanism in patients dialyzed with high permeability membranes. The present study demonstrates that intact bacterial lipopolysaccharide (LPS) molecules may cross cuprophan, AN69 and polysulfone membranes under in vitro conditions simulating in vivo hemodialysis. The experiments used purified LPS from Neisseria meningitidis and LPS from Pseudomonas testosteroni, a bacterial strain grown out from a clinically used dialysate. LPS were purified to homogeneity and radiolabeled. Transmembrane passage of 3H-labeled LPS was observed within the first five minutes of dialysis. A total of 0.1 to 1% of 3H-labeled LPS were recovered in the dialysate compartment after one hour of dialysis. High amounts of LPS, representing 40 to 70% of the amount originally present in the dialysate, were absorbed onto high permeability membranes. Low amounts of LPS were absorbed onto cuprophan membranes. The amount of LPS absorbed decreased with the concentration of LPS in the dialysate. LPS recovered from the blood compartment exhibited the same molecular weight as that used to contaminate the dialysate. Biochemically detectable transmembrane passage of LPS was not associated with that of material detectable using the limulus amebocyte lysate (LAL) assay. An IL-1-inducing activity was, however, detected in the blood compartment upon dialysis with high permeability membranes, as previously found by others with cuprophan membranes

Transmembrane START domain proteins: in silico identification, characterization and expression analysis under stress conditions in chickpea (Cicer arietinum L.).

Science.gov (United States)

Satheesh, Viswanathan; Chidambaranathan, Parameswaran; Jagannadham, Prasanth Tejkumar; Kumar, Vajinder; Jain, Pradeep K; Chinnusamy, Viswanathan; Bhat, Shripad R; Srinivasan, R

2016-01-01

Steroidogenic acute regulatory related transfer (StART) proteins that are involved in transport of lipid molecules, play a myriad of functions in insects, mammals and plants. These proteins consist of a modular START domain of approximately 200 amino acids which binds and transfers the lipids. In the present study we have performed a genome-wide search for all START domain proteins in chickpea. The search identified 36 chickpea genes belonging to the START domain family. Through a phylogenetic tree reconstructed with Arabidopsis, rice, chickpea, and soybean START proteins, we were able to identify four transmembrane START (TM-START) proteins in chickpea. These four proteins are homologous to the highly conserved mammalian phosphatidylcholine transfer proteins. Multiple sequence alignment of all the transmembrane containing START proteins from Arabidopsis, rice, chickpea, and soybean revealed that the amino acid residues to which phosphatidylcholine binds in mammals, is also conserved in all these plant species, implying an important functional role and a very similar mode of action of all these proteins across dicots and monocots. This study characterizes a few of the not so well studied transmembrane START superfamily genes that may be involved in stress signaling. Expression analysis in various tissues showed that these genes are predominantly expressed in flowers and roots of chickpea. Three of the chickpea TM-START genes showed induced expression in response to drought, salt, wound and heat stress, suggesting their role in stress response.

Double hydrogen bonded ferroelectric liquid crystals: A study of field induced transition (FiT)

Science.gov (United States)

Vijayakumar, V. N.; Madhu Mohan, M. L. N.

2009-12-01

A novel series of chiral hydrogen bonded liquid crystals have been isolated. Hydrogen bond was formed between chiral nonmesogen ingredient levo tartaric acid and mesogenic p-n-alkoxybenzoic acids. Phase diagram was constructed from the transition temperatures obtained by DSC and polarizing optical microscopic (POM) studies. Thermal and electrical properties exhibited by three complexes namely LTA+8BA, LTA+7BA and LTA+5BA were discussed. Salient feature of the present work was the observation of a reentrant smectic ordering in LTA+8BA complex designated as C r∗ phase. This reentrant phenomenon was confirmed by DSC thermograms, optical textures of POM and temperature variation of capacitance and dielectric loss studies. Tilt angle was measured in smectic C ∗ and reentrant smectic C r∗ phases. Another interesting feature of the present investigation was the observation of a field induced transition (FiT) in the LTA+ nBA homologous series. Three threshold field values were noticed which give rise to two new phases (E 1 and E 2) induced by electric field and on further enhancement of the applied field the mesogen behaves like an optical shutter. FiT is reversible in the sense that when applied field is removed the original texture was restored.

Effect of storage conditions on graft of polypropylene non-woven fabric induced by electron beam

Energy Technology Data Exchange (ETDEWEB)

Lee, Jin Young; Jeun, Joon Pyo; Kang, Phil Hyun [Radiation Research Dvision for Industry and Environment, Korea Atomic Energy Research Institute, Jeongeup(Korea, Republic of)

2015-05-15

In this study, we fabricated effect of storage conditions on graft of polypropylene (PP) non-woven fabric induced by electron beam. The electron beam irradiations on PP non-woven fabric were carried out over a range of irradiation doses from 25 to 100 kGy to make free radicals on fabric surface. The radical measurement was established by electron spin resonance (ESR) for confirming the changes of the alkyl radical and peroxy radical according to effect of storage time, storage temperature and atmosphere. It was observed that the free radicals were increased with irradiation dose and decreased with storage time due to the continuous oxidation. However, the radical extinction was significantly delayed due to reduced mobility of radicals at extremely low temperature. The degree of graft based on the analysis of ESR was investigated. The conditions of graft reaction were set at a temperature: 60 degrees Celcius, reaction time: 6 hours and styrene monomer concentration: 20 wt%.

High fitness costs of climate change-induced camouflage mismatch.

Science.gov (United States)

Zimova, Marketa; Mills, L Scott; Nowak, J Joshua

2016-03-01

Anthropogenic climate change has created myriad stressors that threaten to cause local extinctions if wild populations fail to adapt to novel conditions. We studied individual and population-level fitness costs of a climate change-induced stressor: camouflage mismatch in seasonally colour molting species confronting decreasing snow cover duration. Based on field measurements of radiocollared snowshoe hares, we found strong selection on coat colour molt phenology, such that animals mismatched with the colour of their background experienced weekly survival decreases up to 7%. In the absence of adaptive response, we show that these mortality costs would result in strong population-level declines by the end of the century. However, natural selection acting on wide individual variation in molt phenology might enable evolutionary adaptation to camouflage mismatch. We conclude that evolutionary rescue will be critical for hares and other colour molting species to keep up with climate change. © 2016 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations.

Directory of Open Access Journals (Sweden)

Bryan D Moyer

Full Text Available BACKGROUND: Using fungiform (FG and circumvallate (CV taste buds isolated by laser capture microdissection and analyzed using gene arrays, we previously constructed a comprehensive database of gene expression in primates, which revealed over 2,300 taste bud-associated genes. Bioinformatics analyses identified hundreds of genes predicted to encode multi-transmembrane domain proteins with no previous association with taste function. A first step in elucidating the roles these gene products play in gustation is to identify the specific taste cell types in which they are expressed. METHODOLOGY/PRINCIPAL FINDINGS: Using double label in situ hybridization analyses, we identified seven new genes expressed in specific taste cell types, including sweet, bitter, and umami cells (TRPM5-positive, sour cells (PKD2L1-positive, as well as other taste cell populations. Transmembrane protein 44 (TMEM44, a protein with seven predicted transmembrane domains with no homology to GPCRs, is expressed in a TRPM5-negative and PKD2L1-negative population that is enriched in the bottom portion of taste buds and may represent developmentally immature taste cells. Calcium homeostasis modulator 1 (CALHM1, a component of a novel calcium channel, along with family members CALHM2 and CALHM3; multiple C2 domains; transmembrane 1 (MCTP1, a calcium-binding transmembrane protein; and anoctamin 7 (ANO7, a member of the recently identified calcium-gated chloride channel family, are all expressed in TRPM5 cells. These proteins may modulate and effect calcium signalling stemming from sweet, bitter, and umami receptor activation. Synaptic vesicle glycoprotein 2B (SV2B, a regulator of synaptic vesicle exocytosis, is expressed in PKD2L1 cells, suggesting that this taste cell population transmits tastant information to gustatory afferent nerve fibers via exocytic neurotransmitter release. CONCLUSIONS/SIGNIFICANCE: Identification of genes encoding multi-transmembrane domain proteins

Collagen induced aggregation of platelets and release of 14C serotonin from platelets depending on temperature and pH during in vitro storage of platelets

International Nuclear Information System (INIS)

Krause, J.

1978-01-01

The paper investigates collagen-induced platelet aggregation and 14 C serotonin release in dependence of age, temperature, and pH value during the storage of the conserved platelets. The optimum pH (with adjusted CO 2 /air mixture) for platelet storage is found to be pH 6.9. The optimum temperature for platelet storage is 4-8 0 C. After 12, 24, or 48 hours of storage at pH 6.9 and 4-8 0 C and subsequent heating of the platelet-rich plasma to 37 0 C for 30 minutes, the values determined for collagen-induced platelet aggregation and 14 C serotonin release rarely differed from the initial values before storage. Cold-induced spontaneous platelet aggregation and serotonin release of the platelets stored at 4-8 0 C can be avoided by 30-60 minutes pre-incubation of the platelets at 37 0 C before transfusions. The in vitro findings for collagen-induced platelet aggregation and 14 C serotonin release indicate that platelet storage for 24-48 hours at pH 6.9 and 4-8 0 C may be permissible also for clinical purposes. The problem remains open whether the clinical effect of these platelets is still sufficient after 48 hours of storage, but literature findings suggest that this may well be the case. (orig.) [de

High density fuel storage racks

International Nuclear Information System (INIS)

Groves, M.D.

1978-01-01

An apparatus is described for the safe and compact storage of nuclear fuel assemblies in an array of discrete open-ended neutron absorbing shields for which the theoretical minimum safe separation distance and cell pitch are known. Open-ended stainless steel end fittings are welded to each end of each shield and the end fittings are welded to each other in side-by-side relation, thereby reducing the cell pitch tolerance due to fabrication uncertainties. In addition, a multiplicity of ridges on the sides of each shield having a height equal to one half the theoretical minimum safe separation distance further reduce shield bowing tolerances. The net tolerance reduction permits a significant increase in the number of fuel assemblies that can be safely contained in a storage area of fixed size

PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection.

Science.gov (United States)

Marshall, Karen E; Hughson, Andrew; Vascellari, Sarah; Priola, Suzette A; Sakudo, Akikazu; Onodera, Takashi; Baron, Gerald S

2017-01-15

Glycosylphosphatidylinositol (GPI) anchoring of the prion protein (PrP C ) influences PrP C misfolding into the disease-associated isoform, PrP res , as well as prion propagation and infectivity. GPI proteins are found in cholesterol- and sphingolipid-rich membrane regions called rafts. Exchanging the GPI anchor for a nonraft transmembrane sequence redirects PrP C away from rafts. Previous studies showed that nonraft transmembrane PrP C variants resist conversion to PrP res when transfected into scrapie-infected N2a neuroblastoma cells, likely due to segregation of transmembrane PrP C and GPI-anchored PrP res in distinct membrane environments. Thus, it remained unclear whether transmembrane PrP C might convert to PrP res if seeded by an exogenous source of PrP res not associated with host cell rafts and without the potential influence of endogenous expression of GPI-anchored PrP C To further explore these questions, constructs containing either a C-terminal wild-type GPI anchor signal sequence or a nonraft transmembrane sequence containing a flexible linker were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2. NpL2 cells have physiological similarities to primary neurons, representing a novel and advantageous model for studying transmissible spongiform encephalopathy (TSE) infection. Cells were infected with inocula from multiple prion strains and in different biochemical states (i.e., membrane bound as in brain microsomes from wild-type mice or purified GPI-anchorless amyloid fibrils). Only GPI-anchored PrP C supported persistent PrP res propagation. Our data provide strong evidence that in cell culture GPI anchor-directed membrane association of PrP C is required for persistent PrP res propagation, implicating raft microdomains as a location for conversion. Mechanisms of prion propagation, and what makes them transmissible, are poorly understood. Glycosylphosphatidylinositol (GPI) membrane anchoring of the prion protein (PrP C

A unified conformational selection and induced fit approach to protein-peptide docking.

Directory of Open Access Journals (Sweden)

Mikael Trellet

Full Text Available Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II, flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.

Fitness declines towards range limits and local adaptation to climate affect dispersal evolution during climate‐induced range shifts

DEFF Research Database (Denmark)

Hargreaves, Anna; Bailey, Susan; Laird, Robert

2015-01-01

Dispersal ability will largely determine whether species track their climatic niches during climate change, a process especially important for populations at contracting (low-latitude/low-elevation) range limits that otherwise risk extinction. We investigate whether dispersal evolution....... We simulate a species distributed continuously along a temperature gradient using a spatially explicit, individual-based model. We compare range-wide dispersal evolution during climate stability vs. directional climate change, with uniform fitness vs. fitness that declines towards range limits (RLs...... at contracting range limits is facilitated by two processes that potentially enable edge populations to experience and adjust to the effects of climate deterioration before they cause extinction: (i) climate-induced fitness declines towards range limits and (ii) local adaptation to a shifting climate gradient...

Cloning and characterization of SCART1, a novel scavenger receptor cysteine-rich type I transmembrane molecule

DEFF Research Database (Denmark)

Holm, Dorte; Fink, Dorte Rosenbek; Grønlund, Jørn

2009-01-01

We have cloned and characterized a novel murine transmembrane molecule, mSCART1 belonging to the scavenger receptor cysteine-rich superfamily. The cDNA encodes a polypeptide chain of 989 amino acids, organized as a type I transmembrane protein that contains eight extracellular SRCR domains followed...

First principles design of a core bioenergetic transmembrane electron-transfer protein

Energy Technology Data Exchange (ETDEWEB)

Goparaju, Geetha; Fry, Bryan A.; Chobot, Sarah E.; Wiedman, Gregory; Moser, Christopher C.; Leslie Dutton, P.; Discher, Bohdana M.

2016-05-01

Here we describe the design, Escherichia coli expression and characterization of a simplified, adaptable and functionally transparent single chain 4-α-helix transmembrane protein frame that binds multiple heme and light activatable porphyrins. Such man-made cofactor-binding oxidoreductases, designed from first principles with minimal reference to natural protein sequences, are known as maquettes. This design is an adaptable frame aiming to uncover core engineering principles governing bioenergetic transmembrane electron-transfer function and recapitulate protein archetypes proposed to represent the origins of photosynthesis. This article is part of a Special Issue entitled Biodesign for Bioenergetics — the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

Insight of Transmembrane Processes of Self-Assembling Nanotubes Based on a Cyclic Peptide Using Coarse Grained Molecular Dynamics Simulation.

Science.gov (United States)

Fu, Yankai; Yan, Tingxuan; Xu, Xia

2017-09-28

Transmembrane self-assembling cyclic peptide (SCP) nanotubes are promising candidates for delivering specific molecules through cell membranes. The detailed mechanisms behind the transmembrane processes, as well as stabilization factors of transmembrane structures, are difficult to elucidate through experiments. In this study, the effects of peptide sequence and oligomeric state on the transmembrane capabilities of SCP nanotubes and the perturbation of embedded SCP nanotubes acting on the membrane were investigated based on coarse grained molecular dynamics simulation. The simulation results reveal that hydrophilic SCP oligomers result in the elevation of the energy barrier while the oligomerization of hydrophobic SCPs causes the reduction of the energy barrier, further leading to membrane insertion. Once SCP nanotubes are embedded, membrane properties such as density, thickness, ordering state and lateral mobility are adjusted along the radial direction. This study provides insight into the transmembrane strategy of SCP nanotubes and sheds light on designing novel transport systems.

TASK-TECHNOLOGY FIT AND PERSON-JOB FIT: A BEAUTY CONTEST TO IMPROVE THE SUCCESS OF INFORMATION SYSTEMS

OpenAIRE

Suryani, Woro Dwi; Sumiyana, Sumiyana

2015-01-01

This study raises the issue that information system success could be enhanced by complementingother factors. This study investigates the success of information systems by inducing2the task-technology fit (TTF) and person-job fit (PJF) into the DeLone and McLean model. Thisstudy aims to examine, among the two induced factors, which one is able to explain andimprove the success of the information systems implementation.The results of this study indicate that the TTF explains the models’ goodnes...

Cyclic high temperature heat storage using borehole heat exchangers

Science.gov (United States)

Boockmeyer, Anke; Delfs, Jens-Olaf; Bauer, Sebastian

2016-04-01

The transition of the German energy supply towards mainly renewable energy sources like wind or solar power, termed "Energiewende", makes energy storage a requirement in order to compensate their fluctuating production and to ensure a reliable energy and power supply. One option is to store heat in the subsurface using borehole heat exchangers (BHEs). Efficiency of thermal storage is increasing with increasing temperatures, as heat at high temperatures is more easily injected and extracted than at temperatures at ambient levels. This work aims at quantifying achievable storage capacities, storage cycle times, injection and extraction rates as well as thermal and hydraulic effects induced in the subsurface for a BHE storage site in the shallow subsurface. To achieve these aims, simulation of these highly dynamic storage sites is performed. A detailed, high-resolution numerical simulation model was developed, that accounts for all BHE components in geometrical detail and incorporates the governing processes. This model was verified using high quality experimental data and is shown to achieve accurate simulation results with excellent fit to the available experimental data, but also leads to large computational times due to the large numerical meshes required for discretizing the highly transient effects. An approximate numerical model for each type of BHE (single U, double U and coaxial) that reduces the number of elements and the simulation time significantly was therefore developed for use in larger scale simulations. The approximate numerical model still includes all BHE components and represents the temporal and spatial temperature distribution with a deviation of less than 2% from the fully discretized model. Simulation times are reduced by a factor of ~10 for single U-tube BHEs, ~20 for double U-tube BHEs and ~150 for coaxial BHEs. This model is then used to investigate achievable storage capacity, injection and extraction rates as well as induced effects for

Activation gating kinetics of GIRK channels are mediated by cytoplasmic residues adjacent to transmembrane domains.

Science.gov (United States)

Sadja, Rona; Reuveny, Eitan

2009-01-01

G-protein-coupled inwardly rectifying potassium channels (GIRK/Kir3.x) are involved in neurotransmission-mediated reduction of excitability. The gating mechanism following G protein activation of these channels likely proceeds from movement of inner transmembrane helices to allow K(+) ions movement through the pore of the channel. There is limited understanding of how the binding of G-protein betagamma subunits to cytoplasmic regions of the channel transduces the signal to the transmembrane regions. In this study, we examined the molecular basis that governs the activation kinetics of these channels, using a chimeric approach. We identified two regions as being important in determining the kinetics of activation. One region is the bottom of the outer transmembrane helix (TM1) and the cytoplasmic domain immediately adjacent (the slide helix); and the second region is the bottom of the inner transmembrane helix (TM2) and the cytoplasmic domain immediately adjacent. Interestingly, both of these regions are sufficient in mediating the kinetics of fast activation gating. This result suggests that there is a cooperative movement of either one of these domains to allow fast and efficient activation gating of GIRK channels.

Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.

Science.gov (United States)

Wei, Shipeng; Roessler, Bryan C; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L; Kirk, Kevin L

2014-07-18

ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server

DEFF Research Database (Denmark)

Käll, Lukas; Krogh, Anders; Sonnhammer, Erik L L

2007-01-01

. The method makes an optimal choice between transmembrane segments and signal peptides, and also allows constrained and homology-enriched predictions. We here present a web interface (http://phobius.cgb.ki.se and http://phobius.binf.ku.dk) to access Phobius. Udgivelsesdato: 2007-Jul......When using conventional transmembrane topology and signal peptide predictors, such as TMHMM and SignalP, there is a substantial overlap between these two types of predictions. Applying these methods to five complete proteomes, we found that 30-65% of all predicted signal peptides and 25-35% of all...

Integrity assessment of a storage tank

Energy Technology Data Exchange (ETDEWEB)

Goncalves, Osorio Correa; Santos, Jose Henrique Gomes dos; Carvalho, Alexis Fernandes [PETROBRAS Transporte S.A. (TRANSPETRO), Rio de Janeiro, RJ (Brazil)

2005-07-01

In the last internal inspection of a 5000 bbl freshwater storage tank located in a shipping terminal, widespread pitting corrosion was detected on the shell courses. In some of these pits, its depth was such that the remaining thickness was bellow the minimum thickness required according to the design code. Nevertheless, this approach is overly conservative since it does not consider the pits size, depth and spacing. Thanks to advances in stress analysis, new tools are available for the evaluation of damaged equipment widely employed in the oil industry such as pressure vessels, piping and storage tanks. In the present work, the authors present the integrity assessment performed on this tank using the Fitness for Service approach using the methods and procedures contained in the document API RP 579 (Fitness-for-service). (author)

Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss

International Nuclear Information System (INIS)

Izquierdo-Vega, Jeannett A.; Sanchez-Gutierrez, Manuel; Razo, Luz Maria del

2008-01-01

Fluorosis, caused by drinking water contamination with inorganic fluoride, is a public health problem in many areas around the world. The aim of the study was to evaluate the effect of environmentally relevant doses of fluoride on in vitro fertilization (IVF) capacity of spermatozoa, and its relationship to spermatozoa mitochondrial transmembrane potential (ΔΨ m ). Male Wistar rats were administered at 5 mg fluoride/kg body mass/24 h, or deionized water orally for 8 weeks. We evaluated several spermatozoa parameters in treated and untreated rats: i) standard quality analysis, ii) superoxide dismutase (SOD) activity, iii) the generation of superoxide anion (O 2 ·- ), iv) lipid peroxidation concentration, v) ultrastructural analyses of spermatozoa using transmission electron microscopy, vi) ΔΨ m , vii) acrosome reaction, and viii) IVF capability. Spermatozoa from fluoride-treated rats exhibited a significant decrease in SOD activity (∼ 33%), accompanied with a significant increase in the generation of O 2 · (∼ 40%), a significant decrease in ΔΨ m (∼ 33%), and a significant increase in lipid peroxidation concentration (∼ 50%), relative to spermatozoa from the control group. Consistent with this finding, spermatozoa from fluoride-treated rats exhibited altered plasmatic membrane. In addition, the percentage of fluoride-treated spermatozoa capable of undergoing the acrosome reaction was decreased relative to control spermatozoa (34 vs. 55%), while the percentage fluoride-treated spermatozoa capable of oocyte fertilization was also significantly lower than the control group (13 vs. 71%). These observations suggest that subchronic exposure to fluoride causes oxidative stress damage and loss of mitochondrial transmembrane potential, resulting in reduced fertility

Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies.

Science.gov (United States)

Bocharov, Eduard V; Lesovoy, Dmitry M; Goncharuk, Sergey A; Goncharuk, Marina V; Hristova, Kalina; Arseniev, Alexander S

2013-11-05

Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via lateral dimerization in the plasma membrane, and plays an important role in human development and disease. Eight different pathogenic mutations, implicated in cancers and growth disorders, have been identified in the FGFR3 transmembrane segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two transmembrane helices pack into a symmetric left-handed dimer, with intermolecular stacking interactions occurring in the dimer central region. Some pathogenic mutations fall within the helix-helix interface, whereas others are located within a putative alternative interface. This implies that although the observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3-mediated transduction across the membrane is complex. We propose an FGFR3 signaling mechanism that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trans-membrane area asymmetry controls the shape of cellular organelles

NARCIS (Netherlands)

Beznoussenko, Galina V; Pilyugin, Sergei S; Geerts, Willie J C; Kozlov, Michael M; Burger, Koert N J; Luini, Alberto; Derganc, Jure; Mironov, Alexander A

2015-01-01

Membrane organelles often have complicated shapes and differ in their volume, surface area and membrane curvature. The ratio between the surface area of the cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines the membrane curvature within different sites of the organelle.

Modelling of a transmembrane evaporation module for desalination of seawater

NARCIS (Netherlands)

Guijt, C.M.; Racz, I.G.; van Heuven, Jan Willem; Reith, T.; de Haan, A.B.

1999-01-01

Transmembrane evaporation (often called membrane distillation) carried out in a countercurrent flow module, in which incoming cold seawater is heated by the condensing product water flow, is a promising technology for low-cost seawater desalination. This paper presents a model for preliminary design

Storage containers for radioactive material

International Nuclear Information System (INIS)

Cassidy, D.A.; Dates, L.R.; Groh, E.F.

1981-01-01

A radioactive material storage system is disclosed for use in the laboratory. This system is composed of the following: a flat base plate with a groove in one surface thereof and a hollow pedestal extending perpendicularly away from the other surface thereof; a sealing gasket in the groove, a cover having a filter therein and an outwardly extending flange which fits over the plate; the groove and the gasket, and a clamp for maintaining the cover and the plate are sealed together, whereby the plate and the cover and the clamp cooperate to provide a storage area for radioactive material readily accessible for use or inventory. Wall mounts are provided to prevent accidental formation of critical masses during storage

Transmembrane adaptor molecules: a new category of lymphoid-cell markers

Czech Academy of Sciences Publication Activity Database

Tedoldi, S.; Paterson, J.C.; Hansmann, M.-L.; Natkunam, Y.; Rüdiger, T.; Angelisová, Pavla; Du, M.Q.; Roberton, H.; Roncador, G.; Sanchez, L.; Pozzobon, M.; Masir, N.; Barry, R.; Pileri, S.; Mason, D.Y.; Marafioti, T.; Hořejší, Václav

2006-01-01

Roč. 107, č. 1 (2006), s. 213-221 ISSN 0006-4971 R&D Projects: GA MŠk(CZ) 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : transmembrane adaptors * PAG * LIME Subject RIV: EC - Immunology Impact factor: 10.370, year: 2006

Molecular Simulations of Sequence-Specific Association of Transmembrane Proteins in Lipid Bilayers

Science.gov (United States)

Doxastakis, Manolis; Prakash, Anupam; Janosi, Lorant

2011-03-01

Association of membrane proteins is central in material and information flow across the cellular membranes. Amino-acid sequence and the membrane environment are two critical factors controlling association, however, quantitative knowledge on such contributions is limited. In this work, we study the dimerization of helices in lipid bilayers using extensive parallel Monte Carlo simulations with recently developed algorithms. The dimerization of Glycophorin A is examined employing a coarse-grain model that retains a level of amino-acid specificity, in three different phospholipid bilayers. Association is driven by a balance of protein-protein and lipid-induced interactions with the latter playing a major role at short separations. Following a different approach, the effect of amino-acid sequence is studied using the four transmembrane domains of the epidermal growth factor receptor family in identical lipid environments. Detailed characterization of dimer formation and estimates of the free energy of association reveal that these helices present significant affinity to self-associate with certain dimers forming non-specific interfaces.

Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.

Science.gov (United States)

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-10-01

Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.

Changes induced by gamma radiation in microsomal membranes of storage of garlic

International Nuclear Information System (INIS)

Perez, M.B.; Croci, C.A.; Aveldano, M.I.

2003-01-01

This study evaluates the effects of the radio inhibition process on garlic bulbs in terms of phase properties of microsomal membranes and their lipid and fatty acid composition. Garlic bulbs were irradiated with an average dose of 60 Gy of 60 Co gamma rays 30-40 days after harvest. The treatment was carried out in the facilities of the National Atomic Energy Commission (CNEA). Rough and smooth microsomal membranes were isolated by ultracentrifugation from tissues of irradiated and non-irradiated storage leaves. Wide angle X-ray diffractograms of both fractions were recorded along 270 days of storage. Lipids were separated by thin layer chromatography. The fatty acid composition of major lipid fractions was studied by gas-liquid chromatography. The diffractograms featured peaks at Bragg spacing of 4.15 Armstrong and 3.75 Armstrong, revealing the presence of a gel (crystalline) phase, while the characteristic peak of the liquid-crystalline phase (4.6 Armstrong) was not observed in both sorts of membranes. Irradiation was found to bring about modifications in the intensity of 4.15 Armstrong and 3.75 Armstrong peaks from smooth microsomal membranes, but not in the behaviour along the studied period. Data from the rough microsomal fraction were erratic. Parallel to these changes, radiation induced significant modifications in the level of smooth microsomal membrane triacylglycerols in relation to phospholipids and their fatty acids. These findings indicate that the storage leaf tissues of garlic are radiosensitive both in terms of physical and chemical properties of their microsomal membranes. From the practical point of view, these results could be the basis for the development of techniques to be applied to storage garlic to evaluate if it was irradiated. (author)

The transmembrane collagen COL-99 guides longitudinally extending axons in C. elegans.

Science.gov (United States)

Taylor, Jesse; Unsoeld, Thomas; Hutter, Harald

2018-06-01

We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it. Vertebrate homologs of COL-99 have been shown to be expressed in mammalian nervous systems and linked to various neurological disease but have not been associated with guidance of extending neurons. col-99 acts genetically with the discoidin domain receptors ddr-1 and ddr-2, which are expressed by neurons affected in col-99 mutants. Discoidin domain receptors are activated by collagens in vertebrates. DDR-1 and DDR-2 may function as receptors for COL-99. Our results establish a novel role for a transmembrane collagen in axonal guidance and asymmetry establishment of the VNC. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of protein dynamics in transmembrane receptor signalling

DEFF Research Database (Denmark)

Wang, Yong; Bugge, Katrine Østergaard; Kragelund, Birthe Brandt

2018-01-01

Cells are dependent on transmembrane receptors to communicate and transform chemical and physical signals into intracellular responses. Because receptors transport 'information', conformational changes and protein dynamics play a key mechanistic role. We here review examples where experiment...... to function. Because the receptors function in a heterogeneous environment and need to be able to switch between distinct functional states, they may be particularly sensitive to small perturbations that complicate studies linking dynamics to function....

Regulation of KV channel voltage-dependent activation by transmembrane β subunits

Directory of Open Access Journals (Sweden)

Xiaohui eSun

2012-04-01

Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

[Research advances in CKLF-like MARVEL transmembrane domain containing member 5].

Science.gov (United States)

Yuan, Ye-qing; Xiao, Yun-bei; Liu, Zhen-hua; Zhang, Xiao-wei; Xu, Tao; Wang, Xiao-feng

2012-12-01

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.

Molecular Insights into the Transmembrane Domain of the Thyrotropin Receptor.

Directory of Open Access Journals (Sweden)

Vanessa Chantreau

Full Text Available The thyrotropin receptor (TSHR is a G protein-coupled receptor (GPCR that is member of the leucine-rich repeat subfamily (LGR. In the absence of crystal structure, the success of rational design of ligands targeting the receptor internal cavity depends on the quality of the TSHR models built. In this subfamily, transmembrane helices (TM 2 and 5 are characterized by the absence of proline compared to most receptors, raising the question of the structural conformation of these helices. To gain insight into the structural properties of these helices, we carried out bioinformatics and experimental studies. Evolutionary analysis of the LGR family revealed a deletion in TM5 but provided no information on TM2. Wild type residues at positions 2.58, 2.59 or 2.60 in TM2 and/or at position 5.50 in TM5 were substituted to proline. Depending on the position of the proline substitution, different effects were observed on membrane expression, glycosylation, constitutive cAMP activity and responses to thyrotropin. Only proline substitution at position 2.59 maintained complex glycosylation and high membrane expression, supporting occurrence of a bulged TM2. The TSHR transmembrane domain was modeled by homology with the orexin 2 receptor, using a protocol that forced the deletion of one residue in the TM5 bulge of the template. The stability of the model was assessed by molecular dynamics simulations. TM5 straightened during the equilibration phase and was stable for the remainder of the simulations. Our data support a structural model of the TSHR transmembrane domain with a bulged TM2 and a straight TM5 that is specific of glycoprotein hormone receptors.

TMS-induced neural noise in sensory cortex interferes with short-term memory storage in prefrontal cortex.

Science.gov (United States)

Bancroft, Tyler D; Hogeveen, Jeremy; Hockley, William E; Servos, Philip

2014-01-01

In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.'s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature.

The effect of newly induced mutations on the fitness of genotypes and populations of yeast (Saccharomyces cerevisiae).

Science.gov (United States)

Orthen, E; Lange, P; Wöhrmann, K

1984-12-01

This paper analyses the fate of artificially induced mutations and their importance to the fitness of populations of the yeast, Saccharomyces cerevisiae, an increasingly important model organism in population genetics. Diploid strains, treated with UV and EMS, were cultured asexually for approximately 540 generations and under conditions where the asexual growth was interrupted by a sexual phase. Growth rates of 100 randomly sampled diploid clones were estimated at the beginning and at the end of the experiment. After the induction of sporulation the growth rates of 100 randomly sampled spores were measured. UV and EMS treatment decreases the average growth rate of the clones significantly but increases the variability in comparison to the untreated control. After selection over approximately 540 generations, variability in growth rates was reduced to that of the untreated control. No increase in mean population fitness was observed. However, the results show that after selection there still exists a large amount of hidden genetic variability in the populations which is revealed when the clones are cultivated in environments other than those in which selection took place. A sexual phase increased the reduction of the induced variability.

Considerations applicable to the transportability of a transportable storage cask at the end of the storage period

International Nuclear Information System (INIS)

Sanders, T.L.; Ottinger, C.A.; Brimhall, J.L.; Creer, J.M.; Gilbert, E.R.; Jones, R.H.; McConnell, P.E.

1991-11-01

Additional spent fuel storage capacity is needed at many nuclear power plant sites where spent fuel storage pools have either reached or are expected to reach maximum capacities before spent fuel can be removed. This analysis examines certain aspects of Transportable Storage Casks (TSC) to assist in the determination of their feasibility as an option for at-reactor dry storage. Factors that can affect in-transport reliability include: the quality of design, development, and fabrication activities; the possibilities of damage or error during loading and closure; in-storage deterioration or unanticipated storage conditions; and the potential for loss of storage period monitoring/measurement data necessary for verifying the TSC fitness-for-transport. The reported effort utilizes a relative reliability comparison of TSCs to Transport-Only Casks (TOC) to identify and prioritize those issues and activities that are unique to TSCs. TSC system recommendations combine certain design and operational features, such as in-service monitoring, pretransport assessments, and conservation design assumptions, which when implemented and verified, should sufficiently ensure that the system will perform as intended in a later transport environment

DOUBLE-EXPONENTIAL FITTING FUNCTION FOR EVALUATION OF COSMIC-RAY-INDUCED NEUTRON FLUENCE RATE IN ARBITRARY LOCATIONS.

Science.gov (United States)

Li, Huailiang; Yang, Yigang; Wang, Qibiao; Tuo, Xianguo; Julian Henderson, Mark; Courtois, Jérémie

2017-12-01

The fluence rate of cosmic-ray-induced neutrons (CRINs) varies with many environmental factors. While many current simulation and experimental studies have focused mainly on the altitude variation, the specific rule that the CRINs vary with geomagnetic cutoff rigidity (which is related to latitude and longitude) was not well considered. In this article, a double-exponential fitting function F=(A1e-A2CR+A3)eB1Al, is proposed to evaluate the CRINs' fluence rate varying with geomagnetic cutoff rigidity and altitude. The fitting R2 can have a value up to 0.9954, and, moreover, the CRINs' fluence rate in an arbitrary location (latitude, longitude and altitude) can be easily evaluated by the proposed function. The field measurements of the CRINs' fluence rate and H*(10) rate in Mt. Emei and Mt. Bowa were carried out using a FHT-762 and LB 6411 neutron prober, respectively, and the evaluation results show that the fitting function agrees well with the measurement results. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Disk Storage Server

CERN Multimedia

This model was a disk storage server used in the Data Centre up until 2012. Each tray contains a hard disk drive (see the 5TB hard disk drive on the main disk display section - this actually fits into one of the trays). There are 16 trays in all per server. There are hundreds of these servers mounted on racks in the Data Centre, as can be seen.

Transmembrane protein diffusion in gel-supported dual-leaflet membranes.

Science.gov (United States)

Wang, Chih-Ying; Hill, Reghan J

2014-11-18

Tools to measure transmembrane-protein diffusion in lipid bilayer membranes have advanced in recent decades, providing a need for predictive theoretical models that account for interleaflet leaflet friction on tracer mobility. Here we address the fully three-dimensional flows driven by a (nonprotruding) transmembrane protein embedded in a dual-leaflet membrane that is supported above and below by soft porous supports (e.g., hydrogel or extracellular matrix), each of which has a prescribed permeability and solvent viscosity. For asymmetric configurations, i.e., supports with contrasting permeability, as realized for cells in contact with hydrogel scaffolds or culture media, the diffusion coefficient can reflect interleaflet friction. Reasonable approximations, for sufficiently large tracers on low-permeability supports, are furnished by a recent phenomenological theory from the literature. Interpreting literature data, albeit for hard-supported membranes, provides a theoretical basis for the phenomenological Stokes drag law as well as strengthening assertions that nonhydrodynamic interactions are important in supported bilayer systems, possibly leading to overestimates of the membrane/leaflet viscosity. Our theory provides a theoretical foundation for future experimental studies of tracer diffusion in gel-supported membranes.

Storage and retrieval of electromagnetic waves with orbital angular momentum via plasmon-induced transparency.

Science.gov (United States)

Bai, Zhengyang; Xu, Datang; Huang, Guoxiang

2017-01-23

We propose a scheme to realize the storage and retrieval of high-dimensional electromagnetic waves with orbital angular momentum (OAM) via plasmon-induced transparency (PIT) in a metamaterial, which consists of an array of meta-atoms constructed by a metallic structure loaded with two varactors. We show that due to PIT effect the system allows the existence of shape-preserving dark-mode plasmonic polaritons, which are mixture of electromagnetic-wave modes and dark oscillatory modes of the meta-atoms and may carry various OAMs. We demonstrate that the slowdown, storage and retrieval of multi-mode electromagnetic waves with OAMs can be achieved through the active manipulation of a control field. Our work raises the possibility for realizing PIT-based spatial multi-mode memory of electromagnetic waves and is promising for practical application of information processing with large capacity by using room-temperature metamaterials.

Effect of flow rate and temperature on transmembrane blood pressure drop in an extracorporeal artificial lung.

Science.gov (United States)

Park, M; Costa, E L V; Maciel, A T; Barbosa, E V S; Hirota, A S; Schettino, G de P; Azevedo, L C P

2014-11-01

Transmembrane pressure drop reflects the resistance of an artificial lung system to blood transit. Decreased resistance (low transmembrane pressure drop) enhances blood flow through the oxygenator, thereby, enhancing gas exchange efficiency. This study is part of a previous one where we observed the behaviour and the modulation of blood pressure drop during the passage of blood through artificial lung membranes. Before and after the induction of multi-organ dysfunction, the animals were instrumented and analysed for venous-venous extracorporeal membrane oxygenation, using a pre-defined sequence of blood flows. Blood flow and revolutions per minute (RPM) of the centrifugal pump varied in a linear fashion. At a blood flow of 5.5 L/min, pre- and post-pump blood pressures reached -120 and 450 mmHg, respectively. Transmembrane pressures showed a significant spread, particularly at blood flows above 2 L/min; over the entire range of blood flow rates, there was a positive association of pressure drop with blood flow (0.005 mmHg/mL/minute of blood flow) and a negative association of pressure drop with temperature (-4.828 mmHg/(°Celsius). These associations were similar when blood flows of below and above 2000 mL/minute were examined. During its passage through the extracorporeal system, blood is exposed to pressure variations from -120 to 450 mmHg. At high blood flows (above 2 L/min), the drop in transmembrane pressure becomes unpredictable and highly variable. Over the entire range of blood flows investigated (0-5500 mL/min), the drop in transmembrane pressure was positively associated with blood flow and negatively associated with body temperature. © The Author(s) 2014.

Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

Directory of Open Access Journals (Sweden)

Balda Maria S

2009-12-01

Full Text Available Abstract Background Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Results Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Conclusions Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.

Sperm storage induces an immunity cost in ants

DEFF Research Database (Denmark)

Baer, Boris; Armitage, Sophie A O; Boomsma, Jacobus J

2006-01-01

Ant queens are among the most long-lived insects known. They mate early in adult life and maintain millions of viable sperm in their sperm storage organ until they die many years later. Because they never re-mate, the reproductive success of queens is ultimately sperm-limited, but it is not known...... what selective forces determine the upper limit to sperm storage. Here we show that sperm storage carries a significant cost of reduced immunity during colony founding. Newly mated queens of the leaf-cutting ant Atta colombica upregulate their immune response shortly after completing their nest burrow...

Human Cytomegalovirus Exploits Interferon-Induced Transmembrane Proteins To Facilitate Morphogenesis of the Virion Assembly Compartment

Science.gov (United States)

Xie, Maorong; Xuan, Baoqin; Shan, Jiaoyu; Pan, Deng; Sun, Yamei; Shan, Zhao; Zhang, Jinping; Yu, Dong

2014-01-01

ABSTRACT Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we

Conformational constraining of inactive and active States of a seven transmembrane receptor by metal ion site engineering in the extracellular end of transmembrane segment V

DEFF Research Database (Denmark)

Rosenkilde, Mette M; David, Ralf; Oerlecke, Ilka

2006-01-01

The extracellular part of transmembrane segment V (TM-V) is expected to be involved in the activation process of 7TM receptors, but its role is far from clear. Here, we study the highly constitutively active CXC-chemokine receptor encoded by human herpesvirus 8 (ORF74-HHV8), in which a metal ion ...

TMFoldWeb: a web server for predicting transmembrane protein fold class.

Science.gov (United States)

Kozma, Dániel; Tusnády, Gábor E

2015-09-17

Here we present TMFoldWeb, the web server implementation of TMFoldRec, a transmembrane protein fold recognition algorithm. TMFoldRec uses statistical potentials and utilizes topology filtering and a gapless threading algorithm. It ranks template structures and selects the most likely candidates and estimates the reliability of the obtained lowest energy model. The statistical potential was developed in a maximum likelihood framework on a representative set of the PDBTM database. According to the benchmark test the performance of TMFoldRec is about 77 % in correctly predicting fold class for a given transmembrane protein sequence. An intuitive web interface has been developed for the recently published TMFoldRec algorithm. The query sequence goes through a pipeline of topology prediction and a systematic sequence to structure alignment (threading). Resulting templates are ordered by energy and reliability values and are colored according to their significance level. Besides the graphical interface, a programmatic access is available as well, via a direct interface for developers or for submitting genome-wide data sets. The TMFoldWeb web server is unique and currently the only web server that is able to predict the fold class of transmembrane proteins while assigning reliability scores for the prediction. This method is prepared for genome-wide analysis with its easy-to-use interface, informative result page and programmatic access. Considering the info-communication evolution in the last few years, the developed web server, as well as the molecule viewer, is responsive and fully compatible with the prevalent tablets and mobile devices.

Structure and function of the cystic fibrosis transmembrane conductance regulator

Directory of Open Access Journals (Sweden)

M.M. Morales

1999-08-01

Full Text Available Cystic fibrosis (CF is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR. Mutations in the CFTR gene may result in a defective processing of its protein and alter the function and regulation of this channel. Mutations are associated with different symptoms, including pancreatic insufficiency, bile duct obstruction, infertility in males, high sweat Cl-, intestinal obstruction, nasal polyp formation, chronic sinusitis, mucus dehydration, and chronic Pseudomonas aeruginosa and Staphylococcus aureus lung infection, responsible for 90% of the mortality of CF patients. The gene responsible for the cellular defect in CF was cloned in 1989 and its protein product CFTR is activated by an increase of intracellular cAMP. The CFTR contains two membrane domains, each with six transmembrane domain segments, two nucleotide-binding domains (NBDs, and a cytoplasmic domain. In this review we discuss the studies that have correlated the role of each CFTR domain in the protein function as a chloride channel and as a regulator of the outwardly rectifying Cl- channels (ORCCs.

Nanodiamond for hydrogen storage: temperature-dependent hydrogenation and charge-induced dehydrogenation.

Science.gov (United States)

Lai, Lin; Barnard, Amanda S

2012-02-21

Carbon-based hydrogen storage materials are one of hottest research topics in materials science. Although the majority of studies focus on highly porous loosely bound systems, these systems have various limitations including use at elevated temperature. Here we propose, based on computer simulations, that diamond nanoparticles may provide a new promising high temperature candidate with a moderate storage capacity, but good potential for recyclability. The hydrogenation of nanodiamonds is found to be easily achieved, in agreement with experiments, though we find the stability of hydrogenation is dependent on the morphology of nanodiamonds and surrounding environment. Hydrogenation is thermodynamically favourable even at high temperature in pure hydrogen, ammonia, and methane gas reservoirs, whereas water vapour can help to reduce the energy barrier for desorption. The greatest challenge in using this material is the breaking of the strong covalent C-H bonds, and we have identified that the spontaneous release of atomic hydrogen may be achieved through charging of hydrogenated nanodiamonds. If the degree of induced charge is properly controlled, the integrity of the host nanodiamond is maintained, which indicates that an efficient and recyclable approach for hydrogen release may be possible. This journal is © The Royal Society of Chemistry 2012

Role of the vaccinia virus O3 protein in cell entry can be fulfilled by its Sequence flexible transmembrane domain

Energy Technology Data Exchange (ETDEWEB)

Satheshkumar, P.S.; Chavre, James; Moss, Bernard, E-mail: bmoss@nih.gov

2013-09-15

The vaccinia virus O3 protein, a component of the entry–fusion complex, is encoded by all chordopoxviruses. We constructed truncation mutants and demonstrated that the transmembrane domain, which comprises two-thirds of this 35 amino acid protein, is necessary and sufficient for interaction with the entry–fusion complex and function in cell entry. Nevertheless, neither single amino acid substitutions nor alanine scanning mutagenesis revealed essential amino acids within the transmembrane domain. Moreover, replication-competent mutant viruses were generated by randomization of 10 amino acids of the transmembrane domain. Of eight unique viruses, two contained only two amino acids in common with wild type and the remainder contained one or none within the randomized sequence. Although these mutant viruses formed normal size plaques, the entry–fusion complex did not co-purify with the mutant O3 proteins suggesting a less stable interaction. Thus, despite low specific sequence requirements, the transmembrane domain is sufficient for function in entry. - Highlights: • The 35 amino acid O3 protein is required for efficient vaccinia virus entry. • The transmembrane domain of O3 is necessary and sufficient for entry. • Mutagenesis demonstrated extreme sequence flexibility compatible with function.

The transmembrane domain of the p75 neurotrophin receptor stimulates phosphorylation of the TrkB tyrosine kinase receptor.

Science.gov (United States)

Saadipour, Khalil; MacLean, Michael; Pirkle, Sean; Ali, Solav; Lopez-Redondo, Maria-Luisa; Stokes, David L; Chao, Moses V

2017-10-06

The function of protein products generated from intramembraneous cleavage by the γ-secretase complex is not well defined. The γ-secretase complex is responsible for the cleavage of several transmembrane proteins, most notably the amyloid precursor protein that results in Aβ, a transmembrane (TM) peptide. Another protein that undergoes very similar γ-secretase cleavage is the p75 neurotrophin receptor. However, the fate of the cleaved p75 TM domain is unknown. p75 neurotrophin receptor is highly expressed during early neuronal development and regulates survival and process formation of neurons. Here, we report that the p75 TM can stimulate the phosphorylation of TrkB (tyrosine kinase receptor B). In vitro phosphorylation experiments indicated that a peptide representing p75 TM increases TrkB phosphorylation in a dose- and time-dependent manner. Moreover, mutagenesis analyses revealed that a valine residue at position 264 in the rat p75 neurotrophin receptor is necessary for the ability of p75 TM to induce TrkB phosphorylation. Because this residue is just before the γ-secretase cleavage site, we then investigated whether the p75(αγ) peptide, which is a product of both α- and γ-cleavage events, could also induce TrkB phosphorylation. Experiments using TM domains from other receptors, EGFR and FGFR1, failed to stimulate TrkB phosphorylation. Co-immunoprecipitation and biochemical fractionation data suggested that p75 TM stimulates TrkB phosphorylation at the cell membrane. Altogether, our results suggest that TrkB activation by p75(αγ) peptide may be enhanced in situations where the levels of the p75 receptor are increased, such as during brain injury, Alzheimer's disease, and epilepsy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of the GXXXG motif in the first transmembrane segment of Japanese encephalitis virus precursor membrane (prM protein

Directory of Open Access Journals (Sweden)

Wu Suh-Chin

2010-05-01

Full Text Available Abstract The interaction between prM and E proteins in flavivirus-infected cells is a major driving force for the assembly of flavivirus particles. We used site-directed mutagenesis to study the potential role of the transmembrane domains of the prM proteins of Japanese encephalitis virus (JEV in prM-E heterodimerization as well as subviral particle formation. Alanine insertion scanning mutagenesis within the GXXXG motif in the first transmembrane segment of JEV prM protein affected the prM-E heterodimerization; its specificity was confirmed by replacing the two glycines of the GXXXG motif with alanine, leucine and valine. The GXXXG motif was found to be conserved in the JEV serocomplex viruses but not other flavivirus groups. These mutants with alanine inserted in the two prM transmembrane segments all impaired subviral particle formation in cell cultures. The prM transmembrane domains of JEV may play importation roles in prM-E heterodimerization and viral particle assembly.

System and methods for predicting transmembrane domains in membrane proteins and mining the genome for recognizing G-protein coupled receptors

Science.gov (United States)

Trabanino, Rene J; Vaidehi, Nagarajan; Hall, Spencer E; Goddard, William A; Floriano, Wely

2013-02-05

The invention provides computer-implemented methods and apparatus implementing a hierarchical protocol using multiscale molecular dynamics and molecular modeling methods to predict the presence of transmembrane regions in proteins, such as G-Protein Coupled Receptors (GPCR), and protein structural models generated according to the protocol. The protocol features a coarse grain sampling method, such as hydrophobicity analysis, to provide a fast and accurate procedure for predicting transmembrane regions. Methods and apparatus of the invention are useful to screen protein or polynucleotide databases for encoded proteins with transmembrane regions, such as GPCRs.

The Impact of the ‘Austrian’ Mutation of the Amyloid Precursor Protein Transmembrane Helix is Communicated to the Hinge Region

DEFF Research Database (Denmark)

Stelzer, Walter; Scharnagl, Christina; Leurs, Ulrike

2016-01-01

The transmembrane helix of the amyloid precursor protein is subject to proteolytic cleavages by γ-secretase at different sites resulting in Aβ peptides of different length and toxicity. A number of point mutations within this transmembrane helix alter the cleavage pattern thus enhancing production...... destabilizes amide hydrogen bonds in the hinge which connects dimerization and cleavage regions. Weaker intrahelical hydrogen bonds at the hinge may enhance helix bending and thereby affect recognition of the transmembrane substrate by the enzyme and/or presentation of its cleavage sites to the catalytic cleft....

Cytochrome oxidase as an indicator of ice storage and frozen storage

DEFF Research Database (Denmark)

Godiksen, Helene; Jessen, Flemming

2001-01-01

in different cods was 21%, and the coefficient of variation of different analyses on the same homogenate was 5%. It was shown that ice storage of muscle samples before they were frozen and thawed resulted in a major freezing-induced activation of cytochrome oxidase activity. The enzyme may therefore be used...... as an indicator of frozen fish to determine if the fish has been stored on ice before freezing. Cytochrome oxidase activity showed also potential as an indicator of frozen storage, as it was possible to distinguish between the frozen storage temperatures -9, -20, and -40 degreesC....

Controlled maritime storage of noxious materials

International Nuclear Information System (INIS)

1984-01-01

The invention relates to an accommodation for the controlled storage of noxious material, especially of radioactive material packed in vessels. The invention provides a storage accommodation far from populated regions, in which this material may be stored during a long period in a safe and controlled way and from which it may be winned back in a simple and cheap way. For that purpose, a floating and submersible construction is designed that may be let down to the sea-bottom at least partially and that is fitted with a closable entrance. (Auth.)

Saturation of the laser-induced narrowband coherent synchrotron radiation process: Experimental observation at a storage ring

Science.gov (United States)

Hosaka, M.; Yamamoto, N.; Takashima, Y.; Szwaj, C.; Le Parquier, M.; Evain, C.; Bielawski, S.; Adachi, M.; Zen, H.; Tanikawa, T.; Kimura, S.; Katoh, M.; Shimada, M.; Takahashi, T.

2013-02-01

We study the efficiency limitation affecting laser-induced coherent synchrotron radiation (CSR) at high laser power. Experiments are made on the UVSOR-II storage ring in conditions of narrowband terahertz CSR emission. While, at moderate power, CSR power increases quadratically with laser power, a noticeable decrease in efficiency and eventually a decrease in CSR power is observed experimentally at high power. Details of the underlying process are analyzed numerically. As the saturation effect depends almost instantaneously on the laser intensity, the saturation occurs locally in longitudinal space. This has important consequences on the modulation pattern induced on the electron bunch.

Accelerated SDS depletion from proteins by transmembrane electrophoresis: Impacts of Joule heating.

Science.gov (United States)

Unterlander, Nicole; Doucette, Alan Austin

2018-02-08

SDS plays a key role in proteomics workflows, including protein extraction, solubilization and mass-based separations (e.g. SDS-PAGE, GELFrEE). However, SDS interferes with mass spectrometry and so it must be removed prior to analysis. We recently introduced an electrophoretic platform, termed transmembrane electrophoresis (TME), enabling extensive depletion of SDS from proteins in solution with exceptional protein yields. However, our prior TME runs required 1 h to complete, being limited by Joule heating which causes protein aggregation at higher operating currents. Here, we demonstrate effective strategies to maintain lower TME sample temperatures, permitting accelerated SDS depletion. Among these strategies, the use of a magnetic stir bar to continuously agitate a model protein system (BSA) allows SDS to be depleted below 100 ppm (>98% removal) within 10 min of TME operations, while maintaining exceptional protein recovery (>95%). Moreover, these modifications allow TME to operate without any user intervention, improving throughput and robustness of the approach. Through fits of our time-course SDS depletion curves to an exponential model, we calculate SDS depletion half-lives as low as 1.2 min. This promising electrophoretic platform should provide proteomics researchers with an effective purification strategy to enable MS characterization of SDS-containing proteins. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HDFITS: Porting the FITS data model to HDF5

Science.gov (United States)

Price, D. C.; Barsdell, B. R.; Greenhill, L. J.

2015-09-01

The FITS (Flexible Image Transport System) data format has been the de facto data format for astronomy-related data products since its inception in the late 1970s. While the FITS file format is widely supported, it lacks many of the features of more modern data serialization, such as the Hierarchical Data Format (HDF5). The HDF5 file format offers considerable advantages over FITS, such as improved I/O speed and compression, but has yet to gain widespread adoption within astronomy. One of the major holdbacks is that HDF5 is not well supported by data reduction software packages and image viewers. Here, we present a comparison of FITS and HDF5 as a format for storage of astronomy datasets. We show that the underlying data model of FITS can be ported to HDF5 in a straightforward manner, and that by doing so the advantages of the HDF5 file format can be leveraged immediately. In addition, we present a software tool, fits2hdf, for converting between FITS and a new 'HDFITS' format, where data are stored in HDF5 in a FITS-like manner. We show that HDFITS allows faster reading of data (up to 100x of FITS in some use cases), and improved compression (higher compression ratios and higher throughput). Finally, we show that by only changing the import lines in Python-based FITS utilities, HDFITS formatted data can be presented transparently as an in-memory FITS equivalent.

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

Directory of Open Access Journals (Sweden)

Lucile Tran

2012-01-01

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

Combined effect of cortical cytoskeleton and transmembrane proteins on domain formation in biomembranes

DEFF Research Database (Denmark)

Sikder, K. U.; Stone, K. A.; Kumar, P. B. S.

2014-01-01

We investigate the combined effects of transmembrane proteins and the subjacent cytoskeleton on the dynamics of phase separation in multicomponent lipid bilayers using computer simulations of a particle-based implicit solvent model for lipid membranes with soft-core interactions. We find that mic......We investigate the combined effects of transmembrane proteins and the subjacent cytoskeleton on the dynamics of phase separation in multicomponent lipid bilayers using computer simulations of a particle-based implicit solvent model for lipid membranes with soft-core interactions. We find...... that microphase separation can be achieved by the protein confinement by the cytoskeleton. Our results have relevance to the finite size of lipid rafts in the plasma membrane of mammalian cells. (C) 2014 AIP Publishing LLC....

Modeling the Structure of SARS 3a Transmembrane Protein Using a ...

Indian Academy of Sciences (India)

Modeling the structure of SARS 3a Transmembrane protein using a ... for the implicit membrane molecular dynamics (MD) simulations. ... The coordinates during the simulation were saved every 500 steps, and were used for analysis. ... the pair list for calculation of nonbonded interactions being updated after every 10 steps.

Molecular cloning and tissue-specific expression analysis of mouse spinesin, a type II transmembrane serine protease 5

International Nuclear Information System (INIS)

Watanabe, Yoshihisa; Okui, Akira; Mitsui, Shinichi; Kawarabuki, Kentaro; Yamaguchi, Tatsuyuki; Uemura, Hidetoshi; Yamaguchi, Nozomi

2004-01-01

We have previously reported novel serine proteases isolated from cDNA libraries of the human and mouse central nervous system (CNS) by PCR using degenerate oligodeoxyribonucleotide primers designed on the basis of the serine protease motifs, AAHC and DSGGP. Here we report a newly isolated serine protease from the mouse CNS. This protease is homologous (77.9% identical) to human spinesin type II transmembrane serine protease 5. Mouse spinesin (m-spinesin) is also composed of (from the N-terminus) a short cytoplasmic domain, a transmembrane domain, a stem region containing a scavenger-receptor-like domain, and a serine protease domain, as is h-spinesin. We also isolated type 1, type 2, and type 3 variant cDNAs of m-spinesin. Full-length spinesin (type 4) and type 3 contain all the domains, whereas type 1 and type 2 variants lack the cytoplasmic, transmembrane, and scavenger-receptor-like domains. Subcellular localization of the variant forms was analyzed using enhanced green fluorescent protein (EGFP) fusion proteins. EGFP-type 4 fusion protein was predominantly localized to the ER, Golgi apparatus, and plasma membrane, whereas EGFP-type 1 was localized to the cytoplasm, reflecting differential classification of m-spinesin variants into transmembrane and cytoplasmic types. We analyzed the distribution of m-spinesin variants in mouse tissues, using RT-PCR with variant-specific primer sets. Interestingly, transmembrane-type spinesin, types 3 and 4, was specifically expressed in the spinal cord, whereas cytoplasmic type, type 1, was expressed in multiple tissues, including the cerebrum and cerebellum. Therefore, m-spinesin variants may have distinct biological functions arising from organ-specific variant expression

Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for Virus-Induced Cytopathic Effect and Interactions between NS2A and NS2B Transmembrane Segments.

Science.gov (United States)

Wu, Ren-Huang; Tsai, Ming-Han; Tsai, Kuen-Nan; Tian, Jia Ni; Wu, Jian-Sung; Wu, Su-Ying; Chern, Jyh-Haur; Chen, Chun-Hong; Yueh, Andrew

2017-06-15

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMS1 to -8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explore the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1 to -4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, -7, -9, and -17 to -19) around pTMS1 and -2 displayed a novel phenotype showing a >1,000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious-virus-like particle yields. HEK-293 cells infected with the six NS2A mutant viruses failed to cause a virus-induced cytopathic effect (CPE) by MitoCapture staining, cell proliferation, and lactate dehydrogenase release assays. Sequencing analyses of pseudorevertant viruses derived from lethal-mutant viruses revealed two consensus reversion mutations, leucine to phenylalanine at codon 181 (L181F) within pTMS7 of NS2A and isoleucine to threonine at codon 114 (I114T) within NS2B. The introduction of an NS2A-L181F mutation into the lethal (NM15, -16, -25, and -33) and CPE-defective (NM7, -9, and -19) mutants substantially rescued virus infectivity and virus-induced CPE, respectively, whereas the NS2B-L114T mutation rescued the NM16, -25, and -33 mutants. In conclusion, the results revealed the essential roles of the N-terminal half of NS2A in RNA replication and virus-induced CPE. Intramolecular interactions between pTMSs of NS2A and intermolecular interactions between the NS2A and NS2B proteins were also implicated. IMPORTANCE The characterization of the N-terminal (current study) and C-terminal halves of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle

The corticosteroid hormone induced factor: a new modulator of KCNQ1 channels?

DEFF Research Database (Denmark)

Jespersen, Thomas; Grunnet, Morten; Rasmussen, Hanne B

2006-01-01

The corticosteroid hormone induced factor (CHIF) is a member of the one-transmembrane segment protein family named FXYD, which also counts phospholemman and the Na,K-pump gamma-subunit. Originally it was suggested that CHIF could induce the expression of the I(Ks) current when expressed in Xenopu...

Biophysical Aspects of Transmembrane Signaling

CERN Document Server

Damjanovich, Sandor

2005-01-01

Transmembrane signaling is one of the most significant cell biological events in the life and death of cells in general and lymphocytes in particular. Until recently biochemists and biophysicists were not accustomed to thinking of these processes from the side of a high number of complex biochemical events and an equally high number of physical changes at molecular and cellular levels at the same time. Both types of researchers were convinced that their findings are the most decisive, having higher importance than the findings of the other scientist population. Both casts were wrong. Life, even at cellular level, has a number of interacting physical and biochemical mechanisms, which finally build up the creation of an "excited" cell that will respond to particular signals from the outer or inner world. This book handles both aspects of the signalling events, and in some cases tries to unify our concepts and help understand the signals that govern the life and death of our cells. Not only the understanding, bu...

Cancer Research Advance in CKLF-like MARVEL Transmembrane Domain Containing Member Family (Review).

Science.gov (United States)

Lu, Jia; Wu, Qian-Qian; Zhou, Ya-Bo; Zhang, Kai-Hua; Pang, Bing-Xin; Li, Liang; Sun, Nan; Wang, Heng-Shu; Zhang, Song; Li, Wen-Jian; Zheng, Wei; Liu, Wei

2016-01-01

CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of genes first reported at international level by Peking University Human Disease Gene Research Center. The gene products are between chemokines and the transmembrane-4 superfamily. Loaceted in several human chromosomes, CMTMs, which are unregulated in kinds of tumors, are potential tumor suppressor genes consisting of CKLF and CMTM1 to CMTM8. CMTMs play important roles in immune, male reproductive and hematopoietic systems. Also, it has been approved that CMTM family has strong connection with diseases of autoimmunity, haematopoietic system and haematopoietic system. The in-depth study in recent years found the close relation between CMTMs and umorigenesis, tumor development and metastasis. CMTM family has a significant clinical value in diagnosis and treatment to the diseases linking to tumor and immune system.

Compact electron storage ring JESCOS with normalconducting or superconducting magnets for X-ray lithography

International Nuclear Information System (INIS)

Anton, F.; Klein, U.; Krischel, D.; Anderberg, B.

1992-01-01

The layouts of a normal conducting electron storage ring and a storage ring with superconducting bending magnets are presented. The storage rings have a critical wavelength of 1 nm and are designed as compact sources for X-ray lithography. Each ring fits into a shielded room with a diameter of 14 m. (author) 3 refs.; 5 figs.; 1 tab

Quality and fertilizing capacity of boar spermatozoa during liquid storage in extender supplemented with different antibiotics.

Science.gov (United States)

Bryła, Magdalena; Trzcińska, Monika

2015-12-01

The aim of the study was to determine the effect of antibiotics on quality parameters and fertilizing capacity of boar sperm during liquid preservation. In the first experiment, semen was diluted in an extender containing 200 μg/mL of gentamicin as a control and diluted in a modified extenders: Ext I (contained 200 μg/mL florfenicol), Ext II (contained 200 μg/mL polymyxin B), Ext III (contained 100 μg/mL gentamicin and 100 μg/mL florfenicol) and Ext IV (contained 100 μg/mL gentamicin and 100 μg/mL polymyxin B). The semen was stored for ten days. Sperm quality was evaluated based on the motility (CASA; TM: total motility; PM: progressive motility), membrane integrity (YO-PRO-1/PI assay), mitochondrial activity (JC-1) and DNA integrity (TUNEL). The highest PM% (62.5 ± 9.6) was observed in Ext III at Day 6 of storage. The highest sperm viability and mitochondrial transmembrane potential was noticed at the end of the storage period in Ext III. Long-term storage did not induce DNA fragmentation in the extenders analyzed. In the second experiment, semen diluted in the control extender and in the extender providing the highest quality spermatozoa on Day 10 (Ext III) was used for artificial insemination (AI) of synchronized gilts. Our studies showed that the highest reproductive performance of inseminated gilts (pregnant gilts: 97.0%, litter size: 11.4 ± 1.2) occurred with Ext III semen dilution. The combination of 100 μg/mL gentamicin and 100 μg/mL florfenicol in the extender maintained sperm motility, membrane integrity and mitochondrial activity and enhanced the higher reproduction success. Copyright © 2015 Elsevier B.V. All rights reserved.

Predictive modeling of transient storage and nutrient uptake: Implications for stream restoration

Science.gov (United States)

O'Connor, Ben L.; Hondzo, Miki; Harvey, Judson W.

2010-01-01

This study examined two key aspects of reactive transport modeling for stream restoration purposes: the accuracy of the nutrient spiraling and transient storage models for quantifying reach-scale nutrient uptake, and the ability to quantify transport parameters using measurements and scaling techniques in order to improve upon traditional conservative tracer fitting methods. Nitrate (NO3–) uptake rates inferred using the nutrient spiraling model underestimated the total NO3– mass loss by 82%, which was attributed to the exclusion of dispersion and transient storage. The transient storage model was more accurate with respect to the NO3– mass loss (±20%) and also demonstrated that uptake in the main channel was more significant than in storage zones. Conservative tracer fitting was unable to produce transport parameter estimates for a riffle-pool transition of the study reach, while forward modeling of solute transport using measured/scaled transport parameters matched conservative tracer breakthrough curves for all reaches. Additionally, solute exchange between the main channel and embayment surface storage zones was quantified using first-order theory. These results demonstrate that it is vital to account for transient storage in quantifying nutrient uptake, and the continued development of measurement/scaling techniques is needed for reactive transport modeling of streams with complex hydraulic and geomorphic conditions.

Relative transmembrane segment rearrangements during BK channel activation resolved by structurally assigned fluorophore–quencher pairing

Science.gov (United States)

Pantazis, Antonios

2012-01-01

Voltage-activated proteins can sense, and respond to, changes in the electric field pervading the cell membrane by virtue of a transmembrane helix bundle, the voltage-sensing domain (VSD). Canonical VSDs consist of four transmembrane helices (S1–S4) of which S4 is considered a principal component because it possesses charged residues immersed in the electric field. Membrane depolarization compels the charges, and by extension S4, to rearrange with respect to the field. The VSD of large-conductance voltage- and Ca-activated K+ (BK) channels exhibits two salient inconsistencies from the canonical VSD model: (1) the BK channel VSD possesses an additional nonconserved transmembrane helix (S0); and (2) it exhibits a “decentralized” distribution of voltage-sensing charges, in helices S2 and S3, in addition to S4. Considering these unique features, the voltage-dependent rearrangements of the BK VSD could differ significantly from the standard model of VSD operation. To understand the mode of operation of this unique VSD, we have optically tracked the relative motions of the BK VSD transmembrane helices during activation, by manipulating the quenching environment of site-directed fluorescent labels with native and introduced Trp residues. Having previously reported that S0 and S4 diverge during activation, in this work we demonstrate that S4 also diverges from S1 and S2, whereas S2, compelled by its voltage-sensing charged residues, moves closer to S1. This information contributes spatial constraints for understanding the BK channel voltage-sensing process, revealing the structural rearrangements in a non-canonical VSD. PMID:22802360

Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase

DEFF Research Database (Denmark)

Desai, D M; Sap, J; Schlessinger, J

1993-01-01

CD45, a transmembrane protein tyrosine phosphatase (PTPase), is required for TCR signaling. Multiple CD45 isoforms, differing in the extracellular domain, are expressed in a tissue- and activation-specific manner, suggesting an important function for this domain. We report that a chimeric protein...... that ligand-mediated regulation of receptor-PTPases may have mechanistic similarities with receptor tyrosine kinases....

Electrochemical platform for the detection of transmembrane proteins reconstituted into liposomes

Czech Academy of Sciences Publication Activity Database

Vacek, J.; Zatloukalová, M.; Geletičová, J.; Kubala, M.; Modriansky, M.; Fekete, Ladislav; Mašek, J.; Hubatka, F.; Turánek, J.

2016-01-01

Roč. 88, č. 8 (2016), s. 4548-4556 ISSN 0003-2700 R&D Projects: GA MŠk LO1409; GA MŠk LM2015088 Institutional support: RVO:68378271 Keywords : detection * transmembrane proteins * liposomes * electrochemistry Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 6.320, year: 2016

Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.

Science.gov (United States)

Merkle, Patrick S; Gotfryd, Kamil; Cuendet, Michel A; Leth-Espensen, Katrine Z; Gether, Ulrik; Loland, Claus J; Rand, Kasper D

2018-05-01

LeuT, a prokaryotic member of the neurotransmitter:sodium symporter (NSS) family, is an established structural model for mammalian NSS counterparts. We investigate the substrate translocation mechanism of LeuT by measuring the solution-phase structural dynamics of the transporter in distinct functional states by hydrogen/deuterium exchange mass spectrometry (HDX-MS). Our HDX-MS data pinpoint LeuT segments involved in substrate transport and reveal for the first time a comprehensive and detailed view of the dynamics associated with transition of the transporter between outward- and inward-facing configurations in a Na + - and K + -dependent manner. The results suggest that partial unwinding of transmembrane helices 1/5/6/7 drives LeuT from a substrate-bound, outward-facing occluded conformation toward an inward-facing open state. These hitherto unknown, large-scale conformational changes in functionally important transmembrane segments, observed for LeuT in detergent-solubilized form and when embedded in a native-like phospholipid bilayer, could be of physiological relevance for the translocation process.

When a transmembrane channel isn't, or how biophysics and biochemistry (mis)communicate.

Science.gov (United States)

Reviakine, Ilya

2018-02-12

Annexins are a family of soluble proteins that bind to acidic phospholipids such as phosphatidylserine in a calcium-dependent manner. The archetypical member of the annexin family is annexin A5. For many years, its function remained unknown despite the availability of a high-resolution structure. This, combined with the observations of specific ion conductance in annexin-bound membranes, fueled speculations about the possible membrane-spanning forms of annexins that functioned as ion channels. The channel hypothesis remained controversial and did not gather sufficient evidence to become accepted. Yet, it continues to draw attention as a framework for interpreting indirect (e.g., biochemical) data. The goal of the mini-review is to examine the data on annexin-lipid interactions from the last ~30 years from the point of view of the controversy between the two lines of inquiry: the well-characterized peripheral assembly of the annexins at membranes vs. their putative transmembrane insertion. In particular, the potential role of lipid rearrangements induced by annexin binding is highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

Emittance growth induced by electron cloud in proton storage rings

CERN Document Server

Benedetto, Elena; Coppa, G

2006-01-01

In proton and positron storage rings with many closely spaced bunches, a large number of electrons can accumulate in the beam pipe due to various mechanisms (photoemission, residual gas ionization, beam-induced multipacting). The so-formed electron cloud interacts with the positively charged bunches, giving rise to instabilities, emittance growth and losses. This phenomenon has been observed in several existing machines such as the CERN Super Proton Synchrotron (SPS), whose operation has been constrained by the electron-cloud problem, and it is a concern for the Large Hadron Collider (LHC), under construction at CERN. The interaction between the beam and the electron cloud has features which cannot be fully taken into account by the conventional and known theories from accelerators and plasma physics. Computer simulations are indispensable for a proper prediction and understanding of the instability dynamics. The main feature which renders the beam-cloud interactions so peculiar is that the the electron cloud...

Archival storage solutions for PACS

Science.gov (United States)

Chunn, Timothy

1997-05-01

While they are many, one of the inhibitors to the wide spread diffusion of PACS systems has been robust, cost effective digital archive storage solutions. Moreover, an automated Nearline solution is key to a central, sharable data repository, enabling many applications such as PACS, telemedicine and teleradiology, and information warehousing and data mining for research such as patient outcome analysis. Selecting the right solution depends on a number of factors: capacity requirements, write and retrieval performance requirements, scaleability in capacity and performance, configuration architecture and flexibility, subsystem availability and reliability, security requirements, system cost, achievable benefits and cost savings, investment protection, strategic fit and more.This paper addresses many of these issues. It compares and positions optical disk and magnetic tape technologies, which are the predominant archive mediums today. Price and performance comparisons will be made at different archive capacities, plus the effect of file size on storage system throughput will be analyzed. The concept of automated migration of images from high performance, high cost storage devices to high capacity, low cost storage devices will be introduced as a viable way to minimize overall storage costs for an archive. The concept of access density will also be introduced and applied to the selection of the most cost effective archive solution.

Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia

Science.gov (United States)

Turner, Mark J.; Saint‐Criq, Vinciane; Patel, Waseema; Ibrahim, Salam H.; Verdon, Bernard; Ward, Christopher; Garnett, James P.; Tarran, Robert; Cann, Martin J.

2015-01-01

Key points Raised arterial blood CO2 (hypercapnia) is a feature of many lung diseases.CO2 has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca2+.Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO3 − transport via pendrin or Na+/HCO3 − cotransporters.These results further support the role of CO2 as a cell signalling molecule and suggests CO2‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs. Abstract Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO2‐induced reduction in anion secretion was not due to a decrease in HCO3 − transport given that neither a change in CFTR‐dependent HCO3 − efflux nor Na+/HCO3 − cotransporter‐dependent HCO3 − influx were CO2‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid

Preventive fraction of physical fitness on risk factors in cardiac patients: Retrospective epidemiological study.

Science.gov (United States)

Caru, Maxime; Kern, Laurence; Bousquet, Marc; Curnier, Daniel

2018-04-26

To quantify the preventive fraction of physical fitness on the risk factors in patients with cardiovascular diseases (CVDs). A total of 249 subjects (205 men and 44 women) suffering from CVD were categorized into four groups, according to their percentage of physical fitness. We calculated the odds ratio to obtain the preventive fraction in order to evaluate the impact of the physical fitness level on the risk factors ( i.e ., abdominal obesity, depression, diabetes, dyslipidemia, hypertension, obesity, overweight and smoking). It is observed that a normal physical fitness level is sufficient to induce a preventive action on abdominal obesity (38%), diabetes (12%), hypertension (33%), obesity (12%) and overweight (11%). Also, the preventive fraction increases with the level of physical fitness, in particular for hypertension (36%) and overweight (16%). A high physical fitness level does not necessarily induce a preventive action in most risk factors, excluding depression. This is the first study which demonstrates that reaching a normal physical fitness level is enough to induce a protection for some risk factors, despite having a CVD.

SCS3 and YFT2 link transcription of phospholipid biosynthetic genes to ER stress and the UPR.

Directory of Open Access Journals (Sweden)

Robyn D Moir

2012-08-01

Full Text Available The ability to store nutrients in lipid droplets (LDs is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT proteins are conserved ER-resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the ancient ortholog of the FIT gene family first identified in mammals has two homologs in Saccharomyces cerevisiae (SCS3 and YFT2 and other fungi of the Saccharomycotina lineage. Despite the coevolution of these genes for more than 170 million years and their divergence from higher eukaryotes, SCS3, YFT2, and the human FIT2 gene retain some common functions: expression of the yeast genes in a human embryonic kidney cell line promotes LD formation, and expression of human FIT2 in yeast rescues the inositol auxotrophy and chemical and genetic phenotypes of strains lacking SCS3. To better understand the function of SCS3 and YFT2, we investigated the chemical sensitivities of strains deleted for either or both genes and identified synthetic genetic interactions against the viable yeast gene-deletion collection. We show that SCS3 and YFT2 have shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid metabolism, vesicular trafficking, transcription of phospholipid biosynthetic genes, and protein synthesis. The genetic data indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates these processes. Part of this mechanism involves a role for SCS3 in communicating changes in the ER (e.g. due to low inositol to Opi1-regulated transcription of phospholipid biosynthetic genes. We conclude that SCS3 and YFT2 are required for normal ER membrane biosynthesis in response to perturbations in lipid metabolism and ER

SiteChar – Methodology for a Fit-for-Purpose Assessment of CO2 Storage Sites in Europe

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Delprat-Jannaud F.

2015-04-01

Full Text Available The FP7-funded SiteChar project examined the entire CO2 geological storage site characterisation process, from the initial feasibility studies through to the final stage of application for a CO2 storage permit based on criteria defined by the relevant European legislation. The SiteChar workflow for CO2 geological storage site characterisation provides a description of all elements of a site characterisation study, as well as guidance to streamline the site characterisation process and make sure that the output covers the aspects mentioned in the European Community (EC Storage Directive. Five potential European storage sites, representative of prospective geological contexts, were considered as test sites for the research work: a North Sea multi-store site (hydrocarbon field and aquifer offshore Scotland; an onshore aquifer in Denmark; an onshore gas field in Poland; an aquifer offshore in Norway; and an aquifer in the Southern Adriatic Sea. This portfolio combines complementary sites that allowed to encompass the different steps of the characterisation workflow. A key innovation was the development of internal ‘dry-run’ permit applications at the Danish and Scottish sites and their review by relevant regulatory authorities. This process helped to refine the site characterisation workflow, and aimed to identify remaining gaps in site-specific characterisation, needed to secure storage permits under the EC Storage Directive as implemented in ‘host’ Member States. SiteChar considered the important aspect of the public awareness and public opinions of these new technologies, in parallel to technical issues, on the onshore Polish and offshore Scottish sites. A new format to assist public opinion-forming processes was tested involving a small sample of local communities. Generic as well as site-specific information was made available to the general and local public via the internet and at information meetings. These exercises provide insight

Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport.

Science.gov (United States)

Pirkmajer, Sergej; Kirchner, Henriette; Lundell, Leonidas S; Zelenin, Pavel V; Zierath, Juleen R; Makarova, Kira S; Wolf, Yuri I; Chibalin, Alexander V

2017-07-15

Small transmembrane proteins such as FXYDs, which interact with Na + ,K + -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca 2+ -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage. We also identified 13 gene subfamilies of FXYDs and propose a revised, phylogeny-based FXYD classification that is consistent across vertebrate species. These findings provide an improved framework for investigating physiological and pathophysiological functions of small transmembrane regulators of ion transport. Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these are members of the FXYD family (FXYD1-12), which regulate Na + ,K + -ATPase, and phospholamban, sarcolipin, myoregulin and DWORF, which regulate the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies. Here we discovered that sea lamprey (Petromyzon marinus), a representative of extant jawless vertebrates (Cyclostomata), expresses an FXYD homologue, which strongly suggests that FXYDs predate the emergence of fishes and other jawed vertebrates (Gnathostomata). Using a combination of sequence-based phylogenetic analysis and conservation of local chromosome context, we determined that FXYDs markedly diversified in the lineages leading to cartilaginous fishes (Chondrichthyes) and bony

Predictive Modeling of Transient Storage and Nutrient Uptake: Implications for Stream Restoration

Energy Technology Data Exchange (ETDEWEB)

O’Connor, Ben L.; Hondzo, Miki; Harvey, Judson W.

2010-12-01

This study examined two key aspects of reactive transport modeling for stream restoration purposes: the accuracy of the nutrient spiraling and transient storage models for quantifying reach-scale nutrient uptake, and the ability to quantify transport parameters using measurements and scaling techniques in order to improve upon traditional conservative tracer fitting methods. Nitrate (NO-3)(NO3-) uptake rates inferred using the nutrient spiraling model underestimated the total NO-3NO3- mass loss by 82%, which was attributed to the exclusion of dispersion and transient storage. The transient storage model was more accurate with respect to the NO-3NO3- mass loss (±20%) and also demonstrated that uptake in the main channel was more significant than in storage zones. Conservative tracer fitting was unable to produce transport parameter estimates for a riffle-pool transition of the study reach, while forward modeling of solute transport using measured/scaled transport parameters matched conservative tracer breakthrough curves for all reaches. Additionally, solute exchange between the main channel and embayment surface storage zones was quantified using first-order theory. These results demonstrate that it is vital to account for transient storage in quantifying nutrient uptake, and the continued development of measurement/scaling techniques is needed for reactive transport modeling of streams with complex hydraulic and geomorphic conditions.

MutHTP: Mutations in Human Transmembrane Proteins.

Science.gov (United States)

A, Kulandaisamy; S, Binny Priya; R, Sakthivel; Tarnovskaya, Svetlana; Bizin, Ilya; Hönigschmid, Peter; Frishman, Dmitrij; Gromiha, M Michael

2018-02-01

We have developed a novel database, MutHTP, which contains information on 183395 disease-associated and 17827 neutral mutations in human transmembrane proteins. For each mutation site MutHTP provides a description of its location with respect to the membrane protein topology, structural environment (if available) and functional features. Comprehensive visualization, search, display and download options are available. The database is publicly available at http://www.iitm.ac.in/bioinfo/MutHTP/. The website is implemented using HTML, PHP and javascript and supports recent versions of all major browsers, such as Firefox, Chrome and Opera. gromiha@iitm.ac.in. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A review of case histories of induced seismicity caused by hydrocarbon production and storage

International Nuclear Information System (INIS)

Vadillo Fernández, L.; Fernández Naranjo, F.J.; Rodríguez Gómez, V.; López Gutiérrez, J.

2017-01-01

In this article we review the stress-strain relationships that take place in the crust during some of the main hydrocarbon production and storage processes: gas extraction; water injection in wells to stimulate the extraction of oil (EOR); unconventional hydrocarbon production by hydraulic fracturing (fracking); disposal of wastewater (saline water) from the extraction of conventional and unconventional hydrocarbons such as saline water return (flowback) of hydraulic fracturing, both with TDS higher than 40000 mg/L. In addition, the type of faults that are more likely to slip and the induced seismicity related to the production and extraction of hydrocarbons are analysed. [es

Transmembrane neural cell-adhesion molecule (NCAM), but not glycosyl-phosphatidylinositol-anchored NCAM, down-regulates secretion of matrix metalloproteinases

DEFF Research Database (Denmark)

Edvardsen, K; Chen, W; Rucklidge, G

1993-01-01

proteinases, and proteinase inhibitors all participate in the construction, maintenance, and remodeling of extracellular matrix by cells. The neural cell-adhesion molecule (NCAM)-negative rat glioma cell line BT4Cn secretes substantial amounts of metalloproteinases, as compared with its NCAM-positive mother......During embryogenesis interactions between cells and extracellular matrix play a central role in the modulation of cell motility, growth, and differentiation. Modulation of matrix structure is therefore crucial during development; extracellular matrix ligands, their receptors, extracellular...... cell line BT4C. We have transfected the BT4Cn cell line with cDNAs encoding the human NCAM-B and -C isoforms. We report here that the expression of transmembrane NCAM-B, but not of glycosyl-phosphatidylinositol-linked NCAM-C, induces a down-regulation of 92-kDa gelatinase (matrix metalloproteinase 9...

Requirement of NMDA receptor reactivation for consolidation and storage of nondeclarative taste memory revealed by inducible NR1 knockout.

Science.gov (United States)

Cui, Zhenzhong; Lindl, Kathryn A; Mei, Bing; Zhang, Shuqing; Tsien, Joe Z

2005-08-01

We employed an inducible, reversible and region-specific gene knockout technique to investigate the requirements for cortical NMDA receptors (NMDAR) during the various stages (acquisition, consolidation and storage, and retrieval) of nondeclarative, hippocampal-independent memory in mice using a conditioned taste aversion memory paradigm. Here we show that temporary knockout of the cortical NMDAR during either the learning or postlearning consolidation stage, but not during the retrieval stage, causes severe performance deficits in the 1-month taste memory retention tests. More importantly, we found that the consolidation and storage of the long-term nondeclarative taste memories requires cortical NMDAR reactivation. Thus, the dynamic engagement of the NMDAR during the postlearning stage leads us to postulate that NMDAR reactivation-mediated synaptic re-entry reinforcement is crucial for overcoming the destabilizing effects intrinsic to synaptic protein turnover and for achieving consolidation and storage of nondeclarative memories in the brain.

Modeling of hydrogen/deuterium dynamics and heat generation on palladium nanoparticles for hydrogen storage and solid-state nuclear fusion.

Science.gov (United States)

Tanabe, Katsuaki

2016-01-01

We modeled the dynamics of hydrogen and deuterium adsorbed on palladium nanoparticles including the heat generation induced by the chemical adsorption and desorption, as well as palladium-catalyzed reactions. Our calculations based on the proposed model reproduce the experimental time-evolution of pressure and temperature with a single set of fitting parameters for hydrogen and deuterium injection. The model we generated with a highly generalized set of formulations can be applied for any combination of a gas species and a catalytic adsorbent/absorbent. Our model can be used as a basis for future research into hydrogen storage and solid-state nuclear fusion technologies.

Stress analysis of hydride bed vessels used for tritium storage

International Nuclear Information System (INIS)

McKillip, S.T.; Bannister, C.E.; Clark, E.A.

1991-01-01

A prototype hydride storage bed, using LaNi 4.25 Al 0.75 as the storage material, was fitted with strain gages to measure strains occurring in the stainless steel bed vessel caused by expansion of the storage powder upon uptake of hydrogen. The strain remained low in the bed as hydrogen was added, up to a bed loading of about 0.5 hydrogen to metal atom ratio (H/M). The strain then increased with increasing hydrogen loading (∼ 0.8 H/M). Different locations exhibited greatly different levels of maximum strain. In no case was the design stress of the vessel exceeded

Fractographic analysis, accuracy of fit and impact strength of acrylic resin

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Fernanda Faot

2008-12-01

Full Text Available This study evaluated accuracy of fit, impact strength, types and morphology of fractures of a microwave acrylic resin polymerized with a cycle alternative to that recommended by the manufacturer. Onda Cryl was polymerized according to the manufacturer's instructions (MC, 3 min at 360 W, 4-min pause, and 3 min at 810 W; and with an alternative cycle (AC of 6 min at 630 W. Accuracy of fit was measured at 3 points at the right (A and left (B ridge crests and at the midline (C on the posterior palatal seal for each denture base (n = 10/group. The measurements were taken immediately after finishing and after 30-day storage in water. The impact strength test (Charpy method was performed with a 40 kJ/cm load (n = 20/group. Fractographic analysis was accomplished for all fragments and the fracture types were characterized by means of their morphology, crack propagation angles and microstructure. Accuracy of fit data were analyzed by ANOVA, impact strength and radius values were compared by the t test, and the fractographic analysis data, by the Wilcoxon Mann-Whitney test. The significance level was fixed at p < 0.05. No statistical differences were found between the two cycles of polymerization used. However, after the 30-day storage period in water, the denture bases showed better fit (P < .05. Most of the fractures were classified as brittle (MD: 70%, AC: 80%. Based on the results of this study, it could be concluded that both polymerization cycles are adequate to polymerize the denture resin studied.

Light storage via slow-light four-wave mixing

International Nuclear Information System (INIS)

Fan, Yun-Fei; Wang, Hai-Hua; Wei, Xiao-Gang; Li, Ai-Jun; Kang, Zhi-Hui; Wu, Jin-Hui; Zhang, Han-Zhuang; Xu, Huai-Liang; Gao, Jin-Yue

2012-01-01

We experimentally demonstrate a light storage via slow-light four-wave mixing in a solid-state medium with a four-level double lambda scheme. Using slow light based on electromagnetically induced transparency, we obtain a slowed four-wave mixing signal pulse together with the slowed probe pulse. During the propagation of light pulses, the storage and retrieval of both the slowed four-wave mixing pulse and the slowed probe pulse are studied by manipulating the intensities of the control fields. -- Highlights: ► A light storage via slow-light four-wave mixing is observed in a solid. ► The probe pulse is slowed under electromagnetically induced transparency. ► A slowed four-wave mixing pulse is obtained by slow light. ► The storage of slowed double pulses is studied.

Promiscuous Seven Transmembrane Receptors Sensing L-α-amino Acids

DEFF Research Database (Denmark)

Smajilovic, Sanela; Wellendorph, Petrine; Bräuner-Osborne, Hans

2014-01-01

A number of nutrient sensing seven trans-membrane (7TM) receptors have been identified and characterized over the past few years. While the sensing mechanisms to carbohydrates and free fatty acids are well understood, the molecular basis of amino acid sensing has recently come to the limelight....... The present review describes the current status of promiscuous L-α-amino acid sensors, the calcium sensing receptor (CaSR), the GPRC6A receptor, the T1R1/T1R3 receptor and also their molecular pharmacology, expression pattern and physiological significance....

"Shrink-to-fit" superhydrophobicity: thermally-induced microscale wrinkling of thin hydrophobic multilayers fabricated on flexible shrink-wrap substrates.

Science.gov (United States)

Manna, Uttam; Carter, Matthew C D; Lynn, David M

2013-06-11

An approach to the design of flexible superhydrophobic surfaces based on thermally induced wrinkling of thin, hydrophobic polymer multilayers on heat-shrinkable polymer films is reported. This approach exploits shrinking processes common to "heat-shrink" plastics, and can thus be used to create "shrink-to-fit" superhydrophobic coatings on complex surfaces, manipulate the dimensions and densities of patterned features, and promote heat-activated repair of full-thickness defects. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vitamin A transport and the transmembrane pore in the cell-surface receptor for plasma retinol binding protein.

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Ming Zhong

Full Text Available Vitamin A and its derivatives (retinoids play diverse and crucial functions from embryogenesis to adulthood and are used as therapeutic agents in human medicine for eye and skin diseases, infections and cancer. Plasma retinol binding protein (RBP is the principal and specific vitamin A carrier in the blood and binds vitamin A at 1:1 ratio. STRA6 is the high-affinity membrane receptor for RBP and mediates cellular vitamin A uptake. STRA6 null mice have severely depleted vitamin A reserves for vision and consequently have vision loss, even under vitamin A sufficient conditions. STRA6 null humans have a wide range of severe pathological phenotypes in many organs including the eye, brain, heart and lung. Known membrane transport mechanisms involve transmembrane pores that regulate the transport of the substrate (e.g., the gating of ion channels. STRA6 represents a new type of membrane receptor. How this receptor interacts with its transport substrate vitamin A and the functions of its nine transmembrane domains are still completely unknown. These questions are critical to understanding the molecular basis of STRA6's activities and its regulation. We employ acute chemical modification to introduce chemical side chains to STRA6 in a site-specific manner. We found that modifications with specific chemicals at specific positions in or near the transmembrane domains of this receptor can almost completely suppress its vitamin A transport activity. These experiments provide the first evidence for the existence of a transmembrane pore, analogous to the pore of ion channels, for this new type of cell-surface receptor.

Generation and Nuclear Translocation of Sumoylated Transmembrane Fragment of Cell Adhesion Molecule L1

Science.gov (United States)

Lutz, David; Wolters-Eisfeld, Gerrit; Joshi, Gunjan; Djogo, Nevena; Jakovcevski, Igor; Schachner, Melitta; Kleene, Ralf

2012-01-01

The functions of the cell adhesion molecule L1 in the developing and adult nervous system are triggered by homophilic and heterophilic interactions that stimulate signal transductions that activate cellular responses. Here, we show that stimulation of signaling by function-triggering L1 antibodies or L1-Fc leads to serine protease-dependent cleavage of full-length L1 at the plasma membrane and generation of a sumoylated transmembrane 70-kDa fragment comprising the intracellular and transmembrane domains and part of the extracellular domain. The 70-kDa transmembrane fragment is transported from the plasma membrane to a late endosomal compartment, released from endosomal membranes into the cytoplasm, and transferred from there into the nucleus by a pathway that depends on importin and chromatin-modifying protein 1. Mutation of the sumoylation site at Lys1172 or of the nuclear localization signal at Lys1147 abolished L1-stimulated generation or nuclear import of the 70-kDa fragment, respectively. Nuclear import of the 70-kDa fragment may activate cellular responses in parallel or in association with phosphorylation-dependent signaling pathways. Alterations in the levels of the 70-kDa fragment during development and in the adult after spinal cord injury or in a mouse model of Alzheimer disease suggest that this fragment is functionally implicated in development, regeneration, neurodegeneration, tumorigenesis, and possibly synaptic plasticity in the mature nervous system. PMID:22431726

Specificity of transmembrane protein palmitoylation in yeast.

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Ayelén González Montoro

Full Text Available Many proteins are modified after their synthesis, by the addition of a lipid molecule to one or more cysteine residues, through a thioester bond. This modification is called S-acylation, and more commonly palmitoylation. This reaction is carried out by a family of enzymes, called palmitoyltransferases (PATs, characterized by the presence of a conserved 50- aminoacids domain called "Asp-His-His-Cys- Cysteine Rich Domain" (DHHC-CRD. There are 7 members of this family in the yeast Saccharomyces cerevisiae, and each of these proteins is thought to be responsible for the palmitoylation of a subset of substrates. Substrate specificity of PATs, however, is not yet fully understood. Several yeast PATs seem to have overlapping specificity, and it has been proposed that the machinery responsible for palmitoylating peripheral membrane proteins in mammalian cells, lacks specificity altogether.Here we investigate the specificity of transmembrane protein palmitoylation in S. cerevisiae, which is carried out predominantly by two PATs, Swf1 and Pfa4. We show that palmitoylation of transmembrane substrates requires dedicated PATs, since other yeast PATs are mostly unable to perform Swf1 or Pfa4 functions, even when overexpressed. Furthermore, we find that Swf1 is highly specific for its substrates, as it is unable to substitute for other PATs. To identify where Swf1 specificity lies, we carried out a bioinformatics survey to identify amino acids responsible for the determination of specificity or Specificity Determination Positions (SDPs and showed experimentally, that mutation of the two best SDP candidates, A145 and K148, results in complete and partial loss of function, respectively. These residues are located within the conserved catalytic DHHC domain suggesting that it could also be involved in the determination of specificity. Finally, we show that modifying the position of the cysteines in Tlg1, a Swf1 substrate, results in lack of palmitoylation, as

Mutation G805R in the transmembrane domain of the LDL receptor gene causes familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor in the endoplasmic reticulum

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Thea Bismo Strøm

2014-01-01

Full Text Available More than 1700 mutations in the low density lipoprotein receptor (LDLR gene have been found to cause familial hypercholesterolemia (FH. These are commonly divided into five classes based upon their effects on the structure and function of the LDLR. However, little is known about the mechanism by which mutations in the transmembrane domain of the LDLR gene cause FH. We have studied how the transmembrane mutation G805R affects the function of the LDLR. Based upon Western blot analyses of transfected HepG2 cells, mutation G805R reduced the amounts of the 120 kDa precursor LDLR in the endoplasmic reticulum. This led to reduced amounts of the mature 160 kDa LDLR at the cell surface. However, significant amounts of a secreted 140 kDa G805R-LDLR ectodomain fragment was observed in the culture media. Treatment of the cells with the metalloproteinase inhibitor batimastat largely restored the amounts of the 120 and 160 kDa forms in cell lysates, and prevented secretion of the 140 kDa ectodomain fragment. Together, these data indicate that a metalloproteinase cleaved the ectodomain of the 120 kDa precursor G805R-LDLR in the endoplasmic reticulum. It was the presence of the polar Arg805 and not the lack of Gly805 which led to ectodomain cleavage. Arg805 also prevented γ-secretase cleavage within the transmembrane domain. It is conceivable that introducing a charged residue within the hydrophobic membrane lipid bilayer, results in less efficient incorporation of the 120 kDa G805R-LDLR in the endoplasmic reticulum membrane and makes it a substrate for metalloproteinase cleavage.

Role of α and β Transmembrane Domains in Integrin Clustering

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Amir Shamloo

2015-11-01

Full Text Available Integrins are transmembrane proteins playing a crucial role in the mechanical signal transduction from the outside to the inside of a cell, and vice versa. Nevertheless, this signal transduction could not be implemented by a single protein. Rather, in order for integrins to be able to participate in signal transduction, they need to be activated and produce clusters first. As integrins consist of α- and β-subunits that are separate in the active state, studying both subunits separately is of a great importance, for, in the active state, the distance between α- and β-subunits is long enough that they do not influence one another significantly. Thus, this study aims to investigate the tendency of transmembrane domains of integrins to form homodimers. We used both Steered and MARTINI Coarse-grained molecular dynamics method to perform our simulations, mainly because of a better resolution and computational feasibility that each of these methods could provide to us. Using the Steered molecular dynamics method for α- and β-subunits, we found that the localized lipid packing prevented them from clustering. Nonetheless, the lipid packing phenomenon was found to be an artifact after investigating this process using a coarse grained (CG model. Exploiting the coarse-grained molecular dynamics simulations, we found that α- and β-subunits tend to form a stable homo-dimer.

LOCO with Constraints and Improved Fitting Technique

International Nuclear Information System (INIS)

Not Available

2007-01-01

LOCO has been a powerful beam-based diagnostics and optics control method for storage rings and synchrotrons worldwide ever since it was established at NSLS by J. Safranek. This method measures the orbit response matrix and optionally the dispersion function of the machine. The data are then fitted to a lattice model by adjusting parameters such as quadrupole and skew quadrupole strengths in the model, BPM gains and rolls, corrector gains and rolls of the measurement system. Any abnormality of the machine that affects the machine optics can then be identified. The resulting lattice model is equivalent to the real machine lattice as seen by the BPMs. Since there are usually two or more BPMs per betatron period in modern circular accelerators, the model is often a very accurate representation of the real machine. According to the fitting result, one can correct the machine lattice to the design lattice by changing the quadrupole and skew quadrupole strengths. LOCO is so important that it is routinely performed at many electron storage rings to guarantee machine performance, especially after the Matlab-based LOCO code became available. However, for some machines, LOCO is not easy to carry out. In some cases, LOCO fitting converges to an unrealistic solution with large changes to the quadrupole strengths ΔK. The quadrupole gradient changes can be so large that the resulting lattice model fails to find a closed orbit and subsequent iterations become impossible. In cases when LOCO converges, the solution can have ΔK that is larger than realistic and often along with a spurious zigzag pattern between adjacent quadrupoles. This degeneracy behavior of LOCO is due to the correlation between the fitting parameters - usually between neighboring quadrupoles. The fitting scheme is therefore less restrictive over certain patterns of changes to these quadrupoles with which the correlated quadrupoles fight each other and the net effect is very inefficient χ 2 reduction, i

FitSKIRT: genetic algorithms to automatically fit dusty galaxies with a Monte Carlo radiative transfer code

Science.gov (United States)

De Geyter, G.; Baes, M.; Fritz, J.; Camps, P.

2013-02-01

We present FitSKIRT, a method to efficiently fit radiative transfer models to UV/optical images of dusty galaxies. These images have the advantage that they have better spatial resolution compared to FIR/submm data. FitSKIRT uses the GAlib genetic algorithm library to optimize the output of the SKIRT Monte Carlo radiative transfer code. Genetic algorithms prove to be a valuable tool in handling the multi- dimensional search space as well as the noise induced by the random nature of the Monte Carlo radiative transfer code. FitSKIRT is tested on artificial images of a simulated edge-on spiral galaxy, where we gradually increase the number of fitted parameters. We find that we can recover all model parameters, even if all 11 model parameters are left unconstrained. Finally, we apply the FitSKIRT code to a V-band image of the edge-on spiral galaxy NGC 4013. This galaxy has been modeled previously by other authors using different combinations of radiative transfer codes and optimization methods. Given the different models and techniques and the complexity and degeneracies in the parameter space, we find reasonable agreement between the different models. We conclude that the FitSKIRT method allows comparison between different models and geometries in a quantitative manner and minimizes the need of human intervention and biasing. The high level of automation makes it an ideal tool to use on larger sets of observed data.

NTAL (non-T cell activation linker):a transmembrane adaptor protein involved in immunoreceptor signaling

Czech Academy of Sciences Publication Activity Database

Brdička, Tomáš; Imrich, Martin; Angelisová, Pavla; Brdičková, Naděžda; Horváth, Ondřej; Špička, Jiří; Hilgert, Ivan; Lusková, Petra; Dráber, Petr; Novák, P.; Engels, N.; Wienands, J.; Simeoni, L.; Osterreicher, J.; Aguado, E.; Malissen, M.; Schraven, B.; Hořejší, Václav

2002-01-01

Roč. 196, č. 12 (2002), s. 16180-16185 ISSN 0022-1007 R&D Projects: GA MŠk LN00A026 Keywords : NTAL * transmembrane adaptor * immunoreceptor signaling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 15.838, year: 2002

Multilayer PV-storage Microgrids Algorithm for the Dispatch of Distributed Network

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Yang Ping

2016-01-01

Full Text Available In recent years, due to the support of our country, PV-storage microgrid develops rapidly. However, the flexible network operation modes of PV-storage microgrid change flexibly and the operating characteristics with a large amout of sources is highly complicated. Based on the existing microgrid coordinate control methods, this paper proposes multilayer PV-storage microgrid algorithm for fitting dispatch of distributed network, which achieves maximum output of renewable energy when meeting the scheduling requirements of network, by building PV-storage microgrid type dynamic simulation system in a variety of conditions in PSCAD. Simulation results show that the heuristic algorithm proposed can achieve microgrid stable operation and satisfy the demands of the dispatch in distributed network.

Transmembrane helical interactions in the CFTR channel pore.

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Jhuma Das

2017-06-01

Full Text Available Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF. Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants. Several CFTR homology models have been developed using bacterial ABC transporters as templates but these have low sequence similarity to CFTR and are not ion channels. Here, we refine an earlier model in an outward (OWF and develop an inward (IWF facing model employing an integrated experimental-molecular dynamics simulation (200 ns approach. Our IWF structure agrees well with a recently solved cryo-EM structure of a CFTR IWF state. We utilize cysteine cross-linking to verify positions and orientations of residues within trans-membrane helices (TMHs of the OWF conformation and to reconstruct a physiologically relevant pore structure. Comparison of pore profiles of the two conformations reveal a radius sufficient to permit passage of hydrated Cl- ions in the OWF but not the IWF model. To identify structural determinants that distinguish the two conformations and possible rearrangements of TMHs within them responsible for channel gating, we perform cross-linking by bifunctional reagents of multiple predicted pairs of cysteines in TMH 6 and 12 and 6 and 9. To determine whether the effects of cross-linking on gating observed are the result of switching of the channel from open to close state, we also treat the same residue pairs with monofunctional reagents in separate experiments. Both types of reagents prevent ion currents indicating that pore blockage is primarily responsible.

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

Directory of Open Access Journals (Sweden)

Koji Mizuhashi

Full Text Available Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119, encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice.First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS and osteoid maturation time (Omt, and significantly decreased mineral apposition rate (MAR and bone formation rate per bone surface (BFR/BS. In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant.Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

Resolving the biophysics of axon transmembrane polarization in a single closed-form description

Energy Technology Data Exchange (ETDEWEB)

Melendy, Robert F., E-mail: rfmelendy@liberty.edu [School of Engineering and Computational Sciences, Liberty University, Lynchburg, Virginia 24515 (United States)

2015-12-28

When a depolarizing event occurs across a cell membrane there is a remarkable change in its electrical properties. A complete depolarization event produces a considerably rapid increase in voltage that propagates longitudinally along the axon and is accompanied by changes in axial conductance. A dynamically changing magnetic field is associated with the passage of the action potential down the axon. Over 75 years of research has gone into the quantification of this phenomenon. To date, no unified model exist that resolves transmembrane polarization in a closed-form description. Here, a simple but formative description of propagated signaling phenomena in the membrane of an axon is presented in closed-form. The focus is on using both biophysics and mathematical methods for elucidating the fundamental mechanisms governing transmembrane polarization. The results presented demonstrate how to resolve electromagnetic and thermodynamic factors that govern transmembrane potential. Computational results are supported by well-established quantitative descriptions of propagated signaling phenomena in the membrane of an axon. The findings demonstrate how intracellular conductance, the thermodynamics of magnetization, and current modulation function together in generating an action potential in a unified closed-form description. The work presented in this paper provides compelling evidence that three basic factors contribute to the propagated signaling in the membrane of an axon. It is anticipated this work will compel those in biophysics, physical biology, and in the computational neurosciences to probe deeper into the classical and quantum features of membrane magnetization and signaling. It is hoped that subsequent investigations of this sort will be advanced by the computational features of this model without having to resort to numerical methods of analysis.

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

Science.gov (United States)

Mizuhashi, Koji; Chaya, Taro; Kanamoto, Takashi; Omori, Yoshihiro; Furukawa, Takahisa

2015-01-01

Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice. First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant. Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

Developing sporophytes transition from an inducible to a constitutive ecological strategy of desiccation tolerance in the moss Aloina ambigua: effects of desiccation on fitness.

Science.gov (United States)

Stark, Lloyd R; Brinda, John C

2015-03-01

Two ecological strategies of desiccation tolerance exist in plants, constitutive and inducible. Because of difficulties in culturing sporophytes, very little is known about desiccation tolerance in this generation and how desiccation affects sexual fitness. Cultured sporophytes and vegetative shoots from a single genotype of the moss Aloina ambigua raised in the laboratory were tested for their strategy of desiccation tolerance by desiccating the shoot-sporophyte complex and vegetative shoots at different intensities, and comparing outcomes with those of undried shoot-sporophyte complexes and vegetative shoots. By using a dehardened clonal line, the effects of field, age and genetic variance among plants were removed. The gametophyte and embryonic sporophyte were found to employ a predominantly inducible strategy of desiccation tolerance, while the post-embryonic sporophyte was found to employ a moderately constitutive strategy of desiccation tolerance. Further, desiccation reduced sporophyte fitness, as measured by sporophyte mass, seta length and capsule size. However, the effects of desiccation on sporophyte fitness were reduced if the stress occurred during embryonic development as opposed to postembryonic desiccation. The effects of desiccation on dehardened sporophytes of a bryophyte are shown for the first time. The transition from one desiccation tolerance strategy to the other in a single structure or generation is shown for only the second time in plants and for the first time in bryophytes. Finding degrees of inducible strategies of desiccation tolerance in different life phases prompts the formulation of a continuum hypothesis of ecological desiccation tolerance in mosses, where desiccation tolerance is not an either/or phenomenon, but varies in degree along a gradient of ecological inducibility. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email

Effects of Pressure, Temperature, Treatment Time, and Storage on Rheological, Textural, and Structural Properties of Heat-Induced Chickpea Gels

Directory of Open Access Journals (Sweden)

María Dolores Alvarez

2015-04-01

Full Text Available Pressure-induced gelatinization of chickpea flour (CF was studied in combination with subsequent temperature-induced gelatinization. CF slurries (with 1:5 flour-to-water ratio and CF in powder form were treated with high hydrostatic pressure (HHP, temperature (T, and treatment time (t at three levels (200, 400, 600 MPa; 10, 25, 50 °C; 5, 15, 25 min. In order to investigate the effect of storage (S, half of the HHP-treated CF slurries were immediately analyzed for changes in oscillatory rheological properties under isothermal heating at 75 °C for 15 min followed by cooling to 25 °C. The other half of the HHP-treated CF slurries were refrigerated (at 4 °C for one week and subsequently analyzed for changes in oscillatory properties under the same heating conditions as the unrefrigerated samples. HHP-treated CF in powder form was analyzed for changes in textural properties of heat-induced CF gels under isothermal heating at 90 °C for 5 min and subsequent cooling to 25 °C. Structural changes during gelatinization were investigated using microscopy. Pressure had a more significant effect on rheological and textural properties, followed by T and treatment t (in that order. Gel aging in HHP-treated CF slurries during storage was supported by rheological measurements.

Fitness

Science.gov (United States)

... gov home http://www.girlshealth.gov/ Home Fitness Fitness Want to look and feel your best? Physical ... are? Check out this info: What is physical fitness? top Physical fitness means you can do everyday ...

Large-scale identification of membrane proteins based on analysis of trypsin-protected transmembrane segments

Czech Academy of Sciences Publication Activity Database

Vít, O.; Man, Petr; Kádek, Alan; Hausner, Jiří; Sklenář, A.; Harant, K.; Novák, Petr; Scigelová, M.; Wofferndin, G.; Petrák, J.

2016-01-01

Roč. 146, SI (2016), s. 15-22 ISSN 1874-3919 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Integral membrane proteins * CNBr * Transmembrane Subject RIV: CE - Biochemistry Impact factor: 3.914, year: 2016

Impact of axial velocity and transmembrane pressure (TMP) on ARP filter performance

Energy Technology Data Exchange (ETDEWEB)

Poirier, M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Burket, P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-02-29

The Savannah River Site (SRS) is currently treating radioactive liquid waste with the Actinide Removal Process (ARP) and the Modular Caustic Side Solvent Extraction Unit (MCU). Recently, the low filter flux through the ARP of approximately 5 gallons per minute has limited the rate at which radioactive liquid waste can be treated. Salt Batch 6 had a lower processing rate and required frequent filter cleaning. Savannah River Remediation (SRR) has a desire to understand the causes of the low filter flux and to increase ARP/MCU throughput. One potential method for increasing filter flux is to adjust the axial velocity and transmembrane pressure (TMP). SRR requested SRNL to conduct bench-scale filter tests to evaluate the effects of axial velocity and transmembrane pressure on crossflow filter flux. The objective of the testing was to determine whether increasing the axial velocity at the ARP could produce a significant increase in filter flux. The authors conducted the tests by preparing slurries containing 6.6 M sodium Salt Batch 6 supernate and 2.5 g MST/L, processing the slurry through a bench-scale crossflow filter unit at varying axial velocity and TMP, and measuring filter flux as a function of time.

How "fun/importance" fit affects performance: relating implicit theories to instructions.

Science.gov (United States)

Bianco, Amy T; Higgins, E Tory; Klem, Adena

2003-09-01

People experience a regulatory fit when they employ means of goal pursuit that fit their regulatory orientation, and this fit increases motivation that can enhance performance. The present studies extend previous research on regulatory fit to the classic motivational variables of fun and importance. They also examine for the first time the effect on performance of the fit between individuals' implicit theories about a task's fun or importance and their strategic engagement of the task as fun or important as induced by task instructions. In all three studies, task performance was better when the external task instructions "fit" rather than did not fit participants' implicit theory for the task. The implications of these findings for understanding the motivational effects of fun and importance are discussed.

Modeling of hydrogen/deuterium dynamics and heat generation on palladium nanoparticles for hydrogen storage and solid-state nuclear fusion

Directory of Open Access Journals (Sweden)

Katsuaki Tanabe

2016-01-01

Full Text Available We modeled the dynamics of hydrogen and deuterium adsorbed on palladium nanoparticles including the heat generation induced by the chemical adsorption and desorption, as well as palladium-catalyzed reactions. Our calculations based on the proposed model reproduce the experimental time-evolution of pressure and temperature with a single set of fitting parameters for hydrogen and deuterium injection. The model we generated with a highly generalized set of formulations can be applied for any combination of a gas species and a catalytic adsorbent/absorbent. Our model can be used as a basis for future research into hydrogen storage and solid-state nuclear fusion technologies.

Hamiltonian inclusive fitness: a fitter fitness concept.

Science.gov (United States)

Costa, James T

2013-01-01

In 1963-1964 W. D. Hamilton introduced the concept of inclusive fitness, the only significant elaboration of Darwinian fitness since the nineteenth century. I discuss the origin of the modern fitness concept, providing context for Hamilton's discovery of inclusive fitness in relation to the puzzle of altruism. While fitness conceptually originates with Darwin, the term itself stems from Spencer and crystallized quantitatively in the early twentieth century. Hamiltonian inclusive fitness, with Price's reformulation, provided the solution to Darwin's 'special difficulty'-the evolution of caste polymorphism and sterility in social insects. Hamilton further explored the roles of inclusive fitness and reciprocation to tackle Darwin's other difficulty, the evolution of human altruism. The heuristically powerful inclusive fitness concept ramified over the past 50 years: the number and diversity of 'offspring ideas' that it has engendered render it a fitter fitness concept, one that Darwin would have appreciated.

Activation of hydrogen storage materials in the Li-Mg-N-H system: Effect on storage properties

International Nuclear Information System (INIS)

Yang, Jun; Sudik, Andrea; Wolverton, C.

2007-01-01

We investigate the thermodynamics, kinetics, and capacity of the hydrogen storage reaction: Li 2 Mg(NH) 2 + 2H 2 ↔ Mg(NH 2 ) 2 + 2LiH. Starting with LiNH 2 and MgH 2 , two distinct procedures have been previously proposed for activating samples to induce the reversible storage reaction. We clarify here the impact of these two activation procedures on the resulting capacity for the Li-Mg-N-H reaction. Additionally, we measure the temperature-dependent kinetic absorption data for this hydrogen storage system. Finally, our experiments confirm the previously reported formation enthalpy (ΔH), hydrogen capacity, and pressure-composition-isotherm (PCI) data, and suggest that this system represents a kinetically (but not thermodynamically) limited system for vehicular on-board storage applications

SCIMP, a transmembrane adaptor protein involved in major histocompatibility complex class II signaling

Czech Academy of Sciences Publication Activity Database

Dráber, Peter; Vonková, Ivana; Štěpánek, Ondřej; Hrdinka, Matouš; Kucová, Markéta; Skopcová, Tereza; Otáhal, Pavel; Angelisová, Pavla; Hořejší, Václav; Yeung, M.; Weiss, A.; Brdička, Tomáš

2011-01-01

Roč. 31, č. 22 (2011), s. 4550-4562 ISSN 0270-7306 R&D Projects: GA MŠk 1M0506; GA ČR GEMEM/09/E011 Institutional research plan: CEZ:AV0Z50520514 Keywords : SCIMP * transmembrane adaptor protein * MHC II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.527, year: 2011

Dissection of seroreactivity against the tryptophan-rich motif of the feline immunodeficiency virus transmembrane glycoprotein

International Nuclear Information System (INIS)

Freer, Giulia; Giannecchini, Simone; Tissot, Alain; Bachmann, Martin F.; Rovero, Paolo; Serres, Pierre Francoise; Bendinelli, Mauro

2004-01-01

Immunogenicity of the tryptophan-rich motif (TrpM) in the membrane-proximal ectodomain of the transmembrane (TM) glycoprotein of feline immunodeficiency virus (FIV) was investigated. Peptide 59, a peptide containing the TrpM of the TM of FIV, was covalently coupled to Qβ phage virus-like particles (Qβ-59) in the attempt to induce potent anti-TrpM B cell responses in cats. All Qβ-59 immunized cats, but not cats that received a mixture of uncoupled Qβ and peptide 59, developed antibodies that reacted with a same epitope in extensive binding and binding competition assays. The epitope recognized was composed of three amino acids, two of which are adjacent. However, Qβ-59-immune sera failed to recognize whole FIV in all binding and neutralization assays performed. Furthermore, no reactivity against the TrpM was detected by screening sera from FIV-infected cats that had reacted with TM peptides, confirming that this epitope does not seem to be serologically functional in the FIV virion. The data suggest that TrpM may not be a suitable target for antiviral vaccine design

Expression and regulation of transmembrane transporters in healthy intestine and gastrointestinal diseases

OpenAIRE

Hruz, Petr

2006-01-01

Transmembrane transporters mediate energy dependent or independent translocation of drugs, potentially toxic compounds, and of various endogenous substrates such as bile acids and bilirubin across membranes. In this thesis the focus is on two classes of transporters, the ATPbinding cassette (ABC) transporters, which mediate ATP dependent transport and the solute carriers (SLC) which use electrochemical gradients for their transport. The transporters are expressed on membranes o...

Biological mechanisms underlying the role of physical fitness in health and resilience

OpenAIRE

Silverman, Marni N.; Deuster, Patricia A.

2014-01-01

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appear...

A microseismic workflow for managing induced seismicity risk as CO₂ storage projects

Energy Technology Data Exchange (ETDEWEB)

Matzel, E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Morency, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pyle, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Templeton, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); White, J. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2015-10-27

It is well established that fluid injection has the potential to induce earthquakes—from microseismicity to large, damaging events—by altering state-of-stress conditions in the subsurface. While induced seismicity has not been a major operational issue for carbon storage projects to date, a seismicity hazard exists and must be carefully addressed. Two essential components of effective seismic risk management are (1) sensitive microseismic monitoring and (2) robust data interpretation tools. This report describes a novel workflow, based on advanced processing algorithms applied to microseismic data, to help improve management of seismic risk. This workflow has three main goals: (1) to improve the resolution and reliability of passive seismic monitoring, (2) to extract additional, valuable information from continuous waveform data that is often ignored in standard processing, and (3) to minimize the turn-around time between data collection, interpretation, and decision-making. These three objectives can allow for a better-informed and rapid response to changing subsurface conditions.

Silo Storage Preconceptual Design

Energy Technology Data Exchange (ETDEWEB)

Stephanie L. Austad; Patrick W. Bragassa; Kevin M Croft; David S Ferguson; Scott C Gladson; Annette L Shafer; John H Weathersby

2012-09-01

The National Nuclear Security Administration (NNSA) has a need to develop and field a low-cost option for the long-term storage of a variety of radiological material. The storage option’s primary requirement is to provide both environmental and physical protection of the materials. Design criteria for this effort require a low initial cost and minimum maintenance over a 50-year design life. In 1999, Argonne National Laboratory-West was tasked with developing a dry silo storage option for the BN-350 Spent Fuel in Aktau Kazakhstan. Argon’s design consisted of a carbon steel cylinder approximately 16 ft long, 18 in. outside diameter and 0.375 in. wall thickness. The carbon steel silo was protected from corrosion by a duplex coating system consisting of zinc and epoxy. Although the study indicated that the duplex coating design would provide a design life well in excess of the required 50 years, the review board was concerned because of the novelty of the design and the lack of historical use. In 2012, NNSA tasked Idaho National Laboratory (INL) with reinvestigating the silo storage concept and development of alternative corrosion protection strategies. The 2012 study, “Silo Storage Concepts, Cathodic Protection Options Study” (INL/EST-12-26627), concludes that the option which best fits the design criterion is a passive cathotic protection scheme, consisting of a carbon steel tube coated with zinc or a zinc-aluminum alloy encapsulated in either concrete or a cement grout. The hot dipped zinc coating option was considered most efficient, but the flame-sprayed option could be used if a thicker zinc coating was determined to be necessary.

Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo

Science.gov (United States)

Lobikin, Maria; Chernet, Brook; Lobo, Daniel; Levin, Michael

2012-12-01

Cancer may result from localized failure of instructive cues that normally orchestrate cell behaviors toward the patterning needs of the organism. Steady-state gradients of transmembrane voltage (Vmem) in non-neural cells are instructive, epigenetic signals that regulate pattern formation during embryogenesis and morphostatic repair. Here, we review molecular data on the role of bioelectric cues in cancer and present new findings in the Xenopus laevis model on how the microenvironment's biophysical properties contribute to cancer in vivo. First, we investigated the melanoma-like phenotype arising from serotonergic signaling by ‘instructor’ cells—a cell population that is able to induce a metastatic phenotype in normal melanocytes. We show that when these instructor cells are depolarized, blood vessel patterning is disrupted in addition to the metastatic phenotype induced in melanocytes. Surprisingly, very few instructor cells need to be depolarized for the hyperpigmentation phenotype to occur; we present a model of antagonistic signaling by serotonin receptors that explains the unusual all-or-none nature of this effect. In addition to the body-wide depolarization-induced metastatic phenotype, we investigated the bioelectrical properties of tumor-like structures induced by canonical oncogenes and cancer-causing compounds. Exposure to carcinogen 4-nitroquinoline 1-oxide (4NQO) induces localized tumors, but has a broad (and variable) effect on the bioelectric properties of the whole body. Tumors induced by oncogenes show aberrantly high sodium content, representing a non-invasive diagnostic modality. Importantly, depolarized transmembrane potential is not only a marker of cancer but is functionally instructive: susceptibility to oncogene-induced tumorigenesis is significantly reduced by forced prior expression of hyperpolarizing ion channels. Importantly, the same effect can be achieved by pharmacological manipulation of endogenous chloride channels, suggesting

Radiative polarization in high-energy storage rings

International Nuclear Information System (INIS)

Mane, S.R.

1989-01-01

Electron and positron beams circulating in high-energy storage rings become spontaneously polarized by the emission of synchrotron radiation. The asymptotic degree of polarization that can be attained is strongly affected by so-called depolarizing resonances. Detailed experimental measurements of the polarization were made SPEAR about ten years ago, but due to lack of a suitable theory only a limited theoretical fit to the data has so far been achieved. The author presents a general formalism for calculating depolarizing resonances, which has been coded into a computer program called SMILE, and use it to fit the SPEAR data. By the use of suitable approximations, the author is able to fit both higher order and nonlinear resonances, and thereby to interpret many hitherto unexplained features in the data, and to resolve a puzzle concerning the asymmetry of certain resonance widths seen in the data. 18 refs., 2 figs

Molecular dynamics study of the solvation of an alpha-helical transmembrane peptide by DMSO

NARCIS (Netherlands)

Duarte, A.M.; Mierlo, van C.P.M.; Hemminga, M.A.

2008-01-01

10-ns molecular dynamics study of the solvation of a hydrophobic transmembrane helical peptide in dimethyl sulfoxide (DMSO) is presented. The objective is to analyze how this aprotic polar solvent is able to solvate three groups of amino acid residues (i.e., polar, apolar, and charged) that are

Epithelial Cell–Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia

Science.gov (United States)

Kamata, Hirofumi; Yamamoto, Kazuko; Wasserman, Gregory A.; Zabinski, Mary C.; Yuen, Constance K.; Lung, Wing Yi; Gower, Adam C.; Belkina, Anna C.; Ramirez, Maria I.; Deng, Jane C.; Quinton, Lee J.; Jones, Matthew R.

2016-01-01

Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-κB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6GbrightCD11bbright neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia. PMID:27064756

Epithelial Cell-Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia.

Science.gov (United States)

Kamata, Hirofumi; Yamamoto, Kazuko; Wasserman, Gregory A; Zabinski, Mary C; Yuen, Constance K; Lung, Wing Yi; Gower, Adam C; Belkina, Anna C; Ramirez, Maria I; Deng, Jane C; Quinton, Lee J; Jones, Matthew R; Mizgerd, Joseph P

2016-09-01

Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-κB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6G(bright)CD11b(bright) neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia.

Ouabain exacerbates activation-induced cell death in human peripheral blood lymphocytes

OpenAIRE

Esteves Mabel B.; Marques-Santos Luis F.; Affonso-Mitidieri Ottília R.; Rumjanek Vivian M.

2005-01-01

Lymphocytes activated by mitogenic lectins display changes in transmembrane potential, an elevation in the cytoplasmic Ca2+ concentrations, proliferation and/or activation induced cell death. Low concentrations of ouabain (an inhibitor of Na+,K+-ATPase) suppress mitogen-induced proliferation and increases cell death. To understand the mechanisms involved, a number of parameters were analyzed using fluorescent probes and flow cytometry. The addition of 100nM ouabain to cultures of peripheral b...

Simulation of a Potential CO2 Storage in the West Paris Basin: Site Characterization and Assessment of the Long-Term Hydrodynamical and Geochemical Impacts Induced by the CO2 Injection

Directory of Open Access Journals (Sweden)

Estublier Audrey

2017-07-01

Full Text Available This article presents the preliminary results of a study carried out as part of a demonstration project of CO2 storage in the Paris Basin. This project funded by ADEME (French Environment and Energy Management Agency and several industrial partners (TOTAL, ENGIE, EDF, Lafarge, Air Liquide, Vallourec aimed to study the possibility to set up an experimental infrastructure of CO2 transport and storage. Regarding the storage, the objectives were: (1 to characterize the selected site by optimizing the number of wells in a CO2 injection case of 200 Mt over 50 years in the Trias, (2 to simulate over time the CO2 migration and the induced pressure field, and (3 to analyze the geochemical behavior of the rock over the long term (1,000 years. The preliminary site characterization study revealed that only the southern area of Keuper succeeds to satisfy this injection criterion using only four injectors. However, a complementary study based on a refined fluid flow model with additional secondary faults concluded that this zone presents the highest potential of CO2 injection but without reaching the objective of 200 Mt with a reasonable number of wells. The simulation of the base scenario, carried out before the model refinement, showed that the overpressure above 0.1 MPa covers an area of 51,869 km2 in the Chaunoy formation, 1,000 years after the end of the injection, which corresponds to the whole West Paris Basin, whereas the CO2 plume extension remains small (524 km2. This overpressure causes brine flows at the domain boundaries and a local overpressure in the studied oil fields. Regarding the preliminary risk analysis of this project, the geochemical effects induced by the CO2 injection were studied by simulating the fluid-rock interactions with a coupled geochemical and fluid flow model in a domain limited to the storage complex. A one-way coupling of two models based on two domains fitting into each other was developed using dynamic boundary

Fisetin induces apoptosis through mitochondrial apoptosis pathway in human uveal melanoma cells.

Science.gov (United States)

Wang, Kai; Hu, Dan-Ning; Lin, Hui-Wen; Yang, Wei-En; Hsieh, Yi-Hsien; Chien, Hsiang-Wen; Yang, Shun-Fa

2018-05-01

Fisetin, a diatery flavonoid, been reported that possess anticancer effects in various cancers. The purpose of the study was to investigate the antitumor effects of fisetin in cultured uveal melanoma cell lines and compared with normal retinal pigment epithelial (RPE) cells. MTT assay was used for evaluating cytotoxic effects of fisetin. Flow cytometry study was used for the determination of apoptosis. JC-1 fluorescent reader was used to determine mitochondrial transmembrane potential changes. The results shown that fisetin dose-dependently decreased the cell viability of uveal melanoma cells but not influenced the cell viability of RPE cells. Apoptosis of uveal melanoma cells was induced by fisetin efficiently. Fisetin inhibited antiapoptotic Bcl-2 family proteins and damaged the mitochondrial transmembrane potential. The levels of proapoptotic Bcl-2 proteins, cytochrome c, and various caspase activities were increased by fisetin. In conclusion, fisetin induces apoptosis of uveal melanoma cells selectively and may be a promising agent to be explored for the treatment of uveal melanoma. © 2018 Wiley Periodicals, Inc.

Recombinant expression in E. coli of human FGFR2 with its transmembrane and extracellular domains

Directory of Open Access Journals (Sweden)

Adam Bajinting

2017-06-01

Full Text Available Fibroblast growth factor receptors (FGFRs are a family of receptor tyrosine kinases containing three domains: an extracellular receptor domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. FGFRs are activated by fibroblast growth factors (FGFs as part of complex signal transduction cascades regulating angiogenesis, skeletal formation, cell differentiation, proliferation, cell survival, and cancer. We have developed the first recombinant expression system in E. coli to produce a construct of human FGFR2 containing its transmembrane and extracellular receptor domains. We demonstrate that the expressed construct is functional in binding heparin and dimerizing. Size exclusion chromatography demonstrates that the purified FGFR2 does not form a complex with FGF1 or adopts an inactive dimer conformation. Progress towards the successful recombinant production of intact FGFRs will facilitate further biochemical experiments and structure determination that will provide insight into how extracellular FGF binding activates intracellular kinase activity.

Computational Search for Improved Ammonia Storage Materials

DEFF Research Database (Denmark)

Jensen, Peter Bjerre; Lysgaard, Steen; Vegge, Tejs

Metal halide ammines, e.g. Mg(NH3)6Cl2 and Sr(NH3)8Cl2, can reversibly store ammonia, with high volumetric hydrogen storage capacities. The storage in the halide ammines is very safe, and the salts are therefore highly relevant as a carbon-free energy carrier in future transportation infrastructure...... selection. The GA is evolving from an initial (random) population and selecting those with highest fitness, a function based on e.g. stability, release temperature, storage capacity and the price of the elements. The search space includes all alkaline earth, 3d and 4d metals in combination with chloride......, bromide or iodide, and mixtures thereof. In total the search space consists of thousands of combinations, which makes a GA ideal, to reduce the number of necessary calculations. We are screening for a one step release from either a hexa or octa ammine, and we have found promising candidates, which...

Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism

Science.gov (United States)

Liberato, Marcelo V.; Silveira, Rodrigo L.; Prates, Érica T.; de Araujo, Evandro A.; Pellegrini, Vanessa O. A.; Camilo, Cesar M.; Kadowaki, Marco A.; Neto, Mario De O.; Popov, Alexander; Skaf, Munir S.; Polikarpov, Igor

2016-04-01

Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials. Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity. Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms. The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite. This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.

Energy Storage Requirements for Achieving 50% Solar Photovoltaic Energy Penetration in California

Energy Technology Data Exchange (ETDEWEB)

Denholm, Paul; Margolis, Robert

2016-08-01

We estimate the storage required to enable PV penetration up to 50% in California (with renewable penetration over 66%), and we quantify the complex relationships among storage, PV penetration, grid flexibility, and PV costs due to increased curtailment. We find that the storage needed depends strongly on the amount of other flexibility resources deployed. With very low-cost PV (three cents per kilowatt-hour) and a highly flexible electric power system, about 19 gigawatts of energy storage could enable 50% PV penetration with a marginal net PV levelized cost of energy (LCOE) comparable to the variable costs of future combined-cycle gas generators under carbon constraints. This system requires extensive use of flexible generation, transmission, demand response, and electrifying one quarter of the vehicle fleet in California with largely optimized charging. A less flexible system, or more expensive PV would require significantly greater amounts of storage. The amount of storage needed to support very large amounts of PV might fit within a least-cost framework driven by declining storage costs and reduced storage-duration needs due to high PV penetration.

Storage of Spent Nuclear Fuel. Specific Safety Guide

International Nuclear Information System (INIS)

2012-01-01

This Safety Guide provides recommendations and guidance on the storage of spent nuclear fuel. It covers all types of storage facilities and all types of spent fuel from nuclear power plants and research reactors. It takes into consideration the longer storage periods that have become necessary owing to delays in the development of disposal facilities and the decrease in reprocessing activities. It also considers developments associated with nuclear fuel, such as higher enrichment, mixed oxide fuels and higher burnup. The Safety Guide is not intended to cover the storage of spent fuel if this is part of the operation of a nuclear power plant or spent fuel reprocessing facility. Guidance is provided on all stages for spent fuel storage facilities, from planning through siting and design to operation and decommissioning, and in particular retrieval of spent fuel. Contents: 1. Introduction; 2. Protection of human health and the environment; 3. Roles and responsibilities; 4. Management system; 5. Safety case and safety assessment; 6. General safety considerations for storage of spent fuel. Appendix I: Specific safety considerations for wet or dry storage of spent fuel; Appendix II: Conditions for specific types of fuel and additional considerations; Annex: I: Short term and long term storage; Annex II: Operational and safety considerations for wet and dry spent fuel storage facilities; Annex III: Examples of sections of operating procedures for a spent fuel storage facility; Annex IV: Site conditions, processes and events for consideration in a safety assessment (external human induced phenomena); Annex V: Site conditions, processes and events for consideration in a safety assessment (external natural phenomena); Annex VI: Site conditions, processes and events for consideration in a safety assessment (external human induced phenomena); Annex VII: Postulated initiating events for consideration in a safety assessment (internal phenomena).

High temperature energy storage performances of methane reforming with carbon dioxide in a tubular packed reactor

International Nuclear Information System (INIS)

Lu, Jianfeng; Chen, Yuan; Ding, Jing; Wang, Weilong

2016-01-01

Highlights: • Energy storage of methane reforming in a tubular packed reactor is investigated. • Thermochemical storage efficiency approaches maximum at optimal temperature. • Sensible heat and heat loss play important roles in the energy storage system. • The reaction and energy storage models of methane reforming reactor are established. • The simulated methane conversion and energy storage efficiency fit with experiments. - Abstract: High temperature heat transfer and energy storage performances of methane reforming with carbon dioxide in tubular packed reactor are investigated under different operating conditions. Experimental results show that the methane reforming in tubular packed reactor can efficiently store high temperature thermal energy, and the sensible heat and heat loss besides thermochemical energy storage play important role in the total energy storage process. When the operating temperature is increased, the thermochemical storage efficiency first increases for methane conversion rising and then decreases for heat loss rising. As the operating temperate is 800 °C, the methane conversion is 79.6%, and the thermochemical storage efficiency and total energy efficiency can be higher than 47% and 70%. According to the experimental system, the flow and reaction model of methane reforming is established using the laminar finite-rate model and Arrhenius expression, and the simulated methane conversion and energy storage efficiency fit with experimental data. Along the flow direction, the fluid temperature in the catalyst bed first decreases because of the endothermic reaction and then increases for the heat transfer from reactor wall. As a conclusion, the maximum thermochemical storage efficiency will be obtained under optimal operating temperature and optimal flow rate, and the total energy efficiency can be increased by the increase of bed conductivity and decrease of heat loss coefficient.

The transmembrane region is responsible for targeting of adaptor protein LAX into "heavy rafts''

Czech Academy of Sciences Publication Activity Database

Hrdinka, Matouš; Otáhal, Pavel; Hořejší, Václav

2012-01-01

Roč. 7, č. 5 (2012), e36330 E-ISSN 1932-6203 R&D Projects: GA ČR GEMEM/09/E011; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : LAX * transmembrane domain * DRM Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

Artificial Diels–Alderase based on the transmembrane protein FhuA

Directory of Open Access Journals (Sweden)

Hassan Osseili

2016-06-01

Full Text Available Copper(I and copper(II complexes were covalently linked to an engineered variant of the transmembrane protein Ferric hydroxamate uptake protein component A (FhuA ΔCVFtev. Copper(I was incorporated using an N-heterocyclic carbene (NHC ligand equipped with a maleimide group on the side arm at the imidazole nitrogen. Copper(II was attached by coordination to a terpyridyl ligand. The spacer length was varied in the back of the ligand framework. These biohybrid catalysts were shown to be active in the Diels–Alder reaction of a chalcone derivative with cyclopentadiene to preferentially give the endo product.

Estimating the Quantity of Wind and Solar Required To Displace Storage-Induced Emissions.

Science.gov (United States)

Hittinger, Eric; Azevedo, Inês M L

2017-11-07

The variable and nondispatchable nature of wind and solar generation has been driving interest in energy storage as an enabling low-carbon technology that can help spur large-scale adoption of renewables. However, prior work has shown that adding energy storage alone for energy arbitrage in electricity systems across the U.S. routinely increases system emissions. While adding wind or solar reduces electricity system emissions, the emissions effect of both renewable generation and energy storage varies by location. In this work, we apply a marginal emissions approach to determine the net system CO 2 emissions of colocated or electrically proximate wind/storage and solar/storage facilities across the U.S. and determine the amount of renewable energy required to offset the CO 2 emissions resulting from operation of new energy storage. We find that it takes between 0.03 MW (Montana) and 4 MW (Michigan) of wind and between 0.25 MW (Alabama) and 17 MW (Michigan) of solar to offset the emissions from a 25 MW/100 MWh storage device, depending on location and operational mode. Systems with a realistic combination of renewables and storage will result in net emissions reductions compared with a grid without those systems, but the anticipated reductions are lower than a renewable-only addition.

Recreational fishing selectively captures individuals with the highest fitness potential.

Science.gov (United States)

Sutter, David A H; Suski, Cory D; Philipp, David P; Klefoth, Thomas; Wahl, David H; Kersten, Petra; Cooke, Steven J; Arlinghaus, Robert

2012-12-18

Fisheries-induced evolution and its impact on the productivity of exploited fish stocks remains a highly contested research topic in applied fish evolution and fisheries science. Although many quantitative models assume that larger, more fecund fish are preferentially removed by fishing, there is no empirical evidence describing the relationship between vulnerability to capture and individual reproductive fitness in the wild. Using males from two lines of largemouth bass (Micropterus salmoides) selectively bred over three generations for either high (HV) or low (LV) vulnerability to angling as a model system, we show that the trait "vulnerability to angling" positively correlates with aggression, intensity of parental care, and reproductive fitness. The difference in reproductive fitness between HV and LV fish was particularly evident among larger males, which are also the preferred mating partners of females. Our study constitutes experimental evidence that recreational angling selectively captures individuals with the highest potential for reproductive fitness. Our study further suggests that selective removal of the fittest individuals likely occurs in many fisheries that target species engaged in parental care. As a result, depending on the ecological context, angling-induced selection may have negative consequences for recruitment within wild populations of largemouth bass and possibly other exploited species in which behavioral patterns that determine fitness, such as aggression or parental care, also affect their vulnerability to fishing gear.

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

Science.gov (United States)

Alvares, Stacy M.; Dunn, Clarence A.; Brown, Tod A.; Wayner, Elizabeth E.; Carter, William G.

2008-01-01

Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and Detergent-Resistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals- possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. PMID:18269919

Transmembrane adaptor proteins in the high-affinity IgE receptor signaling

Czech Academy of Sciences Publication Activity Database

Dráber, Petr; Hálová, Ivana; Levi-Schaffer, F.; Dráberová, Lubica

2012-01-01

Roč. 2, 11.1. (2012), s. 95 ISSN 1664-3224 R&D Projects: GA MŠk 1M0506; GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA AV ČR KAN200520701 Grant - others:AV ČR(CZ) M200520901 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : IgE receptor * LAT/LAT1 * LAX * NTAL/Lab/LAT2 * PAG/Cbp * mast cells * plasma membrane * transmembrane adaptor proteins Subject RIV: EB - Genetics ; Molecular Biology

Transmembrane amyloid-related proteins in CSF as potential biomarkers for Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Inmaculada eLopez-Font

2015-06-01

Full Text Available In the continuing search for new cerebrospinal fluid (CSF biomarkers for Alzheimer’s disease (AD, reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP, as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic activities of some of these secretases, such as BACE1 and TACE, have been investigated as potential AD biomarkers, and it has been assumed that these activities present in human CSF result from the soluble truncated forms of the membrane-bound enzymes. However, we and others recently identified soluble forms of BACE1 and APP in CSF containing the intracellular domains, as well as the multi-pass transmembrane presenilin-1 (PS1 and other subunits of γ-secretase. We also review recent findings that suggest that most of these soluble transmembrane proteins could display self-association properties based on hydrophobic and/or ionic interactions leading to the formation of heteromeric complexes. The oligomerization state of these potential new biomarkers needs to be taken into consideration for assessing their real potential as CSF biomarkers for AD by adequate molecular tools.

Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors

Directory of Open Access Journals (Sweden)

Kelly J Culhane

2015-11-01

Full Text Available Although family B G protein-coupled receptors (GPCRs contain only 15 members, they play key roles in transmembrane signal transduction of hormones. Family B GPCRs are drug targets for developing therapeutics for diseases ranging from metabolic to neurological disorders. Despite their importance, the molecular mechanism of activation of family B GPCRs remains largely unexplored due to the challenges in expression and purification of functional receptors to the quantity for biophysical characterization. Currently, there is no crystal structure available of a full-length family B GPCR. However, structures of key domains, including the extracellular ligand binding regions and seven-helical transmembrane regions, have been solved by X-ray crystallography and NMR, providing insights into the mechanisms of ligand recognition and selectivity, and helical arrangements within the cell membrane. Moreover, biophysical and biochemical methods have been used to explore functions, key residues for signaling, and the kinetics and dynamics of signaling processes. This review summarizes the current knowledge of the signal transduction mechanism of family B GPCRs at the molecular level and comments on the challenges and outlook for mechanistic studies of family B GPCRs.

Numerical analysis of magnetic field in superconducting magnetic energy storage

International Nuclear Information System (INIS)

Kanamaru, Y.; Amemiya, Y.

1991-01-01

This paper reports that the superconducting magnetic energy storage (SMES) is more useful than the other systems of electric energy storage because of larger stored energy and higher efficiency. The other systems are the battery, the flywheel, the pumped-storage power station. Some models of solenoid type SMES are designed in U.S.A. and Japan. But a high magnetic field happens by the large scale SMES in the living environment, and makes the erroneous operations of the computer display, the pacemaker of the heart and the electronic equipments. We study some fit designs of magnetic shielding of the solenoidal type SMES for reduction of the magnetic field in living environment. When some superconducting shielding coils are over the main storage coil, magnetic field reduces remarkably than the case of non shielding coil. The calculated results of the magnetic field are obtained y the finite element method

Biologically Complex Planar Cell Plasma Membranes Supported on Polyelectrolyte Cushions Enhance Transmembrane Protein Mobility and Retain Native Orientation.

Science.gov (United States)

Liu, Han-Yuan; Chen, Wei-Liang; Ober, Christopher K; Daniel, Susan

2018-01-23

Reconstituted supported lipid bilayers (SLB) are widely used as in vitro cell-surface models because they are compatible with a variety of surface-based analytical techniques. However, one of the challenges of using SLBs as a model of the cell surface is the limited complexity in membrane composition, including the incorporation of transmembrane proteins and lipid diversity that may impact the activity of those proteins. Additionally, it is challenging to preserve the transmembrane protein native orientation, function, and mobility in SLBs. Here, we leverage the interaction between cell plasma membrane vesicles and polyelectrolyte brushes to create planar bilayers from cell plasma membrane vesicles that have budded from the cell surface. This approach promotes the direct incorporation of membrane proteins and other species into the planar bilayer without using detergent or reconstitution and preserves membrane constituents. Furthermore, the structure of the polyelectrolyte brush serves as a cushion between the planar bilayer and rigid supporting surface, limiting the interaction of the cytosolic domains of membrane proteins with this surface. Single particle tracking was used to analyze the motion of GPI-linked yellow fluorescent proteins (GPI-YFP) and neon-green fused transmembrane P2X2 receptors (P2X2-neon) and shows that this platform retains over 75% mobility of multipass transmembrane proteins in its native membrane environment. An enzyme accessibility assay confirmed that the protein orientation is preserved and results in the extracellular domain facing toward the bulk phase and the cytosolic side facing the support. Because the platform presented here retains the complexity of the cell plasma membrane and preserves protein orientation and mobility, it is a better representative mimic of native cell surfaces, which may find many applications in biological assays aimed at understanding cell membrane phenomena.

On the value and price-responsiveness of ramp-constrained storage

International Nuclear Information System (INIS)

Faghih, Ali; Roozbehani, Mardavij; Dahleh, Munther A.

2013-01-01

Highlights: • Derived the optimal policy and value function for ramp-constrained storage. • Gave analytic bound on long-term value, and explicit formulas for policy thresholds. • Value of storage saturates as capacity increases, regardless of price volatility. • In expectation, storage can induce high price elasticity near the mean price. • The buy/sell phase transition region in the price-state plane is steep. - Abstract: The primary concerns of this paper are twofold: understanding the value of storage in the presence of ramp constraints and exogenous energy prices, and understanding the implications of the associated optimal storage management policy for qualitative and quantitative characteristics of storage response to real-time prices. The optimal policy, along with the associated finite-horizon time-averaged value of storage, are analytically characterized in this paper. An analytical upper bound on the infinite-horizon time-averaged value of storage is also derived. This bound is valid for any achievable realization of prices when the support of the distribution is fixed, and highlights the dependence of the value of storage on ramp constraints and storage capacity. It is shown that while the value of storage is a non-decreasing function of price volatility, due to the finite ramp rate, the value of storage saturates quickly as the capacity increases, regardless of volatility. To study the implications of the optimal policy, computational experiments are presented that suggest optimal utilization of storage can, in expectation, induce a considerable amount of price elasticity near the average price. Then, a computational framework is presented for characterization of the behavior of storage as a function of price and the state of charge, which illustrates a steep buy/sell phase transition in the price-state plane

Severe Fertility Effects of sheepish Sperm Caused by Failure To Enter Female Sperm Storage Organs in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Masatoshi Tomaru

2018-01-01

Full Text Available In Drosophila, mature sperm are transferred from males to females during copulation, stored in the sperm storage organs of females, and then utilized for fertilization. Here, we report a gene named sheepish (shps of Drosophila melanogaster that is essential for sperm storage in females. shps mutant males, although producing morphologically normal and motile sperm that are effectively transferred to females, produce very few offspring. Direct counts of sperm indicated that the primary defect was correlated to failure of shps sperm to migrate into the female sperm storage organs. Increased sperm motion parameters were seen in the control after transfer to females, whereas sperm from shps males have characteristics of the motion parameters different from the control. The few sperm that occasionally entered the female sperm storage organs showed no obvious defects in fertilization and early embryo development. The female postmating responses after copulation with shps males appeared normal, at least with respect to conformational changes of uterus, mating plug formation, and female remating rates. The shps gene encodes a protein with homology to amine oxidases, including as observed in mammals, with a transmembrane region at the C-terminal end. The shps mutation was characterized by a nonsense replacement in the third exon of CG13611, and shps was rescued by transformants of the wild-type copy of CG13611. Thus, shps may define a new class of gene responsible for sperm storage.

Sustainable Solutions for Nuclear used Fuels Interim Storage

International Nuclear Information System (INIS)

Arslan, Marc; Favet, Dominique; Issard, Herve; Le Jemtel, Amaury; Drevon, Caroline

2014-01-01

AREVA has a unique experience in providing sustainable solutions for used fuel management, fitted with the needs of different customers in the world and with regulation in different countries. These solutions entail both recycling and interim storage technologies. In a first part, we will describe the various types of solutions for Interim Storage of UNF that have been implemented around the world for interim storage at reactor or centralized Pad solution in canisters dry storage, vault type storages for dry storage, dry storage of transportation casks (dual purpose) pools for wet storage, The experience for all these different families of interim storages in which AREVA is involved is extensive and will be discussed with respect to the new challenges: increase of the duration of the interim storage (long term interim storage) increase of burn up of the fuels In a second part of the presentation, special recycling features will be presented. In that case, interim storage of the used fuels is ensured in pools. This provides in the long term good conditions for the behaviour of the fuel and its retrievability. With recycling, the final waste (Universal Canister of vitrified fission products and compacted hulls and end pieces): is stable and licensed in many countries for the final disposal (France, UK, Belgium, NL, Switzerland, Germany, Japan, upcoming: Spain, Australia, Italy). Presents neither safety criticality risks nor proliferation risks (AREVA conditioned HLW and LL-ILW are free of IAEA safeguard constraints thanks to AREVA process high recovery and purification yields). It can therefore be safely stored in interim storage for more than 100 years before final disposal. Some economic considerations will also be discussed. In particular, in the case of long term interim storage of used fuels, there are growing uncertainties regarding the future needs of repackaging and transportation, which can result in future cost overruns. Meanwhile, in the recycling policy

Coordinated movement of cytoplasmic and transmembrane domains of RyR1 upon gating.

Directory of Open Access Journals (Sweden)

Montserrat Samsó

2009-04-01

Full Text Available Ryanodine receptor type 1 (RyR1 produces spatially and temporally defined Ca2+ signals in several cell types. How signals received in the cytoplasmic domain are transmitted to the ion gate and how the channel gates are unknown. We used EGTA or neuroactive PCB 95 to stabilize the full closed or open states of RyR1. Single-channel measurements in the presence of FKBP12 indicate that PCB 95 inverts the thermodynamic stability of RyR1 and locks it in a long-lived open state whose unitary current is indistinguishable from the native open state. We analyzed two datasets of 15,625 and 18,527 frozen-hydrated RyR1-FKBP12 particles in the closed and open conformations, respectively, by cryo-electron microscopy. Their corresponding three-dimensional structures at 10.2 A resolution refine the structure surrounding the ion pathway previously identified in the closed conformation: two right-handed bundles emerging from the putative ion gate (the cytoplasmic "inner branches" and the transmembrane "inner helices". Furthermore, six of the identifiable transmembrane segments of RyR1 have similar organization to those of the mammalian Kv1.2 potassium channel. Upon gating, the distal cytoplasmic domains move towards the transmembrane domain while the central cytoplasmic domains move away from it, and also away from the 4-fold axis. Along the ion pathway, precise relocation of the inner helices and inner branches results in an approximately 4 A diameter increase of the ion gate. Whereas the inner helices of the K+ channels and of the RyR1 channel cross-correlate best with their corresponding open/closed states, the cytoplasmic inner branches, which are not observed in the K+ channels, appear to have at least as important a role as the inner helices for RyR1 gating. We propose a theoretical model whereby the inner helices, the inner branches, and the h1 densities together create an efficient novel gating mechanism for channel opening by relaxing two right

Activation of CD147 with Cyclophilin A Induces the Expression of IFITM1 through ERK and PI3K in THP-1 Cells

Directory of Open Access Journals (Sweden)

Ju-Young Kim

2010-01-01

Full Text Available CD147, as a receptor for Cyclophilins, is a multifunctional transmembrane glycoprotein. In order to identify genes that are induced by activation of CD147, THP-1 cells were stimulated with Cyclophilin A and differentially expressed genes were detected using PCR-based analysis. Interferon-induced transmembrane 1 (IFITM1 was detected to be induced and it was confirmed by RT-PCR and Western blot analysis. CD147-induced expression of IFITM1 was blocked by inhibitors of ERK, PI3K, or NF-κB, but not by inhibitors of p38, JNK, or PKC. IFITM1 appears to mediate inflammatory activation of THP-1 cells since cross-linking of IFITM1 with specific monoclonal antibody against it induced the expression of proinflammatory mediators such as IL-8 and MMP-9. These data indicate that IFITM1 is one of the pro-inflammatory mediators that are induced by signaling initiated by the activation of CD147 in macrophages and activation of ERK, PI3K, and NF-κB is required for the expression of IFITM1.

Rationalization of activity cliffs of a sulfonamide inhibitor of DNA methyltransferases with induced-fit docking.

Science.gov (United States)

Medina-Franco, José L; Méndez-Lucio, Oscar; Yoo, Jakyung

2014-02-21

Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure-activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of 'activity cliffs', e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

Rationalization of Activity Cliffs of a Sulfonamide Inhibitor of DNA Methyltransferases with Induced-Fit Docking

Directory of Open Access Journals (Sweden)

José L. Medina-Franco

2014-02-01

Full Text Available Inhibitors of human DNA methyltransferases (DNMT are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure–activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of ‘activity cliffs’, e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

Intact transmembrane isoforms of the neural cell adhesion molecule are released from the plasma membrane

DEFF Research Database (Denmark)

Olsen, M; Krog, L; Edvardsen, K

1993-01-01

. By density-gradient centrifugation it was shown that shed transmembrane NCAM-B was present in fractions of high, as well as low, density, indicating that a fraction of the shed NCAM is associated with minor plasma membrane fragments. Finally, it was shown that isolated soluble NCAM inhibited cell binding...

MAPK-dependent JA and SA signalling in Nicotiana attenuata affects plant growth and fitness during competition with conspecifics

Science.gov (United States)

2012-01-01

Background Induced defense responses to herbivores are generally believed to have evolved as cost-saving strategies that defer the fitness costs of defense metabolism until these defenses are needed. The fitness costs of jasmonate (JA)-mediated defenses have been well documented. Those of the early signaling units mediating induced resistance to herbivores have yet to be examined. Early signaling components that mediate herbivore-induced defense responses in Nicotiana attenuata, have been well characterized and here we examine their growth and fitness costs during competition with conspecifics. Two mitogen-activated protein kinases (MAPKs), salicylic acid (SA)-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK) are rapidly activated after perception of herbivory and both kinases regulate herbivory-induced JA levels and JA-mediated defense metabolite accumulations. Since JA-induced defenses result in resource-based trade-offs that compromise plant productivity, we evaluated if silencing SIPK (irSIPK) and WIPK (irWIPK) benefits the growth and fitness of plants competiting with wild type (WT) plants, as has been shown for plants silenced in JA-signaling by the reduction of Lipoxygenase 3 (LOX3) levels. Results As expected, irWIPK and LOX3-silenced plants out-performed their competing WT plants. Surprisingly, irSIPK plants, which have the largest reductions in JA signaling, did not. Phytohormone profiling of leaves revealed that irSIPK plants accumulated higher levels of SA compared to WT. To test the hypothesis that these high levels of SA, and their presumed associated fitness costs of pathogen associated defenses in irSIPK plants had nullified the JA-deficiency-mediated growth benefits in these plants, we genetically reduced SA levels in irSIPK plants. Reducing SA levels partially recovered the biomass and fitness deficits of irSIPK plants. We also evaluated whether the increased fitness of plants with reduced SA or JA levels resulted from

BRGLM, Interactive Linear Regression Analysis by Least Square Fit

International Nuclear Information System (INIS)

Ringland, J.T.; Bohrer, R.E.; Sherman, M.E.

1985-01-01

1 - Description of program or function: BRGLM is an interactive program written to fit general linear regression models by least squares and to provide a variety of statistical diagnostic information about the fit. Stepwise and all-subsets regression can be carried out also. There are facilities for interactive data management (e.g. setting missing value flags, data transformations) and tools for constructing design matrices for the more commonly-used models such as factorials, cubic Splines, and auto-regressions. 2 - Method of solution: The least squares computations are based on the orthogonal (QR) decomposition of the design matrix obtained using the modified Gram-Schmidt algorithm. 3 - Restrictions on the complexity of the problem: The current release of BRGLM allows maxima of 1000 observations, 99 variables, and 3000 words of main memory workspace. For a problem with N observations and P variables, the number of words of main memory storage required is MAX(N*(P+6), N*P+P*P+3*N, and 3*P*P+6*N). Any linear model may be fit although the in-memory workspace will have to be increased for larger problems

Microbial kinetic for In-Storage-Psychrophilic Anaerobic Digestion (ISPAD).

Science.gov (United States)

Madani-Hosseini, Mahsa; Mulligan, Catherine N; Barrington, Suzelle

2014-12-15

In-Storage-Psychrophilic-Anaerobic-Digestion (ISPAD) is a wastewater storage tank converted into an anaerobic digestion (AD) system by means of an airtight floating geo-membrane. For process optimization, ISPAD requires modelling with well-established microbial kinetics coefficients. The present objectives were to: obtain kinetics coefficients for the modelling of ISPAD; compare the prediction of the conventional and decomposition fitting approach, an innovative fitting technique used in other fields of science, and; obtain equations to predict the maximum growth rate (μmax) of microbial communities as a function of temperature. The method consisted in conducting specific Substrate Activity Tests (SAT) using ISPAD inoculum to monitor the rate of degradation of specific substrates at 8, 18 and 35 °C. Microbial kinetics coefficients were obtained by fitting the Monod equations to SAT. The statistical procedure of Least Square Error analysis was used to minimize the Sum of Squared Errors (SSE) between the measured ISPAD experimental data and the Monod equation values. Comparing both fitting methods, the decomposition approach gave higher correlation coefficient (R) for most kinetics values, as compared to the conventional approach. Tested to predict μmax with temperature, the Square Root equation better predicted temperature dependency of both acidogens and propionate degrading acetogens, while the Arrhenius equation better predicted that of methanogens and butyrate degrading acetogens. Increasing temperature from 18 to 35 °C did not affect butyrate degrading acetogens, likely because of their dominance, as demonstrated by microbial population estimation. The estimated ISPAD kinetics coefficients suggest a robust psychrophilic and mesophilic coexisting microbial community demonstrating acclimation to ambient temperature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Studies on storage stability of radurised Indian Mackerel (Rastrelliger Kanagurta)

International Nuclear Information System (INIS)

Ghadi, S.V.; Alur, M.D.; Venugopal, V.; Doke, S.N.; Ghosh, S.K.; Lewis, N.F.; Nadkarni, G.B.

1977-01-01

The present report describes the storage stability of mackerel maintained at various temperatures (0deg-20degC). The investigations include radiation-induced shifts in microflora of mackerel during storage, and time-temperature-tolerance (TTT) studies with the unirradiated and radurized mackerel. (author)

Simulations of Skin Barrier Function: Free Energies of Hydrophobic and Hydrophilic Transmembrane Pores in Ceramide Bilayers

NARCIS (Netherlands)

Notman, Rebecca; Anwar, Jamshed; Briels, Willem J.; Noro, Massimo G.; den Otter, Wouter K.

2008-01-01

Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO)

Effect of ionizing radiation on transmembrane potential of Streptococcus

International Nuclear Information System (INIS)

Fomenko, B.S.; Akoev, I.G.

1979-01-01

Treatment of Streptococcus faecalis with ionizing radiation at doses of 5 to 100 krad is shown to reduce the energy-dependent accumulation of dibenzyldimethylammonium (DDA + ) by the cell. Since transmembrane potential is the moving force of DDA + transport across the membrane, the decrease in DDA + accumulation is suggested to be due to potential reduction. This radiation effect was not due to inactivation of the potential-generating mechanism; thus, the ATPase activity and glycolytic activity of the irradiated cells were higher than in the control. At the same time, the membranes exhibited an increased permeability for K + and protons, which is probably due to structural rearrangements in the membranes after irradiation. It is suggested that the potential reduction results from the increase in proton permeability of membranes

Advanced Gas Storage Concepts: Technologies for the Future

Energy Technology Data Exchange (ETDEWEB)

Freeway, Katy (PB-KBB Inc.); Rogers, R.E. (Mississippi State University); DeVries, Kerry L.; Nieland, Joel D.; Ratigan, Joe L.; Mellegard, Kirby D. (RESPEC)

2000-02-01

This full text product includes: 1) A final technical report titled Advanced Underground Gas Storage Concepts, Refrigerated-Mined Cavern Storage and presentations from two technology transfer workshops held in 1998 in Houston, Texas, and Pittsburgh, Pennsylvania (both on the topic of Chilled Gas Storage in Mined Caverns); 2) A final technical report titled Natural Gas Hydrates Storage Project, Final Report 1 October 1997 - 31 May 1999; 3) A final technical report titled Natural Gas Hydrates Storage Project Phase II: Conceptual Design and Economic Study, Final Report 9 June - 10 October 1999; 4) A final technical report titled Commerical Potential of Natural Gas Storage in Lined Rock Caverns (LRC) and presentations from a DOE-sponsored workshop on Alternative Gas Storage Technologies, held Feb 17, 2000 in Pittsburgh, PA; and 5) Phase I and Phase II topical reports titled Feasibility Study for Lowering the Minimum Gas Pressure in Solution-Mined Caverns Based on Geomechanical Analyses of Creep-Induced Damage and Healing.

Health-related physical fitness in healthy untrained men

DEFF Research Database (Denmark)

Milanović, Zoran; Pantelić, Saša; Sporiš, Goran

2015-01-01

The purpose of this study was to determine the effects of recreational soccer (SOC) compared to moderate-intensity continuous running (RUN) on all health-related physical fitness components in healthy untrained men. Sixty-nine participants were recruited and randomly assigned to one of three groups...... weeks and consisted of three 60-min sessions per week. All participants were tested for each of the following physical fitness components: maximal aerobic power, minute ventilation, maximal heart rate, squat jump (SJ), countermovement jump with arm swing (CMJ), sit-and-reach flexibility, and body...... improvements in maximal aerobic power after 12 weeks of soccer training and moderate-intensity running, partly due to large decreases in body mass. Additionally soccer training induced pronounced positive effects on jump performance and flexibility, making soccer an effective broad-spectrum fitness training...

Side-chain liquid crystalline polyesters for optical information storage

DEFF Research Database (Denmark)

Ramanujam, P.S.; Holme, Christian; Hvilsted, Søren

1996-01-01

and holographic storage in one particular polyester are described in detail and polarized Fourier transform infrared spectroscopic data complementing the optical data are presented. Optical and atomic force microscope investigations point to a laser-induced aggregation as responsible for permanent optical storage.......Azobenzene side-chain liquid crystalline polyester structures suitable for permanent optical storage are described. The synthesis and characterization of the polyesters together with differential scanning calorimetry and X-ray investigations are discussed. Optical anisotropic investigations...

INEEL special case waste storage and disposal alternatives

International Nuclear Information System (INIS)

Larson, L.A.; Bishop, C.W.; Bhatt, R.N.

1997-07-01

Special case waste is historically defined as radioactive waste that does not have a path forward or fit into current Department of Energy management plans for final treatment or disposal. The objectives of this report, relative to special case waste at the Idaho National Engineering and Environmental Laboratory, are to (a) identify its current storage locations, conditions, and configuration; (b) review and verify the currently reported inventory; (c) segregate the inventory into manageable categories; (d) identify the portion that has a path forward or is managed under other major programs/projects; (e) identify options for reconfiguring and separating the disposable portions; (f) determine if the special case waste needs to be consolidated into a single storage location; and (g) identify a preferred facility for storage. This report also provides an inventory of stored sealed sources that are potentially greater than Class C or special case waste based on Nuclear Regulatory Commission and Site-Specific Waste Acceptance Criteria

The electrochemistry and modelling of hydrogen storage materials

International Nuclear Information System (INIS)

Kalisvaart, W.P.; Vermeulen, P.; Ledovskikh, A.V.; Danilov, D.; Notten, P.H.L.

2007-01-01

Mg-based alloys are promising hydrogen storage materials because of the high gravimetric energy density of MgH 2 (7.6 wt.%). A major disadvantage, however, is its very slow desorption kinetics. It has been argued that, in contrast to the well-known rutile-structured Mg hydride, hydrided Mg-transition metal alloys have a much more open crystal structure facilitating faster hydrogen transport. In this paper, the electrochemical aspects of new Mg-Sc and Mg-Ti materials will be reviewed. Storage capacities as high as 6.5 wt.% hydrogen have been reached with very favourable discharge kinetics. A theoretical description of hydrogen storage materials has also been developed by our group. A new lattice gas model is presented and successfully applied to simulate the thermodynamic properties of various hydride-forming materials. The simulation results are expressed by parameters corresponding to several energy contributions, for example mutual atomic hydrogen interaction energies. A good fit of the lattice gas model to the experimental data is found in all cases

Development and design of a late-model fitness test instrument based on LabView

Science.gov (United States)

Xie, Ying; Wu, Feiqing

2010-12-01

Undergraduates are pioneers of China's modernization program and undertake the historic mission of rejuvenating our nation in the 21st century, whose physical fitness is vital. A smart fitness test system can well help them understand their fitness and health conditions, thus they can choose more suitable approaches and make practical plans for exercising according to their own situation. following the future trends, a Late-model fitness test Instrument based on LabView has been designed to remedy defects of today's instruments. The system hardware consists of fives types of sensors with their peripheral circuits, an acquisition card of NI USB-6251 and a computer, while the system software, on the basis of LabView, includes modules of user register, data acquisition, data process and display, and data storage. The system, featured by modularization and an open structure, is able to be revised according to actual needs. Tests results have verified the system's stability and reliability.

Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

Directory of Open Access Journals (Sweden)

Heidi O Nousiainen

Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

Energy Technology Data Exchange (ETDEWEB)

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))

1991-06-01

We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

Phase change materials in non-volatile storage

OpenAIRE

Ielmini, Daniele; Lacaita, Andrea L.

2011-01-01

After revolutionizing the technology of optical data storage, phase change materials are being adopted in non-volatile semiconductor memories. Their success in electronic storage is mostly due to the unique properties of the amorphous state where carrier transport phenomena and thermally-induced phase change cooperate to enable high-speed, low-voltage operation and stable data retention possible within the same material. This paper reviews the key physical properties that make this phase so s...

Performance of spectral fitting methods for vegetation fluorescence quantification

NARCIS (Netherlands)

Meroni, M.; Busetto, D.; Colombo, R.; Guanter, L.; Moreno, J.; Verhoef, W.

2010-01-01

The Fraunhofer Line Discriminator (FLD) principle has long been considered as the reference method to quantify solar-induced chlorophyll fluorescence (F) from passive remote sensing measurements. Recently, alternative retrieval algorithms based on the spectral fitting of hyperspectral radiance

Nonpolar interactions between trans-membrane helical EGF peptide and phosphatidylcholines, sphingomyelins and cholesterol. Molecular dynamics simulation studies

NARCIS (Netherlands)

Róg, T.; Murzyn, K.; Karttunen, M.E.J.; Pasenkiewicz-Gierula, M.

2008-01-01

A molecular dynamics simulation study of four lipid bilayers with inserted trans-membrane helical fragment of epithelial growth factor (EGF) receptor (EGF peptide) was performed. The lipid bilayers differ in their lipid composition and consist of (i) unsaturated phosphatidylcholine

Combined effect of cortical cytoskeleton and transmembrane proteins on domain formation in biomembranes

Science.gov (United States)

Sikder, Md. Kabir Uddin; Stone, Kyle A.; Kumar, P. B. Sunil; Laradji, Mohamed

2014-01-01

We investigate the combined effects of transmembrane proteins and the subjacent cytoskeleton on the dynamics of phase separation in multicomponent lipid bilayers using computer simulations of a particle-based implicit solvent model for lipid membranes with soft-core interactions. We find that microphase separation can be achieved by the protein confinement by the cytoskeleton. Our results have relevance to the finite size of lipid rafts in the plasma membrane of mammalian cells. PMID:25106608

A study on the performance valuation of small size water storage electric boiler

International Nuclear Information System (INIS)

Mo, Joung Gun; Shin, Jae Ho; Bae, Chul Whan; Suh, Jeong Se; Chung, Han Shik; Jeong, Hyo Min

2003-01-01

We was made 150L a water storage electric boiler and obtained various performances of the storage, radiant and keeping by experimentation. The storage performance is that the heat were off about 50 minutes after heating start. Then the temperature of outlet was arrived the stead state at 91 deg. C and the storage performance was appeared 93.64%. In the radiant performance, the water temperature was decreased from 90 .deg. C to 44.8 deg. C after 960 minutes. Then the calorific value changed from 675kcal/h to 72kcal/h and the temperature decreased about 50%. The keeping performance showed mean temperature, 67.06 .deg. C according to progress 800 minutes and the maximum temperature drop were 0.2 .deg. C. By the results of the performance valuation, the water storage electric boiler was verified fitted quality on the test prescription of KERI (Korea Electrotechnology Research Institute.)

Fitting PAC spectra with stochastic models: PolyPacFit

Energy Technology Data Exchange (ETDEWEB)

Zacate, M. O., E-mail: zacatem1@nku.edu [Northern Kentucky University, Department of Physics and Geology (United States); Evenson, W. E. [Utah Valley University, College of Science and Health (United States); Newhouse, R.; Collins, G. S. [Washington State University, Department of Physics and Astronomy (United States)

2010-04-15

PolyPacFit is an advanced fitting program for time-differential perturbed angular correlation (PAC) spectroscopy. It incorporates stochastic models and provides robust options for customization of fits. Notable features of the program include platform independence and support for (1) fits to stochastic models of hyperfine interactions, (2) user-defined constraints among model parameters, (3) fits to multiple spectra simultaneously, and (4) any spin nuclear probe.

Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells.

Science.gov (United States)

Huygens, Caroline; Liénart, Stéphanie; Dedobbeleer, Olivier; Stockis, Julie; Gauthy, Emilie; Coulie, Pierre G; Lucas, Sophie

2015-08-14

Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

Science.gov (United States)

Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

2016-10-03

FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

AXAF FITS standard for ray trace interchange

Science.gov (United States)

Hsieh, Paul F.

1993-07-01

A standard data format for the archival and transport of x-ray events generated by ray trace models is described. Upon review and acceptance by the Advanced X-ray Astrophysics Facility (AXAF) Software Systems Working Group (SSWG), this standard shall become the official AXAF data format for ray trace events. The Flexible Image Transport System (FITS) is well suited for the purposes of the standard and was selected to be the basis of the standard. FITS is both flexible and efficient and is also widely used within the astronomical community for storage and transfer of data. In addition, software to read and write FITS format files are widely available. In selecting quantities to be included within the ray trace standard, the AXAF Mission Support team, Science Instruments team, and the other contractor teams were surveyed. From the results of this survey, the following requirements were established: (1) for the scientific needs, each photon should have associated with it: position, direction, energy, and statistical weight; the standard must also accommodate path length (relative phase), and polarization. (2) a unique photon identifier is necessary for bookkeeping purposes; (3) a log of individuals, organizations, and software packages that have modified the data must be maintained in order to create an audit trail; (4) a mechanism for extensions to the basic kernel should be provided; and (5) the ray trace standard should integrate with future AXAF data product standards.

Biomethane storage: Evaluation of technologies, end uses, business models, and sustainability

International Nuclear Information System (INIS)

Budzianowski, Wojciech M.; Brodacka, Marlena

2017-01-01

Highlights: • Biomethane storage integrates the different energy subsystems. • It facilitates adoption of solar and wind energy sources. • It is essential to adequately match storages with their end uses and business models. • Business models must propose, create, and capture value linked with gas storage. • Sustainable is economically viable, environmentally benign, and socially beneficial. - Abstract: Biomethane is a renewable gas that can be turned into dispatchable resource through applying storage techniques. The storage enables the discharge of stored biomethane at any time and place it is required as gas turbine power, heat or transport fuel. Thus the stored biomethane could more efficiently serve various energy applications in the power, transport, heat, and gas systems as well as in industry. Biomethane storage may therefore integrate the different energy subsystems making the whole energy system more efficient. This work provides an overview and evaluation of biomethane storage technologies, end uses, business models and sustainability. It is shown that storage technologies are versatile, have different costs and efficiencies and may serve different end uses. Business models may be created or selected to fit regional spatial contexts, realistic demands for gas storage related services, and the level of available subsidies. By applying storage the sustainability of biomethane is greatly improved in terms of economic viability, reduced environmental impacts and greater social benefits. Stored biomethane may greatly facilitate adoption of intermittent renewable energy sources such as solar and wind. Other findings show that biomethane storage needs to be combined with grid services and other similar services to reduce overall storage costs.

A signaling pathway contributing to platelet storage lesion development: targeting PI3-kinase–dependent Rap1 activation slows storage-induced platelet deterioration

Science.gov (United States)

Schubert, Peter; Thon, Jonathan N.; Walsh, Geraldine M.; Chen, Cindy H.I.; Moore, Edwin D.; Devine, Dana V.; Kast, Juergen

2015-01-01

BACKGROUND The term platelet storage lesion (PSL) describes the structural and biochemical changes in platelets (PLTs) during storage. These are typified by alterations of morphologic features and PLT metabolism leading to reduced functionality and hence reduced viability for transfusion. While the manifestations of the storage lesion are well characterized, the biochemical pathways involved in the initiation of this process are unknown. STUDY DESIGN AND METHODS A complementary proteomic approach has recently been applied to analyze changes in the PLT proteome during storage. By employing stringent proteomic criteria, 12 proteins were identified as significantly and consistently changing in relative concentration over a 7-day storage period. Microscopy, Western blot analysis, flow cytometry, and PLT functionality analyses were used to unravel the involvement of a subset of these 12 proteins, which are connected through integrin signaling in one potential signaling pathway underlying storage lesion development. RESULTS Microscopic analysis revealed changes in localization of glycoprotein IIIa, Rap1, and talin during storage. Rap1 activation was observed to correlate with expression of the PLT activation marker CD62P. PLTs incubated for 7 days with the PI3-kinase inhibitor LY294002 showed diminished Rap1 activation as well as a moderate reduction in integrin αIIbβ3 activation and release of α-granules. Furthermore, this inhibitor seemed to improve PLT integrity and quality during storage as several in vitro probes showed a deceleration of PLT activation. CONCLUSION These results provide the first evidence for a signaling pathway mediating PSL in which PI3-kinase–dependent Rap1 activation leads to integrin αIIbβ3 activation and PLT degranulation. PMID:19497060

DPM — efficient storage in diverse environments

International Nuclear Information System (INIS)

Hellmich, Martin; Furano, Fabrizio; Smith, David; Rocha, Ricardo Brito da; Ayllón, Alejandro Álvarez; Manzi, Andrea; Keeble, Oliver; Calvet, Ivan; Regala, Miguel Antonio

2014-01-01

Recent developments, including low power devices, cluster file systems and cloud storage, represent an explosion in the possibilities for deploying and managing grid storage. In this paper we present how different technologies can be leveraged to build a storage service with differing cost, power, performance, scalability and reliability profiles, using the popular storage solution Disk Pool Manager (DPM/dmlite) as the enabling technology. The storage manager DPM is designed for these new environments, allowing users to scale up and down as they need it, and optimizing their computing centers energy efficiency and costs. DPM runs on high-performance machines, profiting from multi-core and multi-CPU setups. It supports separating the database from the metadata server, the head node, largely reducing its hard disk requirements. Since version 1.8.6, DPM is released in EPEL and Fedora, simplifying distribution and maintenance, but also supporting the ARM architecture beside i386 and x86 6 4, allowing it to run the smallest low-power machines such as the Raspberry Pi or the CuBox. This usage is facilitated by the possibility to scale horizontally using a main database and a distributed memcached-powered namespace cache. Additionally, DPM supports a variety of storage pools in the backend, most importantly HDFS, S3-enabled storage, and cluster file systems, allowing users to fit their DPM installation exactly to their needs. In this paper, we investigate the power-efficiency and total cost of ownership of various DPM configurations. We develop metrics to evaluate the expected performance of a setup both in terms of namespace and disk access considering the overall cost including equipment, power consumptions, or data/storage fees. The setups tested range from the lowest scale using Raspberry Pis with only 700 MHz single cores and a 100 Mbps network connections, over conventional multi-core servers to typical virtual machine instances in cloud settings. We evaluate the

A method for simultaneous linear optics and coupling correction for storage rings with turn-by-turn beam position monitor data

Energy Technology Data Exchange (ETDEWEB)

Yang, Xi [Brookhaven National Laboratory, Upton, Long Island, NY 11973 (United States); Huang, Xiaobiao, E-mail: xiahuang@slac.stanford.edu [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States)

2016-08-21

We propose a method to simultaneously correct linear optics errors and linear coupling for storage rings using turn-by-turn (TbT) beam position monitor (BPM) data. The independent component analysis (ICA) method is used to isolate the betatron normal modes from the measured TbT BPM data. The betatron amplitudes and phase advances of the projections of the normal modes on the horizontal and vertical planes are then extracted, which, combined with dispersion measurement, are used to fit the lattice model. The fitting results are used for lattice correction. The method has been successfully demonstrated on the NSLS-II storage ring.

A method for simultaneous linear optics and coupling correction for storage rings with turn-by-turn beam position monitor data

Energy Technology Data Exchange (ETDEWEB)

Yang, Xi [Brookhaven National Lab. (BNL), Upton, NY (United States); Huang, Xiaobiao [SLAC National Accelerator Lab., Menlo Park, CA (United States)

2016-08-01

We propose a method to simultaneously correct linear optics errors and linear coupling for storage rings using turn-by-turn (TbT) beam position monitor (BPM) data. The independent component analysis (ICA) method is used to isolate the betatron normal modes from the measured TbT BPM data. The betatron amplitudes and phase advances of the projections of the normal modes on the horizontal and vertical planes are then extracted, which, combined with dispersion measurement, are used to fit the lattice model. Furthermore, the fitting results are used for lattice correction. Our method has been successfully demonstrated on the NSLS-II storage ring.

Dynamic sizing of energy storage for hedging wind power forecast uncertainty

DEFF Research Database (Denmark)

Pinson, Pierre; Papefthymiou, George; Klöckl, Bernd

2009-01-01

In market conditions where program responsible parties are penalized for deviations from proposed bids, energy storage can be used for compensating the energy imbalances induced by limited predictability of wind power. The energy storage capacity necessary for performing this task will differ bet...

Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore.

Science.gov (United States)

El Hiani, Yassine; Linsdell, Paul

2015-06-19

As an ion channel, the cystic fibrosis transmembrane conductance regulator must form a continuous pathway for the movement of Cl(-) and other anions between the cytoplasm and the extracellular solution. Both the structure and the function of the membrane-spanning part of this pathway are well defined. In contrast, the structure of the pathway that connects the cytoplasm to the membrane-spanning regions is unknown, and functional roles for different parts of the protein forming this pathway have not been described. We used patch clamp recording and substituted cysteine accessibility mutagenesis to identify positively charged amino acid side chains that attract cytoplasmic Cl(-) ions to the inner mouth of the pore. Our results indicate that the side chains of Lys-190, Arg-248, Arg-303, Lys-370, Lys-1041, and Arg-1048, located in different intracellular loops of the protein, play important roles in the electrostatic attraction of Cl(-) ions. Mutation and covalent modification of these residues have charge-dependent effects on the rate of Cl(-) permeation, demonstrating their functional role in maximization of Cl(-) flux. Other nearby positively charged side chains were not involved in electrostatic interactions with Cl(-). The location of these Cl(-)-attractive residues suggests that cytoplasmic Cl(-) ions enter the pore via a lateral portal located between the cytoplasmic extensions to the fourth and sixth transmembrane helices; a secondary, functionally less relevant portal might exist between the extensions to the 10th and 12th transmembrane helices. These results define the cytoplasmic mouth of the pore and show how it attracts Cl(-) ions from the cytoplasm. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Inverse Problem for 3D coupled Flow-Geomechanics Models and Induced Seismicity: Application to Subsurface Characterization and Seismicity Forecasting in Geologic CO2 Storage

Science.gov (United States)

Castineira, D.; Jha, B.; Juanes, R.

2016-12-01

Carbon Capture and Sequestration (CCS) is regarded as a promising technology to mitigate rising CO2 concentrations in the atmosphere from industrial emissions. However, as a result of the inherent uncertainty that is present in geological structures, assessing the stability of geological faults and quantifying the potential for induced seismicity is a fundamental challenge for practical implementation of CCS. Here we present a formal framework for the solution of the inverse problem associated with coupled flow and geomechanics models of CO2 injection and subsurface storage. Our approach builds from the application of Gaussian Processes, MCMC and posterior predictive analysis to evaluate relevant earthquake attributes (earthquake time, location and magnitude) in 3D synthetic models of CO2 storage under geologic, observational and operational uncertainty. In our approach, we first conduct hundreds of simulations of a high-fidelity 3D computational model for CO2 injection into a deep saline aquifer, dominated by an anticline structure and a fault. This ensemble of realizations accounts for uncertainty in the model parameters (including fault geomechanical and rock properties) and observations (earthquake time, location and magnitude). We apply Gaussian processes (GP) to generate a valid surrogate that closely approximates the behavior of the high fidelity (and computationally intensive) model, and apply hyperparameter optimization and cross-validation techniques in the solution of this multidimensional data-fit problem. The net result of this process is the generation of a fast model that can be effectively used for Bayesian analysis. We then implement Markov chain Monte Carlo (MCMC) to determine the posterior distribution of the model uncertain parameters (given some prior distributions for those parameters and given the likelihood defined in this case by the GP model). Our results show that the resulting posterior distributions correctly converge towards the "true

Fitness club

CERN Multimedia

Fitness club

2011-01-01

General fitness Classes Enrolments are open for general fitness classes at CERN taking place on Monday, Wednesday, and Friday lunchtimes in the Pump Hall (building 216). There are shower facilities for both men and women. It is possible to pay for 1, 2 or 3 classes per week for a minimum of 1 month and up to 6 months. Check out our rates and enrol at: http://cern.ch/club-fitness Hope to see you among us! CERN Fitness Club fitness.club@cern.ch  

Residual stresses and stress corrosion cracking in pipe fittings

International Nuclear Information System (INIS)

Parrington, R.J.; Scott, J.J.; Torres, F.

1994-06-01

Residual stresses can play a key role in the SCC performance of susceptible materials in PWR primary water applications. Residual stresses are stresses stored within the metal that develop during deformation and persist in the absence of external forces or temperature gradients. Sources of residual stresses in pipe fittings include fabrication processes, installation and welding. There are a number of methods to characterize the magnitude and orientation of residual stresses. These include numerical analysis, chemical cracking tests, and measurement (e.g., X-ray diffraction, neutron diffraction, strain gage/hole drilling, strain gage/trepanning, strain gage/section and layer removal, and acoustics). This paper presents 400 C steam SCC test results demonstrating that residual stresses in as-fabricated Alloy 600 pipe fittings are sufficient to induce SCC. Residual stresses present in as-fabricated pipe fittings are characterized by chemical cracking tests (stainless steel fittings tested in boiling magnesium chloride solution) and by the sectioning and layer removal (SLR) technique

The Single Transmembrane Segment of Minimal Sensor DesK Senses Temperature via a Membrane-Thickness Caliper.

Science.gov (United States)

Inda, Maria E; Oliveira, Rafael G; de Mendoza, Diego; Cybulski, Larisa E

2016-11-01

Thermosensors detect temperature changes and trigger cellular responses crucial for survival at different temperatures. The thermosensor DesK is a transmembrane (TM) histidine kinase which detects a decrease in temperature through its TM segments (TMS). Here, we address a key issue: how a physical stimulus such as temperature can be converted into a cellular response. We show that the thickness of Bacillus lipid membranes varies with temperature and that such variations can be detected by DesK with great precision. On the basis of genetic studies and measurements of in vitro activity of a DesK construct with a single TMS (minimal sensor DesK [MS-DesK]), reconstituted in liposomes, we propose an interplay mechanism directed by a conserved dyad, phenylalanine 8-lysine 10. This dyad is critical to anchor the only transmembrane segment of the MS-DesK construct to the extracellular water-lipid interphase and is required for the transmembrane segment of MS-DesK to function as a caliper for precise measurement of membrane thickness. The data suggest that positively charged lysine 10, which is located in the hydrophobic core of the membrane but is close to the water-lipid interface, pulls the transmembrane region toward the water phase to localize its charge at the interface. Nevertheless, the hydrophobic residue phenylalanine 8, located at the N-terminal extreme of the TMS, has a strong tendency to remain in the lipid phase, impairing access of lysine 10 to the water phase. The outcome of this interplay is a fine-tuned sensitivity to membrane thickness that elicits conformational changes that favor different signaling states of the protein. The ability to sense and respond to extracellular signals is essential for cell survival. One example is the cellular response to temperature variation. How do cells "sense" temperature changes? It has been proposed that the bacterial thermosensor DesK acts as a molecular caliper measuring membrane thickness variations that would occur

Integrating experimental and numerical methods for a scenario-based quantitative assessment of subsurface energy storage options

Science.gov (United States)

Kabuth, Alina; Dahmke, Andreas; Hagrey, Said Attia al; Berta, Márton; Dörr, Cordula; Koproch, Nicolas; Köber, Ralf; Köhn, Daniel; Nolde, Michael; Tilmann Pfeiffer, Wolf; Popp, Steffi; Schwanebeck, Malte; Bauer, Sebastian

2016-04-01

Within the framework of the transition to renewable energy sources ("Energiewende"), the German government defined the target of producing 60 % of the final energy consumption from renewable energy sources by the year 2050. However, renewable energies are subject to natural fluctuations. Energy storage can help to buffer the resulting time shifts between production and demand. Subsurface geological structures provide large potential capacities for energy stored in the form of heat or gas on daily to seasonal time scales. In order to explore this potential sustainably, the possible induced effects of energy storage operations have to be quantified for both specified normal operation and events of failure. The ANGUS+ project therefore integrates experimental laboratory studies with numerical approaches to assess subsurface energy storage scenarios and monitoring methods. Subsurface storage options for gas, i.e. hydrogen, synthetic methane and compressed air in salt caverns or porous structures, as well as subsurface heat storage are investigated with respect to site prerequisites, storage dimensions, induced effects, monitoring methods and integration into spatial planning schemes. The conceptual interdisciplinary approach of the ANGUS+ project towards the integration of subsurface energy storage into a sustainable subsurface planning scheme is presented here, and this approach is then demonstrated using the examples of two selected energy storage options: Firstly, the option of seasonal heat storage in a shallow aquifer is presented. Coupled thermal and hydraulic processes induced by periodic heat injection and extraction were simulated in the open-source numerical modelling package OpenGeoSys. Situations of specified normal operation as well as cases of failure in operational storage with leaking heat transfer fluid are considered. Bench-scale experiments provided parameterisations of temperature dependent changes in shallow groundwater hydrogeochemistry. As a

Influence of magnesium sulfate on HCO3/Cl transmembrane exchange rate in human erythrocytes.

Science.gov (United States)

Chernyshova, Ekaterina S; Zaikina, Yulia S; Tsvetovskaya, Galina A; Strokotov, Dmitry I; Yurkin, Maxim A; Serebrennikova, Elena S; Volkov, Leonid; Maltsev, Valeri P; Chernyshev, Andrei V

2016-03-21

Magnesium sulfate (MgSO4) is widely used in medicine but molecular mechanisms of its protection through influence on erythrocytes are not fully understood and are considerably controversial. Using scanning flow cytometry, in this work for the first time we observed experimentally (both in situ and in vitro) a significant increase of HCO3(-)/Cl(-) transmembrane exchange rate of human erythrocytes in the presence of MgSO4 in blood. For a quantitative analysis of the obtained experimental data, we introduced and verified a molecular kinetic model, which describes activation of major anion exchanger Band 3 (or AE1) by its complexation with free intracellular Mg(2+) (taking into account Mg(2+) membrane transport and intracellular buffering). Fitting the model to our in vitro experimental data, we observed a good correspondence between theoretical and experimental kinetic curves that allowed us to evaluate the model parameters and to estimate for the first time the association constant of Mg(2+) with Band 3 as KB~0.07mM, which is in agreement with known values of the apparent Mg(2+) dissociation constant (from 0.01 to 0.1mM) that reflects experiments on enrichment of Mg(2+) at the inner erythrocyte membrane (Gunther, 2007). Results of this work partly clarify the molecular mechanisms of MgSO4 action in human erythrocytes. The method developed allows one to estimate quantitatively a perspective of MgSO4 treatment for a patient. It should be particularly helpful in prenatal medicine for early detection of pathologies associated with the risk of fetal hypoxia. Copyright © 2016 Elsevier Ltd. All rights reserved.

A portable lipid bilayer system for environmental sensing with a transmembrane protein.

Directory of Open Access Journals (Sweden)

Ryuji Kawano

Full Text Available This paper describes a portable measurement system for current signals of an ion channel that is composed of a planar lipid bilayer. A stable and reproducible lipid bilayer is formed in outdoor environments by using a droplet contact method with a micropipette. Using this system, we demonstrated that the single-channel recording of a transmembrane protein (alpha-hemolysin was achieved in the field at a high-altitude (∼3623 m. This system would be broadly applicable for obtaining environmental measurements using membrane proteins as a highly sensitive sensor.

Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

DEFF Research Database (Denmark)

Rosenkilde, M M; Smit, M J; Waldhoer, M

2008-01-01

A number of human and animal herpes viruses encode G-protein coupled receptors with seven transmembrane (7TM) segments-most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for immune evasion, cellular transformation, tissue targeting...... pathogenesis is still poorly understood. Here we focus on the current knowledge of structure, function and trafficking patterns of virally encoded chemokine receptors and further address the putative roles of these receptors in virus survival and host -cell and/or -immune system modulation. Finally, we...

The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor

Directory of Open Access Journals (Sweden)

Buchmeier Michael J

2001-02-01

Full Text Available Abstract Background Recent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (HIV-1, and Ebola virus have shown, first with molecular modeling, and then X-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein. Results Structural models of the transmembrane glycoproteins (GP-2 of the Arenaviruses, lymphochoriomeningitis virus (LCMV and Lassa fever virus, are presented, based on consistent structural propensities despite variation in the amino acid sequence. The principal features of the model, a hydrophobic amino terminus, and two antiparallel helices separated by a glycosylated, antigenic apex, are common to a number of otherwise disparate families of enveloped RNA viruses. Within the first amphipathic helix, demonstrable by circular dichroism of a peptide fragment, there is a highly conserved heptad repeat pattern proposed to mediate multimerization by coiled-coil interactions. The amino terminal 18 amino acids are 28% identical and 50% highly similar to the corresponding region of Ebola, a member of the Filovirus family. Within the second, charged helix just prior to membrane insertion there is also high similarity over the central 18 amino acids in corresponding regions of Lassa and Ebola, which may be further related to the similar region of HIV-1 defining a potent antiviral peptide analogue. Conclusions These findings indicate a common pattern of structure and function among viral transmembrane fusion proteins from a number of virus families. Such a pattern may define a viral transmembrane superfamily that evolved from a common precursor eons ago.

Pressure bump instability in very large cold bore storage rings

International Nuclear Information System (INIS)

Limon, P.

1983-12-01

Calculations have been done to estimate the circulating current necessary to induce the onset of a pressure bump instability in a cold bore storage ring. For a wide range of storage ring parameters, the instability threshold current is more than an order of magnitude higher than the operating current. 4 references, 2 tables

The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses.

Directory of Open Access Journals (Sweden)

Eliran Moshe Reuven

2014-08-01

Full Text Available HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD of the HIV-1 envelope (ENV directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.

Nanoporous microbead supported bilayers: stability, physical characterization, and incorporation of functional transmembrane proteins.

Energy Technology Data Exchange (ETDEWEB)

Davis, Ryan W. (University of New Mexico, Albuquerque, NM); Brozik, James A. (University of New Mexico, Albuquerque, NM); Brozik, Susan Marie; Cox, Jason M. (University of New Mexico, Albuquerque, NM); Lopez, Gabriel P. (University of New Mexico, Albuquerque, NM); Barrick, Todd A. (University of New Mexico, Albuquerque, NM); Flores, Adrean (University of New Mexico, Albuquerque, NM)

2007-03-01

The introduction of functional transmembrane proteins into supported bilayer-based biomimetic systems presents a significant challenge for biophysics. Among the various methods for producing supported bilayers, liposomal fusion offers a versatile method for the introduction of membrane proteins into supported bilayers on a variety of substrates. In this study, the properties of protein containing unilamellar phosphocholine lipid bilayers on nanoporous silica microspheres are investigated. The effects of the silica substrate, pore structure, and the substrate curvature on the stability of the membrane and the functionality of the membrane protein are determined. Supported bilayers on porous silica microspheres show a significant increase in surface area on surfaces with structures in excess of 10 nm as well as an overall decrease in stability resulting from increasing pore size and curvature. Comparison of the liposomal and detergent-mediated introduction of purified bacteriorhodopsin (bR) and the human type 3 serotonin receptor (5HT3R) are investigated focusing on the resulting protein function, diffusion, orientation, and incorporation efficiency. In both cases, functional proteins are observed; however, the reconstitution efficiency and orientation selectivity are significantly enhanced through detergent-mediated protein reconstitution. The results of these experiments provide a basis for bulk ionic and fluorescent dye-based compartmentalization assays as well as single-molecule optical and single-channel electrochemical interrogation of transmembrane proteins in a biomimetic platform.

Soil moisture storage and hillslope stability

NARCIS (Netherlands)

Talebi, A.; Uijlenhoet, R.; Troch, P.A.

2007-01-01

Recently, we presented a steady-state analytical hillslope stability model to study rain-induced shallow landslides. This model is based on kinematic wave dynamics of saturated subsurface storage and the infinite slope stability assumption. Here we apply the model to investigate the effect of

Transmembrane Domain Single-Nucleotide Polymorphisms Impair Expression and Transport Activity of ABC Transporter ABCG2

NARCIS (Netherlands)

Sjostedt, N.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Kidron, H.

2017-01-01

PURPOSE: To study the function and expression of nine naturally occurring single-nucleotide polymorphisms (G406R, F431L, S441N, P480L, F489L, M515R, L525R, A528T and T542A) that are predicted to reside in the transmembrane regions of the ABC transporter ABCG2. METHODS: The transport activity of the

Role of reactive oxygen species and Bcl-2 family proteins in TNF-α-induced apoptosis of lymphocytes.

Science.gov (United States)

Ryazanceva, N V; Novickiy, V V; Zhukova, O B; Biktasova, A K; Chechina, O E; Sazonova, E V; Belkina, M V; Chasovskih, N Yu; Khaitova, Z K

2010-08-01

We studied the in vitro apoptosis-inducing effect of recombinant TNF-α (rTNF-α) on blood lymphocytes from healthy donors. rTNF-α-induced apoptosis was accompanied by an increase in the number of cells with low mitochondrial transmembrane potential, increased intracellular content of reactive oxygen species, reduced content of Bcl-2, Bcl-xL, and Bax proteins, and elevated Bad content. The molecular mechanisms of these changes are discussed.

Mass-storage management for distributed image/video archives

Science.gov (United States)

Franchi, Santina; Guarda, Roberto; Prampolini, Franco

1993-04-01

The realization of image/video database requires a specific design for both database structures and mass storage management. This issue has addressed the project of the digital image/video database system that has been designed at IBM SEMEA Scientific & Technical Solution Center. Proper database structures have been defined to catalog image/video coding technique with the related parameters, and the description of image/video contents. User workstations and servers are distributed along a local area network. Image/video files are not managed directly by the DBMS server. Because of their wide size, they are stored outside the database on network devices. The database contains the pointers to the image/video files and the description of the storage devices. The system can use different kinds of storage media, organized in a hierarchical structure. Three levels of functions are available to manage the storage resources. The functions of the lower level provide media management. They allow it to catalog devices and to modify device status and device network location. The medium level manages image/video files on a physical basis. It manages file migration between high capacity media and low access time media. The functions of the upper level work on image/video file on a logical basis, as they archive, move and copy image/video data selected by user defined queries. These functions are used to support the implementation of a storage management strategy. The database information about characteristics of both storage devices and coding techniques are used by the third level functions to fit delivery/visualization requirements and to reduce archiving costs.

Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development

Directory of Open Access Journals (Sweden)

Lerman Michael I

2009-03-01

Full Text Available Abstract Background Transmembrane CAIX and CAXII are members of the alpha carbonic anhydrase (CA family. They play a crucial role in differentiation, proliferation, and pH regulation. Expression of CAIX and CAXII proteins in tumor tissues is primarily induced by hypoxia and this is particularly true for CAIX, which is regulated by the transcription factor, hypoxia inducible factor-1 (HIF-1. Their distributions in normal adult human tissues are restricted to highly specialized cells that are not always hypoxic. The human fetus exists in a relatively hypoxic environment. We examined expression of CAIX, CAXII and HIF-1α in the developing human fetus and postnatal tissues to determine whether expression of CAIX and CAXII is exclusively regulated by HIF-1. Results The co-localization of CAIX and HIF-1α was limited to certain cell types in embryonic and early fetal tissues. Those cells comprised the primitive mesenchyma or involved chondrogenesis and skin development. Transient CAIX expression was limited to immature tissues of mesodermal origin and the skin and ependymal cells. The only tissues that persistently expressed CAIX protein were coelomic epithelium (mesothelium and its remnants, the epithelium of the stomach and biliary tree, glands and crypt cells of duodenum and small intestine, and the cells located at those sites previously identified as harboring adult stem cells in, for example, the skin and large intestine. In many instances co-localization of CAIX and HIF-1α was not evident. CAXII expression is restricted to cells involved in secretion and water absorption such as parietal cells of the stomach, acinar cells of the salivary glands and pancreas, epithelium of the large intestine, and renal tubules. Co-localization of CAXII with CAIX or HIF-1α was not observed. Conclusion The study has showed that: 1 HIF-1α and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2 There is no evidence of

Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

DEFF Research Database (Denmark)

Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans

1999-01-01

A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...

Beam induced vacuum measurement error in BEPC II

Institute of Scientific and Technical Information of China (English)

无

2011-01-01

When the beam in BEPCII storage ring aborts suddenly, the measured pressure of cold cathode gauges and ion pumps will drop suddenly and decrease to the base pressure gradually. This shows that there is a beam induced positive error in the pressure measurement during beam operation. The error is the difference between measured and real pressures. Right after the beam aborts, the error will disappear immediately and the measured pressure will then be equal to real pressure. For one gauge, we can fit a non-linear pressure-time curve with its measured pressure data 20 seconds after a sudden beam abortion. From this negative exponential decay pumping-down curve, real pressure at the time when the beam starts aborting is extrapolated. With the data of several sudden beam abortions we have got the errors of that gauge in different beam currents and found that the error is directly proportional to the beam current, as expected. And a linear data-fitting gives the proportion coefficient of the equation, which we derived to evaluate the real pressure all the time when the beam with varied currents is on.

Different transport behaviors of NH4 (+) and NH3 in transmembrane cyclic peptide nanotubes.

Science.gov (United States)

Zhang, Mingming; Fan, Jianfen; Xu, Jian; Weng, Peipei; Lin, Huifang

2016-10-01

Two water-filled transmembrane cyclic peptide nanotubes (CPNTs) of 8×cyclo-(WL)n=4,5/POPE were chosen to investigate the dependences of the transport properties of the positive NH4 (+) and neutral NH3 on the channel radius. Molecular dynamic simulations revealed that molecular charge, size, ability to form H-bonds and channel radius all significantly influence the behaviors of NH4 (+) and NH3 in a CPNT. Higher electrostatic interactions, more H-bonds, and water-bridges were found in the NH4 (+) system, resulting in NH4 (+) meeting higher energy barriers, while NH3 can enter, exit and permeate the channels effortlessly. This work sheds a first light on the differences between the mechanisms of NH4 (+) and NH3 moving in a CPNT at an atomic level. Graphical Abstract Snapshot of the simulation system of NH4 (+)_octa-CPNT with an NH4 (+) initially positioned at one mouth of the tube, PMF profiles for single NH4 (+) ion and NH3 molecule moving through water-filled transmembrane CPNTs of 8×cyclo-(WL)n=4,5/POPE and sketch graphs of the possible H-bond forms of NH3 and NH4 (+) with the neighboring water.

Rupturing Giant Plasma Membrane Vesicles to Form Micron-sized Supported Cell Plasma Membranes with Native Transmembrane Proteins.

Science.gov (United States)

Chiang, Po-Chieh; Tanady, Kevin; Huang, Ling-Ting; Chao, Ling

2017-11-09

Being able to directly obtain micron-sized cell blebs, giant plasma membrane vesicles (GPMVs), with native membrane proteins and deposit them on a planar support to form supported plasma membranes could allow the membrane proteins to be studied by various surface analytical tools in native-like bilayer environments. However, GPMVs do not easily rupture on conventional supports because of their high protein and cholesterol contents. Here, we demonstrate the possibility of using compression generated by the air-water interface to efficiently rupture GPMVs to form micron-sized supported membranes with native plasma membrane proteins. We demonstrated that not only lipid but also a native transmembrane protein in HeLa cells, Aquaporin 3 (AQP3), is mobile in the supported membrane platform. This convenient method for generating micron-sized supported membrane patches with mobile native transmembrane proteins could not only facilitate the study of membrane proteins by surface analytical tools, but could also enable us to use native membrane proteins for bio-sensing applications.

Gas-water-rock interactions induced by reservoir exploitation, CO2 sequestration, and other geological storage

International Nuclear Information System (INIS)

Lecourtier, J.

2005-01-01

Here is given a summary of the opening address of the IFP International Workshop: 'gas-water-rock interactions induced by reservoir exploitation, CO 2 sequestration, and other geological storage' (18-20 November 2003). 'This broad topic is of major interest to the exploitation of geological sites since gas-water-mineral interactions determine the physicochemical characteristics of these sites, the strategies to adopt to protect the environment, and finally, the operational costs. Modelling the phenomena is a prerequisite for the engineering of a geological storage, either for disposal efficiency or for risk assessment and environmental protection. During the various sessions, several papers focus on the great achievements that have been made in the last ten years in understanding and modelling the coupled reaction and transport processes occurring in geological systems, from borehole to reservoir scale. Remaining challenges such as the coupling of mechanical processes of deformation with chemical reactions, or the influence of microbiological environments on mineral reactions will also be discussed. A large part of the conference programme will address the problem of mitigating CO 2 emissions, one of the most important issues that our society must solve in the coming years. From both a technical and an economic point of view, CO 2 geological sequestration is the most realistic solution proposed by the experts today. The results of ongoing pilot operations conducted in Europe and in the United States are strongly encouraging, but geological storage will be developed on a large scale in the future only if it becomes possible to predict the long term behaviour of stored CO 2 underground. In order to reach this objective, numerous issues must be solved: - thermodynamics of CO 2 in brines; - mechanisms of CO 2 trapping inside the host rock; - geochemical modelling of CO 2 behaviour in various types of geological formations; - compatibility of CO 2 with oil-well cements

Can membrane-bound carotenoid pigment zeaxanthin carry out a transmembrane proton transfer?

Science.gov (United States)

Kupisz, Kamila; Sujak, Agnieszka; Patyra, Magdalena; Trebacz, Kazimierz; Gruszecki, Wiesław I

2008-10-01

Polar carotenoid pigment zeaxanthin (beta,beta-carotene-3,3'-diol) incorporated into planar lipid membranes formed with diphytanoyl phosphatidylcholine increases the specific electric resistance of the membrane from ca. 4 to 13 x 10(7) Omega cm2 (at 5 mol% zeaxanthin with respect to lipid). Such an observation is consistent with the well known effect of polar carotenoids in decreasing fluidity and structural stabilization of lipid bilayers. Zeaxanthin incorporated into the lipid membrane at 1 mol% has very small effect on the overall membrane resistance but facilitates equilibration of the transmembrane proton gradient, as demonstrated with the application of the H+-sensitive antimony electrodes. Relatively low changes in the electrical potential suggest that the equilibration process may be associated with a symport/antiport activity or with a transmembrane transfer of the molecules of acid. UV-Vis linear dichroism analysis of multibilayer formed with the same lipid-carotenoid system shows that the transition dipole moment of the pigment molecules forms a mean angle of 21 degrees with respect to the axis normal to the plane of the membrane. This means that zeaxanthin spans the membrane and tends to have its two hydroxyl groups anchored in the opposite polar zones of the membrane. Detailed FTIR analysis of beta-carotene and zeaxanthin indicates that the polyene chain of carotenoids is able to form weak hydrogen bonds with water molecules. Possible molecular mechanisms responsible for proton transport by polyenes are discussed, including direct involvement of the polyene chain in proton transfer and indirect effect of the pigment on physical properties of the membrane.

Functional relevance of aromatic residues in the first transmembrane domain of P2X receptors

Czech Academy of Sciences Publication Activity Database

Jindřichová, Marie; Vávra, Vojtěch; Obšil, Tomáš; Stojilkovic, S. S.; Zemková, Hana

2009-01-01

Roč. 109, č. 3 (2009), s. 923-934 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA5011408; GA AV ČR(CZ) IAA500110702; GA AV ČR(CZ) IAA500110910 Institutional research plan: CEZ:AV0Z50110509 Keywords : purinergic receptors * gating * transmembrane domain Subject RIV: FH - Neuro logy Impact factor: 3.999, year: 2009

Point mutations in the transmembrane region of the clic1 ion channel selectively modify its biophysical properties.

Directory of Open Access Journals (Sweden)

Stefania Averaimo

Full Text Available Chloride intracellular Channel 1 (CLIC1 is a metamorphic protein that changes from a soluble cytoplasmic protein into a transmembrane protein. Once inserted into membranes, CLIC1 multimerises and is able to form chloride selective ion channels. Whilst CLIC1 behaves as an ion channel both in cells and in artificial lipid bilayers, its structure in the soluble form has led to some uncertainty as to whether it really is an ion channel protein. CLIC1 has a single putative transmembrane region that contains only two charged residues: arginine 29 (Arg29 and lysine 37 (Lys37. As charged residues are likely to have a key role in ion channel function, we hypothesized that mutating them to neutral alanine to generate K37A and R29A CLIC1 would alter the electrophysiological characteristics of CLIC1. By using three different electrophysiological approaches: i single channel Tip-Dip in artificial bilayers using soluble recombinant CLIC1, ii cell-attached and iii whole-cell patch clamp recordings in transiently transfected HEK cells, we determined that the K37A mutation altered the single-channel conductance while the R29A mutation affected the single-channel open probability in response to variation in membrane potential. Our results show that mutation of the two charged amino acids (K37 and R29 in the putative transmembrane region of CLIC1 alters the biophysical properties of the ion channel in both artificial bilayers and cells. Hence these charged residues are directly involved in regulating its ion channel activity. This strongly suggests that, despite its unusual structure, CLIC1 itself is able to form a chloride ion channel.

Differential expression of a novel seven transmembrane domain protein in epididymal fat from aged and diabetic mice.

Science.gov (United States)

Yang, H; Egan, J M; Rodgers, B D; Bernier, M; Montrose-Rafizadeh, C

1999-06-01

To identify novel seven transmembrane domain proteins from 3T3-L1 adipocytes, we used PCR to amplify 3T3-L1 adipocyte complementary DNA (cDNA) with primers homologous to the N- and C-termini of pancreatic glucagon-like peptide-1 (GLP-1) receptor. We screened a cDNA library prepared from fully differentiated 3T3-L1 adipocytes using a 500-bp cDNA PCR product probe. Herein describes the isolation and characterization of a 1.6-kb cDNA clone that encodes a novel 298-amino acid protein that we termed TPRA40 (transmembrane domain protein of 40 kDa regulated in adipocytes). TPRA40 has seven putative transmembrane domains and shows little homology with the known GLP-1 receptor or with other G protein-coupled receptors. The levels of TPRA40 mRNA and protein were higher in 3T3-L1 adipocytes than in 3T3-L1 fibroblasts. TPRA40 is present in a number of mouse and human tissues. Interestingly, TPRA40 mRNA levels were significantly increased by 2- to 3-fold in epididymal fat of 24-month-old mice vs. young controls as well as in db/db and ob/ob mice vs. nondiabetic control littermates. No difference in TPRA40 mRNA levels was observed in brain, heart, skeletal muscle, liver, or kidney. Furthermore, no difference in TPRA40 expression was detected in brown fat of ob/ob mice when compared with age-matched controls. Taken together, these data suggest that TPRA40 represents a novel membrane-associated protein whose expression in white adipose tissue is altered with aging and type 2 diabetes.

Crystallization and preliminary X-ray diffraction analysis of P30, the transmembrane domain of pertactin, an autotransporter from Bordetella pertussis

International Nuclear Information System (INIS)

Zhu, Yanshi; Black, Isobel; Roszak, Aleksander W.; Isaacs, Neil W.

2007-01-01

P30, the transmembrane C-terminal domain of pertactin from B. pertussis has been crystallized after refolding in vitro. Preliminary X-ray crystallographic data are reported. P30, the 32 kDa transmembrane C-terminal domain of pertactin from Bordetella pertussis, is supposed to form a β-barrel inserted into the outer membrane for the translocation of the passenger domain. P30 was cloned and expressed in inclusion bodies in Escherichia coli. After refolding and purification, the protein was crystallized using the sitting-drop vapour-diffusion method at 292 K. The crystals diffract to a resolution limit of 3.5 Å using synchrotron radiation and belong to the hexagonal space group P6 1 22, with unit-cell parameters a = b = 123.27, c = 134.43 Å

Design of double containment canister cask storage system

International Nuclear Information System (INIS)

Asami, M.; Matsumoto, T.; Oohama, T.; Kuriyama, K.; Kawakami, K.

2004-01-01

Spent fuels discharged from Japanese LWR will be stored as recycled-fuel-resources in interim storage facilities. The concrete cask storage system is one of important forms for the spent fuel interim storage. In Japan, the interim storage facility will be located near the coast, therefore it is important to prevent SCC (Stress Corrosion Cracking) caused by sea salt particles and to assure the containment integrity of the canister which contains spent fuels. KEPCO, NFT and OCL have designed the double containment canister cask storage system that can assure the long-term containment integrity and monitor the containment performance without storage capacity decrease. Major features of the combined canister cask system are shown as follows: This system can survey containment integrity of dual canisters by monitoring the pressure of the gap between canisters. The primary canister has dual lids sealed by welding. The secondary canister has single lid tightened by bolts and sealed by metallic gaskets. The primary canister is contained in the transport cask during transportation, and the gap between the primary canister and the transport cask is filled with He gas. Under storage condition in the concrete cask, the primary canister is contained in the secondary canister, and the gap between these canisters is filled with helium gas. Hence this system can prevent the primary canister to contact sea salt particle in the air and from SCC. Decrease of cooling performance because of the double canister is compensated by fins fitted on the secondary canister surface. Then, this system can prevent the decrease of storage capacity determined by the fuel temperature limit. This system can assure that the primary canister will keep intact for long term storage. Therefore, in the case of pressure down of the gap between canisters, it can be considered that the secondary canister containment is damaged, and the primary canister will be transferred to another secondary canister at the

Hydropower generation and storage, transmission constraints and market power

International Nuclear Information System (INIS)

Johnsen, T.A.

2001-01-01

We study hydropower generation and storage in the presence of uncertainty about future inflows, market power and limited transmission capacity to neighboring regions. Within our simple two-period model, market power leads to too little storage. The monopolist finds it profitable to produce more than the competitive amount in the first period and thereby stores little water in the first of two periods in order to become import constrained in the second period. In addition, little storage reduces the probability of becoming export constrained in the second period, even if the second period exhibits large inflow. Empirical findings for an area in the western part of Norway with only hydropower and high ownership concentration at the supply side, fit well to our theoretical model. We apply a numerical model to examine various policies to reduce the inefficiencies created by the local monopoly. Transmission investments have two effects. First, the export possibilities in the first period increase. More export leads to lower storage in the first period. Second, larger import capacity reduces the market power problem in the second period. The two opposite effects of transmission investments in a case with market power may be unique to hydropower systems. Introducing financial transmission rights enhance the market power of the monopolist in our model. Price caps in both or in the second period only, reduce the strategic value of water storage. (Author)

Fitness Club

CERN Multimedia

Fitness Club

2012-01-01

Open to All: http://cern.ch/club-fitness  fitness.club@cern.ch Boxing Your supervisor makes your life too tough ! You really need to release the pressure you've been building up ! Come and join the fit-boxers. We train three times a week in Bd 216, classes for beginners and advanced available. Visit our website cern.ch/Boxing General Fitness Escape from your desk with our general fitness classes, to strengthen your heart, muscles and bones, improve you stamina, balance and flexibility, achieve new goals, be more productive and experience a sense of well-being, every Monday, Wednesday and Friday lunchtime, Tuesday mornings before work and Thursday evenings after work – join us for one of our monthly fitness workshops. Nordic Walking Enjoy the great outdoors; Nordic Walking is a great way to get your whole body moving and to significantly improve the condition of your muscles, heart and lungs. It will boost your energy levels no end. Pilates A body-conditioning technique de...

Transitioning aluminum clad spent fuels from wet to interim dry storage

International Nuclear Information System (INIS)

Louthan, M.R. Jr.; Iyer, N.C.; Sindelar, R.L.; Peacock, H.B. Jr.

1994-01-01

The United States Department of Energy (DOE) currently owns several hundred metric tons of aluminum clad, spent nuclear fuel and target assemblies. The vast majority of these irradiated assemblies are currently stored in water basins that were designed and operated for short term fuel cooling prior to fuel reprocessing. Recent DOE decisions to severely limit the reprocessing option have significantly lengthened the time of storage, thus increasing the tendency for corrosion induced degradation of the fuel cladding and the underlying core material. The portent of continued corrosion, coupled with the age of existing wet storage facilities and the cost of continuing basin operations, including necessary upgrades to meet current facility standards, may force the DOE to transition these wet stored, aluminum clad spent fuels to interim dry storage. The facilities for interim dry storage have not been developed, partially because fuel storage requirements and specifications for acceptable fuel forms are lacking. In spite of the lack of both facilities and specifications, current plans are to dry store fuels for approximately 40 to 60 years or until firm decisions are developed for final fuel disposition. The transition of the aluminum clad fuels from wet to interim dry storage will require a sequence of drying and canning operations which will include selected fuel preparations such as vacuum drying and conditioning of the storage atmosphere. Laboratory experiments and review of the available literature have demonstrated that successful interim dry storage may also require the use of fuel and canister cleaning or rinsing techniques that preclude, or at least minimize, the potential for the accumulation of chloride and other potentially deleterious ions in the dry storage environment. This paper summarizes an evaluation of the impact of fuel transitioning techniques on the potential for corrosion induced degradation of fuel forms during interim dry storage

FITS: a function-fitting program

Energy Technology Data Exchange (ETDEWEB)

Balestrini, S.J.; Chezem, C.G.

1982-01-01

FITS is an iterating computer program that adjusts the parameters of a function to fit a set of data points according to the least squares criterion and then lists and plots the results. The function can be programmed or chosen from a library that is provided. The library can be expanded to include up to 99 functions. A general plotting routine, contained in the program but useful in its own right, is described separately in an Appendix.

Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity.

Science.gov (United States)

Qiao, Yi; Sun, Jin; Xia, Shufang; Tang, Xue; Shi, Yonghui; Le, Guowei

2014-06-01

Recent studies have investigated the anti-obesity effect of resveratrol, but the pathways through which resveratrol resists obesity are not clear. In the present study, we hypothesize that resveratrol exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes, and in turn, improving fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high-fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several biochemical markers are measured. Fluorescence in situ hybridization and flow cytometry are used to monitor and quantify the changes in gut microbiota. The key genes related to fat storage and metabolism in the liver and visceral adipose tissues are measured by real-time PCR. The results show that resveratrol (200 mg per kg per day) significantly lowers both body and visceral adipose weights, and reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut microbiota dysbiosis induced by the HF diet, including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Enterococcus faecalis, and increasing the growth of Lactobacillus and Bifidobacterium. Furthermore, resveratrol significantly increases the fasting-induced adipose factor (Fiaf, a key gene negatively regulated by intestinal microbes) expression in the intestine. Resveratrol significantly decreases mRNA expression of Lpl, Scd1, Ppar-γ, Acc1, and Fas related to fatty acids synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf expression. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and in turn, through the Fiaf signaling pathway, accelerates the development of obesity.

Transmembrane molecular transport during versus after extremely large, nanosecond electric pulses.

Science.gov (United States)

Smith, Kyle C; Weaver, James C

2011-08-19

Recently there has been intense and growing interest in the non-thermal biological effects of nanosecond electric pulses, particularly apoptosis induction. These effects have been hypothesized to result from the widespread creation of small, lipidic pores in the plasma and organelle membranes of cells (supra-electroporation) and, more specifically, ionic and molecular transport through these pores. Here we show that transport occurs overwhelmingly after pulsing. First, we show that the electrical drift distance for typical charged solutes during nanosecond pulses (up to 100 ns), even those with very large magnitudes (up to 10 MV/m), ranges from only a fraction of the membrane thickness (5 nm) to several membrane thicknesses. This is much smaller than the diameter of a typical cell (∼16 μm), which implies that molecular drift transport during nanosecond pulses is necessarily minimal. This implication is not dependent on assumptions about pore density or the molecular flux through pores. Second, we show that molecular transport resulting from post-pulse diffusion through minimum-size pores is orders of magnitude larger than electrical drift-driven transport during nanosecond pulses. While field-assisted charge entry and the magnitude of flux favor transport during nanosecond pulses, these effects are too small to overcome the orders of magnitude more time available for post-pulse transport. Therefore, the basic conclusion that essentially all transmembrane molecular transport occurs post-pulse holds across the plausible range of relevant parameters. Our analysis shows that a primary direct consequence of nanosecond electric pulses is the creation (or maintenance) of large populations of small pores in cell membranes that govern post-pulse transmembrane transport of small ions and molecules. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced gene 2 (GPR183)

DEFF Research Database (Denmark)

Benned-Jensen, Tau; Norn, Christoffer; Laurent, Stephane

2012-01-01

, the family of G protein-coupled seven transmembrane-spanning receptors (7TM receptors) was added to this group. Specifically, the Epstein-Barr virus-induced gene 2 (EBI2 or GPR183) was shown to be activated by several oxysterols, most potently by 7α,25-dihydroxycholesterol (7α,25-OHC). Nothing is known about...

Regulation of natural competence by the orphan two-component system sensor kinase ChiS involves a non-canonical transmembrane regulator in Vibrio cholerae.

Science.gov (United States)

Yamamoto, Shouji; Mitobe, Jiro; Ishikawa, Takahiko; Wai, Sun Nyunt; Ohnishi, Makoto; Watanabe, Haruo; Izumiya, Hidemasa

2014-01-01

In Vibrio cholerae, 41 chitin-inducible genes, including the genes involved in natural competence for DNA uptake, are governed by the orphan two-component system (TCS) sensor kinase ChiS. However, the mechanism by which ChiS controls the expression of these genes is currently unknown. Here, we report the involvement of a novel transcription factor termed 'TfoS' in this process. TfoS is a transmembrane protein that contains a large periplasmic domain and a cytoplasmic AraC-type DNA-binding domain, but lacks TCS signature domains. Inactivation of tfoS abolished natural competence as well as transcription of the tfoR gene encoding a chitin-induced small RNA essential for competence gene expression. A TfoS fragment containing the DNA-binding domain specifically bound to and activated transcription from the tfoR promoter. Intracellular TfoS levels were unaffected by disruption of chiS and coexpression of TfoS and ChiS in Escherichia coli recovered transcription of the chromosomally integrated tfoR::lacZ gene, suggesting that TfoS is post-translationally modulated by ChiS during transcriptional activation; however, this regulation persisted when the canonical phosphorelay residues of ChiS were mutated. The results presented here suggest that ChiS operates a chitin-induced non-canonical signal transduction cascade through TfoS, leading to transcriptional activation of tfoR. © 2013 John Wiley & Sons Ltd.

Fitness Club

CERN Multimedia

Fitness Club

2011-01-01

The CERN Fitness Club is organising Zumba Classes on the first Wednesday of each month, starting 7 September (19.00 – 20.00). What is Zumba®? It’s an exhilarating, effective, easy-to-follow, Latin-inspired, calorie-burning dance fitness-party™ that’s moving millions of people toward joy and health. Above all it’s great fun and an excellent work out. Price: 22 CHF/person Sign-up via the following form: https://espace.cern.ch/club-fitness/Lists/Zumba%20Subscription/NewForm.aspx For more info: fitness.club@cern.ch

Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding.

Science.gov (United States)

Rosenberg, Mark F; Kamis, Alhaji Bukar; Callaghan, Richard; Higgins, Christopher F; Ford, Robert C

2003-03-07

P-glycoprotein is an ATP-binding cassette transporter that is associated with multidrug resistance and the failure of chemotherapy in human patients. We have previously shown, based on two-dimensional projection maps, that P-glycoprotein undergoes conformational changes upon binding of nucleotide to the intracellular nucleotide binding domains. Here we present the three-dimensional structures of P-glycoprotein in the presence and absence of nucleotide, at a resolution limit of approximately 2 nm, determined by electron crystallography of negatively stained crystals. The data reveal a major reorganization of the transmembrane domains throughout the entire depth of the membrane upon binding of nucleotide. In the absence of nucleotide, the two transmembrane domains form a single barrel 5-6 nm in diameter and about 5 nm deep with a central pore that is open to the extracellular surface and spans much of the membrane depth. Upon binding nucleotide, the transmembrane domains reorganize into three compact domains that are each 2-3 nm in diameter and 5-6 nm deep. This reorganization opens the central pore along its length in a manner that could allow access of hydrophobic drugs (transport substrates) directly from the lipid bilayer to the central pore of the transporter.

[Application of Brownian dynamics to the description of transmembrane ion flow as exemplified by the chloride channel of glycine receptor].

Science.gov (United States)

Boronovskiĭ, S E; Nartsissov, Ia R

2009-01-01

Using the Brownian dynamics of the movement of hydrated ion in a viscous water solution, a mathematical model has been built, which describes the transport of charged particles through a single protein pore in a lipid membrane. The dependences of transmembrane ion currents on ion concentrations in solution have been obtained. It was shown that, if the geometry of a membrane pore is identical to that of the inner part of the glycine receptor channel and there is no ion selectivity, then the values of both chloride and sodium currents are not greater than 0.5 pA at the physiological concentrations of these ions. If local charge heterogeneity caused by charged amino acid residues of transmembrane protein segments is included into the model calculations, the chloride current increases to about 3.7 pA, which exceeds more than seven times the value for sodium ions under the conditions of the complex channel geometry in the range of physiological concentrations of ions in the solution. The model takes changes in the density of charge distribution both inside the channel and near the protein surface into account. The alteration of pore geometry can be also considered as a parameter at the researcher's option. Thus, the model appears as an effective tool for the description of transmembrane currents for other types of membrane channels.

Radiation-induced defects and their recombination processes in the x-ray storage phosphor BaBr2:Eu2+

International Nuclear Information System (INIS)

Secu, M; Schweizer, S; Rogulis, U; Spaeth, J-M

2003-01-01

The recombination processes in the x-ray storage phosphor BaBr 2 :Eu 2+ were investigated by optical and magneto-optical methods. A structure-sensitive investigation of the defects involved in the recombination processes was performed by detecting the microwave-induced changes in the recombination luminescence in a high magnetic field. F centres as well as V K hole centres are created after x-irradiation at low temperatures. The low-energy recombination band peaking at about 460 nm is due to F-V K centre recombinations, whereas the two high energy bands at 282 and 315 nm are probably due to recombinations of self-trapped excitons

Drosophila Ninjurin A induces nonapoptotic cell death.

Directory of Open Access Journals (Sweden)

Sarah Broderick

Full Text Available Ninjurins are conserved transmembrane proteins that are upregulated across species in response to injury and stress. Their biological functions are not understood, in part because there have been few in vivo studies of their function. We analyzed the expression and function of one of three Drosophila Ninjurins, NijA. We found that NijA protein is redistributed to the cell surface in larval immune tissues after septic injury and is upregulated by the Toll pathway. We generated a null mutant of NijA, which displayed no detectable phenotype. In ectopic expression studies, NijA induced cell death, as evidenced by cell loss and acridine orange staining. These dying cells did not display hallmarks of apoptotic cells including TUNEL staining and inhibition by p35, indicating that NijA induced nonapoptotic cell death. In cell culture, NijA also induced cell death, which appeared to be cell autonomous. These in vivo studies identify a new role for the Ninjurin family in inducing nonapoptotic cell death.

A Mitochondria-Dependent Pathway Mediates the Apoptosis of GSE-Induced Yeast

OpenAIRE

Cao, Sishuo; Xu, Wentao; Zhang, Nan; Wang, Yan; Luo, YunBo; He, Xiaoyun; Huang, Kunlun

2012-01-01

Grapefruit seed extract (GSE), which has powerful anti-fungal activity, can induce apoptosis in S. cerevisiae. The yeast cells underwent apoptosis as determined by testing for apoptotic markers of DNA cleavage and typical chromatin condensation by Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and 4,6'-diaminidino-2-phenylindole (DAPI) staining and electron microscopy. The changes of ΔΨmt (mitochondrial transmembrane potential) and ROS (reactive oxygen species) ...

The 19?kDa Mycobacterium tuberculosis Lipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor

OpenAIRE

S?nchez, Alejandro; Espinosa, Patricia; Garc?a, Teresa; Mancilla, Ra?l

2012-01-01

We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (...

Energy storage

International Nuclear Information System (INIS)

Anon.

1992-01-01

This chapter discusses the role that energy storage may have on the energy future of the US. The topics discussed in the chapter include historical aspects of energy storage, thermal energy storage including sensible heat storage, latent heat storage, thermochemical heat storage, and seasonal heat storage, electricity storage including batteries, pumped hydroelectric storage, compressed air energy storage, and superconducting magnetic energy storage, and production and combustion of hydrogen as an energy storage option

Energy storage at the threshold: Smart mobility and the grid of the future

Science.gov (United States)

Crabtree, George

2018-01-01

Energy storage is poised to drive transformations in transportation and the electricity grid that personalize access to mobility and energy services, not unlike the transformation of smart phones that personalized access to people and information. Storage will work with other emerging technologies such as electric vehicles, ride-sharing, self-driving and connected cars in transportation and with renewable generation, distributed energy resources and smart energy management on the grid to create mobility and electricity as services matched to customer needs replacing the conventional one-size-fits-all approach. This survey outlines the prospects, challenges and impacts of the coming mobility and electricity transformations.

Monolayer freeze-fracture autoradiography: quantitative analysis of the transmembrane distribution of radioiodinated concanavalin A

International Nuclear Information System (INIS)

Fisher, K.A.

1982-01-01

The technique of monolayer freeze-fracture autoradiography (MONOFARG) has been developed and the principles, quantitation, and application of the method are described. Cell monolayers attached to polylysine-treated glass were freeze-fractured, shadowed, and coated with dry, Parlodion-supported Ilford L4 photographic emulsion at room temperature. Quantitative aspects of MONOFARG were examined using radioiodinated test systems. Background was routinely -4 grains/μm 2 /day, the highest overall efficiency was between 25% and 45%, and grain density and efficiency were dependent on radiation dose for iodine-125 and D-19 development. Corrected grain densities were linearly proportional to iodine-125 concentration. The method was applied to an examination of the transmembrane distribution of radioiodinated and fluoresceinated concanavalin A ( 125 I-FITC-Con-A). Human erythrocytes were labeled, column-purified, freeze-dried or freeze-fractured, autoradiographed, and examined by electron microscopy. The number of silver grains per square micrometer of unsplit single membrane was essentially identical to that of split extracellular membrane halves. These data demonstrate that 125 I-FITC-Con-A partitions exclusively with the extracellular half of the membrane upon freeze-fracturing and can be used as a quantitative marker for the fraction of extracellular split membrane halves. This method should be able to provide new information about certain transmembrane properties of biological membrane molecules and probes, as well as about the process of freeze-fracture per se

Fitness cost

DEFF Research Database (Denmark)

Nielsen, Karen L.; Pedersen, Thomas M.; Udekwu, Klas I.

2012-01-01

phage types, predominantly only penicillin resistant. We investigated whether isolates of this epidemic were associated with a fitness cost, and we employed a mathematical model to ask whether these fitness costs could have led to the observed reduction in frequency. Bacteraemia isolates of S. aureus...... from Denmark have been stored since 1957. We chose 40 S. aureus isolates belonging to phage complex 83A, clonal complex 8 based on spa type, ranging in time of isolation from 1957 to 1980 and with varyous antibiograms, including both methicillin-resistant and -susceptible isolates. The relative fitness...... of each isolate was determined in a growth competition assay with a reference isolate. Significant fitness costs of 215 were determined for the MRSA isolates studied. There was a significant negative correlation between number of antibiotic resistances and relative fitness. Multiple regression analysis...

Crystallization and preliminary X-ray diffraction analysis of P30, the transmembrane domain of pertactin, an autotransporter from Bordetella pertussis

Energy Technology Data Exchange (ETDEWEB)

Zhu, Yanshi; Black, Isobel; Roszak, Aleksander W.; Isaacs, Neil W., E-mail: n.isaacs@chem.gla.ac.uk [Department of Chemistry and WestChem, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA,Scotland (United Kingdom)

2007-07-01

P30, the transmembrane C-terminal domain of pertactin from B. pertussis has been crystallized after refolding in vitro. Preliminary X-ray crystallographic data are reported. P30, the 32 kDa transmembrane C-terminal domain of pertactin from Bordetella pertussis, is supposed to form a β-barrel inserted into the outer membrane for the translocation of the passenger domain. P30 was cloned and expressed in inclusion bodies in Escherichia coli. After refolding and purification, the protein was crystallized using the sitting-drop vapour-diffusion method at 292 K. The crystals diffract to a resolution limit of 3.5 Å using synchrotron radiation and belong to the hexagonal space group P6{sub 1}22, with unit-cell parameters a = b = 123.27, c = 134.43 Å.

The FitTrack Index as fitness indicator: A pilot study | van Rensburg ...

African Journals Online (AJOL)

Conclusions: These results suggest that the web-based FitTrack Index may be considered an appropriate tool to evaluate exercise capacity and cardiovascular fitness in healthy individuals following an aerobic training programme. Keywords: Aerobic fitness, Exercise ability, Recreational fitness, Cardiovascular fitness, ...

Effect of storage time and framework design on the accuracy of maxillary cobalt-chromium cast removable partial dentures

Science.gov (United States)

Viswambaran, M.; Sundaram, R. K.

2015-01-01

Statement of Problem: Inaccuracies in the fit of palatal major connectors may be related to distortion of the wax pattern due to prolonged storage time and faulty major connector design. Purpose: This in vitro study was carried out to find out the effect of storage time and major connector design on the accuracy of cobalt-chromium cast removable partial dentures (RPDs). Materials and Methods: A brass metal die with a Kennedy Class III, modification 1, the partially edentulous arch was used as a master die. Thirty-six refractory casts were fabricated from the master die. The refractory casts were divided into three groups (Group I: Anterior-posterior palatal bar, Group II: Palatal strap and Group III: Palatal plate) based on the design of maxillary major connector and subdivided into four groups (sub Group A: 01 h, sub Group B: 03 h, Sub Group C: 06 h, and sub Group D: 24 h) based on the storage time. For each group, 12 frameworks were fabricated. The influence of wax pattern storage time and the accuracy of the fit palatal major connector designs on the master die were compared. Casting defects (nodules/incompleteness) of the frameworks were also evaluated before finishing and polishing. Repeated measures analysis of variance was used to analyze the data. Results: The gap discrepancy was least in sub Group A (01 h) followed by sub Group B (03 h) and C (06 h) and most in sub Group D (24 h). Statistically significant differences (P < 0.05 in all locations L1–L5) in the fit of the framework were related to the design of the major connector. The gap discrepancy was least in Group I (anterior-posterior palatal bar) followed by Group II (palatal strap) and most in Group II (palatal plate). Conclusions: It is recommended that the wax patterns for RPD to be invested immediately on completion of the wax procedure. The selection of a major connector design is crucial for an accurate fit of RPD. PMID:26681850

Effect of storage time and framework design on the accuracy of maxillary cobalt-chromium cast removable partial dentures

Directory of Open Access Journals (Sweden)

M Viswambaran

2015-01-01

Full Text Available Statement of Problem: Inaccuracies in the fit of palatal major connectors may be related to distortion of the wax pattern due to prolonged storage time and faulty major connector design. Purpose: This in vitro study was carried out to find out the effect of storage time and major connector design on the accuracy of cobalt-chromium cast removable partial dentures (RPDs. Materials and Methods: A brass metal die with a Kennedy Class III, modification 1, the partially edentulous arch was used as a master die. Thirty-six refractory casts were fabricated from the master die. The refractory casts were divided into three groups (Group I: Anterior-posterior palatal bar, Group II: Palatal strap and Group III: Palatal plate based on the design of maxillary major connector and subdivided into four groups (sub Group A: 01 h, sub Group B: 03 h, Sub Group C: 06 h, and sub Group D: 24 h based on the storage time. For each group, 12 frameworks were fabricated. The influence of wax pattern storage time and the accuracy of the fit palatal major connector designs on the master die were compared. Casting defects (nodules/incompleteness of the frameworks were also evaluated before finishing and polishing. Repeated measures analysis of variance was used to analyze the data. Results: The gap discrepancy was least in sub Group A (01 h followed by sub Group B (03 h and C (06 h and most in sub Group D (24 h. Statistically significant differences (P < 0.05 in all locations L1–L5 in the fit of the framework were related to the design of the major connector. The gap discrepancy was least in Group I (anterior-posterior palatal bar followed by Group II (palatal strap and most in Group II (palatal plate. Conclusions: It is recommended that the wax patterns for RPD to be invested immediately on completion of the wax procedure. The selection of a major connector design is crucial for an accurate fit of RPD.

FITS: a function-fitting program

Energy Technology Data Exchange (ETDEWEB)

Balestrini, S.J.; Chezem, C.G.

1982-08-01

FITS is an iterating computer program that adjusts the parameters of a function to fit a set of data points according to the least squares criterion and then lists and plots the results. The function can be programmed or chosen from a library that is provided. The library can be expanded to include up to 99 functions. A general plotting routine, contained in the program but useful in its own right, is described separately in Appendix A. An example problem file and its solution is given in Appendix B.

Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family.

Directory of Open Access Journals (Sweden)

Douglas R Boettner

2008-01-01

Full Text Available Entamoeba histolytica is the cause of amebic colitis and liver abscess. This parasite induces apoptosis in host cells and utilizes exposed ligands such as phosphatidylserine to ingest the apoptotic corpses and invade deeper into host tissue. The purpose of this work was to identify amebic proteins involved in the recognition and ingestion of dead cells. A member of the transmembrane kinase family, phagosome-associated TMK96 (PATMK, was identified in a proteomic screen for early phagosomal proteins. Anti-peptide affinity-purified antibody produced against PATMK demonstrated that it was a type I integral membrane protein that was expressed on the trophozoite surface, and that co-localized with human erythrocytes at the site of contact. The role of PATMK in erythrophagocytosis in vitro was demonstrated by: (i incubation of ameba with anti-PATMK antibodies; (ii PATMK mRNA knock-down using a novel shRNA expression system; and (iii expression of a carboxy-truncation of PATMK (PATMK(delta932. Expression of the carboxy-truncation of PATMK(delta932 also caused a specific reduction in the ability of E. histolytica to establish infection in the intestinal model of amebiasis, however these amebae retained the ability to cause hepatic abscesses when directly injected in the liver. In conclusion, PATMK was identified as a member of the TMK family that participates in erythrophagocytosis and is uniquely required for intestinal infection.

Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family.

Science.gov (United States)

Boettner, Douglas R; Huston, Christopher D; Linford, Alicia S; Buss, Sarah N; Houpt, Eric; Sherman, Nicholas E; Petri, William A

2008-01-01

Entamoeba histolytica is the cause of amebic colitis and liver abscess. This parasite induces apoptosis in host cells and utilizes exposed ligands such as phosphatidylserine to ingest the apoptotic corpses and invade deeper into host tissue. The purpose of this work was to identify amebic proteins involved in the recognition and ingestion of dead cells. A member of the transmembrane kinase family, phagosome-associated TMK96 (PATMK), was identified in a proteomic screen for early phagosomal proteins. Anti-peptide affinity-purified antibody produced against PATMK demonstrated that it was a type I integral membrane protein that was expressed on the trophozoite surface, and that co-localized with human erythrocytes at the site of contact. The role of PATMK in erythrophagocytosis in vitro was demonstrated by: (i) incubation of ameba with anti-PATMK antibodies; (ii) PATMK mRNA knock-down using a novel shRNA expression system; and (iii) expression of a carboxy-truncation of PATMK (PATMK(delta932)). Expression of the carboxy-truncation of PATMK(delta932) also caused a specific reduction in the ability of E. histolytica to establish infection in the intestinal model of amebiasis, however these amebae retained the ability to cause hepatic abscesses when directly injected in the liver. In conclusion, PATMK was identified as a member of the TMK family that participates in erythrophagocytosis and is uniquely required for intestinal infection.

Wii Fit U intensity and enjoyment in adults.

Science.gov (United States)

Tripette, Julien; Murakami, Haruka; Ando, Takafumi; Kawakami, Ryoko; Tanaka, Noriko; Tanaka, Shigeho; Miyachi, Motohiko

2014-08-26

The Wii Fit series (Nintendo Inc., Japan) provides active video games (AVGs) to help adults to maintain a sufficient level of daily physical activity (PA). The second generation of home AVG consoles is now emerging with new game modalities (including a portable mini screen in the case of the new Wii U). The present study was performed to investigate the intensity and enjoyment of Wii Fit U games among adults. Metabolic equivalent (METs, i.e., intensity) of the Wii Fit U activities were evaluated using metabolic chambers in 16 sedentary adults (8 women and 8 men). A short version of the physical activity enjoyment scale was completed for each activity. Wii Fit U activities were distributed over a range from 2.2  ±  0.4 METs (Hula dance) to 4.7  ±  1.2 (Hip-hop dance). Seven activities were classified as light-intensity PA (game modality does not induce higher METs. Men exercised at higher intensities than women. There was no correlation between enjoyment and MET values in women or men. More and more moderate-intensity activities are available through video gaming, but the average intensity (3.2  ±  0.6) is still low. Users should be aware that AVGs alone cannot fulfill the recommendations for PA, and the video games industry still must innovate further to enhance gaming intensity and make the tool more attractive to health and fitness professionals.

Physical Fitness Assessment.

Science.gov (United States)

Valdes, Alice

This document presents baseline data on physical fitness that provides an outline for assessing the physical fitness of students. It consists of 4 tasks and a 13-item questionnaire on fitness-related behaviors. The fitness test evaluates cardiorespiratory endurance by a steady state jog; muscular strength and endurance with a two-minute bent-knee…

Resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.

Science.gov (United States)

Muregi, Francis W; Ohta, Isao; Masato, Uchijima; Kino, Hideto; Ishih, Akira

2011-01-01

The greatest impediment to effective malaria control is drug resistance in Plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy. To generate resistance, P. berghei NK65 was subjected to 5-fluoroorotate (FOA, an inhibitor of thymidylate synthase, TS) pressure in mice. After 15 generations of drug pressure, the 2% DT (the delay time for proliferation of parasites to 2% parasitaemia, relative to untreated wild-type controls) reduced from 8 days to 4, equalling the controls. Drug sensitivity studies confirmed that FOA-resistance was stable. During serial passaging in the absence of drug, resistant parasite maintained low growth rates (parasitaemia, 15.5%±2.9, 7 dpi) relative to the wild-type (45.6%±8.4), translating into resistance cost of fitness of 66.0%. The resistant parasite showed an apoptosis-like death, as confirmed by light and transmission electron microscopy and corroborated by oligonucleosomal DNA fragmentation. The resistant parasite was less fit than the wild-type, which implies that in the absence of drug pressure in the field, the wild-type alleles may expand and allow drugs withdrawn due to resistance to be reintroduced. FOA resistance led to depleted dTTP pools, causing thymineless parasite death via apoptosis. This supports the tenet that unicellular eukaryotes, like metazoans, also undergo apoptosis. This is the first report where resistance to a chemical stimulus and not the stimulus itself is shown to induce apoptosis in a unicellular parasite. This finding is relevant in cancer therapy, since thymineless cell death induced by resistance to TS-inhibitors can further be optimized via inhibition of pyrimidine salvage enzymes, thus providing a synergistic impact. We conclude that since apoptosis is a process that can be pharmacologically modulated, the parasite's apoptotic machinery may be exploited as a novel drug target in malaria and other protozoan

SERODS: a new medium for high-density optical data storage

Science.gov (United States)

Vo-Dinh, Tuan; Stokes, David L.

1998-10-01

A new optical dada storage technology based on the surface- enhanced Raman scattering (SERS) effect has been developed for high-density optical memory and three-dimensional data storage. With the surface-enhanced Raman optical data storage (SERODS) technology, the molecular interactions between the optical layer molecules and the nanostructured metal substrate are modified by the writing laser, changing their SERS properties to encode information as bits. Since the SERS properties are extremely sensitive to molecular nano- environments, very small 'spectrochemical holes' approaching the diffraction limit can be produced for the writing process. The SERODS device uses a reading laser to induce the SERS emission of molecules on the disk and a photometric detector tuned to the frequency of the RAMAN spectrum to retrieve the stored information. The results illustrate that SERODS is capable of three-dimensional data storage and has the potential to achieve higher storage density than currently available optical data storage systems.

Potential problem areas: extended storage of low-level radioactive waste

Energy Technology Data Exchange (ETDEWEB)

Siskind, B.

1985-01-01

If a state or regional compact does not have adequate disposal capacity for low-level radioactive waste (LLRW), then extended storage of certain LLRW may be necessary. The Nuclear Regulatory Commission (NRC) has contracted with Brookhaven National Laboratory to address the technical issues of extended storage. The dual objectives of this study are (1) to provide practical technical assessments for NRC to consider in evaluating specific proposals for extended storage and (2) to help ensure adequate consideration by NRC, Agreement States, and licensees of potential problems that may arise from existing or proposed extended storage practices. Storage alternatives are considered in order to characterize the likely storage environments for these wastes. In particular, the range of storage alternatives considered and being implemented by the nuclear power plant utilities is described. The properties of the waste forms and waste containers are discussed. An overview is given of the performance of the waste package and its contents during storage (e.g., radiolytic gas generation, corrosion) and of the effects of extended storage on the performance of the waste package after storage (e.g., radiation-induced embrittlement of polyethylene, the weakening of steel containers by corrosion). Additional information and actions required to address these concerns, including possible mitigative measures, are discussed. 26 refs., 1 tab.

Deorphanizing the human transmembrane genome: A landscape of uncharacterized membrane proteins.

Science.gov (United States)

Babcock, Joseph J; Li, Min

2014-01-01

The sequencing of the human genome has fueled the last decade of work to functionally characterize genome content. An important subset of genes encodes membrane proteins, which are the targets of many drugs. They reside in lipid bilayers, restricting their endogenous activity to a relatively specialized biochemical environment. Without a reference phenotype, the application of systematic screens to profile candidate membrane proteins is not immediately possible. Bioinformatics has begun to show its effectiveness in focusing the functional characterization of orphan proteins of a particular functional class, such as channels or receptors. Here we discuss integration of experimental and bioinformatics approaches for characterizing the orphan membrane proteome. By analyzing the human genome, a landscape reference for the human transmembrane genome is provided.

Intense picosecond pulsed electric fields induce apoptosis through a mitochondrial-mediated pathway in HeLa cells

Science.gov (United States)

HUA, YUAN-YUAN; WANG, XIAO-SHU; ZHANG, YU; YAO, CHEN-GUO; ZHANG, XI-MING; XIONG, ZHENG-AI

2012-01-01

The application of pulsed electric fields (PEF) is emerging as a new technique for tumor therapy. Picosecond pulsed electric fields (psPEF) can be transferred to target deep tissue non-invasively and precisely, but the research of the biological effects of psPEF on cells is limited. Electric theory predicts that intense psPEF will target mitochondria and lead to changes in transmembrane potential, therefore, it is hypothesized that it can induce mitochondrial-mediated apoptosis. HeLa cells were exposed to psPEF in this study to investigate this hypothesis. MTT assay demonstrated that intense psPEF significantly inhibited the proliferation of HeLa cells in a dose-dependent manner. Typical characteristics of apoptosis in HeLa cells were observed, using transmission electron microscopy. Loss of mitochondrial transmembrane potential was explored using laser scanning confocal microscopy with Rhodamine-123 (Rh123) staining. Furthermore, the mitochondrial apoptotic events were also confirmed by western blot analysis for the release of cytochrome C and apoptosis-inducing factor from mitochondria into the cytosol. In addition, activation of caspase-3, caspase-9, upregulation of Bax, p53 and downregulation of Bcl-2 were observed in HeLa cells also indicating apoptosis. Taken together, these results demonstrate that intense psPEF induce cell apoptosis through a mitochondrial-mediated pathway. PMID:22307872

Polarized gas targets for storage rings

International Nuclear Information System (INIS)

Holt, R.J.

1990-01-01

It is widely recognized that polarized gas targets in electron storage rings represent a new opportunity for precision nuclear physics studies. New developments in polarized target technology specific to internal applications will be discussed. In particular, polarized gas targets have been used in the VEPP-3 electron ring in Novosibirsk. A simple storage cell was used to increase the total target thickness by a factor of 15 over the simple gas jet target from an atomic beam source. Results from the initial phase of this project will be reported. In addition, the plans for increasing the luminosity by an additional order or magnitude will be presented. The application of this work to polarized hydrogen and deuterium targets for the HERA ring will be noted. The influence of beam-induced depolarization, a phenomena encountered in short-pulse electron storage rings, will be discussed. Finally, the performance tests of laser-driven sources will be presented. 8 refs., 12 figs., 1 tab

Defining the transmembrane helix of M2 protein from influenza A by molecular dynamics simulations in a lipid bilayer

NARCIS (Netherlands)

Forrest, LR; Tieleman, DP; Sansom, MSP

Integral membrane proteins containing at least one transmembrane (TM) alpha-helix are believed to account for between 20% and 30% of most genomes. There are several algorithms that accurately predict the number and position of TM helices within,a membrane protein sequence. However, these methods

Self-Assembling Organic Nanopores as Synthetic Transmembrane Channels with Tunable Functions

Science.gov (United States)

Wei, Xiaoxi

A long-standing goal in the area of supramolecular self-assembly involves the development of synthetic ion/water channels capable of mimicking the mass-transport characteristics of biological channels and pores. Few examples of artificial transmembrane channels with large lumen, high conductivity and selectivity are known. A review of pronounced biological transmembrane protein channels and some representative synthetic models have been provided in Chapter 1, followed by our discovery and initial investigation of shape-persistent oligoamide and phenylene ethynylene macrocycles as synthetic ion/water channels. In Chapter 2, the systematic structural modification of oligoamide macrocycles 1, the so-called first-generation of these shape-persistent macrocycles, has led to third-generation macrocycles 3. The third generation was found to exhibit unprecedented, strong intermolecular association in both the solid state and solution via multiple techniques including X-ray diffraction (XRD), SEM, and 1H NMR. Fluorescence spectroscopy paired with dynamic light scattering (DLS) revealed that macrocycles 3 can assemble into a singly dispersed nanotubular structure in solution. The resultant self-assembling pores consisting of 3 were examined by HPTS-LUVs assays and BLM studies (Chapter 3) and found to form cation-selective (PK+/PCl- = 69:1) transmembrane ion channels with large conductance (200 ˜ 2000 pS for alkali cations) and high stability with open times reaching to 103 seconds. Tuning the aggregation state of macrocycles by choosing an appropriate polar solvent mixture (i.e., 3:1, THF:DMF, v/v) and concentration led to the formation of ion channels with well-defined square top behavior. A parallel study using DLS to examine the size of aggregates was used in conjunction with channel activity assays (LUVs/BLM) to reveal the effects of the aggregation state on channel activity. Empirical evidence now clearly indicates that a preassembled state, perhaps that of a

PheVI:09 (Phe6.44) as a sliding microswitch in seven-transmembrane (7TM) G protein-coupled receptor activation

DEFF Research Database (Denmark)

Valentin-Hansen, Louise; Holst, Birgitte; Frimurer, Thomas M

2012-01-01

In seven-transmembrane (7TM), G protein-coupled receptors, highly conserved residues function as microswitches, which alternate between different conformations and interaction partners in an extended allosteric interface between the transmembrane segments performing the large scale conformational......-V into a tight pocket generated by five hydrophobic residues protruding from TM-III and TM-V. Of these, the residue in position III:16 (3.40) (often an Ile or Val) appears to function as a barrier or gate for the transition between inactive and active conformation. Mutational analysis showed that PheVI:09...... an aromatic microswitch that stabilizes the active, outward tilted conformation of TM-VI relative to TM-III by sliding into a tight hydrophobic pocket between TM-III and TM-V and that the hydrophobic residue in position III:16 constitutes a gate for this transition....

Digital superconductive electronics: where does it fit?

International Nuclear Information System (INIS)

Bedard, F.D.

1997-01-01

Superconductivity has been pursuing the world of digital electronics ever since 1956. During all this time its supporters have emphasized the 'obvious' advantages of 'low power' and 'unmatched device speed'. However, still no digital electronics product is in a system; silicon-based digital devices overwhelm all others in the applications world. This is true today, in spite of even faster superconductive devices and circuits as well as greatly reduced power. The major issues that must be faced and resolved in order to insert this immature technology into the market place are the following: (i) What is the problem for which we are the enabling solution? (ii) Is it important enough to warrant the 'inconvenience' of cryogenics? (iii) Can we make the cryogenics 'transparent' to the user? (iv) Can we interface to the ubiquitous room-temperature electronics? (v) At what size (chip count, MCM count) are we attractive? In spite of the customer reluctance, there are some very important niches which this technology can fit provided that we take lessons from those which support the silicon 'master'. Magnetics (data storage), GaAs (optical communications) and optics (communications, storage) are all examples. These questions of system applications, examples of small- or large-scale uses and the problems to be solved will be discussed together with competing technology alternatives. (author)

Extrinsic pseudocapacitve Li-ion storage of SnS anode via lithiation-induced structural optimization on cycling

Science.gov (United States)

Lian, Qingwang; Zhou, Gang; Liu, Jiatu; Wu, Chen; Wei, Weifeng; Chen, Libao; Li, Chengchao

2017-10-01

Here, we report a new enhanced extrinsic pseudocapacitve Li-ion storage mechanism via lithiation-induced structural optimization strategy. The flower-like C@SnS and bulk SnS exhibit initial capacity decay and subsequent increase of capacity on cycling. After a long-term lithiation/delithiation process, flower-like C@SnS and bulk SnS exhibit improved rate performance and reversible capacity in comparison with those of initial state. Moreover, a high capacity of 530 mAh g-1 is still remained even after 1550 cycles at a high current density of 5.0 A g-1 for flower-like C@SnS after pre-lithiation of 350 cycles. According to the comprehensive analysis of structural evolution and electrochemical performance, it demonstrates that SnS electrodes experience crystal size reduction and further amorphization on cycling, which enhances the reversibility of conversion reaction for SnS, leading to increasing capacity. On the other hand, surface-dominated extrinsic pseudocapacitive contribution results in enhanced rate performance because electrodes expose a large fraction of Li+ sites on surface or near-surface region with structural optimization on cycling. This study reveals that extrinsic pseudocapacitance of SnS can be stimulated via lithiation-induced structural optimization, which gives rise to high-rate and long-lived performances.

Extended storage of low-level radioactive waste: potential problem areas

International Nuclear Information System (INIS)

Siskind, B.; Dougherty, D.R.; MacKenzie, D.R.

1985-12-01

If a state or state compact does not have adequate disposal capacity for low-level radioactive waste (LLRW) by 1986 as required by the Low-Level Waste Policy Act, then extended storage of certain LLRW may be necessary. In this report, extended storage of LLRW is considered in order to determine for the Nuclear Regulatory Commission areas of concern and actions recommended to resolve these concerns. The focus is on the properties and performance of the waste form and waste container. Storage alternatives are considered in order to characterize the likely storage environments for these wastes. The areas of concern about extended storage of LLRW are grouped into two categories: (1) Performance of the waste form and/or container during storage, e.g., radiolytic gas generation, radiation-enhanced degradation of polymeric materials, and corrosion. (2) Effects of extended storage on the properties of the waste form and/or container that are important after storage (e.g., radiation-induced embrittlement of high-density polyethylene and the weakening of steel containers resulting from corrosion). A discussion is given of additional information and actions required to address these concerns

Fitness Level Modulates Intraocular Pressure Responses to Strength Exercises.

Science.gov (United States)

Vera, Jesús; Jiménez, Raimundo; Redondo, Beatríz; Cárdenas, David; García-Ramos, Amador

2018-06-01

Purpose/Aim: The execution of strength exercises has demonstrated to increase the intraocular pressure (IOP) levels, and it may have a negative impact on the ocular health. We aimed to explore the influence of fitness level on the acute IOP response to strength exercises performed under different loading conditions, as well as to test whether the IOP responses differ between the bench press and jump squat when performed against the same relative loads. Forty military personnel males were divided in two subgroups (20 high-fit and 20 low-fit) based on their relative to body mass one-repetition maximum (1-RM). Participants performed an incremental loading test in the bench press and jump squat exercises, and IOP was assessed before and after each repetition by rebound tonometry. IOP increased immediately after executing both exercises (p e., high-fit and low-fit) and in both exercises (R 2 range: 0.81-1.00). Higher fitness level attenuated the IOP rise produced by both exercises (p < 0.01 in both cases). The bench press induced higher IOP increments than the jump squat for both groups at relative loads of ~50%1-RM and ~60%1-RM (p < 0.01 in all cases). These data indicate that IOP increases as a consequence of performing strength exercises, being the increment accentuated with the increase of the load and in the bench press compared to the jump squat exercise. Of special importance would be that the IOP responses were significantly reduced in high-fit individuals. These findings should be addressed in glaucoma patients.

On the ''circular vacuum noise'' in electron storage rings

International Nuclear Information System (INIS)

Rosu, H.

1992-02-01

We clarify in some essential points the proposal of Bell and Leinaas to measure the circular Unruh effect in storage rings. In particular the term 'circular Unruh effect' is inappropriate and should be replaced by the better 'circular vacuum noise'. This concept has been used by Takagi in his PTP Supplement of 1986 and corresponds best to the BL discussion. The BL resonance behavior does not fit to the SPEAR first order betatron resonance at 3.605 GeV, but of course, the real experimental situation is much more complicated, corresponding, as a matter of fact, to the rather general term 'synchrotron noise'. The detailed aspects of the synchrotron noise are, as yet, not very well understood. Besides, the much more practical accelerator jargon is to be preferred. We also include a section with comments on radiometry at storage rings. (author). 27 refs

Energy Storage.

Science.gov (United States)

Eaton, William W.

Described are technological considerations affecting storage of energy, particularly electrical energy. The background and present status of energy storage by batteries, water storage, compressed air storage, flywheels, magnetic storage, hydrogen storage, and thermal storage are discussed followed by a review of development trends. Included are…

The Association Between Self-Rated Fitness and Cardiorespiratory Fitness in Adults

DEFF Research Database (Denmark)

Jensen, Karina Gregersen; Rosthøj, Susanne; Linneberg, Allan

2018-01-01

To assess criterion validity of a single item question on self-rated physical fitness against objectively measured cardiorespiratory fitness. From the Health2008 study 749 men and women between 30 and 60 years of age rated their fitness as excellent, very good, good, fair or poor. Cardiorespiratory...... fitness was estimated with the watt-max test. Agreement between self-rated and objectively measured physical fitness was assessed by Cohen's weighted kappa coefficient. Correlation was determined by Goodman & Kruskal's gamma correlation coefficient. All analyses were stratified according to gender. Data...... from 323 men and 426 women were analysed. There was a slight agreement between self-rated and objectively measured fitness in men (weighted kappa: 0.18, [95%CI: 0.13;0.23]) and a fair agreement in women (weighted kappa: 0.27, [95%CI: 0.22;0.32]). In both genders, self-rated fitness was positively...

Duties of the Physikalisch-Technische Bundesanstalt (PTB) in connection with radioactive waste safeguarding and ultimate storage

International Nuclear Information System (INIS)

Roethemeyer, H.

1977-01-01

An outline of the history and duties of the Physikalisch-Technische Bundesanstalt (PTB) is to illustrate that the new duties of the PTB in connection with radioactive substance safeguarding and ultimate storage fit in very well with the range of duties of the PTB. The organisatory and technical accomplishment of these duties in cooperation with a building and operating company and with industry is explained. The department of the PTB for the 'safeguarding and ultimate storage of radioactive wastes' has an examining, appraising and licensing function in connection with construction, operation and shutdown of safety facilities. Methods for the safeguarding and ultimate storage of all the radioactive wastes in the Federal Republic of Germany are described. (HS) [de

FItness programy a individuální přístup ve fitness

OpenAIRE

Rambous, Milan

2008-01-01

Souhrn: Tato diplomová práce se zabývá problematikou fitness programů a individuálru'ho přístupu ve fitness centrech. Celé téma zahrnuje rozpracování postupu při vytváření fitness programů a roli osobního trenéra ve fitness. Dále jsou zde uvedeny specifika některých fitness programů a v empirické části pak příklad dvou individuálních fitness programů. Název práce: Fitness programy a individuálnípřístup ve fitness Title: FITNESS PROGRAMS AND INDIVIDUAL CARE IN FITNESS Cíle práce: 1. podrobný p...

Injection into the LNLS UVX electron storage ring

International Nuclear Information System (INIS)

Lin, Liu

1991-01-01

To inject the 1.15 GeV electron storage ring - UVX - a beam from a linear accelerator - MAIRA - is used. The electrons are injected and accumulated at low energy (100MeV) until the nominal current of 100 mA is reached and than are ramped to the nominal energy. A study on a conventional injection scheme has been carried out. Two injection modes are investigated: injection with the phase ellipse parameters matched and mismatched to the ring's acceptance. The mismatched mode is optimized to fit the maximum of the injected beam into the acceptance

Nuclear fuel storage

International Nuclear Information System (INIS)

Bevilacqua, F.

1981-01-01

A nuclear fuel storage apparatus for use in a water-filled pool is fabricated of a material such as stainless steel in the form of an egg crate structure having vertically extending openings. Fuel may be stored in this basic structure in a checkerboard pattern with high enrichment fuel, or in all openings when the fuel is of low effective enrichment. Inserts of a material such as stainless steel are adapted to fit within these openings so that a water gap and, therefore, a flux trap is formed between adjacent fuel storage locations. These inserts may be added at a later time and fuel of a higher enrichment may be stored in each opening. When it is desired to store fuel of still greater enrichment, poison plates may be added to the water gap formed by the installed insert plates, or substituted for the insert plates. Alternately, or in addition, fuel may be installed in high neutron absorption poison boxes which surround the fuel assembly. The stainless steel inserts and the poison plates are each not required until the capacity of the basic egg crate structure is approached. Purchase of these items can, therefore, be deferred for many years. Should the fuel to be stored be of higher enrichment than initially forecast, the deferred decision on the poison plates makes it possible to obtain increased poison in the plates to satisfy the newly discovered requirement

Underground Storage Tanks - Storage Tank Locations

Data.gov (United States)

NSGIC Education | GIS Inventory — A Storage Tank Location is a DEP primary facility type, and its sole sub-facility is the storage tank itself. Storage tanks are aboveground or underground, and are...

Computer code FIT

International Nuclear Information System (INIS)

Rohmann, D.; Koehler, T.

1987-02-01

This is a description of the computer code FIT, written in FORTRAN-77 for a PDP 11/34. FIT is an interactive program to decude position, width and intensity of lines of X-ray spectra (max. length of 4K channels). The lines (max. 30 lines per fit) may have Gauss- or Voigt-profile, as well as exponential tails. Spectrum and fit can be displayed on a Tektronix terminal. (orig.) [de

Localization of the transmembrane proteoglycan syndecan-4 and its regulatory kinases in costameres of rat cardiomyocytes: a deconvolution microscopic study

DEFF Research Database (Denmark)

VanWinkle, W Barry; Snuggs, Mark B; De Hostos, Eugenio L

2002-01-01

Syndecan-4 (syn-4), a transmembrane heparan sulfate-containing proteoglycan, is unique among the four members of the syndecan family in its specific cellular localization to complex cytoskeletal adhesion sites, i.e., focal adhesions. During early phenotypic redifferentiation of neonatal cardiomyo...

The effects of temperature on the crystalline properties and resistant starch during storage of white bread.

Science.gov (United States)

Sullivan, William R; Hughes, Jeff G; Cockman, Russell W; Small, Darryl M

2017-08-01

Resistant starch (RS) can form during storage of foods, thereby bestowing a variety of potential health benefits. The purpose of the current study has been to determine the influence of storage temperature and time on the crystallinity and RS content of bread. Loaves of white bread were baked and stored at refrigeration, frozen and room temperatures with analysis over a period of zero to seven days. RS determination and X-ray diffraction (XRD) were used to evaluate the influence of storage temperature and time on total crystallinity and RS content. The rate of starch recrystallisation was affected by storage temperature and time, where refrigeration temperatures accelerated RS formation and total crystallinity more than storage time at both frozen and room temperature. A strong statistical model has been established between RS formation in bread and XRD patterns, having a 96.7% fit indicating the potential of XRD to measure RS concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification and functional comparison of seven-transmembrane G-protein-coupled BILF1 receptors in recently discovered nonhuman primate lymphocryptoviruses

DEFF Research Database (Denmark)

Spiess, Katja; Fares, Suzan; Sparre-Ulrich, Alexander H

2015-01-01

Coevolution of herpesviruses with their respective host has resulted in a delicate balance between virus-encoded immune evasion mechanisms and host antiviral immunity. BILF1 encoded by human Epstein-Barr virus (EBV) is a 7-transmembrane (7TM) G-protein-coupled receptor (GPCR) with multiple immuno...

Estimating fault stability and sustainable fluid pressures for underground storage of CO2 in porous rock

International Nuclear Information System (INIS)

Streit, J.E.; Hillis, R.R.

2004-01-01

Geomechanical modelling of fault stability is an integral part of Australia's GEODISC research program to ensure the safe storage of carbon dioxide in subsurface reservoirs. Storage of CO 2 in deep saline formations or depleted hydrocarbon reservoirs requires estimates of sustainable fluid pressures that will not induce fracturing or create fault permeability that could lead to CO 2 escape. Analyses of fault stability require the determination of fault orientations, ambient pore fluid pressures and in situ stresses in a potential storage site. The calculation of effective stresses that act on faults and reservoir rocks lead then to estimates of fault slip tendency and fluid pressures sustainable during CO 2 storage. These parameters can be visualized on 3D images of fault surfaces or in 2D projections. Faults that are unfavourably oriented for reactivation can be identified from failure plots. In depleted oil and gas fields, modelling of fault and rock stability needs to incorporate changes of the pre-production stresses that were induced by hydrocarbon production and associated pore pressure depletion. Such induced stress changes influence the maximum sustainable formation pressures and CO 2 storage volumes. Hence, determination of in situ stresses and modelling of fault stability are essential prerequisites for the safe engineering of subsurface CO 2 injection and the modelling of storage capacity. (author)

Effect of Tissue Heterogeneity on the Transmembrane Potential of Type-1 Spiral Ganglion Neurons: A Simulation Study.

Science.gov (United States)

Sriperumbudur, Kiran Kumar; Pau, Hans Wilhelm; van Rienen, Ursula

2018-03-01

Electric stimulation of the auditory nerve by cochlear implants has been a successful clinical intervention to treat the sensory neural deafness. In this pathological condition of the cochlea, type-1 spiral ganglion neurons in Rosenthal's canal play a vital role in the action potential initiation. Various morphological studies of the human temporal bones suggest that the spiral ganglion neurons are surrounded by heterogeneous structures formed by a variety of cells and tissues. However, the existing simulation models have not considered the tissue heterogeneity in the Rosenthal's canal while studying the electric field interaction with spiral ganglion neurons. Unlike the existing models, we have implemented the tissue heterogeneity in the Rosenthal's canal using a computationally inexpensive image based method in a two-dimensional finite element model. Our simulation results suggest that the spatial heterogeneity of surrounding tissues influences the electric field distribution in the Rosenthal's canal, and thereby alters the transmembrane potential of the spiral ganglion neurons. In addition to the academic interest, these results are especially useful to understand how the latest tissue regeneration methods such as gene therapy and drug-induced resprouting of peripheral axons, which probably modify the density of the tissues in the Rosenthal's canal, affect the cochlear implant functionality.

Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components

DEFF Research Database (Denmark)

Kücükakin, Bülent; Kocak, Volkan; Lykkesfeldt, Jens

2011-01-01

of buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days. Study design and methods. Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35......, respectively. The samples were analysed for various biomarkers expressing the oxidative stress and inflammation, including malondialdehyde (MDA), α-tocopherol (AT), dehydroascorbic acid (DHA), ascorbate (ASC), YKL-40 and interleukin-6 (IL-6). Results. The levels ofMDA, ASC, DHA, IL-6 and YKL-40 changed...... significantly during the storage period (p oxidative and inflammatory stress during a storage period...

The FORCE Fitness Profile--Adding a Measure of Health-Related Fitness to the Canadian Armed Forces Operational Fitness Evaluation.

Science.gov (United States)

Gagnon, Patrick; Spivock, Michael; Reilly, Tara; Mattie, Paige; Stockbrugger, Barry

2015-11-01

In 2013, the Canadian Armed Forces (CAF) implemented the Fitness for Operational Requirements of Canadian Armed Forces Employment (FORCE), a field expedient fitness test designed to predict the physical requirements of completing common military tasks. Given that attaining this minimal physical fitness standard may not represent a challenge to some personnel, a fitness incentive program was requested by the chain of command to recognize and reward fitness over and above the minimal standard. At the same time, it was determined that the CAF would benefit from a measure of general health-related fitness, in addition to this measure of operational fitness. The resulting incentive program structure is based on gender and 8 age categories. The results on the 4 elements of the FORCE evaluation were converted to a point scale from which normative scores were derived, where the median score corresponds to the bronze level, and silver, gold, and platinum correspond to a score which is 1, 2, and 3 SDs above this median, respectively. A suite of rewards including merit board point toward promotions and recognition on the uniform and material rewards was developed. A separate group rewards program was also tabled, to recognize achievements in fitness at the unit level. For general fitness, oxygen capacity was derived from FORCE evaluation results and combined with a measure of abdominal circumference. Fitness categories were determined based on relative risks of mortality and morbidity for each age and gender group. Pilot testing of this entire program was performed with 624 participants to assess participants' reactions to the enhanced test, and also to verify logistical aspects of the electronic data capture, calculation, and transfer system. The newly dubbed fitness profile program was subsequently approved by the senior leadership of the CAF and is scheduled to begin a phased implementation in June 2015.

Conformational Selection and Induced Fit for RNA Polymerase and RNA/DNA Hybrid Backtracked Recognition

Directory of Open Access Journals (Sweden)

Haifeng eChen

2015-11-01

Full Text Available RNA polymerase catalyzes transcription with a high fidelity. If DNA/RNA mismatch or DNA damage occurs downstream, a backtracked RNA polymerase can proofread this situation. However, the backtracked mechanism is still poorly understood. Here we have performed multiple explicit-solvent molecular dynamics (MD simulations on bound and apo DNA/RNA hybrid to study backtracked recognition. MD simulations at room temperature suggest that specific electrostatic interactions play key roles in the backtracked recognition between the polymerase and DNA/RNA hybrid. Kinetics analysis at high temperature shows that bound and apo DNA/RNA hybrid unfold via a two-state process. Both kinetics and free energy landscape analyses indicate that bound DNA/RNA hybrid folds in the order of DNA/RNA contracting, the tertiary folding and polymerase binding. The predicted Φ-values suggest that C7, G9, dC12, dC15 and dT16 are key bases for the backtracked recognition of DNA/RNA hybrid. The average RMSD values between the bound structures and the corresponding apo ones and Kolmogorov-Smirnov (KS P test analyses indicate that the recognition between DNA/RNA hybrid and polymerase might follow an induced fit mechanism for DNA/RNA hybrid and conformation selection for polymerase. Furthermore, this method could be used to relative studies of specific recognition between nucleic acid and protein.

Exploiting hydrophobicity for efficient production of transmembrane helices for structure determination by NMR spectroscopy

DEFF Research Database (Denmark)

Bugge, Katrine Østergaard; Steinocher, Helena; Brooks, Andrew J.

2015-01-01

-labeled protein. In this work, we have exploited the hydrophobic nature of membrane proteins to develop a simple and efficient production scheme for isotope-labeled single-pass transmembrane domains (TMDs) with or without intrinsically disordered regions. We have evaluated the applicability and limitations...... of the strategy using seven membrane protein variants that differ in their overall hydrophobicity and length and show a recovery for suitable variants of >70%. The developed production scheme is cost-efficient and easy to implement and has the potential to facilitate an increase in the number of structures...

Pentameric ligand-gated ion channels exhibit distinct transmembrane domain archetypes for folding/expression and function.

Science.gov (United States)

Therien, J P Daniel; Baenziger, John E

2017-03-27

Although transmembrane helix-helix interactions must be strong enough to drive folding, they must still permit the inter-helix movements associated with conformational change. Interactions between the outermost M4 and adjacent M1 and M3 α-helices of pentameric ligand-gated ion channels have been implicated in folding and function. Here, we evaluate the role of different physical interactions at this interface in the function of two prokaryotic homologs, GLIC and ELIC. Strikingly, disruption of most interactions in GLIC lead to either a reduction or a complete loss of expression and/or function, while analogous disruptions in ELIC often lead to gains in function. Structural comparisons suggest that GLIC and ELIC represent distinct transmembrane domain archetypes. One archetype, exemplified by GLIC, the glycine and GABA receptors and the glutamate activated chloride channel, has extensive aromatic contacts that govern M4-M1/M3 interactions and that are essential for expression and function. The other archetype, exemplified by ELIC and both the nicotinic acetylcholine and serotonin receptors, has relatively few aromatic contacts that are detrimental to function. These archetypes likely have evolved different mechanisms to balance the need for strong M4 "binding" to M1/M3 to promote folding/expression, and the need for weaker interactions that allow for greater conformational flexibility.

Impact of biofilm accumulation on transmembrane and feed channel pressure drop: Effects of crossflow velocity, feed spacer and biodegradable nutrient

KAUST Repository

Dreszer, C.; Flemming, H. C.; Zwijnenburg, A.; Kruithof, J. C.; Vrouwenvelder, Johannes S.

2014-01-01

. As biodegradable nutrient, acetate was dosed to the feed water (1.0 and 0.25mgL-1 carbon) to enhance biofilm accumulation in the monitors. The studies showed that biofilm formation caused an increased transmembrane resistance and feed channel pressure drop

Investigation of physical detection markers in irradiated foods under different radiation sources and post-irradiation storage conditions

Energy Technology Data Exchange (ETDEWEB)

Kwon, Joong Ho; Kim, Gui Ran; Ahn, Jae Jun; Kim, Dong Gil; Jin, Qiong Wen; Park, Ju Hwan; Lee, Ji Hyun [Kyungpook National University, Daegu (Korea, Republic of)

2010-04-15

In PSL analysis, all unirradiated samples showed less than 700 (negative) photon counts (PCs). At 5 kGy, spice samples showed PCs in range of 700-5,000 (intermediate), while grains, legumes, root-crops, and seasonings samples showed PCs over 5,000 (positive). This PSL based-detection of radiation treatment was possible even after 24 months of storage. In TL analysis, TL glow curve was characteristically different between unirradiated and irradiated samples. Glow curves were observed in temperature ranges of 150-250 .deg. C for irradiated and over 300 .deg. C for unirradiated samples. TL ratio (TL{sub 1}/TL{sub 2}) provided valuable additional confirmations as unirradiated sample showed values less than 0.1, while irradiated sample showed more than 0.1. However, with storage time, TL intensity and TL ratio decreased but discrimination was still possible even after storage of 24 months. Samples stored at room temperature with exposure to direct or indirect light enhanced the mentioned decrease of TL intensity and TL ratio as compared to low temperature storage in dark room. In ESR analysis, legumes and spices showed radiation-induced cellulose radicals, while seasonings showed multi-component signals of radiation-induced crystalline sugar radical. These radiation-induced radicals could be potential markers for the detection of radiation treatments in subjected samples. The decreasing trend was also found for radiation-specific ESR signals of cellulose and crystalline sugar radicals during storage. However, radiation-induced radicals in legumes, powdered pepper and seasonings were detectable even after 6 months of storage

A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER

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Haga Christopher L

2007-09-01

Full Text Available Abstract Background In mouse the cytokine interleukin-7 (IL-7 is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. Results Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER. The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR, a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart. Conclusion The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.

Scenario simulation based assessment of subsurface energy storage

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Beyer, C.; Bauer, S.; Dahmke, A.

2014-12-01

Energy production from renewable sources such as solar or wind power is characterized by temporally varying power supply. The politically intended transition towards renewable energies in Germany („Energiewende") hence requires the installation of energy storage technologies to compensate for the fluctuating production. In this context, subsurface energy storage represents a viable option due to large potential storage capacities and the wide prevalence of suited geological formations. Technologies for subsurface energy storage comprise cavern or deep porous media storage of synthetic hydrogen or methane from electrolysis and methanization, or compressed air, as well as heat storage in shallow or moderately deep porous formations. Pressure build-up, fluid displacement or temperature changes induced by such operations may affect local and regional groundwater flow, geomechanical behavior, groundwater geochemistry and microbiology. Moreover, subsurface energy storage may interact and possibly be in conflict with other "uses" like drinking water abstraction or ecological goods and functions. An utilization of the subsurface for energy storage therefore requires an adequate system and process understanding for the evaluation and assessment of possible impacts of specific storage operations on other types of subsurface use, the affected environment and protected entities. This contribution presents the framework of the ANGUS+ project, in which tools and methods are developed for these types of assessments. Synthetic but still realistic scenarios of geological energy storage are derived and parameterized for representative North German storage sites by data acquisition and evaluation, and experimental work. Coupled numerical hydraulic, thermal, mechanical and reactive transport (THMC) simulation tools are developed and applied to simulate the energy storage and subsurface usage scenarios, which are analyzed for an assessment and generalization of the imposed THMC

Neutrino Signals in Electron-Capture Storage-Ring Experiments

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Avraham Gal

2016-06-01

Full Text Available Neutrino signals in electron-capture decays of hydrogen-like parent ions P in storage-ring experiments at GSI are reconsidered, with special emphasis placed on the storage-ring quasi-circular motion of the daughter ions D in two-body decays P → D + ν e . It is argued that, to the extent that daughter ions are detected, these detection rates might exhibit modulations with periods of order seconds, similar to those reported in the GSI storage-ring experiments for two-body decay rates. New dedicated experiments in storage rings, or using traps, could explore these modulations.

The MARVEL transmembrane motif of occludin mediates oligomerization and targeting to the basolateral surface in epithelia.

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Yaffe, Yakey; Shepshelovitch, Jeanne; Nevo-Yassaf, Inbar; Yeheskel, Adva; Shmerling, Hedva; Kwiatek, Joanna M; Gaus, Katharina; Pasmanik-Chor, Metsada; Hirschberg, Koret

2012-08-01

Occludin (Ocln), a MARVEL-motif-containing protein, is found in all tight junctions. MARVEL motifs are comprised of four transmembrane helices associated with the localization to or formation of diverse membrane subdomains by interacting with the proximal lipid environment. The functions of the Ocln MARVEL motif are unknown. Bioinformatics sequence- and structure-based analyses demonstrated that the MARVEL domain of Ocln family proteins has distinct evolutionarily conserved sequence features that are consistent with its basolateral membrane localization. Live-cell microscopy, fluorescence resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) were used to analyze the intracellular distribution and self-association of fluorescent-protein-tagged full-length human Ocln or the Ocln MARVEL motif excluding the cytosolic C- and N-termini (amino acids 60-269, FP-MARVEL-Ocln). FP-MARVEL-Ocln efficiently arrived at the plasma membrane (PM) and was sorted to the basolateral PM in filter-grown polarized MDCK cells. A series of conserved aromatic amino acids within the MARVEL domain were found to be associated with Ocln dimerization using BiFC. FP-MARVEL-Ocln inhibited membrane pore growth during Triton-X-100-induced solubilization and was shown to increase the membrane-ordered state using Laurdan, a lipid dye. These data demonstrate that the Ocln MARVEL domain mediates self-association and correct sorting to the basolateral membrane.

Simulations of skin barrier function: free energies of hydrophobic and hydrophilic transmembrane pores in ceramide bilayers.

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Notman, Rebecca; Anwar, Jamshed; Briels, W J; Noro, Massimo G; den Otter, Wouter K

2008-11-15

Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier function of the skin. We have used the potential of mean constraint force (PMCF) method to calculate the free energy of pore formation in ceramide bilayers in both the innate gel phase and in the DMSO-induced fluidized state. Our simulations show that the fluid phase bilayers form archetypal water-filled hydrophilic pores similar to those observed in phospholipid bilayers. In contrast, the rigid gel-phase bilayers develop hydrophobic pores. At the relatively small pore diameters studied here, the hydrophobic pores are empty rather than filled with bulk water, suggesting that they do not compromise the barrier function of ceramide membranes. A phenomenological analysis suggests that these vapor pores are stable, below a critical radius, because the penalty of creating water-vapor and tail-vapor interfaces is lower than that of directly exposing the strongly hydrophobic tails to water. The PMCF free energy profile of the vapor pore supports this analysis. The simulations indicate that high DMSO concentrations drastically impair the barrier function of the skin by strongly reducing the free energy required for pore opening.

Gas storage materials, including hydrogen storage materials

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Mohtadi, Rana F; Wicks, George G; Heung, Leung K; Nakamura, Kenji

2013-02-19

A material for the storage and release of gases comprises a plurality of hollow elements, each hollow element comprising a porous wall enclosing an interior cavity, the interior cavity including structures of a solid-state storage material. In particular examples, the storage material is a hydrogen storage material such as a solid state hydride. An improved method for forming such materials includes the solution diffusion of a storage material solution through a porous wall of a hollow element into an interior cavity.

New perspectives on potential hydrogen storage materials using high pressure.

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Song, Yang

2013-09-21

In addressing the global demand for clean and renewable energy, hydrogen stands out as the most suitable candidate for many fuel applications that require practical and efficient storage of hydrogen. Supplementary to the traditional hydrogen storage methods and materials, the high-pressure technique has emerged as a novel and unique approach to developing new potential hydrogen storage materials. Static compression of materials may result in significant changes in the structures, properties and performance that are important for hydrogen storage applications, and often lead to the formation of unprecedented phases or complexes that have profound implications for hydrogen storage. In this perspective article, 22 types of representative potential hydrogen storage materials that belong to four major classes--simple hydride, complex hydride, chemical hydride and hydrogen containing materials--were reviewed. In particular, their structures, stabilities, and pressure-induced transformations, which were reported in recent experimental works together with supporting theoretical studies, were provided. The important contextual aspects pertinent to hydrogen storage associated with novel structures and transitions were discussed. Finally, the summary of the recent advances reviewed and the insight into the future research in this direction were given.

Can exercise increase fitness and reduce weight in patients with schizophrenia and depression?

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Jesper eKrogh

2014-07-01

Full Text Available BackgroundPsychiatric patients have a reduced life expectancy of 15 to 20 years compared to the general population. Most years of lost life are due to excess mortality from somatic diseases. Sedentary lifestyle and medication is partly responsible for the high frequency of metabolic syndrome in this patient group and low levels of physical activity is associated with increased risk of cardiovascular disease, diabetes and all-cause mortality. This study aimed to review trials allocating patients with either schizophrenia or depression to exercise interventions for effect on cardiovascular fitness, strength and weight.MethodsWe searched Pubmed, Embase, and Psycinfo including randomized clinical trial allocating patients with either schizophrenia or depression to isolated exercise interventions.ResultsWe identified five trials including patients with schizophrenia and found little evidence that exercise could increase cardiovascular fitness or decrease weight. Nine exercise trials for patients with depression were identified increasing cardiovascular fitness by 11-30% and strength by 33-37%. No evidence in favor of exercise for weight reduction was found.ConclusionBased on the current evidence isolated exercise interventions are unlikely to improve cardiovascular fitness or induce weight loss in patients with schizophrenia. In patients with depression exercise interventions are likely to induce clinically relevant short term effects, however, due to lack of reporting little is known about the effect on cardiovascular fitness beyond the intervention and weight reduction. Future exercise trials regarding patients with mental illness should preferably measure changes in cardiovascular strength, repetition maximum and anthropometric outcomes. Ideally participants should be assessed beyond the intervention

Land Water Storage within the Congo Basin Inferred from GRACE Satellite Gravity Data

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Crowley, John W.; Mitrovica, Jerry X.; Bailey, Richard C.; Tamisiea, Mark E.; Davis, James L.

2006-01-01

GRACE satellite gravity data is used to estimate terrestrial (surface plus ground) water storage within the Congo Basin in Africa for the period of April, 2002 - May, 2006. These estimates exhibit significant seasonal (30 +/- 6 mm of equivalent water thickness) and long-term trends, the latter yielding a total loss of approximately 280 km(exp 3) of water over the 50-month span of data. We also combine GRACE and precipitation data set (CMAP, TRMM) to explore the relative contributions of the source term to the seasonal hydrological balance within the Congo Basin. We find that the seasonal water storage tends to saturate for anomalies greater than 30-44 mm of equivalent water thickness. Furthermore, precipitation contributed roughly three times the peak water storage after anomalously rainy seasons, in early 2003 and 2005, implying an approximately 60-70% loss from runoff and evapotranspiration. Finally, a comparison of residual land water storage (monthly estimates minus best-fitting trends) in the Congo and Amazon Basins shows an anticorrelation, in agreement with the 'see-saw' variability inferred by others from runoff data.

Identification of eight novel mutations in a collaborative analysis of a part of the second transmembrane domain of the CFTR gene

Energy Technology Data Exchange (ETDEWEB)

Mercier, B.; Audrezet, M.P.; Guillermit, H.; Quere, I.; Verlingue, C.; Ferec, C. (CDTS, Brest (France)); Lissens, W.; Bonduelle, M.; Liebaers, I. (University Hospital VUB, Brussels (Belgium)); Novelli, G.; Sangiuolo, F.; Dallapiccola, B. (IRCCS, Rotondo (Italy)); Kalaydjieva, L. (Inst. of Obstetrics, Sofia (Bulgaria)); Arce, M. De; Cashman, S. (Trinity College, Dublin (Ireland)); Kapranov, N. (NRC of medical Genetics, Moscow (Russian Federation)); Canki Klain, N. (Tozd Univerzitetna Ginekoloska Klinika, Ljubljana (Yugoslavia)); Lenoir, G. (Hopital des Enfants Malades Necker, Paris (France)); Chauveau, P. (Centre Hospitalier General, Le Havre (France)); Lanaerts, C. (Centre Hospitalier Regional et Universitaire, Amiens (France)); Rault, G. (Centre Helio-Marin, Roscoff (France))

1993-04-01

Cystic fibrosis transmembrane conductance regulator (CFTR), the gene responsible, when mutated, for cystic fibrosis (CF), spans over 230 kb on the long arm of chromosome 7 and is composed of 27 exons. The most common mutation responsible for CF worldwide is the deletion of a phenylalanine amino acid at codon 508 in the first nucleotide-binding fold and accounts for approximately 70% of CF chromosomes studied. More than 250 other mutations have been reported through the CF Genetic Analysis Consortium. The majority of the mutations previously described lie in the two nucleotide-binding folds. To explore exhaustively other regions of the gene, particularly exons coding for transmembrane domains, the authors have initiated a collaborative study between different laboratories to screen 369 non-[Delta]F508 CF chromosomes of seven ethnic European populations (Belgian, French, Breton, Irish, Italian, Yugoslavian, Russian). Among these chromosomes carrying an unidentified mutation, 63 were from Brittany, 50 of various French origin, 45 of Irish origin, 56 of Italian origin, 41 of Belgian origin, 2 of Turkish origin, 38 of Yugoslavian origin, 22 of Russian origin, and 52 of Bulgarian origin. Diagnostic criteria for CF included at least one positive sweat test and pulmonary disease with or without pancreatic disease. Using a denaturing gradient gel electrophoresis (DGGE) assay, they have identified eight novel mutations in exon 17b coding for part of the second transmembrane domain of the CFTR and they describe them in this report. 8 refs., 1 fig., 1 tab.

EVALUATION OF SODIUM CHLORIDE CRYSTALLIZATION IN MEMBRANE DISTILLATION CRYSTALLIZATION APPLIED TO WATER DESALINATION

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Y. N. Nariyoshi

Full Text Available Abstract Crystallization in a Direct Contact Membrane Distillation (DCMD process was studied both theoretically and experimentally. A mathematical model was proposed in order to predict the transmembrane flux in DCMD. The model fitted well experimental data for the system NaCl-H2O from undersaturated to supersaturated conditions in a specially designed crystallization setup at a bench scale. It was found that higher transmembrane fluxes induce higher temperature and concentration polarizations, as well as higher supersaturation in the vicinity of the solution-vapor interface. In this region, the supersaturation ratio largely exceeded the metastable limit for NaCl crystallization for the whole range of transmembrane fluxes of 0.37 to 1.54 kg/ (m2 h, implying that heterogeneous primary nucleation occurred close to such interface either in solution or on the membrane surface. Solids formed in solution accounted for 14 to 36% of the total solids, whereas solid formed on the membrane surface (fouling was responsible for 6 to 19%. The remaining solids deposited on other surfaces such as in pumps and pipe fittings. It was also discovered that, by increasing the supersaturation ratio, heterogeneous nucleation in solution increased and on the membrane surface decreased. Heterogeneous nuclei in solution grew in size both by a molecular mechanism and by agglomeration. Single crystals were cubic shaped with well-formed edges and dominant size of about 40 µm whereas agglomerates were about 240 µm in size. The approach developed here may be applied to understanding crystallization phenomena in Membrane Distillation Crystallization (MDC processes of any scale.

Comparing side chain packing in soluble proteins, protein-protein interfaces, and transmembrane proteins.

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Gaines, J C; Acebes, S; Virrueta, A; Butler, M; Regan, L; O'Hern, C S

2018-05-01

We compare side chain prediction and packing of core and non-core regions of soluble proteins, protein-protein interfaces, and transmembrane proteins. We first identified or created comparable databases of high-resolution crystal structures of these 3 protein classes. We show that the solvent-inaccessible cores of the 3 classes of proteins are equally densely packed. As a result, the side chains of core residues at protein-protein interfaces and in the membrane-exposed regions of transmembrane proteins can be predicted by the hard-sphere plus stereochemical constraint model with the same high prediction accuracies (>90%) as core residues in soluble proteins. We also find that for all 3 classes of proteins, as one moves away from the solvent-inaccessible core, the packing fraction decreases as the solvent accessibility increases. However, the side chain predictability remains high (80% within 30°) up to a relative solvent accessibility, rSASA≲0.3, for all 3 protein classes. Our results show that ≈40% of the interface regions in protein complexes are "core", that is, densely packed with side chain conformations that can be accurately predicted using the hard-sphere model. We propose packing fraction as a metric that can be used to distinguish real protein-protein interactions from designed, non-binding, decoys. Our results also show that cores of membrane proteins are the same as cores of soluble proteins. Thus, the computational methods we are developing for the analysis of the effect of hydrophobic core mutations in soluble proteins will be equally applicable to analyses of mutations in membrane proteins. © 2018 Wiley Periodicals, Inc.

Evaluating the economic cost of natural gas strategic storage restrictions

International Nuclear Information System (INIS)

Ejarque, Joao Miguel

2011-01-01

The European Commission wants to implement a single market for gas. One of the components of this market is a regulated provision for ''security of supply'' which consists of rules for the implementation and use of a given reserve stock of gas. We investigate the impact of this policy on the profitability of a storage operator, using data from Denmark and Italy. Keeping storage capacity constant, the costs of the strategic stock are around 20% of the value of the storage market for Denmark, and 16% for Italy. This cost is due to the inability to extract arbitrage profits from the captive stock. Furthermore, the strategic storage restriction induces behavior that would virtually never be replicated by a private storage operator in an unconstrained market, in particular in the first 6 months of the year when unconstrained firms empty their reservoirs much faster, suggesting the strategic restriction is unnecessarily distorting the market. (author)

Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice.

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Leonora E Long

Full Text Available The cannabis constituent cannabidiol (CBD possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ(9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT received vehicle or CBD (1, 50 or 100 mg/kg i.p. for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT(2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg also selectively increased GABA(A receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT(2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.

Incorporation of transmembrane hydroxide transport into the chemiosmotic theory.

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de Grey, A D

1999-10-01

A cornerstone of textbook bioenergetics is that oxidative ATP synthesis in mitochondria requires, in normal conditions of internal and external pH, a potential difference (delta psi) of well over 100 mV between the aqueous compartments that the energy-transducing membrane separates. Measurements of delta psi inferred from diffusion of membrane-permeant ions confirm this, but those using microelectrodes consistently find no such delta psi--a result ostensibly irreconcilable with the chemiosmotic theory. Transmembrane hydroxide transport necessarily accompanies mitochondrial ATP synthesis, due to the action of several carrier proteins; this nullifies some of the proton transport by the respiratory chain. Here, it is proposed that these carriers' structure causes the path of this "lost" proton flow to include a component perpendicular to the membrane but within the aqueous phases, so maintaining a steady-state proton-motive force between the water at each membrane surface and in the adjacent bulk medium. The conflicting measurements of delta psi are shown to be consistent with the response of this system to its chemical environment.

Sugar-mediated semidian oscillation of gene expression in the cassava storage root regulates starch synthesis

Energy Technology Data Exchange (ETDEWEB)

Jansson, Christer; Baguma, Yona; Sun, Chuanxin; Boren, Mats; Olsson, Helena; Rosenqvist, Sara; Mutisya, Joel; Rubaihayo, Patrick R.; Jansson, Christer

2008-01-15

Starch branching enzyme (SBE) activity in the cassava storage root exhibited a diurnal fluctuation, dictated by a transcriptional oscillation of the corresponding SBE genes. The peak of SBE activity coincided with the onset of sucrose accumulation in the storage, and we conclude that the oscillatory mechanism keeps the starch synthetic apparatus in the storage root sink in tune with the flux of sucrose from the photosynthetic source. When storage roots were uncoupled from the source, SBE expression could be effectively induced by exogenous sucrose. Turanose, a sucrose isomer that cannot be metabolized by plants, mimicked the effect of sucrose, demonstrating that downstream metabolism of sucrose was not necessary for signal transmission. Also glucose and glucose-1-P induced SBE expression. Interestingly, induction by sucrose, turanose and glucose but not glucose-1-P sustained an overt semidian (12-h) oscillation in SBE expression and was sensitive to the hexokinase (HXK) inhibitor glucosamine. These results suggest a pivotal regulatory role for HXK during starch synthesis. Abscisic acid (ABA) was another potent inducer of SBE expression. Induction by ABA was similar to that of glucose-1-P in that it bypassed the semidian oscillator. Both the sugar and ABA signaling cascades were disrupted by okadaic acid, a protein phosphatase inhibitor. Based on these findings, we propose a model for sugar signaling in regulation of starch synthesis in the cassava storage root.

There is no fitness but fitness, and the lineage is its bearer

Science.gov (United States)

2016-01-01

Inclusive fitness has been the cornerstone of social evolution theory for more than a half-century and has matured as a mathematical theory in the past 20 years. Yet surprisingly for a theory so central to an entire field, some of its connections to evolutionary theory more broadly remain contentious or underappreciated. In this paper, we aim to emphasize the connection between inclusive fitness and modern evolutionary theory through the following fact: inclusive fitness is simply classical Darwinian fitness, averaged over social, environmental and demographic states that members of a gene lineage experience. Therefore, inclusive fitness is neither a generalization of classical fitness, nor does it belong exclusively to the individual. Rather, the lineage perspective emphasizes that evolutionary success is determined by the effect of selection on all biological and environmental contexts that a lineage may experience. We argue that this understanding of inclusive fitness based on gene lineages provides the most illuminating and accurate picture and avoids pitfalls in interpretation and empirical applications of inclusive fitness theory. PMID:26729925

There is no fitness but fitness, and the lineage is its bearer.

Science.gov (United States)

Akçay, Erol; Van Cleve, Jeremy

2016-02-05

Inclusive fitness has been the cornerstone of social evolution theory for more than a half-century and has matured as a mathematical theory in the past 20 years. Yet surprisingly for a theory so central to an entire field, some of its connections to evolutionary theory more broadly remain contentious or underappreciated. In this paper, we aim to emphasize the connection between inclusive fitness and modern evolutionary theory through the following fact: inclusive fitness is simply classical Darwinian fitness, averaged over social, environmental and demographic states that members of a gene lineage experience. Therefore, inclusive fitness is neither a generalization of classical fitness, nor does it belong exclusively to the individual. Rather, the lineage perspective emphasizes that evolutionary success is determined by the effect of selection on all biological and environmental contexts that a lineage may experience. We argue that this understanding of inclusive fitness based on gene lineages provides the most illuminating and accurate picture and avoids pitfalls in interpretation and empirical applications of inclusive fitness theory. © 2016 The Author(s).

The design, fabrication, and testing of WETF high-quality, long-term-storage, secondary containment vessels

International Nuclear Information System (INIS)

Fisher, Kane J.

2000-01-01

Los Alamos National Laboratory's Weapons Engineering Tritium Facility (WETF) requires secondary containment vessels to store primary tritium containment vessels. The primary containment vessel provides the first boundary for tritium containment. The primary containment vessel is stored within a secondary containment vessel that provides the secondary boundary for tritium containment. WETF requires high-quality, long-term-storage, secondary tritium containment vessels that fit within a Mound-designed calorimeter. In order to qualify the WETF high-quality, long-term-storage, secondary containment vessels for use at WETF, steps have been taken to ensure the appropriate design, adequate testing, quality in fabrication, and acceptable documentation

Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

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T.I. Omotayo

2015-04-01

Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

The cystic fibrosis transmembrane recruiter the alter ego of CFTR as a multi-kinase anchor.

Science.gov (United States)

Mehta, Anil

2007-11-01

This review focuses on a newly discovered interaction between protein kinases involved in cellular energetics, a process that may be disturbed in cystic fibrosis for unknown reasons. I propose a new model where kinase-mediated cellular transmission of energy provides mechanistic insight to a latent role of the cystic fibrosis transmembrane conductance regulator (CFTR). I suggest that CFTR acts as a multi-kinase recruiter to the apical epithelial membrane. My group finds that, in the cytosol, two protein kinases involved in cell energy homeostasis, nucleoside diphosphate kinase (NDPK) and AMP-activated kinase (AMPK), bind one another. Preliminary data suggest that both can also bind CFTR (function unclear). The disrupted role of this CFTR-kinase complex as 'membrane transmitter to the cell' is proposed as an alternative paradigm to the conventional ion transport mediated and CFTR/chloride-centric view of cystic fibrosis pathogenesis. Chloride remains important, but instead, chloride-induced control of the phosphohistidine content of one kinase component (NDPK, via a multi-kinase complex that also includes a third kinase, CK2; formerly casein kinase 2). I suggest that this complex provides the necessary near-equilibrium conditions needed for efficient transmission of phosphate energy to proteins controlling cellular energetics. Crucially, a new role for CFTR as a kinase controller is proposed with ionic concentration acting as a signal. The model posits a regulatory control relay for energy sensing involving a cascade of protein kinases bound to CFTR.

Fitness Club

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Fitness Club

2010-01-01

Nordic Walking Please note that the subscriptions for the general fitness classes from July to December are open: Subscriptions general fitness classes Jul-Dec 2010 Sign-up to the Fitness Club mailing list here Nordic Walking: Sign-up to the Nordic Walking mailing list here Beginners Nordic walking lessons Monday Lunchtimes (rdv 12:20 for 12:30 departure) 13.09/20.09/27.09/04.10 11.10/18.10/08.11/15.11 22.11/29.11/06.12/20.12 Nordic walking lessons Tuesday evenings (rdv 17:50 for 18:00 departure) 07.09/14.09/21.09/28.09 05.10/12.10/19.10/26.10 Intermediate/Advanced Nordic walking outings (follow the nordic walking lessons before signing up for the outings) every Thursday from 16.09 - 16.12, excluding 28.10 and 09.12 Subscriptions and info: fitness.club@cern.ch  

Post-thaw sperm characteristics following long-term storage of boar semen in liquid nitrogen.

Science.gov (United States)

Fraser, L; Strzeżek, J; Kordan, W

2014-06-30

This study investigated the effect of long-term liquid nitrogen storage of semen from individual boars on post-thaw sperm characteristics. Ejaculates, collected from five Polish large white (PLW) and five Polish landrace (PLR) boars, were frozen using a standard cryopreservation protocol. Post-thaw analysis was performed within a week (Period 1) and 42-48 months (Period 2) of semen storage in liquid nitrogen. Post-thaw sperm assessments included total motility, mitochondrial function (JC-1/PI assay), plasma membrane integrity (SYBR-14/PI assay), osmotic resistance test (ORT), lipid peroxidation (LPO) status and DNA fragmentation, analysed by the neutral Comet assay. Individual boar variability within breed and cryostorage periods had significant effects on the analysed parameters of frozen-thawed spermatozoa. Prolonged semen storage in liquid nitrogen (Period 2) induced a marked reduction in post-thaw sperm motility, mitochondrial function and plasma membrane integrity in most of the boars. Post-thaw semen of eight boars exhibited a marked decrease in osmotic resistance of the sperm acrosomal membrane, whereas a significant increase in the sperm cryo-susceptibility to induced LPO and DNA fragmentation was observed only in three boars after long-term semen storage. Additionally, frozen-thawed spermatozoa of PLR boars exhibited significantly lower osmotic resistance of the acrosomal membrane than PLW boars following prolonged semen storage in liquid nitrogen. The results of this study provide evidence of ageing processes in frozen-thawed boar spermatozoa following prolonged cryostorage. It seems that, even though cryopreservation allows long-term semen storage in liquid nitrogen, spermatozoa from individual boars are more susceptible to cryo-induced damage. Copyright © 2014 Elsevier B.V. All rights reserved.

Stress induced enhanced polarization in multilayer BiFeO3/BaTiO3 structure with improved energy storage properties

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Savita Sharma

2015-10-01

Full Text Available Present work reports the fabrication of a multilayer (5-layer structure of BiFeO3(BFO/BaTiO3(BTO using spin-coating technique. The crystallographic structure, surface morphology and ferroelectric behavior of multilayer structure in metal-ferroelectric-metal capacitor have been studied. Le-Bail refinement of X-ray diffraction data revealed the formation of polycrystalline pure perovskite phase with induced stress. The values of remnant (Pr and saturation polarization (Ps for BFO/BTO multilayer structure are found to be 38.14 μC/cm2 and 71.54 μC/cm2 respectively, which are much higher than the corresponding values reported for bare BFO thin film. A large value of dielectric constant of 187 has been obtained for multilayer structure with a low leakage current density of 1.09 × 10−7 A/cm2 at applied bias of 10 V. The BFO/BTO multilayer structure favors the enhanced energy storage capacity as compared to bare BFO thin film with improved values of energy-density and charge-discharge efficiency as 121 mJ/cm3 and 59% respectively, suggesting futuristic energy storage applications.

Block Storage Service: Status and Performance

CERN Document Server

Van der Ster, Daniel

2014-01-01

This memo summarizes the current status of the Ceph block storage service as it is used for OpenStack Cinder Volumes and Glance Images as of May 2014. We present the block storage activity on the current cluster, measuring IOPS and latencies, and present a cost/benefit analysis of using SSDs to optimize the cost and performance efficiency of the service. During tests in collaboration with IT-CF, we have concluded that by adding SSDs as the synchronous write journals (used to guarantee data durability), we are able increase the IOPS capacity by 4-5 times, at a cost of decreasing the available volume by 20%. Further, the testing has shown that the Ceph implementation is able to operate at the limit of the hardware performance; software-induced performance limitations were not yet observed in either the spinning disk or SSD configurations. In addition, we believe that increasing small write performance with SSDs is applicable only to the block storage use-case; high-bandwidth use-cases such as physics data stora...

Evidence for conjugated linoleic acid-induced embryonic mortality that is independent of egg storage conditions and changes in egg relative fatty acids.

Science.gov (United States)

Leone, V A; Stransky, D L; Aydin, R; Cook, M E

2009-09-01

Three experiments were performed to determine the effect of conjugated linoleic acid (CLA) on embryonic development in the absence of vitelline membrane disruption. In experiment 1, when eggs from control and CLA (0.5%)-fed hens were stored at 21 or 15 degrees C for 48 h, mineral movement between the yolk and albumen was not observed (with the exception of Mg and Na). Also, it was found that CLA-induced changes in yolk fatty acid content (e.g., increased saturated fatty acids and CLA) had begun to change after 5 d of feeding hens CLA, and no differences were detected in fatty acid composition after 14 d. In experiment 2, the hatchability of eggs incubated directly after oviposition or stored 24 h at 21 or 15 degrees C was determined from hens fed control or 0.5% CLA diets. Regardless of storage conditions, CLA reduced hatchability. These data showed that CLA elicits negative effects on hatchability independent of vitelline membrane disruption or egg storage condition. In experiment 3, eggs were collected from hens fed 0 or 1% CLA daily for 3 wk, stored at 21 degrees C for 24 h, and incubated. Not only did CLA decrease hatchability, the data showed as the days of CLA feeding increased, the days of survival during incubation decreased. Average days of embryonic survival during incubation for the CLA group diminished to 18.0, 13.4, and 6.3 d for wk 1, 2, and 3 of CLA feeding, respectively, and control remained at 20.6, 20.8, and 19.8 for the 3 wk. These studies suggested that without the disruption of the vitelline membrane, hatchability and embryonic days of survival were significantly reduced by maternal CLA feeding in comparison to control-fed hens. Evidence that embryos die earlier the longer the hens are fed CLA, even though no additional changes in the fatty acid content of eggs were found, suggested that factors other than storage and egg yolk fatty acid composition played a role in CLA-induced embryonic mortality.

PC-Cluster based Storage System Architecture for Cloud Storage

OpenAIRE

Yee, Tin Tin; Naing, Thinn Thu

2011-01-01

Design and architecture of cloud storage system plays a vital role in cloud computing infrastructure in order to improve the storage capacity as well as cost effectiveness. Usually cloud storage system provides users to efficient storage space with elasticity feature. One of the challenges of cloud storage system is difficult to balance the providing huge elastic capacity of storage and investment of expensive cost for it. In order to solve this issue in the cloud storage infrastructure, low ...

Storage rack for spent nuclear fuels

International Nuclear Information System (INIS)

Kiyama, Yoichi.

1996-01-01

A storage rack comprises a number of rack cells for containing spent nuclear fuels and two upper and lower rack support plates. Small through holes are formed to lateral walls of the rack cell each at a position slightly above the position of the upper rack support plate. Finger members each having a protrusion which fits the small through hole is secured at the upper surface of the upper rack support plate. The finger member is a metal leaf-spring erected at the periphery of a rack insertion hole of the rack support plate. Gaps for allowing thermal expansion of the rack cell are formed each between the edge of the rack cell insertion hole of the rack support plate and the rack cell, and between the lower edge of the small through hole on a side wall of the rack cell and the lower portion of the protrusion of the finger member. If the rack cell is inserted to a bottom, the protrusion of the finger member fits the small through hole on the side of the rack cell. With such a constitution, the rack cell is prevented from withdrawing in conjunction with removal of fuels. (I.N.)

ROOT - A C++ Framework for Petabyte Data Storage, Statistical Analysis and Visualization

CERN Document Server

Naumann, Axel; Ballintijn, Maarten; Bellenot, Bertrand; Biskup, Marek; Brun, Rene; Buncic, Nenad; Canal, Philippe; Casadei, Diego; Couet, Olivier; Fine, Valery; Franco, Leandro; Ganis, Gerardo; Gheata, Andrei; Gonzalez~Maline, David; Goto, Masaharu; Iwaszkiewicz, Jan; Kreshuk, Anna; Marcos Segura, Diego; Maunder, Richard; Moneta, Lorenzo; Offermann, Eddy; Onuchin, Valeriy; Panacek, Suzanne; Rademakers, Fons; Russo, Paul; Tadel, Matevz

2009-01-01

ROOT is an object-oriented C++ framework conceived in the high-energy physics (HEP) community, designed for storing and analyzing petabytes of data in an efficient way. Any instance of a C++ class can be stored into a ROOT file in a machine-independent compressed binary format. In ROOT the TTree object container is optimized for statistical data analysis over very large data sets by using vertical data storage techniques. These containers can span a large number of files on local disks, the web, or a number of different shared file systems. In order to analyze this data, the user can chose out of a wide set of mathematical and statistical functions, including linear algebra classes, numerical algorithms such as integration and minimization, and various methods for performing regression analysis (fitting). In particular, the RooFit package allows the user to perform complex data modeling and fitting while the RooStats library provides abstractions and implementations for advance...

Cardiorespiratory fitness, BMI, and risk of hypertension: the HYPGENE study.

Science.gov (United States)

Rankinen, Tuomo; Church, Timothy S; Rice, Treva; Bouchard, Claude; Blair, Steven N

2007-10-01

Cardiorespiratory fitness and regular physical activity are inversely associated with the risk of hypertension, and exercise training has been shown to lower elevated blood pressure (BP). Genetic factors contribute significantly to the interindividual differences in endurance training-induced changes in BP. However, similar data on the genotype-by-fitness interactions on the risk of hypertension are scarce. In 2000, we started a systematic collection of blood samples from all consenting subjects of the Aerobics Center Longitudinal Study (ACLS) with a goal to generate a resource for studies addressing genotype-by-fitness interaction effects on various health-related end points. Here, we introduce the rationale and design of the first study based on the ACLS genetics resource focusing on hypertension as the health outcome (HYPGENE study), and we report the associations of cardiorespiratory fitness and body mass index (BMI) with the risk of hypertension. All HYPGENE subjects (N = 1234) were healthy and normotensive at their first clinic visit. Cases (N = 629) developed hypertension during the follow-up period (mean 8.7 yr), whereas controls (N = 605) remained normotensive (mean follow-up 10.1 yr). Cardiorespiratory fitness was the strongest predictor of the hypertension risk, with each maximal metabolic equivalent unit being associated with a 19% lower risk (95% confidence interval [95% CI], 12-24%). Each baseline BMI unit was associated with a 9% higher hypertension risk (95% CI, 4-13%). However, the association of BMI was greatly attenuated (odds ratio 1.04 [95% CI, 0.99-1.09]) when fitness also was included in the model. The HYPGENE study will provide an excellent resource to address hypotheses regarding the genetic basis of hypertension while taking cardiorespiratory fitness level into account.

Current indirect fitness and future direct fitness are not incompatible.

Science.gov (United States)

Brahma, Anindita; Mandal, Souvik; Gadagkar, Raghavendra

2018-02-01

In primitively eusocial insects, many individuals function as workers despite being capable of independent reproduction. Such altruistic behaviour is usually explained by the argument that workers gain indirect fitness by helping close genetic relatives. The focus on indirect fitness has left open the question of whether workers are also capable of getting direct fitness in the future in spite of working towards indirect fitness in the present. To investigate this question, we recorded behavioural profiles of all wasps on six naturally occurring nests of Ropalidia marginata , and then isolated all wasps in individual plastic boxes, giving them an opportunity to initiate nests and lay eggs. We found that 41% of the wasps successfully did so. Compared to those that failed to initiate nests, those that did were significantly younger, had significantly higher frequency of self-feeding behaviour on their parent nests but were not different in the levels of work performed in the parent nests. Thus ageing and poor feeding, rather than working for their colonies, constrain individuals for future independent reproduction. Hence, future direct fitness and present work towards gaining indirect fitness are not incompatible, making it easier for worker behaviour to be selected by kin selection or multilevel selection. © 2018 The Author(s).

Understanding the Risk of Chloride Induced Stress Corrosion Cracking of Interim Storage Containers for the Dry Storage of Spent Nuclear Fuel: Evolution of Brine Chemistry on the Container Surface

International Nuclear Information System (INIS)

Enos, David; Bryan, Charles R.

2015-01-01

Although the susceptibility of austenitic stainless steels to chloride-induced stress corrosion cracking is well known, uncertainties exist in terms of the environmental conditions that exist on the surface of the storage containers. While a diversity of salts is present in atmospheric aerosols, many of these are not stable when placed onto a heated surface. Given that the surface temperature of any container storing spent nuclear fuel will be well above ambient, it is likely that salts deposited on its surface may decompose or degas. To characterize this effect, relevant single and multi-salt mixtures are being evaluated as a function of temperature and relative humidity to establish the rates of degassing, as well as the likely final salt and brine chemistries that will remain on the canister surface.

Understanding the Risk of Chloride Induced Stress Corrosion Cracking of Interim Storage Containers for the Dry Storage of Spent Nuclear Fuel: Evolution of Brine Chemistry on the Container Surface.

Energy Technology Data Exchange (ETDEWEB)

Enos, David; Bryan, Charles R.

2015-10-01

Although the susceptibility of austenitic stainless steels to chloride-induced stress corrosion cracking is well known, uncertainties exist in terms of the environmental conditions that exist on the surface of the storage containers. While a diversity of salts is present in atmospheric aerosols, many of these are not stable when placed onto a heated surface. Given that the surface temperature of any container storing spent nuclear fuel will be well above ambient, it is likely that salts deposited on its surface may decompose or degas. To characterize this effect, relevant single and multi-salt mixtures are being evaluated as a function of temperature and relative humidity to establish the rates of degassing, as well as the likely final salt and brine chemistries that will remain on the canister surface.

Unge, sundhed og fitness

DEFF Research Database (Denmark)

Jensen, Jens-Ole

2003-01-01

Artiklen redegør for udbredelsen af fitness blandt unge og diskuterer, hvor det er blevet så populært at dyrke fitness.......Artiklen redegør for udbredelsen af fitness blandt unge og diskuterer, hvor det er blevet så populært at dyrke fitness....

Transcending the Curricular Barrier between Fitness and Reading with FitLit

Science.gov (United States)

Opitz, Michael F.

2011-01-01

The author discusses how FitLit, children's literature that spotlights the multiple aspects of health and well-being, offers a vehicle for integrating reading and fitness into existing classroom routines such as guided reading, read-alouds, independent reading, and reading and writing workshop. Sample FitLit titles are provided as well as a…

Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR).

Science.gov (United States)

Rosenberg, Mark F; Kamis, Alhaji Bukar; Aleksandrov, Luba A; Ford, Robert C; Riordan, John R

2004-09-10

The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that is mutated in patients suffering from cystic fibrosis. Here we report the purification and first crystallization of wild-type human CFTR. Functional characterization of the material showed it to be highly active. Electron crystallography of negatively stained two-dimensional crystals of CFTR has revealed the overall architecture of this channel for two different conformational states. These show a strong structural homology to two conformational states of another eukaryotic ATP-binding cassette transporter, P-glycoprotein. In contrast to P-glycoprotein, however, both conformational states can be observed in the presence of a nucleotide, which may be related to the role of CFTR as an ion channel rather than a transporter. The hypothesis that the two conformations could represent the "open" and "closed" states of the channel is considered.

SOLID-STATE STORAGE DEVICE WITH PROGRAMMABLE PHYSICAL STORAGE ACCESS

DEFF Research Database (Denmark)

2017-01-01

a storage device action request, and the storage device evaluating a first rule of the one or more rules by determining if the received request fulfills request conditions comprised in the first rule, and in the affirmative the storage device performing request actions comprised in the first rule......Embodiments of the present invention includes a method of operating a solid-state storage device, comprising a storage device controller in the storage device receiving a set of one or more rules, each rule comprising (i) one or more request conditions to be evaluated for a storage device action...... request received from a host computer, and (ii) one or more request actions to be performed on a physical address space of a non-volatile storage unit in the solid-state storage device in case the one or more request conditions are fulfilled; the method further comprises: the storage device receiving...

Simulations of Skin Barrier Function: Free Energies of Hydrophobic and Hydrophilic Transmembrane Pores in Ceramide Bilayers

OpenAIRE

Notman, Rebecca; Anwar, Jamshed; Briels, W. J.; Noro, Massimo G.; den Otter, Wouter K.

2008-01-01

Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier function of the skin. We have used the potential of mean constraint force (PMCF) method to calculate the free energy of pore formation in ceramide bilayers in both the innate gel pha...

Synergy effects of fluoxetine and variability in temperature lead to proportionally greater fitness costs in Daphnia: A multigenerational test.

Science.gov (United States)

Barbosa, Miguel; Inocentes, Núrya; Soares, Amadeu M V M; Oliveira, Miguel

2017-12-01

Increased variability in water temperature is predicted to impose disproportionally greater fitness costs than mean increase in temperature. Additionally, water contaminants are currently a major source of human-induced stress likely to produce fitness costs. Global change models forecast an increase in these two human-induced stressors. Yet, in spite the growing interest in understanding how organisms respond to global change, the joint fitness effects of water pollution and increased variability in temperature remain unclear. Here, using a multigenerational design, we test the hypothesis that exposure to high concentrations of fluoxetine, a human medicine commonly found in freshwater systems, causes increased lifetime fitness costs, when associated with increased variability in temperature. Although fluoxetine and variability in temperature elicited some fitness cost when tested alone, when both stressors acted together the costs were disproportionally greater. The combined effect of fluoxetine and variability in temperature led to a reduction of 37% in lifetime reproductive success and a 17.9% decrease in population growth rate. Interestingly, fluoxetine and variability in temperature had no effect on the probability of survival. Freshwater systems are among the most imperilled ecosystems, often exposed to multiple human-induced stressors. Our results indicate that organisms face greater fitness risk when exposed to multiple stressors at the same time than when each stress acts alone. Our study highlights the importance of using a multi-generational approach to fully understand individual environmental tolerance and its responses to a global change scenario in aquatic systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Femtoslicing in Storage Rings

CERN Document Server

Khan, Shaukat

2005-01-01

The generation of ultrashort synchrotron radiation pulses by laser-induced energy modulation of electrons and their subsequent transverse displacement, now dubbed "femtoslicing," was demonstrated at the Advanced Light Source in Berkeley. More recently, a femtoslicing user facility was commissioned at the BESSY storage ring in Berlin, and another project is in progress at the Swiss Light Source. The paper reviews the principle of femtoslicing, its merits and shortcomings, as well as the variations of its technical implementation. Various diagnostics techniques to detect successful laser-electron interaction are discussed and experimental results are presented.

Laser induced uranium fluorescence as an analytical method

International Nuclear Information System (INIS)

Krutman, I.

1985-01-01

A laser induced fluorescence system was developed to measure uranium trace level amounts in aqueous solution with reliable and simple materials and electronics. A nitrogen pulsed laser was built with the storage energy capacitor directly coupled to laser tube electrodes as a transmission line device. This laser operated at 3Hz repetition rate with peak intensity around 21 Kw and temporal width of 4.5 x 10 -9 s. A sample compartment made of rigid PVC and a photomultiplier housing of aluminium were constructed and assembled forming a single integrated device. As a result of this prototype system we made several analytical measurements with U dissolved in nitric acid to obtain a calibration curve. We obtained a straight line from a plot of U concentration versus fluorescence intensity fitted by a least square method that produced a regression coefficient of 0.994. The lower limit of U determination was 30 ppb -+ 3.5%. (Author) [pt

Requirement of transmembrane domain for CD154 association to lipid rafts and subsequent biological events.

Directory of Open Access Journals (Sweden)

Nadir Benslimane

Full Text Available Interaction of CD40 with CD154 leads to recruitment of both molecules into lipid rafts, resulting in bi-directional cell activation. The precise mechanism by which CD154 is translocated into lipid rafts and its impact on CD154 signaling remain largely unknown. Our aim is to identify the domain of CD154 facilitating its association to lipid rafts and the impact of such association on signaling events and cytokine production. Thus, we generated Jurkat cell lines expressing truncated CD154 lacking the cytoplasmic domain or chimeric CD154 in which the transmembrane domain was replaced by that of transferrin receptor I, known to be excluded from lipid rafts. Our results show that cell stimulation with soluble CD40 leads to the association of CD154 wild-type and CD154-truncated, but not CD154-chimera, with lipid rafts. This is correlated with failure of CD154-chimera to activate Akt and p38 MAP kinases, known effectors of CD154 signaling. We also found that CD154-chimera lost the ability to promote IL-2 production upon T cell stimulation with anti-CD3/CD28 and soluble CD40. These results demonstrate the implication of the transmembrane domain of CD154 in lipid raft association, and that this association is necessary for CD154-mediated Akt and p38 activation with consequent enhancement of IL-2 production.

Physiological and pharmacological characterization of transmembrane acid extruders in cultured human umbilical artery smooth muscle cells

Directory of Open Access Journals (Sweden)

Gunng-Shinng Chen

2015-01-01

Full Text Available Background: Intracellular pH (pH i is a pivotal factor for cellular functions and homeostasis. Apart from passive intracellular buffering capacity, active transmembrane transporters responsible for kinetic changes of pH i impacts. Acid extrusion transporters such as Na + /H + exchanger (NHE and Na + /HCO3− cotransporter (NBC have been found to be activated when cells are in an acidic condition in different cell types. However, such far, the pH i regulators have not been characterized in human umbilical artery smooth muscle cells (HUASMCs. Materials and Methods: We, therefore, investigated the mechanism of pH i recovery from intracellular acidosis, induced by NH 4 Cl-prepulse, using pH-sensitive fluorescence dye: 2′,7′-bis(2-carboxethyl-5(6-carboxy-fluorescein in HUASMCs. Cultured HUASMCs were derived from the segments of the human umbilical artery that were obtained from women undergoing children delivery. Results: The resting pH i is 7.23 ± 0.03 when cells in HEPES (nominally HCO 3− -free buffered solution. The resting pH i is higher as 7.27 ± 0.03 when cells in CO 2 /HCO3− -buffered solution. In HEPES-buffered solution, a pH i recovery following induced intracellular acidosis could be inhibited completely by 30 μM HOE 694 (a specific NHE inhibitor or by removing [Na +]o . In 5% CO2/HCO3− -buffered solution, 30 μM HOE 694 slowed the pH i recovery from the induced intracellular acidosis only. On the contrary, HOE 694 adding together with 0.2 mM 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (a specific NBC inhibitor or removal of [Na +]o entirely blocked the acid extrusion. By using Western blot technique, we demonstrated that four different isoforms of NBC, that is, SLC4A8 (NBCBE, SLC4A7 (NBCn1, SLC4A5 (NBCe2 and SLC4A4 (NBCe1, co-exist in the HUASMCs. Conclusions: We demonstrate, for the 1 st time, that apart from the housekeeping NHE1, another Na + couple HCO3− -transporter, that is, NBC, functionally coexists to

Developing new transportable storage casks for interim dry storage

International Nuclear Information System (INIS)

Hayashi, K.; Iwasa, K.; Araki, K.; Asano, R.

2004-01-01

Transportable storage metal casks are to be consistently used during transport and storage for AFR interim dry storage facilities planning in Japan. The casks are required to comply with the technical standards of regulations for both transport (hereinafter called ''transport regulation'') and storage (hereafter called ''storage regulation'') to maintain safety functions (heat transfer, containment, shielding and sub-critical control). In addition to these requirements, it is not planned in normal state to change the seal materials during storage at the storage facility, therefore it is requested to use same seal materials when the casks are transported after storage period. The dry transportable storage metal casks that satisfy the requirements have been developed to meet the needs of the dry storage facilities. The basic policy of this development is to utilize proven technology achieved from our design and fabrication experience, to carry out necessary verification for new designs and to realize a safe and rational design with higher capacity and efficient fabrication

Dynamic monitoring of transmembrane potential changes: a study of ion channels using an electrical double layer-gated FET biosensor.

Science.gov (United States)

Pulikkathodi, Anil Kumar; Sarangadharan, Indu; Chen, Yi-Hong; Lee, Geng-Yen; Chyi, Jen-Inn; Lee, Gwo-Bin; Wang, Yu-Lin

2018-03-27

In this research, we have designed, fabricated and characterized an electrical double layer (EDL)-gated AlGaN/GaN high electron mobility transistor (HEMT) biosensor array to study the transmembrane potential changes of cells. The sensor array platform is designed to detect and count circulating tumor cells (CTCs) of colorectal cancer (CRC) and investigate cellular bioelectric signals. Using the EDL FET biosensor platform, cellular responses can be studied in physiological salt concentrations, thereby eliminating complex automation. Upon investigation, we discovered that our sensor response follows the transmembrane potential changes of captured cells. Our whole cell sensor platform can be used to monitor the dynamic changes in the membrane potential of cells. The effects of continuously changing electrolyte ion concentrations and ion channel blocking using cadmium are investigated. This methodology has the potential to be used as an electrophysiological probe for studying ion channel gating and the interaction of biomolecules in cells. The sensor can also be a point-of-care diagnostic tool for rapid screening of diseases.

Thermal Instability Induced Oriented 2D Pores for Enhanced Sodium Storage.

Science.gov (United States)

Kong, Lingjun; Xie, Chen-Chao; Gu, Haichen; Wang, Chao-Peng; Zhou, Xianlong; Liu, Jian; Zhou, Zhen; Li, Zhao-Yang; Zhu, Jian; Bu, Xian-He

2018-04-19

Hierarchical porous structures are highly desired for various applications. However, it is still challenging to obtain such materials with tunable architectures. Here, this paper reports hierarchical nanomaterials with oriented 2D pores by taking advantages of thermally instable bonds in vanadium-based metal-organic frameworks (MOFs). High-temperature calcination of these MOFs accompanied by the loss of coordinated water molecules and other components enables the formation of orderly slit-like 2D pores in vanadium oxide/porous carbon nanorods (VO x /PCs). This unique combination leads to an increase of the reactive surface area. In addition, optimized VO x /PCs demonstrate high-rate capability and ultralong cycling life for sodium storage. The assembled full cells also show high capacity and cycling stability. This report provides an effective strategy for producing MOFs-derived composites with hierarchical porous architectures for energy storage. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microwave-induced solid-state synthesis of TiO2(B) nanobelts with enhanced lithium-storage properties

International Nuclear Information System (INIS)

Qiao Yun; Hu Xianluo; Huang Yunhui

2012-01-01

A fast and economical route based on an efficient microwave-induced solid-state process has been developed to synthesize metastable TiO 2 (B) nanobelts with widths of 30–100 nm and lengths up to a few micrometers on a large scale. This new method reduces the synthesis time for the preparation of TiO 2 (B) nanobelts to less than half an hour, allowing the screening of a wide range of reaction conditions for optimizing and scaling up the production and facilitating the formation of metastable phase TiO 2 (B). The as-formed TiO 2 (B) nanobelts exhibit enhanced lithium-storage performances, compared with the TiO 2 (B) product obtained by the conventional heating. This study provides a new way for large-scale industrial production of high-quality metastable TiO 2 (B) nanostructures. The products were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy.

Development of a Threshold Model to Predict Germination of Populus tomentosa Seeds after Harvest and Storage under Ambient Condition

Science.gov (United States)

Wang, Wei-Qing; Cheng, Hong-Yan; Song, Song-Quan

2013-01-01

Effects of temperature, storage time and their combination on germination of aspen (Populus tomentosa) seeds were investigated. Aspen seeds were germinated at 5 to 30°C at 5°C intervals after storage for a period of time under 28°C and 75% relative humidity. The effect of temperature on aspen seed germination could not be effectively described by the thermal time (TT) model, which underestimated the germination rate at 5°C and poorly predicted the time courses of germination at 10, 20, 25 and 30°C. A modified TT model (MTT) which assumed a two-phased linear relationship between germination rate and temperature was more accurate in predicting the germination rate and percentage and had a higher likelihood of being correct than the TT model. The maximum lifetime threshold (MLT) model accurately described the effect of storage time on seed germination across all the germination temperatures. An aging thermal time (ATT) model combining both the TT and MLT models was developed to describe the effect of both temperature and storage time on seed germination. When the ATT model was applied to germination data across all the temperatures and storage times, it produced a relatively poor fit. Adjusting the ATT model to separately fit germination data at low and high temperatures in the suboptimal range increased the models accuracy for predicting seed germination. Both the MLT and ATT models indicate that germination of aspen seeds have distinct physiological responses to temperature within a suboptimal range. PMID:23658654

Fodbold Fitness

DEFF Research Database (Denmark)

Bennike, Søren

Samfundet forandrer sig og ligeså gør danskernes idrætsmønstre. Fodbold Fitness, der er afhandlingens omdrejningspunkt, kan iagttages som en reaktion på disse forandringer. Afhandlingen ser nærmere på Fodbold Fitness og implementeringen af dette, der ingenlunde er nogen let opgave. Bennike bidrager...

Characterization of the single transmembrane domain of human receptor activity-modifying protein 3 in adrenomedullin receptor internalization

International Nuclear Information System (INIS)

Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Nozaki, Naomi; Kato, Johji

2012-01-01

Highlights: ► RAMP3 mediates CLR internalization much less effectively than does RAMP2. ► The RAMP3 TMD participates in the negative regulation of CLR/RAMP3 internalization. ► A new strategy of promoting internalization and resensitization of the receptor was found. -- Abstract: Two receptor activity-modifying proteins (RAMP2 and RAMP3) enable calcitonin receptor-like receptor (CLR) to function as two heterodimeric receptors (CLR/RAMP2 and CLR/RAMP3) for adrenomedullin (AM), a potent cardiovascular protective peptide. Following AM stimulation, both receptors undergo rapid internalization through a clathrin-dependent pathway, after which CLR/RAMP3, but not CLR/RAMP2, can be recycled to the cell surface for resensitization. However, human (h)RAMP3 mediates CLR internalization much less efficiently than does hRAMP2. Therefore, the molecular basis of the single transmembrane domain (TMD) and the intracellular domain of hRAMP3 during AM receptor internalization was investigated by transiently transfecting various RAMP chimeras and mutants into HEK-293 cells stably expressing hCLR. Flow cytometric analysis revealed that substituting the RAMP3 TMD with that of RAMP2 markedly enhanced AM-induced internalization of CLR. However, this replacement did not enhance the cell surface expression of CLR, [ 125 I]AM binding affinity or AM-induced cAMP response. More detailed analyses showed that substituting the Thr 130 –Val 131 sequence in the RAMP3 TMD with the corresponding sequence (Ile 157 –Pro 158 ) from RAMP2 significantly enhanced AM-mediated CLR internalization. In contrast, substituting the RAMP3 target sequence with Ala 130 –Ala 131 did not significantly affect CLR internalization. Thus, the RAMP3 TMD participates in the negative regulation of CLR/RAMP3 internalization, and the aforementioned introduction of the Ile–Pro sequence into the RAMP3 TMD may be a strategy for promoting receptor internalization/resensitization.

Regenesys utility scale energy storage. Overview report of combined energy storage and renewable generation

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-07-01

The first part of the paper briefly discusses the advantages and disadvantages of various forms of renewable energy sources with respect to the United Kingdom. It discusses the intermittent nature of wind and solar power and the less intermittent nature of hydro power and energy from biomass. The need to store energy generated, particularly from the intermittent sources, is discussed with special reference to electric batteries and pumped storage. If the energy cannot be stored and delivered when required, then the commercial viability of the source will be adversely affected - the economics and how this fits with NETA are discussed briefly. The second part of the paper is an overview of some relevant literature discussing (a) how the problems of fluctuating supplies may be managed, (b) an analytical assessment of the contribution from wind farms, (c) how fluctuations in wind power can be smoothed using sodium-sulfur batteries, (d) how small generators can get together and reduce trading costs and imbalance exposure under NETA, (e) the benefits of large-scale energy storage to network management and embedded generation, (f) distribution networks, (g) embedded generation and network management issues and (h) costs and benefits of embedded generation. The work was carried out as part of the DTI New and Renewable Energy Programme managed by Future Energy Solutions.

Regenesys utility scale energy storage. Overview report of combined energy storage and renewable generation

International Nuclear Information System (INIS)

2004-01-01

The first part of the paper briefly discusses the advantages and disadvantages of various forms of renewable energy sources with respect to the United Kingdom. It discusses the intermittent nature of wind and solar power and the less intermittent nature of hydro power and energy from biomass. The need to store energy generated, particularly from the intermittent sources, is discussed with special reference to electric batteries and pumped storage. If the energy cannot be stored and delivered when required, then the commercial viability of the source will be adversely affected - the economics and how this fits with NETA are discussed briefly. The second part of the paper is an overview of some relevant literature discussing (a) how the problems of fluctuating supplies may be managed, (b) an analytical assessment of the contribution from wind farms, (c) how fluctuations in wind power can be smoothed using sodium-sulfur batteries, (d) how small generators can get together and reduce trading costs and imbalance exposure under NETA, (e) the benefits of large-scale energy storage to network management and embedded generation, (f) distribution networks, (g) embedded generation and network management issues and (h) costs and benefits of embedded generation. The work was carried out as part of the DTI New and Renewable Energy Programme managed by Future Energy Solutions

Fire protection in ammunition storage spaces on board naval craft: An evaluation of the water application rate

NARCIS (Netherlands)

Lindström, J.; Rahm, M.; Hiltz, J.; Boonacker, B.; Wal, R. van der; Haara, M.

2012-01-01

Ammunition storage spaces on naval vessels are commonly fitted with drencher systems that are designed to prevent ordnance reaching a temperature where it might explode due to fast or slow “cook‐off”. Many of these systems are traditional low pressure water spray systems that are required by the

Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

Science.gov (United States)

Liang, Junshi; Chen, Pengyu; Dong, Bojun; Huang, Zihan; Zhao, Kongyin; Yan, Li-Tang

2016-05-09

Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

Human-induced Terrestrial Water Storage Change: A Global Analysis using Hydrological Models and GRACE

Science.gov (United States)

Felfelani, F.; Pokhrel, Y. N.

2016-12-01

Hydrological models and data derived from the Gravity Recovery and Climate Experiment (GRACE) satellite mission are used to study terrestrial water storage (TWS) change; however, both have disadvantages that necessitate the integrated use of them. While GRACE doesn't disintegrate the vertical storage into its components, most models do not account for human activities. Here we use two Land Surface Models (LSMs), i.e., HiGW-MAT and PCRGLOBWB that fully couple natural and human drivers of changes in water cycle, explicitly simulating the changes in various TWS compartments. We first evaluate the models performance with GRACE observations. Then, we quantify the human footprint over global river basins located in different geographic and climate regions. To quantify human impacts, a new framework is proposed based on the GRACE observations (representing both climate variability and human activities) together with the natural simulation of LSMs using water budget equation (P-ET-R; P for precipitation, ET for evapotranspiration, and R for runoff). Finally, we examine the uncertainty in TWS simulations arising from the uncertainties in forcing data. Results indicate that, in snow-dominated regions, PCRGLOBWB generally fails to reproduce neither the interannual variability of observed TWS nor the seasonal cycle, while HiGW-MAT model shows significantly better results. In basins with human signatures, PCRGLOBWB generally shows better agreement with GRACE compared to HiGW-MAT. It is found that HiGW-MAT tends to overestimate groundwater depletion in basins with human impacts (e.g., Amudarya, Colorado, Euphrates and Indus), which results in larger negative interannual TWS trend compared to GRACE. Euphrates and Ganges river basins experience the highest human-induced TWS deficit rates (2.08 cm/yr and 1.94 cm/yr, respectively) during the simulation period of 2002-2010. Uncertainty analysis of results from the same model but with different forcing data suggests a high standard

Azorhizobium caulinodans Transmembrane Chemoreceptor TlpA1 Involved in Host Colonization and Nodulation on Roots and Stems

Directory of Open Access Journals (Sweden)

Wei Liu

2017-07-01

Full Text Available Azorhizobium caulinodans ORS571 is a motile soil bacterium that interacts symbiotically with legume host Sesbania rostrata, forming nitrogen-fixing root and stem nodules. Bacterial chemotaxis plays an important role in establishing this symbiotic relationship. To determine the contribution of chemotaxis to symbiosis in A. caulinodans ORS571-S. rostrata, we characterized the function of TlpA1 (transducer-like protein in A. caulinodans, a chemoreceptor predicted by SMART (Simple Modular Architecture Research Tool, containing two N-terminal transmembrane regions. The tlpA1 gene is located immediately upstream of the unique che gene cluster and is transcriptionally co-oriented. We found that a ΔtlpA1 mutant is severely impaired for chemotaxis to various organic acids, glycerol and proline. Furthermore, biofilm forming ability of the strain carrying the mutation is reduced under certain growth conditions. Interestingly, competitive colonization ability on S. rostrata root surfaces is impaired in the ΔtlpA1 mutant, suggesting that chemotaxis of the A. caulinodans ORS571 contributes to root colonization. We also found that TlpA1 promotes competitive nodulation not only on roots but also on stems of S. rostrata. Taken together, our data strongly suggest that TlpA1 is a transmembrane chemoreceptor involved in A. caulinodans-S. rostrata symbiosis.

Comparing Person Organization Fit and Person Job Fit

Directory of Open Access Journals (Sweden)

Kadir Ardıç

2016-07-01

Full Text Available Although there have been many studies conducted to analyze the effects of person-organization fit (POF and person-job fit (PJF on individual outcomes, little is known about which of these fit associates stronger with individual variables (i.e., intention to quit job, IQJ, and perceived individual performance, PIP. Therefore the purpose of the study is to compare the relationships of PJF and POF with IQJ and PIP. The sample of the study consists of security guards working at a private company's civil aviation safety department. Totally 98 security guards participated to the research. Results indicated that, the relationships of PJF and POF with IQJ and PIP were not significantly different. Consequently the results indicate that POF and PJF associate similarly with critical individual outcomes.

Developing new transportable storage casks for interim dry storage

Energy Technology Data Exchange (ETDEWEB)

Hayashi, K.; Iwasa, K.; Araki, K.; Asano, R. [Hitachi Zosen Diesel and Engineering Co., Ltd., Tokyo (Japan)

2004-07-01

Transportable storage metal casks are to be consistently used during transport and storage for AFR interim dry storage facilities planning in Japan. The casks are required to comply with the technical standards of regulations for both transport (hereinafter called ''transport regulation'') and storage (hereafter called ''storage regulation'') to maintain safety functions (heat transfer, containment, shielding and sub-critical control). In addition to these requirements, it is not planned in normal state to change the seal materials during storage at the storage facility, therefore it is requested to use same seal materials when the casks are transported after storage period. The dry transportable storage metal casks that satisfy the requirements have been developed to meet the needs of the dry storage facilities. The basic policy of this development is to utilize proven technology achieved from our design and fabrication experience, to carry out necessary verification for new designs and to realize a safe and rational design with higher capacity and efficient fabrication.

A note on Poisson goodness-of-fit tests for ionizing radiation induced chromosomal aberration samples.

Science.gov (United States)

Higueras, Manuel; González, J E; Di Giorgio, Marina; Barquinero, J F

2018-05-18

To present Poisson exact goodness-of-fit tests as alternatives and complements to the asymptotic u-test, which is the most widely used in cytogenetic biodosimetry, to decide whether a sample of chromosomal aberrations in blood cells comes from an homogeneous or inhomogeneous exposure. Three Poisson exact goodness-of-fit test from the literature are introduced and implemented in the R environment. A Shiny R Studio application, named GOF Poisson, has been updated for the purpose of giving support to this work. The three exact tests and the u-test are applied in chromosomal aberration data from clinical and accidental radiation exposure patients. It is observed how the u-test is not an appropriate approximation in small samples with small yield of chromosomal aberrations. Tools are provided to compute the three exact tests, which is not as trivial as the implementation of the u-test. Poisson exact goodness-of-fit tests should be considered jointly to the u-test for detecting inhomogeneous exposures in the cytogenetic biodosimetry practice.

The FIT Model - Fuel-cycle Integration and Tradeoffs

International Nuclear Information System (INIS)

Piet, Steven J.; Soelberg, Nick R.; Bays, Samuel E.; Pereira, Candido; Pincock, Layne F.; Shaber, Eric L.; Teague, Melissa C.; Teske, Gregory M.; Vedros, Kurt G.

2010-01-01

All mass streams from fuel separation and fabrication are products that must meet some set of product criteria - fuel feedstock impurity limits, waste acceptance criteria (WAC), material storage (if any), or recycle material purity requirements such as zirconium for cladding or lanthanides for industrial use. These must be considered in a systematic and comprehensive way. The FIT model and the 'system losses study' team that developed it (Shropshire2009, Piet2010) are an initial step by the FCR and D program toward a global analysis that accounts for the requirements and capabilities of each component, as well as major material flows within an integrated fuel cycle. This will help the program identify near-term R and D needs and set longer-term goals. The question originally posed to the 'system losses study' was the cost of separation, fuel fabrication, waste management, etc. versus the separation efficiency. In other words, are the costs associated with marginal reductions in separations losses (or improvements in product recovery) justified by the gains in the performance of other systems? We have learned that that is the wrong question. The right question is: how does one adjust the compositions and quantities of all mass streams, given uncertain product criteria, to balance competing objectives including cost? FIT is a method to analyze different fuel cycles using common bases to determine how chemical performance changes in one part of a fuel cycle (say used fuel cooling times or separation efficiencies) affect other parts of the fuel cycle. FIT estimates impurities in fuel and waste via a rough estimate of physics and mass balance for a set of technologies. If feasibility is an issue for a set, as it is for 'minimum fuel treatment' approaches such as melt refining and AIROX, it can help to make an estimate of how performances would have to change to achieve feasibility.

Fitness club

CERN Multimedia

Fitness club

2013-01-01

  Nordic Walking Classes Come join the Nordic walking classes and outings offered by the CERN Fitness Club starting September 2013. Our licensed instructor Christine offers classes for people who’ve never tried Nordic Walking and who would like to learn the technique, and outings for people who have completed the classes and enjoy going out as a group. Course 1: Tuesdays 12:30 - 13:30 24 September, 1 October, 8 October, 15 October Course 2: Tuesdays 12:30 - 13:30 5 November, 12 November, 19 November, 26 November Outings will take place on Thursdays (12:30 to 13:30) from 12 September 2013. We meet at the CERN Club Barracks car park (close to Entrance A) 10 minutes before departure. Prices: 50 CHF for 4 classes, including the 10 CHF Club membership. Payments made directly to instructor. Renting Poles: Poles can be rented from Christine at 5 CHF / hour. Subscription: Please subscribe at: http://cern.ch/club-fitness Looking forward to seeing you among us! Fitness Club FitnessClub@c...

Fitness Club

CERN Multimedia

Fitness Club

2012-01-01

Get in Shape for Summer with the CERN Fitness Club Saturday 23 June 2012 from 14:30 to 16.30 (doors open at 14.00) Germana’s Fitness Workshop. Build strength and stamina, sculpt and tone your body and get your heart pumping with Germana’s workout mixture of Cardio Attack, Power Pump, Power Step, Cardio Combat and Cross-Training. Where: 216 (Pump room – equipped with changing rooms and showers). What to wear: comfortable clothes and indoor sports shoes + bring a drink! How much: 15 chf Sign up here: https://espace.cern.ch/club-fitness/Lists/Test_Subscription/NewForm.aspx? Join the Party and dance yourself into shape at Marco + Marials Zumba Masterclass. Saturday 30 June 2012 from 15:00 to 16:30 Marco + Mariel’s Zumba Masterclass Where: 216 (Pump room – equipped with changing rooms and showers). What to wear: comfortable clothes and indoor sports shoes + bring a drink! How much: 25 chf Sign up here: https://espace.cern.ch/club-fitness/Lists/Zumba%20...

Fitness Club

CERN Multimedia

Fitness Club

2012-01-01

  The CERN Fitness Club is pleased to announce its new early morning class which will be taking place on: Tuesdays from 24th April 07:30 to 08:15 216 (Pump Hall, close to entrance C) – Facilities include changing rooms and showers. The Classes: The early morning classes will focus on workouts which will help you build not only strength and stamina, but will also improve your balance, and coordination. Our qualified instructor Germana will accompany you throughout the workout  to ensure you stay motivated so you achieve the best results. Sign up and discover the best way to start your working day full of energy! How to subscribe? We invite you along to a FREE trial session, if you enjoy the activity, please sign up via our website: https://espace.cern.ch/club-fitness/Activities/SUBSCRIBE.aspx. * * * * * * * * Saturday 28th April Get in shape for the summer at our fitness workshop and zumba dance party: Fitness workshop with Germana 13:00 to 14:30 - 216 (Pump Hall) Price...

Corruption of host seven-transmembrane proteins by pathogenic microbes: a common theme in animals and plants?

Science.gov (United States)

Panstruga, Ralph; Schulze-Lefert, Paul

2003-04-01

Human diseases like AIDS, malaria, and pneumonia are caused by pathogens that corrupt host chemokine G-protein coupled receptors for molecular docking. Comparatively, little is known about plant host factors that are required for pathogenesis and that may serve as receptors for the entry of pathogenic microbes. Here, we review potential analogies between human chemokine receptors and the plant seven-transmembrane MLO protein, a candidate serving a dual role as docking molecule and defence modulator for the phytopathogenic powdery mildew fungus.

Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator

NARCIS (Netherlands)

A. Luciani (Alessandro); V.R. Villella (Valeria Rachela); S. Esposito (Susanna); M. Gavina (Manuela); I. Russo (Ilaria); M. Silano (Marco); S. Guido (Stefano); M. Pettoello-Mantovani (Massimo); R. Carnuccio (Rosa); B.J. Scholte (Bob); A. de Matteis (Antonella); M.C. Maiuri (Maria Chiara); V. Raia (Valeria); A. Luini (Alberto); H.K. Kroemer (Heyo); L. Maiuri (Luigi)

2012-01-01

textabstractChannel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded

Autism as the Low-Fitness Extreme of a Parentally Selected Fitness Indicator.

Science.gov (United States)

Shaner, Andrew; Miller, Geoffrey; Mintz, Jim

2008-12-01

Siblings compete for parental care and feeding, while parents must allocate scarce resources to those offspring most likely to survive and reproduce. This could cause offspring to evolve traits that advertise health, and thereby attract parental resources. For example, experimental evidence suggests that bright orange filaments covering the heads of North American coot chicks may have evolved for this fitness-advertising purpose. Could any human mental disorders be the equivalent of dull filaments in coot chicks-low-fitness extremes of mental abilities that evolved as fitness indicators? One possibility is autism. Suppose that the ability of very young children to charm their parents evolved as a parentally selected fitness indicator. Young children would vary greatly in their ability to charm parents, that variation would correlate with underlying fitness, and autism could be the low-fitness extreme of this variation. This view explains many seemingly disparate facts about autism and leads to some surprising and testable predictions.

Energy storage

Science.gov (United States)

Kaier, U.

1981-04-01

Developments in the area of energy storage are characterized, with respect to theory and laboratory, by an emergence of novel concepts and technologies for storing electric energy and heat. However, there are no new commercial devices on the market. New storage batteries as basis for a wider introduction of electric cars, and latent heat storage devices, as an aid for solar technology applications, with satisfactory performance standards are not yet commercially available. Devices for the intermediate storage of electric energy for solar electric-energy systems, and for satisfying peak-load current demands in the case of public utility companies are considered. In spite of many promising novel developments, there is yet no practical alternative to the lead-acid storage battery. Attention is given to central heat storage for systems transporting heat energy, small-scale heat storage installations, and large-scale technical energy-storage systems.

Research Advances in CKLFSF-like MARVEL Transmembrane Domain Containing Member 3.

Science.gov (United States)

Hu, Feng-zhan; Sheng, Zheng-zuo; Qin, Cai-peng; Xu, Tao

2016-06-10

CKLF-like MARVEL transmembrane domain containing member/chemokine-like factor super family member (CKLFSF/CMTM) is a novel tumor suppressor gene. CMTM3 is broadly expressed in normal human tissues and evolutionary conserved,especially in testis,spleen,and some cells of peripheral blood mononuclear cells. However,its expression is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM3 may inhibit the proliferation,migration,and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear,CKLFSF3/CMTM3 is closely connected with immune system and associated with sex during tumorigenesis. The study advances of CKLFSF3/CMTM3 are elaborated in this review as CMTM3 may be a new target in the gene therapies for tumors,especially genitourinary tumors,while further studies on CMTM3 and its anti-tumor mechanisms are warranted.

ROOT — A C++ framework for petabyte data storage, statistical analysis and visualization

CERN Document Server

Antcheva, I; Bellenot, B; Biskup,1, M; Brun, R; Buncic, N; Canal, Ph; Casadei, D; Couet, O; Fine, V; Franco,1, L; Ganis, G; Gheata, A; Gonzalez Maline, D; Goto, M; Iwaszkiewicz, J; Kreshuk, A; Marcos Segura, D; Maunder, R; Moneta, L; Naumann, A; Offermann, E; Onuchin, V; Panacek, S; Rademakers, F; Russo, P; Tadel, M

2009-01-01

ROOT is an object-oriented C++ framework conceived in the high-energy physics (HEP) community, designed for storing and analyzing petabytes of data in an efficient way. Any instance of a C++ class can be stored into a ROOT file in a machine-independent compressed binary format. In ROOT the TTree object container is optimized for statistical data analysis over very large data sets by using vertical data storage techniques. These containers can span a large number of files on local disks, the web, or a number of different shared file systems. In order to analyze this data, the user can chose out of a wide set of mathematical and statistical functions, including linear algebra classes, numerical algorithms such as integration and minimization, and various methods for performing regression analysis (fitting). In particular, the RooFit package allows the user to perform complex data modeling and fitting while the RooStats library provides abstractions and implementations for advanced statistical tools. Multivariat...

Serum-dependent selective expression of EhTMKB1-9, a member of Entamoeba histolytica B1 family of transmembrane kinases.

Directory of Open Access Journals (Sweden)

Shiteshu Shrimal

Full Text Available Entamoeba histolytica transmembrane kinases (EhTMKs can be grouped into six distinct families on the basis of motifs and sequences. Analysis of the E. histolytica genome revealed the presence of 35 EhTMKB1 members on the basis of sequence identity (>or=95%. Only six homologs were full length containing an extracellular domain, a transmembrane segment and an intracellular kinase domain. Reverse transcription followed by polymerase chain reaction (RT-PCR of the kinase domain was used to generate a library of expressed sequences. Sequencing of randomly picked clones from this library revealed that about 95% of the clones were identical with a single member, EhTMKB1-9, in proliferating cells. On serum starvation, the relative number of EhTMKB1-9 derived sequences decreased with concomitant increase in the sequences derived from another member, EhTMKB1-18. The change in their relative expression was quantified by real time PCR. Northern analysis and RNase protection assay were used to study the temporal nature of EhTMKB1-9 expression after serum replenishment of starved cells. The results showed that the expression of EhTMKB1-9 was sinusoidal. Specific transcriptional induction of EhTMKB1-9 upon serum replenishment was further confirmed by reporter gene (luciferase expression and the upstream sequence responsible for serum responsiveness was identified. EhTMKB1-9 is one of the first examples of an inducible gene in Entamoeba. The protein encoded by this member was functionally characterized. The recombinant kinase domain of EhTMKB1-9 displayed protein kinase activity. It is likely to have dual specificity as judged from its sensitivity to different kinase inhibitors. Immuno-localization showed EhTMKB1-9 to be a surface protein which decreased on serum starvation and got relocalized on serum replenishment. Cell lines expressing either EhTMKB1-9 without kinase domain, or EhTMKB1-9 antisense RNA, showed decreased cellular proliferation and target cell

Enhanced Shear-induced Platelet Aggregation Due to Low-temperature Storage

Science.gov (United States)

2013-07-01

Grewal PK, Wandall HH, Josefsson EC, Sorensen AL, Larson G, Marth JD, Hartwig JH, Hoffmeister KM. Dual roles for hepatic lectin receptors in the clearance ...PLT aggregation due to low temperature storage may be a beneficial strategy to prevent severe bleeding in trauma . P latelets (PLTs) are transfused to...prevent bleed- ing due to thrombocytopenia associated with hematologic malignancies or to manage severe blood loss during surgery or trauma . PLTs are

Monitoring of the Proton Electrochemical Gradient in Reconstituted Vesicles: Quantitative Measurements of Both Transmembrane Potential and Intravesicular pH by Ratiometric Fluorescent Probes

Czech Academy of Sciences Publication Activity Database

Holoubek, A.; Večeř, J.; Sigler, Karel

2007-01-01

Roč. 17, - (2007), s. 201-213 ISSN 1053-0509 Institutional research plan: CEZ:AV0Z50200510 Keywords : transmembrane potential * intracellular ph * oxonol dyes Subject RIV: EE - Microbiology, Virology Impact factor: 2.101, year: 2007

PBMR spent fuel bulk dry storage heat removal - HTR2008-58170

International Nuclear Information System (INIS)

De Wet, G. J.; Dent, C.

2008-01-01

A low decay heat (implying Spent Fuel (SF) pebbles older than 8-9 years) bulk dry storage section is proposed to supplement a 12-tank wet storage section. Decay heat removal by passive means must be guaranteed, taking into account the fact that dry storage vessels are under ground and inside the building footprint. Cooling takes place when ambient air (drawn downwards from ground level) passes on the outside of the 6 tanks' vessel containment (and gamma shielding), which is in a separate room inside the building, but outside PBMR building confinement and open to atmosphere. Access for loading/unloading of SF pebbles is only from the top of a tank, which is inside PBMR building confinement. No radioactive substances can therefore leak into atmosphere, as vessel design will take into account corrosion allowance. In this paper, it is shown (using CFD (Computational Fluid Dynamics) modelling and analytical analyses) that natural convection and draught induced flow combine to remove decay heat in a self-sustaining process. Decay heat is the energy source, which powers the draught inducing capability of the dry storage modular cell system: the more decay heat, the bigger the drive to expel heated air through a higher outlet and entrain cool ambient air from ground level to the bottom of the modular cell. (authors)

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

Science.gov (United States)

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

2015-10-07

Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

Radiation-induced defects and their recombination processes in the x-ray storage phosphor BaBr sub 2 :Eu sup 2 sup +

CERN Document Server

Secu, M; Rogulis, U; Spaeth, J M

2003-01-01

The recombination processes in the x-ray storage phosphor BaBr sub 2 :Eu sup 2 sup + were investigated by optical and magneto-optical methods. A structure-sensitive investigation of the defects involved in the recombination processes was performed by detecting the microwave-induced changes in the recombination luminescence in a high magnetic field. F centres as well as V sub K hole centres are created after x-irradiation at low temperatures. The low-energy recombination band peaking at about 460 nm is due to F-V sub K centre recombinations, whereas the two high energy bands at 282 and 315 nm are probably due to recombinations of self-trapped excitons.

Independent Review of Tank 241-AY-101 Fitness for Service

International Nuclear Information System (INIS)

Stewart, Charles W.; Bush, Spencer H.; Delegard, Calvin H.; Elmore, Monte R.; Johnson, A Burton Jr.; Pardini, Allan F.; Posakony, Gerald J.; Simonen, Fredric A.; Terry, Michael T.; Zapp, Philip E.

2003-01-01

Video inspections in the annulus of Hanford double-shell waste storage tank 241-AY-101 in 2001 and earlier showed rust over large areas of the primary and secondary tank walls. These observations led to extensive on-destructive inspections and analyses to determine the extent and severity of the corrosion and correction of several operational deficiencies that contributed to the problem. PNNL has performed an independent review of the accumulated evidence from these efforts to determine whether unacceptable conditions were corrected and the current condition of the tank meets or exceeds technical and operational requirements. The findings of this review are the subject of this report. The conclusion is that AY-101 is fit for service without restriction subject to several recommendations for further inspections and analyses

Dimers of G-Protein Coupled Receptors as Versatile Storage and Response Units

Directory of Open Access Journals (Sweden)

Michael S. Parker

2014-03-01

Full Text Available The status and use of transmembrane, extracellular and intracellular domains in oligomerization of heptahelical G-protein coupled receptors (GPCRs are reviewed and for transmembrane assemblies also supplemented by new experimental evidence. The transmembrane-linked GPCR oligomers typically have as the minimal unit an asymmetric ~180 kDa pentamer consisting of receptor homodimer or heterodimer and a G-protein αβγ subunit heterotrimer. With neuropeptide Y (NPY receptors, this assembly is converted to ~90 kDa receptor monomer-Gα complex by receptor and Gα agonists, and dimers/heteropentamers are depleted by neutralization of Gαi subunits by pertussis toxin. Employing gradient centrifugation, quantification and other characterization of GPCR dimers at the level of physically isolated and identified heteropentamers is feasible with labeled agonists that do not dissociate upon solubilization. This is demonstrated with three neuropeptide Y (NPY receptors and could apply to many receptors that use large peptidic agonists.

Limitations of inclusive fitness.

Science.gov (United States)

Allen, Benjamin; Nowak, Martin A; Wilson, Edward O

2013-12-10

Until recently, inclusive fitness has been widely accepted as a general method to explain the evolution of social behavior. Affirming and expanding earlier criticism, we demonstrate that inclusive fitness is instead a limited concept, which exists only for a small subset of evolutionary processes. Inclusive fitness assumes that personal fitness is the sum of additive components caused by individual actions. This assumption does not hold for the majority of evolutionary processes or scenarios. To sidestep this limitation, inclusive fitness theorists have proposed a method using linear regression. On the basis of this method, it is claimed that inclusive fitness theory (i) predicts the direction of allele frequency changes, (ii) reveals the reasons for these changes, (iii) is as general as natural selection, and (iv) provides a universal design principle for evolution. In this paper we evaluate these claims, and show that all of them are unfounded. If the objective is to analyze whether mutations that modify social behavior are favored or opposed by natural selection, then no aspect of inclusive fitness theory is needed.

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

Science.gov (United States)

Yüksel, Melih; Power, Jeffrey J; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike

2016-01-01

In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.

Getting CSR communication fit

DEFF Research Database (Denmark)

Schmeltz, Line

2017-01-01

Companies experience increasing legal and societal pressure to communicate about their corporate social responsibility (CSR) engagements from a number of different publics. One very important group is that of young consumers who are predicted to be the most important and influential consumer group...... in the near future. From a value- theoretical base, this article empirically explores the role and applicability of ‘fit’ in strategic CSR communication targeted at young consumers. Point of departure is taken in the well-known strategic fit (a logical link between a company’s CSR commitment and its core...... values) and is further developed by introducing two additional fits, the CSR- Consumer fit and the CSR-Consumer-Company fit (Triple Fit). Through a sequential design, the three fits are empirically tested and their potential for meeting young consumers’ expectations for corporate CSR messaging...

Automated ligand fitting by core-fragment fitting and extension into density

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Klei, Herbert; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2006-01-01

An automated ligand-fitting procedure has been developed and tested on 9327 ligands and (F o − F c )exp(iϕ c ) difference density from macromolecular structures in the Protein Data Bank. A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 Å) from the Protein Data Bank (PDB) into (F o − F c )exp(iϕ c ) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 Å (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10–100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58–73% over all resolution ranges tested

Quality control of fresh sweet corn in controlled freezing-point storage

African Journals Online (AJOL)

Jane

2011-10-24

Oct 24, 2011 ... packaging on alleviating chilling injury during CF storage were also ... investigated. MATERIALS AND METHODS. Plant material and experimental design .... Sugar, as one of osmotic active substances, can be induced by cold ...

Function and expression of cystic fibrosis transmembrane conductance regulator after small intestinal transplantation in mice.

Directory of Open Access Journals (Sweden)

Penghong Song

Full Text Available The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR mediates HCO3(- and Cl(- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3(- and Cl(- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (I(sc techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3(- and Cl(- secretions in mice, but forskolin-stimulated HCO3(- and Cl(- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001. The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001, and the mRNA and protein expression levels of tumor necrosis factor α (TNFα were markedly increased in donor jejunal mucosae of mice (P<0.001, compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα.

Compressed gas fuel storage system

Science.gov (United States)

Wozniak, John J.; Tiller, Dale B.; Wienhold, Paul D.; Hildebrand, Richard J.

2001-01-01

A compressed gas vehicle fuel storage system comprised of a plurality of compressed gas pressure cells supported by shock-absorbing foam positioned within a shape-conforming container. The container is dimensioned relative to the compressed gas pressure cells whereby a radial air gap surrounds each compressed gas pressure cell. The radial air gap allows pressure-induced expansion of the pressure cells without resulting in the application of pressure to adjacent pressure cells or physical pressure to the container. The pressure cells are interconnected by a gas control assembly including a thermally activated pressure relief device, a manual safety shut-off valve, and means for connecting the fuel storage system to a vehicle power source and a refueling adapter. The gas control assembly is enclosed by a protective cover attached to the container. The system is attached to the vehicle with straps to enable the chassis to deform as intended in a high-speed collision.

Impact of biofilm accumulation on transmembrane and feed channel pressure drop: Effects of crossflow velocity, feed spacer and biodegradable nutrient

KAUST Repository

Dreszer, C.

2014-03-01

Biofilm formation causes performance loss in spiral-wound membrane systems. In this study a microfiltration membrane was used in experiments to simulate fouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) membrane modules without the influence of concentration polarization. The resistance of a microfiltration membrane is much lower than the intrinsic biofilm resistance, enabling the detection of biofilm accumulation in an early stage. The impact of biofilm accumulation on the transmembrane (biofilm) resistance and feed channel pressure drop as a function of the crossflow velocity (0.05 and 0.20ms-1) and feed spacer presence was studied in transparent membrane biofouling monitors operated at a permeate flux of 20Lm-2h-1. As biodegradable nutrient, acetate was dosed to the feed water (1.0 and 0.25mgL-1 carbon) to enhance biofilm accumulation in the monitors. The studies showed that biofilm formation caused an increased transmembrane resistance and feed channel pressure drop. The effect was strongest at the highest crossflow velocity (0.2ms-1) and in the presence of a feed spacer. Simulating conditions as currently applied in nanofiltration and reverse osmosis installations (crossflow velocity 0.2ms-1 and standard feed spacer) showed that the impact of biofilm formation on performance, in terms of transmembrane and feed channel pressure drop, was strong. This emphasized the importance of hydrodynamics and feed spacer design. Biomass accumulation was related to the nutrient load (nutrient concentration and linear flow velocity). Reducing the nutrient concentration of the feed water enabled the application of higher crossflow velocities. Pretreatment to remove biodegradable nutrient and removal of biomass from the membrane elements played an important part to prevent or restrict biofouling. © 2013 Elsevier Ltd.

Childhood cardiorespiratory fitness, muscular fitness and adult measures of glucose homeostasis.

Science.gov (United States)

Fraser, Brooklyn J; Blizzard, Leigh; Schmidt, Michael D; Juonala, Markus; Dwyer, Terence; Venn, Alison J; Magnussen, Costan G

2018-02-14

To assess whether childhood cardiorespiratory fitness (CRF) and muscular fitness phenotypes (strength, power, endurance) predict adult glucose homeostasis measures. Prospective longitudinal study. Study examining participants who had physical fitness measured in childhood (aged 7-15 years) and who attended follow-up clinics approximately 20 years later and provided a fasting blood sample which was tested for glucose and insulin. Physical fitness measurements included muscular strength (right and left grip, shoulder flexion, shoulder and leg extension), power (standing long jump distance) and endurance (number of push-ups in 30s), and CRF (1.6km run duration). In adulthood, fasting glucose and insulin levels were used to derive glucose homeostasis measures of insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β). A standard deviation increase in childhood CRF or muscular strength (males) was associated with fasting glucose (CRF: β=-0.06mmol/L), fasting insulin (CRF: β=-0.73mU/L; strength: β=-0.40mU/L), HOMA2-IR (CRF: β=-0.06; strength: β=-0.05) and HOMA2-β (CRF: β=-3.06%; strength: β=-2.62%) in adulthood, independent of the alternative fitness phenotype (all p0.06). CRF and muscular fitness in childhood were inversely associated with measures of fasting insulin, insulin resistance and beta cell function in adulthood. Childhood CRF and muscular fitness could both be potential independent targets for strategies to help reduce the development of adverse glucose homeostasis. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Energy storage crystalline gel materials for 3D printing application

Science.gov (United States)

Mao, Yuchen; Miyazaki, Takuya; Gong, Jin; Zhu, Meifang

2017-04-01

Phase change materials (PCMs) are considered one of the most reliable latent heat storage and thermoregulation materials. In this paper, a vinyl monomer is used to provide energy storage capacity and synthesize gel with phase change property. The side chain of copolymer form crystal microcell to storage/release energy through phase change. The crosslinking structure of the copolymer can protect the crystalline micro-area maintaining the phase change stable in service and improving the mechanical strength. By selecting different monomers and adjusting their ratios, we design the chemical structure and the crystallinity of gels, which in further affect their properties, such as strength, flexibility, thermal absorb/release transition temperature, transparency and the water content. Using the light-induced polymerization 3D printing techniques, we synthesize the energy storage gel and shape it on a 3D printer at the same time. By optimizing the 3D printing conditions, including layer thickness, curing time and light source, etc., the 3D printing objects are obtained.

Experimental Investigation of Jet-Induced Mixing of a Large Liquid Hydrogen Storage Tank

Science.gov (United States)

Lin, C. S.; Hasan, M. M.; Vandresar, N. T.

1994-01-01

Experiments have been conducted to investigate the effect of fluid mixing on the depressurization of a large liquid hydrogen storage tank. The test tank is approximately ellipsoidal, having a volume of 4.89 m(exp 3) and an average wall heat flux of 4.2 W/m(exp 2) due to external heat input. A mixer unit was installed near the bottom of the tank to generate an upward directed axial jet flow normal to the liquid-vapor interface. Mixing tests were initiated after achieving thermally stratified conditions in the tank either by the introduction of hydrogen gas into the tank or by self-pressurization due to ambient heat leak through the tank wall. The subcooled liquid jet directed towards the liquid-vapor interface by the mixer induced vapor condensation and caused a reduction in tank pressure. Tests were conducted at two jet submergence depths for jet Reynolds numbers from 80,000 to 495,000 and Richardson numbers from 0.014 to 0.52. Results show that the rate of tank pressure change is controlled by the competing effects of subcooled jet flow and the free convection boundary layer flow due to external tank wall heating. It is shown that existing correlations for mixing time and vapor condensation rate based on small scale tanks may not be applicable to large scale liquid hydrogen systems.

A phase transition induces chaos in a predator-prey ecosystem with a dynamic fitness landscape.

Science.gov (United States)

Gilpin, William; Feldman, Marcus W

2017-07-01

In many ecosystems, natural selection can occur quickly enough to influence the population dynamics and thus future selection. This suggests the importance of extending classical population dynamics models to include such eco-evolutionary processes. Here, we describe a predator-prey model in which the prey population growth depends on a prey density-dependent fitness landscape. We show that this two-species ecosystem is capable of exhibiting chaos even in the absence of external environmental variation or noise, and that the onset of chaotic dynamics is the result of the fitness landscape reversibly alternating between epochs of stabilizing and disruptive selection. We draw an analogy between the fitness function and the free energy in statistical mechanics, allowing us to use the physical theory of first-order phase transitions to understand the onset of rapid cycling in the chaotic predator-prey dynamics. We use quantitative techniques to study the relevance of our model to observational studies of complex ecosystems, finding that the evolution-driven chaotic dynamics confer community stability at the "edge of chaos" while creating a wide distribution of opportunities for speciation during epochs of disruptive selection-a potential observable signature of chaotic eco-evolutionary dynamics in experimental studies.

A concept of an electricity storage system with 50 MWh storage capacity

Directory of Open Access Journals (Sweden)

Józef Paska

2012-06-01

Full Text Available Electricity storage devices can be divided into indirect storage technology devices (involving electricity conversion into another form of energy, and direct storage (in an electric or magnetic fi eld. Electricity storage technologies include: pumped-storage power plants, BES Battery Energy Storage, CAES Compressed Air Energy Storage, Supercapacitors, FES Flywheel Energy Storage, SMES Superconducting Magnetic Energy Storage, FC Fuel Cells reverse or operated in systems with electrolysers and hydrogen storage. These technologies have diff erent technical characteristics and economic parameters that determine their usability. This paper presents two concepts of an electricity storage tank with a storage capacity of at least 50 MWh, using the BES battery energy storage and CAES compressed air energy storage technologies.

Tritium storage

International Nuclear Information System (INIS)

Hircq, B.

1990-01-01

This document represents a synthesis relative to tritium storage. After indicating the main storage particularities as regards tritium, storages under gaseous and solid form are after examined before establishing choices as a function of the main criteria. Finally, tritium storage is discussed regarding tritium devices associated to Fusion Reactors and regarding smaller devices [fr

Fitness: Tips for Staying Motivated

Science.gov (United States)

Healthy Lifestyle Fitness Fitness is for life. Motivate yourself with these practical tips. By Mayo Clinic Staff Have ... 27, 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/fitness/art-20047624 . Mayo Clinic ...

Energy storage

International Nuclear Information System (INIS)

2012-01-01

After having outlined the importance of energy storage in the present context, this document outlines that it is an answer to economic, environmental and technological issues. It proposes a brief overview of the various techniques of energy storage: under the form of chemical energy (hydrocarbons, biomass, hydrogen production), thermal energy (sensitive or latent heat storage), mechanical energy (potential energy by hydraulic or compressed air storage, kinetic energy with flywheels), electrochemical energy (in batteries), electric energy (super-capacitors, superconductor magnetic energy storage). Perspectives are briefly evoked

Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles.

Science.gov (United States)

Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A

2010-01-01

Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5min decreased [(3)H]NE uptake capacity, an effect characterized by a robust decrease in the V(max) of the transport of [(3)H]NE. As expected, reserpine did not displace the binding of [(3)H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [(3)H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [(3)H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca(2+)/Ca(2+)-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [(3)H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, alpha-methyl-p-tyrosine, increased [(3)H]NE uptake and eliminated the inhibitory effects of reserpine on [(3)H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca(2+)-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.

A person-environment fit approach to volunteerism : Volunteer personality fit and culture fit as predictors of affective outcomes

NARCIS (Netherlands)

Van Vianen, Annelies E. M.; Nijstad, Bernard A.; Voskuijl, Olga F.

2008-01-01

This study employed a person-environment (P-E) fit approach to explaining volunteer satisfaction, affective commitment, and turnover intentions. It was hypothesized that personality fit would explain additional variance in volunteer affective outcomes above and beyond motives to volunteer. This

A person-environment fit approach to volunteerism: Volunteer personality-fit and culture-fit as predictors of affective outcomes

NARCIS (Netherlands)

van Vianen, A.E.M.; Nijstad, B.A.; Voskuijl, O.F.

2008-01-01

This study employed a person-environment (P-E) fit approach to explaining volunteer satisfaction, affective commitment, and turnover intentions. It was hypothesized that personality fit would explain additional variance in volunteer affective outcomes above and beyond motives to volunteer. This

Direct Observation of Heavy-Tailed Storage Times of Bed Load Tracer Particles Causing Anomalous Superdiffusion

Science.gov (United States)

Bradley, D. Nathan

2017-12-01

A consensus has formed that the step length distribution of fluvial bed load is thin tailed and that the observed anomalous superdiffusion of bed load tracer particles must arise from heavy-tailed resting times. However, heavy-tailed resting times have never been directly observed in the field over multiple floods. Using 9 years of data from a large bed load tracer experiment, I show that the spatial variance of the tracer plume scales faster than linearly with integrated excess stream power, indicating anomalous superdiffusion. The superdiffusion is caused by a heavy-tailed distribution of observed storage times that is fit with a truncated Pareto distribution with a tail parameter that is predicted by anomalous diffusion theory. The heavy-tailed distribution of storage times causes the tracer virtual velocity to slow over time, indicated by a sublinear increase in the mean displacement that is predicted by the storage time distribution tail parameter.

Physical Fitness: Get Your Body Moving

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Physical Fitness: Get Your Body Moving; Exercise; does exercise help quit smoking; exercises after quitting smoking; exercise after smoking; exercise and quitting smoking; exercise and smoking; smoking articles; articles about smoking; articles on smoking; articles about smoking; article on smoking; health articles on smoking; smoking article; benefits of physical activity; benefits for physical activity; benefit of physical activity; benefits to physical activity; daily physical activities; daily physical activity; healthy physical activities; healthy physical activity; health activities; activity for health; exercise physical activity and health; health activities; health activities for kids; health and fitness activities; health benefits for physical activity; health benefits from physical activity; health benefits of physical activity; health benefits physical activity; health promotion activities; physical exercise; exercise and physical activity; exercise and physical health; exercise for physical fitness; health benefits of physical fitness; how to do physical exercise; physical activity and exercise; physical activity exercise; physical health; physical health and fitness; physical health and wellness; physical health benefits; physical Health fitness; what are the benefits of physical fitness; physical fitness; about physical fitness; benefits of physical fitness; how to improve physical fitness; physical fitness; physical fitness article; fitness; fitness article; fitness articles; fitness plans; health and fitness; exercise; benefits of regular exercise on health; exercise plan; exercise tips; routine; best work out routine for overweight women

Chronic anthropogenic noise disrupts glucocorticoid signaling and has multiple effects on fitness in an avian community.

Science.gov (United States)

Kleist, Nathan J; Guralnick, Robert P; Cruz, Alexander; Lowry, Christopher A; Francis, Clinton D

2018-01-23

Anthropogenic noise is a pervasive pollutant that decreases environmental quality by disrupting a suite of behaviors vital to perception and communication. However, even within populations of noise-sensitive species, individuals still select breeding sites located within areas exposed to high noise levels, with largely unknown physiological and fitness consequences. We use a study system in the natural gas fields of northern New Mexico to test the prediction that exposure to noise causes glucocorticoid-signaling dysfunction and decreases fitness in a community of secondary cavity-nesting birds. In accordance with these predictions, and across all species, we find strong support for noise exposure decreasing baseline corticosterone in adults and nestlings and, conversely, increasing acute stressor-induced corticosterone in nestlings. We also document fitness consequences with increased noise in the form of reduced hatching success in the western bluebird ( Sialia mexicana ), the species most likely to nest in noisiest environments. Nestlings of all three species exhibited accelerated growth of both feathers and body size at intermediate noise amplitudes compared with lower or higher amplitudes. Our results are consistent with recent experimental laboratory studies and show that noise functions as a chronic, inescapable stressor. Anthropogenic noise likely impairs environmental risk perception by species relying on acoustic cues and ultimately leads to impacts on fitness. Our work, when taken together with recent efforts to document noise across the landscape, implies potential widespread, noise-induced chronic stress coupled with reduced fitness for many species reliant on acoustic cues.

Direct fitness of group living mammals varies with breeding strategy, climate and fitness estimates.

Science.gov (United States)

Ebensperger, Luis A; Rivera, Daniela S; Hayes, Loren D

2012-09-01

1. Understanding how variation in fitness relates to variation in group living remains critical to determine whether this major aspect of social behaviour is currently adaptive. 2. Available evidence in social mammals aimed to examine this issue remains controversial. Studies show positive (i.e. potentially adaptive), neutral or even negative fitness effects of group living. 3. Attempts to explain this variation rely on intrinsic and extrinsic factors to social groups. Thus, relatively more positive fitness effects are predicted in singularly breeding as opposed to plural breeding species. Fitness effects of sociality in turn may depend on ecological conditions (i.e. extrinsic factors) that influence associated benefits and costs. 4. We used meta-analytic tools to review how breeding strategy or ecological conditions influence the effect size associated with direct fitness-sociality relationships reported in the mammalian literature. Additionally, we determined how taxonomic affiliation of species studied, different fitness and sociality measures used, and major climatic conditions of study sites explained any variation in direct fitness effect size. 5. We found group living had modest, yet positive effects on direct fitness. This generally adaptive scenario was contingent not only upon breeding strategy and climate of study sites, but also on fitness measures examined. Thus, positive and significant effects characterized singular as opposed to plural breeding strategies. 6. We found more positive fitness effects on studies conducted in tropical as opposed to temperate or arid climates. More positive and significant effects were noted on studies that relied on group fecundity, male fecundity and offspring survival as measures of fitness. 7. To conclude, direct fitness consequences of mammalian group living are driven by interspecific differences in breeding strategy and climate conditions. Other factors not examined in this study, namely individual variation in

Microkinetic Modeling of Lean NO_x Trap Storage and Regeneration

Energy Technology Data Exchange (ETDEWEB)

Larson, Richard S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Chakravarthy, V. Kalyana [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Pihl, Josh A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Daw, C. Stuart [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2011-12-01

A microkinetic chemical reaction mechanism capable of describing both the storage and regeneration processes in a fully formulated lean NOx trap (LNT) is presented. The mechanism includes steps occurring on the precious metal, barium oxide (NOx storage), and cerium oxide (oxygen storage) sites of the catalyst. The complete reaction set is used in conjunction with a transient plug flow reactor code (including boundary layer mass transfer) to simulate not only a set of long storage/regeneration cycles with a CO/H2 reductant, but also a series of steady flow temperature sweep experiments that were previously analyzed with just a precious metal mechanism and a steady state code neglecting mass transfer. The results show that, while mass transfer effects are generally minor, NOx storage is not negligible during some of the temperature ramps, necessitating a re-evaluation of the precious metal kinetic parameters. The parameters for the entire mechanism are inferred by finding the best overall fit to the complete set of experiments. Rigorous thermodynamic consistency is enforced for parallel reaction pathways and with respect to known data for all of the gas phase species involved. It is found that, with a few minor exceptions, all of the basic experimental observations can be reproduced with the transient simulations. In addition to accounting for normal cycling behavior, the final mechanism should provide a starting point for the description of further LNT phenomena such as desulfation and the role of alternative reductants.

Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.

Science.gov (United States)

Gozu, Hulya; Avsar, Melike; Bircan, Rifat; Claus, Maren; Sahin, Serap; Sezgin, Ozlem; Deyneli, Oguzhan; Paschke, Ralf; Cirakoglu, Beyazit; Akalin, Sema

2005-04-01

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Solid state deuterium nuclear magnetic resonance detection of transmembrane-potential-driven tetraphenylphosphonium redistribution across Giant Unilamellar Vesicle bilayers

International Nuclear Information System (INIS)

Franzin, Carla Maria Mirella

1995-01-01

It has been demonstrated that deuterium nuclear magnetic resonance ( 2 H NMR) of Giant Unilamellar Vesicles (GUVs) consisting of specifically choline-deuterated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and cholesterol can be used to monitor the transbilayer redistribution of tetraphenylphosphonium (TPP + ) in response to a transmembrane potential (δψ tm ). The 2 H quadrupolar splittings (δν Q 's) measured reflect the level of TPP + bound at the membrane surface due to the latter's effect on the membrane surface electrostatic potential, ψ s . Results reveal the appearance of two distinct δν Q 's, due to differences in bound TPP + at the inner versus the outer monolayer in response to a δψ tm . The observed values of the δν Q 's agree with theoretical predictions based on a derived mathematical model that takes into account δψ tm , plus ψ s , plus the equilibrium binding of TPP + from solution onto the membrane surface, plus the sensitivity of δν Q to the amount of bound TPP + . This model identifies experimental factors that lead to improvements in spectral resolution. Henceforth, 2 H NMR is a valuable tool for quantifying transmembrane asymmetries of ψ s . (author)

Analysis of radicals induced in irradiated foods

International Nuclear Information System (INIS)

Kishida, Keigo; Kaimori, Yoshihiko; Kawamura, Shoei; Sakamoto, Yuhki; Nakamura, Hideo; Ukai, Mitsuko; Kikuchi, Masahiro; Shimoyama, Yuhei; Kobayashi, Yasuhiko

2012-01-01

By electron spin resonance (ESR) spectroscopy, we revealed free radicals in γ-ray irradiated foods; black pepper, green coffee bean and ginseng. We also analyzed the decay behavior of radiation induced free radicals during storage of irradiated foods. The ESR spectrum of experimental irradiated foods consists of a sextet signal centered at g=2.0 and a singlet signal at the same g-value position and a singlet signal at g=4.0. The singlet signal at g=2.0 is originated from organic free radicals and its peak intensity showed the dependence of γ-ray irradiation dose levels. The signal intensity was decreased during storage. Only after 3 hours of radiation treatment the peak intensity was decreased fast and after that the intensity was decreased slowly. The relaxation times, T 1 and T 2 , of radiation induced free radicals showed the variations before and after irradiation. During long time storage period it was shown that T 1 was increased and T 2 was decreased. By analysis of decay process using the simulation methods based on the theory of reaction speed, it is considered that at least two kinds of radicals were induced in irradiated foods during long time storage. (author)

Direct benefits of choosing a high-fitness mate can offset the indirect costs associated with intralocus sexual conflict.

Science.gov (United States)

Pischedda, Alison; Chippindale, Adam K

2017-06-01

Intralocus sexual conflict generates a cost to mate choice: high-fitness partners transmit genetic variation that confers lower fitness to offspring of the opposite sex. Our earlier work in the fruit fly, Drosophila melanogaster, revealed that these indirect genetic costs were sufficient to reverse potential "good genes" benefits of sexual selection. However, mate choice can also confer direct fitness benefits by inducing larger numbers of progeny. Here, we consider whether direct benefits through enhanced fertility could offset the costs associated with intralocus sexual conflict in D. melanogaster. Using hemiclonal analysis, we found that females mated to high-fitness males produced 11% more offspring compared to those mated to low-fitness males, and high-fitness females produced 34% more offspring than low-fitness females. These direct benefits more than offset the reduction in offspring fitness caused by intralocus sexual conflict, creating a net fitness benefit for each sex to pairing with a high-fitness partner. Our findings highlight the need to consider both direct and indirect effects when investigating the fitness impacts of mate choice. Direct fitness benefits may shelter sexually antagonistic alleles from selection, suggesting a novel mechanism for the maintenance of fitness variation. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Efficient numerical simulation of heat storage in subsurface georeservoirs

Science.gov (United States)

Boockmeyer, A.; Bauer, S.

2015-12-01

The transition of the German energy market towards renewable energy sources, e.g. wind or solar power, requires energy storage technologies to compensate for their fluctuating production. Large amounts of energy could be stored in georeservoirs such as porous formations in the subsurface. One possibility here is to store heat with high temperatures of up to 90°C through borehole heat exchangers (BHEs) since more than 80 % of the total energy consumption in German households are used for heating and hot water supply. Within the ANGUS+ project potential environmental impacts of such heat storages are assessed and quantified. Numerical simulations are performed to predict storage capacities, storage cycle times, and induced effects. For simulation of these highly dynamic storage sites, detailed high-resolution models are required. We set up a model that accounts for all components of the BHE and verified it using experimental data. The model ensures accurate simulation results but also leads to large numerical meshes and thus high simulation times. In this work, we therefore present a numerical model for each type of BHE (single U, double U and coaxial) that reduces the number of elements and the simulation time significantly for use in larger scale simulations. The numerical model includes all BHE components and represents the temporal and spatial temperature distribution with an accuracy of less than 2% deviation from the fully discretized model. By changing the BHE geometry and using equivalent parameters, the simulation time is reduced by a factor of ~10 for single U-tube BHEs, ~20 for double U-tube BHEs and ~150 for coaxial BHEs. Results of a sensitivity study that quantify the effects of different design and storage formation parameters on temperature distribution and storage efficiency for heat storage using multiple BHEs are then shown. It is found that storage efficiency strongly depends on the number of BHEs composing the storage site, their distance and

Staphylococcus aureus α-Toxin Induces Actin Filament Remodeling in Human Airway Epithelial Model Cells.

Science.gov (United States)

Ziesemer, Sabine; Eiffler, Ina; Schönberg, Alfrun; Müller, Christian; Hochgräfe, Falko; Beule, Achim G; Hildebrandt, Jan-Peter

2018-04-01

Exposure of cultured human airway epithelial model cells (16HBE14o-, S9) to Staphylococcus aureus α-toxin (hemolysin A, Hla) induces changes in cell morphology and cell layer integrity that are due to the inability of the cells to maintain stable cell-cell or focal contacts and to properly organize their actin cytoskeletons. The aim of this study was to identify Hla-activated signaling pathways involved in regulating the phosphorylation level of the actin-depolymerizing factor cofilin. We used recombinant wild-type hemolysin A (rHla) and a variant of Hla (rHla-H35L) that is unable to form functional transmembrane pores to treat immortalized human airway epithelial cells (16HBE14o-, S9) as well as freshly isolated human nasal tissue. Our results indicate that rHla-mediated changes in cofilin phosphorylation require the formation of functional Hla pores in the host cell membrane. Formation of functional transmembrane pores induced hypophosphorylation of cofilin at Ser3, which was mediated by rHla-induced attenuation of p21-activated protein kinase and LIM kinase activities. Because dephosphorylation of pSer3-cofilin results in activation of this actin-depolymerizing factor, treatment of cells with rHla resulted in loss of actin stress fibers from the cells and destabilization of cell shape followed by the appearance of paracellular gaps in the cell layers. Activation of protein kinase A or activation of small GTPases (Rho, Rac, Cdc42) do not seem to be involved in this response.

Exercise in muscle glycogen storage diseases

DEFF Research Database (Denmark)

Preisler, Nicolai Rasmus; Haller, Ronald G; Vissing, John

2015-01-01

exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies...... that have examined the effect of regular exercise training in different types of GSD. Finally, we consider how oral substrate supplementation can improve exercise tolerance and we discuss the precautions that apply to persons with GSD that engage in exercise.......Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase...

Fire hazards analysis for W-413, West Area Tank Farm Storage and Staging Facility

International Nuclear Information System (INIS)

Huckfeldt, R.A.; Lott, D.T.

1994-01-01

In accordance with DOE Order 5480.7A, a Fire Hazards Analysis must be performed for all new facilities. The purpose of the analysis is to comprehensively assess the risk from fire within individual fire areas in relation to proposed fire protection so as to ascertain whether the fire protection objectives of the Order are met. The Order acknowledges a graded approach commensurate with the hazards involved. Tank Farms Operations must sore/stage material and equipment such as pipes, fittings, conduit, instrumentation and others related items until work packages are ready to work. Consumable materials, such as nut, bolts and welding rod, are also requires to be stored for routine and emergency work. Connex boxes and open storage is currently used for much of the storage because of the limited space at and 272WA. Safety issues based on poor housekeeping and material deteriorating due to weather damage has resulted from this inadequate storage space. It has been determined that a storage building in close proximity to the Tank Farm work force would be cost effective. This facility is classified as a safety class 4 building

Measurement and Modeling of Respiration Rate of Tomato (Cultivar Roma) for Modified Atmosphere Storage.

Science.gov (United States)

Kandasamy, Palani; Moitra, Ranabir; Mukherjee, Souti

2015-01-01

Experiments were conducted to determine the respiration rate of tomato at 10, 20 and 30 °C using closed respiration system. Oxygen depletion and carbon dioxide accumulation in the system containing tomato was monitored. Respiration rate was found to decrease with increasing CO2 and decreasing O2 concentration. Michaelis-Menten type model based on enzyme kinetics was evaluated using experimental data generated for predicting the respiration rate. The model parameters that obtained from the respiration rate at different O2 and CO2 concentration levels were used to fit the model against the storage temperatures. The fitting was fair (R2 = 0.923 to 0.970) when the respiration rate was expressed as O2 concentation. Since inhibition constant for CO2 concentration tended towards negetive, the model was modified as a function of O2 concentration only. The modified model was fitted to the experimental data and showed good agreement (R2 = 0.998) with experimentally estimated respiration rate.

Implementation of dipolar direct current (DDC) collision-induced dissociation in storage and transmission modes on a quadrupole/time-of-flight tandem mass spectrometer.

Science.gov (United States)

Webb, Ian K; Londry, Frank A; McLuckey, Scott A

2011-09-15

Means for effecting dipolar direct current collision-induced dissociation (DDC CID) on a quadrupole/time-of-flight in a mass spectrometer have been implemented for the broadband dissociation of a wide range of analyte ions. The DDC fragmentation method in electrodynamic storage and transmission devices provides a means for inducing fragmentation of ions over a large mass-to-charge range simultaneously. It can be effected within an ion storage step in a quadrupole collision cell that is operated as a linear ion trap or as ions are continuously transmitted through the collision cell. A DDC potential is applied across one pair of rods in the quadrupole collision cell of a QqTOF hybrid mass spectrometer to effect fragmentation. In this study, ions derived from a small drug molecule, a model peptide, a small protein, and an oligonucleotide were subjected to the DDC CID method in either an ion trapping or an ion transmission mode (or both). Several key experimental parameters that affect DDC CID results, such as time, voltage, low mass cutoff, and bath gas pressure, are illustrated with protonated leucine enkephalin. The DDC CID dissociation method gives a readily tunable, broadband tool for probing the primary structures of a wide range of analyte ions. The method provides an alternative to the narrow resonance conditions of conventional ion trap CID and it can access more extensive sequential fragmentation, depending upon conditions. The DDC CID approach constitutes a collision analog to infrared multiphoton dissociation (IRMPD). Copyright © 2011 John Wiley & Sons, Ltd.

Catalytic combustion of propane in a membrane reactor with separate feed of reactants—II. Operation in presence of trans-membrane pressure gradients

NARCIS (Netherlands)

Saracco, Guido; Veldsink, Jan Willem; Versteeg, Geert F.; Swaaij, Wim P.M. van

1995-01-01

This is the second communication of a series dealing with an experimental and modelling study on propane catalytic combustion in a membrane reactor with separate feed of reactants. In paper I the behaviour of the reactor in the absence of trans-membrane pressure gradients was presented and

Dry storage of MTR spent fuel from the Argentine radioisotope production reactor RA-3

International Nuclear Information System (INIS)

Di Marco, A.; Gillaume, E.J.; Ruggirello, G.; Zaweruchi, A.

1996-01-01

The nuclear fuel elements of the RA-3 reactor consist in 19 rectangular fuel plates held in position by two lateral structural plates. The whole assembly is coupled to the lower nozzles that fits in the reactor core grid. The inner plates are 1.5 mm thick, 70.5 mm wide and 655 mm long and the outer plates are 100 mm longer. The fuel plates are formed by a core of an AI-U alloy co-laminated between two plates of Al. Enrichment is 90% 235 U. After being extracted from the reactor, the fuel elements have been let to cool down in the reactor storage pool and finally moved to the storage facility. This facility is a grid of vertical underground channels connected by a piping system. The system is filled with processed and controlled water. At the present the storage capacity of the facility is near to be depleted and some indications of deterioration of the fuel elements has been detected. Due to the present status of the facility and the spent fuel stored there, a decision has been taken to proceed to modify the present underwater storage to dry storage. The project consist in: a) Decontamination and conditioning of the storage channels to prepare them for dry storage. b) Disassembly of the fuel elements in hot cells in order to can only the active fuel plates in an adequate tight canister. c) The remnant structural pieces will be treated as low level waste. (author). 10 figs

Effect of irradiation on Nε-carboxymethyl-lysine and Nε-carboxyethyl-lysine formation in cooked meat products during storage

International Nuclear Information System (INIS)

Yu, Ligang; He, Zhiyong; Zeng, Maomao; Zheng, Zongping; Chen, Jie

2016-01-01

This study investigated the effects of irradiation on N ε -carboxymethyl-lysine (CML) and N ε -carboxyethyl-lysine (CEL) formation in cooked red and white meats during storage. The results showed that irradiation did not affect CML/CEL formation (0 weeks). After 6 weeks, CML/CEL contents in the irradiated samples exhibited a higher growth rate than the non-irradiated samples, especially the red meat. The results of electron spin resonance spectrometry and 2-Thiobarbituric acid-reactive substances suggested irradiation had induced free-radical reactions and accelerated lipid oxidation during storage. A linear correlation (r=0.810–0.906, p<0.01) was found between the loss of polyunsaturated fatty acids content and increase of CML/CEL content in the irradiated samples after 0 and 6 weeks of storage. The results indicate that irradiation-induced lipid oxidation promotes CML/CEL formation, and CML/CEL formation by the lipid oxidation pathways may be an important pathway for CML/CEL accumulation in irradiated meat products during storage. - Highlights: • The effect of irradiation on CML and CEL formation in meat products is investigated. • CML and CEL contents in irradiated meat products exhibit a higher growth rate than non-irradiated samples. • PUFAs oxidation induced by irradiation promotes CML and CEL formation. • Lipid oxidation pathways are an important pathway for CML and CEL accumulation in irradiated samples during storage.

Biased and Constitutive Signaling in the CC-Chemokine Receptor CCR5 by manipulating the Interface between Transmembrane Helix 6 and 7

DEFF Research Database (Denmark)

Steen, Anne; Thiele, Stefanie; Guo, Dong

2013-01-01

The equilibrium state of CCR5 is manipulated here toward either activation or inactivation by introduction of single amino acid substitutions in the transmembrane domains (TMs) 6 and 7. Insertion of a steric hindrance mutation in the center of TM7 (G286F in position VII:09/7.42) resulted in biase...

Cost and implications of a middle-term program for storage of spent fuel in a nuclear power station (BWR)

International Nuclear Information System (INIS)

Mochon, J.L.; Quintana, R.

1978-01-01

The experience gained with the Cofrentes Nuclear Power Station Project is presented. Originally the station had two spent fuel storage pools, in the fuel building, plus a little pool inside the containment, and all were to be fitted with extensive aluminium storage racks with a total capacity for 1+-1/3 cores. Due to the present world situation with regard to the ''back-end''of the fuel cycle, it was decided to enlarge the pools size and to change the design of the racks, to obtain a final storage capacity of 5+-1/4 cores, so covering over 18 years of operation. The changes introduced in the project, as well as its costs, and the possibilities of election still open are examined in the paper. (author)

Extensive fitness and human cooperation

NARCIS (Netherlands)

van Hateren, J. H.

2015-01-01

Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to increase their fitness. The combined effect is known

"Getting Fit Basically Just Means, Like, Nonfat": Children's Lessons in Fitness and Fatness

Science.gov (United States)

Powell, Darren; Fitzpatrick, Katie

2015-01-01

Current concerns about a childhood obesity crisis and children's physical activity levels have combined to justify fitness lessons as a physical education practice in New Zealand primary (elementary) schools. Researchers focused on children's understandings of fitness lessons argue that they construct fitness as a quest for an "ideal"…

Stress induced enhanced polarization in multilayer BiFeO{sub 3}/BaTiO{sub 3} structure with improved energy storage properties

Energy Technology Data Exchange (ETDEWEB)

Sharma, Savita [Department of Physics and Astrophysics, University of Delhi, Delhi (India); Department of Applied Physics, Delhi Technological University, Delhi (India); Tomar, Monika [Physics Department, Miranda House, University of Delhi, Delhi (India); Kumar, Ashok [CSIR-National Physical Laboratory, Dr. K.S .Krishnan Marg, Delhi (India); Puri, Nitin K. [Department of Applied Physics, Delhi Technological University, Delhi (India); Gupta, Vinay, E-mail: vgupta@physics.du.ac.in, E-mail: drguptavinay@gmail.com [Department of Physics and Astrophysics, University of Delhi, Delhi (India)

2015-10-15

Present work reports the fabrication of a multilayer (5-layer) structure of BiFeO{sub 3}(BFO)/BaTiO{sub 3}(BTO) using spin-coating technique. The crystallographic structure, surface morphology and ferroelectric behavior of multilayer structure in metal-ferroelectric-metal capacitor have been studied. Le-Bail refinement of X-ray diffraction data revealed the formation of polycrystalline pure perovskite phase with induced stress. The values of remnant (P{sub r}) and saturation polarization (P{sub s}) for BFO/BTO multilayer structure are found to be 38.14 μC/cm{sup 2} and 71.54 μC/cm{sup 2} respectively, which are much higher than the corresponding values reported for bare BFO thin film. A large value of dielectric constant of 187 has been obtained for multilayer structure with a low leakage current density of 1.09 × 10{sup −7} A/cm{sup 2} at applied bias of 10 V. The BFO/BTO multilayer structure favors the enhanced energy storage capacity as compared to bare BFO thin film with improved values of energy-density and charge-discharge efficiency as 121 mJ/cm{sup 3} and 59% respectively, suggesting futuristic energy storage applications.

Adiposity, Aerobic Fitness, Muscle Fitness, and Markers of Inflammation in Children

DEFF Research Database (Denmark)

Steene-Johannessen, Jostein; Kolle, Elin; Andersen, Lars Bo

2013-01-01

PURPOSE: The purpose of this study was to describe levels of inflammation markers in Norwegian children and to examine the associations of adiposity, aerobic fitness and muscle fitness with markers of inflammation. METHODS: In 2005-2006, 1467 9-year-olds wererandomly selected from all regions...... explosive, isometric and endurance strength. Aerobic fitness was measured directly during a maximal cycle ergometer test. Adiposity was expressed as waist circumference (WC). RESULTS: The girls had significantly higher levels of CRP, leptin, adiponectin and resistin and lower levels of TNF-α compared...

Extended storage of low-level radioactive waste: potential problem areas

International Nuclear Information System (INIS)

Siskind, B.; Dougherty, D.R.; MacKenzie, D.R.

1985-01-01

If a state or state compact does not have adequate disposal capacity for low-level radioactive waste (LLRW) by 1986 as required by the Low-Level Waste Policy Act, then extended storage of certain LLRW may be necessary. The issue of extended storage of LLRW is addressed in order to determine for the Nuclear Regulatory Commission the areas of concern and the actions recommended to resolve these concerns. The focus is on the properties and behavior of the waste form and waste container. Storage alternatives are considered in order to characterize the likely storage environments for these wastes. The areas of concern about extended storage of LLRW are grouped into two categories: 1. Behavior of the waste form and/or container during storage, e.g., radiolytic gas generation, radiation-enhanced degradation of polymeric materials, and corrosion. 2. Effects of extended storage on the properties of the waste form and/or container that are important after storage (e.g., radiation-induced oxidative embrittlement of high-density polyethylene and the weakening of steel containers resulting from corrosion by the waste). The additional information and actions required to address these concerns are discussed and, in particular, it is concluded that further information is needed on the rates of corrosion of container material by Class A wastes and on the apparent dose-rate dependence of radiolytic processes in Class B and C waste packages. Modifications to the guidance for solidified wastes and high-integrity containers in NRC's Technical Position on Waste Form are recommended. 27 references

Thermochemical Heat Storage: from Reaction Storage Density to System Storage Density

NARCIS (Netherlands)

Jong, A.J. de; Vliet, L.D. van; Hoegaerts, C.L.G.; Roelands, C.P.M.; Cuypers, R.

2016-01-01

Long-term and compact storage of solar energy is crucial for the eventual transition to a 100% renewable energy economy. For this, thermochemical materials provide a promising solution. The compactness of a long-term storage system is determined by the thermochemical reaction, operating conditions,

Analysis and Design of Cryogenic Pressure Vessels for Automotive Hydrogen Storage

Science.gov (United States)

Espinosa-Loza, Francisco Javier

Cryogenic pressure vessels maximize hydrogen storage density by combining the high pressure (350-700 bar) typical of today's composite pressure vessels with the cryogenic temperature (as low as 25 K) typical of low pressure liquid hydrogen vessels. Cryogenic pressure vessels comprise a high-pressure inner vessel made of carbon fiber-coated metal (similar to those used for storage of compressed gas), a vacuum space filled with numerous sheets of highly reflective metalized plastic (for high performance thermal insulation), and a metallic outer jacket. High density of hydrogen storage is key to practical hydrogen-fueled transportation by enabling (1) long-range (500+ km) transportation with high capacity vessels that fit within available spaces in the vehicle, and (2) reduced cost per kilogram of hydrogen stored through reduced need for expensive structural material (carbon fiber composite) necessary to make the vessel. Low temperature of storage also leads to reduced expansion energy (by an order of magnitude or more vs. ambient temperature compressed gas storage), potentially providing important safety advantages. All this is accomplished while simultaneously avoiding fuel venting typical of cryogenic vessels for all practical use scenarios. This dissertation describes the work necessary for developing and demonstrating successive generations of cryogenic pressure vessels demonstrated at Lawrence Livermore National Laboratory. The work included (1) conceptual design, (2) detailed system design (3) structural analysis of cryogenic pressure vessels, (4) thermal analysis of heat transfer through cryogenic supports and vacuum multilayer insulation, and (5) experimental demonstration. Aside from succeeding in demonstrating a hydrogen storage approach that has established all the world records for hydrogen storage on vehicles (longest driving range, maximum hydrogen storage density, and maximum containment of cryogenic hydrogen without venting), the work also

Radiation-induced structural changes. 3

International Nuclear Information System (INIS)

Kondo, Yasuhiro; Matsuyama, Tomochika; Ogasawara, Masaaki

1993-05-01

This meeting is the fourth of series meetings on the structural change in materials induced by ionizing radiation. The present meeting was organized to discuss specifically on the x-ray storage phosphors such as BaFBr:Eu 2+ or RbI x Br 1-x :Tl and to get a clear understanding of the present status of the research on the storage mechanisms, nature of the rare earth impurities, and the optical properties of BaFBr. It was also expected that all the participants became aware of unsolved problems in these storage materials and that some of them would start research work on the storage phosphors. Therefore this report was edited mainly to provide basic knowledge correlated with the storage phosphors and related phenomena rather than to report simply on the experimental results. (J.P.N.)

NMR studies of transmembrane electron transport in human erythrocytes

International Nuclear Information System (INIS)

Kennett, E.C.; Bubb, W.A.; Kuchel, P.W.

2002-01-01

Full text: Electron transport systems exist in the plasma membranes of all cells. These systems appear to play a role in cell growth and proliferation, intracellular signalling, hormone responses, apoptotic events, cell defence and perhaps most importantly they enable the cell to respond to changes in the redox state of both the intra- and extracellular environments. Previously, 13 C NMR has been used to study transmembrane electron transport in human erythrocytes, specifically the reduction of extracellular 13 C-ferricyanide. NMR is a particularly useful tool for studying such systems as changes in the metabolic state of the cell can be observed concomitantly with extracellular reductase activity. We investigated the oxidation of extracellular NADH by human erythrocytes using 1 H and 31 P NMR spectroscopy. Recent results for glucose-starved human erythrocytes indicate that, under these conditions, extracellular NADH can be oxidised at the plasma membrane with the electron transfer across the membrane resulting in reduction of intracellular NAD + . The activity is inhibited by known trans-plasma membrane electron transport inhibitors (capsaicin and atebrin) and is unaffected by inhibition of the erythrocyte Band 3 anion transporter. These results suggest that electron import from extracellular NADH allows the cell to re-establish a reducing environment after the normal redox balance is disturbed

A Stepwise Fitting Procedure for automated fitting of Ecopath with Ecosim models

Directory of Open Access Journals (Sweden)

Erin Scott

2016-01-01

Full Text Available The Stepwise Fitting Procedure automates testing of alternative hypotheses used for fitting Ecopath with Ecosim (EwE models to observation reference data (Mackinson et al. 2009. The calibration of EwE model predictions to observed data is important to evaluate any model that will be used for ecosystem based management. Thus far, the model fitting procedure in EwE has been carried out manually: a repetitive task involving setting >1000 specific individual searches to find the statistically ‘best fit’ model. The novel fitting procedure automates the manual procedure therefore producing accurate results and lets the modeller concentrate on investigating the ‘best fit’ model for ecological accuracy.

Research on Improved VSG Control Algorithm Based on Capacity-Limited Energy Storage System

Directory of Open Access Journals (Sweden)

Yanfeng Ma

2018-03-01

Full Text Available A large scale of renewable energy employing grid connected electronic inverters fail to contribute inertia or damping to power systems, and, therefore, may bring negative effects to the stability of power system. As a solution, an advanced Virtual Synchronous Generator (VSG control technology based on Hamilton approach is introduced in this paper firstly to support the frequency and enhance the suitability and robustness of the system. The charge and discharge process of power storage devices forms the virtual inertia and damping of VSG, and, therefore, limits on storage capacity may change the coefficients of VSG. To provide a method in keeping system output in an acceptable level with the capacity restriction in a transient period, an energy control algorithm is designed for VSG adaptive control. Finally, simulations are conducted in DIgSILENT to demonstrate the correctness of the algorithm. The demonstration shows: (1 the proposed control model aims at better system robustness and stability; and (2 the model performs in the environment closer to practical engineering by fitting the operation state of storage system.