Dimerization and oligomerization of the chaperone calreticulin

DEFF Research Database (Denmark)

Jørgensen, Charlotte S; Ryder, L Rebekka; Steinø, Anne

2003-01-01

protein. Using PAGE, urea gradient gel electrophoresis, capillary electrophoresis and MS, we show that dimerization through the SH group can be induced by lowering the pH to 5-6, heating, or under conditions that favour partial unfolding such as urea concentrations above 2.6 m or SDS concentrations above...... that favour partial unfolding or an intramolecular local conformational change that allows oligomerization, resulting in a heterogeneous mixture of oligomers consisting of up to 10 calreticulin monomers. The oligomeric calreticulin was very stable, but oligomerization was partially reversed by addition of 8 m...

Genetic noise control via protein oligomerization

Energy Technology Data Exchange (ETDEWEB)

Ghim, C; Almaas, E

2008-06-12

Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamical role of protein-protein associations. We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast protein binding-unbinding kinetics, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its intrinsic switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of phenotypically important toggle switches, and nested positive feedback loops in

Crystal Structure of the Oligomeric Form of Lassa Virus Matrix Protein Z.

Science.gov (United States)

Hastie, Kathryn M; Zandonatti, Michelle; Liu, Tong; Li, Sheng; Woods, Virgil L; Saphire, Erica Ollmann

2016-05-01

The arenavirus matrix protein Z is highly multifunctional and occurs in both monomeric and oligomeric forms. The crystal structure of a dodecamer of Z from Lassa virus, presented here, illustrates a ring-like structure with a highly basic center. Mutagenesis demonstrates that the dimeric interface within the dodecamer and a Lys-Trp-Lys triad at the center of the ring are important for oligomerization. This structure provides an additional template to explore the many functions of Z. The arenavirus Lassa virus causes hundreds of thousands of infections each year, many of which develop into fatal hemorrhagic fever. The arenavirus matrix protein Z is multifunctional, with at least four distinct roles. Z exists in both monomeric and oligomeric forms, each of which likely serves a specific function in the viral life cycle. Here we present the dodecameric form of Lassa virus Z and demonstrate that Z forms a "wreath" with a highly basic center. This structure and that of monomeric Z now provide a pair of critical templates by which the multiple roles of Z in the viral life cycle may be interpreted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Reversible peptide oligomerization over nanoscale gold surfaces

Directory of Open Access Journals (Sweden)

Kazushige Yokoyama

2015-11-01

Full Text Available A selective oligomeric formation of amyloid beta 1-40 (Ab1-40 monomers over a nanogold colloidal surface was investigated. An unfolded Ab1-40 monomer is considered to construct a dimer or trimer based oligomeric form with its hydrophobic segment placing outward under an acidic condition. Under a basic condition, a conformation of Ab is expected to take a folded monomeric form with its hydrophilic segment folded inward, avoiding the networking with residual colloidal particles. The most probable oligomeric form constructed over a 20 nm gold colloidal surface within a 25 ℃ to 65 ℃ temperature range is a dimer based unit and that over 30 or 40 nm gold colloidal surface below 15 ℃ is concluded to be a trimer based unit. However, selective oligomerization was not successfully reproduced under the rest of the conditions. A dipole-induced dipole interaction must cause a flexible structural change between folded and unfolded forms.

Polymorphism and mesomorphism of oligomeric surfactants: effect of the degree of oligomerization.

Science.gov (United States)

Jurašin, D; Pustak, A; Habuš, I; Šmit, I; Filipović-Vinceković, N

2011-12-06

A series of cationic oligomeric surfactants (quaternary dodecyldimethylammonium ions with two, three, or four chains connected by an ethylene spacer at the headgroup level, abbreviated as dimer, trimer, and tetramer) were synthesized and characterized. The influence of the degree of oligomerization on their polymorphic and mesomorphic properties was investigated by means of X-ray diffraction, polarizing optical microscopy, thermogravimetry, and differential scanning calorimetry. All compounds display layered arrangements with interdigitated dodecyl chains. The increase in the degree of oligomerization increases the interlayer distance and decreases the ordering in the solid phase; whereas the dimer sample is fully crystalline with well-developed 3D ordering and the trimer and tetramer crystallize as highly ordered crystal smectic phases. The number of thermal phase transitions and sequence of phases are markedly affected by the number of dodecyl chains. Anhydrous samples exhibit polymorphism and thermotropic mesomorphism of the smectic type, with the exception of the tetramer that displays only transitions at higher temperature associated with decomposition and melting. All hydrated compounds form lyotropic mesophases showing reversible phase transitions upon heating and cooling. The sequence of liquid-crystalline phases for the dimer, typical of concentrated ionic surfactant systems, comprises a hexagonal phase at lower temperatures and a smectic phase at higher temperatures. In contrast, the trimer and tetramer reveal textures of the hexagonal phase. © 2011 American Chemical Society

Assessment of Escherichia coli selenophosphate synthetase oligomeric states by analytical ultracentrifugation and small angle X-ray scattering

Energy Technology Data Exchange (ETDEWEB)

Silva, I.R.; Faim, F.M.; Oliveira Neto, M.; Thiemann, O.H. [Universidade de Sao Paulo (USP-SC), Sao Carlos, SP (Brazil); Borges, J.C. [Universidade de Sao Paulo (IQSC/USP), Sao Carlos, SP (Brazil). Inst. de Quimica

2012-07-01

Full text: Selenium is an essential micronutrient for many organisms and is present in selenium-containing proteins as selenocysteine (Sec) and RNAs as selenouridine. Specific selenium incorporation into selenoproteins and RNAs requires the generation of a biologically active selenium donor compound, selenophosphate, which is produced from the activation of selenide with adenosine 5-triphosphate (ATP) in a reaction catalyzed by Selenophosphate Synthetase (SELD). Therefore, SELD is a key enzyme of the selenium pathway in the cell. The Escherichia coli SELD open reading frame was cloned into pET28a (Novagen) expression vector and the recombinant protein was over expressed in Escherichia coli BL21(DE3) strain. In order to purify the protein, we used metal-chelate affinity chromatography followed by a gel filtration step. Analytical Ultracentrifugation (AUC) and Small Angle X-ray Scattering (SAXS) were employed to study the oligomeric states of the soluble protein. The results of AUC revealed dimer-tetramer and tetramer-octamer equilibrium at low concentrations of protein, with dissociation constants of 70 2 and 560 40 M, respectively. Moreover, the SAXS results pointed the oligomeric state of the protein at higher concentrations as predominantly dimeric and the p(r) and the SAXS envelope revealed the SELD as elongated. We also performed initial crystallization trials with protein samples at 7 mg/ml in 96-well sitting-drop crystallization plates at room temperature using a crystallization robot. Needle crystals appeared after some days. X-ray diffraction for these crystals were tested in the MX2 beamline at the Brazilian Synchrotron Laboratory (LNLS Campinas). We are now working to improve these crystals in order to obtain suitable crystals for structure determination. (author)

Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system.

Science.gov (United States)

Rovira, X; Vivó, M; Serra, J; Roche, D; Strange, P G; Giraldo, J

2009-01-01

Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

Protic Cationic Oligomeric Ionic Liquids of the Urethane Type

DEFF Research Database (Denmark)

Shevchenko, V. V.; Stryutsky, A. V.; Klymenko, N. S.

2014-01-01

Protic oligomeric cationic ionic liquids of the oligo(ether urethane) type are synthesized via the reaction of an isocyanate prepolymer based on oligo(oxy ethylene)glycol with M = 1000 with hexamethylene-diisocyanate followed by blocking of the terminal isocyanate groups with the use of amine...... derivatives of imidazole, pyridine, and 3-methylpyridine and neutralization of heterocycles with ethanesulfonic acid and p-toluenesulfonic acid. The structures and properties of the synthesized oligomeric ionic liquids substantially depend on the structures of the ionic groups. They are amorphous at room...... temperature, but ethanesulfonate imidazolium and pyridinium oligomeric ionic liquids form a low melting crystalline phase. The proton conductivities of the oligomeric ionic liquids are determined by the type of cation in the temperature range 80-120 degrees C under anhydrous conditions and vary within five...

Assessing heterogeneity in oligomeric AAA+ machines.

Science.gov (United States)

Sysoeva, Tatyana A

2017-03-01

ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

Different domains are critical for oligomerization compatibility of different connexins

Science.gov (United States)

MARTÍNEZ, Agustín D.; MARIPILLÁN, Jaime; ACUÑA, Rodrigo; MINOGUE, Peter J.; BERTHOUD, Viviana M.; BEYER, Eric C.

2011-01-01

Oligomerization of connexins is a critical step in gap junction channel formation. Some members of the connexin family can oligomerize with other members and form functional heteromeric hemichannels [e.g. Cx43 (connexin 43) and Cx45], but others are incompatible (e.g. Cx43 and Cx26). To find connexin domains important for oligomerization, we constructed chimaeras between Cx43 and Cx26 and studied their ability to oligomerize with wild-type Cx43, Cx45 or Cx26. HeLa cells co-expressing Cx43, Cx45 or Cx26 and individual chimaeric constructs were analysed for interactions between the chimaeras and the wild-type connexins using cell biological (subcellular localization by immunofluorescence), functional (intercellular diffusion of microinjected Lucifer yellow) and biochemical (sedimentation velocity through sucrose gradients) assays. All of the chimaeras containing the third transmembrane domain of Cx43 interacted with wild-type Cx43 on the basis of co-localization, dominant-negative inhibition of intercellular communication, and altered sedimentation velocity. The same chimaeras also interacted with co-expressed Cx45. In contrast, immunofluorescence and intracellular diffusion of tracer suggested that other domains influenced oligomerization compatibility when chimaeras were co-expressed with Cx26. Taken together, these results suggest that amino acids in the third transmembrane domain are critical for oligomerization with Cx43 and Cx45. However, motifs in different domains may determine oligomerization compatibility in members of different connexin subfamilies. PMID:21348854

Oligomerization of a Glucagon-like Peptide 1 Analog: Bridging Experiment and Simulations

DEFF Research Database (Denmark)

Frederiksen, Tine Maja; Sønderby, Pernille; Ryberg, Line A.

2015-01-01

The glucagon-like peptide 1 (GLP-1) analog, liraglutide, is a GLP-1 agonist and is used in the treatment of type-2 diabetes mellitus and obesity. From a pharmaceutical perspective, it is important to know the oligomerization state of liraglutide with respect to stability. Compared to GLP-1...

An engineered allosteric switch in leucine-zipper oligomerization.

Science.gov (United States)

Gonzalez, L; Plecs, J J; Alber, T

1996-06-01

Controversy remains about the role of core side-chain packing in specifying protein structure. To investigate the influence of core packing on the oligomeric structure of a coiled coil, we engineered a GCN4 leucine zipper mutant that switches from two to three strands upon binding the hydrophobic ligands cyclohexane and benzene. In solution these ligands increased the apparent thermal stability and the oligomerization order of the mutant leucine zipper. The crystal structure of the peptide-benzene complex shows a single benzene molecule bound at the engineered site in the core of the trimer. These results indicate that coiled coils are well-suited to function as molecular switches and emphasize that core packing is an important determinant of oligomerization specificity.

Polyhedral Oligomeric Silsesquioxane (POSS)-Containing Polymer Nanocomposites

Science.gov (United States)

Ayandele, Ebunoluwa; Sarkar, Biswajit; Alexandridis, Paschalis

2012-01-01

Hybrid materials with superior structural and functional properties can be obtained by incorporating nanofillers into polymer matrices. Polyhedral oligomeric silsesquioxane (POSS) nanoparticles have attracted much attention recently due to their nanometer size, the ease of which these particles can be incorporated into polymeric materials and the unique capability to reinforce polymers. We review here the state of POSS-containing polymer nanocomposites. We discuss the influence of the incorporation of POSS into polymer matrices via chemical cross-linking or physical blending on the structure of nanocomposites, as affected by surface functional groups, and the POSS concentration. PMID:28348318

Oligomerization in health and disease

CERN Document Server

Giraldo, Jesus

2013-01-01

This special volume of Progress in Molecular Biology and Translational Science focuses on oligomerization in health and disease. Contributions from leading authorities Informs and updates on all the latest developments in the field.

Biophysical characterization of GPCR oligomerization

DEFF Research Database (Denmark)

Mathiasen, Signe

level, and revealed the existence of several dimerization interfaces, each with specific kinetics. Finally we investigated how a property of the membrane solubilizing GPCRs affected oligomerization. We observed a dramatic decrease in oligomer stability with increasing geometrical membrane curvature. We...

Protein dimerization and oligomerization in biology

National Research Council Canada - National Science Library

Matthews, Jacqueline M

2012-01-01

.... However, protein function is so often linked to both homo- and hetero-oligomerization and many heterologous interactions likely evolved from homologous interaction, so this volume also covers many...

Reversibility and two state behaviour in the thermal unfolding of oligomeric TIM barrel proteins.

Science.gov (United States)

Romero-Romero, Sergio; Costas, Miguel; Rodríguez-Romero, Adela; Alejandro Fernández-Velasco, D

2015-08-28

Temperature is one of the main variables that modulate protein function and stability. Thermodynamic studies of oligomeric proteins, the dominant protein natural form, have been often hampered because irreversible aggregation and/or slow reactions are common. There are no reports on the reversible equilibrium thermal unfolding of proteins composed of (β/α)8 barrel subunits, albeit this "TIM barrel" topology is one of the most abundant and versatile in nature. We studied the eponymous TIM barrel, triosephosphate isomerase (TIM), belonging to five species of different bacterial taxa. All of them were found to be catalytically efficient dimers. The three-dimensional structure of four enzymes was solved at high/medium resolution. Irreversibility and kinetic control were observed in the thermal unfolding of two TIMs, while for the other three the thermal unfolding was found to follow a two-state equilibrium reversible process. Shifts in the global stability curves of these three proteins are related to the organismal temperature range of optimal growth and modulated by variations in maximum stability temperature and in the enthalpy change at that temperature. Reversibility appears to correlate with the low isoelectric point, the absence of a residual structure in the unfolded state, small cavity volume in the native state, low conformational stability and a low melting temperature. Furthermore, the strong coupling between dimer dissociation and monomer unfolding may reduce aggregation and favour reversibility. It is therefore very thought-provoking to find that a common topological ensemble, such as the TIM barrel, can unfold/refold in the Anfinsen way, i.e. without the help of the cellular machinery.

octamethyl-polyhedral oligomeric silsesquioxanes nanocomposites ...

Indian Academy of Sciences (India)

In this study, biodegradable poly(p-dioxanone) (PPDO)/octamethyl-polyhedral oligomeric silsesquioxanes (ome-POSS) nanocomposites were fabricated by the simple solution casting method with various ome-POSS loadings. Scanning electron microscopic observations indicate that ome-POSS is well dispersed in the ...

RNAi reduces expression and intracellular retention of mutant cartilage oligomeric matrix protein.

Directory of Open Access Journals (Sweden)

Karen L Posey

2010-04-01

Full Text Available Mutations in cartilage oligomeric matrix protein (COMP, a large extracellular glycoprotein expressed in musculoskeletal tissues, cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. These mutations lead to massive intracellular retention of COMP, chondrocyte death and loss of growth plate chondrocytes that are necessary for linear growth. In contrast, COMP null mice have only minor growth plate abnormalities, normal growth and longevity. This suggests that reducing mutant and wild-type COMP expression in chondrocytes may prevent the toxic cellular phenotype causing the skeletal dysplasias. We tested this hypothesis using RNA interference to reduce steady state levels of COMP mRNA. A panel of shRNAs directed against COMP was tested. One shRNA (3B reduced endogenous and recombinant COMP mRNA dramatically, regardless of expression levels. The activity of the shRNA against COMP mRNA was maintained for up to 10 weeks. We also demonstrate that this treatment reduced ER stress. Moreover, we show that reducing steady state levels of COMP mRNA alleviates intracellular retention of other extracellular matrix proteins associated with the pseudoachondroplasia cellular pathology. These findings are a proof of principle and the foundation for the development of a therapeutic intervention based on reduction of COMP expression.

Oligomerization and polymerization of the filovirus matrix protein VP40

International Nuclear Information System (INIS)

Timmins, Joanna; Schoehn, Guy; Kohlhaas, Christine; Klenk, Hans-Dieter; Ruigrok, Rob W.H.; Weissenhorn, Winfried

2003-01-01

The matrix protein VP40 from Ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. Here we show that the N-terminal domain of VP40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. Octamer formation depends largely on the interaction with nucleic acids, which in turn confers in vitro SDS resistance. Refolding experiments with a nucleic acid free N-terminal domain preparation reveal a mostly dimeric form of VP40, which is transformed into an SDS resistant octamer upon incubation with E. coli nucleic acids. In addition, we demonstrate that the N-terminal domain of Marburg virus VP40 also folds into ringlike structures, similar to Ebola virus VP40. Interestingly, Marburg virus VP40 rings reveal a high tendency to polymerize into rods composed of stacked rings. These results may suggest distinct roles for different oligomeric forms of VP40 in the filovirus life cycle

Zn(2+) site engineering at the oligomeric interface of the dopamine transporter

DEFF Research Database (Denmark)

Norgaard-Nielsen, Kristine; Norregaard, Lene; Hastrup, Hanne

2002-01-01

Increasing evidence suggests that Na(+)/Cl(-)-dependent neurotransmitter transporters exist as homo-oligomeric proteins. However, the functional implication of this oligomerization remains unclear. Here we demonstrate the engineering of a Zn(2+) binding site at the predicted dimeric interface...

Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

Science.gov (United States)

Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

2014-03-01

Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

Science.gov (United States)

Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

2014-01-01

Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. PMID:24658080

Oligomerization of optineurin and its oxidative stress- or E50K mutation-driven covalent cross-linking: possible relationship with glaucoma pathology.

Directory of Open Access Journals (Sweden)

Jie Gao

Full Text Available The optineurin gene, OPTN, is one of the causative genes of primary open-angle glaucoma. Although oligomerization of optineurin in cultured cells was previously observed by gel filtration analysis and blue native gel electrophoresis (BNE, little is known about the characteristics of optineurin oligomers. Here, we aimed to analyze the oligomeric state of optineurin and factors affecting oligomerization, such as environmental stimuli or mutations in OPTN. Using BNE or immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE, we demonstrated that both endogenous and transfected optineurin exist as oligomers, rather than monomers, in NIH3T3 cells. We also applied an in situ proximity ligation assay to visualize the self-interaction of optineurin in fixed HeLaS3 cells and found that the optineurin oligomers were localized diffusely in the cytoplasm. Optineurin oligomers were usually detected as a single band of a size equal to that of the optineurin monomer upon SDS-PAGE, while an additional protein band of a larger size was observed when cells were treated with H2O2. We showed that larger protein complex is optineurin oligomers by immunoprecipitation and termed it covalent optineurin oligomers. In cells expressing OPTN bearing the most common glaucoma-associated mutation, E50K, covalent oligomers were formed even without H2O2 stimulation. Antioxidants inhibited the formation of E50K-induced covalent oligomers to various degrees. A series of truncated constructs of OPTN was used to reveal that covalent oligomers may be optineurin trimers and that the ubiquitin-binding domain is essential for formation of these trimers. Our results indicated that optineurin trimers may be the basic unit of these oligomers. The oligomeric state can be affected by many factors that induce covalent bonds, such as H2O2 or E50K, as demonstrated here; this provides novel insights into the pathogenicity of E50K. Furthermore

Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

Directory of Open Access Journals (Sweden)

Wei-ling Cui

2016-01-01

Full Text Available Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group. As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

Arc is a flexible modular protein capable of reversible self-oligomerization

Science.gov (United States)

Myrum, Craig; Baumann, Anne; Bustad, Helene J.; Flydal, Marte Innselset; Mariaule, Vincent; Alvira, Sara; Cuéllar, Jorge; Haavik, Jan; Soulé, Jonathan; Valpuesta, José Maria; Márquez, José Antonio; Martinez, Aurora; Bramham, Clive R.

2015-01-01

The immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskeletal structures or other polyanionic surfaces, whereas the C-terminal domain is acidic and stabilized by ionic conditions that promote oligomerization. Upon binding of presenilin-1 (PS1) peptide, hArc undergoes a large structural change. A non-synonymous genetic variant of hArc (V231G) showed properties similar to the wild-type (WT) protein. We conclude that hArc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes. PMID:25748042

Transient oligomerization of the SARS-CoV N protein--implication for virus ribonucleoprotein packaging.

Science.gov (United States)

Chang, Chung-ke; Chen, Chia-Min Michael; Chiang, Ming-hui; Hsu, Yen-lan; Huang, Tai-huang

2013-01-01

The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.

Membrane-mediated oligomerization of G protein coupled receptors and its implications for GPCR function

Directory of Open Access Journals (Sweden)

Stefan Gahbauer

2016-10-01

Full Text Available The dimerization or even oligomerization of G protein coupled receptors (GPCRs causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signalling complexes. Recent findings further suggest that the surrounding membrane, i.e. its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.

Zn(2+) site engineering at the oligomeric interface of the dopamine transporter.

Science.gov (United States)

Norgaard-Nielsen, Kristine; Norregaard, Lene; Hastrup, Hanne; Javitch, Jonathan A; Gether, Ulrik

2002-07-31

Increasing evidence suggests that Na(+)/Cl(-)-dependent neurotransmitter transporters exist as homo-oligomeric proteins. However, the functional implication of this oligomerization remains unclear. Here we demonstrate the engineering of a Zn(2+) binding site at the predicted dimeric interface of the dopamine transporter (DAT) corresponding to the external end of transmembrane segment 6. Upon binding to this site, which involves a histidine inserted in position 310 (V310H) and the endogenous Cys306 within the same DAT molecule, Zn(2+) potently inhibits [(3)H]dopamine uptake. These data provide indirect evidence that conformational changes critical for the translocation process may occur at the interface between two transporter molecules in the oligomeric structure.

DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

Science.gov (United States)

Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

2009-08-07

DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

Crystal structures from the Plasmodium peroxiredoxins: new insights into oligomerization and product binding.

Science.gov (United States)

Qiu, Wei; Dong, Aiping; Pizarro, Juan C; Botchkarsev, Alexei; Min, Jinrong; Wernimont, Amy K; Hills, Tanya; Hui, Raymond; Artz, Jennifer D

2012-03-19

Plasmodium falciparum is the protozoan parasite primarily responsible for more than one million malarial deaths, annually, and is developing resistance to current therapies. Throughout its lifespan, the parasite is subjected to oxidative attack, so Plasmodium antioxidant defences are essential for its survival and are targets for disease control. To further understand the molecular aspects of the Plasmodium redox system, we solved 4 structures of Plasmodium peroxiredoxins (Prx). Our study has confirmed PvTrx-Px1 to be a hydrogen peroxide (H2O2)-sensitive peroxiredoxin. We have identified and characterized the novel toroid octameric oligomer of PyTrx-Px1, which may be attributed to the interplay of several factors including: (1) the orientation of the conserved surface/buried arginine of the NNLA(I/L)GRS-loop; and (2) the C-terminal tail positioning (also associated with the aforementioned conserved loop) which facilitates the intermolecular hydrogen bond between dimers (in an A-C fashion). In addition, a notable feature of the disulfide bonds in some of the Prx crystal structures is discussed. Finally, insight into the latter stages of the peroxiredoxin reaction coordinate is gained. Our structure of PyPrx6 is not only in the sulfinic acid (RSO2H) form, but it is also with glycerol bound in a way (not previously observed) indicative of product binding. The structural characterization of Plasmodium peroxiredoxins provided herein provides insight into their oligomerization and product binding which may facilitate the targeting of these antioxidant defences. Although the structural basis for the octameric oligomerization is further understood, the results yield more questions about the biological implications of the peroxiredoxin oligomerization, as multiple toroid configurations are now known. The crystal structure depicting the product bound active site gives insight into the overoxidation of the active site and allows further characterization of the leaving group

Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.

Science.gov (United States)

Yuan, Ping; Leser, George P; Demeler, Borries; Lamb, Robert A; Jardetzky, Theodore S

2008-09-01

The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high alpha-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface.

Directory of Open Access Journals (Sweden)

Miguel Xavier van Bemmelen

Full Text Available The chicken acid-sensing ion channel ASIC1 has been crystallized as a homotrimer. We address here the oligomeric state of the functional ASIC1 in situ at the cell surface. The oligomeric states of functional ASIC1a and mutants with additional cysteines introduced in the extracellular pore vestibule were resolved on SDS-PAGE. The functional ASIC1 complexes were stabilized at the cell surface of Xenopus laevis oocytes or CHO cells either using the sulfhydryl crosslinker BMOE, or sodium tetrathionate (NaTT. Under these different crosslinking conditions ASIC1a migrates as four distinct oligomeric states that correspond by mass to multiples of a single ASIC1a subunit. The relative importance of each of the four ASIC1a oligomers was critically dependent on the availability of cysteines in the transmembrane domain for crosslinking, consistent with the presence of ASIC1a homo-oligomers. The expression of ASIC1a monomers, trimeric or tetrameric concatemeric cDNA constructs resulted in functional channels. The resulting ASIC1a complexes are resolved as a predominant tetramer over the other oligomeric forms, after stabilization with BMOE or NaTT and SDS-PAGE/western blot analysis. Our data identify a major ASIC1a homotetramer at the surface membrane of the cell expressing functional ASIC1a channel.

Induced oligomerization targets Golgi proteins for degradation in lysosomes.

Science.gov (United States)

Tewari, Ritika; Bachert, Collin; Linstedt, Adam D

2015-12-01

Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which mediate sorting in the canonical Golgi-to-lysosome pathway. GPP130 oligomerization was induced using either Mn or a self-interacting version of the FKBP domain. Inhibition of GGA1 or clathrin specifically blocked GPP130 redistribution, suggesting recognition of the aggregated GPP130 by the GGA1/clathrin-sorting complex. Unexpectedly, however, GPP130's cytoplasmic domain was not required, and redistribution also occurred after removal of GPP130 sequences needed for its normal cycling. Therefore, to test whether aggregate recognition might be a general phenomenon rather than one involving a specific GPP130 determinant, we induced homo-oligomerization of two unrelated Golgi-targeted constructs using the FKBP strategy. These were targeted to the cis- and trans-Golgi, respectively, using domains from mannosidase-1 and galactosyltransferase. Significantly, upon oligomerization, each redistributed to peripheral punctae and was degraded. This occurred in the absence of detectable UPR activation. These findings suggest the unexpected presence of quality control in the Golgi that recognizes aggregated Golgi proteins and targets them for degradation in lysosomes. © 2015 Tewari et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Inside-out signaling promotes dynamic changes in the carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) oligomeric state to control its cell adhesion properties.

Science.gov (United States)

Patel, Prerna C; Lee, Hannah S W; Ming, Aaron Y K; Rath, Arianna; Deber, Charles M; Yip, Christopher M; Rocheleau, Jonathan V; Gray-Owen, Scott D

2013-10-11

Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) can engage in both cis-homophilic (parallel) oligomerization and trans-homophilic (anti-parallel) binding. In this study, we establish that the CEACAM1 transmembrane domain has a propensity to form cis-dimers via the transmembrane-embedded (432)GXXXG(436) motif and that this basal state is overcome when activated calmodulin binds to the CEACAM1 cytoplasmic domain. Although mutation of the (432)GXXXG(436) motif reduced CEACAM1 oligomerization, it did not affect surface localization of the receptor or influence CEACAM1-dependent cellular invasion by the pathogenic Neisseria. The mutation did, however, have a striking effect on CEACAM1-dependent cellular aggregation, increasing both the kinetics of cell-cell association and the size of cellular aggregates formed. CEACAM1 association with tyrosine kinase c-Src and tyrosine phosphatases SHP-1 and SHP-2 was not affected by the (432)GXXXG(436) mutation, consistent with their association with the monomeric form of wild type CEACAM1. Collectively, our results establish that a dynamic oligomer-to-monomer shift in surface-expressed CEACAM1 facilitates trans-homophilic binding and downstream effector signaling.

Transient oligomerization of the SARS-CoV N protein--implication for virus ribonucleoprotein packaging.

Directory of Open Access Journals (Sweden)

Chung-ke Chang

Full Text Available The nucleocapsid (N phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD. A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.

Thermal Degradation Mechanism of a Thermostable Polyester Stabilized with an Open-Cage Oligomeric Silsesquioxane

Directory of Open Access Journals (Sweden)

Yolanda Bautista

2017-12-01

Full Text Available A polyester composite was prepared through the polymerization of an unsaturated ester resin with styrene and an open-cage oligomeric silsesquioxane with methacrylate groups. The effect of the open-cage oligomeric silsesquioxane on the thermal stability of the thermostable polyester was studied using both thermogravimetric analysis and differential thermal analysis. The results showed that the methacryl oligomeric silsesquioxane improved the thermal stability of the polyester. The decomposition mechanism of the polyester/oligomer silsesquioxane composite was proposed by Fourier transform infrared spectroscopy (FTIR analysis of the volatiles.

Oligomerization process

Science.gov (United States)

Smith, L.A. Jr.; Hearn, D.; Jones, E.M. Jr.

1991-03-26

A liquid phase process is described for oligomerization of C[sub 4] and C[sub 5] isoolefins or the etherification thereof with C[sub 1] to C[sub 6] alcohols wherein the reactants are contacted in a reactor with a fixed bed acid cation exchange resin catalyst at an LHSV of 5 to 20, pressure of 0 to 400 psig and temperature of 120 to 300 F wherein the improvement is the operation of the reactor at a pressure to maintain the reaction mixture at its boiling point whereby at least a portion but less than all of the reaction mixture is vaporized. By operating at the boiling point and allowing a portion of the reaction mixture to vaporize, the exothermic heat of reaction is dissipated by the formation of more boil up and the temperature in the reactor is controlled. 2 figures.

Methyl methacrylate oligomerically-modified clay and its poly(methyl methacrylate) nanocomposites

International Nuclear Information System (INIS)

Zheng Xiaoxia; Jiang, David D.; Wilkie, Charles A.

2005-01-01

A methyl methacrylate oligomerically-modified clay was used to prepare poly(methyl methacrylate) clay nanocomposites by melt blending and the effect of the clay loading level on the modified clay and corresponding nanocomposite was studied. These nanocomposites were characterized by X-ray diffraction, transmission electron microscopy, thermogravimetric analysis and cone calorimetry. The results show a mixed intercalated/delaminated morphology with good nanodispersion. The compatibility between the methylacrylate-subsituted clay and poly(methyl methacrylate) (PMMA) are greatly improved compared to other oligomerically-modified clays

Involvement of C-Terminal Histidines in Soybean PM1 Protein Oligomerization and Cu2+ Binding.

Science.gov (United States)

Liu, Guobao; Liu, Ke; Gao, Yang; Zheng, Yizhi

2017-06-01

Late embryogenesis abundant (LEA) proteins are widely distributed among plant species, where they contribute to abiotic stress tolerance. LEA proteins can be classified into seven groups according to conserved sequence motifs. The PM1 protein from soybean, which belongs to the Pfam LEA_1 group, has been shown previously to be at least partially natively unfolded, to bind metal ions and potentially to stabilize proteins and membranes. Here, we investigated the role of the PM1 C-terminal domain and in particular the multiple histidine residues in this half of the protein. We constructed recombinant plasmids expressing full-length PM1 and two truncated forms, PM1-N and PM1-C, which represent the N- and C-terminal halves of the protein, respectively. Immunoblotting and cross-linking experiments showed that full-length PM1 forms oligomers and high molecular weight (HMW) complexes in vitro and in vivo, while PM1-C, but not PM1-N, also formed oligomers and HMW complexes in vitro. When the histidine residues in PM1 and PM1-C were chemically modified, oligomerization was abolished, suggesting that histidines play a key role in this process. Furthermore, we demonstrated that high Cu2+ concentrations promote oligomerization and induce PM1 and PM1-C to form HMW complexes. Therefore, we speculate that PM1 proteins not only maintain ion homeostasis in the cytoplasm, but also potentially stabilize and protect other proteins during abiotic stress by forming a large, oligomeric molecular shield around biological targets. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function

Directory of Open Access Journals (Sweden)

Davey Megan J

2010-09-01

Full Text Available Abstract Background Minichromosome maintenance proteins (Mcm 2, 3, 4, 5, 6 and 7 are related by sequence and form a variety of complexes that unwind DNA, including Mcm4/6/7. A Mcm4/6/7 trimer forms one half of the Mcm2-7 hexameric ring and can be thought of as the catalytic core of Mcm2-7, the replicative helicase in eukaryotic cells. Oligomeric analysis of Mcm4/6/7 suggests that it forms a hexamer containing two Mcm4/6/7 trimers, however, under certain conditions trimeric Mcm4/6/7 has also been observed. The functional significance of the different Mcm4/6/7 oligomeric states has not been assessed. The results of such an assessment would have implications for studies of both Mcm4/6/7 and Mcm2-7. Results Here, we show that Saccharomyces cerevisiae Mcm4/6/7 reconstituted from individual subunits exists in an equilibrium of oligomeric forms in which smaller oligomers predominate in the absence of ATP. In addition, we found that ATP, which is required for Mcm4/6/7 activity, shifts the equilibrium towards larger oligomers, likely hexamers of Mcm4/6/7. ATPγS and to a lesser extent ADP also shift the equilibrium towards hexamers. Study of Mcm4/6/7 complexes containing mutations that interfere with the formation of inter-subunit ATP sites (arginine finger mutants indicates that full activity of Mcm4/6/7 requires all of its ATP sites, which are formed in a hexamer and not a trimer. In keeping with this observation, Mcm4/6/7 binds DNA as a hexamer. Conclusions The minimal functional unit of Mcm4/6/7 is a hexamer. One of the roles of ATP binding by Mcm4/6/7 may be to stabilize formation of hexamers.

Oligomerization of G protein-coupled receptors: computational methods.

Science.gov (United States)

Selent, J; Kaczor, A A

2011-01-01

Recent research has unveiled the complexity of mechanisms involved in G protein-coupled receptor (GPCR) functioning in which receptor dimerization/oligomerization may play an important role. Although the first high-resolution X-ray structure for a likely functional chemokine receptor dimer has been deposited in the Protein Data Bank, the interactions and mechanisms of dimer formation are not yet fully understood. In this respect, computational methods play a key role for predicting accurate GPCR complexes. This review outlines computational approaches focusing on sequence- and structure-based methodologies as well as discusses their advantages and limitations. Sequence-based approaches that search for possible protein-protein interfaces in GPCR complexes have been applied with success in several studies, but did not yield always consistent results. Structure-based methodologies are a potent complement to sequence-based approaches. For instance, protein-protein docking is a valuable method especially when guided by experimental constraints. Some disadvantages like limited receptor flexibility and non-consideration of the membrane environment have to be taken into account. Molecular dynamics simulation can overcome these drawbacks giving a detailed description of conformational changes in a native-like membrane. Successful prediction of GPCR complexes using computational approaches combined with experimental efforts may help to understand the role of dimeric/oligomeric GPCR complexes for fine-tuning receptor signaling. Moreover, since such GPCR complexes have attracted interest as potential drug target for diverse diseases, unveiling molecular determinants of dimerization/oligomerization can provide important implications for drug discovery.

Fingolimod phosphate attenuates oligomeric amyloid β-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons.

Directory of Open Access Journals (Sweden)

Yukiko Doi

Full Text Available The neurodegenerative processes that underlie Alzheimer's disease are mediated, in part, by soluble oligomeric amyloid β, a neurotoxic protein that inhibits hippocampal long-term potentiation, disrupts synaptic plasticity, and induces the production of reactive oxygen species. Here we show that the sphingosine-1-phosphate (S1P receptor (S1PR agonist fingolimod phosphate (FTY720-P-a new oral drug for multiple sclerosis-protects neurons against oligomeric amyloid β-induced neurotoxicity. We confirmed that primary mouse cortical neurons express all of the S1P receptor subtypes and FTY720-P directly affects the neurons. Treatment with FTY720-P enhanced the expression of brain-derived neurotrophic factor (BDNF in neurons. Moreover, blocking BDNF-TrkB signaling with a BDNF scavenger, TrkB inhibitor, or ERK1/2 inhibitor almost completely ablated these neuroprotective effects. These results suggested that the neuroprotective effects of FTY720-P are mediated by upregulated neuronal BDNF levels. Therefore, FTY720-P may be a promising therapeutic agent for neurodegenerative diseases, such as Alzheimer's disease.

N-Glycosylation instead of cholesterol mediates oligomerization and apical sorting of GPI-APs in FRT cells.

Science.gov (United States)

Imjeti, Naga Salaija; Lebreton, Stéphanie; Paladino, Simona; de la Fuente, Erwin; Gonzalez, Alfonso; Zurzolo, Chiara

2011-12-01

Sorting of glycosylphosphatidyl-inositol--anchored proteins (GPI-APs) in polarized epithelial cells is not fully understood. Oligomerization in the Golgi complex has emerged as the crucial event driving apical segregation of GPI-APs in two different kind of epithelial cells, Madin-Darby canine kidney (MDCK) and Fisher rat thyroid (FRT) cells, but whether the mechanism is conserved is unknown. In MDCK cells cholesterol promotes GPI-AP oligomerization, as well as apical sorting of GPI-APs. Here we show that FRT cells lack this cholesterol-driven oligomerization as apical sorting mechanism. In these cells both apical and basolateral GPI-APs display restricted diffusion in the Golgi likely due to a cholesterol-enriched membrane environment. It is striking that N-glycosylation is the critical event for oligomerization and apical sorting of GPI-APs in FRT cells but not in MDCK cells. Our data indicate that at least two mechanisms exist to determine oligomerization in the Golgi leading to apical sorting of GPI-APs. One depends on cholesterol, and the other depends on N-glycosylation and is insensitive to cholesterol addition or depletion.

Controlling amyloid-beta peptide(1-42) oligomerization and toxicity by fluorinated nanoparticles.

Science.gov (United States)

Saraiva, Ana M; Cardoso, Isabel; Pereira, M Carmo; Coelho, Manuel A N; Saraiva, Maria João; Möhwald, Helmuth; Brezesinski, Gerald

2010-09-03

The amyloid-beta peptide (Abeta) is a major fibrillar component of neuritic plaques in Alzheimer's disease brains and is related to the pathogenesis of the disease. Soluble oligomers that precede fibril formation have been proposed as the main neurotoxic species that contributes to neurodegeneration and dementia. We hypothesize that oligomerization and cytotoxicity can be repressed by nanoparticles (NPs) that induce conformational changes in Abeta42. We show here that fluorinated and hydrogenated NPs with different abilities to change Abeta42 conformation influence oligomerization as assessed by atomic force microscopy, immunoblot and SDS-PAGE. Fluorinated NPs, which promote an increase in alpha-helical content, exert an antioligomeric effect, whereas hydrogenated analogues do not and lead to aggregation. Cytotoxicity assays confirmed our hypothesis by indicating that the conformational conversion of Abeta42 into an alpha-helical-enriched secondary structure also has antiapoptotic activity, thereby increasing the viability of cells treated with oligomeric species.

Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri.

Science.gov (United States)

Burgess, Jamie L; Jones, Heather B; Kumar, Prashant; Toth, Ronald T; Middaugh, C Russell; Antony, Edwin; Dickenson, Nicholas E

2016-05-01

Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents. © 2016 The Protein Society.

DNA structure modulates the oligomerization properties of the AAV initiator protein Rep68.

Directory of Open Access Journals (Sweden)

Jorge Mansilla-Soto

2009-07-01

Full Text Available Rep68 is a multifunctional protein of the adeno-associated virus (AAV, a parvovirus that is mostly known for its promise as a gene therapy vector. In addition to its role as initiator in viral DNA replication, Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19. Rep68 is a member of the superfamily 3 (SF3 helicases, along with the well-studied initiator proteins simian virus 40 large T antigen (SV40-LTag and bovine papillomavirus (BPV E1. Structurally, SF3 helicases share two domains, a DNA origin interaction domain (OID and an AAA(+ motor domain. The AAA(+ motor domain is also a structural feature of cellular initiators and it functions as a platform for initiator oligomerization. Here, we studied Rep68 oligomerization in vitro in the presence of different DNA substrates using a variety of biophysical techniques and cryo-EM. We found that a dsDNA region of the AAV origin promotes the formation of a complex containing five Rep68 subunits. Interestingly, non-specific ssDNA promotes the formation of a double-ring Rep68, a known structure formed by the LTag and E1 initiator proteins. The Rep68 ring symmetry is 8-fold, thus differing from the hexameric rings formed by the other SF3 helicases. However, similiar to LTag and E1, Rep68 rings are oriented head-to-head, suggesting that DNA unwinding by the complex proceeds bidirectionally. This novel Rep68 quaternary structure requires both the DNA binding and AAA(+ domains, indicating cooperativity between these regions during oligomerization in vitro. Our study clearly demonstrates that Rep68 can oligomerize through two distinct oligomerization pathways, which depend on both the DNA structure and cooperativity of Rep68 domains. These findings provide insight into the dynamics and oligomeric adaptability of Rep68 and serve as a step towards understanding the role of this multifunctional protein during AAV DNA replication and site-specific integration.

Effect Of Oligomeric Enteral Nutrition On Symptoms Of Acute Radiation Enteritis

International Nuclear Information System (INIS)

Dubinsky, P.

2008-01-01

Radiotherapy of abdominal and pelvic tumours is frequently associated with acute radiation enteritis. Predominant symptoms include diarrhea, watery stools, abdominal pain, nausea and vomiting. There are very few effective interventions available for this condition. Enteral oligomeric nutrition has been used in bowel diseases with functional failure similar to radiation enteritis. The aim of presented work was to observe occurrence of symptoms of radiation enteritis in patients undergoing abdominal or pelvic radiotherapy. Apart from diet and pharmacological therapy, oral oligomeric enteral nutrition (Peptisorb Powder Nutricia) at the dose of 1000 - 2000 ml per day was administered for minimum of 4 days. Planned period of administration was 14 days and longer. Symptoms of radiation enteritis were evaluated at the beginning and in the end of administration. Prevalence of all evaluated symptoms of radiation enteritis was decreased and difference was statistically significant for diarrhea, watery stools, abdominal pain, nausea and vomiting. The use of evaluated oligomeric nutritional support might, in conjunction with pharmacotherapy and diet, alleviate symptoms of acute radiation enteritis and maintain nutritional status of patients. (author)

Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function

Directory of Open Access Journals (Sweden)

Shekhtman Alexander

2009-04-01

Full Text Available Abstract Background Human S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins that are associated with many diseases including cancer, chronic inflammation and neurological disorders. S100A12 is an important factor in host/parasite defenses and in the inflammatory response. Like several other S100 proteins, it binds zinc and copper in addition to calcium. Mechanisms of zinc regulation have been proposed for a number of S100 proteins e.g. S100B, S100A2, S100A7, S100A8/9. The interaction of S100 proteins with their targets is strongly dependent on cellular microenvironment. Results The aim of the study was to explore the factors that influence S100A12 oligomerization and target interaction. A comprehensive series of biochemical and biophysical experiments indicated that changes in the concentration of calcium and zinc led to changes in the oligomeric state of S100A12. Surface plasmon resonance confirmed that the presence of both calcium and zinc is essential for the interaction of S100A12 with one of its extracellular targets, RAGE – the Receptor for Advanced Glycation End products. By using a single-molecule approach we have shown that the presence of zinc in tissue culture medium favors both the oligomerization of exogenous S100A12 protein and its interaction with targets on the cell surface. Conclusion We have shown that oligomerization and target recognition by S100A12 is regulated by both zinc and calcium. Our present work highlighted the potential role of calcium-binding S100 proteins in zinc metabolism and, in particular, the role of S100A12 in the cross talk between zinc and calcium in cell signaling.

Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

Science.gov (United States)

Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

1989-10-05

Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

Genetic noise control via protein oligomerization

Directory of Open Access Journals (Sweden)

Almaas Eivind

2008-11-01

Full Text Available Abstract Background Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Results We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch, integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast binding-unbinding kinetics among proteins, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced state from randomly being induced (uninduced. Conclusion The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of regulatory circuits

Concentration-dependent oligomerization of cross-linked complexes between ferredoxin and ferredoxin–NADP+ reductase

International Nuclear Information System (INIS)

Kimata-Ariga, Yoko; Kubota-Kawai, Hisako; Lee, Young-Ho; Muraki, Norifumi; Ikegami, Takahisa; Kurisu, Genji; Hase, Toshiharu

2013-01-01

Highlights: •Cross-linked complexes of ferredoxin (Fd) and Fd–NADP + reductase form oligomers. •In the crystal structures, Fd- and FNR moieties swap across the molecules. •The complexes exhibit concentration-dependent oligomerization at sub-milimolar order. -- Abstract: Ferredoxin–NADP + reductase (FNR) forms a 1:1 complex with ferredoxin (Fd), and catalyzes the electron transfer between Fd and NADP + . In our previous study, we prepared a series of site-specifically cross-linked complexes of Fd and FNR, which showed diverse electron transfer properties. Here, we show that X-ray crystal structures of the two different Fd–FNR cross-linked complexes form oligomers by swapping Fd and FNR moieties across the molecules; one complex is a dimer from, and the other is a successive multimeric form. In order to verify whether these oligomeric structures are formed only in crystal, we investigated the possibility of the oligomerization of these complexes in solution. The mean values of the particle size of these cross-linked complexes were shown to increase with the rise of protein concentration at sub-milimolar order, whereas the size of dissociable wild-type Fd:FNR complex was unchanged as analyzed by dynamic light scattering measurement. The oligomerization products were detected by SDS–PAGE after chemical cross-linking of these complexes at the sub-milimolar concentrations. The extent and concentration-dependent profile of the oligomerizaion were differentiated between the two cross-linked complexes. These results show that these Fd–FNR cross-linked complexes exhibit concentration-dependent oligomerization, possibly through swapping of Fd and FNR moieties also in solution. These findings lead to the possibility that some native multi-domain proteins may present similar phenomenon in vivo

Cobalt Oxide on N-Doped Carbon for 1-Butene Oligomerization to Produce Linear Octenes

Energy Technology Data Exchange (ETDEWEB)

Zhao, Dongting [Department; Xu, Zhuoran [Department; Chada, Joseph P. [Department; Carrero, Carlos A. [Department; Rosenfeld, Devon C. [The Dow Chemical Company, 2301 N. Brazosport Boulevard, Freeport, Texas 77541-3257, United States; Rogers, Jessica L. [The Dow Chemical Company, 2301 N. Brazosport Boulevard, Freeport, Texas 77541-3257, United States; Hermans, Ive [Department; Huber, George W. [Department

2017-10-02

Cobalt oxide supported on N-doped carbon catalysts were investigated for 1-butene oligomerization. The materials were synthesized by treating activated carbon with nitric acid and subsequently with NH3 at 200, 400, 600, and 800 °C, followed by impregnation with cobalt. The 1-butene oligomerization selectivity increased with ammonia treatment temperature of the carbon support. The oligomerization selectivity of cobalt oxide on N-doped carbon synthesized at 800 °C (800A-CoOx/N-C) is 2.6 times higher than previously reported cobalt oxide on N-doped carbon synthesized with NH4OH (2A-CoOx/N-C). Over 70% of the butene dimers were linear C8 olefins for all catalysts. The oligomerization selectivity increased with 1-butene conversion. The catalysts were characterized by elemental analysis, N2 adsorption, X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), and X-ray photoelectron spectroscopy (XPS). The nitrogen content of the catalysts increases with ammonia treatment temperature as confirmed by elemental analysis. The surface content of pyridinic nitrogen with a binding energy of 398.4 ± 0.1 eV increased with ammonia treatment temperature as evidenced by deconvolution of N 1s XPS spectra.

Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

Directory of Open Access Journals (Sweden)

Laxton Kevin

2010-05-01

Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

RIG-I self-oligomerization is either dispensable or very transient for signal transduction.

Directory of Open Access Journals (Sweden)

Jade Louber

Full Text Available Effective host defence against viruses depends on the rapid triggering of innate immunity through the induction of a type I interferon (IFN response. To this end, microbe-associated molecular patterns are detected by dedicated receptors. Among them, the RIG-I-like receptors RIG-I and MDA5 activate IFN gene expression upon sensing viral RNA in the cytoplasm. While MDA5 forms long filaments in vitro upon activation, RIG-I is believed to oligomerize after RNA binding in order to transduce a signal. Here, we show that in vitro binding of synthetic RNA mimicking that of Mononegavirales (Ebola, rabies and measles viruses leader sequences to purified RIG-I does not induce RIG-I oligomerization. Furthermore, in cells devoid of endogenous functional RIG-I-like receptors, after activation of exogenous Flag-RIG-I by a 62-mer-5'ppp-dsRNA or by polyinosinic:polycytidylic acid, a dsRNA analogue, or by measles virus infection, anti-Flag immunoprecipitation and specific elution with Flag peptide indicated a monomeric form of RIG-I. Accordingly, when using the Gaussia Luciferase-Based Protein Complementation Assay (PCA, a more sensitive in cellula assay, no RIG-I oligomerization could be detected upon RNA stimulation. Altogether our data indicate that the need for self-oligomerization of RIG-I for signal transduction is either dispensable or very transient.

Human α4β2 nicotinic acetylcholine receptor as a novel target of oligomeric α-synuclein.

Directory of Open Access Journals (Sweden)

Qiang Liu

Full Text Available Cigarette smoking is associated with a decreased incidence of Parkinson disease (PD through unknown mechanisms. Interestingly, a decrease in the numbers of α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs in PD patients suggests an α4β2-nAChR-mediated cholinergic deficit in PD. Although oligomeric forms of α-synuclein have been recognized to be toxic and involved in the pathogenesis of PD, their direct effects on nAChR-mediated cholinergic signaling remains undefined. Here, we report for the first time that oligomeric α-synuclein selectively inhibits human α4β2-nAChR-mediated currents in a dose-dependent, non-competitive and use-independent manner. We show that pre-loading cells with guanyl-5'-yl thiophosphate fails to prevent this inhibition, suggesting that the α-synuclein-induced inhibition of α4β2-nAChR function is not mediated by nAChR internalization. By using a pharmacological approach and cultures expressing transfected human nAChRs, we have shown a clear effect of oligomeric α-synuclein on α4β2-nAChRs, but not on α4β4- or α7-nAChRs, suggesting nAChR subunit selectivity of oligomeric α-synuclein-induced inhibition. In addition, by combining the size exclusion chromatography and atomic force microscopy (AFM analyses, we find that only large (>4 nm oligomeric α-synuclein aggregates (but not monomeric, small oligomeric or fibrillar α-synuclein aggregates exhibit the inhibitory effect on human α4β2-nAChRs. Collectively, we have provided direct evidence that α4β2-nAChR is a sensitive target to mediate oligomeric α-synuclein-induced modulation of cholinergic signaling, and our data imply that therapeutic strategies targeted toward α4β2-nAChRs may have potential for developing new treatments for PD.

Catalytic oligomerization of terminal alkynes promoted by organo-f-complexes

International Nuclear Information System (INIS)

Straub, T.; Haskel, A.; Eisen, M.S.

1995-01-01

Organoactinides of the type Cp* 2 AcMe 2 (Cp*=C 5 Me 5 ; Ac=Th, U) are active catalyst precursors for the oligomerization of terminal alkynes HC triple-bond CR (R=alkyl, aryl, SiMe 3 ). The regioselectivity and the extent of oligomerization strongly depend on the alkyne substituent R, whereas the catalytic reactivity is similar for 1 and 2. In the presence of one of these organoactinides, for example, HCCSiMe 3 regioselectively oligomerizes to the head-to-tail dimer 3 (5%) and the trimer 4 (95%). 1 and 2 react with the terminal alkynes, releasing methane, to the corresponding bisacetylide complexes which are active species and in the catalytic reactions. The bisacetylide complex (η 5 -C 5 Me 5 ) 2 U(CCPh) 2 was identified by proton NMR spectroscopy. Subsequent insertion of alkyne molecules in the actinide-carbon σ-bonds leads to the formation of actinide-alkenyl complexes. The turnover limiting step is the release of the organic oligomer from the actinide-organyl complex. A species of the latter has been spectroscopically characterized in the trimerization reaction of HCCSiMe 3 . In this poster, the catalytic reactivity of the actinide alkyls 1 and 2 with various mono-substituted alkynes as well as the spectroscopic characterization of the key organometallic intermediate complexes in the catalytic cycle and a detailed mechanistic discussion are given

Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Aβ oligomerization.

Directory of Open Access Journals (Sweden)

Yiying Zhang

Full Text Available Accumulation and deposition of β-amyloid protein (Aβ are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase Aβ accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble Aβ oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and Aβ oligomerization in vitro and in vivo. Naïve and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for Aβ; neonatal mice; and conditioned cell culture media containing secreted human Aβ40 or Aβ42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of Aβ. Finally, isoflurane alone induces Aβ42, but not Aβ40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of Aβ42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced Aβ42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients.

N-(1-Pyrenyl Maleimide Induces Bak Oligomerization and Mitochondrial Dysfunction in Jurkat Cells

Directory of Open Access Journals (Sweden)

Pei-Rong Huang

2015-01-01

Full Text Available N-(1-pyrenyl maleimide (NPM is a fluorescent reagent that is frequently used as a derivatization agent for the detection of thio-containing compounds. NPM has been shown to display a great differential cytotoxicity against hematopoietic cancer cells. In this study, the molecular mechanism by which NPM induces apoptosis was examined. Here, we show that treatment of Jurkat cells with NPM leads to Bak oligomerization, loss of mitochondrial membrane potential (Δψm, and release of cytochrome C from mitochondria to cytosol. Induction of Bak oligomerization appears to play a critical role in NPM-induced apoptosis, as downregulation of Bak by shRNA significantly prevented NPM-induced apoptosis. Inhibition of caspase 8 by Z-IETD-FMK and/or depletion of Bid did not affect NPM-induced oligomerization of Bak. Taken together, these results suggest that NPM-induced apoptosis is mediated through a pathway that is independent of caspase-8 activation.

Oligomerization of optically active N-(4-hydroxyphenylmandelamide in the presence of β-cyclodextrin and the minor role of chirality

Directory of Open Access Journals (Sweden)

Helmut Ritter

2014-10-01

Full Text Available The oxidative oligomerization of a chiral mandelamide derivative (N-(4-hydroxyphenylmandelamide, 1 was performed in the presence of horseradish peroxidase, laccase and N,N'-bis(salicylideneethylenediamine-iron(II to obtain chiral oligophenols 2. The low enantioselectivity of the enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was investigated. In addition, the poor influence of cyclodextrin on the enantioselectivity of enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was studied.

40 CFR 721.3100 - Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine. 721.3100 Section 721.3100 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.3100 Oligomeric silicic acid ester compound with a...

Iron-induced oligomerization of human FXN^81-210 and bacterial CyaY frataxin and the effect of iron chelators

DEFF Research Database (Denmark)

Ahlgren, Eva Christina; Fekry, Mostafa; Wiemann, Mathias

2017-01-01

long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks...

A Free Energy Barrier Caused by the Refolding of an Oligomeric Intermediate Controls the Lag Time of Amyloid Formation by hIAPP.

Science.gov (United States)

Serrano, Arnaldo L; Lomont, Justin P; Tu, Ling-Hsien; Raleigh, Daniel P; Zanni, Martin T

2017-11-22

Transiently populated oligomers formed en route to amyloid fibrils may constitute the most toxic aggregates associated with many amyloid-associated diseases. Most nucleation theories used to describe amyloid aggregation predict low oligomer concentrations and do not take into account free energy costs that may be associated with structural rearrangements between the oligomer and fiber states. We have used isotope labeling and two-dimensional infrared spectroscopy to spectrally resolve an oligomeric intermediate during the aggregation of the human islet amyloid protein (hIAPP or amylin), the protein associated with type II diabetes. A structural rearrangement includes the F 23 G 24 A 25 I 26 L 27 region of hIAPP, which starts from a random coil structure, evolves into ordered β-sheet oligomers containing at least 5 strands, and then partially disorders in the fibril structure. The supercritical concentration is measured to be between 150 and 250 μM, which is the thermodynamic parameter that sets the free energy of the oligomers. A 3-state kinetic model fits the experimental data, but only if it includes a concentration independent free energy barrier >3 kcal/mol that represents the free energy cost of refolding the oligomeric intermediate into the structure of the amyloid fibril; i.e., "oligomer activation" is required. The barrier creates a transition state in the free energy landscape that slows fibril formation and creates a stable population of oligomers during the lag phase, even at concentrations below the supercritical concentration. Largely missing in current kinetic models is a link between structure and kinetics. Our experiments and modeling provide evidence that protein structural rearrangements during aggregation impact the populations and kinetics of toxic oligomeric species.

Chemical activation of bituminous coal for hampering oligomerization of organic contaminants.

Science.gov (United States)

Yan, Liang; Sorial, George A

2011-12-15

Activated carbons prepared by KOH activation of bituminous coal were studied for hampering oligomerization of phenolic compounds on its surface. A total of 24 activated carbons with different microporosity and BET surface area were created. The effect of the different variables of the activation process (KOH/bituminous coal ratio, heating temperature, activation time, and flow rate of nitrogen gas) on critical carbon parameters was analyzed. The impact of activated carbon on oligomerization was examined by conducting isotherm experiments at a neutral pH on Carbon(exp) produced with optimal characteristics and granular activated carbon (GAC) F400 for phenol, 2-methylphenol and 2-ethylphenol. These isotherms were collected under anoxic (absence of molecular oxygen) and oxic (presence of molecular oxygen) conditions. The single solute adsorption of phenol, 2-methylphenol and 2-ethylphenol on Carbon(exp) showed no obvious differences between oxic and anoxic environment, which indicated that the Carbon(exp) sample is very effective in hampering the oligomerization of phenolic compounds under oxic conditions. On the other hand, F400, which have lower micropore percentage and BET surface area, significant increases in the adsorptive capacity had been observed when molecular oxygen was present. Copyright © 2011 Elsevier B.V. All rights reserved.

MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.

Directory of Open Access Journals (Sweden)

Manuel Hora

Full Text Available Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS, using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms.

Homologous ELISA for detection of oligomeric human TNF: properties of the assay.

Science.gov (United States)

Petyovka, N; Lyach, L; Voitenok, N N

1995-10-26

In order to quantify oligomeric human tumor necrosis factor-alpha (TNF), we have developed a sensitive homologous enzyme-linked immunosorbent assay (Hm-ELISA) using the same monoclonal antibody (MoAb) for both solid and liquid phase. Different anti-TNF MoAb have been compared in terms of their efficacy in the Hm-ELISA, affinity, neutralization capacity and epitope specificity. The data suggest, that effectiveness in the Hm-ELISA may represent a novel characteristic of MoAb. Of the MoAbs tested, 5 N was capable of recognizing oligomeric TNF in the Hm-ELISA with a detection limit of 15 pg/ml. Furthermore, using Hm-ELISA against human TNF, interleukin-8 (IL-8) and lymphotoxin, we have demonstrated that these cytokines are oligomeric in physiological solutions, but are converted into monomeric forms in the presence of the non-ionic detergent Tween 20. High salt buffer was employed to abrogate a nonspecific false positive reaction in the Hm-ELISA found in nearly half of the plasma samples obtained from healthy subjects. Finally, a good correlation between the Hm-ELISA and the L929 bioassay was observed for natural and recombinant TNF measured in human plasma.

Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis

DEFF Research Database (Denmark)

Bjørnhart, Birgitte; Juul, Anders; Nielsen, Susan

2009-01-01

Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity in patients...

Polybenzoxazine/Polyhedral Oligomeric Silsesquioxane (POSS Nanocomposites

Directory of Open Access Journals (Sweden)

Mohamed Gamal Mohamed

2016-06-01

Full Text Available The organic/inorganic hybrid materials from polyhedral oligomeric silsesquioxane (POSS, inorganic nanoparticles and polybenzoxazine (PBZ have received much interesting recently due to their excellent thermal and mechanical properties, flame retardance, low dielectric constant, well-defined inorganic framework at nanosized scale level, and higher performance relative to those of non-hybrid PBZs. This review describes the synthesis, dielectric constants, and thermal, rheological, and mechanical properties of covalently bonded mono- and multifunctionalized benzoxazine POSS hybrids, other functionalized benzoxazine POSS derivatives, and non-covalently (hydrogen bonded benzoxazine POSS composites.

High Content Analysis of Compositional Heterogeneities to Study GPCR Oligomerization

DEFF Research Database (Denmark)

Walsh, Samuel McEwen

In this thesis I demonstrate how the natural compositional heterogeneities of synthetic and living cell model systems can be used to quantitate the mechanics of G-protein coupled receptor (GPCR) oligomerization with Förster resonance energy transfer (FRET). The thesis is structured around three a...

Receptor oligomerization in family B1 of G-protein-coupled receptors

DEFF Research Database (Denmark)

Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

2012-01-01

, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

Directory of Open Access Journals (Sweden)

Anat Frydman-Marom

Full Text Available An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ play a key role in Alzheimer's disease (AD pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt, which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

Screening of drugs inhibiting in vitro oligomerization of Cu/Zn-superoxide dismutase with a mutation causing amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

Itsuki Anzai

2016-08-01

Full Text Available Dominant mutations in Cu/Zn-superoxide dismutase (SOD1 gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS. A major pathological hallmark of this disease is abnormal accumulation of mutant SOD1 oligomers in the affected spinal motor neurons. While no effective therapeutics for SOD1-ALS is currently available, SOD1 oligomerization will be a good target for developing cures of this disease. Recently, we have reproduced the formation of SOD1 oligomers abnormally cross-linked via disulfide bonds in a test tube. Using our in vitro model of SOD1 oligomerization, therefore, we screened 640 FDA-approved drugs for inhibiting the oligomerization of SOD1 proteins, and three effective classes of chemical compounds were identified. Those hit compounds will provide valuable information on the chemical structures for developing a novel drug candidate suppressing the abnormal oligomerization of mutant SOD1 and possibly curing the disease.

Physiological relevance of plant 2-Cys peroxiredoxin overoxidation level and oligomerization status.

Science.gov (United States)

Cerveau, Delphine; Ouahrani, Djelloul; Marok, Mohamed Amine; Blanchard, Laurence; Rey, Pascal

2016-01-01

Peroxiredoxins are ubiquitous thioredoxin-dependent peroxidases presumed to display, upon environmental constraints, a chaperone function resulting from a redox-dependent conformational switch. In this work, using biochemical and genetic approaches, we aimed to unravel the factors regulating the redox status and the conformation of the plastidial 2-Cys peroxiredoxin (2-Cys PRX) in plants. In Arabidopsis, we show that in optimal growth conditions, the overoxidation level mainly depends on the availability of thioredoxin-related electron donors, but not on sulfiredoxin, the enzyme reducing the 2-Cys PRX overoxidized form. We also observed that upon various physiological temperature, osmotic and light stress conditions, the overoxidation level and oligomerization status of 2-Cys PRX can moderately vary depending on the constraint type. Further, no major change was noticed regarding protein conformation in water-stressed Arabidopsis, barley and potato plants, whereas species-dependent up- and down-variations in overoxidation were observed. In contrast, both 2-Cys PRX overoxidation and oligomerization were strongly induced during a severe oxidative stress generated by methyl viologen. From these data, revealing that the oligomerization status of plant 2-Cys PRX does not exhibit important variation and is not tightly linked to the protein redox status upon physiologically relevant environmental constraints, the possible in planta functions of 2-Cys PRX are discussed. © 2015 John Wiley & Sons Ltd.

An Investigation of Chemical Landscapes in Aqueous Electrosprays by Tracking Oligomerization of Isoprene

KAUST Repository

Junior, Adair Gallo

2017-12-01

Electrospray ionization mass spectrometry (ESIMS) is widely used to characterize neutral and ionic species in solvents. Typically, electrical, thermal, and pneumatic potentials are applied to create electrosprays from which charged ionic species are ejected for downstream analysis by mass spectrometry. Most recently, ESIMS has been exploited to investigate ambient proton transfer reactions at air-water interfaces in real time. We assessed the validity of these experiments via complementary laboratory experiments. Specifically, we characterized the products of two reaction scenarios via ESIMS and proton nuclear magnetic resonance (1H-NMR): (i) emulsions of pH-adjusted water and isoprene (C5H8) that were mechanically agitated, and (ii) electrosprays of pH-adjusted water that were collided with gas-phase isoprene. Our experiments unambiguously demonstrate that, while isoprene does not oligomerize in emulsions, it does undergo protonation and oligomerization in electrosprays, both with and without pH-adjusted water, confirming that C-C bonds form along myriad high-energy pathways during electrospray ionization. We also compared our experimental results with some quantum mechanics simulations of isoprene molecules interacting with hydronium at different hydration levels (gas versus liquid phase). In agreement with our experiments, the kinetic barriers to protonation and oligomerization of isoprene were inaccessible under ambient conditions. Rather, the gas-phase chemistries during electrospray ionization drove the oligomerization of isoprene. Therefore, we consider that ESIMS could induce artifacts in interfacial reactions. These findings warrant a reassessment of previous reports on tracking chemistries under ambient conditions at liquid-vapor interfaces via ESIMS. Further, we took some high-speed images of electrosprays where it was possible to observe the main characteristics of the phenomena, i.e. Taylor cone, charge separation, and Coulomb fission. Finally, we took

Catalysis of the Oligomerization of O-Phospho-Serine, Aspartic Acid, or Glutamic Acid by Cationic Micelles

Science.gov (United States)

Bohler, Christof; Hill, Aubrey R., Jr.; Orgel, Leslie E.

1996-01-01

Treatment of relatively concentrated aqueous solutions of 0-phospho-serine (50 mM), aspartic acid (100 mM) or glutamic acid (100 mM) with carbonyldiimidazole leads to the formation of an activated intermediate that oligomerizes efficiently. When the concentration of amino acid is reduced tenfold, few long oligomers can be detected. Positively-charged cetyltrimethyl ammonium bromide micelles concentrate the negatively-charged activated intermediates of the amino acids at their surfaces and catalyze efficient oligomerization even from dilute solutions.

MxiN Differentially Regulates Monomeric and Oligomeric Species of the Shigella Type Three Secretion System ATPase Spa47.

Science.gov (United States)

Case, Heather B; Dickenson, Nicholas E

2018-04-17

Shigella rely entirely on the action of a single type three secretion system (T3SS) to support cellular invasion of colonic epithelial cells and to circumvent host immune responses. The ATPase Spa47 resides at the base of the Shigella needle-like type three secretion apparatus (T3SA), supporting protein secretion through the apparatus and providing a likely means for native virulence regulation by Shigella and a much needed target for non-antibiotic therapeutics to treat Shigella infections. Here, we show that MxiN is a differential regulator of Spa47 and that its regulatory impact is determined by the oligomeric state of the Spa47 ATPase, with which it interacts. In vitro and in vivo characterization shows that interaction of MxiN with Spa47 requires the six N-terminal residues of Spa47 that are also necessary for stable Spa47 oligomer formation and activation. This interaction with MxiN negatively influences the activity of Spa47 oligomers while upregulating the ATPase activity of monomeric Spa47. Detailed kinetic analyses of monomeric and oligomeric Spa47 in the presence and absence of MxiN uncover additional mechanistic insights into the regulation of Spa47 by MxiN, suggesting that the MxiN/Spa47 species resulting from interaction with monomeric and oligomeric Spa47 are functionally distinct and that both could be involved in Shigella T3SS regulation. Uncovering regulation of Spa47 by MxiN addresses an important gap in the current understanding of how Shigella controls T3SA activity and provides the first description of differential T3SS ATPase regulation by a native T3SS protein.

Interference with RUNX1/ETO Leukemogenic Function by Cell-Penetrating Peptides Targeting the NHR2 Oligomerization Domain

Directory of Open Access Journals (Sweden)

Yvonne Bartel

2013-01-01

Full Text Available The leukemia-associated fusion protein RUNX1/ETO is generated by the chromosomal translocation t(8;21 which appears in about 12% of all de novo acute myeloid leukemias (AMLs. Essential for the oncogenic potential of RUNX1/ETO is the oligomerization of the chimeric fusion protein through the nervy homology region 2 (NHR2 within ETO. In previous studies, we have shown that the intracellular expression of peptides containing the NHR2 domain inhibits RUNX1/ETO oligomerization, thereby preventing cell proliferation and inducing differentiation of RUNX1/ETO transformed cells. Here, we show that introduction of a recombinant TAT-NHR2 fusion polypeptide into the RUNX1/ETO growth-dependent myeloid cell line Kasumi-1 results in decreased cell proliferation and increased numbers of apoptotic cells. This effect was highly specific and mediated by binding the TAT-NHR2 peptide to ETO sequences, as TAT-polypeptides containing the oligomerization domain of BCR did not affect cell proliferation or apoptosis in Kasumi-1 cells. Thus, the selective interference with NHR2-mediated oligomerization by peptides represents a challenging but promising strategy for the inhibition of the leukemogenic potential of RUNX1/ETO in t(8;21-positive leukemia.

Protic ionic liquids based on the dimeric and oligomeric anions: [(AcO)xH(x-1)]-.

Science.gov (United States)

Johansson, K M; Izgorodina, E I; Forsyth, M; MacFarlane, D R; Seddon, K R

2008-05-28

We describe a fluidity and conductivity study as a function of composition in N-methylpyrrolidine-acetic acid mixtures. The simple 1 : 1 acid-base mixture appears to form an ionic liquid, but its degree of ionicity is quite low and such liquids are better thought of as poorly dissociated mixtures of acid and base. The composition consisting of 3 moles acetic acid and 1 mole N-methylpyrrolidine is shown to form the highest ionicity mixture in this binary due to the presence of oligomeric anionic species [(AcO)(x)H(x-1)](-) stabilised by hydrogen bonds. These oligomeric species, being weaker bases than the acetate anion, shift the proton transfer equilibrium towards formation of ionic species, thus generating a higher degree of ionicity than is present at the 1 : 1 composition. A Walden plot analysis, thermogravimetric behaviour and proton NMR data, as well as ab initio calculations of the oligomeric species, all support this conclusion.

Design of a minimal protein oligomerization domain by a structural approach.

Science.gov (United States)

Burkhard, P; Meier, M; Lustig, A

2000-12-01

Because of the simplicity and regularity of the alpha-helical coiled coil relative to other structural motifs, it can be conveniently used to clarify the molecular interactions responsible for protein folding and stability. Here we describe the de novo design and characterization of a two heptad-repeat peptide stabilized by a complex network of inter- and intrahelical salt bridges. Circular dichroism spectroscopy and analytical ultracentrifugation show that this peptide is highly alpha-helical and 100% dimeric tinder physiological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic strength. The correctness of the rational design principles used here is supported by details of the atomic structure of the peptide deduced from X-ray crystallography. The structure of the peptide shows that it is not a molten globule but assumes a unique, native-like conformation. This de novo peptide thus represents an attractive model system for the design of a molecular recognition system.

Multiple-state Feshbach resonances mediated by high-order couplings

International Nuclear Information System (INIS)

Hemming, Christopher J.; Krems, Roman V.

2008-01-01

We present a study of multistate Feshbach resonances mediated by high-order couplings. Our analysis focuses on a system with one open scattering state and multiple bound states. The scattering state is coupled to one off-resonant bound state and multiple Feshbach resonances are induced by a sequence of indirect couplings between the closed channels. We derive a general recursive expression that can be used to fit the experimental data on multistate Feshbach resonances involving one continuum state and several bound states and present numerical solutions for several model systems. Our results elucidate general features of multistate Feshbach resonances induced by high-order couplings and suggest mechanisms for controlling collisions of ultracold atoms and molecules with external fields

Cartilage oligomeric matrix protein specific antibodies are pathogenic

DEFF Research Database (Denmark)

Geng, Hui; Nandakumar, Kutty Selva; Pramhed, Anna

2012-01-01

-specific monoclonal antibodies (mAbs). METHODS: B cell immunodominant regions on the COMP molecule were measured with a novel enzyme-linked immunosorbent assay using mammalian expressed full-length mouse COMP as well as a panel of recombinant mouse COMP fragments. 18 mAbs specific to COMP were generated......ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage. Earlier, we developed a new mouse model for rheumatoid arthritis using COMP. This study was undertaken to investigate the epitope specificity and immunopathogenicity of COMP...

Receptor Oligomerization as a Process Modulating Cellular Semiotics

DEFF Research Database (Denmark)

Giorgi, Franco; Bruni, Luis Emilio; Maggio, Roberto

2010-01-01

be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure...... at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy...

Multiple scroll wave chimera states

Science.gov (United States)

Maistrenko, Volodymyr; Sudakov, Oleksandr; Osiv, Oleksiy; Maistrenko, Yuri

2017-06-01

We report the appearance of three-dimensional (3D) multiheaded chimera states that display cascades of self-organized spatiotemporal patterns of coexisting coherence and incoherence. We demonstrate that the number of incoherent chimera domains can grow additively under appropriate variations of the system parameters generating thereby head-adding cascades of the scroll wave chimeras. The phenomenon is derived for the Kuramoto model of N 3 identical phase oscillators placed in the unit 3D cube with periodic boundary conditions, parameters being the coupling radius r and phase lag α. To obtain the multiheaded chimeras, we perform the so-called `cloning procedure' as follows: choose a sample single-headed 3D chimera state, make appropriate scale transformation, and put some number of copies of them into the unit cube. After that, start numerical simulations with slightly perturbed initial conditions and continue them for a sufficiently long time to confirm or reject the state existence and stability. In this way it is found, that multiple scroll wave chimeras including those with incoherent rolls, Hopf links and trefoil knots admit this sort of multiheaded regeneration. On the other hand, multiple 3D chimeras without spiral rotations, like coherent and incoherent balls, tubes, crosses, and layers appear to be unstable and are destroyed rather fast even for arbitrarily small initial perturbations.

Elucidation of amyloid beta-protein oligomerization mechanisms: discrete molecular dynamics study.

Science.gov (United States)

Urbanc, B; Betnel, M; Cruz, L; Bitan, G; Teplow, D B

2010-03-31

Oligomers of amyloid beta-protein (Abeta) play a central role in the pathology of Alzheimer's disease. Of the two predominant Abeta alloforms, Abeta(1-40) and Abeta(1-42), Abeta(1-42) is more strongly implicated in the disease. We elucidated the structural characteristics of oligomers of Abeta(1-40) and Abeta(1-42) and their Arctic mutants, [E22G]Abeta(1-40) and [E22G]Abeta(1-42). We simulated oligomer formation using discrete molecular dynamics (DMD) with a four-bead protein model, backbone hydrogen bonding, and residue-specific interactions due to effective hydropathy and charge. For all four peptides under study, we derived the characteristic oligomer size distributions that were in agreement with prior experimental findings. Unlike Abeta(1-40), Abeta(1-42) had a high propensity to form paranuclei (pentameric or hexameric) structures that could self-associate into higher-order oligomers. Neither of the Arctic mutants formed higher-order oligomers, but [E22G]Abeta(1-40) formed paranuclei with a similar propensity to that of Abeta(1-42). Whereas the best agreement with the experimental data was obtained when the charged residues were modeled as solely hydrophilic, further assembly from spherical oligomers into elongated protofibrils was induced by nonzero electrostatic interactions among the charged residues. Structural analysis revealed that the C-terminal region played a dominant role in Abeta(1-42) oligomer formation whereas Abeta(1-40) oligomerization was primarily driven by intermolecular interactions among the central hydrophobic regions. The N-terminal region A2-F4 played a prominent role in Abeta(1-40) oligomerization but did not contribute to the oligomerization of Abeta(1-42) or the Arctic mutants. The oligomer structure of both Arctic peptides resembled Abeta(1-42) more than Abeta(1-40), consistent with their potentially more toxic nature.

Kinetic Analysis for Macrocyclizations Involving Anionic Template at the Transition State

Directory of Open Access Journals (Sweden)

Vicente Martí-Centelles

2012-01-01

competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes.

An Intramolecular Salt Bridge in Bacillus thuringiensis Cry4Ba Toxin Is Involved in the Stability of Helix α-3, Which Is Needed for Oligomerization and Insecticidal Activity.

Science.gov (United States)

Pacheco, Sabino; Gómez, Isabel; Sánchez, Jorge; García-Gómez, Blanca-Ines; Soberón, Mario; Bravo, Alejandra

2017-10-15

Bacillus thuringiensis three-domain Cry toxins kill insects by forming pores in the apical membrane of larval midgut cells. Oligomerization of the toxin is an important step for pore formation. Domain I helix α-3 participates in toxin oligomerization. Here we identify an intramolecular salt bridge within helix α-3 of Cry4Ba (D111-K115) that is conserved in many members of the family of three-domain Cry toxins. Single point mutations such as D111K or K115D resulted in proteins severely affected in toxicity. These mutants were also altered in oligomerization, and the mutant K115D was more sensitive to protease digestion. The double point mutant with reversed charges, D111K-K115D, recovered both oligomerization and toxicity, suggesting that this salt bridge is highly important for conservation of the structure of helix α-3 and necessary to promote the correct oligomerization of the toxin. IMPORTANCE Domain I has been shown to be involved in oligomerization through helix α-3 in different Cry toxins, and mutations affecting oligomerization also elicit changes in toxicity. The three-dimensional structure of the Cry4Ba toxin reveals an intramolecular salt bridge in helix α-3 of domain I. Mutations that disrupt this salt bridge resulted in changes in Cry4Ba oligomerization and toxicity, while a double point reciprocal mutation that restored the salt bridge resulted in recovery of toxin oligomerization and toxicity. These data highlight the role of oligomer formation as a key step in Cry4Ba toxicity. Copyright © 2017 American Society for Microbiology.

The role of oligomerization and cooperative regulation in protein function: the case of tryptophan synthase.

Directory of Open Access Journals (Sweden)

M Qaiser Fatmi

Full Text Available The oligomerization/co-localization of protein complexes and their cooperative regulation in protein function is a key feature in many biological systems. The synergistic regulation in different subunits often enhances the functional properties of the multi-enzyme complex. The present study used molecular dynamics and Brownian dynamics simulations to study the effects of allostery, oligomerization and intermediate channeling on enhancing the protein function of tryptophan synthase (TRPS. TRPS uses a set of α/β-dimeric units to catalyze the last two steps of L-tryptophan biosynthesis, and the rate is remarkably slower in the isolated monomers. Our work shows that without their binding partner, the isolated monomers are stable and more rigid. The substrates can form fairly stable interactions with the protein in both forms when the protein reaches the final ligand-bound conformations. Our simulations also revealed that the α/β-dimeric unit stabilizes the substrate-protein conformation in the ligand binding process, which lowers the conformation transition barrier and helps the protein conformations shift from an open/inactive form to a closed/active form. Brownian dynamics simulations with a coarse-grained model illustrate how protein conformations affect substrate channeling. The results highlight the complex roles of protein oligomerization and the fine balance between rigidity and dynamics in protein function.

Influence of oligomeric resins on traction and rolling resistance of silica tire treads

NARCIS (Netherlands)

Vleugels, N.; Pille-Wolf, W.; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

2016-01-01

This study concerns the silica-reinforcement of synthetic rubber compounds for passenger tire treads with the objective to gain insight into the beneficial effects of oligomeric resins, derived from natural and synthetic monomers, on the major tire performance factors: rolling resistance and (wet)

Influence of oligomeric resins on traction and rolling resistance of silica tire treads

NARCIS (Netherlands)

Vleugels, N.; Pille-Wolf, W.; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

2013-01-01

This study concerns the silica-reinforcement of synthetic rubber compounds for passenger tire treads with the objective to gain insight into the beneficial effects of oligomeric resins, derived from natural and synthetic monomers, on the major tire performance factors: Rolling Resistance and (Wet)

Hydration effect on the electronic transport properties of oligomeric phenylene ethynylene molecular junctions

International Nuclear Information System (INIS)

Zong-Liang, Li; Huai-Zhi, Li; Yong, Ma; Guang-Ping, Zhang; Chuan-Kui, Wang

2010-01-01

A first-principles computational method based on the hybrid density functional theory is developed to simulate the electronic transport properties of oligomeric phenylene ethynylene molecular junctions with H 2 O molecules accumulated in the vicinity as recently reported by Na et al. [Nanotechnology 18 424001 (2007)]. The numerical results show that the hydrogen bonds between the oxygen atoms of the oligomeric phenylene ethynylene molecule and H 2 O molecules result in the localisation of the molecular orbitals and lead to the lower transition peaks. The H 2 O molecular chains accumulated in the vicinity of the molecular junction can not only change the electronic structure of the molecular junctions, but also open additional electronic transport pathways. The obvious influence of H 2 O molecules on the electronic structure of the molecular junction and its electronic transport properties is thus demonstrated. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Multiplicities of states od equivalent fermion shells

International Nuclear Information System (INIS)

Savukinas, A.Yu.; Glembotskij, I.I.

1980-01-01

Classification of states of three or four equivalent fermions has been studied, i.e. possible terms and their multiplicities have been determined. For this purpose either the group theory or evident expressions for the fractional-parentage coefficients have been used. In the first approach the formulas obtained by other authors for the multiplicities of terms through the characters of the transformation matrices of bond moments have been used. This approach happens to be more general as compared with the second one, as expressions for the fractional-parentage coefficients in many cases are not known. The multiplicities of separate terms have been determined. It has been shown that the number of terms of any multiplicity becomes constant when l or j is increased [ru

Mechanics of the mannitol transporter from Escherichia coli : substrate-probing and oligomeric structure

NARCIS (Netherlands)

Veldhuis, Gertjan

2006-01-01

Gertjan Veldhuis bestudeerde de mannitoltransporter van Escherichia coli, EnzymeIImtl (EIImtl), om meer inzicht te krijgen in het bindingsmechanisme en de oligomere toestand van dit membraaneiwit. Hij concludeerde onder andere dat dimeer EIImtl één mannitol bindt, de dimeer zeer stabiel is en dat

The Agrobacterium tumefaciens Transcription Factor BlcR Is Regulated via Oligomerization

Energy Technology Data Exchange (ETDEWEB)

Pan, Yi; Fiscus, Valena; Meng, Wuyi; Zheng, Zhida; Zhang, Lian-Hui; Fuqua, Clay; Chen, Lingling (IMCB-Singapore); (Indiana)

2012-02-08

The Agrobacterium tumefaciens BlcR is a member of the emerging isocitrate lyase transcription regulators that negatively regulates metabolism of {gamma}-butyrolactone, and its repressing function is relieved by succinate semialdehyde (SSA). Our crystal structure showed that BlcR folded into the DNA- and SSA-binding domains and dimerized via the DNA-binding domains. Mutational analysis identified residues, including Phe{sup 147}, that are important for SSA association; BlcR{sup F147A} existed as tetramer. Two BlcR dimers bound to target DNA and in a cooperative manner, and the distance between the two BlcR-binding sequences in DNA was critical for BlcR-DNA association. Tetrameric BlcR{sup F147A} retained DNA binding activity, and importantly, this activity was not affected by the distance separating the BlcR-binding sequences in DNA. SSA did not dissociate tetrameric BlcR{sup F147A} or BlcR{sup F147A}-DNA. As well as in the SSA-binding site, Phe{sup 147} is located in a structurally flexible loop that may be involved in BlcR oligomerization. We propose that SSA regulates BlcR DNA-binding function via oligomerization.

Single-molecule diffusometry reveals the nucleotide-dependent oligomerization pathways of Nicotiana tabacum Rubisco activase

Science.gov (United States)

Wang, Quan; Serban, Andrew J.; Wachter, Rebekka M.; Moerner, W. E.

2018-03-01

Oligomerization plays an important role in the function of many proteins, but a quantitative picture of the oligomer distribution has been difficult to obtain using existing techniques. Here we describe a method that combines sub-stoichiometric labeling and recently developed single-molecule diffusometry to measure the size distribution of oligomers under equilibrium conditions in solution, one molecule at a time. We use this technique to characterize the oligomerization behavior of Nicotiana tabacum (Nt) Rubisco activase (Nt-Rca), a chaperone-like AAA-plus ATPase essential in regulating carbon fixation during photosynthesis. We directly observed monomers, dimers, and a tetramer/hexamer mixture and extracted their fractional abundance as a function of protein concentration. We show that the oligomerization pathway of Nt-Rca is nucleotide dependent: ATPγS binding strongly promotes tetramer/hexamer formation from dimers and results in a preferred tetramer/hexamer population for concentrations in the 1-10 μM range. Furthermore, we directly observed dynamic assembly and disassembly processes of single complexes in real time and from there estimated the rate of subunit exchange to be ˜0.1 s-1 with ATPγS. On the other hand, ADP binding destabilizes Rca complexes by enhancing the rate of subunit exchange by >2 fold. These observations provide a quantitative starting point to elucidate the structure-function relations of Nt-Rca complexes. We envision the method to fill a critical gap in defining and quantifying protein assembly pathways in the small-oligomer regime.

Direct Evidence of Intrinsic Blue Fluorescence from Oligomeric Interfaces of Human Serum Albumin.

Science.gov (United States)

Bhattacharya, Arpan; Bhowmik, Soumitra; Singh, Amit K; Kodgire, Prashant; Das, Apurba K; Mukherjee, Tushar Kanti

2017-10-10

The molecular origin behind the concentration-dependent intrinsic blue fluorescence of human serum albumin (HSA) is not known yet. This unusual blue fluorescence is believed to be a characteristic feature of amyloid-like fibrils of protein/peptide and originates due to the delocalization of peptide bond electrons through the extended hydrogen bond networks of cross-β-sheet structure. Herein, by combining the results of spectroscopy, size exclusion chromatography, native gel electrophoresis, and confocal microscopy, we have shown that the intrinsic blue fluorescence of HSA exclusively originates from oligomeric interfaces devoid of any amyloid-like fibrillar structure. Our study suggests that this low energy fluorescence band is not due to any particular residue/sequence, but rather it is a common feature of self-assembled peptide bonds. The present findings of intrinsic blue fluorescence from oligomeric interfaces pave the way for future applications of this unique visual phenomenon for early stage detection of various protein aggregation related human diseases.

Degenerate ground states and multiple bifurcations in a two-dimensional q-state quantum Potts model.

Science.gov (United States)

Dai, Yan-Wei; Cho, Sam Young; Batchelor, Murray T; Zhou, Huan-Qiang

2014-06-01

We numerically investigate the two-dimensional q-state quantum Potts model on the infinite square lattice by using the infinite projected entangled-pair state (iPEPS) algorithm. We show that the quantum fidelity, defined as an overlap measurement between an arbitrary reference state and the iPEPS ground state of the system, can detect q-fold degenerate ground states for the Z_{q} broken-symmetry phase. Accordingly, a multiple bifurcation of the quantum ground-state fidelity is shown to occur as the transverse magnetic field varies from the symmetry phase to the broken-symmetry phase, which means that a multiple-bifurcation point corresponds to a critical point. A (dis)continuous behavior of quantum fidelity at phase transition points characterizes a (dis)continuous phase transition. Similar to the characteristic behavior of the quantum fidelity, the magnetizations, as order parameters, obtained from the degenerate ground states exhibit multiple bifurcation at critical points. Each order parameter is also explicitly demonstrated to transform under the Z_{q} subgroup of the symmetry group of the Hamiltonian. We find that the q-state quantum Potts model on the square lattice undergoes a discontinuous (first-order) phase transition for q=3 and q=4 and a continuous phase transition for q=2 (the two-dimensional quantum transverse Ising model).

Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

International Nuclear Information System (INIS)

Egorov, V. V.; Gorshkov, A. N.; Murugova, T. N.; Vasin, A. V.; Lebedev, D. V.; Isaev-Ivanov, V. V.; Kiselev, O. I.

2016-01-01

Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551–560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed

Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

Energy Technology Data Exchange (ETDEWEB)

Egorov, V. V., E-mail: vlaegur@omrb.pnpi.spb.ru [National Research Center “Kurchatov Institute”, Konstantinov Petersburg Nuclear Physics Institute (Russian Federation); Gorshkov, A. N. [Ministry of Health of the Russian Federation, Research Institute of Influenza (Russian Federation); Murugova, T. N. [Joint Institute for Nuclear Research (Russian Federation); Vasin, A. V. [Ministry of Health of the Russian Federation, Research Institute of Influenza (Russian Federation); Lebedev, D. V.; Isaev-Ivanov, V. V. [National Research Center “Kurchatov Institute”, Konstantinov Petersburg Nuclear Physics Institute (Russian Federation); Kiselev, O. I. [Ministry of Health of the Russian Federation, Research Institute of Influenza (Russian Federation)

2016-01-15

Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551–560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed.

Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

Science.gov (United States)

Egorov, V. V.; Gorshkov, A. N.; Murugova, T. N.; Vasin, A. V.; Lebedev, D. V.; Isaev-Ivanov, V. V.; Kiselev, O. I.

2016-01-01

Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551-560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed.

Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization

NARCIS (Netherlands)

Simons, Peter J.; van den Pangaart, Petra S.; Aerts, Johannes M. F. G.; Boon, Louis

2007-01-01

Adiponectin and, especially, its oligomeric complex composition have been suggested to be critical in determining insulin sensitivity. Pro-inflammatory cytokines play an important role in the development of insulin resistance in obesity and associated diseases. Therefore, we investigated the effect

Detection of Amyloid Beta (Aβ) Oligomeric Composition Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS)

Science.gov (United States)

Wang, Jasmine S.-H.; Whitehead, Shawn N.; Yeung, Ken K.-C.

2018-02-01

The use of MALDI MS as a fast and direct method to detect the Aβ oligomers of different masses is examined in this paper. Experimental results suggest that Aβ oligomers are ionized and detected as singly charged ions, and thus, the resulting mass spectrum directly reports the oligomer size distribution. Validation experiments were performed to verify the MS data against artifacts. Mass spectra collected from modified Aβ peptides with different propensities for aggregation were compared. Generally, the relative intensities of multimers were higher from samples where oligomerization was expected to be more favorable, and vice versa. MALDI MS was also able to detect the differences in oligomeric composition before and after the incubation/oligomerization step. Such differences in sample composition were also independently confirmed with an in vitro Aβ toxicity study on primary rat cortical neurons. An additional validation was accomplished through removal of oligomers from the sample using molecular weight cutoff filters; the resulting MS data correctly reflected the removal at the expected cutoff points. The results collectively validated the ability of MALDI MS to assess the monomeric/multimeric composition of Aβ samples. [Figure not available: see fulltext.

Purification, crystallization and preliminary crystallographic analysis of Est-Y29: a novel oligomeric β-lactamase

International Nuclear Information System (INIS)

Kim, SeungBum; Joo, Sangbum; Yoon, Sangyoung; Kim, Sungsoo; Moon, Jongkook; Ryu, Yeonwoo; Kim, Kyeong Kyu; Kim, T. Doohun

2009-01-01

Est-Y29, a novel oligomeric class C β-lactamase from a metagenomic library, was crystallized in space group I4 1 and diffraction data were collected to 1.49 Å resolution. β-Lactam antibiotics such as penicillins and cephalosporins have a four-atom ring as a common element in their structure. The β-lactamases, which catalyze the inactivation of these antibiotics, are of great interest because of their high incidence in pathogenic bacteria. A novel oligomeric class C β-lactamase (Est-Y29) from a metagenomic library was expressed, purified and crystallized. The recombinant protein was expressed in Escherichia coli with an N-terminal 6×His tag and purified to homogeneity. EstY-29 was crystallized and X-ray intensity data were collected to 1.49 Å resolution using synchrotron radiation

Structural basis for TatA oligomerization: an NMR study of Escherichia coli TatA dimeric structure.

Directory of Open Access Journals (Sweden)

Yi Zhang

Full Text Available Many proteins are transported across lipid membranes by protein translocation systems in living cells. The twin-arginine transport (Tat system identified in bacteria and plant chloroplasts is a unique system that transports proteins across membranes in their fully-folded states. Up to date, the detailed molecular mechanism of this process remains largely unclear. The Escherichia coli Tat system consists of three essential transmembrane proteins: TatA, TatB and TatC. Among them, TatB and TatC form a tight complex and function in substrate recognition. The major component TatA contains a single transmembrane helix followed by an amphipathic helix, and is suggested to form the translocation pore via self-oligomerization. Since the TatA oligomer has to accommodate substrate proteins of various sizes and shapes, the process of its assembly stands essential for understanding the translocation mechanism. A structure model of TatA oligomer was recently proposed based on NMR and EPR observations, revealing contacts between the transmembrane helices from adjacent subunits. Herein we report the construction and stabilization of a dimeric TatA, as well as the structure determination by solution NMR spectroscopy. In addition to more extensive inter-subunit contacts between the transmembrane helices, we were also able to observe interactions between neighbouring amphipathic helices. The side-by-side packing of the amphipathic helices extends the solvent-exposed hydrophilic surface of the protein, which might be favourable for interactions with substrate proteins. The dimeric TatA structure offers more detailed information of TatA oligomeric interface and provides new insights on Tat translocation mechanism.

Type IX Collagen Gene Mutations Can Result in Multiple Epiphyseal Dysplasia That Is Associated With Osteochondritis Dissecans and a Mild Myopathy

NARCIS (Netherlands)

Jackson, Gail C.; Marcus-Soekarman, Dominique; Stolte-Dijkstra, Irene; Verrips, Aad; Taylor, Jacqueline A.; Briggs, Michael D.

Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix

Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.

NARCIS (Netherlands)

Jackson, G.C.; Marcus-Soekarman, D.; Stolte-Dijkstra, I.; Verrips, A.; Taylor, J.A.; Briggs, M.D.

2010-01-01

Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix

Compositional mining of multiple object API protocols through state abstraction.

Science.gov (United States)

Dai, Ziying; Mao, Xiaoguang; Lei, Yan; Qi, Yuhua; Wang, Rui; Gu, Bin

2013-01-01

API protocols specify correct sequences of method invocations. Despite their usefulness, API protocols are often unavailable in practice because writing them is cumbersome and error prone. Multiple object API protocols are more expressive than single object API protocols. However, the huge number of objects of typical object-oriented programs poses a major challenge to the automatic mining of multiple object API protocols: besides maintaining scalability, it is important to capture various object interactions. Current approaches utilize various heuristics to focus on small sets of methods. In this paper, we present a general, scalable, multiple object API protocols mining approach that can capture all object interactions. Our approach uses abstract field values to label object states during the mining process. We first mine single object typestates as finite state automata whose transitions are annotated with states of interacting objects before and after the execution of the corresponding method and then construct multiple object API protocols by composing these annotated single object typestates. We implement our approach for Java and evaluate it through a series of experiments.

Fluorescence reporters for Hfq oligomerization and RNA annealing

Science.gov (United States)

Panja, Subrata; Woodson, Sarah A.

2015-01-01

Fluorescence spectroscopy is a sensitive technique for detecting protein-protein, protein-RNA and RNA-RNA interactions, requiring only nanomolar concentrations of labeled components. Fluorescence anisotropy provides information about the assembly of multi-subunit proteins, while molecular beacons provide a sensitive and quantitative reporter for base pairing between complementary RNAs. Here we present a detailed protocol for labeling Hfq protein with cyanine 3-maleimide and dansyl chloride to study the protein oligomerization and RNA binding by semi-native polyacrylamide gel electrophoresis (PAGE) and fluorescence anisotropy. We also present a detailed protocol for measuring the rate of annealing between a molecular beacon and a target RNA in the presence of Hfq using a stopped-flow spectrometer. PMID:25579597

Electron Microscopy Structural Insights into CPAP Oligomeric Behavior

DEFF Research Database (Denmark)

Alvarez-Cabrera, Ana L; Delgado, Sandra; Gil-Carton, David

2017-01-01

Centrosomal P4.1-associated protein (CPAP) is a cell cycle regulated protein fundamental for centrosome assembly and centriole elongation. In humans, the region between residues 897-1338 of CPAP mediates interactions with other proteins and includes a homodimerization domain. CPAP mutations cause...... into clearly different regular 3D maps (putatively corresponding to dimers and tetramers) and direct observation of individual images representing other complexes of HsCPAP(897-1338) (i.e., putative flexible monomers and higher-order multimers), we report a dynamic oligomeric behavior of this protein, where...... of different oligomers of CPAP, suggesting further insights to understand how this protein works, contributing to the elucidation of control mechanisms for centriole biogenesis....

Multi-objective optimization of linear multi-state multiple sliding window system

International Nuclear Information System (INIS)

Konak, Abdullah; Kulturel-Konak, Sadan; Levitin, Gregory

2012-01-01

This paper considers the optimal element sequencing in a linear multi-state multiple sliding window system that consists of n linearly ordered multi-state elements. Each multi-state element can have different states: from complete failure up to perfect functioning. A performance rate is associated with each state. The failure of type i in the system occurs if for any i (1≤i≤I) the cumulative performance of any r i consecutive elements is lower than w i . The element sequence strongly affects the probability of any type of system failure. The sequence that minimizes the probability of certain type of failure can provide high probability of other types of failures. Therefore the optimization problem for the multiple sliding window system is essentially multi-objective. The paper formulates and solves the multi-objective optimization problem for the multiple sliding window systems. A multi-objective Genetic Algorithm is used as the optimization engine. Illustrative examples are presented.

The cysteines of the extracellular loop are crucial for trafficking of human organic cation transporter 2 to the plasma membrane and are involved in oligomerization.

Science.gov (United States)

Brast, Sabine; Grabner, Alexander; Sucic, Sonja; Sitte, Harald H; Hermann, Edwin; Pavenstädt, Hermann; Schlatter, Eberhard; Ciarimboli, Giuliano

2012-03-01

Human organic cation transporter 2 (hOCT2) is involved in transport of many endogenous and exogenous organic cations, mainly in kidney and brain cells. Because the quaternary structure of transmembrane proteins plays an essential role for their cellular trafficking and function, we investigated whether hOCT2 forms oligomeric complexes, and if so, which part of the transporter is involved in the oligomerization. A yeast 2-hybrid mating-based split-ubiquitin system (mbSUS), fluorescence resonance energy transfer, Western blot analysis, cross-linking experiments, immunofluorescence, and uptake measurements of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium were applied to human embryonic kidney 293 (HEK293) cells transfected with hOCT2 and partly also to freshly isolated human proximal tubules. The role of cysteines for oligomerization and trafficking of the transporter to the plasma membranes was investigated in cysteine mutants of hOCT2. hOCT2 formed oligomers both in the HEK293 expression system and in native human kidneys. The cysteines of the large extracellular loop are important to enable correct folding, oligomeric assembly, and plasma membrane insertion of hOCT2. Mutation of the first and the last cysteines of the loop at positions 51 and 143 abolished oligomer formation. Thus, the cysteines of the extracellular loop are important for correct trafficking of the transporter to the plasma membrane and for its oligomerization.

Chaperonin of Group I: Oligomeric Spectrum and Biochemical and Biological Implications

Directory of Open Access Journals (Sweden)

Silvia Vilasi

2018-01-01

Full Text Available Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM, is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still incompletely understood. Chaperonin I in eukaryotes occurs in various locations, not just the mitochondrion, which is its canonical place of residence and function. Eukaryotic Chaperonin I, namely Hsp60 (designated HSP60 or HSPD1 in humans has, indeed, been found in the cytosol; the plasma-cell membrane; on the outer surface of cells; in the intercellular space; in biological liquids such as lymph, blood, and cerebrospinal fluid; and in secretions, for instance saliva and urine. Hsp60 has also been found in cell-derived vesicles such as exosomes. The functions of Hsp60 in all these non-canonical locales are still poorly characterized and one of the questions not yet answered is in what form, i.e., monomer or oligomer, is the chaperonin present in these non-canonical locations. In view of the steady increase in interest on chaperonopathies over the last several years, we have studied human HSP60 to determine its role in various diseases, its locations in cells and tissues and migrations in the body, and its post-translational modifications that might have an impact on its location and function. We also carried out experiments to characterize the oligomeric status of extramitochondrial of HSP60 in solution. Here, we provide an overview of our results, focusing on

Multiple electron generation in a sea of electronic states

Science.gov (United States)

Witzel, Wayne; Shabaev, Andrew; Efros, Alexander; Hellberg, Carl; Verne, Jacobs

2009-03-01

In traditional bulk semiconductor photovoltaics (PVs), each photon may excite a single electron-hole, wasting excess energy beyond the band-gap as heat. In nanocrystals, multiple excitons can be generated from a single photon, enhancing the PV current. Multiple electron generation (MEG) may result from Coulombic interactions of the confined electrons. Previous investigations have been based on incomplete or over-simplified electronic-state representations. We present results of quantum simulations that include hundreds of thousands of configuration states and show how the complex dynamics, even in a closed electronic system, yields a saturated MEG effect on a femtosecond timescale. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Understanding the Influence of oligomeric resins on traction and rolling resistance of silica tire treads

NARCIS (Netherlands)

Vleugels, N.; Pille-Wolf, W.; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

2015-01-01

This study concerns the silica reinforcement of styrene–butadiene rubber compounds for passenger car tire treads, with the objective of gaining greater insight into the beneficial effects of oligomeric resins. The major tire performance factors predicted are rolling resistance and (wet) skid

Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl Substituted Polyhedral Oligomeric Silsesquioxanes (Postprint)

National Research Council Canada - National Science Library

Drazowski, Daniel B; Lee, Andre; Haddad, Timothy S

2007-01-01

Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different styrene content were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules...

Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl Substituted Polyhedral Oligomeric Silsesquioxanes (preprint)

National Research Council Canada - National Science Library

Drazkowski, Daniel B; Lee, Andre; Haddad, Timothy S

2006-01-01

Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different styrene content were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules...

State Politics and Education: An Examination of Selected Multiple-State Case Studies.

Science.gov (United States)

Burlingame, Martin; Geske, Terry G.

1979-01-01

Reviews the multiple-state case study literature, highlights some findings, discusses several methodological issues, and concludes with suggestions for possible research agendas. Urges students and researchers to be more actively critical of the assumptions and findings of these studies. (Author/IRT)

The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

Science.gov (United States)

Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

2012-08-03

N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

Catalytic Oligomerization of Terminal Alkynes by Lanthanide Carbyls (η5-C5Me5)2LnCH(SiMe3)2 (Ln = Y, La, Ce)

NARCIS (Netherlands)

Heeres, H.J.; Teuben, J.H.

1991-01-01

Lanthanide and group 3 carbyls Cp*2LnCH(SiMe3)2 (1, Ln = Y; 2, Ln = La; 3, Ln = Ce) are active catalyst precursors for the oligomerization of terminal alkynes HC≡CR (R = alkyl, aryl, SiMe3). The regioselectivity and the extent of oligomerization depend strongly on the lanthanide applied as well as

Ultrafast preparation of a polyhedral oligomeric silsesquioxane-based ionic liquid hybrid monolith via photoinitiated polymerization, and its application to capillary electrochromatography of aromatic compounds.

Science.gov (United States)

Zhang, Bingyu; Lei, Xiaoyun; Deng, Lijun; Li, Minsheng; Yao, Sicong; Wu, Xiaoping

2018-06-06

An ionic liquid hybrid monolithic capillary column was prepared within 7 min via photoinitiated free-radical polymerization of an ionic liquid monomer (1-butyl-3-vinylimidazolium-bis[(trifluoromethyl)sulfonyl]imide); VBIMNTF 2 ) and a methacryl substituted polyhedral oligomeric silsesquioxane (POSS-MA) acting as a cross-linker. The effects of composition of prepolymerization solution and initiation time on the porous structure and electroosmotic flow (EOF) of monolithic column were investigated. The hybrid monolith was characterized by scanning electron microscopy and FTIR. Owing to the introduction of a rigid nanosized POSS silica core and ionic liquids with multiple interaction sites, the monolithic column has a well-defined 3D skeleton morphology, good mechanical stability, and a stable anodic electroosmotic flow. The hybrid monolithic stationary phase was applied to the capillary electrochromatographic separation of various alkylbenzenes, phenols, anilines and polycyclic aromatic hydrocarbons (PAHs). The column efficiency is highest (98,000 plates/m) in case of alkylbenzenes. Mixed-mode retention mechanisms including hydrophobic interactions, π-π stacking, electrostatic interaction and electrophoretic mobility can be observed. This indicates the potential of this material in terms of efficient separation of analytes of different structural type. Graphical Abstract Preparation of a mixed-mode ionic liquid hybrid monolithic column via photoinitiated polymerization of methacryl substituted polyhedral oligomeric silsesquioxane (POSS-MA) and 1-butyl-3-vinylimidazolium-bis[(trifluoromethyl)sulfonyl]imide (VBIMNTF 2 ) ionic liquid for use in capillary electrochromatography.

N-way FRET microscopy of multiple protein-protein interactions in live cells.

Directory of Open Access Journals (Sweden)

Adam D Hoppe

Full Text Available Fluorescence Resonance Energy Transfer (FRET microscopy has emerged as a powerful tool to visualize nanoscale protein-protein interactions while capturing their microscale organization and millisecond dynamics. Recently, FRET microscopy was extended to imaging of multiple donor-acceptor pairs, thereby enabling visualization of multiple biochemical events within a single living cell. These methods require numerous equations that must be defined on a case-by-case basis. Here, we present a universal multispectral microscopy method (N-Way FRET to enable quantitative imaging for any number of interacting and non-interacting FRET pairs. This approach redefines linear unmixing to incorporate the excitation and emission couplings created by FRET, which cannot be accounted for in conventional linear unmixing. Experiments on a three-fluorophore system using blue, yellow and red fluorescent proteins validate the method in living cells. In addition, we propose a simple linear algebra scheme for error propagation from input data to estimate the uncertainty in the computed FRET images. We demonstrate the strength of this approach by monitoring the oligomerization of three FP-tagged HIV Gag proteins whose tight association in the viral capsid is readily observed. Replacement of one FP-Gag molecule with a lipid raft-targeted FP allowed direct observation of Gag oligomerization with no association between FP-Gag and raft-targeted FP. The N-Way FRET method provides a new toolbox for capturing multiple molecular processes with high spatial and temporal resolution in living cells.

Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

Directory of Open Access Journals (Sweden)

Diego M Presman

2014-03-01

Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

Energy Technology Data Exchange (ETDEWEB)

Chang, Chung-ke [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Wu, Tzong-Huah [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Institute of Biochemistry, Academia Sinica, Taipei 115, Taiwan (China); Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan (China); Wu, Chu-Ya [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Graduate Institute of Engineering, National Taiwan University of Science and Technology, Taipei 106, Taiwan (China); Chiang, Ming-hui; Toh, Elsie Khai-Woon [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Hsu, Yin-Chih; Lin, Ku-Feng [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Liao, Yu-heng [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Huang, Tai-huang, E-mail: bmthh@gate.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Department of Physics, National Taiwan Normal University, Taipei 106, Taiwan (China); Huang, Joseph Jen-Tse, E-mail: jthuang@chem.sinica.edu.tw [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)

2012-08-24

Highlights: Black-Right-Pointing-Pointer The N-terminus of TDP-43 contains an independently folded structural domain (NTD). Black-Right-Pointing-Pointer The structural domains of TDP-43 are arranged in a beads-on-a-string fashion. Black-Right-Pointing-Pointer The NTD promotes TDP-43 oligomerization in a concentration-dependent manner. Black-Right-Pointing-Pointer The NTD may assist nucleic acid-binding activity of TDP-43. -- Abstract: TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43.

Angle-resolved photoemission extended fine structure: Multiple layers of emitters and multiple initial states

International Nuclear Information System (INIS)

Huff, W.R.A.; Kellar, S.A.; Moler, E.J.; California Univ., Berkeley, CA; Chen, Y.; Wu, H.; Shirley, D.A.; Hussain, Z.

1995-01-01

Recently, angle-resolved photoemission extended fine structure (ARPEFS) has been applied to experimental systems involving multiple layers of emitters and non-s core-level photoemission in an effort to broaden the utility of the technique. Most of the previous systems have been comprised of atomic or molecular overlayers adsorbed onto a single-crystal, metal surface and the photoemission data were taken from an s atomic core-level in the overlayer. For such a system, the acquired ARPEFS data is dominated by the p o final state wave backscattering from the substrate atoms and is well understood. In this study, we investigate ARPEFS as a surface-region structure determination technique when applied to experimental systems comprised of multiple layers of photoemitters and arbitrary initial state core-level photoemission. Understanding the data acquired from multiple layers of photoemitters is useful for studying multilayer interfaces, ''buried'' surfaces, and clean crystals in ultra- high vacuum. The ability to apply ARPEFS to arbitrary initial state core-level photoemission obviously opens up many systems to analysis. Efforts have been ongoing to understand such data in depth. We present clean Cu(111) 3s, 3p, and 3d core-level, normal photoemission data taken on a high resolution soft x-ray beamline 9.3.2 at the Advanced Light Source in Berkeley, California and clean Ni(111) 3p normal photoemission data taken at the National Synchrotron Light Source in Upton, New York, USA

Mechanism of the electrochemical oligomerization of thionaphteneindole: a spectroscopic study

Science.gov (United States)

Poggi, Gabriella; Casalbore Miceli, Giuseppe; Beggiato, Giancarlo; Emmi, Salvatore S.

1997-10-01

The UV, visible and NIR spectra recorded during electrolysis of TNI in CH 2Cl 2 have been studied as a function of electrolysis time and of the quantity of charge exchanged. Among the oligomeric species that might be responsible for the behaviour observed, particular attention has been devoted to dimers of TNI characterized by different charges, presence of unpaired electrons, and deprotonation of the amino hydrogens. A sample of these species has been described theoretically by means of the PM3 semiempirical hamiltonian and their spectra have been computed giving results in reasonable agreement with the observed transitions.

78 FR 65561 - D-Glucopyranose, oligomeric, decyl octyl glycosides; Exemption from the Requirement of a Tolerance

Science.gov (United States)

2013-11-01

... metabolize D-glucopyranose, oligomeric, C 10 -C 16 -alkyl glycosides to water-soluble substances... polyoxyethylene polymers and fatty acids; carriers such as clay and diatomaceous earth; thickeners such as... exposure through drinking water and in residential settings, but does not include occupational exposure...

Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts.

Science.gov (United States)

Hollands, Wendy J; Voorspoels, Stefan; Jacobs, Griet; Aaby, Kjersti; Meisland, Ane; Garcia-Villalba, Rocio; Tomas-Barberan, Francisco; Piskula, Mariusz K; Mawson, Deborah; Vovk, Irena; Needs, Paul W; Kroon, Paul A

2017-04-28

There is a lack of data for individual oligomeric procyanidins in apples and apple extracts. Our aim was to develop, validate and evaluate an analytical method for the separation, identification and quantification of monomeric and oligomeric flavanols in apple extracts. To achieve this, we prepared two types of flavanol extracts from freeze-dried apples; one was an epicatechin-rich extract containing ∼30% (w/w) monomeric (-)-epicatechin which also contained oligomeric procyanidins (Extract A), the second was an oligomeric procyanidin-rich extract depleted of epicatechin (Extract B). The parameters considered for method optimisation were HPLC columns and conditions, sample heating, mass of extract and dilution volumes. The performance characteristics considered for method validation included standard linearity, method sensitivity, precision and trueness. Eight laboratories participated in the method evaluation. Chromatographic separation of the analytes was best achieved utilizing a Hilic column with a binary mobile phase consisting of acidic acetonitrile and acidic aqueous methanol. The final method showed linearity for epicatechin in the range 5-100μg/mL with a correlation co-efficient >0.999. Intra-day and inter-day precision of the analytes ranged from 2 to 6% and 2 to 13% respectively. Up to dp3, trueness of the method was >95% but decreased with increasing dp. Within laboratory precision showed RSD values <5 and 10% for monomers and oligomers, respectively. Between laboratory precision was 4 and 15% (Extract A) and 7 and 30% (Extract B) for monomers and oligomers, respectively. An analytical method for the separation, identification and quantification of procyanidins in an apple extract was developed, validated and assessed. The results of the inter-laboratory evaluation indicate that the method is reliable and reproducible. Copyright © 2017. Published by Elsevier B.V.

Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe-S cluster assembly centers.

Science.gov (United States)

Galeano, B K; Ranatunga, W; Gakh, O; Smith, D Y; Thompson, J R; Isaya, G

2017-06-21

Early studies of the bacterial Fe-S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe-S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1. Here, in the absence of Yfh1, Isu1 was found to exist in two forms, one mostly monomeric with limited tendency to dimerize, and one with a strong propensity to oligomerize. Whereas the monomeric form is stabilized by zinc, the loss of zinc promotes formation of dimer and higher order oligomers. However, upon binding to oligomeric Yfh1, both forms take on a similar symmetrical trimeric configuration that places the Fe-S cluster coordinating residues of Isu1 in close proximity of iron-binding residues of Yfh1. This configuration is suitable for docking of Nfs1 in a manner that provides a structural context for coordinate iron and sulfur donation to the scaffold. Moreover, distinct structural features suggest that in physiological conditions the zinc-regulated abundance of monomeric vs. oligomeric Isu1 yields [Yfh1]·[Isu1] complexes with different Isu1 configurations that afford unique functional properties for Fe-S cluster assembly and delivery.

Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor

DEFF Research Database (Denmark)

Presman, Diego M; Ogara, M Florencia; Stortz, Martín

2014-01-01

Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation wi...

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to oligomeric procyanidins (OPCs) from grape (Vitis vinifera L.) seeds and improvement of visual adaptation to the dark (ID 680) pursuant to Article 13(1) of Regulation

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to oligomeric procyanidins (OPCs) from grape (Vitis vinifera L.) seeds and improvement of visual adaptation to the dark. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA...... has received from Member States or directly from stakeholders. The food constituent that is the subject of the health claim is oligomeric procyanidins (OPCs) from grape (Vitis vinifera L.) seeds. The Panel considers that OPCs from grape (Vitis vinifera L.) seeds are sufficiently characterised....... The claimed effect is “ocular system: OPCs play an important role in the structure and physiological functions of cornea, OPCs protect the cornea and improve visual adaptation to low luminances”. The target population is assumed to be the general population. In the context of the proposed wordings...

Oligomeric adiponectin forms and their complexes in the blood of healthy donors and patients with type 2 diabetes mellitus.

Science.gov (United States)

Kogan, Alexander E; Filatov, Vladimir L; Kolosova, Olga V; Katrukha, Ivan A; Mironova, Ekaterina V; Zhuravleva, Natalya S; Nagibin, Oleg A; Kara, Andrei N; Bereznikova, Anastasiya V; Katrukha, Alexey G

2013-01-01

Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric forms, namely low-, medium-, and high-molecular-weight forms. Adn may serve as a risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were (1) to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric forms, (2) to design immunoassays suitable for measuring the Adn forms present in human blood, and (3) to investigate the changes in Adn forms that occur in patients with T2DM. Gel filtration, fluoroimmunoassays, and Western blotting were utilized as major techniques in this study. MAbs recognizing various oligomeric forms of Adn were obtained. Complexes between Adn and complement component C1q and between the low molecular weight form of Adn and albumin were described in human blood. A decrease in the total Adn and Adn-albumin complex levels in the blood of patients with T2DM and no difference in the levels of the Adn-C1q complex in comparison with healthy volunteers were demonstrated. An Adn94-Adn63 fluoroimmunoassay was selected as the technique that most accurately measured the mass ratio of Adn oligomers in blood samples, and an Adn214-Adn27 assay that measured the low-molecular-weight form of Adn only.

Feasibility of a multiple-choice mini mental state examination for chronically critically ill patients.

Science.gov (United States)

Miguélez, Marta; Merlani, Paolo; Gigon, Fabienne; Verdon, Mélanie; Annoni, Jean-Marie; Ricou, Bara

2014-08-01

Following treatment in an ICU, up to 70% of chronically critically ill patients present neurocognitive impairment that can have negative effects on their quality of life, daily activities, and return to work. The Mini Mental State Examination is a simple, widely used tool for neurocognitive assessment. Although of interest when evaluating ICU patients, the current version is restricted to patients who are able to speak. This study aimed to evaluate the feasibility of a visual, multiple-choice Mini Mental State Examination for ICU patients who are unable to speak. The multiple-choice Mini Mental State Examination and the standard Mini Mental State Examination were compared across three different speaking populations. The interrater and intrarater reliabilities of the multiple-choice Mini Mental State Examination were tested on both intubated and tracheostomized ICU patients. Mixed 36-bed ICU and neuropsychology department in a university hospital. Twenty-six healthy volunteers, 20 neurological patients, 46 ICU patients able to speak, and 30 intubated or tracheostomized ICU patients. None. Multiple-choice Mini Mental State Examination results correlated satisfactorily with standard Mini Mental State Examination results in all three speaking groups: healthy volunteers: intraclass correlation coefficient = 0.43 (95% CI, -0.18 to 0.62); neurology patients: 0.90 (95% CI, 0.82-0.95); and ICU patients able to speak: 0.86 (95% CI, 0.70-0.92). The interrater and intrarater reliabilities were good (0.95 [0.87-0.98] and 0.94 [0.31-0.99], respectively). In all populations, a Bland-Altman analysis showed systematically higher scores using the multiple-choice Mini Mental State Examination. Administration of the multiple-choice Mini Mental State Examination to ICU patients was straightforward and produced exploitable results comparable to those of the standard Mini Mental State Examination. It should be of interest for the assessment and monitoring of the neurocognitive

State estimation of chemical engineering systems tending to multiple solutions

Directory of Open Access Journals (Sweden)

N. P. G. Salau

2014-09-01

Full Text Available A well-evaluated state covariance matrix avoids error propagation due to divergence issues and, thereby, it is crucial for a successful state estimator design. In this paper we investigate the performance of the state covariance matrices used in three unconstrained Extended Kalman Filter (EKF formulations and one constrained EKF formulation (CEKF. As benchmark case studies we have chosen: a a batch chemical reactor with reversible reactions whose system model and measurement are such that multiple states satisfy the equilibrium condition and b a CSTR with exothermic irreversible reactions and cooling jacket energy balance whose nonlinear behavior includes multiple steady-states and limit cycles. The results have shown that CEKF is in general the best choice of EKF formulations (even if they are constrained with an ad hoc clipping strategy which avoids undesired states for such case studies. Contrary to a clipped EKF formulation, CEKF incorporates constraints into an optimization problem, which minimizes the noise in a least square sense preventing a bad noise distribution. It is also shown that, although the Moving Horizon Estimation (MHE provides greater robustness to a poor guess of the initial state, converging in less steps to the actual states, it is not justified for our examples due to the high additional computational effort.

In situ oligomerization of 2-(thiophen-3-yl)acetate intercalated into Zn{sub 2}Al layered double hydroxide

Energy Technology Data Exchange (ETDEWEB)

Tronto, Jairo, E-mail: jairotronto@ufv.br [Universidade Federal de Viçosa, Instituto de Ciências Exatas e Tecnológicas, Campus de Rio Parsanaíba, Rodovia BR 354 km 310, Cx. Postal 22, CEP, 38.810-000 Rio Paranaíba, MG (Brazil); Pinto, Frederico G.; Costa, Liovando M. da [Universidade Federal de Viçosa, Instituto de Ciências Exatas e Tecnológicas, Campus de Rio Parsanaíba, Rodovia BR 354 km 310, Cx. Postal 22, CEP, 38.810-000 Rio Paranaíba, MG (Brazil); Leroux, Fabrice; Dubois, Marc [Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand (France); CNRS, UMR 6296, ICCF, BP 80026, F-6317 Clermont-Ferrand (France); Valim, João B. [Universidade de São Paulo, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Departamento de Química, Av. dos Bandeirantes 3900, CEP 14.040-901, Ribeirão Preto, SP (Brazil)

2015-01-15

A layered double hydroxide (LDH) with cation composition Zn{sub 2}Al was intercalated with 2-(thiophen-3-yl)acetate (3-TA) monomers. To achieve in situ polymerization and/or oligomerization of the intercalated monomers, soft thermal treatments were carried out, and subsequent hybrid LDH materials were analyzed by means of several characterization techniques using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), {sup 13}C CP–MAS nuclear magnetic resonance (NMR), electron spin resonance (EPR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), inductively coupled plasma optical emission spectroscopy (ICP–OES), and elemental analysis. PXRD analysis suggested that the intercalated monomers formed a bilayer. Thermal treatment of the hybrid LDH assembly above 120 °C provokes partially the breakdown of the layered structure, generating the phase zincite. EPR results indicated that vicinal monomers (oligomerization) were bound to each other after hydrothermal or thermal treatment, leading to a polaron response characteristic of electron conductivity localized on a restricted number of thiophene-based monomer segments. Localized unpaired electrons exist in the material and interact with the {sup 27}Al nuclei of the LDH layers by superhyperfine coupling. These unpaired electrons also interact with the surface of ZnO (O{sup 2−} vacancies), formed during the thermal treatments. - Graphical abstract: We synthesized a layered double hydroxide (LDH) with cation composition Zn{sub 2}Al, intercalated with 2-(thiophen-3-yl)acetate (3-TA) monomers, by coprecipitation at constant pH. We thermally treated the material, to achieve in situ polymerization and/or oligomerization of the intercalated monomers. - Highlights: • A Zn{sub 2}Al–LDH was intercalated with 2-(thiophen-3-yl)acetate monomers. • To achieve in situ oligomerization of the monomers, thermal treatments were made. �

Quantum Query Complexity for Searching Multiple Marked States from an Unsorted Database

International Nuclear Information System (INIS)

Shang Bin

2007-01-01

An important and usual sort of search problems is to find all marked states from an unsorted database with a large number of states. Grover's original quantum search algorithm is for finding single marked state with uncertainty, and it has been generalized to the case of multiple marked states, as well as been modified to find single marked state with certainty. However, the query complexity for finding all multiple marked states has not been addressed. We use a generalized Long's algorithm with high precision to solve such a problem. We calculate the approximate query complexity, which increases with the number of marked states and with the precision that we demand. In the end we introduce an algorithm for the problem on a 'duality computer' and show its advantage over other algorithms.

Deterministic integer multiple firing depending on initial state in Wang model

Energy Technology Data Exchange (ETDEWEB)

Xie Yong [Institute of Nonlinear Dynamics, MSSV, Department of Engineering Mechanics, Xi' an Jiaotong University, Xi' an 710049 (China)]. E-mail: yxie@mail.xjtu.edu.cn; Xu Jianxue [Institute of Nonlinear Dynamics, MSSV, Department of Engineering Mechanics, Xi' an Jiaotong University, Xi' an 710049 (China); Jiang Jun [Institute of Nonlinear Dynamics, MSSV, Department of Engineering Mechanics, Xi' an Jiaotong University, Xi' an 710049 (China)

2006-12-15

We investigate numerically dynamical behaviour of the Wang model, which describes the rhythmic activities of thalamic relay neurons. The model neuron exhibits Type I excitability from a global view, but Type II excitability from a local view. There exists a narrow range of bistability, in which a subthreshold oscillation and a suprathreshold firing behaviour coexist. A special firing pattern, integer multiple firing can be found in the certain part of the bistable range. The characteristic feature of such firing pattern is that the histogram of interspike intervals has a multipeaked structure, and the peaks are located at about integer multiples of a basic interspike interval. Since the Wang model is noise-free, the integer multiple firing is a deterministic firing pattern. The existence of bistability leads to the deterministic integer multiple firing depending on the initial state of the model neuron, i.e., the initial values of the state variables.

Deterministic integer multiple firing depending on initial state in Wang model

International Nuclear Information System (INIS)

Xie Yong; Xu Jianxue; Jiang Jun

2006-01-01

We investigate numerically dynamical behaviour of the Wang model, which describes the rhythmic activities of thalamic relay neurons. The model neuron exhibits Type I excitability from a global view, but Type II excitability from a local view. There exists a narrow range of bistability, in which a subthreshold oscillation and a suprathreshold firing behaviour coexist. A special firing pattern, integer multiple firing can be found in the certain part of the bistable range. The characteristic feature of such firing pattern is that the histogram of interspike intervals has a multipeaked structure, and the peaks are located at about integer multiples of a basic interspike interval. Since the Wang model is noise-free, the integer multiple firing is a deterministic firing pattern. The existence of bistability leads to the deterministic integer multiple firing depending on the initial state of the model neuron, i.e., the initial values of the state variables

Development of Biodegradable Poly(citrate)-Polyhedral Oligomeric Silsesquioxanes Hybrid Elastomers with High Mechanical Properties and Osteogenic Differentiation Activity.

Science.gov (United States)

Du, Yuzhang; Yu, Meng; Chen, Xiaofeng; Ma, Peter X; Lei, Bo

2016-02-10

Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.

Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

Science.gov (United States)

Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

2016-02-23

We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

Synthesis and characterization of polyhedral oligomeric titanized silsesquioxane: A new biocompatible cage like molecule for biomedical application

Energy Technology Data Exchange (ETDEWEB)

Yahyaei, Hossein [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Mohseni, Mohsen, E-mail: mmohseni@aut.ac.ir [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Ghanbari, Hossein [Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Messori, Massimo [Dipartimento di Ingegneria ‘Enzo Ferrari’, Università di Modena e Reggio Emilia, Modena (Italy)

2016-04-01

Organic–inorganic hybrid materials have shown improved properties to be used as biocompatible coating in biomedical applications. Polyhedral oligomeric silsesquioxane (POSS) containing coatings are among hybrid materials showing promising properties for these applications. In this work an open cage POSS has been reacted with a titanium alkoxide to end cap the POSS molecule with titanium atom to obtain a so called polyhedral oligomeric metalized silsesquioxane (POMS). The synthesized POMS was characterized by FTIR, RAMAN and UV–visible spectroscopy as well as {sup 29}Si NMR and matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) techniques. Appearance of peaks at 920 cm{sup −1} in FTIR and 491 cm{sup −1} and 1083 cm{sup −1} in Raman spectra confirmed Si–O–Ti linkage formation. It was also demonstrated that POMS was in a monomeric form. To evaluate the biocompatibility of hybrids films, pristine POSS and synthesized POMS were used in synthesis of a polycarbonate urethane polymer. Results revealed that POMS containing hybrid, not only had notable thermal and mechanical stability compared to POSS containing one, as demonstrated by DSC and DMTA analysis, they also showed controlled surface properties in such a manner that hydrophobicity and biocompatibility were both reachable to give rise to improved cell viability in presence of human umbilical vein endothelial cells (HUVEC) and MRC-5 cells. - Highlight: • Polyhedral Oligomeric Metalized Silsesquioxane (POMS) based on titanium was synthesized. • POMS can improve mechanical properties of polyurethane. • POMS increases hydrophobicity of polyurethane. • POMS is a unique nanocage to enhance biocompatibility of polyurethane.

Molecular cloning and functional characterization of duck nucleotide-binding oligomerization domain 1 (NOD1).

Science.gov (United States)

Li, Huilin; Jin, Hui; Li, Yaqian; Liu, Dejian; Foda, Mohamed Frahat; Jiang, Yunbo; Luo, Rui

2017-09-01

Nucleotide-binding oligomerization domain 1 (NOD1) is an imperative cytoplasmic pattern recognition receptor (PRR) and considered as a key member of the NOD-like receptor (NLR) family which plays a critical role in innate immunity through sensing microbial components derived from bacterial peptidoglycan. In the current study, the full-length of duck NOD1 (duNOD1) cDNA from duck embryo fibroblasts (DEFs) was cloned. Multiple sequence alignment and phylogenetic analysis demonstrated that duNOD1 exhibited a strong evolutionary relationship with chicken and rock pigeon NOD1. Tissue-specific expression analysis showed that duNOD1 was widely distributed in various organs, with the highest expression observed in the liver. Furthermore, duNOD1 overexpression induced NF-κB activation in DEFs and the CARD domain is crucial for duNOD1-mediated NF-κB activation. In addition, silencing the duNOD1 decreased the activity of NF-κB in DEFs stimulated by iE-DAP. Overexpression of duNOD1 significantly increased the expression of TNF-α, IL-6, and RANTES in DEFs. These findings highlight the crucial role of duNOD1 as an intracellular sensor in duck innate immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Single Site Silica Supported Tetramethyl Niobium by the SOMC Strategy: Synthesis, Characterization and Structure-Activity Relationship in Ethylene Oligomerization Reaction

KAUST Repository

Hamieh, Ali Imad Ali

2017-06-06

Silica supported Tetramethyl niobium complex [(≡SiO)NbMe4] 2 has been isolated by surface alkylation of [(≡SiO-)NbCl3Me] 1 with dimethyl zinc in pentane. 1 can be easily synthesized by grafting of NbCl3Me2 on to the surface of partially dehydroxylated silica by the SOMC strategy. Precise structural analysis was carried out by the FTIR, advance solid state NMR, elemental analysis and mass balance techniques (gas quantification after treating 2 with degassed water) . Complex 1 was found to be active in the ethylene oligomerization to produce up to C30, whereas to our surprise complex 2 selectively dimerizes ethylene into 1-butene in the absence of a co-catalyst at the same conversion levels.

Single Site Silica Supported Tetramethyl Niobium by the SOMC Strategy: Synthesis, Characterization and Structure-Activity Relationship in Ethylene Oligomerization Reaction

KAUST Repository

Hamieh, Ali Imad Ali; Dey, Raju; Nekoueishahraki, Bijan; Samantaray, Manoja; Chen, Yin; Abou-Hamad, Edy; Basset, Jean-Marie

2017-01-01

Silica supported Tetramethyl niobium complex [(≡SiO)NbMe4] 2 has been isolated by surface alkylation of [(≡SiO-)NbCl3Me] 1 with dimethyl zinc in pentane. 1 can be easily synthesized by grafting of NbCl3Me2 on to the surface of partially dehydroxylated silica by the SOMC strategy. Precise structural analysis was carried out by the FTIR, advance solid state NMR, elemental analysis and mass balance techniques (gas quantification after treating 2 with degassed water) . Complex 1 was found to be active in the ethylene oligomerization to produce up to C30, whereas to our surprise complex 2 selectively dimerizes ethylene into 1-butene in the absence of a co-catalyst at the same conversion levels.

The role of Vif oligomerization and RNA chaperone activity in HIV-1 replication.

Science.gov (United States)

Batisse, Julien; Guerrero, Santiago; Bernacchi, Serena; Sleiman, Dona; Gabus, Caroline; Darlix, Jean-Luc; Marquet, Roland; Tisné, Carine; Paillart, Jean-Christophe

2012-11-01

The viral infectivity factor (Vif) is essential for the productive infection and dissemination of HIV-1 in non-permissive cells that involve most natural HIV-1 target cells. Vif counteracts the packaging of two cellular cytidine deaminases named APOBEC3G (A3G) and A3F by diverse mechanisms including the recruitment of an E3 ubiquitin ligase complex and the proteasomal degradation of A3G/A3F, the inhibition of A3G mRNA translation or by a direct competition mechanism. In addition, Vif appears to be an active partner of the late steps of viral replication by participating in virus assembly and Gag processing, thus regulating the final stage of virion formation notably genomic RNA dimerization and by inhibiting the initiation of reverse transcription. Vif is a small pleiotropic protein with multiple domains, and recent studies highlighted the importance of Vif conformation and flexibility in counteracting A3G and in binding RNA. In this review, we will focus on the oligomerization and RNA chaperone properties of Vif and show that the intrinsic disordered nature of some Vif domains could play an important role in virus assembly and replication. Experimental evidence demonstrating the RNA chaperone activity of Vif will be presented. Copyright © 2012 Elsevier B.V. All rights reserved.

Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis

DEFF Research Database (Denmark)

Happonen, Kaisa E; Saxne, Tore; Aspberg, Anders

2010-01-01

Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthr...

Interplay of histidine residues of the Alzheimer’s disease Aβ peptide governs its Zn-induced oligomerization

Science.gov (United States)

Istrate, Andrey N.; Kozin, Sergey A.; Zhokhov, Sergey S.; Mantsyzov, Alexey B.; Kechko, Olga I.; Pastore, Annalisa; Makarov, Alexander A.; Polshakov, Vladimir I.

2016-02-01

Conformational changes of Aβ peptide result in its transformation from native monomeric state to the toxic soluble dimers, oligomers and insoluble aggregates that are hallmarks of Alzheimer’s disease (AD). Interactions of zinc ions with Aβ are mediated by the N-terminal Aβ1-16 domain and appear to play a key role in AD progression. There is a range of results indicating that these interactions trigger the Aβ plaque formation. We have determined structure and functional characteristics of the metal binding domains derived from several Aβ variants and found that their zinc-induced oligomerization is governed by conformational changes in the minimal zinc binding site 6HDSGYEVHH14. The residue H6 and segment 11EVHH14, which are part of this site are crucial for formation of the two zinc-mediated interaction interfaces in Aβ. These structural determinants can be considered as promising targets for rational design of the AD-modifying drugs aimed at blocking pathological Aβ aggregation.

Oligomerization of glycine and alanine catalyzed by iron oxides: implications for prebiotic chemistry.

Science.gov (United States)

Shanker, Uma; Bhushan, Brij; Bhattacharjee, G; Kamaluddin

2012-02-01

Iron oxide minerals are probable constituents of the sediments present in geothermal regions of the primitive earth. They might have adsorbed different organic monomers (amino acids, nucleotides etc.) and catalyzed polymerization processes leading to the formation of the first living cell. In the present work we tested the catalytic activity of three forms of iron oxides (Goethite, Akaganeite and Hematite) in the intermolecular condensation of each of the amino acids glycine and L-alanine. The effect of zinc oxide and titanium dioxide on the oligomerization has also been studied. Oligomerization studies were performed for 35 days at three different temperatures 50, 90 and 120°C without applying drying/wetting cycling. The products formed were characterized by HPLC and ESI-MS techniques. All three forms of iron oxides catalyzed peptide bond formation (23.2% of gly2 and 10.65% of ala2). The reaction was monitored every 7 days. Formation of peptides was observed to start after 7 days at 50°C. Maximum yield of peptides was found after 35 days at 90°C. Reaction at 120°C favors formation of diketopiperazine derivatives. It is also important to note that after 35 days of reaction, goethite produced dimer and trimer with the highest yield among the oxides tested. We suggest that the activity of goethite could probably be due to its high surface area and surface acidity.

Resting‐state connectivity of pre‐motor cortex reflects disability in multiple sclerosis

DEFF Research Database (Denmark)

Dogonowski, Anne-Marie; Siebner, Hartwig Roman; Soelberg Sørensen, P.

2013-01-01

Objective To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). Materials and methods A total of 27 patients with relapsing–remitting MS (RR-MS) and 15 patients with secondary...... progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8...... between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. Results The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity...

Styrene oligomerization as a molecular probe reaction for zeolite acidity: a UV-Vis spectroscopy and DFT study

NARCIS (Netherlands)

Buurmans, I.L.C.; Pidko, E.A.; Groot, de J.M.; Stavitski, E.; Santen, van R.A.; Weckhuysen, B.M.

2010-01-01

A series of H-ZSM-5 crystallites with different framework Si/Al ratios was studied by analyzing the kinetics and reaction mechanism of the oligomerization of 4-fluorostyrene as molecular probe reaction for Brønsted acidity. The formation of carbocationic species was followed by UV-Vis spectroscopy.

Size dependent deactivation of the excited state of DHICA

DEFF Research Database (Denmark)

Gauden, Magdalena; Pezzella, Alessandro; Panzella, Lucia

2008-01-01

Melanin is a natural pigment mainly responsible for the protection of skin and eyes from UV damage. 5,6- dihydroxyindole- 2 carboxylic acid (DHICA) is a key melanin building block. We have investigated the excited state dynamics of DHICA as well as its derivatives and oligomeric units using...

Preparation of polyhedral oligomeric silsesquioxane based imprinted monolith.

Science.gov (United States)

Li, Fang; Chen, Xiu-Xiu; Huang, Yan-Ping; Liu, Zhao-Sheng

2015-12-18

Polyhedral oligomeric silsesquioxane (POSS) was successfully applied, for the first time, to prepare imprinted monolithic column with high porosity and good permeability. The imprinted monolithic column was synthesized with a mixture of PSS-(1-Propylmethacrylate)-heptaisobutyl substituted (MA 0702), naproxon (template), 4-vinylpyridine, and ethylene glycol dimethacrylate, in ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4). The influence of synthesis parameters on the retention factor and imprinting effect, including the amount of MA 0702, the ratio of template to monomer, and the ratio of monomer to crosslinker, was investigated. The greatest imprinting factor on the imprinted monolithic column prepared with MA 0702 was 22, about 10 times higher than that prepared in absence of POSS. The comparisons between MIP monoliths synthesized with POSS and without POSS were made in terms of permeability, column efficiency, surface morphology and pore size distribution. In addition, thermodynamic and Van Deemter analysis were used to evaluate the POSS-based MIP monolith. Copyright © 2015 Elsevier B.V. All rights reserved.

Wall locking and multiple nonlinear states of magnetic islands

International Nuclear Information System (INIS)

Persson, Mikael; Australian National Univ., Canberra, ACT

1994-01-01

The nonlinear evolution of magnetic islands is analysed in configurations with multiple resonant magnetic surfaces. The existence of multiple nonlinear steady states, is discussed. These are shown to be associated with states where the dynamics around the different rational surfaces are coupled or decoupled and in the presence of a wall of finite resistivity may correspond wall-locked or non-wall-locked magnetic islands. For the case of strong wall stabilization the locking is shown to consist of two different phases. During the first phase the locking of the plasma at the different rational surfaces occurs. Only when the outermost resonant magnetic surface has locked to the inner surfaces can the actual wall locking process take place. Consequently, wall locking, of a global mode, involving more than one rational surface, can be prevented by the decoupling of the resonant magnetic surfaces by plasma rotation. Possible implications on tokamak experiments are discussed. (author)

Relation between catalyst-assisted transformation and multiple-copy transformation for bipartite pure states

International Nuclear Information System (INIS)

Feng Yuan; Duan Runyao; Ying Mingsheng

2006-01-01

We show that in some cases, catalyst-assisted entanglement transformation cannot be implemented by multiple-copy transformation for pure states. This fact, together with the result we obtained in R. Y. Duan, Y. Feng, X. Li, and M. S. Ying, Phys. Rev. A 71, 042319 (2005), namely that the latter can be completely implemented by the former, indicates that catalyst-assisted transformation is strictly more powerful than multiple-copy transformation. For the purely probabilistic setting we find, however, these two kinds of transformations are geometrically equivalent in the sense that the sets of pure states that can be converted into a given pure state with maximal probabilities not less than a given value have the same closure, regardless of whether catalyst-assisted transformation or multiple-copy transformation is used

Synaptic transmission block by presynaptic injection of oligomeric amyloid beta

Science.gov (United States)

Moreno, Herman; Yu, Eunah; Pigino, Gustavo; Hernandez, Alejandro I.; Kim, Natalia; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

2009-01-01

Early Alzheimer's disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)Aβ42, but not oAβ40 or extracellular oAβ42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oAβ42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD. PMID:19304802

Glycerol-Induced Aggregation of the Oligomeric L-Asparaginase II from E. coli Monitored with ATR-FTIR

Directory of Open Access Journals (Sweden)

Koba Adeishvili

2001-06-01

Full Text Available Abstract: In this paper attenuated total reflectance Fourier transform infrared spectroscopy has been employed for the study of the structural composition of aggregates of the oligomeric L-asparaginase II from E.coli formed in the presence of glycerol after the induction of refolding of the protein. Apart from the perfect coincidence of the secondary structure composition of EcA2 as determined by FTIR and crystallography [1], it has also been shown that secondary structure of protein in asparaginase deposits is similar to that of the native conformation: 20.7% extended, 22.3% disordered, 31.4% helix and 25.6% turn/bend/β sheet. Certain structural similarities in the range of experimental error was observed for all three protein deposits presented in this paper, indicating a common structural basis for the composition of this types of aggregates. It is concluded that in the constitution of such precipitates, a partially folded (molten globule like state(s is involved, and its stabilisation is a key factor leading to the aggregation. The results presented in this paper might serve to be a good explanation and an excellent basis for the fundamental theory of protein (oligomers precipitation by osmotic substances.

Increasing atmospheric CO2 overrides the historical legacy of multiple stable biome states in Africa.

Science.gov (United States)

Moncrieff, Glenn R; Scheiter, Simon; Bond, William J; Higgins, Steven I

2014-02-01

The dominant vegetation over much of the global land surface is not predetermined by contemporary climate, but also influenced by past environmental conditions. This confounds attempts to predict current and future biome distributions, because even a perfect model would project multiple possible biomes without knowledge of the historical vegetation state. Here we compare the distribution of tree- and grass-dominated biomes across Africa simulated using a dynamic global vegetation model (DGVM). We explicitly evaluate where and under what conditions multiple stable biome states are possible for current and projected future climates. Our simulation results show that multiple stable biomes states are possible for vast areas of tropical and subtropical Africa under current conditions. Widespread loss of the potential for multiple stable biomes states is projected in the 21st Century, driven by increasing atmospheric CO2 . Many sites where currently both tree-dominated and grass-dominated biomes are possible become deterministically tree-dominated. Regions with multiple stable biome states are widespread and require consideration when attempting to predict future vegetation changes. Testing for behaviour characteristic of systems with multiple stable equilibria, such as hysteresis and dependence on historical conditions, and the resulting uncertainty in simulated vegetation, will lead to improved projections of global change impacts. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

N-terminal aliphatic residues dictate the structure, stability, assembly, and small molecule binding of the coiled-coil region of cartilage oligomeric matrix protein.

Science.gov (United States)

Gunasekar, Susheel K; Asnani, Mukta; Limbad, Chandani; Haghpanah, Jennifer S; Hom, Wendy; Barra, Hanna; Nanda, Soumya; Lu, Min; Montclare, Jin Kim

2009-09-15

The coiled-coil domain of cartilage oligomeric matrix protein (COMPcc) assembles into a homopentamer that naturally recognizes the small molecule 1,25-dihydroxyvitamin D(3) (vit D). To identify the residues critical for the structure, stability, oligomerization, and binding to vit D as well as two other small molecules, all-trans-retinol (ATR) and curcumin (CCM), here we perform an alanine scanning mutagenesis study. Ten residues lining the hydrophobic pocket of COMPcc were mutated into alanine; of the mutated residues, the N-terminal aliphatic residues L37, L44, V47, and L51 are responsible for maintaining the structure and function. Furthermore, two polar residues, T40 and Q54, within the N-terminal region when converted into alanine improve the alpha-helical structure, stability, and self-assembly behavior. Helical stability, oligomerization, and binding appear to be linked in a manner in which mutations that abolish helical structure and assembly bind poorly to vit D, ATR, and CCM. These results provide not only insight into COMPcc and its functional role but also useful guidelines for the design of stable, pentameric coiled-coils capable of selectively storing and delivering various small molecules.

Structure of the large terminase from a hyperthermophilic virus reveals a unique mechanism for oligomerization and ATP hydrolysis.

Science.gov (United States)

Xu, Rui-Gang; Jenkins, Huw T; Antson, Alfred A; Greive, Sandra J

2017-12-15

The crystal structure of the large terminase from the Geobacillus stearothermophilus bacteriophage D6E shows a unique relative orientation of the N-terminal adenosine triphosphatase (ATPase) and C-terminal nuclease domains. This monomeric 'initiation' state with the two domains 'locked' together is stabilized via a conserved C-terminal arm, which may interact with the portal protein during motor assembly, as predicted for several bacteriophages. Further work supports the formation of an active oligomeric state: (i) AUC data demonstrate the presence of oligomers; (ii) mutational analysis reveals a trans-arginine finger, R158, indispensable for ATP hydrolysis; (iii) the location of this arginine is conserved with the HerA/FtsK ATPase superfamily; (iv) a molecular docking model of the pentamer is compatible with the location of the identified arginine finger. However, this pentameric model is structurally incompatible with the monomeric 'initiation' state and is supported by the observed increase in kcat of ATP hydrolysis, from 7.8 ± 0.1 min-1 to 457.7 ± 9.2 min-1 upon removal of the C-terminal nuclease domain. Taken together, these structural, biophysical and biochemical data suggest a model where transition from the 'initiation' state into a catalytically competent pentameric state, is accompanied by substantial domain rearrangements, triggered by the removal of the C-terminal arm from the ATPase active site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Characterization and ageing study of poly(lactic acid) films plasticized with oligomeric lactic acid

OpenAIRE

Burgos, Nuria; Martino, Verónica P.; Jiménez, Alfonso

2013-01-01

Poly(lactic acid) (PLA) was melt-blended with a bio-based oligomeric lactic acid (OLA) plasticizer at different concentrations between 15 wt% and 25 wt% in order to enhance PLA ductility and to get a fully biodegradable material with potential application in films manufacturing. OLA was an efficient plasticizer for PLA, as it caused a significant decrease on glass transition temperature (Tg) while improving considerably ductile properties. Only one Tg value was observed in all cases and no ap...

Classification of Multiple Seizure-Like States in Three Different Rodent Models of Epileptogenesis.

Science.gov (United States)

Guirgis, Mirna; Serletis, Demitre; Zhang, Jane; Florez, Carlos; Dian, Joshua A; Carlen, Peter L; Bardakjian, Berj L

2014-01-01

Epilepsy is a dynamical disease and its effects are evident in over fifty million people worldwide. This study focused on objective classification of the multiple states involved in the brain's epileptiform activity. Four datasets from three different rodent hippocampal preparations were explored, wherein seizure-like-events (SLE) were induced by the perfusion of a low - Mg(2+) /high-K(+) solution or 4-Aminopyridine. Local field potentials were recorded from CA3 pyramidal neurons and interneurons and modeled as Markov processes. Specifically, hidden Markov models (HMM) were used to determine the nature of the states present. Properties of the Hilbert transform were used to construct the feature spaces for HMM training. By sequentially applying the HMM training algorithm, multiple states were identified both in episodes of SLE and nonSLE activity. Specifically, preSLE and postSLE states were differentiated and multiple inner SLE states were identified. This was accomplished using features extracted from the lower frequencies (1-4 Hz, 4-8 Hz) alongside those of both the low- (40-100 Hz) and high-gamma (100-200 Hz) of the recorded electrical activity. The learning paradigm of this HMM-based system eliminates the inherent bias associated with other learning algorithms that depend on predetermined state segmentation and renders it an appropriate candidate for SLE classification.

Advanced topics in control and estimation of state-multiplicative noisy systems

CERN Document Server

Gershon, Eli

2013-01-01

Advanced Topics in Control and Estimation of State-Multiplicative Noisy Systems begins with an introduction and extensive literature survey. The text proceeds to cover solutions of measurement-feedback control and state problems and the formulation of the Bounded Real Lemma for both continuous- and discrete-time systems. The continuous-time reduced-order and stochastic-tracking control problems for delayed systems are then treated. Ideas of nonlinear stability are introduced for infinite-horizon systems, again, in both the continuous- and discrete-time cases. The reader is introduced to six practical examples of noisy state-multiplicative control and filtering associated with various fields of control engineering. The book is rounded out by a three-part appendix containing stochastic tools necessary for a proper appreciation of the text: a basic introduction to nonlinear stochastic differential equations and aspects of switched systems and peak to peak  optimal control and filtering. Advanced Topics in Contr...

Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

Science.gov (United States)

Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

2009-07-01

The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

Computational multiple steady states for enzymatic esterification of ethanol and oleic acid in an isothermal CSTR.

Science.gov (United States)

Ho, Pang-Yen; Chuang, Guo-Syong; Chao, An-Chong; Li, Hsing-Ya

2005-05-01

The capacity of complex biochemical reaction networks (consisting of 11 coupled non-linear ordinary differential equations) to show multiple steady states, was investigated. The system involved esterification of ethanol and oleic acid by lipase in an isothermal continuous stirred tank reactor (CSTR). The Deficiency One Algorithm and the Subnetwork Analysis were applied to determine the steady state multiplicity. A set of rate constants and two corresponding steady states are computed. The phenomena of bistability, hysteresis and bifurcation are discussed. Moreover, the capacity of steady state multiplicity is extended to the family of the studied reaction networks.

Multifunctional Mesoporous Ionic Gels and Scaffolds Derived from Polyhedral Oligomeric Silsesquioxanes.

Science.gov (United States)

Lee, Jin Hong; Lee, Albert S; Lee, Jong-Chan; Hong, Soon Man; Hwang, Seung Sang; Koo, Chong Min

2017-02-01

A new methodology for fabrication of inorganic-organic hybrid ionogels and scaffolds is developed through facile cross-linking and solution extraction of a newly developed ionic polyhedral oligomeric silsesquioxane with inorganic core. Through design of various cationic tertiary amines, as well as cross-linkable functional groups on each arm of the inorganic core, high-performance ionogels are fabricated with excellent electrochemical stability and unique ion conduction behavior, giving superior lithium ion battery performance. Moreover, through solvent extraction of the liquid components, hybrid scaffolds with well-defined, interconnected mesopores are utilized as heterogeneous catalysts for the CO 2 -catalyzed cycloaddition of epoxides. Excellent catalytic performance, as well as highly efficient recyclability are observed when compared to other previous literature materials.

Computational Study of the Effect of Confinement within Microporous Structures on the Activity and Selectivity of Metallocene Catalysts for Ethylene Oligomerization

KAUST Repository

Toulhoat, Hervé; Lontsi Fomena, Mireille; de Bruin, Theodorus

2011-01-01

The effect of confinement within some zeolitic structures on the activity and selectivity of metallocene catalysts for the ethylene oligomerization has been investigated using grand canonical Monte Carlo simulations (GCMC). The following zeolite

Computational Study of the Effect of Confinement within Microporous Structures on the Activity and Selectivity of Metallocene Catalysts for Ethylene Oligomerization

KAUST Repository

Toulhoat, Hervé

2011-03-02

The effect of confinement within some zeolitic structures on the activity and selectivity of metallocene catalysts for the ethylene oligomerization has been investigated using grand canonical Monte Carlo simulations (GCMC). The following zeolite (host) frameworks displaying different pore sizes, have been studied as solid hosts: mazzite (MAZ), AIPO-8 (AET), UTD-1F (DON), faujasite (FAU), and VPI-5 (VFI). Intermediates and transition states involved in the ethylene trimerization reaction catalyzed by a Ti-based catalyst [(η5-C5H4CMe2C6H 5)TiCl3/MAO] have been used as sorbates (guests). We have demonstrated linear correlations with slope aH,j between the adsorption enthalpy and the molecular volume Vm of the sorbates, each holding for a given microporous host below a host-specific threshold V mmax,j. Beyond this maximal molecular volume, the adsorption vanishes due to steric exclusion. aH,j increases, and Vmmax,j decreases with decreasing host pore size, in line with the confinement concept. We moreover showed that, in the limit of vanishing loading (Henry regime), the enthalpies and entropies of adsorption in a given host are linearly correlated. We have defined a host-specific confinement compensation temperature a j, which refers to a temperature where the stabilizing adsorption enthalpic interactions are canceled out against the loss in entropy. However, calculated aj are much larger than the operating temperatures. With a setup microkinetic model, we predict that the activity and selectivity of the confined Ti-catalyst in ethylene oligomerization can be significantly altered with respect to homogeneous phase conditions, since the adsorption free energies of transition states and intermediates also become functions of aH,j and Vm. We have applied this theory to predict the optimum host pore size to get maximum α-octene production, instead of α-hexene, which is primarily produced in the homogeneous phase. We also predict a significantly increased activity for

Kinetics in Signal Transduction Pathways Involving Promiscuous Oligomerizing Receptors Can Be Determined by Receptor Specificity : Apoptosis Induction by TRAIL

NARCIS (Netherlands)

Szegezdi, Eva; van der Sloot, Almer M.; Mahalingam, Devalingam; O'Leary, Lynda; Cool, Robbert H.; Munoz, Ines G.; Montoya, Guillermo; Quax, Wim J.; de Jong, Steven; Samali, Afshin; Serrano, Luis

Here we show by computer modeling that kinetics and outcome of signal transduction in case of hetero-oligomerizing receptors of a promiscuous ligand largely depend on the relative amounts of its receptors. Promiscuous ligands can trigger the formation of nonproductive receptor complexes, which slows

Structure-properties relationships of polyhedral oligomeric silsesquioxane (POSS filled PS nanocomposites

Directory of Open Access Journals (Sweden)

J. J. Schwab

2012-07-01

Full Text Available The polyhedral oligomeric silsesquioxane (POSS additivated polystyrene (PS based nanocomposites were prepared by melt processing and the structure-properties relationships of the POSS-PS systems were compared to those of the neat PS. In order to investigate the effect of these structural parameters on the final properties of the polymer nanocomposites, five different kinds of POSS samples were used, in particular, POSS with different inorganic cage and with different organic pendent groups. The rheological investigation suggests clearly that the POSS acts as a plasticizer and that the processability of the PS was positively modified. The affinity between the POSS samples and the PS matrix was estimated by the calculated theoretical solubility parameters, considering the Hoy’s method and by morphology analysis. Minor difference between the solubility parameter of POSS and the matrix means better compatibility and no aggregation tendency. Furthermore, the POSS loading leads to a decrease of the rigidity, of the glass transition temperature and of the damping factor of the nanocomposite systems. The loading of different POSS molecules with open cage leads to a more pronounced effect on all the investigated properties that the loading of the POSS molecules with closed cage. Moreover, the melt properties are significantly influenced by the type of inorganic framework, by the type of the pendent organic groups and by the interaction between the POSS organic groups and the host matrix, while, the solid state properties appears to be influenced more by the kind of cage.

Hedgehog Buckyball: A High-Symmetry Complete Polyhedral Oligomeric Silsesquioxane (POSS

Directory of Open Access Journals (Sweden)

Yu Hu

2016-08-01

Full Text Available In this study, we report UV-MALDI-TOF MS evidence of a fullerene-like silsesquioxane, a high-symmetry polyhedral oligomeric silsesquioxane (POSS or SSO formulated as R60-Si60O90 or T60 (T = RSiO1.5. The T60 preparation can be performed using a normal hydrolytic condensation of [(3-methacryloxypropyl]trimethoxysilane (MPMS as an example. Theoretically, four 3sp3 hybrid orbitals (each containing an unpaired electron of a Si atom are generated before the bond formation. Then it bonds to another four atom electrons using the four generated hybrid orbitals which produced a stable configuration. This fullerene-like silsesquioxane should exhibit much more functionality, activity and selectivity and is easier to assemble than the double bonds in a fullerene.

Construction of porous cationic frameworks by crosslinking polyhedral oligomeric silsesquioxane units with N-heterocyclic linkers

OpenAIRE

Chen, Guojian; Zhou, Yu; Wang, Xiaochen; Li, Jing; Xue, Shuang; Liu, Yangqing; Wang, Qian; Wang, Jun

2015-01-01

In fields of materials science and chemistry, ionic-type porous materials attract increasing attention due to significant ion-exchanging capacity for accessing diversified applications. Facing the fact that porous cationic materials with robust and stable frameworks are very rare, novel tactics that can create new type members are highly desired. Here we report the first family of polyhedral oligomeric silsesquioxane (POSS) based porous cationic frameworks (PCIF-n) with enriched poly(ionic li...

Immobilization of isolated FI catalyst on polyhedral oligomeric silsesquioxane-functionalized silica for the synthesis of weakly entangled polyethylene.

Science.gov (United States)

Li, Wei; Yang, Huaqin; Zhang, Jingjing; Mu, Jingshan; Gong, Dirong; Wang, Xiaodong

2016-09-25

Polyhedral oligomeric silsesquioxanes (POSSs) were adsorbed on methylaluminoxane-activated silica for the immobilization of fluorinated bis(phenoxyimine)Ti complexes (FI catalyst). These POSSs have been characterized as horizontal spacers isolating the active sites and hindering the chain overlap in polymerization. The heterogeneous catalyst exhibits considerable activity in the synthesis of weakly entangled polyethylene.

Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

Science.gov (United States)

Yongky, Andrew; Lee, Jongchan; Le, Tung; Mulukutla, Bhanu Chandra; Daoutidis, Prodromos; Hu, Wei-Shou

2015-07-01

Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells. © 2015 Wiley Periodicals, Inc.

Nonlinear behavior of multiple-helicity resistive interchange modes near marginally stable states

International Nuclear Information System (INIS)

Sugama, Hideo; Nakajima, Noriyoshi; Wakatani, Masahiro.

1991-05-01

Nonlinear behavior of resistive interchange modes near marginally stable states is theoretically studied under the multiple-helicity condition. Reduced fluid equations in the sheared slab configuration are used in order to treat a local transport problem. With the use of the invariance property of local reduced fluid model equations under a transformation between the modes with different rational surfaces, weakly nonlinear theories for single-helicity modes by Hamaguchi and Nakajima are extended to the multiple-helicity case and applied to the resistive interchange modes. We derive the nonlinear amplitude equations of the multiple-helicity modes, from which the convective transport in the saturated state is obtained. It is shown how the convective transport is enhanced by nonlinear interaction between modes with different rational surfaces compared with the single-helicity case. We confirm that theoretical results are in good agreement with direct numerical simulations. (author)

Thermo-mechanical characterization of a monochlorophenyl, hepta isobutyl polyhedral oligomeric silsesquioxane/polystyrene composite

International Nuclear Information System (INIS)

Blanco, Ignazio; Bottino, Francesco A.; Cicala, Gianluca; Cozzo, Giulia; Latteri, Alberta; Recca, Antonino

2014-01-01

The thermal and mechanical properties of a monochlorophenyl, hepta isobutyl Polyhedral Oligomeric Silsesquioxane/Polystyrene (ph,hib-POSS/PS) composite were studied and compared with those of pristine polymer. ph,hib-POSS/PS system was prepared by solubilization and precipitation of Polystyrene (PS) in the presence of POSS. Scanning Electron Microscopy (SEM) was performed to check the distribution of the filler in the polymer matrix. Dynamic Mechanical Analysis (DMA) was carried out to measure viscoelastic properties of solid samples. Degradations were carried out into a thermobalance and the obtained thermogravimetric (TG) and differential thermogravimetric (DTG) curves were discussed and interpreted

An Asymmetric Deuterium Labeling Strategy to Identify Interprotomer and Intraprotomer NOEs in Oligomeric Proteins

International Nuclear Information System (INIS)

Jasanoff, Alan

1998-01-01

A major difficulty in determining the structure of an oligomeric protein by NMR is the problem of distinguishing inter- from intraprotomer NOEs. In order to address this issue in studies of the 27 kD compact trimeric domain of the MHC class II-associated invariant chain, we compared the 13C NOESY-HSQC spectrum of a uniformly 13C-labeled trimer with the spectrum of the same trimer labeled with 13C in only one protomer, and with deuterium in the other two protomers. The spectrum of the unmixed trimer included both inter- and intraprotomer NOEs while the spectrum of the mixed trimer included only intraprotomer peaks. NOEs clearly absent from the spectrum of the mixed trimer could be confidently assigned to interprotomer interactions. Asymmetrically labeled trimers were isolated by refolding a 13C-labeled shorter form of the protein with a 2H-labeled longer form, chromatographically purifying trimers with only one short chain, and then processing with trypsin to yield only protomers with the desired N- and C-termini. In contrast to earlier studies, in which statistical mixtures of differently labeled protomers were analyzed, our procedure generated only a well-defined 1:2 oligomer, and no other mixed oligomers were present. This increased the maximum possible concentration of NMR-active protomers and thus the sensitivity of the experiments. Related methods should be applicable to many oligomeric proteins, particularly those with slow protomer exchange rates

Nanomolar oligomerization and selective co-aggregation of α-synuclein pathogenic mutants revealed by single-molecule fluorescence

Science.gov (United States)

Sierecki, Emma; Giles, Nichole; Bowden, Quill; Polinkovsky, Mark E.; Steinbeck, Janina; Arrioti, Nicholas; Rahman, Diya; Bhumkar, Akshay; Nicovich, Philip R.; Ross, Ian; Parton, Robert G.; Böcking, Till; Gambin, Yann

2016-01-01

Protein aggregation is a hallmark of many neurodegenerative diseases, notably Alzheimer’s and Parkinson’s disease. Parkinson’s disease is characterized by the presence of Lewy bodies, abnormal aggregates mainly composed of α-synuclein. Moreover, cases of familial Parkinson’s disease have been linked to mutations in α-synuclein. In this study, we compared the behavior of wild-type (WT) α-synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T). To this end, single-molecule fluorescence detection was coupled to cell-free protein expression to measure precisely the oligomerization of proteins without purification, denaturation or labelling steps. In these conditions, we could detect the formation of oligomeric and pre-fibrillar species at very short time scale and low micromolar concentrations. The pathogenic mutants surprisingly segregated into two classes: one group forming large aggregates and fibrils while the other tending to form mostly oligomers. Strikingly, co-expression experiments reveal that members from the different groups do not generally interact with each other, both at the fibril and monomer levels. Together, this data paints a completely different picture of α-synuclein aggregation, with two possible pathways leading to the development of fibrils. PMID:27892477

Lithium-Ion Battery Online Rapid State-of-Power Estimation under Multiple Constraints

Directory of Open Access Journals (Sweden)

Shun Xiang

2018-01-01

Full Text Available The paper aims to realize a rapid online estimation of the state-of-power (SOP with multiple constraints of a lithium-ion battery. Firstly, based on the improved first-order resistance-capacitance (RC model with one-state hysteresis, a linear state-space battery model is built; then, using the dual extended Kalman filtering (DEKF method, the battery parameters and states, including open-circuit voltage (OCV, are estimated. Secondly, by employing the estimated OCV as the observed value to build the second dual Kalman filters, the battery SOC is estimated. Thirdly, a novel rapid-calculating peak power/SOP method with multiple constraints is proposed in which, according to the bisection judgment method, the battery’s peak state is determined; then, one or two instantaneous peak powers are used to determine the peak power during T seconds. In addition, in the battery operating process, the actual constraint that the battery is under is analyzed specifically. Finally, three simplified versions of the Federal Urban Driving Schedule (SFUDS with inserted pulse experiments are conducted to verify the effectiveness and accuracy of the proposed online SOP estimation method.

Structural adaptation of the subunit interface of oligomeric thermophilic and hyperthermophilic enzymes.

Science.gov (United States)

Maugini, Elisa; Tronelli, Daniele; Bossa, Francesco; Pascarella, Stefano

2009-04-01

Enzymes from thermophilic and, particularly, from hyperthermophilic organisms are surprisingly stable. Understanding of the molecular origin of protein thermostability and thermoactivity attracted the interest of many scientist both for the perspective comprehension of the principles of protein structure and for the possible biotechnological applications through application of protein engineering. Comparative studies at sequence and structure levels were aimed at detecting significant differences of structural parameters related to protein stability between thermophilic and hyperhermophilic structures and their mesophilic homologs. Comparative studies were useful in the identification of a few recurrent themes which the evolution utilized in different combinations in different protein families. These studies were mostly carried out at the monomer level. However, maintenance of a proper quaternary structure is an essential prerequisite for a functional macromolecule. At the environmental temperatures experienced typically by hyper- and thermophiles, the subunit interactions mediated by the interface must be sufficiently stable. Our analysis was therefore aimed at the identification of the molecular strategies adopted by evolution to enhance interface thermostability of oligomeric enzymes. The variation of several structural properties related to protein stability were tested at the subunit interfaces of thermophilic and hyperthermophilic oligomers. The differences of the interface structural features observed between the hyperthermophilic and thermophilic enzymes were compared with the differences of the same properties calculated from pairwise comparisons of oligomeric mesophilic proteins contained in a reference dataset. The significance of the observed differences of structural properties was measured by a t-test. Ion pairs and hydrogen bonds do not vary significantly while hydrophobic contact area increases specially in hyperthermophilic interfaces. Interface

Synthesis and characterization of an octaimidazolium-based polyhedral oligomeric silsesquioxanes ionic liquid by an ion-exchange reaction.

Science.gov (United States)

Tan, Jinglin; Ma, Depeng; Sun, Xingrong; Feng, Shengyu; Zhang, Changqiao

2013-04-07

Preparation of POSS-min-DS, an octaimidazolium-based polyhedral oligomeric silsesquioxanes (POSS) room temperature ionic liquid, by an ion-exchange reaction between POSS and sodium dodecyl sulfate was reported. Octaimidazolium-based POSS was synthesized with more than 98% yield within 3 h. POSS-min-DS and octaimidazolium-based POSS were confirmed by (1)H, (13)C, and (29)Si NMR, FT-IR and elemental analysis.

Oligomeric protein structure networks: insights into protein-protein interactions

Directory of Open Access Journals (Sweden)

Brinda KV

2005-12-01

Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

Steady State Analysis of Stochastic Systems with Multiple Time Delays

Science.gov (United States)

Xu, W.; Sun, C. Y.; Zhang, H. Q.

In this paper, attention is focused on the steady state analysis of a class of nonlinear dynamic systems with multi-delayed feedbacks driven by multiplicative correlated Gaussian white noises. The Fokker-Planck equations for delayed variables are at first derived by Novikov's theorem. Then, under small delay assumption, the approximate stationary solutions are obtained by the probability density approach. As a special case, the effects of multidelay feedbacks and the correlated additive and multiplicative Gaussian white noises on the response of a bistable system are considered. It is shown that the obtained analytical results are in good agreement with experimental results in Monte Carlo simulations.

Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects

Energy Technology Data Exchange (ETDEWEB)

Kawaji, Hiroyuki [Department of Orthopaedic Surgery, Sanyudo Hospital, 6-1-219 Chuou, Yonezawa, Yamagata 992-0045 (Japan); Nishimura, Gen [Department of Radiology, Nasu Chuou Hospital, Tochigi (Japan); Watanabe, Sobei; Sasaki, Akira; Sano, Tokuhisa [Department of Orthopaedic Surgery, Tohoku Kohsei-Nenkin Hospital, Miyagi (Japan); Mabuchi, Akihiko; Ikeda, Toshiyuki; Ikegawa, Shiro [Laboratory for Bone and Joint Diseases, SNP Research Center, Tokyo (Japan); Ohashi, Hirofumi [Division of Medical Genetics, Saitama Children' s Medical Center, Saitama (Japan)

2002-12-01

We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects. (orig.)

Polyhedral oligomeric silsequioxane monolayer as a nanoporous interlayer for preparation of low-k dielectric films

International Nuclear Information System (INIS)

Liu, Y-L; Liu, C-S; Cho, C-I; Hwu, M-J

2007-01-01

Polyhedral oligomeric silsequioxane (POSS) monomer was fixed to a silicon surface by reacting octakis(glycidyldimethylsiloxy)octasilsesquioxane (OG-POSS) with the OH-terminated silicon surface in the presence of tin (II) chloride. The POSS cage layer then served as a nanoporous interlayer to reduce the dielectric constants of polyimide films on silicon surfaces. The chemical structure and surface morphology of OG-POSS modified silicon surfaces were characterized with XPS. With the introduction of a POSS nanopored interlayer, the dielectric constants of polyimide films were reduced

Protein phosphatase 2a (PP2A binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3

Directory of Open Access Journals (Sweden)

Jones Candace A

2011-10-01

residues lying between striatin's calmodulin-binding and WD-domains and recruits the PP2A A/C heterodimer to its coiled-coil/oligomerization domain. Residues outside the previously reported coiled-coil domain of striatin are necessary for its oligomerization. Striatin-associated PP2A is critical for Mst3 dephosphorylation and inactivation. Upon inhibition of PP2A, Mst3 activation appears to involve autophosphorylation of multiple activation loop phosphorylation sites. Mob3 can associate with striatin sequences C-terminal to the Mst3 binding site but also with sequences proximal to striatin-associated PP2A, consistent with a possible role for Mob 3 in the regulation of Mst3 by PP2A.

Multiple-state quantum Otto engine, 1D box system

Energy Technology Data Exchange (ETDEWEB)

Latifah, E., E-mail: enylatifah@um.ac.id [Laboratory of Theoretical Physics and Natural Philosophy, Physics Department, Institut Teknologi Sepuluh Nopember, ITS, Surabaya, Indonesia and Physics Department, Malang State University (Indonesia); Purwanto, A. [Laboratory of Theoretical Physics and Natural Philosophy, Physics Department, Institut Teknologi Sepuluh Nopember, ITS, Surabaya (Indonesia)

2014-03-24

Quantum heat engines produce work using quantum matter as their working substance. We studied adiabatic and isochoric processes and defined the general force according to quantum system. The processes and general force are used to evaluate a quantum Otto engine based on multiple-state of one dimensional box system and calculate the efficiency. As a result, the efficiency depends on the ratio of initial and final width of system under adiabatic processes.

Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's Aβ peptide

International Nuclear Information System (INIS)

Garvey, Megan; Tepper, Katharina; Haupt, Caroline; Knuepfer, Uwe; Klement, Karolin; Meinhardt, Jessica; Horn, Uwe; Balbach, Jochen; Faendrich, Marcus

2011-01-01

Highlights: → Sodium phosphate buffer accelerated Aβ(1-40) nucleation relative to HEPES. → Aβ(1-40) fibrils formed in the two buffers show only minor structural differences. → NMR revealed that Aβ(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of Aβ peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of Aβ and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of Aβ peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of Aβ fibrillation. The three histidine residues at positions 6, 13 and 14 of Aβ(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

Resting-state connectivity of pre-motor cortex reflects disability in multiple sclerosis.

Science.gov (United States)

Dogonowski, A-M; Siebner, H R; Soelberg Sørensen, P; Paulson, O B; Dyrby, T B; Blinkenberg, M; Madsen, K H

2013-11-01

To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). A total of 27 patients with relapsing-remitting MS (RR-MS) and 15 patients with secondary progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8 between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity of left PMd showed a positive linear relation with clinical disability in patients with MS. This effect was stronger when considering the group of patients with RR-MS alone, whereas patients with SP-MS showed no increase in coupling strength between left PMd and the motor resting-state network with increasing clinical disability. No significant relation between motor resting-state connectivity of the right PMd and clinical disability was detected in MS. The increase in functional coupling between left PMd and the motor resting-state network with increasing clinical disability can be interpreted as adaptive reorganization of the motor system to maintain motor function, which appears to be limited to the relapsing-remitting stage of the disease. © 2013 John Wiley & Sons A/S.

Density of states calculations and multiple-scattering theory for photons

International Nuclear Information System (INIS)

Moroz, A.

1994-05-01

The density of states for a finite or an infinite cluster of scatterers in the case of both, electrons and photons, can be represented in a general form as the sum over all Krein-Friedel contributions of individual scatterers and a contribution due to the presence of multiple scatterers. The latter is given by the sum over all periodic orbits between different scatterers. General three dimensional multiple-scattering theory for electromagnetic waves in the presence of scatterers of arbitrary shape is presented. Vector structure constants are calculated and general rules for obtaining them from known scalar structure constants are given. The KKR equations for photons are explicitly written down. (author). 22 refs., 2 figs

Free-energy landscape of protein oligomerization from atomistic simulations

Science.gov (United States)

Barducci, Alessandro; Bonomi, Massimiliano; Prakash, Meher K.; Parrinello, Michele

2013-01-01

In the realm of protein–protein interactions, the assembly process of homooligomers plays a fundamental role because the majority of proteins fall into this category. A comprehensive understanding of this multistep process requires the characterization of the driving molecular interactions and the transient intermediate species. The latter are often short-lived and thus remain elusive to most experimental investigations. Molecular simulations provide a unique tool to shed light onto these complex processes complementing experimental data. Here we combine advanced sampling techniques, such as metadynamics and parallel tempering, to characterize the oligomerization landscape of fibritin foldon domain. This system is an evolutionarily optimized trimerization motif that represents an ideal model for experimental and computational mechanistic studies. Our results are fully consistent with previous experimental nuclear magnetic resonance and kinetic data, but they provide a unique insight into fibritin foldon assembly. In particular, our simulations unveil the role of nonspecific interactions and suggest that an interplay between thermodynamic bias toward native structure and residual conformational disorder may provide a kinetic advantage. PMID:24248370

Constitutive homo- and hetero-oligomerization of TbetaRII-B, an alternatively spliced variant of the mouse TGF-beta type II receptor

DEFF Research Database (Denmark)

Krishnaveni, Manda S; Hansen, Jakob Lerche; Seeger, Werner

2006-01-01

, but the oligomerization pattern and dynamics of TbetaRII splice variants in live cells has not been demonstrated thus far. Using co-immunoprecipitation and bioluminescence resonance energy transfer (BRET), we demonstrate that the mouse TbetaRII receptor splice variant TbetaRII-B is capable of forming ligand...

Relaxation height in energy landscapes : an application to multiple metastable states

NARCIS (Netherlands)

Cirillo, E.N.M.; Nardi, F.R.

2012-01-01

The study of systems with multiple (not necessarily degenerate) metastable states presents subtle difficulties from the mathematical point of view related to the variational problem that has to be solved in these cases. We introduce the notion of relaxation height in a general energy landscape and

Photo-polymerization of photocurable resins containing polyhedral oligomeric silsesquioxane methacrylate

International Nuclear Information System (INIS)

Lin, Ho-May; Wu, Shi-Yin; Chang, Feng-Chih; Yen, Ying-Chieh

2011-01-01

Photocurable resins, bisphenol A propoxylate glycerolate diacrylate (BPA-PGDA, containing two hydroxyl) and bisphenol A propoxylate diacrylate (BPA-PDA), with fixed photoinitiator (Irgacure 907) concentration and various contents of methacrylisobutyl polyhedral oligomeric silsesquioxane (MI-POSS) were prepared and characterized by FTIR spectroscopy, scanning electron microscope and differential photocalorimetry. The MI-POSS molecules form crystals or aggregated particles in the cured resin matrix. The BPA-PGDA series photocurable resins show higher viscosity and lower photo-polymerization reactivity than the BPA-PDA series resins. The photo-polymerization rate and conversion of BPA-PGDA series are improved with increasing MI-POSS content. On the contrary, the photo-polymerization behavior of BPA-PDA series photocurable resins remains nearly unchanged by the addition of MI-POSS. Hydrogen-bonding interaction between the hydroxyl of BPA-PGDA and the siloxane of MI-POSS tends to attract and concentrate these acrylate double bonds around MI-POSS particles and thus enhances the photo-polymerization rate and conversion.

Exceptionally High Electric Double Layer Capacitances of Oligomeric Ionic Liquids.

Science.gov (United States)

Matsumoto, Michio; Shimizu, Sunao; Sotoike, Rina; Watanabe, Masayoshi; Iwasa, Yoshihiro; Itoh, Yoshimitsu; Aida, Takuzo

2017-11-15

Electric double layer (EDL) capacitors are promising as next-generation energy accumulators if their capacitances and operation voltages are both high. However, only few electrolytes can simultaneously fulfill these two requisites. Here we report that an oligomeric ionic liquid such as IL4 TFSI with four imidazolium ion units in its structure provides a wide electrochemical window of ∼5.0 V, similar to monomeric ionic liquids. Furthermore, electrochemical impedance measurements using Au working electrodes demonstrated that IL4 TFSI exhibits an exceptionally high EDL capacitance of ∼66 μF/cm 2 , which is ∼6 times as high as those of monomeric ionic liquids so far reported. We also found that an EDL-based field effect transistor (FET) using IL4 TFSI as a gate dielectric material and SrTiO 3 as a channel material displays a very sharp transfer curve with an enhanced carrier accumulation capability of ∼64 μF/cm 2 , as determined by Hall-effect measurements.

Multiple climate and sea ice states on a coupled Aquaplanet

Science.gov (United States)

Rose, B.; Ferreira, D.; Marshall, J.

2010-12-01

A fully coupled atmosphere-ocean-sea ice GCM is used to explore the climates of Earth-like planets with no continents and idealized ocean basin geometries. We find three qualitatively different stable equilibria under identical external forcing: an equable ice-free climate, a cold climate with ice caps extending into mid-latitudes, and a completely ice-covered "Snowball" state. These multiple states persist for millennia with no drift despite a full seasonal cycle and vigorous internal variability of the system on all time scales. The behavior of the coupled system is rationalized through an extension of the Budyko-Sellers model to include explicit ocean heat transport (OHT), and the insulation of the ice-covered sea surface. Sensitivity tests are also conducted with a slab ocean GCM with prescribed OHT. From these we conclude that albedo feedback and ocean circulation both play essential roles in the maintenance of the multiple states. OHT in the coupled system is dominated by a wind-driven subtropical cell carrying between 2 and 3 PW of thermal energy out of the deep tropics, most of which converges in the subtropics to lower mid-latitudes. This convergence pattern (similar to modern Earth) is robust to changes in the ocean basin geometry, and is directly responsible for the stabilization of the large ice cap. OHT also plays an essential but indirect role in the maintenance of the ice-free pole in the warm states, by driving an enhanced poleward atmospheric latent heat flux. The hysteresis loop for transitions between the warm and large ice cap states spans a much smaller range of parameter space (e.g. ±1.8% variations in solar constant) than the transitions in and out of the Snowball. Three qualitatively different climate states for the same external forcing in a coupled GCM: ice-free, large ice cap, and Snowball. SST and sea ice thickness are plotted. Similar results are found in a pure Aquaplanet (lower) and a "RidgeWorld" with a global-scale ocean basin

Mathematical Modeling of Loop Heat Pipes with Multiple Capillary Pumps and Multiple Condensers. Part 1; Stead State Stimulations

Science.gov (United States)

Hoang, Triem T.; OConnell, Tamara; Ku, Jentung

2004-01-01

Loop Heat Pipes (LHPs) have proven themselves as reliable and robust heat transport devices for spacecraft thermal control systems. So far, the LHPs in earth-orbit satellites perform very well as expected. Conventional LHPs usually consist of a single capillary pump for heat acquisition and a single condenser for heat rejection. Multiple pump/multiple condenser LHPs have shown to function very well in ground testing. Nevertheless, the test results of a dual pump/condenser LHP also revealed that the dual LHP behaved in a complicated manner due to the interaction between the pumps and condensers. Thus it is redundant to say that more research is needed before they are ready for 0-g deployment. One research area that perhaps compels immediate attention is the analytical modeling of LHPs, particularly the transient phenomena. Modeling a single pump/single condenser LHP is difficult enough. Only a handful of computer codes are available for both steady state and transient simulations of conventional LHPs. No previous effort was made to develop an analytical model (or even a complete theory) to predict the operational behavior of the multiple pump/multiple condenser LHP systems. The current research project offered a basic theory of the multiple pump/multiple condenser LHP operation. From it, a computer code was developed to predict the LHP saturation temperature in accordance with the system operating and environmental conditions.

Efficient light-emitting devices based on platinum-complexes-anchored polyhedral oligomeric silsesquioxane materials

KAUST Repository

Yang, Xiaohui

2010-08-24

The synthesis, photophysical, and electrochemical characterization of macromolecules, consisting of an emissive platinum complex and carbazole moieties covalently attached to a polyhedral oligomeric silsesquioxane (POSS) core, is reported. Organic light-emitting devices based on these POSS materials exhibit a peak external quantum efficiency of ca. 8%, which is significantly higher than that of the analogous devices with a physical blend of the platinum complexes and a polymer matrix, and they represent noticeable improvement in the device efficiency of solution-processable phosphorescent excimer devices. Furthermore, the ratio of monomer and excimer/aggregate electroluminescent emission intensity, as well as the device efficiency, increases as the platinum complex moiety presence on the POSS macromolecules decreases. © 2010 American Chemical Society.

Two Schemes for Generation of Entanglement for Vibronic Collective States of Multiple Trapped Ions

International Nuclear Information System (INIS)

Yang Wenxing; Li Jiahua; Zheng Anshou

2007-01-01

We propose two schemes to prepare entanglement for the vibronic collective states of multiple trapped ions. The first scheme aims to generating multipartite entanglement for vibrational modes of trapped ions, which only requires a single laser beam tuned to the ionic carrier frequency. Our scheme works in the mediated excitation regime, in which the corresponding Rabi frequency is equal to the trap frequency. Beyond their fundamental importance, these states may be of interest for experimental studies on decoherence since the present scheme operates in a fast way. The second scheme aims to preparing the continuous variable multimode maximally Greenberger-Horne-Zeilinger state. The distinct advantage is that the operation time is only limited by the available laser intensity, not by the inherent mechanisms such as off-resonant excitations. This makes it promising to obtain entanglement of multiple coherent and squeezing states with desired amplitudes in a reasonable time.

Oxygen entry through multiple pathways in T-state human hemoglobin.

Science.gov (United States)

Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

2013-05-23

The heme oxygen (O2) binding site of human hemoglobin (HbA) is buried in the interior of the protein, and there is a debate over the O2 entry pathways from solvent to the binding site. As a first step to understand HbA O2 binding process at the atomic level, we detected all significant multiple O2 entry pathways from solvent to the binding site in the α and β subunits of the T-state tetramer HbA by utilizing ensemble molecular dynamics (MD) simulation. By executing 128 independent 8 ns MD trajectories in O2-rich aqueous solvent, we simulated the O2 entry processes and obtained 141 and 425 O2 entry events in the α and β subunits of HbA, respectively. We developed the intrinsic pathway identification by clustering method to achieve a persuasive visualization of the multiple entry pathways including both the shapes and relative importance of each pathway. The rate constants of O2 entry estimated from the MD simulations correspond to the experimentally observed values, suggesting that O2 ligands enter the binding site through multiple pathways. The obtained multiple pathway map can be utilized for future detailed analysis of HbA O2 binding process.

Oligomeric rare-earth metal cluster complexes with endohedral transition metal atoms

Energy Technology Data Exchange (ETDEWEB)

Steinberg, Simon; Zimmermann, Sina; Brühmann, Matthias; Meyer, Eva; Rustige, Christian; Wolberg, Marike; Daub, Kathrin; Bell, Thomas; Meyer, Gerd, E-mail: gerd.meyer@uni-koeln.de

2014-11-15

Comproportionation reactions of rare-earth metal trihalides (RX{sub 3}) with the respective rare-earth metals (R) and transition metals (T) led to the formation of 22 oligomeric R cluster halides encapsulating T, in 19 cases for the first time. The structures of these compounds were determined by single-crystal X-ray diffraction and are composed of trimers ((T{sub 3}R{sub 11})X{sub 15}-type, P6{sub 3}/m), tetramers ((T{sub 4}R{sub 16})X{sub 28}(R{sub 4}) (P-43m), (T{sub 4}R{sub 16})X{sub 20} (P4{sub 2}/nnm), (T{sub 4}R{sub 16})X{sub 24}(RX{sub 3}){sub 4} (I4{sub 1}/a) and (T{sub 4}R{sub 16})X{sub 23} (C2/m) types of structure) and pentamers ((Ru{sub 5}La{sub 14}){sub 2}Br{sub 39}, Cc) of (TR{sub r}){sub n} (n=2–5) clusters. These oligomers are further enveloped by inner (X{sup i}) as well as outer (X{sup a}) halido ligands, which possess diverse functionalities and interconnect like oligomers through i–i, i–a and/or a–i bridges. The general features of the crystal structures for these new compounds are discussed and compared to literature entries as well as different structure types with oligomeric T centered R clusters. Dimers and tetramers originating from the aggregation of (TR{sub 6}) octahedra via common edges are more frequent than trimers and pentamers, in which the (TR{sub r}) clusters share common faces. - Graphical abstract: Rare earth-metal cluster complexes with endohedral transition metal atoms (TR{sub 6}) may connect via common edges or faces to form dimers, trimers, tetramers and pentamers of which the tetramers are the most prolific. Packing effects and electron counts play an important role. - Highlights: • Rare-earth metal cluster complexes encapsulate transition metal atoms. • Oligomers are built via connection of octahedral clusters via common edges or faces. • Dimers through pentamers with closed structures are known. • Tetramers including a tetrahedron of endohedral atoms are the most prolific.

Accelerated Enveloping Distribution Sampling: Enabling Sampling of Multiple End States while Preserving Local Energy Minima.

Science.gov (United States)

Perthold, Jan Walther; Oostenbrink, Chris

2018-05-17

Enveloping distribution sampling (EDS) is an efficient approach to calculate multiple free-energy differences from a single molecular dynamics (MD) simulation. However, the construction of an appropriate reference-state Hamiltonian that samples all states efficiently is not straightforward. We propose a novel approach for the construction of the EDS reference-state Hamiltonian, related to a previously described procedure to smoothen energy landscapes. In contrast to previously suggested EDS approaches, our reference-state Hamiltonian preserves local energy minima of the combined end-states. Moreover, we propose an intuitive, robust and efficient parameter optimization scheme to tune EDS Hamiltonian parameters. We demonstrate the proposed method with established and novel test systems and conclude that our approach allows for the automated calculation of multiple free-energy differences from a single simulation. Accelerated EDS promises to be a robust and user-friendly method to compute free-energy differences based on solid statistical mechanics.

Solid-state framing camera with multiple time frames

Energy Technology Data Exchange (ETDEWEB)

Baker, K. L.; Stewart, R. E.; Steele, P. T.; Vernon, S. P.; Hsing, W. W.; Remington, B. A. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States)

2013-10-07

A high speed solid-state framing camera has been developed which can operate over a wide range of photon energies. This camera measures the two-dimensional spatial profile of the flux incident on a cadmium selenide semiconductor at multiple times. This multi-frame camera has been tested at 3.1 eV and 4.5 keV. The framing camera currently records two frames with a temporal separation between the frames of 5 ps but this separation can be varied between hundreds of femtoseconds up to nanoseconds and the number of frames can be increased by angularly multiplexing the probe beam onto the cadmium selenide semiconductor.

Multiple-copy state discrimination: Thinking globally, acting locally

International Nuclear Information System (INIS)

Higgins, B. L.; Pryde, G. J.; Wiseman, H. M.; Doherty, A. C.; Bartlett, S. D.

2011-01-01

We theoretically investigate schemes to discriminate between two nonorthogonal quantum states given multiple copies. We consider a number of state discrimination schemes as applied to nonorthogonal, mixed states of a qubit. In particular, we examine the difference that local and global optimization of local measurements makes to the probability of obtaining an erroneous result, in the regime of finite numbers of copies N, and in the asymptotic limit as N→∞. Five schemes are considered: optimal collective measurements over all copies, locally optimal local measurements in a fixed single-qubit measurement basis, globally optimal fixed local measurements, locally optimal adaptive local measurements, and globally optimal adaptive local measurements. Here an adaptive measurement is one in which the measurement basis can depend on prior measurement results. For each of these measurement schemes we determine the probability of error (for finite N) and the scaling of this error in the asymptotic limit. In the asymptotic limit, it is known analytically (and we verify numerically) that adaptive schemes have no advantage over the optimal fixed local scheme. Here we show moreover that, in this limit, the most naive scheme (locally optimal fixed local measurements) is as good as any noncollective scheme except for states with less than 2% mixture. For finite N, however, the most sophisticated local scheme (globally optimal adaptive local measurements) is better than any other noncollective scheme for any degree of mixture.

The Over-Barrier Resonant States and Multi-Channel Scattering in Multiple Quantum Wells

Directory of Open Access Journals (Sweden)

A Polupanov

2016-09-01

Full Text Available We demonstrate an explicit numerical method for accurate calculation of the scattering matrix and its poles, and apply this method to describe the multi-channel scattering in the multiple quantum-wells structures. The S-matrix is continued analytically to the unphysical region of complex energy values. Results of calculations show that there exist one or more S-matrix poles, corresponding to the over-barrier resonant states critical for the effect of the absolute reflection of holes in the energy range where only the heavy ones may propagate over barriers in a structure. Light- and heavy-hole states are described by the Luttinger Hamiltonian matrix. In contrast to the single quantum-well case, at some parameters of a multiple quantum-wells structure the number of S-matrix poles may exceed that of the absolute reflection peaks, and at different values of parameters the absolute reflection peak corresponds to different resonant states. The imaginary parts of the S-matrix poles and hence the lifetimes of resonant states as well as the widths of resonant peaks of absolute reflection depend drastically on the quantum-well potential depth. In the case of shallow quantum wells there is in fact a long-living over-barrier resonant hole state.

Antibodies against alpha-synuclein reduce oligomerization in living cells.

Directory of Open Access Journals (Sweden)

Thomas Näsström

Full Text Available Recent research implicates soluble aggregated forms of α-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson's disease and related disorders. The pathway by which α-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligomers are initially formed. Here, we used H4 neuroglioma cells expressing α-synuclein fused to hemi:GFP constructs to study the effects of α-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that cells treated for 48 h with monoclonal antibodies internalized antibodies to various degrees. C-terminal and oligomer-selective α-synuclein antibodies reduced the extent of α-synuclein dimerization/oligomerization, as indicated by decreased GFP fluorescence signal. Furthermore, ELISA measurements on lysates and conditioned media from antibody treated cells displayed lower α-synuclein levels compared to untreated cells, suggesting increased protein turnover. Taken together, our results propose that extracellular administration of monoclonal antibodies can modify or inhibit early steps in the aggregation process of α-synuclein, thus providing further support for passive immunization against diseases with α-synuclein pathology.

Jumping magneto-electric states of electrons in semiconductor multiple quantum wells

International Nuclear Information System (INIS)

Pfeffer, Pawel; Zawadzki, Wlodek

2011-01-01

Orbital and spin electron states in semiconductor multiple quantum wells in the presence of an external magnetic field transverse to the growth direction are considered. Rectangular wells of GaAs/GaAlAs and InAs/AlSb are taken as examples. It is shown that, in addition to magneto-electric states known from one-well systems, there appear magneto-electric states having a much stronger dependence of energies on a magnetic field and exhibiting an interesting anti-crossing behavior. The origin of these states is investigated and it is shown that the strong field dependence of the energies is related to an unusual 'jumping' behavior of their wavefunctions between quantum wells as the field increases. The ways of investigating the jumping states by means of interband magneto-luminescence transitions or intraband cyclotron-like transitions are considered and it is demonstrated that the jumping states can be observed. The spin g factors of electrons in the jumping states are calculated using the real values of the spin–orbit interaction and bands' nonparabolicity for the semiconductors in question. It is demonstrated that the jumping states offer a wide variety of the spin g factors

Hexokinase 2 from Saccharomyces cerevisiae: regulation of oligomeric structure by in vivo phosphorylation at serine-14.

Science.gov (United States)

Behlke, J; Heidrich, K; Naumann, M; Müller, E C; Otto, A; Reuter, R; Kriegel, T

1998-08-25

Homodimeric hexokinase 2 from Saccharomyces cerevisiae is known to have two sites of phosphorylation: for serine-14 the modification in vivo increases with glucose exhaustion [Kriegel et al. (1994) Biochemistry 33, 148-152], while for serine-157 it occurs in vitro with ATP in the presence of nonphosphorylateable five-carbon analogues of glucose [Heidrich et al. (1997) Biochemistry 36, 1960-1964]. We show now by site-directed mutagenesis and sedimentation analysis that serine-14 phosphorylation affects the oligomeric state of hexokinase, its substitution by glutamate causing complete dissociation; glutamate exchange for serine-157 does not. Phosphorylation of wild-type hexokinase at serine-14 likewise causes dissociation in vitro. In view of the higher glucose affinity of monomeric hexokinase and the high hexokinase concentration in yeast [Womack, F., and Colowick, S. P. (1978) Arch. Biochem. Biophys. 191, 742-747; Mayes, E. L., Hoggett, J. G., and Kellett, G. L. (1983) Eur. J. Biochem. 133, 127-134], we speculate that the in vivo phosphorylation at serine-14 as transiently occurring in glucose derepression might provide a mechanism to improve glucose utilization from low level and/or that nuclear localization of the monomer might be involved in the signal transduction whereby glucose causes catabolite repression.

Multiple states in the late Eocene ocean circulation

Science.gov (United States)

Baatsen, M. L. J.; von der Heydt, A. S.; Kliphuis, M.; Viebahn, J.; Dijkstra, H. A.

2018-04-01

The Eocene-Oligocene Transition (EOT) marks a major step within the Cenozoic climate in going from a greenhouse into an icehouse state, with the formation of a continental-scale Antarctic ice sheet. The roles of steadily decreasing CO2 concentrations versus changes in ocean circulation at the EOT are still debated and the threshold for Antarctic glaciation is obscured by uncertainties in global geometry. Here, a detailed study of the late Eocene ocean circulation is carried out using an ocean general circulation model under two slightly different geography reconstructions of the middle-to-late Eocene (38 Ma). Using the same atmospheric forcing, both geographies give a profoundly different equilibrium ocean circulation state. The underlying reason for this sensitivity is the presence of multiple equilibria characterised by either North or South Pacific deep water formation. A possible shift from a southern towards a northern overturning circulation would result in significant changes in the global heat distribution and consequently make the Southern Hemisphere climate more susceptible for significant cooling and ice sheet formation on Antarctica.

Oligomeric forms of the metastasis-related Mts1 (S100A4) protein stimulate neuronal differentiation in cultures of rat hippocampal neurons

DEFF Research Database (Denmark)

Novitskaya, V; Grigorian, M; Kriajevska, M

2000-01-01

protein family. The oligomeric but not the dimeric form of Mts1 strongly induces differentiation of cultured hippocampal neurons. A mutant with a single Y75F amino acid substitution, which stabilizes the dimeric form of Mts1, is unable to promote neurite extension. Disulfide bonds do not play an essential...

Fluorescence excitation involving multiple electron transition states of N{sub 2} and CO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Wu, C.Y.R.; Chen, F.Z.; Hung, T.; Judge, D.L. [Univ. of Southern California, Los Angeles, CA (United States)

1997-04-01

The electronic states and electronic structures of N{sub 2} and CO{sub 2} in the 8-50 eV energy region have been studied extensively both experimentally and theoretically. In the energy region higher than 25 eV there exists many electronic states including multiple electron transition (MET) states which are responsible for producing most of the dissociative photoionization products. The electronic states at energies higher than 50 eV have been mainly determined by Auger spectroscopy, double charge transfer, photofragment spectroscopy and ion-ion coincidence spectroscopy. The absorption and ionization spectra of these molecules at energies higher than 50 eV mainly show a monotonic decrease in cross section values and exhibit structureless features. The decay channels of MET and Rydberg (or superexcited) states include autoionization, ionization, dissociative ionization, predissociation, and dissociation while those of single ion and multiple ion states may involve predissociation. and dissociation processes. The study of fluorescence specifically probes electronically excited species resulting from the above-mentioned decay channels and provides information for understanding the competition among these channels.

Insight into the template effect of vesicles on the laccase-catalyzed oligomerization of N-phenyl-1,4-phenylenediamine from Raman spectroscopy and cyclic voltammetry measurements

Science.gov (United States)

Ležaić, Aleksandra Janoševic; Luginbühl, Sandra; Bajuk-Bogdanović, Danica; Pašti, Igor; Kissner, Reinhard; Rakvin, Boris; Walde, Peter; Ćirić-Marjanović, Gordana

2016-08-01

We report about the first Raman spectroscopy study of a vesicle-assisted enzyme-catalyzed oligomerization reaction. The aniline dimer N-phenyl-1,4-phenylenediamine (= p-aminodiphenylamine, PADPA) was oxidized and oligomerized with Trametes versicolor laccase and dissolved O2 in the presence of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) vesicles (80-100 nm diameter) as templates. The conversion of PADPA into oligomeric products, poly(PADPA), was monitored during the reaction by in situ Raman spectroscopy. The results obtained are compared with UV/vis/NIR and EPR measurements. All three complementary methods indicate that at least some of the poly(PADPA) products, formed in the presence of AOT vesicles, resemble the conductive emeraldine salt form of polyaniline (PANI-ES). The Raman measurements also show that structural units different from those of “ordinary” PANI-ES are present too. Without vesicles PANI-ES-like products are not obtained. For the first time, the as-prepared stable poly(PADPA)-AOT vesicle suspension was used directly to coat electrodes (without product isolation) for investigating redox activities of poly(PADPA) by cyclic voltammetry (CV). CV showed that poly(PADPA) produced with vesicles is redox active not only at pH 1.1-as expected for PANI-ES-but also at pH 6.0, unlike PANI-ES and poly(PADPA) synthesized without vesicles. This extended pH range of the redox activity of poly(PADPA) is important for applications.

Higgsplosion: Solving the hierarchy problem via rapid decays of heavy states into multiple Higgs bosons

Science.gov (United States)

Khoze, Valentin V.; Spannowsky, Michael

2018-01-01

We introduce and discuss two inter-related mechanisms operative in the electroweak sector of the Standard Model at high energies. Higgsplosion, the first mechanism, occurs at some critical energy in the 25 to 103 TeV range, and leads to an exponentially growing decay rate of highly energetic particles into multiple Higgs bosons. We argue that this is a well-controlled non-perturbative phenomenon in the Higgs-sector which involves the final state Higgs multiplicities n in the regime nλ ≫ 1 where λ is the Higgs self-coupling. If this mechanism is realised in nature, the cross-sections for producing ultra-high multiplicities of Higgs bosons are likely to become observable and even dominant in this energy range. At the same time, however, the apparent exponential growth of these cross-sections at even higher energies will be tamed and automatically cut-off by a related Higgspersion mechanism. As a result, and in contrast to previous studies, multi-Higgs production does not violate perturbative unitarity. Building on this approach, we then argue that the effects of Higgsplosion alter quantum corrections from very heavy states to the Higgs boson mass. Above a certain energy, which is much smaller than their masses, these states would rapidly decay into multiple Higgs bosons. The heavy states become unrealised as they decay much faster than they are formed. The loop integrals contributing to the Higgs mass will be cut off not by the masses of the heavy states, but by the characteristic loop momenta where their decay widths become comparable to their masses. Hence, the cut-off scale would be many orders of magnitude lower than the heavy mass scales themselves, thus suppressing their quantum corrections to the Higgs boson mass.

Oligomerization of adenosin-5´-O-ylmethylphosphonate, an isopolar AMP analogue: Evaluation of the route to short oligoadenylates

Czech Academy of Sciences Publication Activity Database

Pressová, Martina; Buděšínský, Miloš; Kóšiová, Ivana; Kopecký, V. Jr.; Cvačka, Josef; Kašička, Václav; Šimák, Ondřej; Točík, Zdeněk; Rosenberg, Ivan

2010-01-01

Roč. 93, č. 3 (2010), s. 277-289 ISSN 0006-3525 R&D Projects: GA MŠk(CZ) LC06077; GA MŠk(CZ) LC06061; GA AV ČR KAN200520801; GA ČR GA203/09/0820; GA ČR GA202/09/0193 Grant - others:EMIL-FW6(XE) 503569 Institutional research plan: CEZ:AV0Z40550506 Keywords : spontaneous oligomerization * oligoadenylates * phosphonate linkage Subject RIV: CC - Organic Chemistry Impact factor: 2.572, year: 2010

Simultaneous estimation of multiple phases in digital holographic interferometry using state space analysis

Science.gov (United States)

Kulkarni, Rishikesh; Rastogi, Pramod

2018-05-01

A new approach is proposed for the multiple phase estimation from a multicomponent exponential phase signal recorded in multi-beam digital holographic interferometry. It is capable of providing multidimensional measurements in a simultaneous manner from a single recording of the exponential phase signal encoding multiple phases. Each phase within a small window around each pixel is appproximated with a first order polynomial function of spatial coordinates. The problem of accurate estimation of polynomial coefficients, and in turn the unwrapped phases, is formulated as a state space analysis wherein the coefficients and signal amplitudes are set as the elements of a state vector. The state estimation is performed using the extended Kalman filter. An amplitude discrimination criterion is utilized in order to unambiguously estimate the coefficients associated with the individual signal components. The performance of proposed method is stable over a wide range of the ratio of signal amplitudes. The pixelwise phase estimation approach of the proposed method allows it to handle the fringe patterns that may contain invalid regions.

Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

Science.gov (United States)

Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

2003-03-14

Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

International Nuclear Information System (INIS)

Wu, Zhengliang L.; Zhou, Hui; Ethen, Cheryl M.; Reinhold, Vernon N.

2016-01-01

The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and "3H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain why

Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

Energy Technology Data Exchange (ETDEWEB)

Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Zhou, Hui [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States); Ethen, Cheryl M. [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States)

2016-04-29

The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and {sup 3}H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain

Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

Directory of Open Access Journals (Sweden)

Guoshi Li

2017-10-01

Full Text Available The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh and norepinephrine (NE and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

A S52P mutation in the 'α-crystallin domain' of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function.

Science.gov (United States)

Nandi, Sandip K; Rehna, Elengikal A A; Panda, Alok K; Shiburaj, Sugathan; Dharmalingam, Kuppamuthu; Biswas, Ashis

2013-12-01

Mycobacterium leprae HSP18 is a small heat shock protein (sHSP). It is a major immunodominant antigen of M. leprae pathogen. Previously, we have reported the existence of two M. leprae HSP18 variants in various leprotic patients. One of the variants has serine at position 52, whereas the other one has proline at the same position. We have also reported that HSP18 having proline at position 52 (HSP18P(52)) is a nonameric protein and exhibits chaperone function. However, the structural and functional characterization of wild-type HSP18 having serine at position 52 (HSP18S(52)) is yet to be explored. Furthermore, the implications of the S52P mutation on the structure and chaperone function of HSP18 are not well understood. Therefore, we cloned and purified these two HSP18 variants. We found that HSP18S(52) is also a molecular chaperone and an oligomeric protein. Intrinsic tryptophan fluorescence and far-UV CD measurements revealed that the S52P mutation altered the tertiary and secondary structure of HSP18. This point mutation also reduced the oligomeric assembly and decreased the surface hydrophobicity of HSP18, as revealed by HPLC and 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid binding studies, respectively. Mutant protein was less stable against thermal and chemical denaturation and was more susceptible towards tryptic cleavage than wild-type HSP18. HSP18P(52) had lower chaperone function and was less effective in protecting thermal killing of Escherichia coli than HSP18S(52). Taken together, our data suggest that serine 52 is important for the larger oligomerization and chaperone function of HSP18. Because both variants differ in stability and function, they may have different roles in the survival of M. leprae in infected hosts. © 2013 FEBS.

Addressing Single and Multiple Bad Data in the Modern PMU-based Power System State Estimation

DEFF Research Database (Denmark)

Khazraj, Hesam; Silva, Filipe Miguel Faria da; Bak, Claus Leth

2017-01-01

utilization in state estimation can detect and identify single and multiple bad data in redundant and critical measurements. To validate simulations, IEEE 30 bus system are implemented in PowerFactory and Matlab is used to solve proposed state estimation using postprocessing of PMUs and mixed methods. Bad...

A New Star-shaped Carbazole Derivative with Polyhedral Oligomeric Silsesquioxane Core: Crystal Structure and Unique Photoluminescence Property.

Science.gov (United States)

Xu, Zixuan; Yu, Tianzhi; Zhao, Yuling; Zhang, Hui; Zhao, Guoyun; Li, Jianfeng; Chai, Lanqin

2016-01-01

A new inorganic–organic hybrid material based on polyhedral oligomeric silsesquioxane (POSS) capped with carbazolyl substituents, octakis[3-(carbazol-9-yl)propyldimethylsiloxy]-silsesquioxane (POSS-8Cz), was successfully synthesized and characterized. The X-ray crystal structure of POSS-8Cz were described. The photophysical properties of POSS-8Cz were investigated by using UV–vis,photoluminescence spectroscopic analysis. The hybrid material exhibits blue emission in the solution and the solid film.The morphology and thermal stablity properties were measured by X-ray diffraction (XRD) and TG-DTA analysis.

The continuous end-state comfort effect: weighted integration of multiple biases.

Science.gov (United States)

Herbort, Oliver; Butz, Martin V

2012-05-01

The grasp orientation when grasping an object is frequently aligned in anticipation of the intended rotation of the object (end-state comfort effect). We analyzed grasp orientation selection in a continuous task to determine the mechanisms underlying the end-state comfort effect. Participants had to grasp a box by a circular handle-which allowed for arbitrary grasp orientations-and then had to rotate the box by various angles. Experiments 1 and 2 revealed both that the rotation's direction considerably determined grasp orientations and that end-postures varied considerably. Experiments 3 and 4 further showed that visual stimuli and initial arm postures biased grasp orientations if the intended rotation could be easily achieved. The data show that end-state comfort but also other factors determine grasp orientation selection. A simple mechanism that integrates multiple weighted biases can account for the data.

Multiple-state based power control for multi-radio multi-channel wireless mesh networks

CSIR Research Space (South Africa)

Olwal, TO

2009-01-01

Full Text Available Multi-Radio Multi-Channel (MRMC) systems are key to power control problems in wireless mesh networks (WMNs). In this paper, we present asynchronous multiple-state based power control for MRMC WMNs. First, WMN is represented as a set of disjoint...

Hydrolyzable Tannins of Tamaricaceous Plants. 7.1 Structures and Cytotoxic Properties of Oligomeric Ellagitannins from Leaves of Tamarix nilotica and Cultured Tissues of Tamarix tetrandra.

Science.gov (United States)

Orabi, Mohamed A A; Taniguchi, Shoko; Sakagami, Hiroshi; Yoshimura, Morio; Amakura, Yoshiaki; Hatano, Tsutomu

2016-04-22

Partially unacylated new oligomeric hydrolyzable tannins, nilotinin T2 (1, trimer) and nilotinin Q1 (2, tetramer), together with four known trimers, nilotinin T1 (3) and hirtellins T1-T3 (4-6), and a dimer, tamarixinin B (7), were isolated from the aqueous acetone extracts of leaves of Tamarix nilotica. Among them, the new trimer 1 and the known trimers 4 and 6, in addition to the partially unacylated new trimer nilotinin T3 (8), the known dimers nilotinin D3 (9) and tamarixinin C (10), and the monomer tellimagrandin I (11), were isolated from the cultured shoots of Tamarix tetrandra. The structures of the new hydrolyzable tannins were established by chromatographic analyses and extensive 1D and 2D NMR, HRESI-TOFMS, and ECD spectroscopic experiments. Among the new oligomeric tannins, the particular unacylated position of a glucose core is attributed to a possible biosynthetic route. Isolation of the same oligomeric tannins from cultured shoots of T. tetrandra emphasizes the unique biogenetic ability of the obtained cultures on production of the structurally and biologically characteristic tamaricaceous tannins commonly produced by the intact Tamarix plants. Additionally, tannins obtained in the present study together with gemin D (12) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-β-d-glucose (13), from our previous investigation of the leaves of T. nilotica, exhibited variable tumor-specific cytotoxic effects. The ellagitannin trimers 4, 6, and 8 and the dimer 9 exerted predominant tumor-selective cytotoxic effects with high specificity toward human promyelocytic leukemia cells.

Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild-type H5N1 influenza challenge and controls viral loads better than subunit H5N1 vaccine by eliciting high-affinity antibodies.

Science.gov (United States)

Verma, Swati; Dimitrova, Milena; Munjal, Ashok; Fontana, Juan; Crevar, Corey J; Carter, Donald M; Ross, Ted M; Khurana, Surender; Golding, Hana

2012-11-01

Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.

Abnormal Multiple Charge Memory States in Exfoliated Few-Layer WSe2 Transistors.

Science.gov (United States)

Chen, Mikai; Wang, Yifan; Shepherd, Nathan; Huard, Chad; Zhou, Jiantao; Guo, L J; Lu, Wei; Liang, Xiaogan

2017-01-24

To construct reliable nanoelectronic devices based on emerging 2D layered semiconductors, we need to understand the charge-trapping processes in such devices. Additionally, the identified charge-trapping schemes in such layered materials could be further exploited to make multibit (or highly desirable analog-tunable) memory devices. Here, we present a study on the abnormal charge-trapping or memory characteristics of few-layer WSe 2 transistors. This work shows that multiple charge-trapping states with large extrema spacing, long retention time, and analog tunability can be excited in the transistors made from mechanically exfoliated few-layer WSe 2 flakes, whereas they cannot be generated in widely studied few-layer MoS 2 transistors. Such charge-trapping characteristics of WSe 2 transistors are attributed to the exfoliation-induced interlayer deformation on the cleaved surfaces of few-layer WSe 2 flakes, which can spontaneously form ambipolar charge-trapping sites. Our additional results from surface characterization, charge-retention characterization at different temperatures, and density functional theory computation strongly support this explanation. Furthermore, our research also demonstrates that the charge-trapping states excited in multiple transistors can be calibrated into consistent multibit data storage levels. This work advances the understanding of the charge memory mechanisms in layered semiconductors, and the observed charge-trapping states could be further studied for enabling ultralow-cost multibit analog memory devices.

Carbon Domains on MoS2/TiO2 System via Catalytic Acetylene Oligomerization: Synthesis, Structure, and Surface Properties

Directory of Open Access Journals (Sweden)

Sara Cravanzola

2017-11-01

Full Text Available Carbon domains have been obtained at the surface of a MoS2/TiO2 (Evonik, P25 system via oligomerization and cyclotrimerization reactions involved in the interaction of the photoactive material with acetylene. Firstly, MoS2 nanosheets have been synthesized at the surface of TiO2, via sulfidation of a molybdenum oxide precursor with H2S (bottom-up method. Secondly, the morphology and the structure, the optical and the vibrational properties of the obtained materials, for each step of the synthesis procedure, have been investigated by microscopy and spectroscopy methods. In particular, transmission electron microscopy images provide a simple tool to highlight the effectiveness of the sulfidation process, thus showing 1L, 2L, and stacked MoS2 nanosheets anchored to the surface of TiO2 nanoparticles. Lastly, in-situ FTIR spectroscopy investigation gives insights into the nature of the oligomerized species, showing that the formation of both polyenic and aromatic systems can be taken into account, being their formation promoted by both Ti and Mo catalytic sites. This finding gives an opportunity for the assembly of extended polyenic, polyaromatic, or mixed domains firmly attached at the surface of photoactive materials. The presented approach, somehow different from the carbon adding or doping processes of TiO2, is of potential interest for the advanced green chemistry and energy conversion/transport applications.

Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

Directory of Open Access Journals (Sweden)

Chi-Fai Lau

2014-01-01

Full Text Available Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD, there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ, but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

Formation of semisolid, oligomerized aqueous SOA: lab simulations of cloud processing.

Science.gov (United States)

Hawkins, Lelia N; Baril, Molly J; Sedehi, Nahzaneen; Galloway, Melissa M; De Haan, David O; Schill, Gregory P; Tolbert, Margaret A

2014-02-18

Glyoxal, methylglyoxal, glycolaldehyde, and hydroxyacetone form N-containing and oligomeric compounds during simulated cloud processing with small amines. Using a novel hygroscopicity tandem differential mobility analysis (HTDMA) system that allows varied humidification times, the hygroscopic growth (HG) of each of the resulting products of simulated cloud processing was measured. Continuous water uptake (gradual deliquescence) was observed beginning at ∼ 40% RH for all aldehyde-methylamine products. Particles containing ionic reaction products of either glyoxal or glycine were most hygroscopic, with HG between 1.16 and 1.20 at 80% RH. Longer humidification times (up to 20 min) produced an increase in growth factors for glyoxal-methylamine (19% by vol) and methylglyoxal-methylamine (8% by vol) aerosol, indicating that unusually long equilibration times can be required for HTDMA measurements of such particles. Glyoxal- and methylglyoxal-methylamine aerosol particles shattered in Raman microscopy impact-flow experiments, revealing that the particles were semisolid. Similar experiments on glycolaldehyde- and hydroxyacetone-methylamine aerosol found that the aerosol particles were liquid when dried for glyoxal > glycolaldehyde = hydroxyacetone, likely caused by the speed of oligomer formation in each system.

Assembly of the intrinsic factor domains and oligomerization of the protein in the presence of cobalamin

DEFF Research Database (Denmark)

Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars

2004-01-01

oligomerized. A mixture of two fragments IF(30) + IF(20) and Cbl produced a firm complex, IF(30+20).Cbl, which could not associate to dimers. In contrast to IF(30+20).Cbl, the saturated full-length monomers IF(50).Cbl dimerized with K(d) approximately 1 microM. We suggest a two-domain organization of the full......-length protein, where two distant units, IF(30) and IF(20), can be assembled only by Cbl. They are connected by a protease-sensitive link, whose native structure is likely to be important for dimerization. However, linkage between two domains is not compulsory for Cbl binding. Advantages of the two...

Inference and learning in sparse systems with multiple states

International Nuclear Information System (INIS)

Braunstein, A.; Ramezanpour, A.; Zhang, P.; Zecchina, R.

2011-01-01

We discuss how inference can be performed when data are sampled from the nonergodic phase of systems with multiple attractors. We take as a model system the finite connectivity Hopfield model in the memory phase and suggest a cavity method approach to reconstruct the couplings when the data are separately sampled from few attractor states. We also show how the inference results can be converted into a learning protocol for neural networks in which patterns are presented through weak external fields. The protocol is simple and fully local, and is able to store patterns with a finite overlap with the input patterns without ever reaching a spin-glass phase where all memories are lost.

A comparative study of symptoms in multiple lacunar state and MRI findings

International Nuclear Information System (INIS)

Shibata, Youichi

1993-01-01

A multiple lacunar state is considered to cause gait disturbance, pseudobulbar palsy, or silent stroke. In the present study, these symptoms is multiple lacunar state and the incidences of abnormal findings on magnetic resonance imaging (MRI) were investigated comparatively. Thirty-eight patients (23 males and 15 females; average age 73.6 y.o.) with ischemic cerebral lesions on T 2 weighted images of MRI were studied. In the group with gait disturbance only, the incidences of widening of the ventricular system and periventricular hyperintensity (PVH) around the frontal horn were significantly high compared with the group with silent stroke (p<0.01, p<0.005; respectively), and hyperintensity area of the semioval center were demonstrated prominently in the regions perfused by anterior cerebral artery. In the group with pseudobulbar palsy only, the incidences of PVH around the posterior part of the lateral ventricle and hyperintensity area of the basal ganglion region were significantly high as compared with the group with silent stroke (p<0.01, p<0.05; respectively), and hyperintensity area of the semioval center were demonstrated prominently in the regions perfused by middle cerebral artery. (author)

A comparative study of symptoms in multiple lacunar state and MRI findings

Energy Technology Data Exchange (ETDEWEB)

Shibata, Youichi (Saint Marianna Univ., Kawasaki (Japan). School of Medicine)

1993-10-01

A multiple lacunar state is considered to cause gait disturbance, pseudobulbar palsy, or silent stroke. In the present study, these symptoms is multiple lacunar state and the incidences of abnormal findings on magnetic resonance imaging (MRI) were investigated comparatively. Thirty-eight patients (23 males and 15 females; average age 73.6 y.o.) with ischemic cerebral lesions on T[sub 2] weighted images of MRI were studied. In the group with gait disturbance only, the incidences of widening of the ventricular system and periventricular hyperintensity (PVH) around the frontal horn were significantly high compared with the group with silent stroke (p<0.01, p<0.005; respectively), and hyperintensity area of the semioval center were demonstrated prominently in the regions perfused by anterior cerebral artery. In the group with pseudobulbar palsy only, the incidences of PVH around the posterior part of the lateral ventricle and hyperintensity area of the basal ganglion region were significantly high as compared with the group with silent stroke (p<0.01, p<0.05; respectively), and hyperintensity area of the semioval center were demonstrated prominently in the regions perfused by middle cerebral artery. (author).

(Pressure + volume + temperature) properties for binary oligomeric solutions of poly(ethylene glycol mono-4-octylphenyl ether) with 1-octanol or acetophenone at pressures up to 50 MPa

International Nuclear Information System (INIS)

Lee, M.-J.; Ku, T.-J.; Lin Homu

2009-01-01

Densities were measured with a high-pressure densitometer for two binary oligomeric systems of poly(ethylene glycol mono-4-octylphenyl ether) (PEGOPE) with 1-octanol or acetophenone at temperatures from 298.15 K to 348.15 K and pressures up to 50 MPa. While the excess volumes are negative in (acetophenone + PEGOPE) over the entire composition range, those are found to change from positive to negative with increasing mole fraction of the solvent in (1-octanol + PEGOPE). The pressure-effect on the liquid densities can be represented accurately by the Tait equation. Moreover, an empirical equation with two characteristic parameters correlates well the PVT data over the entire experimental conditions for each binary system. The experimental specific volumes were also correlated with the Flory-Orwoll-Vrij (FOV) and the Schotte equations of state to within the experimental uncertainty.

Real-Time Radar-Based Tracking and State Estimation of Multiple Non-Conformant Aircraft

Science.gov (United States)

Cook, Brandon; Arnett, Timothy; Macmann, Owen; Kumar, Manish

2017-01-01

In this study, a novel solution for automated tracking of multiple unknown aircraft is proposed. Many current methods use transponders to self-report state information and augment track identification. While conformant aircraft typically report transponder information to alert surrounding aircraft of its state, vehicles may exist in the airspace that are non-compliant and need to be accurately tracked using alternative methods. In this study, a multi-agent tracking solution is presented that solely utilizes primary surveillance radar data to estimate aircraft state information. Main research challenges include state estimation, track management, data association, and establishing persistent track validity. In an effort to realize these challenges, techniques such as Maximum a Posteriori estimation, Kalman filtering, degree of membership data association, and Nearest Neighbor Spanning Tree clustering are implemented for this application.

Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain

International Nuclear Information System (INIS)

Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A.

2011-01-01

With the aim of forming the ‘lock-washer’ conformation of the origin-binding domain of SV40 large T antigen in solution, using structure-based analysis an intermolecular disulfide bridge was engineered into the origin-binding domain to generate higher order oligomers in solution. The 1.7 Å resolution structure shows that the mutant forms a spiral in the crystal and has the de novo disulfide bond at the protein interface, although structural rearrangements at the interface are observed relative to the wild type. The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS–PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner

Changes in the oligomerization potential of the division inhibitor UgtP co-ordinate Bacillus subtilis cell size with nutrient availability.

Science.gov (United States)

Chien, An-Chun; Zareh, Shannon Kian Gharabiklou; Wang, Yan Mei; Levin, Petra Anne

2012-11-01

How cells co-ordinate size with growth and development is a major, unresolved question in cell biology. In previous work we identified the glucosyltransferase UgtP as a division inhibitor responsible for increasing the size of Bacillus subtilis cells under nutrient-rich conditions. In nutrient-rich medium, UgtP is distributed more or less uniformly throughout the cytoplasm and concentrated at the cell poles and/or the cytokinetic ring. Under these conditions, UgtP interacts directly with FtsZ to inhibit division and increase cell size. Conversely, under nutrient-poor conditions, UgtP is sequestered away from FtsZ in punctate foci, and division proceeds unimpeded resulting in a reduction in average cell size. Here we report that nutrient-dependent changes in UgtP's oligomerization potential serve as a molecular rheostat to precisely co-ordinate B. subtilis cell size with nutrient availability. Our data indicate UgtP interacts with itself and the essential cell division protein FtsZ in a high-affinity manner influenced in part by UDP glucose, an intracellular proxy for nutrient availability. These findings support a model in which UDP-glc-dependent changes in UgtP's oligomerization potential shift the equilibrium between UgtP•UgtP and UgtP•FtsZ, fine-tuning the amount of FtsZ available for assembly into the cytokinetic ring and with it cell size. © 2012 Blackwell Publishing Ltd.

IntraGolgi distribution of the Conserved Oligomeric Golgi (COG) complex

International Nuclear Information System (INIS)

Vasile, Eliza; Oka, Toshihiko; Ericsson, Maria; Nakamura, Nobuhiro; Krieger, Monty

2006-01-01

The Conserved Oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein involved in membrane trafficking and glycoconjugate synthesis. COG appears to participate in retrograde vesicular transport and is required to maintain normal Golgi structure and function. COG mutations interfere with normal transport, distribution, and/or stability of Golgi proteins associated with glycoconjugate synthesis and trafficking, and lead to failure of spermatogenesis in Drosophila melanogaster, misdirected migration of gonadal distal tip cells in Caenorhabditis elegans, and type II congenital disorders of glycosylation in humans. The mechanism by which COG influences Golgi structure and function is unclear. Immunogold electron microscopy was used to visualize the intraGolgi distribution of a functional, hemagglutinin epitope-labeled COG subunit, Cog1-HA, that complements the Cog1-deficiency in Cog1-null Chinese hamster ovary cells. COG was found to be localized primarily on or in close proximity to the tips and rims of the Golgi's cisternae and their associated vesicles and on vesicles and vesiculo-tubular structures seen on both the cis and trans-Golgi Network faces of the cisternal stacks, in some cases on COPI containing vesicles. These findings support the proposal that COG is directly involved in controlling vesicular retrograde transport of Golgi resident proteins throughout the Golgi apparatus

Joint estimation over multiple individuals improves behavioural state inference from animal movement data.

Science.gov (United States)

Jonsen, Ian

2016-02-08

State-space models provide a powerful way to scale up inference of movement behaviours from individuals to populations when the inference is made across multiple individuals. Here, I show how a joint estimation approach that assumes individuals share identical movement parameters can lead to improved inference of behavioural states associated with different movement processes. I use simulated movement paths with known behavioural states to compare estimation error between nonhierarchical and joint estimation formulations of an otherwise identical state-space model. Behavioural state estimation error was strongly affected by the degree of similarity between movement patterns characterising the behavioural states, with less error when movements were strongly dissimilar between states. The joint estimation model improved behavioural state estimation relative to the nonhierarchical model for simulated data with heavy-tailed Argos location errors. When applied to Argos telemetry datasets from 10 Weddell seals, the nonhierarchical model estimated highly uncertain behavioural state switching probabilities for most individuals whereas the joint estimation model yielded substantially less uncertainty. The joint estimation model better resolved the behavioural state sequences across all seals. Hierarchical or joint estimation models should be the preferred choice for estimating behavioural states from animal movement data, especially when location data are error-prone.

Dynamical and technological consequences of multiple isolas of steady states in a catalytic fluidised-bed reactor

Directory of Open Access Journals (Sweden)

Bizon Katarzyna

2017-09-01

Full Text Available Steady-state characteristics of a catalytic fluidised bed reactor and its dynamical consequences are analyzed. The occurrence of an untypical steady-state structure manifesting in a form of multiple isolas is described. A two-phase bubbling bed model is used for a quantitative description of the bed of catalyst. The influence of heat exchange intensity and a fluidisation ratio onto the generation of isolated solution branches is presented for two kinetic schemes. Dynamical consequences of the coexistence of such untypical branches of steady states are presented. The impact of linear growth of the fluidisation ratio and step change of the cooling medium temperature onto the desired product yield is analyzed. The results presented in this study confirm that the identification of a region of the occurrence of multiple isolas is important due to their strong impact both on the process start-up and its control.

[Multiple-Victimisation due to Armed Conflict and Emotional Distress in the State of Magdalena, Colombia].

Science.gov (United States)

Campo-Arias, Adalberto; Sanabria, Adriana R; Ospino, Anyelly; Guerra, Valeria M; Caamaño, Beatriz H

Emotional distress is common in Colombian armed conflict victims. Multiple-victimisation is associated with an increase in emotional distress than victimisation due a single event. However, the association between poly-victimisation and emotional distress among victims of the armed conflict in Colombia has not been documented. To study the association between multiple-victimisation and emotional distress in victims of armed conflict in the State of Magdalena, Colombia. A cross-sectional study was designed, with a secondary analysis of registration of the Psychosocial Care Program and Victim Integral Health (PAPSIVI) in the State of Magdalena, from 2013 to 2014. The profile formula grouped demographic variables, victimising events, and a set of symptoms of emotional distress (perceived discrimination, depressive and anxiety-stress). Odds ratio (OR, 95%CI) were established as measures of association. A total of 943 people were included, with 67.4% women, and ages between18 and 94 years (mean 47.9±14.2). A total of 109 (11.7%) suffered from multiple victimisation. Multiple victimisation events were associated with more emotional distress, depressive symptoms (OR=1.5; 95%CI, 1.3-1.8), perceived stigma (OR=1.3; 95%CI, 1.1-1.5), and anxiety-stress (OR=1.2; 95%CI 1.0-1.4) than a single event. There is more emotional distress in multiple victimisations than in a single victimisation event during armed conflict in this region of Colombia. Further studies are required on this topic. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Effects of Bentonite on p-Methoxybenzyl Acetate: A Theoretical Model for Oligomerization via an Electrophilic-Substitution Mechanism

Directory of Open Access Journals (Sweden)

Manuel Salmón

2011-02-01

Full Text Available Tonsil Actisil FF, a commercial bentonitic clay, promotes the formation of a series of electrophilic-aromatic-substitution products from para-methoxybenzyl acetate in carbon disulfide. The molecules obtained correspond to linear isomeric dimers, trimers, tetramers and a pentamer, according to their spectroscopic data. A clear indication of the title mechanistic pathway for the oligomerization growth was obtained from the analysis of a set of computational-chemistry calculations using the density-functional-theory level B3LYP/6-311++G(d,p. The corresponding conclusions were based on the computed dipole moments, the HOMO/LUMO distributions, and a natural-populations analysis of the studied molecules.

What Factors Influence States' Capacity to Report Children's Health Care Quality Measures? A Multiple-Case Study.

Science.gov (United States)

Christensen, Anna L; Petersen, Dana M; Burton, Rachel A; Forsberg, Vanessa C; Devers, Kelly J

2017-01-01

Objectives The objective of this study was to describe factors that influence the ability of state Medicaid agencies to report the Centers for Medicare & Medicaid Services' (CMS) core set of children's health care quality measures (Child Core Set). Methods We conducted a multiple-case study of four high-performing states participating in the Children's Health Insurance Program Reauthorization Act (CHIPRA) Quality Demonstration Grant Program: Illinois, Maine, Pennsylvania, and Oregon. Cases were purposively selected for their diverse measurement approaches and used data from 2010 to 2015, including 154 interviews, semiannual grant progress reports, and annual public reports on Child Core Set measures. We followed Yin's multiple-case study methodology to describe how and why each state increased the number of measures reported to CMS. Results All four states increased the number of Child Core Set measures reported to CMS during the grant period. Each took a different approach to reporting, depending on the available technical, organizational, and behavioral inputs in the state. Reporting capacity was influenced by a state's Medicaid data availability, ability to link to other state data systems, past experience with quality measurement, staff time and technical expertise, and demand for the measures. These factors were enhanced by CHIPRA Quality Demonstration grant funding and other federal capacity building activities, as hypothesized in our conceptual framework. These and other states have made progress reporting the Child Core Set since 2010. Conclusion With financial support and investment in state data systems and organizational factors, states can overcome challenges to reporting most of the Child Core Set measures.

The long N-terminus of the human monocarboxylate transporter 8 is a target of ubiquitin-dependent proteasomal degradation which regulates protein expression and oligomerization capacity.

Science.gov (United States)

Zwanziger, Denise; Schmidt, Mathias; Fischer, Jana; Kleinau, Gunnar; Braun, Doreen; Schweizer, Ulrich; Moeller, Lars Christian; Biebermann, Heike; Fuehrer, Dagmar

2016-10-15

Monocarboxylate transporter 8 (MCT8) equilibrates thyroid hormones between the extra- and the intracellular sides. MCT8 exists either with a short or a long N-terminus, but potential functional differences between both variants are yet not known. We, therefore, generated MCT8 constructs which are different in N-terminal length: MCT8(1-613), MCT8(25-613), MCT8(49-613) and MCT8(75-613). The M75G substitution prevents translation of MCT8(75-613) and ensures expression of full-length MCT8 protein. The K56G substitution was made to prevent ubiquitinylation. Cell-surface expression, localization and proteasomal degradation were investigated using C-terminally GFP-tagged MCT8 constructs (HEK293 and MDCK1 cells) and oligomerization capacity was determined using N-terminally HA- and C-terminally FLAG-tagged MCT8 constructs (COS7 cells). MCT8(1-613)-GFP showed a lower protein expression than the shorter MCT8(75-613)-GFP protein. The proteasome inhibitor lactacystin increased MCT8(1-613)-GFP protein amount, suggesting proteasomal degradation of MCT8 with the long N-terminus. Ubiquitin conjugation of MCT8(1-613)-GFP was found by immuno-precipitation. A diminished ubiquitin conjugation caused by K56G substitution resulted in increased MCT8(1-613)-GFP protein expression. Sandwich ELISA was performed to investigate if the bands at higher molecular weight observed in Western blot analysis are due to MCT8 oligomerization, which was indeed shown. Our data imply a role of the long N-terminus of MCT8 as target of ubiquitin-dependent proteasomal degradation affecting MCT8 amount and subsequently oligomerization capacity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transparent cellulose/polyhedral oligomeric silsesquioxane nanocomposites with enhanced UV-shielding properties.

Science.gov (United States)

Feng, Ye; Zhang, Jinming; He, Jiasong; Zhang, Jun

2016-08-20

The solubility of eight types of polyhedral oligomeric silsesquioxane (POSS) derivatives in an ionic liquid 1-allyl-3-methylimidazolium chloride (AmimCl) and the dispersion of POSS in cellulose matrix were examined. Only a special POSS containing both aminophenyl and nitrophenyl groups (POSS-AN, NH2:NO2=2:6) was selected to prepare nanocomposites, because of its good solubility in AmimCl and high stability during the preparation process. POSS-AN nanoparticles were uniformly dispersed in a cellulose matrix with a size of 30-40nm, and so the resultant cellulose/POSS-AN nanocomposite films were transparent. The mechanical properties of the films achieved a maximum tensile strength of 190MPa after addition of 2wt% POSS-AN. Interestingly, all of the cellulose/POSS-AN films exhibited high UV-absorbing capability. For the 15wt% cellulose/POSS-AN film, the transmittance of UVA (315-400nm) and UVB (280-315nm) was only 9.1% and nearly 0, respectively. The UV aging and shielding experiments showed that the transparent cellulose/POSS-AN nanocomposite films possessed anti-UV aging and UV shielding properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

In-situ photocrosslinkable nanohybrid elastomer based on polybutadiene/polyhedral oligomeric silsesquioxane

Energy Technology Data Exchange (ETDEWEB)

Mirmohammadi, Seyed Amin, E-mail: mirmohammadi.sa@gmail.com [Department of Polymerization Engineering, Iran Polymer and Petrochemical Institute (IPPI), P. O. Box: 14965/115, Tehran (Iran, Islamic Republic of); Nekoomanesh-Haghighi, Mehdi, E-mail: m.nekoomanesh@ippi.ac.ir [Department of Polymerization Engineering, Iran Polymer and Petrochemical Institute (IPPI), P. O. Box: 14965/115, Tehran (Iran, Islamic Republic of); Mohammadian Gezaz, Somayyeh [Department of Chemical Engineering, Payame Noor University (PNU), P. O. Box: 19395-3697, Tehran (Iran, Islamic Republic of); Bahri-Laleh, Naeimeh [Department of Polymerization Engineering, Iran Polymer and Petrochemical Institute (IPPI), P. O. Box: 14965/115, Tehran (Iran, Islamic Republic of); Atai, Mohammad [Department of Polymer Science, Iran Polymer and Petrochemical Institute (IPPI), P. O. Box: 14965/115, Tehran (Iran, Islamic Republic of)

2016-11-01

Hydroxyl functionalized nano-sized POSS or ethyleneglycol as diol monomers was incorporated to hydroxyl-terminated polybutadiene (HTPBD) chain in the presence of fumaryl chloride as extender. Blue light photocrosslinking system based on camphorquinone (photoinitiator) and dimethylaminoethyl methacrylate (accelerator) was applied to cure these two synthesized fumarate based macromers. Self-crosslinkability of unsaturated macromers and also crosslinking in presence of a reactive diluent were investigated in absence and presence of 1,4-butanediol dimethacrylate, respectively. Finally, photocured samples were characterized by XRD, SEM, equilibrium swelling study, TGA, DMTA, AFM and cell culture. The results showed that incorporation of POSS nanoparticle into the polymer matrix with a perfect distribution and dispersion can enhance thermal stability, mechanical and biocompatibility properties which can prove a good potential of this in-situ photocrosslinkable nanohybrid in medical applications. - Highlights: • Polyhedral oligomeric silsesquioxane was incorporated to HTPBD by fumaryl chloride as extender. • A reactive diluent was used to improve photocrosslinking process of the unsaturated nanohybrid elastomers. • Nanohybrids showed enhanced properties such as thermal stability, mechanical and biocompatibility. • Improved properties were obtained for photocured samples in presence of reactive diluent.

Multiple Climate States of Habitable Exoplanets: The Role of Obliquity and Irradiance

International Nuclear Information System (INIS)

Kilic, C.; Raible, C. C.; Stocker, T. F.

2017-01-01

Stable, steady climate states on an Earth-size planet with no continents are determined as a function of the tilt of the planet’s rotation axis (obliquity) and stellar irradiance. Using a general circulation model of the atmosphere coupled to a slab ocean and a thermodynamic sea ice model, two states, the Aquaplanet and the Cryoplanet, are found for high and low stellar irradiance, respectively. In addition, four stable states with seasonally and perennially open water are discovered if comprehensively exploring a parameter space of obliquity from 0° to 90° and stellar irradiance from 70% to 135% of the present-day solar constant. Within 11% of today’s solar irradiance, we find a rich structure of stable states that extends the area of habitability considerably. For the same set of parameters, different stable states result if simulations are initialized from an aquaplanet or a cryoplanet state. This demonstrates the possibility of multiple equilibria, hysteresis, and potentially rapid climate change in response to small changes in the orbital parameters. The dynamics of the atmosphere of an aquaplanet or a cryoplanet state is investigated for similar values of obliquity and stellar irradiance. The atmospheric circulation substantially differs in the two states owing to the relative strength of the primary drivers of the meridional transport of heat and momentum. At 90° obliquity and present-day solar constant, the atmospheric dynamics of an Aquaplanet state and one with an equatorial ice cover is analyzed.

Multiple Climate States of Habitable Exoplanets: The Role of Obliquity and Irradiance

Energy Technology Data Exchange (ETDEWEB)

Kilic, C.; Raible, C. C.; Stocker, T. F., E-mail: stocker@climate.unibe.ch [Climate and Environmental Physics, Physics Institute, University of Bern (Switzerland)

2017-08-01

Stable, steady climate states on an Earth-size planet with no continents are determined as a function of the tilt of the planet’s rotation axis (obliquity) and stellar irradiance. Using a general circulation model of the atmosphere coupled to a slab ocean and a thermodynamic sea ice model, two states, the Aquaplanet and the Cryoplanet, are found for high and low stellar irradiance, respectively. In addition, four stable states with seasonally and perennially open water are discovered if comprehensively exploring a parameter space of obliquity from 0° to 90° and stellar irradiance from 70% to 135% of the present-day solar constant. Within 11% of today’s solar irradiance, we find a rich structure of stable states that extends the area of habitability considerably. For the same set of parameters, different stable states result if simulations are initialized from an aquaplanet or a cryoplanet state. This demonstrates the possibility of multiple equilibria, hysteresis, and potentially rapid climate change in response to small changes in the orbital parameters. The dynamics of the atmosphere of an aquaplanet or a cryoplanet state is investigated for similar values of obliquity and stellar irradiance. The atmospheric circulation substantially differs in the two states owing to the relative strength of the primary drivers of the meridional transport of heat and momentum. At 90° obliquity and present-day solar constant, the atmospheric dynamics of an Aquaplanet state and one with an equatorial ice cover is analyzed.

Multiple steady states detection in a packed-bed reactive distillation column using bifurcation analysis

DEFF Research Database (Denmark)

Ramzan, Naveed; Faheem, Muhammad; Gani, Rafiqul

2010-01-01

A packed reactive distillation column producing ethyl tert-butyl ether from tert-butyl alcohol and ethanol was simulated for detection of multiple steady states using Aspen Plus®. A rate-based approach was used to make the simulation model more realistic. A base-case was first developed and fine...

Eicosanoyl-5-hydroxytryptamide (EHT prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid.

Directory of Open Access Journals (Sweden)

Kesava Asam

Full Text Available Soluble forms of oligomeric beta-amyloid (Aβ are thought to play a central role in Alzheimer's disease (AD. Transgenic manipulation of methylation of the serine/threonine protein phosphatase, PP2A, was recently shown to alter the sensitivity of mice to AD-related impairments resulting from acute exposure to elevated levels of Aβ. In addition, eicosanoyl-5-hydroxytryptamide (EHT, a naturally occurring component from coffee beans that modulates PP2A methylation, was shown to confer therapeutic benefits in rodent models of AD and Parkinson's disease. Here, we tested the hypothesis that EHT protects animals from the pathological effects of exposure to elevated levels of soluble oligomeric Aβ. We treated mice with EHT-containing food at two different doses and assessed the sensitivity of these animals to Aβ-induced behavioral and electrophysiological impairments. We found that EHT administration protected animals from Aβ-induced cognitive impairments in both a radial-arm water maze and contextual fear conditioning task. We also found that both chronic and acute EHT administration prevented Aβ-induced impairments in long-term potentiation. These data add to the accumulating evidence suggesting that interventions with pharmacological agents, such as EHT, that target PP2A activity may be therapeutically beneficial for AD and other neurological conditions.

Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization.

Science.gov (United States)

Li, Xin; Shu, Chang; Yi, Guanghui; Chaton, Catherine T; Shelton, Catherine L; Diao, Jiasheng; Zuo, Xiaobing; Kao, C Cheng; Herr, Andrew B; Li, Pingwei

2013-12-12

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-β gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and IFN-β reporter assays of cGAS mutants demonstrated that interactions at both DNA binding sites are essential for cGAS activation. Mutagenesis and DNA binding studies showed that the two sites bind dsDNA cooperatively and that site B plays a critical role in DNA binding. The structure of mouse cGAS bound to dsDNA and 2',5' cGAMP provided insight into the catalytic mechanism of cGAS. These results demonstrated that cGAS is activated by dsDNA-induced oligomerization. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of redox environment on the oligomerization of higher molecular weight adiponectin

Directory of Open Access Journals (Sweden)

Nuñez Martha

2011-05-01

Full Text Available Abstract Background Adiponectin is an adipocyte-secreted hormone with insulin-sensitizing and anti-inflammatory actions. The assembly of trimeric, hexameric, and higher molecular weight (HMW species of adiponectin is a topic of significant interest because physiological actions of adiponectin are oligomer-specific. In addition, adiponectin assembly is an example of oxidative oligomerization of multi-subunit protein complexes in endoplasmic reticulum (ER. Results We previously reported that trimers assemble into HMW adiponectin via intermediates stabilized by disulfide bonds, and complete oxidation of available cysteines locks adiponectin in hexameric conformation. In this study, we examined the effects of redox environment on the rate of oligomer formation and the distribution of oligomers. Reassembly of adiponectin under oxidizing conditions accelerated disulfide bonding but favored formation of hexamers over the HMW species. Increased ratios of HMW to hexameric adiponectin could be achieved rapidly under oxidizing conditions by promoting disulfide rearrangement. Conclusions Based upon these observations, we propose oxidative assembly of multi-subunit adiponectin complexes in a defined and stable redox environment is favored under oxidizing conditions coupled with high rates of disulfide rearrangement.

Solid-State Neutron Multiplicity Counting System Using Commercial Off-the-Shelf Semiconductor Detectors

Energy Technology Data Exchange (ETDEWEB)

Rozhdestvenskyy, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-08-09

This work iterates on the first demonstration of a solid-state neutron multiplicity counting system developed at Lawrence Livermore National Laboratory by using commercial off-the-shelf detectors. The system was demonstrated to determine the mass of a californium-252 neutron source within 20% error requiring only one-hour measurement time with 20 cm² of active detector area.

Homogeneous Stabilizer by State Feedback for Switched Nonlinear Systems Using Multiple Lyapunov Functions’ Approach

Directory of Open Access Journals (Sweden)

Hui Ye

2017-01-01

Full Text Available This paper investigates the problem of global stabilization for a class of switched nonlinear systems using multiple Lyapunov functions (MLFs. The restrictions on nonlinearities are neither linear growth condition nor Lipschitz condition with respect to system states. Based on adding a power integrator technique, we design homogeneous state feedback controllers of all subsystems and a switching law to guarantee that the closed-loop system is globally asymptotically stable. Finally, an example is given to illustrate the validity of the proposed control scheme.

S. aureus MscL is a pentamer in vivo but of variable stoichiometries in vitro: implications for detergent-solubilized membrane proteins.

Directory of Open Access Journals (Sweden)

Michael R Dorwart

Full Text Available While the bacterial mechanosensitive channel of large conductance (MscL is the best studied biological mechanosensor and serves as a paradigm for how a protein can sense and respond to membrane tension, the simple matter of its oligomeric state has led to debate, with models ranging from tetramers to hexamers. Indeed, two different oligomeric states of the bacterial mechanosensitive channel MscL have been resolved by X-ray crystallography: The M. tuberculosis channel (MtMscL is a pentamer, while the S. aureus protein (SaMscL forms a tetramer. Because several studies suggest that, like MtMscL, the E. coli MscL (EcoMscL is a pentamer, we re-investigated the oligomeric state of SaMscL. To determine the structural organization of MscL in the cell membrane we developed a disulfide-trapping approach. Surprisingly, we found that virtually all SaMscL channels in vivo are pentameric, indicating this as the physiologically relevant and functional oligomeric state. Complementing our in vivo results, we purified SaMscL and assessed its oligomeric state using three independent approaches (sedimentation equilibrium centrifugation, crosslinking, and light scattering and established that SaMscL is a pentamer when solubilized in Triton X-100 and C(8E(5 detergents. However, performing similar experiments on SaMscL solubilized in LDAO, the detergent used in the crystallographic study, confirmed the tetrameric oligomerization resolved by X-ray crystallography. We further demonstrate that this stoichiometric shift is reversible by conventional detergent exchange experiments. Our results firmly establish the pentameric organization of SaMscL in vivo. Furthermore they demonstrate that detergents can alter the subunit stoichiometry of membrane protein complexes in vitro; thus, in vivo assays are necessary to firmly establish a membrane protein's true functionally relevant oligomeric state.

S. aureus MscL is a pentamer in vivo but of variable stoichiometries in vitro: implications for detergent-solubilized membrane proteins.

Science.gov (United States)

Dorwart, Michael R; Wray, Robin; Brautigam, Chad A; Jiang, Youxing; Blount, Paul

2010-12-07

While the bacterial mechanosensitive channel of large conductance (MscL) is the best studied biological mechanosensor and serves as a paradigm for how a protein can sense and respond to membrane tension, the simple matter of its oligomeric state has led to debate, with models ranging from tetramers to hexamers. Indeed, two different oligomeric states of the bacterial mechanosensitive channel MscL have been resolved by X-ray crystallography: The M. tuberculosis channel (MtMscL) is a pentamer, while the S. aureus protein (SaMscL) forms a tetramer. Because several studies suggest that, like MtMscL, the E. coli MscL (EcoMscL) is a pentamer, we re-investigated the oligomeric state of SaMscL. To determine the structural organization of MscL in the cell membrane we developed a disulfide-trapping approach. Surprisingly, we found that virtually all SaMscL channels in vivo are pentameric, indicating this as the physiologically relevant and functional oligomeric state. Complementing our in vivo results, we purified SaMscL and assessed its oligomeric state using three independent approaches (sedimentation equilibrium centrifugation, crosslinking, and light scattering) and established that SaMscL is a pentamer when solubilized in Triton X-100 and C(8)E(5) detergents. However, performing similar experiments on SaMscL solubilized in LDAO, the detergent used in the crystallographic study, confirmed the tetrameric oligomerization resolved by X-ray crystallography. We further demonstrate that this stoichiometric shift is reversible by conventional detergent exchange experiments. Our results firmly establish the pentameric organization of SaMscL in vivo. Furthermore they demonstrate that detergents can alter the subunit stoichiometry of membrane protein complexes in vitro; thus, in vivo assays are necessary to firmly establish a membrane protein's true functionally relevant oligomeric state.

Predicting hearing thresholds and occupational hearing loss with multiple-frequency auditory steady-state responses.

Science.gov (United States)

Hsu, Ruey-Fen; Ho, Chi-Kung; Lu, Sheng-Nan; Chen, Shun-Sheng

2010-10-01

An objective investigation is needed to verify the existence and severity of hearing impairments resulting from work-related, noise-induced hearing loss in arbitration of medicolegal aspects. We investigated the accuracy of multiple-frequency auditory steady-state responses (Mf-ASSRs) between subjects with sensorineural hearing loss (SNHL) with and without occupational noise exposure. Cross-sectional study. Tertiary referral medical centre. Pure-tone audiometry and Mf-ASSRs were recorded in 88 subjects (34 patients had occupational noise-induced hearing loss [NIHL], 36 patients had SNHL without noise exposure, and 18 volunteers were normal controls). Inter- and intragroup comparisons were made. A predicting equation was derived using multiple linear regression analysis. ASSRs and pure-tone thresholds (PTTs) showed a strong correlation for all subjects (r = .77 ≈ .94). The relationship is demonstrated by the equationThe differences between the ASSR and PTT were significantly higher for the NIHL group than for the subjects with non-noise-induced SNHL (p tool for objectively evaluating hearing thresholds. Predictive value may be lower in subjects with occupational hearing loss. Regardless of carrier frequencies, the severity of hearing loss affects the steady-state response. Moreover, the ASSR may assist in detecting noise-induced injury of the auditory pathway. A multiple linear regression equation to accurately predict thresholds was shown that takes into consideration all effect factors.

Quantized levitation states of superconducting multiple-ring systems

International Nuclear Information System (INIS)

Haley, S.B.; Fink, H.J.

1996-01-01

The quantized levitation, trapped, and suspension states of a magnetic microsphere held in equilibrium by two fixed superconducting (SC) microrings are calculated by minimizing the free energy of the system. Each state is a discrete function of two independent fluxoid quantum numbers of the rings. When the radii of the SC rings are of the same order as the Ginzburg-Landau coherence length ξ(T), the system exhibits a small set of gravity and temperature-dependent levels. The levels of a weakly magnetized particle are sensitive functions of the gravitational field, indicating potential application as an accelerometer, and for trapping small magnetic particles in outer space or on Earth. The equilibrium states of a SC ring levitated by another SC ring are also calculated. copyright 1996 The American Physical Society

Simultaneous separation and identification of oligomeric procyanidins and anthocyanin-derived pigments in raw red wine by HPLC-UV-ESI-MSn.

Science.gov (United States)

Pati, S; Losito, I; Gambacorta, G; La Notte, E; Palmisano, F; Zambonin, P G

2006-07-01

Samples of raw red wine (Primitivo di Manduria, Apulia, Southern Italy) were analysed without any pre-treatment (except 1:2 dilution with water) using HPLC with detection based on UV absorbance and Electrospray Ionisation Sequential Mass Spectrometry (ESI-MSn, with n = 1-3) in a series configuration. In particular, absorbance at 520 nm was monitored for UV detection in order to identify pigments responsible for wine colour. On the other hand, two subsequent stages of MS detection based on positive ions were adopted. The first consisted of an explorative MS acquisition, aimed at the individuation of the m/z ratios for positively charged compounds; the second was based on fragmentation of the detected ions within an ion trap analyser, followed by MS/MS and, if required, MS3 acquisitions. The synergy between UV detection and MSn analysis led to the identification of 41 pigments, which can be classified into five groups: grape anthocyanins, pyranoanthocyanins, vinyl-linked anthocyanin-flavanol pigments, ethyl-bridged anthocyanin-flavanol pigments and flavanol-anthocyanin compounds. Many isomeric and oligomeric structures were found within each group. A further class of compounds, not absorbing in the visible spectrum, could be also characterised by ESI-MSn and corresponded to B-type procyanidins, i.e. proanthocyanidins arising from C4-->C8/C4-->C6 couplings between catechin or epicatechin units. In particular, oligomeric structures (from dimers to pentamers), often present with several isomers, were identified and their fragmentation patterns clarified.

Human proton coupled folic acid transporter is a monodisperse oligomer in the lauryl maltose neopentyl glycol solubilized state.

Science.gov (United States)

Aduri, Nanda G; Ernst, Heidi A; Prabhala, Bala K; Bhatt, Shweta; Boesen, Thomas; Gajhede, Michael; Mirza, Osman

2018-01-08

The human proton coupled folic acid transporter PCFT is the major import route for dietary folates. Mutations in the gene encoding PCFT cause hereditary folic acid malabsorption, which manifests itself by compromised folate absorption from the intestine and also in impaired folate transport into the central nervous system. Since its recent discovery, PCFT has been the subject of numerous biochemical studies aiming at understanding its structure and mechanism. One major focus has been its oligomeric state, with some reports supporting oligomers and others a monomer. Here, we report the overexpression and purification of recombinant PCFT. Following detergent screening, n-Dodecyl β-D-maltoside (DDM) and lauryl maltose neopentyl glycol (LMNG) were chosen for further work as they exhibited the most optimal solubilization. We found that purified detergent solubilized PCFT was able to bind folic acid, thus indicating a functionally active protein. Size exclusion chromatography showed that PCFT in DDM was polydisperse; the LMNG preparation was clearly monodisperse but with shorter retention time than the major DDM peak. To assess the oligomeric state negative stain electron microscopy was performed which showed a particle with the size of a PCFT dimer. Copyright © 2017 Elsevier Inc. All rights reserved.

Dancing multiplicity states supported by a carboxylated group in dicopper structures bonded to O2

KAUST Repository

Poater, Albert

2013-01-29

The present study pretends to assign the correct multiplicity state to dinuclear copper complexes when interacting with free molecular oxygen. Recently, the formation of a bridge butterfly μ-η2: η2-peroxo dicopper core structure stabilized by the direct interaction of the counterion, a carboxylate group that allows the double bridge linking both metal-centre atoms, was characterized by crystallography. This system was assigned as a diradical singlet with Ms = 0. However, after new calculations it has turned out to be triplet (Ms = 1) despite the stabilization for this latter multiplicity state is not high. Here, the factors that contribute to make this structure display a multiplicity different with respect to the previously expected diradical singlet are described. In the present theoretical study, the roles of the αSp ligand constraints and the counterion are unravelled. On the other hand, the relative stability between the butterfly μ-η2: η2-peroxo structure and the isomeric bis(μ-oxo) species is also on discussion. Despite the relative stabilities of all these either structural or electronic isomeric species are supposed to depend on the computational method, which is a difficulty to reach a definite conclusion about the nature of the active species, all DFT methods using either pure or not pure DFT functionals here reach the same conclusion, favoring the triplet as the ground state for the butterfly μ-η2: η2-peroxo dicopper core structure, and the bis(μ-oxo) species when removing the benzoate counterion. © Springer-Verlag Berlin Heidelberg 2013.

Variations in community exposure to lahar hazards from multiple volcanoes in Washington State (USA)

Science.gov (United States)

Diefenbach, Angela K.; Wood, Nathan J.; Ewert, John W.

2015-01-01

Understanding how communities are vulnerable to lahar hazards provides critical input for effective design and implementation of volcano hazard preparedness and mitigation strategies. Past vulnerability assessments have focused largely on hazards posed by a single volcano, even though communities and officials in many parts of the world must plan for and contend with hazards associated with multiple volcanoes. To better understand community vulnerability in regions with multiple volcanic threats, we characterize and compare variations in community exposure to lahar hazards associated with five active volcanoes in Washington State, USA—Mount Baker, Glacier Peak, Mount Rainier, Mount Adams and Mount St. Helens—each having the potential to generate catastrophic lahars that could strike communities tens of kilometers downstream. We use geospatial datasets that represent various population indicators (e.g., land cover, residents, employees, tourists) along with mapped lahar-hazard boundaries at each volcano to determine the distributions of populations within communities that occupy lahar-prone areas. We estimate that Washington lahar-hazard zones collectively contain 191,555 residents, 108,719 employees, 433 public venues that attract visitors, and 354 dependent-care facilities that house individuals that will need assistance to evacuate. We find that population exposure varies considerably across the State both in type (e.g., residential, tourist, employee) and distribution of people (e.g., urban to rural). We develop composite lahar-exposure indices to identify communities most at-risk and communities throughout the State who share common issues of vulnerability to lahar-hazards. We find that although lahars are a regional hazard that will impact communities in different ways there are commonalities in community exposure across multiple volcanoes. Results will aid emergency managers, local officials, and the public in educating at-risk populations and developing

77 FR 34211 - Modification of Multiple Compulsory Reporting Points; Continental United States, Alaska and Hawaii

Science.gov (United States)

2012-06-11

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 71 [Docket No. FAA-2012-0130; Airspace Docket No. 12-AWA-2] RIN 2120-AA66 Modification of Multiple Compulsory Reporting Points; Continental United States, Alaska and Hawaii AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final...

Electron pumping of the ground state of 21Ne. Transfers and multiple diffusion processes

International Nuclear Information System (INIS)

Stoeckel, F.; Lombardi, M.

1978-01-01

The electron-pumping process of the ground state of 21 Ne has been studied. It is demonstrated how in a neon cell at a pressure of 10 -4 to 10 -2 torr, a high frequency discharge can create a nuclear spin alignment in the fundamental level (I=3/2) when the excited levels are themselves aligned. The nuclear alignment is observed by monitoring the change of the linear polarization of several optical transitions during the magnetic resonance of the fundamental level. Various transfers of the alignments are investigated and a detailed study of the influence of the multiple diffusion is carried out. The multiple diffusion produces a depolarization and a relaxation of the nuclear spin. A theoretical calculation has been made for a two-level system with a J=1 radiative level and a J=0 ground state. Experimentally a relaxation time of the nuclear alignment varying from 37 ms to 240 ms is observed when the neon pressure decreases from 10 -2 to 10 -4 torr [fr

Multiple epiphyseal dysplasia: radiographic abnormalities correlated with genotype

Energy Technology Data Exchange (ETDEWEB)

Unger, S.L. [Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States); Briggs, M.D.; Holden, P. [Wellcome Trust Centre for Cell-Matrix Research, University of Manchester (United Kingdom); Zabel, B. [Children' s Hospital, Univ. of Mainz (Germany); Ala-Kokko, L.; Paassilta, P.; Lohiniva, J. [Dept. of Medical Biochemistry, Univ. of Oulu (Finland); Rimoin, D.L. [Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States); Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA (United States); Lachman, R.S. [Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States); Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA (United States); Department of Radiology, UCLA School of Medicine, Los Angeles, CA (United States); Cohn, D.H. [Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States); Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA (United States)

2001-01-01

Multiple epiphyseal dysplasia (MED) is an osteochondrodysplasia characterized clinically by mild short stature and early-onset degenerative joint disease and radiographically by epiphyseal hypoplasia/dysplasia. MED is genetically heterogeneous, with autosomal dominant cases resulting from mutations in at least three genes: the cartilage oligomeric matrix protein (COMP) gene (EDM1) and the COL9A2 (EDM2) and COL9A3 (EDM3) genes of type IX procollagen. We present here a comparison of the radiographic phenotypes of MED patients with type IX collagen gene mutations and those with COMP gene mutations. We reviewed radiographs from two patients with MED produced by COMP mutations, two families with COL9A2 mutations, and one family with a mutation in COL9A3. The data demonstrated that the patients with type IX collagen defects had more severe joint involvement at the knees and relative hip sparing, while the patients with COMP mutations had significant involvement at the capital femoral epiphyses and irregular acetabuli. This pattern of joint involvement was consistent regardless of overall degree of severity of the phenotype. (orig.)

A New Attribute Control Chart using Multiple Dependent State Repetitive Sampling

KAUST Repository

Aldosari, Mansour Sattam; Aslam, Muhammad; Jun, Chi-Hyuck

2017-01-01

In this manuscript, a new attribute control chart using multiple dependent state repetitive sampling is designed. The operational procedure and structure of the proposed control chart is given. The required measures to determine the average run length (ARL) for in-control and out-of-control processes are given. Tables of ARLs are reported for various control chart parameters. The proposed control chart is more sensitive in detecting a small shift in the process as compared to the existing attribute control charts. The simulation study shows the efficiency of the proposed chart over the existing charts. An example is given for the illustration purpose.

A New Attribute Control Chart using Multiple Dependent State Repetitive Sampling

KAUST Repository

Aldosari, Mansour Sattam

2017-03-25

In this manuscript, a new attribute control chart using multiple dependent state repetitive sampling is designed. The operational procedure and structure of the proposed control chart is given. The required measures to determine the average run length (ARL) for in-control and out-of-control processes are given. Tables of ARLs are reported for various control chart parameters. The proposed control chart is more sensitive in detecting a small shift in the process as compared to the existing attribute control charts. The simulation study shows the efficiency of the proposed chart over the existing charts. An example is given for the illustration purpose.

Use of wiener nonlinear MPC to control a CSTR with multiple steady state

OpenAIRE

Lusson Cervantes, A.; Agamennoni, O.E.; Figueroa, J.L.

2003-01-01

In this paper a Nonlinear Model Predictive Control based on a Wiener Model with a Piecewise Linear gain is presented. The major advantages of this algorithm is that it retains all the interesting properties of the classical linear MPC and the computations are easy to solve due to the canonical structure of the nonlinear gain. The proposed control scheme is applied to a nonlinear CSTR that presents multiple steady states.

Sedimentation Velocity Analysis of Large Oligomeric Chromatin Complexes Using Interference Detection.

Science.gov (United States)

Rogge, Ryan A; Hansen, Jeffrey C

2015-01-01

Sedimentation velocity experiments measure the transport of molecules in solution under centrifugal force. Here, we describe a method for monitoring the sedimentation of very large biological molecular assemblies using the interference optical systems of the analytical ultracentrifuge. The mass, partial-specific volume, and shape of macromolecules in solution affect their sedimentation rates as reflected in the sedimentation coefficient. The sedimentation coefficient is obtained by measuring the solute concentration as a function of radial distance during centrifugation. Monitoring the concentration can be accomplished using interference optics, absorbance optics, or the fluorescence detection system, each with inherent advantages. The interference optical system captures data much faster than these other optical systems, allowing for sedimentation velocity analysis of extremely large macromolecular complexes that sediment rapidly at very low rotor speeds. Supramolecular oligomeric complexes produced by self-association of 12-mer chromatin fibers are used to illustrate the advantages of the interference optics. Using interference optics, we show that chromatin fibers self-associate at physiological divalent salt concentrations to form structures that sediment between 10,000 and 350,000S. The method for characterizing chromatin oligomers described in this chapter will be generally useful for characterization of any biological structures that are too large to be studied by the absorbance optical system. © 2015 Elsevier Inc. All rights reserved.

Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis: relation to growth and disease activity

DEFF Research Database (Denmark)

Bjørnhart, Birgitte; Juul, Anders; Nielsen, Susan

2009-01-01

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity...... in patients with recent-onset juvenile idiopathic arthritis (JIA). COMP levels in JIA and healthy children were compared with those in healthy adults. Plasma levels of insulin-like growth factor I (IGF-1), which has been associated with COMP expression and growth velocity, were studied in parallel. METHODS......: 87 patients with JIA entered the study, including oligoarticular JIA (n = 34), enthesitis-related arthritis (n = 8), polyarticular rheumatoid factor (RF)-positive JIA (n = 2), polyarticular RF-negative JIA (n = 27), systemic JIA (n = 6), and undifferentiated JIA (n = 10). Plasma levels of COMP were...

Dielectric properties of polyhedral oligomeric silsesquioxane (POSS)-based nanocomposites at 77k

International Nuclear Information System (INIS)

Pan, Ming-Jen; Gorzkowski, Edward; McAllister, Kelly

2011-01-01

The goal of this study is to develop dielectric nanocomposites for high energy density applications at liquid nitrogen temperature by utilizing a unique nano-material polyhedral oligomeric silsesquioxanes (POSS). A POSS molecule is consisted of a silica cage core with 8 silicon and 12 oxygen atoms and organic functional groups attached to the corners of the cage. In this study, we utilize POSS for the fabrication of nanocomposites both as a silica nanoparticle filler to enhance the breakdown strength and as a surfactant for effective dispersion of high permittivity ceramic nanoparticles in a polymer matrix. The matrix materials selected for the study are polyvinylidene fluoride (PVDF) and poly(methyl methacrylate) (PMMA). The ceramic nanoparticles are barium strontium titanate (BST 50/50) and strontium titanate. The dielectric properties of the solution-cast nanocomposites films were correlated to the composition and processing conditions. We determined that the addition of POSS did not provide enhanced dielectric performance in PVDF- and PMMA-based materials at either room temperature or 77K. In addition, we found that the dielectric breakdown strength of PMMA is lower at 77K than at room temperature, contradicting literature data.

Polyhedral oligomeric silsesquioxane (POSS)–poly(ethylene glycol) (PEG) hybrids as injectable biomaterials

International Nuclear Information System (INIS)

Engstrand, Johanna; López, Alejandro; Engqvist, Håkan; Persson, Cecilia

2012-01-01

One of the major issues with the currently available injectable biomaterials for hard tissue replacement is the mismatch between their mechanical properties and those of the surrounding bone. Hybrid bone cements that combine the benefits of tough polymeric and bioactive ceramic materials could become a good alternative. In this work, polyhedral oligomeric silsesquioxane (POSS) was copolymerized with poly(ethylene glycol) (PEG) to form injectable in situ cross-linkable hybrid cements. The hybrids were characterized in terms of their mechanical, rheological, handling and in vitro bioactive properties. The results indicated that hybridization improves the mechanical and bioactive properties of POSS and PEG. The Young moduli of the hybrids were lower than those of commercial cements and more similar to those of cancellous bone. Furthermore, the strength of the hybrids was similar to that of commercial cements. Calcium deficient hydroxyapatite grew on the surface of the hybrids after 28 days in PBS, indicating bioactivity. The study showed that PEG–POSS-based hybrid materials are a promising alternative to commercial bone cements. (paper)

Using State-Wide Multiple Measures for School Leadership and Management: Costs Incurred vs. Benefits Gained

Science.gov (United States)

Hentschke, Guilbert; Wohlstetter, Priscilla; Hirman, Jennifer; Zeehandelaar, Dara

2011-01-01

In this article, we examine the utility and value of multiple measures of school performance for school leaders and managers. The research was conducted within the context of the state of California through an investigation of how operators, managers and authorisers of autonomous "charter" (publicly financed but privately operated)…

Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein

International Nuclear Information System (INIS)

Hoetzel, Isidro; Cheevers, William P.

2005-01-01

The caprine arthritis-encephalitis (CAEV) and ovine maedi-visna (MVV) viruses are resistant to antibody neutralization, a feature shared with all other lentiviruses. Whether the CAEV gp135 receptor binding site(s) (RBS) in the functional surface envelope glycoprotein (Env) is protected from antibody binding, allowing the virus to resist neutralization, is not known. Two CAEV gp135 regions were identified by extrapolating a gp135 structural model that could affect binding of antibodies to the RBS: the V1 region and a short sequence analogous in position to the human immunodeficiency virus type 1 gp120 loop B postulated to be located between two major domains of CAEV gp135. Mutation of isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7-299 which recognizes an epitope overlapping the gp135 RBS. The I166A mutation also stabilized or exposed the F7-299 epitope in anionic detergent buffers, indicating that the I166A mutation induces conformational changes and stabilizes the RBS of soluble gp135 and enhances Mab F7-299 binding. In contrast, the affinity of a V1 deletion mutant of gp135 for the receptor and Mab F7-299 and its structural stability did not differ from that of the wild-type gp135. However, both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell fusion activity and binding of Mab F7-299 to the oligomeric Env. Therefore, the CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent and independent of Env oligomerization which are disrupted by the V1 deletion and the I166A mutation, respectively. In addition, we found a correlation between side-chain β-branching at amino acid position 166 and binding of Mab F7-299 to oligomeric Env and cell-to-cell fusion, suggesting local secondary structure constraints in the region around isoleucine-166 as one determinant of gp135 RBS exposure and antibody binding

Depressive state and chronic fatigue in multiple sclerosis and neuromyelitis optica.

Science.gov (United States)

Akaishi, Tetsuya; Nakashima, Ichiro; Misu, Tatsuro; Fujihara, Kazuo; Aoki, Masashi

2015-06-15

Depression and chronic fatigue are frequently present in multiple sclerosis (MS); however, the prevalence rates have not been investigated in neuromyelitis optica (NMO). Thirty-nine consecutive NMO and 75 MS patients were compared using self-rating questionnaires for depressive states, daily activity, and fatigue, as well as serum carnitine levels. A subgroup of patients with low carnitine levels were re-evaluated regarding depression and fatigue after levocarnitine treatment. Depression and fatigue were equally prevalent in MS and NMO and were strongly correlated with one another. Measurement of the serum carnitine levels and the administration of levocarnitine did not appear to be beneficial. Copyright © 2015 Elsevier B.V. All rights reserved.

Memory State Feedback RMPC for Multiple Time-Delayed Uncertain Linear Systems with Input Constraints

Directory of Open Access Journals (Sweden)

Wei-Wei Qin

2014-01-01

Full Text Available This paper focuses on the problem of asymptotic stabilization for a class of discrete-time multiple time-delayed uncertain linear systems with input constraints. Then, based on the predictive control principle of receding horizon optimization, a delayed state dependent quadratic function is considered for incorporating MPC problem formulation. By developing a memory state feedback controller, the information of the delayed plant states can be taken into full consideration. The MPC problem is formulated to minimize the upper bound of infinite horizon cost that satisfies the sufficient conditions. Then, based on the Lyapunov-Krasovskii function, a delay-dependent sufficient condition in terms of linear matrix inequality (LMI can be derived to design a robust MPC algorithm. Finally, the digital simulation results prove availability of the proposed method.

Data in support of the identification of neuronal and astrocyte proteins interacting with extracellularly applied oligomeric and fibrillar α-synuclein assemblies by mass spectrometry.

Science.gov (United States)

Shrivastava, Amulya Nidhi; Redeker, Virginie; Fritz, Nicolas; Pieri, Laura; Almeida, Leandro G; Spolidoro, Maria; Liebmann, Thomas; Bousset, Luc; Renner, Marianne; Léna, Clément; Aperia, Anita; Melki, Ronald; Triller, Antoine

2016-06-01

α-Synuclein (α-syn) is the principal component of Lewy bodies, the pathophysiological hallmark of individuals affected by Parkinson disease (PD). This neuropathologic form of α-syn contributes to PD progression and propagation of α-syn assemblies between neurons. The data we present here support the proteomic analysis used to identify neuronal proteins that specifically interact with extracellularly applied oligomeric or fibrillar α-syn assemblies (conditions 1 and 2, respectively) (doi: 10.15252/embj.201591397[1]). α-syn assemblies and their cellular partner proteins were pulled down from neuronal cell lysed shortly after exposure to exogenous α-syn assemblies and the associated proteins were identified by mass spectrometry using a shotgun proteomic-based approach. We also performed experiments on pure cultures of astrocytes to identify astrocyte-specific proteins interacting with oligomeric or fibrillar α-syn (conditions 3 and 4, respectively). For each condition, proteins interacting selectively with α-syn assemblies were identified by comparison to proteins pulled-down from untreated cells used as controls. The mass spectrometry data, the database search and the peak lists have been deposited to the ProteomeXchange Consortium database via the PRIDE partner repository with the dataset identifiers PRIDE: PXD002256 to PRIDE: PXD002263 and doi: 10.6019/PXD002256 to 10.6019/PXD002263.

Flow cytometry evidence of human granulocytes interaction with polyhedral oligomeric silsesquioxanes: effect of nanoparticle charge

International Nuclear Information System (INIS)

Renò, Filippo; Rizzi, Manuela; Pittarella, Pamela; Carniato, Fabio; Olivero, Francesco; Marchese, Leonardo

2013-01-01

Nanoparticles (NPs) entering the human body are immediately confronted with the innate part of human immune system. In particular, monocyte and neutrophil granulocytes readily clear particles by phagocytosis, even if in the case of NPs the uptake mechanism may be classified as macropinocytosis. Among engineered nanoparticles, in the last years, siliceous materials have emerged as promising materials for several applications ranging from catalysis to biomedical. The polyhedral oligomeric silsesquioxanes (POSS) are nanodimensional, easily synthesizable molecular compounds and POSS-based systems are promising carriers for biological molecules. In this work, the ability of human granulocytes to uptake positively and negatively charged POSS was measured using a simple flow cytometry analysis based on cell size modifications. The data obtained showed that after a 30 min exposure only positive NPs were uptaken by human granulocyte using both macropinocytosis and clathrin-mediated mechanisms as demonstrated by uptake inhibition mediated by amiloride and chlorpromazine. (paper)

Lack of Both Nucleotide-Binding Oligomerization Domain-Containing Proteins 1 and 2 Primes T Cells for Activation-Induced Cell Death.

Science.gov (United States)

Kasimsetty, Sashi G; Shigeoka, Alana A; Scheinok, Andrew A; Gavin, Amanda L; Ulevitch, Richard J; McKay, Dianne B

2017-08-01

Nucleotide-binding oligomerization domain (Nod)-containing proteins Nod1 and Nod2 play important roles in the innate immune response to pathogenic microbes, but mounting data suggest these pattern recognition receptors might also play key roles in adaptive immune responses. Targeting Nod1 and Nod2 signaling pathways in T cells is likely to provide a new strategy to modify inflammation in a variety of disease states, particularly those that depend on Ag-induced T cell activation. To better understand how Nod1 and Nod2 proteins contribute to adaptive immunity, this study investigated their role in alloantigen-induced T cell activation and asked whether their absence might impact in vivo alloresponses using a severe acute graft versus host disease model. The study provided several important observations. We found that the simultaneous absence of Nod1 and Nod2 primed T cells for activation-induced cell death. T cells from Nod1 × 2 -/- mice rapidly underwent cell death upon exposure to alloantigen. The Nod1 × 2 -/- T cells had sustained p53 expression that was associated with downregulation of its negative regulator MDM2. In vivo, mice transplanted with an inoculum containing Nod1 × 2 -/- T cells were protected from severe graft versus host disease. The results show that the simultaneous absence of Nod1 and Nod2 is associated with accelerated T cell death upon alloantigen encounter, suggesting these proteins might provide new targets to ameliorate T cell responses in a variety of inflammatory states, including those associated with bone marrow or solid organ transplantation. Copyright © 2017 by The American Association of Immunologists, Inc.

Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

DEFF Research Database (Denmark)

Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

2008-01-01

ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

An integrated probabilistic risk analysis decision support methodology for systems with multiple state variables

International Nuclear Information System (INIS)

Sen, P.; Tan, John K.G.; Spencer, David

1999-01-01

Probabilistic risk analysis (PRA) methods have been proven to be valuable in risk and reliability analysis. However, a weak link seems to exist between methods for analysing risks and those for making rational decisions. The integrated decision support system (IDSS) methodology presented in this paper attempts to address this issue in a practical manner. In consists of three phases: a PRA phase, a risk sensitivity analysis (SA) phase and an optimisation phase, which are implemented through an integrated computer software system. In the risk analysis phase the problem is analysed by the Boolean representation method (BRM), a PRA method that can deal with systems with multiple state variables and feedback loops. In the second phase the results obtained from the BRM are utilised directly to perform importance and risk SA. In the third phase, the problem is formulated as a multiple objective decision making problem in the form of multiple objective reliability optimisation. An industrial example is included. The resultant solutions of a five objective reliability optimisation are presented, on the basis of which rational decision making can be explored

Storage of multiple single-photon pulses emitted from a quantum dot in a solid-state quantum memory

Science.gov (United States)

Tang, Jian-Shun; Zhou, Zong-Quan; Wang, Yi-Tao; Li, Yu-Long; Liu, Xiao; Hua, Yi-Lin; Zou, Yang; Wang, Shuang; He, De-Yong; Chen, Geng; Sun, Yong-Nan; Yu, Ying; Li, Mi-Feng; Zha, Guo-Wei; Ni, Hai-Qiao; Niu, Zhi-Chuan; Li, Chuan-Feng; Guo, Guang-Can

2015-01-01

Quantum repeaters are critical components for distributing entanglement over long distances in presence of unavoidable optical losses during transmission. Stimulated by the Duan–Lukin–Cirac–Zoller protocol, many improved quantum repeater protocols based on quantum memories have been proposed, which commonly focus on the entanglement-distribution rate. Among these protocols, the elimination of multiple photons (or multiple photon-pairs) and the use of multimode quantum memory are demonstrated to have the ability to greatly improve the entanglement-distribution rate. Here, we demonstrate the storage of deterministic single photons emitted from a quantum dot in a polarization-maintaining solid-state quantum memory; in addition, multi-temporal-mode memory with 1, 20 and 100 narrow single-photon pulses is also demonstrated. Multi-photons are eliminated, and only one photon at most is contained in each pulse. Moreover, the solid-state properties of both sub-systems make this configuration more stable and easier to be scalable. Our work will be helpful in the construction of efficient quantum repeaters based on all-solid-state devices. PMID:26468996

Substitution of proline32 by α-methylproline preorganizes β2-microglobulin for oligomerization but not for aggregation into amyloids.

Science.gov (United States)

Torbeev, Vladimir; Ebert, Marc-Olivier; Dolenc, Jozica; Hilvert, Donald

2015-02-25

Conversion of soluble folded proteins into insoluble amyloids generally proceeds in three distinct mechanistic stages: (1) initial protein misfolding into aggregation-competent conformers, (2) subsequent formation of oligomeric species and, finally, (3) self-assembly into extended amyloid fibrils. In the work reported herein, we interrogated the amyloidogenesis mechanism of human β2-microglobulin (β2m), which is thought to be triggered by a pivotal cis-trans isomerization of a proline residue at position 32 in the polypeptide, with nonstandard amino acids. Using chemical protein synthesis we prepared a β2m analogue in which Pro32 was replaced by the conformationally constrained amino acid α-methylproline (MePro). The strong propensity of MePro to adopt a trans prolyl bond led to enhanced population of a non-native [trans-MePro32]β2m protein conformer, which readily formed oligomers at neutral pH. In the presence of the antibiotic rifamycin SV, which inhibits amyloid growth of wild-type β2m, [MePro32]β2m was nearly quantitatively converted into different spherical oligomeric species. Self-assembly into amyloid fibrils was not observed in the absence of seeding, however, even at low pH (<3), where wild-type β2m spontaneously forms amyloids. Nevertheless, we found that aggregation-preorganized [MePro32]β2m can act in a prion-like fashion, templating misfolded conformations in a natively folded protein. Overall, these results provide detailed insight into the role of cis-trans isomerization of Pro32 and ensuing structural rearrangements that lead to initial β2m misfolding and aggregation. They corroborate the view that conformational protein dynamics enabled by reversible Pro32 cis-trans interconversion rather than simple population of the trans conformer is critical for both nucleation and subsequent growth of β2m amyloid structures.

Active site CP-loop dynamics modulate substrate binding, catalysis, oligomerization, stability, over-oxidation and recycling of 2-Cys Peroxiredoxins.

Science.gov (United States)

Kamariah, Neelagandan; Eisenhaber, Birgit; Eisenhaber, Frank; Grüber, Gerhard

2018-04-01

Peroxiredoxins (Prxs) catalyse the rapid reduction of hydrogen peroxide, organic hydroperoxide and peroxynitrite, using a fully conserved peroxidatic cysteine (C P ) located in a conserved sequence Pxxx(T/S)xxC P motif known as C P -loop. In addition, Prxs are involved in cellular signaling pathways and regulate several redox-dependent process related disease. The effective catalysis of Prxs is associated with alterations in the C P -loop between reduced, Fully Folded (FF), and oxidized, Locally Unfolded (LU) conformations, which are linked to dramatic changes in the oligomeric structure. Despite many studies, little is known about the precise structural and dynamic roles of the C P -loop on Prxs functions. Herein, the comprehensive biochemical and biophysical studies on Escherichia coli alkyl hydroperoxide reductase subunit C (EcAhpC) and the C P -loop mutants, EcAhpC-F45A and EcAhpC-F45P reveal that the reduced form of the C P -loop adopts conformational dynamics, which is essential for effective peroxide reduction. Furthermore, the point mutants alter the structure and dynamics of the reduced form of the C P -loop and, thereby, affect substrate binding, catalysis, oligomerization, stability and overoxidiation. In the oxidized form, due to restricted C P -loop dynamics, the EcAhpC-F45P mutant favours a decamer formation, which enhances the effective recycling by physiological reductases compared to wild-type EcAhpC. In addition, the study reveals that residue F45 increases the specificity of Prxs-reductase interactions. Based on these studies, we propose an evolution of the C P -loop with confined sequence conservation within Prxs subfamilies that might optimize the functional adaptation of Prxs into various physiological roles. Copyright © 2018 Elsevier Inc. All rights reserved.

Hydroxychloroquine induces inhibition of collagen type II and oligomeric matrix protein COMP expression in chondrocytes

Directory of Open Access Journals (Sweden)

Tao Li

2016-06-01

Full Text Available The aim of this study was to investigate the effect of hydroxychloroquine on the level of collagen type II and oligomeric matrix protein COMP expression in chondrocytes of knee osteoarthritis. The rate of growth in cartilage cells was analyzed using MTT assay whereas the Col-2 and COMP expression levels were detected by RT-PCR and Western blotting analyses. For the determination of MMP-13 expression, ELISA test was used. The results revealed no significant change in the rate of cartilage cell proliferation in hydroxychloroquine-treated compared to untreated cells. Hydroxychloro-quine treatment exhibited concentration- and time-dependent effect on the inhibition of collagen type II and COMP expression in chondrocytes. However, its treatment caused a significant enhancement in the expression levels of MMP-13 compared to the untreated cells. Therefore, hydroxychloro-quine promotes expression of MMP-13 and reduces collagen type II and COMP expression levels in chondrocytes without any significant change in the growth of cells.

High-multiplicity processes

International Nuclear Information System (INIS)

Shelkov, G.; Sisakyan, A.; Mandzhavidze, I.

1999-01-01

We wish to demonstrate that investigation of asymptotically high multiplicity (AHM) hadron reactions may solve, or at least clear up, a number of problems unsolvable by other ways. We would lean upon the idea: (i) the reactions final state entropy is proportional to multiplicity and, by this reason, just in the AHM domain one may expect the equilibrium final state and (ii) the AHM final state is cold because of the energy-momentum conservation laws. This means that the collective phenomena may become important in the AHM domain. The possibility of hard processes dominance is considered also

Bayesian state space models for dynamic genetic network construction across multiple tissues.

Science.gov (United States)

Liang, Yulan; Kelemen, Arpad

2016-08-01

Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

Science.gov (United States)

Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

2016-11-01

Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

Multiple solutions of steady-state Poisson–Nernst–Planck equations with steric effects

International Nuclear Information System (INIS)

Lin, Tai-Chia; Eisenberg, Bob

2015-01-01

Experiments measuring currents through single protein channels show unstable currents. Channels switch between ‘open’ or ‘closed’ states in a spontaneous stochastic process called gating. Currents are either (nearly) zero or at a definite level, characteristic of each type of protein, independent of time, once the channel is open. The steady state Poisson–Nernst–Planck equations with steric effects (PNP-steric equations) describe steady current through the open channel quite well, in a wide variety of conditions. Here we study the existence of multiple solutions of steady state PNP-steric equations to see if they themselves, without modification or augmentation, can describe two levels of current. We prove that there are two steady state solutions of PNP-steric equations for (a) three types of ion species (two types of cations and one type of anion) with a positive constant permanent charge, and (b) four types of ion species (two types of cations and their counter-ions) with a constant permanent charge but no sign condition. The excess currents (due to steric effects) associated with these two steady state solutions are derived and expressed as two distinct formulas. Our results indicate that PNP-steric equations may become a useful model to study spontaneous gating of ion channels. Spontaneous gating is thought to involve small structural changes in the channel protein that perhaps produce large changes in the profiles of free energy that determine ion flow. Gating is known to be modulated by external structures. Both can be included in future extensions of our present analysis. (paper)

Multiwalled carbon nanotubes@octavinyl polyhedral oligomeric silsesquioxanes nanocomposite preparation via cross-linking reaction in acidic media

Energy Technology Data Exchange (ETDEWEB)

Somasekharan, Lakshmipriya; Thomas, Sabu [Mahatma Gandhi University, International and Interuniversity Centre for Nanoscience and Nanotechnology (India); Comoy, Corinne [Université de Lorraine, SRSMC, UMR 7565 (France); Sivasankarapillai, Anilkumar [NSS Hindu College (India); Kalarikkal, Nandakumar [Mahatma Gandhi University, International and Interuniversity Centre for Nanoscience and Nanotechnology (India); Lamouroux, Emmanuel, E-mail: Emmanuel.Lamouroux@univ-lorraine.fr [Université de Lorraine, SRSMC, UMR 7565 (France)

2016-11-15

Multiwalled carbon nanotubes have unique properties allowing their use in a wide range of applications—from microelectronics to biomedical and polymer fields. Nevertheless, a crucial aspect for their use resides in the ease of handling them during the process. Here, we report a facile route to prepare multiwalled carbon nanotubes@octavinyl polyhedral oligomeric silsesquioxanes (MWCNT@POSS) nanocomposite. The method involves the formation of a covalent bond between carboxylated MWCNTs and OV-POSS using acid-catalyzed electrophilic addition reaction. The resulting nanocomposite have been characterized by Fourier transform infrared spectroscopy (FTIR), powder X-Ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). The results confirmed that the formation of MWCNT@POSS nanocomposite did not deteriorate MWCNT structure or morphology. Here, we used a 1:1 ratio of carboxylated MWCNTs and OV-POSS and the POSS content in the nanocomposite was 39.5 wt%.

Exact criteria for uniqueness and multiplicity of an nth order chemical reaction via catastrophe theory approach. [Determines boundaries between unique and multiple steady state conditions

Energy Technology Data Exchange (ETDEWEB)

Chang, H C; Calo, J M

1979-01-01

A simple, generalized technique for the exact determination of the boundaries between regions of unique and of multiple solutions to certain nonlinear equations was developed by applying catastrophe theory to the mapping of implicit and explicit functions. Its application to an nth order reaction in continuous stirred tank reactor (CSTR) yields exact, explicit expressions for the boundaries between regions of single and multiple steady states, expressed in terms of the dimensionless heat transfer coefficient and activation energy. An exact implicit expression for the boundaries between regions of uniqueness and multiplicity was also derived for an nth order reaction in a catalyst particle with an intraparticle concentration gradient and uniform temperature and is fully demonstrated for the first-order reaction. In addition, explicit criteria were developed by assuming the limits on d ln g/d ln q, where g is the effectiveness factor and q the Thiele modulus, proposed by van den Bosch and Luss.

Novel thixotropic gel electrolytes based on dicationic bis-imidazolium salts for quasi-solid-state dye-sensitized solar cells

Science.gov (United States)

Kim, Jun Young; Kim, Tae Ho; Kim, Dong Young; Park, Nam-Gyu; Ahn, Kwang-Duk

Novel thixotropic gel electrolytes have been successfully prepared by utilizing oligomeric poly(ethylene oxide) (PEO)-based bis-imidazolium diiodide salts and hydrophilic silica nanoparticles for application in quasi-solid-state dye-sensitized solar cells (DSSCs). The thixotropic gel-state of the ionic liquid-based composite electrolytes is confirmed by observing the typical hysteresis loop and temporary hydrogen bonding. On using the PEO-based composite electrolyte, a quasi-solid-state DSSC exhibited highly improved properties such as easy penetration of the electrolyte into the cell without leakage, long-term stability, high open-circuit voltage without the use of 4- tert-butylpyridine, and a high energy-conversion efficiency of 5.25% under AM 1.5 illumination (100 mW cm -2).

Adaptive behaviour and multiple equilibrium states in a predator-prey model.

Science.gov (United States)

Pimenov, Alexander; Kelly, Thomas C; Korobeinikov, Andrei; O'Callaghan, Michael J A; Rachinskii, Dmitrii

2015-05-01

There is evidence that multiple stable equilibrium states are possible in real-life ecological systems. Phenomenological mathematical models which exhibit such properties can be constructed rather straightforwardly. For instance, for a predator-prey system this result can be achieved through the use of non-monotonic functional response for the predator. However, while formal formulation of such a model is not a problem, the biological justification for such functional responses and models is usually inconclusive. In this note, we explore a conjecture that a multitude of equilibrium states can be caused by an adaptation of animal behaviour to changes of environmental conditions. In order to verify this hypothesis, we consider a simple predator-prey model, which is a straightforward extension of the classic Lotka-Volterra predator-prey model. In this model, we made an intuitively transparent assumption that the prey can change a mode of behaviour in response to the pressure of predation, choosing either "safe" of "risky" (or "business as usual") behaviour. In order to avoid a situation where one of the modes gives an absolute advantage, we introduce the concept of the "cost of a policy" into the model. A simple conceptual two-dimensional predator-prey model, which is minimal with this property, and is not relying on odd functional responses, higher dimensionality or behaviour change for the predator, exhibits two stable co-existing equilibrium states with basins of attraction separated by a separatrix of a saddle point. Copyright © 2015 Elsevier Inc. All rights reserved.

DFT study on the impact of the methylaluminoxane cocatalyst in ethylene oligomerization using a titanium-based catalyst

KAUST Repository

Pasha, Farhan Ahmad; Basset, Jean-Marie; Toulhoat, Hervé ; De Bruin, Theodorus J M

2015-01-01

A computational study within the framework of density functional theory is presented on the oligomerization of ethylene to yield 1-hexene using [(η5-C5H4CMe2C6H5)]TiCl3/MAO] catalyst. This study explicitly takes into account a methylaluminoxane (MAO) cocatalyst model, where the MAO cluster has become an anionic species after having abstracted one chloride anion, yielding a cationic activated catalyst. Hence, the reaction profile was calculated using the zwitterionic system, and the potential energy surface has been compared to the cationic catalytic system. Modest differences were found between the two free energy profiles. However, we show for the first time that the use of a realistic zwitterionic model is required to obtain a Brønsted-Evans-Polanyi relationship between the energy barriers and reaction energies.

DFT study on the impact of the methylaluminoxane cocatalyst in ethylene oligomerization using a titanium-based catalyst

KAUST Repository

Pasha, Farhan Ahmad

2015-01-26

A computational study within the framework of density functional theory is presented on the oligomerization of ethylene to yield 1-hexene using [(η5-C5H4CMe2C6H5)]TiCl3/MAO] catalyst. This study explicitly takes into account a methylaluminoxane (MAO) cocatalyst model, where the MAO cluster has become an anionic species after having abstracted one chloride anion, yielding a cationic activated catalyst. Hence, the reaction profile was calculated using the zwitterionic system, and the potential energy surface has been compared to the cationic catalytic system. Modest differences were found between the two free energy profiles. However, we show for the first time that the use of a realistic zwitterionic model is required to obtain a Brønsted-Evans-Polanyi relationship between the energy barriers and reaction energies.

Multiple-valued logic design based on the multiple-peak BiCMOS-NDR circuits

Directory of Open Access Journals (Sweden)

Kwang-Jow Gan

2016-06-01

Full Text Available Three different multiple-valued logic (MVL designs using the multiple-peak negative-differential-resistance (NDR circuits are investigated. The basic NDR element, which is made of several Si-based metal-oxide-semiconductor field-effect-transistor (MOS and SiGe-based heterojunction-bipolar-transistor (HBT devices, can be implemented by using a standard BiCMOS process. These MVL circuits are designed based on the triggering-pulse control, saw-tooth input signal, and peak-control methods, respectively. However, there are some transient states existing between the multiple stable levels for the first two methods. These states might affect the circuit function in practical application. As a result, our proposed peak-control method for the MVL design can be used to overcome these transient states.

Using Images, Metaphor, and Hypnosis in Integrating Multiple Personality and Dissociative States: A Review of the Literature.

Science.gov (United States)

Crawford, Carrie L.

1990-01-01

Reviews literature on hypnosis, imagery, and metaphor as applied to the treatment and integration of those with multiple personality disorder (MPD) and dissociative states. Considers diagnostic criteria of MPD; explores current theories of etiology and treatment; and suggests specific examples of various clinical methods of treatment using…

Localized versus itinerant states created by multiple oxygen vacancies in SrTiO3

Science.gov (United States)

Jeschke, Harald O.; Shen, Juan; Valentí, Roser

2015-02-01

Oxygen vacancies in strontium titanate surfaces (SrTiO3) have been linked to the presence of a two-dimensional electron gas with unique behavior. We perform a detailed density functional theory study of the lattice and electronic structure of SrTiO3 slabs with multiple oxygen vacancies, with a main focus on two vacancies near a titanium dioxide terminated SrTiO3 surface. We conclude based on total energies that the two vacancies preferably inhabit the first two layers, i.e. they cluster vertically, while in the direction parallel to the surface, the vacancies show a weak tendency towards equal spacing. Analysis of the nonmagnetic electronic structure indicates that oxygen defects in the surface TiO2 layer lead to population of Ti {{t}2g} states and thus itinerancy of the electrons donated by the oxygen vacancy. In contrast, electrons from subsurface oxygen vacancies populate Ti eg states and remain localized on the two Ti ions neighboring the vacancy. We find that both the formation of a bound oxygen-vacancy state composed of hybridized Ti 3eg and 4p states neighboring the oxygen vacancy as well as the elastic deformation after extracting oxygen contribute to the stabilization of the in-gap state.

Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

Science.gov (United States)

Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

2014-01-01

Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

Directory of Open Access Journals (Sweden)

Jun eWang

2014-03-01

Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

DEFF Research Database (Denmark)

Lou, Chenguang; Christensen, Niels Johan; Martos Maldonado, Manuel Cristo

2017-01-01

by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex......, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12nm) in solution was revealed to be independent of concentration. The topological folding...

MED, COMP, multilayered and NEIN: an overview of multiple epiphyseal dysplasia

Energy Technology Data Exchange (ETDEWEB)

Lachman, Ralph S. [International Skeletal Dysplasia Registry, UCLA School of Medicine, Radiological Services, Department of Pediatrics, Los Angeles, CA (United States); International Skeletal Dysplasia Registry, Los Angeles, CA (United States); Krakow, Deborah; Cohn, Daniel H.; Rimoin, David L. [International Skeletal Dysplasia Registry, UCLA School of Medicine, Radiological Services, Department of Pediatrics, Los Angeles, CA (United States)

2005-02-01

This overview covers the group of disorders that presents radiographically as multiple epiphyseal dysplasia (MED). The disorders include ''classic MED'' (Ribbing and Fairbank types): MED that is caused by mutations in the cartilage oligomeric matrix protein (COMP), type IX collagen, and matrilin 3 genes (MATN3); and MED with multilayered patella, brachydactyly, and clubbed feet resultant from mutations in gene defect diastrophic dysplasia (DTDST). The recently identified gene/molecular abnormalities in these disorders have made more exact identification possible in many cases, although clinical testing is not always available. However, there are specific radiographic findings that allow the accurate diagnosis to be made, thus potentially guiding which molecular defect(s) should be investigated. The modes of inheritance of these distinct MED conditions are not identical. When a specific diagnosis is made, proper genetic counseling as well as prognostication, management issues and complications can be delineated to the patient and family. This review will include the mechanics of diagnostic and molecular triage for these disorders. (orig.)

Structural Analysis of Polyhedral Oligomeric Silsesquioxane Coated SiC Nanoparticles and Their Applications in Thermoset Polymers

International Nuclear Information System (INIS)

Reza-E-Rabby, M.; Jeelani, Sh.; Rangari, V. K.

2015-01-01

The SiC nanoparticles (NPs) were sonochemically coated with Octa Isobutyl (OI) polyhedral oligomeric silsesquioxane (POSS) to create a compatible interface between particle and thermoset polymer. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) techniques were used to analyze the structure of OI-POSS coated SiC nanoparticles. These results revealed the formation of a covalent bonding between SiC and OI-POSS. The transmission electron microscopy (TEM) analysis of OI-POSS coated SiC nanoparticles has also shown the indication of attachment between these two nanoparticles. The OI-POSS coated SiC nanoparticles were further reinforced into a thermoset resin system in order to evaluate mechanical and thermal properties of nano composites. The flexural strength, modulus, and glass transition temperature were found to be enhanced while SiC and OI-POSS coated SiC were infused into epoxy system compared to those properties of neat epoxy resin

Structural Analysis of Polyhedral Oligomeric Silsesquioxane Coated SiC Nanoparticles and Their Applications in Thermoset Polymers

Directory of Open Access Journals (Sweden)

Md. Reza-E-Rabby

2015-01-01

Full Text Available The SiC nanoparticles (NPs were sonochemically coated with OctaIsobutyl (OI polyhedral oligomeric silsesquioxane (POSS to create a compatible interface between particle and thermoset polymer. X-ray photoelectron spectroscopy (XPS, Fourier transform infrared spectroscopy (FTIR, and X-ray diffraction (XRD techniques were used to analyze the structure of OI-POSS coated SiC nanoparticles. These results revealed the formation of a covalent bonding between SiC and OI-POSS. The transmission electron microscopy (TEM analysis of OI-POSS coated SiC nanoparticles has also shown the indication of attachment between these two nanoparticles. The OI-POSS coated SiC nanoparticles were further reinforced into a thermoset resin system in order to evaluate mechanical and thermal properties of nanocomposites. The flexural strength, modulus, and glass transition temperature were found to be enhanced while SiC and OI-POSS coated SiC were infused into epoxy system compared to those properties of neat epoxy resin.

Dicke states in multiple quantum dots

Science.gov (United States)

Sitek, Anna; Manolescu, Andrei

2013-10-01

We present a theoretical study of the collective optical effects which can occur in groups of three and four quantum dots. We define conditions for stable subradiant (dark) states, rapidly decaying super-radiant states, and spontaneous trapping of excitation. Each quantum dot is treated like a two-level system. The quantum dots are, however, realistic, meaning that they may have different transition energies and dipole moments. The dots interact via a short-range coupling which allows excitation transfer across the dots, but conserves the total population of the system. We calculate the time evolution of single-exciton and biexciton states using the Lindblad equation. In the steady state the individual populations of each dot may have permanent oscillations with frequencies given by the energy separation between the subradiant eigenstates.

Data in support of the identification of neuronal and astrocyte proteins interacting with extracellularly applied oligomeric and fibrillar α-synuclein assemblies by mass spectrometry

Directory of Open Access Journals (Sweden)

Amulya Nidhi Shrivastava

2016-06-01

Full Text Available α-Synuclein (α-syn is the principal component of Lewy bodies, the pathophysiological hallmark of individuals affected by Parkinson disease (PD. This neuropathologic form of α-syn contributes to PD progression and propagation of α-syn assemblies between neurons. The data we present here support the proteomic analysis used to identify neuronal proteins that specifically interact with extracellularly applied oligomeric or fibrillar α-syn assemblies (conditions 1 and 2, respectively (doi: 10.15252/embj.201591397 [1]. α-syn assemblies and their cellular partner proteins were pulled down from neuronal cell lysed shortly after exposure to exogenous α-syn assemblies and the associated proteins were identified by mass spectrometry using a shotgun proteomic-based approach. We also performed experiments on pure cultures of astrocytes to identify astrocyte-specific proteins interacting with oligomeric or fibrillar α-syn (conditions 3 and 4, respectively. For each condition, proteins interacting selectively with α-syn assemblies were identified by comparison to proteins pulled-down from untreated cells used as controls. The mass spectrometry data, the database search and the peak lists have been deposited to the ProteomeXchange Consortium database via the PRIDE partner repository with the dataset identifiers PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD002256 to PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD002263 and doi: 10.6019/http://www.ebi.ac.uk/pride/archive/projects/PXD002256 to 10.6019/http://www.ebi.ac.uk/pride/archive/projects/PXD002263.

Vegetation engineers marsh morphology through multiple competing stable states

Science.gov (United States)

Marani, Marco; Da Lio, Cristina; D’Alpaos, Andrea

2013-01-01

Marshes display impressive biogeomorphic features, such as zonation, a mosaic of extensive vegetation patches of rather uniform composition, exhibiting sharp transitions in the presence of extremely small topographic gradients. Although generally associated with the accretion processes necessary for marshes to keep up with relative sea level rise, competing environmental constraints, and ecologic controls, zonation is still poorly understood in terms of the underlying biogeomorphic mechanisms. Here we find, through observations and modeling interpretation, that zonation is the result of coupled geomorphological–biological dynamics and that it stems from the ability of vegetation to actively engineer the landscape by tuning soil elevation within preferential ranges of optimal adaptation. We find multiple peaks in the frequency distribution of observed topographic elevation and identify them as the signature of biologic controls on geomorphodynamics through competing stable states modulated by the interplay of inorganic and organic deposition. Interestingly, the stable biogeomorphic equilibria correspond to suboptimal rates of biomass production, a result coherent with recent observations. The emerging biogeomorphic structures may display varying degrees of robustness to changes in the rate of sea level rise and sediment availability, with implications for the overall resilience of marsh ecosystems to climatic changes. PMID:23401529

Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice

Directory of Open Access Journals (Sweden)

Waijiao Cai

2018-03-01

Full Text Available Alpha-synuclein (αSyn is encoded by the first causal gene identified in Parkinson's disease (PD and is the main component of Lewy bodies, a pathological hallmark of PD. aSyn-based animal models have contributed to our understanding of PD pathophysiology and to the development of therapeutics. Overexpression of human wildtype αSyn by viral vectors in rodents recapitulates the loss of dopaminergic neurons from the substantia nigra, another defining pathological feature of the disease. The development of a rat model exhibiting bimolecular fluorescence complementation (BiFC of αSyn by recombinant adeno-associated virus facilitates detection of the toxic αSyn oligomers species. We report here neurochemical, neuropathological and behavioral characterization of BiFC of αSyn in mice. Overexpression and oligomerization of αSyn through BiFC is detected by conjugated fluorescence. Reduced striatal dopamine and loss of nigral dopaminergic neurons are accompanied neuroinflammation and abnormal motor activities. Our mouse model may provide a valuable tool to study the role of αSyn in PD and to explore therapeutic approaches. Keywords: Parkinson's disease, Alpha-synuclein, Mouse model, Oligomers, Neuroinflammation

Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick.

Directory of Open Access Journals (Sweden)

Angélique Igel-Egalon

2017-09-01

Full Text Available Mammalian prions, the pathogens that cause transmissible spongiform encephalopathies, propagate by self-perpetuating the structural information stored in the abnormally folded, aggregated conformer (PrPSc of the host-encoded prion protein (PrPC. To date, no structural model related to prion assembly organization satisfactorily describes how strain-specified structural information is encoded and by which mechanism this information is transferred to PrPC. To achieve progress on this issue, we correlated the PrPSc quaternary structural transition from three distinct prion strains during unfolding and refolding with their templating activity. We reveal the existence of a mesoscopic organization in PrPSc through the packing of a highly stable oligomeric elementary subunit (suPrP, in which the strain structural determinant (SSD is encoded. Once kinetically trapped, this elementary subunit reversibly loses all replicative information. We demonstrate that acquisition of the templating interface and infectivity requires structural rearrangement of suPrP, in concert with its condensation. The existence of such an elementary brick scales down the SSD support to a small oligomer and provide a basis of reflexion for prion templating process and propagation.

Synthesis of POSS-based ionic conductors with low glass transition temperatures for efficient solid-state dye-sensitized solar cells.

Science.gov (United States)

Zhang, Wei; Wang, Zhong-Sheng

2014-07-09

Replacing liquid-state electrolytes with solid-state electrolytes has been proven to be an effective way to improve the durability of dye-sensitized solar cells (DSSCs). We report herein the synthesis of amorphous ionic conductors based on polyhedral oligomeric silsesquioxane (POSS) with low glass transition temperatures for solid-state DSSCs. As the ionic conductor is amorphous and in the elastomeric state at the operating temperature of DSSCs, good pore filling in the TiO2 film and good interfacial contact between the solid-state electrolyte and the TiO2 film can be guaranteed. When the POSS-based ionic conductor containing an allyl group is doped with only iodine as the solid-state electrolyte without any other additives, power conversion efficiency of 6.29% has been achieved with good long-term stability under one-sun soaking for 1000 h.

Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

Science.gov (United States)

Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

2014-01-01

Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

Novel thixotropic gel electrolytes based on dicationic bis-imidazolium salts for quasi-solid-state dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Jun Young [Department of Polymer Science and Engineering, SungKyunKwan University, Suwon, Kyunggi-do 440-746 (Korea); Functional Polymer Lab., Korea Institute of Science and Technology, Seoul 136-791 (Korea); Kim, Tae Ho [Department of Polymer Science and Engineering, SungKyunKwan University, Suwon, Kyunggi-do 440-746 (Korea); Kim, Dong Young; Park, Nam-Gyu [Energy Materials Research Center, Korea Institute of Science and Technology, Seoul 136-791 (Korea); Ahn, Kwang-Duk [Functional Polymer Lab., Korea Institute of Science and Technology, Seoul 136-791 (Korea)

2008-01-03

Novel thixotropic gel electrolytes have been successfully prepared by utilizing oligomeric poly(ethylene oxide) (PEO)-based bis-imidazolium diiodide salts and hydrophilic silica nanoparticles for application in quasi-solid-state dye-sensitized solar cells (DSSCs). The thixotropic gel-state of the ionic liquid-based composite electrolytes is confirmed by observing the typical hysteresis loop and temporary hydrogen bonding. On using the PEO-based composite electrolyte, a quasi-solid-state DSSC exhibited highly improved properties such as easy penetration of the electrolyte into the cell without leakage, long-term stability, high open-circuit voltage without the use of 4-tert-butylpyridine, and a high energy-conversion efficiency of 5.25% under AM 1.5 illumination (100 mW cm{sup -2}). (author)

Real Time Robot Soccer Game Event Detection Using Finite State Machines with Multiple Fuzzy Logic Probability Evaluators

Directory of Open Access Journals (Sweden)

Elmer P. Dadios

2009-01-01

Full Text Available This paper presents a new algorithm for real time event detection using Finite State Machines with multiple Fuzzy Logic Probability Evaluators (FLPEs. A machine referee for a robot soccer game is developed and is used as the platform to test the proposed algorithm. A novel technique to detect collisions and other events in microrobot soccer game under inaccurate and insufficient information is presented. The robots' collision is used to determine goalkeeper charging and goal score events which are crucial for the machine referee's decisions. The Main State Machine (MSM handles the schedule of event activation. The FLPE calculates the probabilities of the true occurrence of the events. Final decisions about the occurrences of events are evaluated and compared through threshold crisp probability values. The outputs of FLPEs can be combined to calculate the probability of an event composed of subevents. Using multiple fuzzy logic system, the FLPE utilizes minimal number of rules and can be tuned individually. Experimental results show the accuracy and robustness of the proposed algorithm.

Photoelectron Spectroscopy and Density Functional Theory Studies of Iron Sulfur (FeS)m- (m = 2-8) Cluster Anions: Coexisting Multiple Spin States.

Science.gov (United States)

Yin, Shi; Bernstein, Elliot R

2017-10-05

Iron sulfur cluster anions (FeS) m - (m = 2-8) are studied by photoelectron spectroscopy (PES) at 3.492 eV (355 nm) and 4.661 eV (266 nm) photon energies, and by density functional theory (DFT) calculations. The most probable structures and ground state spin multiplicities for (FeS) m - (m = 2-8) clusters are tentatively assigned through a comparison of their theoretical and experiment first vertical detachment energy (VDE) values. Many spin states lie within 0.5 eV of the ground spin state for the larger (FeS) m - (m ≥ 4) clusters. Theoretical VDEs of these low lying spin states are in good agreement with the experimental VDE values. Therefore, multiple spin states of each of these iron sulfur cluster anions probably coexist under the current experimental conditions. Such available multiple spin states must be considered when evaluating the properties and behavior of these iron sulfur clusters in real chemical and biological systems. The experimental first VDEs of (FeS) m - (m = 1-8) clusters are observed to change with the cluster size (number m). The first VDE trends noted can be related to the different properties of the highest singly occupied molecular orbitals (NBO, HSOMOs) of each cluster anion. The changing nature of the NBO/HSOMO of these (FeS) m - (m = 1-8) clusters from a p orbital on S, to a d orbital on Fe, and to an Fe-Fe bonding orbital is probably responsible for the observed increasing trend for their first VDEs with respect to m.

Two intestinal specific nuclear factors binding to the lactase-phlorizin hydrolase and sucrase-isomaltase promoters are functionally related oligomeric molecules

DEFF Research Database (Denmark)

Troelsen, J T; Mitchelmore, C; Sjöström, H

1994-01-01

Lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) are enterocyte-specific gene products. The identification of regulatory cis-elements in the promoter of these two genes has enabled us to carry out comparative studies of the corresponding intestinal-specific nuclear factors (NF-LPH1...... and SIF1-BP). Electrophoretic mobility shift assays demonstrated that the two nuclear factors compete for binding on the same cis-elements. The molecular size of the DNA binding polypeptide is estimated to be approximately 50 kDa for both factors. In the native form the factors are found as 250 k......Da oligomeric complexes. Based on these results NF-LPH1 and SIF1-BP are suggested to be either identical or closely related molecules....

Alpha B- and βA3-crystallins containing d-aspartic acids exist in a monomeric state.

Science.gov (United States)

Sakaue, Hiroaki; Takata, Takumi; Fujii, Norihiko; Sasaki, Hiroshi; Fujii, Noriko

2015-01-01

Crystallin stability and subunit-subunit interaction are essential for eye lens transparency. There are three types of crystallins in lens, designated as α-, β-, and γ-crystallins. Alpha-crystallin is a hetero-polymer of about 800kDa, consisting of 35-40 subunits of two different αA- and αB-subunits, each of 20kDa. The β/γ-crystallin superfamily comprises oligomeric β-crystallin (2-6 subunits) and monomeric γ-crystallin. Since lens proteins have very long half-lives, they undergo numerous post-translational modifications including racemization, isomerization, deamidation, oxidation, glycation, and truncation, which may decrease crystallin solubility and ultimately cause cataract formation. Racemization and isomerization of aspartyl (Asp) residues have been detected only in polymeric α- and oligomeric β-crystallin, while the situation in monomeric γ-crystallin has not been studied. Here, we investigated the racemization and isomerization of Asp in the γ-crystallin fraction of elderly donors. The results show that Asp residues of γS-, γD- and γC-crystallins were not racemized and isomerized. However, strikingly, we found that a portion of αB-crystallin and βA3-crystallin moved to the lower molecular weight fraction which is the same size of γ-crystallin. In those fractions, Asp-96 of αB-crystallin and Asp-37 of βA3-crystallin were highly inverted, which do not occur in the native lens higher molecular weight fraction. Our results indicate the possibility that the inversion of Asp residues may induce dissociation of αB- and βA3-crystallins from the polymeric and oligomeric states. This is the first report that stereoinversion of amino acids disturbs lens protein assembly in aged human lens. Copyright © 2014 Elsevier B.V. All rights reserved.

Multicore Magnetic Nanoparticles Coated with Oligomeric Micelles: Characterization and Potential for the Extraction of Contaminants over a Wide Polarity Range.

Science.gov (United States)

Naous, Mohamed; García-Gómez, Diego; López-Jiménez, Francisco José; Bouanani, Farida; Lunar, María Loreto; Rubio, Soledad

2017-01-17

Oligomeric micelles from sodium undecylenate (oSUD) were chemisorbed to magnetic iron oxide nanoparticles (MNPs) through a single-step synthetic route involving the simultaneous nanoparticle formation and functionalization in an aqueous medium. The resulting spherical nanoparticles (MNPs-oSUD) consisted of a concatenation of iron oxide cores, with an average size of 7.7 nm, bound by oSUD micelles (particle average diameter of ca. 200 nm). Micellar coverage was ∼50% of the MNP-oSUD (by weight) and offered multiple retention mechanisms (e.g., dispersion, hydrogen bonding, polar, and ionic) for solute solubilization while keeping it intact during analyte elution. The high density of micelles and variety of interactions provided by this sorbent rendered it highly efficient for the extraction of aromatic amines in a wide polarity range (log K ow values from -0.80 to 4.05) from textiles, urine, and wastewater. Extraction took 5 min, no cleanup or evaporation of the extracts was needed and the method, based on LC-MS/MS quantitation, proved matrix-independent. Recoveries for 17 aromatic amines in samples were in the range of 93%-123% while those with negative log K ow values were in the range of 69%-87%. Detection limits for aromatic amines in textiles (0.007-2 mg kg -1 ) were well below the limits legislated by the European Union (EU) (30 mg kg -1 ) and those in urine and wastewater (0.004-1.5 μg L -1 ) were at the level usually found in real-world applications. All the analyzed samples were positive in aromatic amines. The easy synthesis and excellent extraction properties of MNPs-oSUD anticipate their high potential not only for multiresidue analysis but also in other fields such as water remediation.

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

Science.gov (United States)

Fang, Weidong; Chen, Huiyue; Wang, Hansheng; Zhang, Han; Liu, Mengqi; Puneet, Munankami; Lv, Fajin; Cheng, Oumei; Wang, Xuefeng; Lu, Xiurong; Luo, Tianyou

2015-12-01

The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome. © 2015 International Parkinson and Movement Disorder Society.

Nucleotide-Binding Oligomerization Domain-1 and -2 Play No Role in Controlling Brucella abortus Infection in Mice

Directory of Open Access Journals (Sweden)

Fernanda S. Oliveira

2012-01-01

Full Text Available Nucleotide-binding oligomerization domain proteins (NODs are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. Further, several in vivo studies have demonstrated a role for Nod1 and Nod2 in host defense against bacterial pathogens. Here, we demonstrated that macrophages from NOD1-, NOD2-, and Rip2-deficient mice produced lower levels of TNF-α following infection with live Brucella abortus compared to wild-type mice. Similar reduction on cytokine synthesis was not observed for IL-12 and IL-6. However, NOD1, NOD2, and Rip2 knockout mice were no more susceptible to infection with virulent B. abortus than wild-type mice. Additionally, spleen cells from NOD1-, NOD2-, and Rip2-deficient mice showed unaltered production of IFN-γ compared to C57BL/6 mice. Taken together, this study demonstrates that NOD1, NOD2 and Rip2 are dispensable for the control of B. abortus during in vivo infection.

Preparation of polyhedral oligomeric silsesquioxane based hybrid monoliths by ring-opening polymerization for capillary LC and CEC.

Science.gov (United States)

Lin, Hui; Zhang, Zhenbin; Dong, Jing; Liu, Zhongshan; Ou, Junjie; Zou, Hanfa

2013-09-01

A new organic-inorganic hybrid monolith was prepared by the ring-opening polymerization of octaglycidyldimethylsilyl polyhedral oligomeric silsesquioxane (POSS) with 1,4-butanediamine (BDA) using 1-propanol, 1,4-butanediol, and PEG 10,000 as a porogenic system. Benefiting from the moderate phase separation process, the resulting poly(POSS-co-BDA) hybrid monolith possessed a uniform microstructure and exhibited excellent performance in chromatographic applications. Neutral, acidic, and basic compounds were successfully separated on the hybrid monolith in capillary LC (cLC), and high column efficiencies were achieved in all of the separations. In addition, as the amino groups could generate a strong EOF, the hybrid monolith was also applied in CEC for the separation of neutral and polar compounds, and a satisfactory performance was obtained. These results demonstrate that the poly(POSS-co-BDA) hybrid monolith is a good separation media in chromatographic separations of various types of compounds by both cLC and CEC. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional significance of the oligomeric structure of the Na,K-pump from radiation inactivation and ligand binding

International Nuclear Information System (INIS)

Norby, J.G.; Jensen, J.

1991-01-01

The present article is concerned with the oligomeric structure and function of the Na,K-pump (Na,K-ATPase). The questions we have addressed, using radiation inactivation and target size analysis as well as ligand binding, are whether the minimal structural unit and the functional unit have more than one molecule of the catalytic subunit, alpha. The authors first discuss the fundamentals of the radiation inactivation method and emphasize the necessity for rigorous internal standardization with enzymes of known molecular mass. They then demonstrate that the radiation inactivation of Na,K-ATPase is a stepwise process which leads to intermediary fragments of the alpha-subunit with partial catalytic activity. From the target size analysis it is most likely that the membrane-bound Na,K-ATPase is structurally organized as a diprotomer containing two alpha-subunits. Determination of ADP- and ouabain-binding site stoichiometry favors a theory with one substrate site per (alpha beta) 2. 47 references

FEASIBILITY ANALYSIS FOR INSTALLING A CIRCULATING FLUIDIZED BED BOILER FOR COFIRING MULTIPLE BIOFUELS AND OTHER WASTES WITH COAL AT PENN STATE UNIVERSITY

International Nuclear Information System (INIS)

Bruce G. Miller; Sharon Falcone Miller; Robert Cooper; Douglas Donovan; John Gaudlip; Matthew Lapinsky; William Serencsits; Neil Raskin; Dale Lamke; Joseph J. Battista

2001-01-01

The Pennsylvania State University, under contract to the U.S. Department of Energy (DOE), National Energy Technology Laboratory (NETL) is performing a feasibility analysis on installing a state-of-the-art circulating fluidized bed (CFB) boiler and ceramic filter emission control device at Penn State's University Park campus for cofiring multiple biofuels and other wastes with coal, and developing a test program to evaluate cofiring multiple biofuels and coal-based feedstocks. Penn State currently operates an aging stoker-fired steam plant at its University Park campus and has spent considerable resources over the last ten to fifteen years investigating boiler replacements and performing life extension studies. This effort, in combination with a variety of agricultural and other wastes generated at the agricultural-based university and the surrounding rural community, has led Penn State to assemble a team of fluidized bed and cofiring experts to assess the feasibility of installing a CFB boiler for cofiring biomass and other wastes along with coal-based fuels. The objective of the project is being accomplished using a team that includes personnel from Penn State's Energy Institute and the Office of Physical Plant, Foster Wheeler Energy Services, Inc., and Cofiring Alternatives

A composite state method for ensemble data assimilation with multiple limited-area models

Directory of Open Access Journals (Sweden)

Matthew Kretschmer

2015-04-01

Full Text Available Limited-area models (LAMs allow high-resolution forecasts to be made for geographic regions of interest when resources are limited. Typically, boundary conditions for these models are provided through one-way boundary coupling from a coarser resolution global model. Here, data assimilation is considered in a situation in which a global model supplies boundary conditions to multiple LAMs. The data assimilation method presented combines information from all of the models to construct a single ‘composite state’, on which data assimilation is subsequently performed. The analysis composite state is then used to form the initial conditions of the global model and all of the LAMs for the next forecast cycle. The method is tested by using numerical experiments with simple, chaotic models. The results of the experiments show that there is a clear forecast benefit to allowing LAM states to influence one another during the analysis. In addition, adding LAM information at analysis time has a strong positive impact on global model forecast performance, even at points not covered by the LAMs.

Influence of oligomeric herbicidal ionic liquids with MCPA and Dicamba anions on the community structure of autochthonic bacteria present in agricultural soil

Energy Technology Data Exchange (ETDEWEB)

Ławniczak, Ł., E-mail: lukasz.k.lawniczak@wp.pl [Department of Chemical Technology, Poznan University of Technology, 60-965 Poznan (Poland); Syguda, A., E-mail: Anna.Syguda@put.poznan.pl [Department of Chemical Technology, Poznan University of Technology, 60-965 Poznan (Poland); Borkowski, A., E-mail: a.borkowski@uw.edu.pl [Faculty of Geology, University of Warsaw, 02-089 Warsaw (Poland); Cyplik, P., E-mail: pcyplik@wp.pl [Department of Biotechnology and Food Microbiology, University of Life Sciences in Poznan, 60-627 Poznan (Poland); Marcinkowska, K., E-mail: k.marcinkowska@iorpib.poznan.pl [Institute of Plant Protection - National Research Institute, Poznan 60-318 (Poland); Wolko, Ł., E-mail: wolko@o2.pl [Department of Biochemistry and Biotechnology, Poznań University of Life Sciences in Poznan, 60-632 Poznan (Poland); Praczyk, T., E-mail: t.praczyk@iorpib.poznan.pl [Institute of Plant Protection - National Research Institute, Poznan 60-318 (Poland); Chrzanowski, Ł., E-mail: Lukasz.Chrzanowski@put.poznan.pl [Department of Chemical Technology, Poznan University of Technology, 60-965 Poznan (Poland); Pernak, J., E-mail: Juliusz.Pernak@put.poznan.pl [Department of Chemical Technology, Poznan University of Technology, 60-965 Poznan (Poland)

2016-09-01

The aim of this study was to evaluate the impact of selected herbicidal ionic liquids (HILs), which exhibit high efficacy in terms of weed control and low toxicity, but may be persistent due to limited biodegradability, on the community structure of autochthonic bacteria present in agricultural soil. Four different oligomeric HILs (with two types of cations and different ratio of herbicidal anions) were synthesized and characterized by employing {sup 1}H and {sup 13}C NMR. The results of biodegradation assay indicated that none of the tested HILs could be classified as readily biodegradable (biodegradation rate ranged from 0 to 7%). The conducted field studies confirmed that the herbicidal efficacy of the HILs was higher compared to the reference herbicide mixture by 10 to 30%, depending on the dose and weed species. After termination of field studies, the soil treated with the tested HILs was subjected to next generation sequencing in order to investigate the potential changes in the bacterial community structure. Proteobacteria was the dominant phylum in all studied samples. Treatment with the studied HILs resulted in an increase of Actinobacteria compared to the reference herbicidal mixture. Differenced among the studied HILs were generally associated with a significantly higher abundance of Bacteroidetes in case of 1-HIL-Dicamba 1/3 and Firmicutes in case of 2-HIL-Dicamba 1/3. - Highlights: • Impact of herbicidal ionic liquids on bacterial community structure was studied. • Oligomeric herbicidal ionic liquids were effective but not readily biodegradable. • Next generation sequencing was used to evaluate shifts in bacterial abundance. • Treatment during field trials resulted in changes at class and species level. • Use of herbicidal ionic liquids affects the structure of autochthonic soil bacteria.

Influence of oligomeric herbicidal ionic liquids with MCPA and Dicamba anions on the community structure of autochthonic bacteria present in agricultural soil

International Nuclear Information System (INIS)

Ławniczak, Ł.; Syguda, A.; Borkowski, A.; Cyplik, P.; Marcinkowska, K.; Wolko, Ł.; Praczyk, T.; Chrzanowski, Ł.; Pernak, J.

2016-01-01

The aim of this study was to evaluate the impact of selected herbicidal ionic liquids (HILs), which exhibit high efficacy in terms of weed control and low toxicity, but may be persistent due to limited biodegradability, on the community structure of autochthonic bacteria present in agricultural soil. Four different oligomeric HILs (with two types of cations and different ratio of herbicidal anions) were synthesized and characterized by employing "1H and "1"3C NMR. The results of biodegradation assay indicated that none of the tested HILs could be classified as readily biodegradable (biodegradation rate ranged from 0 to 7%). The conducted field studies confirmed that the herbicidal efficacy of the HILs was higher compared to the reference herbicide mixture by 10 to 30%, depending on the dose and weed species. After termination of field studies, the soil treated with the tested HILs was subjected to next generation sequencing in order to investigate the potential changes in the bacterial community structure. Proteobacteria was the dominant phylum in all studied samples. Treatment with the studied HILs resulted in an increase of Actinobacteria compared to the reference herbicidal mixture. Differenced among the studied HILs were generally associated with a significantly higher abundance of Bacteroidetes in case of 1-HIL-Dicamba 1/3 and Firmicutes in case of 2-HIL-Dicamba 1/3. - Highlights: • Impact of herbicidal ionic liquids on bacterial community structure was studied. • Oligomeric herbicidal ionic liquids were effective but not readily biodegradable. • Next generation sequencing was used to evaluate shifts in bacterial abundance. • Treatment during field trials resulted in changes at class and species level. • Use of herbicidal ionic liquids affects the structure of autochthonic soil bacteria.

Coatings of molecularly imprinted polymers based on polyhedral oligomeric silsesquioxane for open tubular capillary electrochromatography.

Science.gov (United States)

Zhao, Qing-Li; Zhou, Jin; Zhang, Li-Shun; Huang, Yan-Ping; Liu, Zhao-Sheng

2016-05-15

Polyhedral oligomeric silsesquioxane (POSS) was successfully applied, for the first time, to prepare imprinted monolithic coating for capillary electrochromatography. The imprinted monolithic coating was synthesized with a mixture of PSS-(1-Propylmethacrylate)-heptaisobutyl substituted (MA 0702), S-amlodipine (template), methacrylic acid (functional monomer), and 2-methacrylamidopropyl methacrylate (crosslinker), in a porogenic mixture of toluene-isooctane. The influence of synthesis parameters on the imprinting effect and separation performance, including the amount of MA 0702, the ratio of template to monomer, and the ratio of monomer to crosslinker, was investigated. The greatest resolution for enantiomers separation on the imprinted monolithic column prepared with MA 0702 was up to 22.3, about 2 times higher than that prepared in absence of the POSS. Column efficiency on the POSS-based MIP coatings was beyond 30,000 plate m(-1). The comparisons between MIP coating synthesized with the POSS and without the POSS were made in terms of selectivity, column efficiency, and resolution. POSS-based MIP capillaries with naproxen or zopiclone was also prepared and separation of enantiomers can be achieved. Copyright © 2016 Elsevier B.V. All rights reserved.

Construction of porous cationic frameworks by crosslinking polyhedral oligomeric silsesquioxane units with N-heterocyclic linkers

Science.gov (United States)

Chen, Guojian; Zhou, Yu; Wang, Xiaochen; Li, Jing; Xue, Shuang; Liu, Yangqing; Wang, Qian; Wang, Jun

2015-06-01

In fields of materials science and chemistry, ionic-type porous materials attract increasing attention due to significant ion-exchanging capacity for accessing diversified applications. Facing the fact that porous cationic materials with robust and stable frameworks are very rare, novel tactics that can create new type members are highly desired. Here we report the first family of polyhedral oligomeric silsesquioxane (POSS) based porous cationic frameworks (PCIF-n) with enriched poly(ionic liquid)-like cationic structures, tunable mesoporosities, high surface areas (up to 1,025 m2 g-1) and large pore volumes (up to 0.90 cm3 g-1). Our strategy is designing the new rigid POSS unit of octakis(chloromethyl)silsesquioxane and reacting it with the rigid N-heterocyclic cross-linkers (typically 4,4‧-bipyridine) for preparing the desired porous cationic frameworks. The PCIF-n materials possess large surface area, hydrophobic and special anion-exchanging property, and thus are used as the supports for loading guest species PMo10V2O405- the resultant hybrid behaves as an efficient heterogeneous catalyst for aerobic oxidation of benzene and H2O2-mediated oxidation of cyclohexane.

Morphological evolution in dewetting polystyrene/polyhedral oligomeric silsesquioxane thin film bilayers.

Science.gov (United States)

Paul, Rituparna; Karabiyik, Ufuk; Swift, Michael C; Hottle, John R; Esker, Alan R

2008-05-06

Morphological evolution in dewetting thin film bilayers of polystyrene (PS) and a polyhedral oligomeric silsesquioxane (POSS), trisilanolphenyl-POSS (TPP), was studied as a function of annealing temperature and annealing time. The results demonstrate unique dewetting morphologies in PS/TPP bilayers at elevated temperatures that are significantly different from those typically observed in dewetting polymer/polymer bilayers. During temperature ramp studies by optical microscopy (OM) in the reflection mode, PS/TPP bilayers form cracks with a weak optical contrast at approximately 130 degrees C. The crack formation is attributed to tensile stresses within the upper TPP layer. The weak optical contrast of the cracks observed in the bilayers for annealing temperatures below approximately 160 degrees C is consistent with the cracking and dewetting of only the upper TPP layer from the underlying PS layer. The optical contrast of the morphological features is significantly enhanced at annealing temperatures of >160 degrees C. This observation suggests dewetting of both the upper TPP and the lower PS layers that results in the exposure of the silicon substrate. Upon annealing the PS/TPP bilayers at 200 degrees C in a temperature jump experiment, the upper TPP layer undergoes instantaneous cracking as observed by OM. These cracks in the upper TPP layer serve as nucleation sites for rapid dewetting and aggregation of the TPP layer, as revealed by OM and atomic force microscopy (AFM). X-ray photoelectron spectroscopy (XPS) results indicated that dewetting of the lower PS layer ensued for annealing times >5 min and progressed up to 90 min. For annealing times >90 min, OM, AFM, and XPS results revealed complete dewetting of both the layers with the formation of TPP encapsulated PS droplets.

Energy Management Strategy Based on Multiple Operating States for a Photovoltaic/Fuel Cell/Energy Storage DC Microgrid

Directory of Open Access Journals (Sweden)

Ying Han

2017-01-01

Full Text Available It is a great challenge for DC microgrids with stochastic renewable sources and volatility loads to achieve better operation performance. This study proposes an energy management strategy based on multiple operating states for a DC microgrid, which is comprised of a photovoltaic (PV array, a proton exchange membrane fuel cell (PEMFC system, and a battery bank. This proposed strategy can share the power properly and keep the bus voltage steady under different operating states (the state of charge (SOC of the battery bank, loading conditions, and PV array output power. In addition, a microgrids test platform is established. In order to verify the effectiveness of the proposed energy management strategy, the strategy is implemented in a hardware system and experimentally tested under different operating states. The experimental results illustrate the good performance of the proposed control strategy for the DC microgrid under different scenarios of power generation and load demand.

Multiple stable states of a periodically driven electron spin in a quantum dot using circularly polarized light

Science.gov (United States)

Korenev, V. L.

2011-06-01

The periodical modulation of circularly polarized light with a frequency close to the electron spin resonance frequency induces a sharp change of the single electron spin orientation. Hyperfine interaction provides a feedback, thus fixing the precession frequency of the electron spin in the external and the Overhauser field near the modulation frequency. The nuclear polarization is bidirectional and the electron-nuclear spin system (ENSS) possesses a few stable states. The same physics underlie the frequency-locking effect for two-color and mode-locked excitations. However, the pulsed excitation with mode-locked laser brings about the multitudes of stable states in ENSS in a quantum dot. The resulting precession frequencies of the electron spin differ in these states by the multiple of the modulation frequency. Under such conditions ENSS represents a digital frequency converter with more than 100 stable channels.

Recovery from an acute relapse is associated with changes in motor resting-state connectivity in multiple sclerosis

DEFF Research Database (Denmark)

Dogonowski, Anne-Marie; Blinkenberg, Morten; Paulson, Olaf B.

2016-01-01

Resting-state functional MRI (rs-fMRI) of the brain has been successfully used to identify altered functional connectivity in the motor network in multiple sclerosis (MS).1 In clinically stable patients with MS, we recently demonstrated increased coupling between the basal ganglia and the motor...... network.1 Accordingly, rs-fMRI in MS is particularly suited to investigate functional reorganisation of the motor network in the remission phase after a relapse because the resting-state connectivity pattern is not influenced by interindividual differences in motor ability and task performance....... In this prospective rs-fMRI study, we mapped acute changes in resting-state motor connectivity in 12 patients with relapsing forms of MS presenting with an acute relapse involving an upper limb paresis. Previous functional MRI (fMRI) studies have shown that the activation of sensorimotor areas was stronger and more...

Endohedral complexes of Polyhedral Oligomeric Silsesquioxane (POSS) cages with transition metal dihydrides

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiqiao; Corn, John; Hagelberg, Frank, E-mail: hagelber@etsu.edu

2013-11-29

Highlights: • Comparative studies of POSS cages with endohedral metal dihydrides. • Exothermic inclusion was found for the T{sub 10} cage with MH{sub 2}, M = Ti, Ru, Os, Pt. • Within this group of metal atoms, the only exothermic MH{sub 4}@T{sub m} unit is that with M = Os. • Enhanced hydrogen atom density, as compared to free MH{sub 4}, was found in the cage. • No exothermic solutions were identified for MH{sub 6}@T{sub 10}. - Abstract: Polyhedral Oligomeric Silsesquioxane (POSS) cages are investigated in terms of their potential to enclose small metal hydrides, with the objective of defining conditions that maximize the number of encapsulated hydrogen atoms. Systems of the form MH{sub 2n}@T{sub m}, where n = 1–3, m = 8, 10, and M comprises metal atom species of the groups IV, VI, VIII, X, and XII, are studied by methods of ab initio and density functional theory (DFT). The resulting composites are categorized with respect to their structural and energetic features. For MH{sub 2}@T{sub 8}, it is found in all cases considered that including MH{sub 2} into the POSS cage is an endothermic process. For MH{sub 2}@T{sub 10} and M = Ti, Ru, Os, Pt, inclusion of the MH{sub 2} guest into the cage turns out to be exothermic, and also leaves the cage intact. For MH{sub 4}@T{sub m}, this behavior is only observed for one system, OsH{sub 4}@T{sub 10}.

The Amsterdam Resting-State Questionnaire reveals multiple phenotypes of resting-state cognition

Science.gov (United States)

Diaz, B. Alexander; Van Der Sluis, Sophie; Moens, Sarah; Benjamins, Jeroen S.; Migliorati, Filippo; Stoffers, Diederick; Den Braber, Anouk; Poil, Simon-Shlomo; Hardstone, Richard; Van't Ent, Dennis; Boomsma, Dorret I.; De Geus, Eco; Mansvelder, Huibert D.; Van Someren, Eus J. W.; Linkenkaer-Hansen, Klaus

2013-01-01

Resting-state neuroimaging is a dominant paradigm for studying brain function in health and disease. It is attractive for clinical research because of its simplicity for patients, straightforward standardization, and sensitivity to brain disorders. Importantly, non-sensory experiences like mind wandering may arise from ongoing brain activity. However, little is known about the link between ongoing brain activity and cognition, as phenotypes of resting-state cognition—and tools to quantify them—have been lacking. To facilitate rapid and structured measurements of resting-state cognition we developed a 50-item self-report survey, the Amsterdam Resting-State Questionnaire (ARSQ). Based on ARSQ data from 813 participants assessed after 5 min eyes-closed rest in their home, we identified seven dimensions of resting-state cognition using factor analysis: Discontinuity of Mind, Theory of Mind, Self, Planning, Sleepiness, Comfort, and Somatic Awareness. Further, we showed that the structure of cognition was similar during resting-state fMRI and EEG, and that the test-retest correlations were remarkably high for all dimensions. To explore whether inter-individual variation of resting-state cognition is related to health status, we correlated ARSQ-derived factor scores with psychometric scales measuring depression, anxiety, and sleep quality. Mental health correlated positively with Comfort and negatively with Discontinuity of Mind. Finally, we show that sleepiness may partially explain a resting-state EEG profile previously associated with Alzheimer's disease. These findings indicate that the ARSQ readily provides information about cognitive phenotypes and that it is a promising tool for research on the neural correlates of resting-state cognition in health and disease. PMID:23964225

Hexameric oligomerization of mitochondrial peroxiredoxin PrxIIF and formation of an ultrahigh affinity complex with its electron donor thioredoxin Trx-o.

Science.gov (United States)

Barranco-Medina, Sergio; Krell, Tino; Bernier-Villamor, Laura; Sevilla, Francisca; Lázaro, Juan-José; Dietz, Karl-Josef

2008-01-01

Mitochondria from plants, yeast, and animals each contain at least one peroxiredoxin (Prx) that is involved in peroxide detoxification and redox signalling. The supramolecular dynamics of atypical type II Prx targeted to the mitochondrion was addressed in pea. Microcalorimetric (ITC) titrations identified an extremely high-affinity binding between the mitochondrial PsPrxIIF and Trx-o with a K(D) of 126+/-14 pM. Binding was driven by a favourable enthalpy change (DeltaH= -60.6 kcal mol(-1)) which was counterbalanced by unfavourable entropy changes (TDeltaS= -47.1 kcal mol(-1)). This is consistent with the occurrence of large conformational changes during binding which was abolished upon site-directed mutaganesis of the catalytic C59S and C84S. The redox-dependent interaction was confirmed by gel filtration of mitochondrial extracts and co-immunoprecipitation from extracts. The heterocomplex of PsPrxIIF and Trx-o reduced peroxide substrates more efficiently than free PsPrxIIF suggesting that Trx-o serves as an efficient and specific electron donor to PsPrxIIF in vivo. Other Trx-s tested by ITC analysis failed to interact with PsPrxIIF indicating a specific recognition of PsPrxIIF by Trx-o. PsPrxIIF exists primarily as a dimer or a hexamer depending on the redox state. In addition to the well-characterized oligomerization of classical 2-Cys Prx the results also show that atypical Prx undergo large structural reorganization with implications for protein-protein interaction and function.

The Amsterdam Resting-State Questionnaire reveals multiple phenotypes of resting-state cognition

Directory of Open Access Journals (Sweden)

B. Alexander eDiaz

2013-08-01

Full Text Available Resting-state neuroimaging is a dominant paradigm for studying brain function in health and disease. It is attractive for clinical research because of its simplicity for patients, straightforward standardization, and sensitivity to brain disorders. Importantly, non-sensory experiences like mind wandering may arise from ongoing brain activity. However, little is known about the link between ongoing brain activity and cognition, as phenotypes of resting-state cognition—and tools to quantify them—have been lacking. To facilitate rapid and structured measurements of resting-state cognition we developed a 50-item self-report survey, the Amsterdam Resting-State Questionnaire (ARSQ. Based on ARSQ data from 813 participants assessed after five minutes eyes-closed rest in their home, we identified seven dimensions of resting-state cognition using factor analysis: Discontinuity of Mind, Theory of Mind, Self, Planning, Sleepiness, Comfort, and Somatic Awareness. Further, we showed that the structure of cognition was similar during resting-state fMRI and EEG, and that the test-retest correlations were remarkably high for all dimensions. To explore whether inter-individual variation of resting-state cognition is related to health status, we correlated ARSQ-derived factor scores with psychometric scales measuring depression, anxiety, and sleep quality. Mental health correlated positively with Comfort and negatively with Discontinuity of Mind. Finally, we show that sleepiness may partially explain a resting-state EEG profile previously associated with Alzheimer’s disease. These findings indicate that the ARSQ readily provides information about cognitive phenotypes and that it is a promising tool for research on the neural correlates of resting-state cognition in health and disease.

Post-coma persons emerging from a minimally conscious state with multiple disabilities make technology-aided phone contacts with relevant partners

NARCIS (Netherlands)

Lancioni, G.E.; Singh, N.N.; O'Reilly, M.F.; Sigafoos, J.; Oliva, D.; Campodonico, F.; D'Amico, F.; Buonocunto, F.; Sacco, V.; Didden, H.C.M.

2013-01-01

Post-coma individuals emerging from a minimally conscious state with multiple disabilities may enjoy contact with relevant partners (e.g., family members and friends), but may not have easy access to them. These two single-case studies assessed whether those individuals could make contact with

Multiple-Pulse Operation and Bound States of Solitons in Passive Mode-Locked Fiber Lasers

Directory of Open Access Journals (Sweden)

A. Komarov

2012-01-01

Full Text Available We present results of our research on a multiple-pulse operation of passive mode-locked fiber lasers. The research has been performed on basis of numerical simulation. Multihysteresis dependence of both an intracavity energy and peak intensities of intracavity ultrashort pulses on pump power is found. It is shown that the change of a number of ultrashort pulses in a laser cavity can be realized by hard as well as soft regimes of an excitation and an annihilation of new solitons. Bound steady states of interacting solitons are studied for various mechanisms of nonlinear losses shaping ultrashort pulses. Possibility of coding of information on basis of soliton trains with various bonds between neighboring pulses is discussed. The role of dispersive wave emitted by solitons because of lumped intracavity elements in a formation of powerful soliton wings is analyzed. It is found that such powerful wings result in large bounding energies of interacting solitons in steady states. Various problems of a soliton interaction in passive mode-locked fiber lasers are discussed.

Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health--a randomized controlled clinical pilot study.

Science.gov (United States)

Weseler, Antje R; Ruijters, Erik J B; Drittij-Reijnders, Marie-José; Reesink, Koen D; Haenen, Guido R M M; Bast, Aalt

2011-01-01

Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded. In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets. In the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, Pbenefit of an 8 weeks supplementation with 200 mg/d MOF in humans. ClinicalTrials.gov NCT00742287.

Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation

Science.gov (United States)

Meng, Guoyu; Spahich, Nicole; Kenjale, Roma; Waksman, Gabriel; St Geme, Joseph W

2011-01-01

Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell–cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae HapS passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell–cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap–Hap dimerization and higher degrees of multimerization through its F1–F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell–cell interaction and formation of complex microcolonies. PMID:21841773

Self-association of the Lentivirus protein, Nef

Directory of Open Access Journals (Sweden)

Garcia J Victor

2010-09-01

Full Text Available Abstract Background The HIV-1 pathogenic factor, Nef, is a multifunctional protein present in the cytosol and on membranes of infected cells. It has been proposed that a spatial and temporal regulation of the conformation of Nef sequentially matches Nef's multiple functions to the process of virion production. Further, it has been suggested that dimerization is required for multiple Nef activities. A dimerization interface has been proposed based on intermolecular contacts between Nefs within hexagonal Nef/FynSH3 crystals. The proposed dimerization interface consists of the hydrophobic B-helix and flanking salt bridges between R105 and D123. Here, we test whether Nef self-association is mediated by this interface and address the overall significance of oligomerization. Results By co-immunoprecipitation assays, we demonstrated that HIV-1Nef exists as monomers and oligomers with about half of the Nef protomers oligomerized. Nef oligomers were found to be present in the cytosol and on membranes. Removal of the myristate did not enhance the oligomerization of soluble Nef. Also, SIVNef oligomerizes despite lacking a dimerization interface functionally homologous to that proposed for HIV-1Nef. Moreover, HIV-1Nef and SIVNef form hetero-oligomers demonstrating the existence of homologous oligomerization interfaces that are distinct from that previously proposed (R105-D123. Intracellular cross-linking by formaldehyde confirmed that SF2Nef dimers are present in intact cells, but surprisingly self-association was dependent on R105, but not D123. SIVMAC239Nef can be cross-linked at its only cysteine, C55, and SF2Nef is also cross-linked, but at C206 instead of C55, suggesting that Nefs exhibit multiple dimeric structures. ClusPro dimerization analysis of HIV-1Nef homodimers and HIV-1Nef/SIVNef heterodimers identified a new potential dimerization interface, including a dibasic motif at R105-R106 and a six amino acid hydrophobic surface. Conclusions We have

Single Site Mutations in the Hetero-oligomeric Mrp Antiporter from Alkaliphilic Bacillus pseudofirmus OF4 That Affect Na+/H+ Antiport Activity, Sodium Exclusion, Individual Mrp Protein Levels, or Mrp Complex Formation*

OpenAIRE

Morino, Masato; Natsui, Shinsuke; Ono, Tomohiro; Swartz, Talia H.; Krulwich, Terry A.; Ito, Masahiro

2010-01-01

Mrp systems are widely distributed and structurally complex cation/proton antiporters. Antiport activity requires hetero-oligomeric complexes of all six or seven hydrophobic Mrp proteins (MrpA–MrpG). Here, a panel of site-directed mutants in conserved or proposed motif residues was made in the Mrp Na+(Li+)/H+ antiporter from an alkaliphilic Bacillus. The mutant operons were expressed in antiporter-deficient Escherichia coli KNabc and assessed for antiport properties, support of sodium resista...

An Empirical Method to Fuse Partially Overlapping State Vectors for Distributed State Estimation

NARCIS (Netherlands)

Sijs, J.; Hanebeck, U.; Noack, B.

2013-01-01

State fusion is a method for merging multiple estimates of the same state into a single fused estimate. Dealing with multiple estimates is one of the main concerns in distributed state estimation, where an estimated value of the desired state vector is computed in each node of a networked system.

Multiple neural states of representation in short-term memory? It's a matter of attention.

Science.gov (United States)

Larocque, Joshua J; Lewis-Peacock, Jarrod A; Postle, Bradley R

2014-01-01

Short-term memory (STM) refers to the capacity-limited retention of information over a brief period of time, and working memory (WM) refers to the manipulation and use of that information to guide behavior. In recent years it has become apparent that STM and WM interact and overlap with other cognitive processes, including attention (the selection of a subset of information for further processing) and long-term memory (LTM-the encoding and retention of an effectively unlimited amount of information for a much longer period of time). Broadly speaking, there have been two classes of memory models: systems models, which posit distinct stores for STM and LTM (Atkinson and Shiffrin, 1968; Baddeley and Hitch, 1974); and state-based models, which posit a common store with different activation states corresponding to STM and LTM (Cowan, 1995; McElree, 1996; Oberauer, 2002). In this paper, we will focus on state-based accounts of STM. First, we will consider several theoretical models that postulate, based on considerable behavioral evidence, that information in STM can exist in multiple representational states. We will then consider how neural data from recent studies of STM can inform and constrain these theoretical models. In the process we will highlight the inferential advantage of multivariate, information-based analyses of neuroimaging data (fMRI and electroencephalography (EEG)) over conventional activation-based analysis approaches (Postle, in press). We will conclude by addressing lingering questions regarding the fractionation of STM, highlighting differences between the attention to information vs. the retention of information during brief memory delays.

Multiple neural states of representation in short-term memory? It's a matter of attention

Directory of Open Access Journals (Sweden)

Joshua J Larocque

2014-01-01

Full Text Available Short-term memory (STM refers to the capacity-limited retention of information over a brief period of time, and working memory (WM refers to the manipulation and use of that information to guide behavior. In recent years it has become apparent that STM and WM interact and overlap with other cognitive processes, including attention (the selection of a subset of information for further processing and long-term memory (LTM – the encoding and retention of an effectively unlimited amount of information for a much longer period of time. Broadly speaking, there have been two classes of memory models: systems models, which posit distinct stores for STM and LTM (Atkinson & Shiffrin, 1968; Baddeley & Hitch, 1974; and state-based models, which posit a common store with different activation states corresponding to STM and LTM (Cowan, 1995; McElree, 1996; Oberauer, 2002. In this paper, we will focus on state-based accounts of STM. First, we will consider several theoretical models that postulate, based on considerable behavioral evidence, that information in STM can exist in multiple representational states. We will then consider how neural data from recent studies of STM can inform and constrain these theoretical models. In the process we will highlight the inferential advantage of multivariate, information-based analyses of neuroimaging data (fMRI and EEG over conventional activation-based analysis approaches (Postle, in press. We will conclude by addressing lingering questions regarding the fractionation of STM, highlighting differences between the attention to information vs. the retention of information during brief memory delays.

Generalized Grover's Algorithm for Multiple Phase Inversion States

Science.gov (United States)

Byrnes, Tim; Forster, Gary; Tessler, Louis

2018-02-01

Grover's algorithm is a quantum search algorithm that proceeds by repeated applications of the Grover operator and the Oracle until the state evolves to one of the target states. In the standard version of the algorithm, the Grover operator inverts the sign on only one state. Here we provide an exact solution to the problem of performing Grover's search where the Grover operator inverts the sign on N states. We show the underlying structure in terms of the eigenspectrum of the generalized Hamiltonian, and derive an appropriate initial state to perform the Grover evolution. This allows us to use the quantum phase estimation algorithm to solve the search problem in this generalized case, completely bypassing the Grover algorithm altogether. We obtain a time complexity of this case of √{D /Mα }, where D is the search space dimension, M is the number of target states, and α ≈1 , which is close to the optimal scaling.

One motif to bind them: A small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs.

Science.gov (United States)

Lock, Antonia; Forfar, Rachel; Weston, Cathryn; Bowsher, Leo; Upton, Graham J G; Reynolds, Christopher A; Ladds, Graham; Dixon, Ann M

2014-12-01

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs. Copyright © 2014. Published by Elsevier B.V.

Biochemical and Structural Analysis of Hormone-sensitive Lipase Homolog EstE7: Insight into the Stabilized Dimerization of HSL-Homolog Proteins

International Nuclear Information System (INIS)

Nam, Ki Hyun; Park, Sung Ha; Lee, Won Ho; Hwang, Kwang Yeon

2010-01-01

Hormone sensitive lipase (HSL) plays a major role in energy homeostasis and lipid metabolism. Several crystal structures of HSL-homolog proteins have been identified, which has led to a better understanding of its molecular function. HSLhomolog proteins exit as both monomer and dimer, but the biochemical and structural basis for such oligomeric states has not been successfully elucidated. Therefore, we determined the crystal structure of HSL-homolog protein EstE7 from a metagenome library at 2.2 A resolution and characterized the oligomeric states of EstE7 both structurally and biochemically. EstE7 protein prefers the dimeric state in solution, which is supported by its higher enzymatic activity in the dimeric state. In the crystal form, EstE7 protein shows two-types of dimeric interface. Specifically, dimerization via the external β8-strand occurred through tight association between two pseudosymmetric folds via salt bridges, hydrogen bonds and van der Waals interactions. This dimer formation was similar to that of other HSL-homolog protein structures such as AFEST, BEFA, and EstE1. We anticipate that our results will provide insight into the oligomeric state of HSLhomolog proteins

Prolonged Exposure of Cortical Neurons to Oligomeric Amyloid-β Impairs NMDA Receptor Function Via NADPH Oxidase-Mediated ROS Production: Protective Effect of Green Tea (--Epigallocatechin-3-Gallate

Directory of Open Access Journals (Sweden)

Yan He

2011-01-01

Full Text Available Excessive production of Aβ (amyloid β-peptide has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease. Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species in neurons through an NMDA (N-methyl-D-aspartate-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III-tetrakis(4-benzoic acid-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pretreatment of neurons with EGCG [(–-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.

A Kolmogorov-type competition model with multiple coexistence states and its applications to plant competition for sunlight

Science.gov (United States)

Just, Winfried; Nevai, Andrew L.

2008-12-01

It is demonstrated that a Kolmogorov-type competition model featuring species allocation and gain functions can possess multiple coexistence statesE Two examples are constructed: one in which the two competing species possess rectangular allocation functions but distinct gain functions, and the other in which one species has a rectangular allocation function, the second species has a bi-rectangular allocation function, and the two species share a common gain function. In both examples, it is shown that the species nullclines may intersect multiple times within the interior of the first quadrant, thus creating both locally stable and unstable equilibrium points. These results have important applications in the study of plant competition for sunlight, in which the allocation functions describe the vertical placement of leaves for two competing species, and the gain functions represent rates of photosynthesis performed by leaves at different heights when shaded by overlying leaves belonging to either species.

Functional and structural studies of the disulfide isomerase DsbC from the plant pathogen Xylella fastidiosa reveals a redox-dependent oligomeric modulation in vitro.

Science.gov (United States)

Santos, Clelton A; Toledo, Marcelo A S; Trivella, Daniela B B; Beloti, Lilian L; Schneider, Dilaine R S; Saraiva, Antonio M; Crucello, Aline; Azzoni, Adriano R; Souza, Alessandra A; Aparicio, Ricardo; Souza, Anete P

2012-10-01

Xylella fastidiosa is a Gram-negative bacterium that grows as a biofilm inside the xylem vessels of susceptible plants and causes several economically relevant crop diseases. In the present study, we report the functional and low-resolution structural characterization of the X. fastidiosa disulfide isomerase DsbC (XfDsbC). DsbC is part of the disulfide bond reduction/isomerization pathway in the bacterial periplasm and plays an important role in oxidative protein folding. In the present study, we demonstrate the presence of XfDsbC during different stages of X. fastidiosa biofilm development. XfDsbC was not detected during X. fastidiosa planktonic growth; however, after administering a sublethal copper shock, we observed an overexpression of XfDsbC that also occurred during planktonic growth. These results suggest that X. fastidiosa can use XfDsbC in vivo under oxidative stress conditions similar to those induced by copper. In addition, using dynamic light scattering and small-angle X-ray scattering, we observed that the oligomeric state of XfDsbC in vitro may be dependent on the redox environment. Under reducing conditions, XfDsbC is present as a dimer, whereas a putative tetrameric form was observed under nonreducing conditions. Taken together, our findings demonstrate the overexpression of XfDsbC during biofilm formation and provide the first structural model of a bacterial disulfide isomerase in solution. © 2012 The Authors Journal compilation © 2012 FEBS.

High-Performance Oligomeric Catholytes for Effective Macromolecular Separation in Nonaqueous Redox Flow Batteries.

Science.gov (United States)

Hendriks, Koen H; Robinson, Sophia G; Braten, Miles N; Sevov, Christo S; Helms, Brett A; Sigman, Matthew S; Minteer, Shelley D; Sanford, Melanie S

2018-02-28

Nonaqueous redox flow batteries (NRFBs) represent an attractive technology for energy storage from intermittent renewable sources. In these batteries, electrical energy is stored in and extracted from electrolyte solutions of redox-active molecules (termed catholytes and anolytes) that are passed through an electrochemical flow cell. To avoid battery self-discharge, the anolyte and catholyte solutions must be separated by a membrane in the flow cell. This membrane prevents crossover of the redox active molecules, while simultaneously allowing facile transport of charge-balancing ions. A key unmet challenge for the field is the design of redox-active molecule/membrane pairs that enable effective electrolyte separation while maintaining optimal battery properties. Herein, we demonstrate the development of oligomeric catholytes based on tris(dialkylamino)cyclopropenium (CP) salts that are specifically tailored for pairing with size-exclusion membranes composed of polymers of intrinsic microporosity (PIMs). Systematic studies were conducted to evaluate the impact of oligomer size/structure on properties that are crucial for flow battery performance, including cycling stability, charge capacity, solubility, electron transfer kinetics, and crossover rates. These studies have led to the identification of a CP-derived tetramer in which these properties are all comparable, or significantly improved, relative to the monomeric counterpart. Finally, a proof-of-concept flow battery is demonstrated by pairing this tetrameric catholyte with a PIM membrane. After 6 days of cycling, no crossover is detected, demonstrating the promise of this approach. These studies provide a template for the future design of other redox-active oligomers for this application.

Multiple-Access Quantum-Classical Networks

Science.gov (United States)

Razavi, Mohsen

2011-10-01

A multi-user network that supports both classical and quantum communication is proposed. By relying on optical code-division multiple access techniques, this system offers simultaneous key exchange between multiple pairs of network users. A lower bound on the secure key generation rate will be derived for decoy-state quantum key distribution protocols.

Alternative stable states generated by ontogenetic niche shift in the presence of multiple resource use.

Directory of Open Access Journals (Sweden)

Takefumi Nakazawa

2011-02-01

Full Text Available It has been suggested that when juveniles and adults use different resources or habitats, alternative stable states (ASS may exist in systems coupled by an ontogenetic niche shift. However, mainly the simplest system, i.e., the one-consumer-two-resource system, has been studied previously, and little is known about the development of ASS existing in more complex systems. Here, I theoretically investigated the development of ASS caused by an ontogenetic niche shift in the presence of multiple resource use. I considered three independent scenarios; (i additional resources, (ii multiple habitats, and (iii interstage resource sharing. The model analyses illustrate that relative balance between the total resource availability in the juvenile and adult habitats is crucial for the development of ASS. This balance is determined by factors such as local habitat productivity, subsidy inputs, colonization area, and foraging mobility. Furthermore, it is also shown that interstage resource sharing generally suppresses ASS. These results suggest that the anthropogenic impacts of habitat modifications (e.g., fragmentation and destruction or interaction modifications (e.g., changes in ontogeny and foraging behavior propagate through space and may cause or prevent regime shifts in the regional community structure.

Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus

DEFF Research Database (Denmark)

Lauritsen, Iben; Willemoës, Martin; Jensen, Kaj Frank

2011-01-01

CTP synthase catalyzes the last committed step in de novo pyrimidine-nucleotide biosynthesis. Active CTP synthase is a tetrameric enzyme composed of a dimer of dimers. The tetramer is favoured in the presence of the substrate nucleotides ATP and UTP; when saturated with nucleotide, the tetramer...... completely dominates the oligomeric state of the enzyme. Furthermore, phosphorylation has been shown to regulate the oligomeric states of the enzymes from yeast and human. The crystal structure of a dimeric form of CTP synthase from Sulfolobus solfataricus has been determined at 2.5 Å resolution...

MULTIPLE PERSONALITY: CASE REPORT STUDY

Directory of Open Access Journals (Sweden)

Miloš Židanik

2004-07-01

Full Text Available Background. Multiple personality disorder is characterised by splited individual ego-states and splited professional community arguing whether this disorder actually exists or not.Methods. In this case report study a supportive psychodynamic psychotherapy of a patient with multiple personality disorder is presented, that lasted for 4.5 years and resulted in ego-reintegration.Conclusions. The spliting between different ego-states is powered by unneutralised aggression with the possibility of hetero- and autoaggressive behaviour. Therefore the patient in the analytically oriented psychotherapeutic process is at high risk and a safe therapeutic (e. g. in-patient setting has to be provided.

Analysis of monomeric and oligomeric organophosphorus flame retardants in fish muscle tissues using liquid chromatography–electrospray ionization tandem mass spectrometry: Application to Nile tilapia (Oreochromis niloticus) from an e-waste processing area in northern Vietnam

OpenAIRE

Matsukami, Hidenori; Suzuki, Go; Tue, Nguyen Minh; Tuyen, Le Huu; Viet, Pham Hung; Takahashi, Shin; Tanabe, Shinsuke; Takigami, Hidetaka

2016-01-01

Using electrospray ionization tandem mass spectrometry combined with liquid chromatography (LC), a novel analytical method was developed to quantify eight monomeric organophosphorus flame retardants (m-PFRs) and three oligomeric organophosphorus flame retardants (o-PFRs) in fish muscle samples. The optimization and validation experiments indicate that the developed method can determine accurately the concentrations of analytes in fish muscle samples. The recoveries of analytes in fish muscle ...

Nonlinear-drifted Brownian motion with multiple hidden states for remaining useful life prediction of rechargeable batteries

Science.gov (United States)

Wang, Dong; Zhao, Yang; Yang, Fangfang; Tsui, Kwok-Leung

2017-09-01

Brownian motion with adaptive drift has attracted much attention in prognostics because its first hitting time is highly relevant to remaining useful life prediction and it follows the inverse Gaussian distribution. Besides linear degradation modeling, nonlinear-drifted Brownian motion has been developed to model nonlinear degradation. Moreover, the first hitting time distribution of the nonlinear-drifted Brownian motion has been approximated by time-space transformation. In the previous studies, the drift coefficient is the only hidden state used in state space modeling of the nonlinear-drifted Brownian motion. Besides the drift coefficient, parameters of a nonlinear function used in the nonlinear-drifted Brownian motion should be treated as additional hidden states of state space modeling to make the nonlinear-drifted Brownian motion more flexible. In this paper, a prognostic method based on nonlinear-drifted Brownian motion with multiple hidden states is proposed and then it is applied to predict remaining useful life of rechargeable batteries. 26 sets of rechargeable battery degradation samples are analyzed to validate the effectiveness of the proposed prognostic method. Moreover, some comparisons with a standard particle filter based prognostic method, a spherical cubature particle filter based prognostic method and two classic Bayesian prognostic methods are conducted to highlight the superiority of the proposed prognostic method. Results show that the proposed prognostic method has lower average prediction errors than the particle filter based prognostic methods and the classic Bayesian prognostic methods for battery remaining useful life prediction.

Ion Channel Conformation and Oligomerization Assessment by Site-Directed Spin Labeling and Pulsed-EPR.

Science.gov (United States)

Pliotas, Christos

2017-01-01

Mechanosensitive (MS) ion channels are multimeric integral membrane proteins that respond to increased lipid bilayer tension by opening their nonselective pores to release solutes and relieve increased cytoplasmic pressure. These systems undergo major conformational changes during gating and the elucidation of their mechanism requires a deep understanding of the interplay between lipids and proteins. Lipids are responsible for transmitting lateral tension to MS channels and therefore play a key role in obtaining a molecular-detail model for mechanosensation. Site-directed spin labeling combined with electron paramagnetic resonance (EPR) spectroscopy is a powerful spectroscopic tool in the study of proteins. The main bottleneck for its use relates to challenges associated with successful isolation of the protein of interest, introduction of paramagnetic labels on desired sites, and access to specialized instrumentation and expertise. The design of sophisticated experiments, which combine a variety of existing EPR methodologies to address a diversity of specific questions, require knowledge of the limitations and strengths, characteristic of each particular EPR method. This chapter is using the MS ion channels as paradigms and focuses on the application of different EPR techniques to ion channels, in order to investigate oligomerization, conformation, and the effect of lipids on their regulation. The methodology we followed, from the initial strategic selection of mutants and sample preparation, including protein purification, spin labeling, reconstitution into lipid mimics to the complete set-up of the pulsed-EPR experiments, is described in detail. © 2017 Elsevier Inc. All rights reserved.

Preparation of Greenberger-Horne-Zeilinger entangled states with multiple superconducting quantum-interference device qubits or atoms in cavity QED

International Nuclear Information System (INIS)

Yang Chuiping; Han Siyuan

2004-01-01

A scheme is proposed for generating Greenberger-Horne-Zeilinger (GHZ) entangled states of multiple superconducting quantum-interference device (SQUID) qubits by the use of a microwave cavity. The scheme operates essentially by creating a single photon through an auxiliary SQUID built in the cavity and performing a joint multiqubit phase shift with assistance of the cavity photon. It is shown that entanglement can be generated using this method, deterministic and independent of the number of SQUID qubits. In addition, we show that the present method can be applied to preparing many atoms in a GHZ entangled state, with tolerance to energy relaxation during the operation

A simplified approach for evaluating multiple test outcomes and multiple disease states in relation to the exercise thallium-201 stress test in suspected coronary artery disease

International Nuclear Information System (INIS)

Pollock, S.G.; Watson, D.D.; Gibson, R.S.; Beller, G.A.; Kaul, S.

1989-01-01

This study describes a simplified approach for the interpretation of electrocardiographic and thallium-201 imaging data derived from the same patient during exercise. The 383 patients in this study had also undergone selective coronary arteriography within 3 months of the exercise test. This matrix approach allows for multiple test outcomes (both tests positive, both negative, 1 test positive and 1 negative) and multiple disease states (no coronary artery disease vs 1-vessel vs multivessel coronary artery disease). Because this approach analyzes the results of 2 test outcomes simultaneously rather than serially, it also negates the lack of test independence, if such an effect is present. It is also demonstrated that ST-segment depression on the electrocardiogram and defects on initial thallium-201 images provide conditionally independent information regarding the presence of coronary artery disease in patients without prior myocardial infarction. In contrast, ST-segment depression on the electrocardiogram and redistribution on the delayed thallium-201 images may not provide totally independent information regarding the presence of exercise-induced ischemia in patients with or without myocardial infarction

Search for microscopic black holes in a like-sign dimuon final state using large track multiplicity with the ATLAS detector

Czech Academy of Sciences Publication Activity Database

Aad, G.; Abajyan, T.; Abbott, B.; Böhm, Jan; Chudoba, Jiří; Havránek, Miroslav; Hejbal, Jiří; Jakoubek, Tomáš; Kepka, Oldřich; Kupčo, Alexander; Kůs, Vlastimil; Lysák, Roman; Lokajíček, Miloš; Marčišovský, Michal; Mikeštíková, Marcela; Myška, Miroslav; Němeček, Stanislav; Růžička, Pavel; Schovancová, Jaroslava; Šícho, Petr; Staroba, Pavel; Svatoš, Michal; Taševský, Marek; Tic, Tomáš; Vrba, Václav

2013-01-01

Roč. 88, č. 7 (2013), "072001-1"-"072001-22" ISSN 1550-7998 R&D Projects: GA MŠk(CZ) LG13009 Institutional support: RVO:68378271 Keywords : tracks * multiplicity * final state * dimuon * same sign * black hole * mass * gravitation * model * ATLAS * CERN LHC Coll * background Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 4.864, year: 2013

Optimization of oligomeric enzyme activity in ionic liquids using Rhodotorula glutinis yeast phenylalanine ammonia lyase.

Science.gov (United States)

Barron, Christiaan C; Sponagle, Brandon J D; Arivalagan, Pugazhendhi; D'Cunha, Godwin B

2017-01-01

Phenylalanine ammonia lyase (E.C.4.3.1.24, PAL) activity of Rhodotorula glutinis yeast has been demonstrated in four commonly used ionic liquids. PAL forward reaction was carried out in 1-butyl-3-methylimidazolium methyl sulfate ([BMIM][MeSO 4 ]), 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF 4 ]), 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF 6 ]) and 1-butyl-3-methylimidazolium lactate ([BMIM][lactate]). Our experiments have revealed that PAL is catalytically active in ionic liquids and the enzyme activity in ([BMIM][PF 6 ]) is comparable to that obtained in aqueous buffer medium. Different conditions were optimized for maximal PAL forward activity including time of incubation (30.0min) L -phenylalanine substrate concentration (30.0mM), nature of buffer (50.0mM Tris-HCl), pH (9.0), temperature (37°C), and speed of agitation (100 rev min -1 ). Under these optimized conditions, about 83% conversion of substrate to product was obtained for the PAL forward reaction that was determined using UV spectroscopy at 290nm. PAL reverse reaction in ([BMIM][PF 6 ]) was determined spectrophotometrically at 520nm; and about 59% substrate conversion was obtained. This data provides further knowledge in enzyme biocatalysis in non-aqueous media, and may be of importance when studying the function of other oligomeric/multimeric proteins and enzymes in ionic liquids. Copyright © 2016 Elsevier Inc. All rights reserved.

Unusual Emission of Polystyrene-Based Alternating Copolymers Incorporating Aminobutyl Maleimide Fluorophore-Containing Polyhedral Oligomeric Silsesquioxane Nanoparticles

Directory of Open Access Journals (Sweden)

Mohamed Gamal Mohamed

2017-03-01

Full Text Available In this study, we synthesized an unusual 2-aminobutyl maleimide isobutyl polyhedral oligomeric silsesquioxane (MIPOSS-NHBu monomer lacking conventional fluorescent groups. We then prepared poly(styrene-alt-2-aminobutyl maleimide isobutyl POSS [poly(S-alt-MIPOSS-NHBu] and poly(4-acetoxystyrene-alt-2-aminobutyl maleimide isobutyl POSS [poly(AS-alt-MIPOSS-NHBu] copolymers through facile free radical copolymerizations using azobisisobutyronitrile as the initiator and tetrahydrofuran as the solvent. A poly(4-hydroxystyrene-alt-2-aminobutyl maleimide isobutyl POSS [poly(HS-alt-MIPOSS-NHBu] copolymer was prepared through acetoxyl hydrazinolysis of poly(AS-alt-MIPOSS-NHBu. We employed 1H, 13C, and 29Si nuclear magnetic resonance spectroscopy; Fourier transform infrared spectroscopy; differential scanning calorimetry; and photoluminescence spectroscopy to investigate the structures and the thermal and optical properties of the monomers and novel POSS-containing alternating copolymers. Intramolecular hydrogen bonding between the amino and dihydrofuran-2,5-dione group and clustering of the locked C=O groups from the POSS nanoparticles in the MIPOSS-NHBu units restricted the intramolecular motion of the polymer chain, causing it to exhibit strong light emission. As a result, the MIPOSS-NHBu monomer and the poly(AS-alt-MIPOSS-NHBu copolymer both have potential applicability in the detection of metal ions with good selectivity.

Epoxy networks reinforced with polyhedral oligomeric silsesquioxanes: structure and segmental dynamics as studied by solid-state NMR

Czech Academy of Sciences Publication Activity Database

Brus, Jiří; Urbanová, Martina; Strachota, Adam

2008-01-01

Roč. 41, č. 2 (2008), s. 372-386 ISSN 0024-9297 R&D Projects: GA AV ČR IAA400500602 Institutional research plan: CEZ:AV0Z40500505 Keywords : solid-state NMR * polymer networks * polysilsequioxanes Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.407, year: 2008

Multimodal Nonlinear Optical Imaging for Sensitive Detection of Multiple Pharmaceutical Solid-State Forms and Surface Transformations.

Science.gov (United States)

Novakovic, Dunja; Saarinen, Jukka; Rojalin, Tatu; Antikainen, Osmo; Fraser-Miller, Sara J; Laaksonen, Timo; Peltonen, Leena; Isomäki, Antti; Strachan, Clare J

2017-11-07

Two nonlinear imaging modalities, coherent anti-Stokes Raman scattering (CARS) and sum-frequency generation (SFG), were successfully combined for sensitive multimodal imaging of multiple solid-state forms and their changes on drug tablet surfaces. Two imaging approaches were used and compared: (i) hyperspectral CARS combined with principal component analysis (PCA) and SFG imaging and (ii) simultaneous narrowband CARS and SFG imaging. Three different solid-state forms of indomethacin-the crystalline gamma and alpha forms, as well as the amorphous form-were clearly distinguished using both approaches. Simultaneous narrowband CARS and SFG imaging was faster, but hyperspectral CARS and SFG imaging has the potential to be applied to a wider variety of more complex samples. These methodologies were further used to follow crystallization of indomethacin on tablet surfaces under two storage conditions: 30 °C/23% RH and 30 °C/75% RH. Imaging with (sub)micron resolution showed that the approach allowed detection of very early stage surface crystallization. The surfaces progressively crystallized to predominantly (but not exclusively) the gamma form at lower humidity and the alpha form at higher humidity. Overall, this study suggests that multimodal nonlinear imaging is a highly sensitive, solid-state (and chemically) specific, rapid, and versatile imaging technique for understanding and hence controlling (surface) solid-state forms and their complex changes in pharmaceuticals.

Concomitant production of cellulase and xylanase by thermophilic mould Sporotrichum thermophile in solid state fermentation and their applicability in bread making.

Science.gov (United States)

Bala, Anju; Singh, Bijender

2017-06-01

Sporotrichum thermophile BJAMDU5 secreted high titres of xylanolytic and cellulolytic enzymes in solid state fermentation using mixture of wheat straw and cotton oil cake (ratio 1:1) at 45 °C, pH 5.0 after 72 h inoculated with 2.9 × 10 7  CFU/mL conidiospores. Supplementation of solid medium with lactose and ammonium sulphate further enhanced the production of hydrolytic enzymes. Among different surfactants studied, Tween 80 enhanced the production of all enzymes [3455 U/g DMR (dry mouldy residue), 879.26 U/g DMR, 976.28 U/g DMR and 35.10 U/g DMR for xylanase, CMCase (Carboxymethylcellulase), FPase (Filter paper activity) and β-glucosidase, respectively] as compared to other surfactants. Recycling of solid substrate reduced the production of all these enzymes after second cycle. End products analysis by TLC showed the ability of hydrolytic enzymes of S. thermophile to liberate monomeric (xylose and glucose) as well as oligomeric (xylobiose, cellobiose and higher ones) sugars. Supplementation of enzyme resulted in improved nutritional properties of the bread. Formation of oligomeric sugars by xylanase enzyme of S. thermophile BJAMDU5 make it a good candidate in food industry.

Hadron multiplicity as the limit of jet multiplicity at high resolution

International Nuclear Information System (INIS)

Lupia, S.; Ochs, W.

1998-01-01

Recently exact numerical results from the evolution equation for parton multiplicities in QCD jets have been obtained. A comparison with various approximate results is presented. A good description is obtained not only of the jet multiplicities measured at LEP-1 but also of the hadron multiplicities for cm s energies above 1.6 GeV in e + e - annihilation. The solution suggests that a final state hadron can be represented by a jet in the limit of small (nonperturbative) k perpendicular to cut-off Q 0 . In this description using as adjustable parameters only the QCD scale Λ and the cut-off Q 0 , the coupling α s can be seen to rise towards large values above unity at low energies. (orig.)

Multiple neural states of representation in short-term memory? It’s a matter of attention

Science.gov (United States)

LaRocque, Joshua J.; Lewis-Peacock, Jarrod A.; Postle, Bradley R.

2014-01-01

Short-term memory (STM) refers to the capacity-limited retention of information over a brief period of time, and working memory (WM) refers to the manipulation and use of that information to guide behavior. In recent years it has become apparent that STM and WM interact and overlap with other cognitive processes, including attention (the selection of a subset of information for further processing) and long-term memory (LTM—the encoding and retention of an effectively unlimited amount of information for a much longer period of time). Broadly speaking, there have been two classes of memory models: systems models, which posit distinct stores for STM and LTM (Atkinson and Shiffrin, 1968; Baddeley and Hitch, 1974); and state-based models, which posit a common store with different activation states corresponding to STM and LTM (Cowan, 1995; McElree, 1996; Oberauer, 2002). In this paper, we will focus on state-based accounts of STM. First, we will consider several theoretical models that postulate, based on considerable behavioral evidence, that information in STM can exist in multiple representational states. We will then consider how neural data from recent studies of STM can inform and constrain these theoretical models. In the process we will highlight the inferential advantage of multivariate, information-based analyses of neuroimaging data (fMRI and electroencephalography (EEG)) over conventional activation-based analysis approaches (Postle, in press). We will conclude by addressing lingering questions regarding the fractionation of STM, highlighting differences between the attention to information vs. the retention of information during brief memory delays. PMID:24478671

Reliability improvement of a-Si:H thin film transistors on plastic substrate with saturation in deep state after multiple bending cycles

International Nuclear Information System (INIS)

Lee, M.H.; Chen, P.-G.; Hsu, C.-C.

2013-01-01

For flexible electronic applications, the disordered bonds of a-Si:H may generate a redistribution of trapped states with mechanical strain. During mechanical strain, the deep states are redistributed in a Gaussian distribution and are dissimilar to ordinary acceptor-like deep states, which manifest with exponential distributions. The redistributed deep states may saturate with multiple mechanical bending cycles, and it would improve the reliability with drain current stress of a-Si:H TFTs (thin film transistors) on flexible substrates. We conclude that it is possible to produce low-cost and highly uniform active-matrix organic light emitting diodes systems for use in flexible display applications using a-Si:H TFTs array backplanes. - Highlights: • The stress stability of a-Si:H TFTs (thin-film transistors) was improved after bending cycles. • The saturated deep states after bending were confirmed. • The simulation and extracted gap state density of a-Si:H TFT under strain was calculated

Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure

Energy Technology Data Exchange (ETDEWEB)

Korasick, David A. [Department of Biochemistry, University of Missouri, Columbia MO USA; Singh, Harkewal [Department of Chemistry, University of Missouri, Columbia MO USA; Pemberton, Travis A. [Department of Chemistry, University of Missouri, Columbia MO USA; Luo, Min [Department of Chemistry, University of Missouri, Columbia MO USA; Dhatwalia, Richa [Department of Chemistry, University of Missouri, Columbia MO USA; Tanner, John J. [Department of Biochemistry, University of Missouri, Columbia MO USA; Department of Chemistry, University of Missouri, Columbia MO USA

2017-08-01

Many enzymes form homooligomers, yet the functional significance of self-association is seldom obvious. Herein, we examine the connection between oligomerization and catalytic function for proline utilization A (PutA) enzymes. PutAs are bifunctional enzymes that catalyze both reactions of proline catabolism. Type A PutAs are the smallest members of the family, possessing a minimal domain architecture consisting of N-terminal proline dehydrogenase and C-terminal l-glutamate-γ-semialdehyde dehydrogenase modules. Type A PutAs form domain-swapped dimers, and in one case (Bradyrhizobium japonicum PutA), two of the dimers assemble into a ring-shaped tetramer. Whereas the dimer has a clear role in substrate channeling, the functional significance of the tetramer is unknown. To address this question, we performed structural studies of four-type A PutAs from two clades of the PutA tree. The crystal structure of Bdellovibrio bacteriovorus PutA covalently inactivated by N-propargylglycine revealed a fold and substrate-channeling tunnel similar to other PutAs. Small-angle X-ray scattering (SAXS) and analytical ultracentrifugation indicated that Bdellovibrio PutA is dimeric in solution, in contrast to the prediction from crystal packing of a stable tetrameric assembly. SAXS studies of two other type A PutAs from separate clades also suggested that the dimer predominates in solution. To assess whether the tetramer of B. japonicum PutA is necessary for catalytic function, a hot spot disruption mutant that cleanly produces dimeric protein was generated. The dimeric variant exhibited kinetic parameters similar to the wild-type enzyme. These results implicate the domain-swapped dimer as the core structural and functional unit of type A PutAs.

Oligomeric state of hypoxanthine-guanine phosphoribosyltransferase from Mycobacterium tuberculosis

Czech Academy of Sciences Publication Activity Database

Eng, W. S.; Keough, D. T.; Hocková, Dana; Winzor, D. J.; Guddat, L. W.

2017-01-01

Roč. 135, Apr (2017), s. 6-14 ISSN 0300-9084 R&D Projects: GA ČR(CZ) GA16-06049S Institutional support: RVO:61388963 Keywords : enzyme inhibitors * acyclic nucleoside phosphonates * 6-oxopurine phosphoribosyltransferase Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.112, year: 2016

Effects of marine protected areas on overfished fishing stocks with multiple stable states.

Science.gov (United States)

Takashina, Nao; Mougi, Akihiko

2014-01-21

Marine protected areas (MPAs) have attracted much attention as a tool for sustainable fisheries management, restoring depleted fisheries stocks and maintaining ecosystems. However, even with total exclusion of fishing effort, depleted stocks sometimes show little or no recovery over a long time period. Here, using a mathematical model, we show that multiple stable states may hold the key to understanding the tendency for fisheries stocks to recover because of MPAs. We find that MPAs can have either a positive effect or almost no effect on the recovery of depleted fishing stocks, depending on the fish migration patterns and the fishing policies. MPAs also reinforce ecological resilience, particularly for migratory species. In contrast to previous reports, our results show that MPAs have small or sometimes negative effects on the recovery of sedentary species. Unsuitable MPA planning might result in low effectiveness or even deterioration of the existing condition. © 2013 Elsevier Ltd. All rights reserved.

Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

Directory of Open Access Journals (Sweden)

Joao Arezes

Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

Energy independent scaling of the ridge and final state description of high multiplicity p +p collisions at √{s }=7 and 13 TeV

Science.gov (United States)

Sarkar, Debojit

2018-02-01

An energy independent scaling of the near-side ridge yield at a given multiplicity has been observed by the ATLAS and the CMS collaborations in p +p collisions at √{s }=7 and 13 TeV. Such a striking feature of the data can be successfully explained by approaches based on initial state momentum space correlation generated due to gluon saturation. In this paper, we try to examine if such a scaling is also an inherent feature of the approaches that employ strong final state interaction in p +p collisions. We find that hydrodynamical modeling of p +p collisions using EPOS 3 shows a violation of such scaling. The current study can, therefore, provide important new insights on the origin of long-range azimuthal correlations in high multiplicity p +p collisions at the LHC energies.

Hadron multiplicity as the limit of jet multiplicity at high resolution

Energy Technology Data Exchange (ETDEWEB)

Lupia, S.; Ochs, W. [Max-Planck-Institut fuer Physik, Muenchen (Germany). Werner-Heisenberg-Institut

1998-05-01

Recently exact numerical results from the evolution equation for parton multiplicities in QCD jets have been obtained. A comparison with various approximate results is presented. A good description is obtained not only of the jet multiplicities measured at LEP-1 but also of the hadron multiplicities for cm s energies above 1.6 GeV in e{sup +}e{sup -} annihilation. The solution suggests that a final state hadron can be represented by a jet in the limit of small (nonperturbative) k {sub perpendicular} {sub to} cut-off Q{sub 0}. In this description using as adjustable parameters only the QCD scale {Lambda} and the cut-off Q{sub 0}, the coupling {alpha}{sub s} can be seen to rise towards large values above unity at low energies. (orig.). 8 refs.

Multiple acquisition of magic angle spinning solid-state NMR experiments using one receiver: Application to microcrystalline and membrane protein preparations

Science.gov (United States)

Gopinath, T.; Veglia, Gianluigi

2015-04-01

Solid-state NMR spectroscopy of proteins is a notoriously low-throughput technique. Relatively low-sensitivity and poor resolution of protein samples require long acquisition times for multidimensional NMR experiments. To speed up data acquisition, we developed a family of experiments called Polarization Optimized Experiments (POE), in which we utilized the orphan spin operators that are discarded in classical multidimensional NMR experiments, recovering them to allow simultaneous acquisition of multiple 2D and 3D experiments, all while using conventional probes with spectrometers equipped with one receiver. POE allow the concatenation of multiple 2D or 3D pulse sequences into a single experiment, thus potentially combining all of the aforementioned advances, boosting the capability of ssNMR spectrometers at least two-fold without the addition of any hardware. In this perspective, we describe the first generation of POE, such as dual acquisition MAS (or DUMAS) methods, and then illustrate the evolution of these experiments into MEIOSIS, a method that enables the simultaneous acquisition of multiple 2D and 3D spectra. Using these new pulse schemes for the solid-state NMR investigation of biopolymers makes it possible to obtain sequential resonance assignments, as well as distance restraints, in about half the experimental time. While designed for acquisition of heteronuclei, these new experiments can be easily implemented for proton detection and coupled with other recent advancements, such as dynamic nuclear polarization (DNP), to improve signal to noise. Finally, we illustrate the application of these methods to microcrystalline protein preparations as well as single and multi-span membrane proteins reconstituted in lipid membranes.

Landau levels and shallow donor states in GaAs/AlGaAs multiple quantum wells at megagauss magnetic fields

Science.gov (United States)

Zybert, M.; Marchewka, M.; Sheregii, E. M.; Rickel, D. G.; Betts, J. B.; Balakirev, F. F.; Gordon, M.; Stier, A. V.; Mielke, C. H.; Pfeffer, P.; Zawadzki, W.

2017-03-01

Landau levels and shallow donor states in multiple GaAs/AlGaAs quantum wells (MQWs) are investigated by means of the cyclotron resonance at megagauss magnetic fields. Measurements of magneto-optical transitions were performed in pulsed fields up to 140 T and temperatures from 6-300 K. The 14 ×14 P.p band model for GaAs is used to interpret free-electron transitions in a magnetic field. Temperature behavior of the observed resonant structure indicates, in addition to the free-electron Landau states, contributions of magnetodonor states in the GaAs wells and possibly in the AlGaAs barriers. The magnetodonor energies are calculated using a variational procedure suitable for high magnetic fields and accounting for conduction band nonparabolicity in GaAs. It is shown that the above states, including their spin splitting, allow one to interpret the observed magneto-optical transitions in MQWs in the middle infrared region. Our experimental and theoretical results at very high magnetic fields are consistent with the picture used previously for GaAs/AlGaAs MQWs at lower magnetic fields.

The Border Multiple

DEFF Research Database (Denmark)

of European borders by looking at border practices in the light of the mobility turn, and thus as dynamic, multiple, diverse and best expressed in everyday experiences of people living at and with borders, rather than focusing on static territorial divisions between states and regions at geopolitical level...

Prediction of the association state of insulin using spectral parameters.

Science.gov (United States)

Uversky, Vladimir N; Garriques, Liza Nielsen; Millett, Ian S; Frokjaer, Sven; Brange, Jens; Doniach, Sebastian; Fink, Anthony L

2003-04-01

Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray scattering (SAXS). The mutants showed different degrees of association (monomer, dimers, tetramers, and hexamers) at neutral pH. A correlation was shown between the accessibility of tyrosines to acrylamide quenching and the degree of association of the insulin mutants. The near-UV CD spectra of the insulins were affected by protein association and by mutation-induced structural perturbations. However, the shape and intensity of difference CD spectra, obtained by subtraction of the spectra measured in 20% acetic acid (where all insulin species were monomeric) from the corresponding spectra measured at neutral pH, correlate well with the degree of insulin association. In fact, the near-UV CD difference spectra for monomeric, dimeric, tetrameric, and hexameric insulin are very distinctive, both in terms of intensity and shape. The results show that the spectral properties of the insulins reflect their state of association, and can be used to predict their oligomeric state. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:847-858, 2003

Hadron multiplicities at COMPASS

Energy Technology Data Exchange (ETDEWEB)

Du Fresne von Hohenesche, Nicolas [Institut fuer Kernphysik, Universitaet Mainz, Johann-Joachim-Becher-Weg 45, 55128 Mainz (Germany); Collaboration: COMPASS Collaboration

2014-07-01

Quark fragmentation functions (FF) D{sub q}{sup h}(z,Q{sup 2}) describe final-state hadronization of quarks q into hadrons h. The FFs can be extracted from hadron multiplicities produced in semi-inclusive deep inelastic scattering. The COMPASS collaboration has recently measured charged hadron multiplicities for identified pions and kaons using a 160 GeV/c muon beam impinging on an iso-scalar target. The data cover a large kinematical range and provide an important input for global QCD analyses of world data at NLO, aiming at the determination of FFs in particular in the strange quark sector. The newest results from COMPASS on pion and kaon multiplicities will be presented.

Multiple Autonomous Vehicles for Minefield Reconnaissance and Mapping

Science.gov (United States)

1997-12-01

NPS-ME-97-008 NAVAL POSTGRADUATE SCHOOL Monterey, California ItC A D- 19980421 131 =C QUALTY Ui Ji.CTEJ) THESIS MULTIPLE AUTONOMOUS VEHICLES FOR...MULTIPLE AUTONOMOUS VEHICLES FOR MINEFIELD 5. FUNDING NUMBERS RECONNAISSANCE AND MAPPING N0001497WX30039 6. AUTHOR(S) Jack A. Starr 7. PERFORMING... AUTONOMOUS VEHICLES FOR MINEFIELD RECONNAISSANCE AND MAPPING Jack A. Starr Lieutenant, United States Navy B.S., Oregon State University, 1991 Submitted in

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations

Science.gov (United States)

Glover, William J.; Mori, Toshifumi; Schuurman, Michael S.; Boguslavskiy, Andrey E.; Schalk, Oliver; Stolow, Albert; Martínez, Todd J.

2018-04-01

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 11Bu (ππ*) state and non-adiabatically coupled dark 21Ag state of BD. Importantly, AIMS allows for on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 11Bu state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1Bu or the dark 21Ag state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.

Exploring resting-state EEG brain oscillatory activity in relation to cognitive functioning in multiple sclerosis.

Science.gov (United States)

Keune, Philipp M; Hansen, Sascha; Weber, Emily; Zapf, Franziska; Habich, Juliane; Muenssinger, Jana; Wolf, Sebastian; Schönenberg, Michael; Oschmann, Patrick

2017-09-01

Neurophysiologic monitoring parameters related to cognition in Multiple Sclerosis (MS) are sparse. Previous work reported an association between magnetoencephalographic (MEG) alpha-1 activity and information processing speed. While this remains to be replicated by more available electroencephalographic (EEG) methods, also other established EEG markers, e.g. the slow-wave/fast-wave ratio (theta/beta ratio), remain to be explored in this context. Performance on standard tests addressing information processing speed and attention (Symbol-Digit Modalities Test, SDMT; Test of Attention Performance, TAP) was examined in relation to resting-state EEG alpha-1 and alpha-2 activity and the theta/beta ratio in 25MS patients. Increased global alpha-1 and alpha-2 activity and an increased frontal theta/beta ratio (pronounced slow-wave relative to fast-wave activity) were associated with lower SDMT processing speed. In an exploratory analysis, clinically impaired attention was associated with a significantly increased frontal theta/beta ratio whereas alpha power did not show sensitivity to clinical impairment. EEG global alpha power and the frontal theta/beta ratio were both associated with attention. The theta/beta ratio involved potential clinical sensitivity. Resting-state EEG recordings can be obtained during the routine clinical process. The examined resting-state measures may represent feasible monitoring parameters in MS. This notion should be explored in future intervention studies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Multiple Multidentate Halogen Bonding in Solution, in the Solid State, and in the (Calculated) Gas Phase.

Science.gov (United States)

Jungbauer, Stefan H; Schindler, Severin; Herdtweck, Eberhardt; Keller, Sandro; Huber, Stefan M

2015-09-21

The binding properties of neutral halogen-bond donors (XB donors) bearing two multidentate Lewis acidic motifs toward halides were investigated. Employing polyfluorinated and polyiodinated terphenyl and quaterphenyl derivatives as anion receptors, we obtained X-ray crystallographic data of the adducts of three structurally related XB donors with tetraalkylammonium chloride, bromide, and iodide. The stability of these XB complexes in solution was determined by isothermal titration calorimetry (ITC), and the results were compared to X-ray analyses as well as to calculated binding patterns in the gas phase. Density functional theory (DFT) calculations on the gas-phase complexes indicated that the experimentally observed distortion of the XB donors during multiple multidentate binding can be reproduced in 1:1 complexes with halides, whereas adducts with two halides show a symmetric binding pattern in the gas phase that is markedly different from the solid state structures. Overall, this study demonstrates the limitations in the transferability of binding data between solid state, solution, and gas phase in the study of complex multidentate XB donors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Technology-Aided Leisure and Communication Opportunities for Two Post-Coma Persons Emerged from a Minimally Conscious State and Affected by Multiple Disabilities

Science.gov (United States)

Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Buonocunto, Francesca; Sacco, Valentina; Navarro, Jorge; Lanzilotti, Crocifissa; De Tommaso, Marina; Megna, Marisa; Oliva, Doretta

2013-01-01

This study assessed technology-aided programs for helping two post-coma persons, who had emerged from a minimally conscious state and were affected by multiple disabilities, to (a) engage with leisure stimuli and request caregiver's procedures, (b) send out and listen to text messages for communication with distant partners, and (c) combine…

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth.

Science.gov (United States)

Foley, Joseph; Hill, Shannon E; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-09-28

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the

Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth

Science.gov (United States)

Foley, Joseph; Hill, Shannon E.; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

2013-09-01

Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the

Association of Nucleotide-binding Oligomerization Domain Receptors with Peptic Ulcer and Gastric Cancer.

Science.gov (United States)

Mohammadian Amiri, Rajeeh; Tehrani, Mohsen; Taghizadeh, Shirin; Shokri-Shirvani, Javad; Fakheri, Hafez; Ajami, Abolghasem

2016-10-01

Host innate immunity can affect the clinical outcomes of Helicobacter pylori infection, including gastritis, gastric ulcer, gastric adenocarcinoma, and MALT lymphoma. Nucleotide binding oligomerization domain (NOD)-1 and -2 are two molecules of innate immunity which are involved in the host defense against H. pylori. This study aimed to evaluate the effect of the expression level of NOD1 and NOD2 on the susceptibility to gastric cancer as well as peptic ulcer in individuals with H. pylori infection. The gene expression levels of these molecules were compared in three groups of non-ulcer dyspepsia (NUD) as a control group (n=52); peptic ulcer disease (PUD), (n=53); and gastric cancer (GC), (n=39). Relative expression levels of NOD1 in patients with GC were higher than those of NUD and PUD (p<0.001 and P<0.001, respectively). Similarly in case of NOD1, PUD group showed higher level of expression than NUD group (p<0.01). However, there was no significant difference between H. pylori -positive and -negative patients in NUD, PUD, or GC groups. Moreover, the expression levels of NOD2 showed no significant difference among NUD, PUD, or GC groups, while among H. pylori-positive patients, it was higher in GC group than NUD  and PUD groups (p<0.05 and p<0.01, respectively). In addition, positive correlation coefficients were attained between NOD1 and NOD2 expressions in patients with NUD (R2 Linear=0.349, p<0.001), PUD (R2 Linear=0.695, p<0.001), and GC (R2 Linear=0.385, p<0.001). Collectively, the results suggest that the chronic activation of NOD1 and NOD2 receptors might play a role in the development of gastric cancer.

The Multiple Intelligences Teaching Method and Mathematics ...

African Journals Online (AJOL)

The Multiple Intelligences teaching approach has evolved and been embraced widely especially in the United States. The approach has been found to be very effective in changing situations for the better, in the teaching and learning of any subject especially mathematics. Multiple Intelligences teaching approach proposes ...

Analysis of oligomeric transition of silkworm small heat shock protein sHSP20.8 using high hydrostatic pressure native PAGE

Science.gov (United States)

Fujisawa, Tetsuro; Ueda, Toshifumi; Kameyama, Keiichi; Aso, Yoichi; Ishiguro, Ryo

2013-06-01

The small heat shock proteins (sHSPs) solubilize thermo-denatured proteins without adenosine triphosphate energy consumption to facilitate protein refolding. sHSP20.8 is one of the silkworm (Bombyx mori) sHSPs having only one cystein in the N-terminal domain: Cys43. We report a simple measurement of oligomeric transition of sHSP20.8 using high hydrostatic pressure native polyacrylamide gel electrophoresis (high hydrostatic pressure (HP) native polyacrylamide gel electrophoresis (PAGE)). At ambient pressure under oxydative condition, the native PAGE of thermal transition of sHSP20.8 oligomer displayed a cooperative association. In contrast, HP native PAGE clearly demonstrated that sHSP20.8 dissociated at 80 MPa and 25°C, and the resultant molecular species gradually reassociated with time under that condition. In addition, the reassociation process was suppressed in the presence of the reductant. These results are consistent with the idea that sHSP20.8 oligomer temporally dissociates at the first thermo-sensing step and reassociates with the oxidation of Cys43.

Findings of Multiple Myeloma in Afro-Caribbean Patients in the United States

Directory of Open Access Journals (Sweden)

Ashtami Banavali

2018-02-01

Full Text Available Background: Multiple myeloma (MM is the second most common malignancy in the United States and has a higher incidence in the black and Afro-Caribbean population. There remain limited data on disease presentation and clinical characteristics in this patient group in the United States. The clinical profile of MM in this underrepresented patient group is described here. Methods: This retrospective study was conducted at Kings County Hospital, an urban New York City hospital in a majority Afro-Caribbean neighborhood. Data from patients diagnosed with MM from 2000 through 2013 were collected from the institution’s tumor registry. Clinical and demographic characteristics of these patients were then analyzed. Results: Patients with a diagnosis of MM were identified (N = 287. Data were available for 231 patients and of these, 97% self-identified as black. 55% were female, and there was a male-to-female ratio of 1:1.2. The mean age of female patients was 64 years; that of male patients was 63 years. Of the 231 patients, 81% had anemia, 68% had bone lesions, 47% had renal impairment, and 29% had hypercalcemia. Low levels of monoclonal protein were present in 27% of patients and 57% had disease of International Staging System stages I and II. Women had higher BMI than men. Conclusion: The mean age of presentation of MM in Afro-Caribbean patients is similar to that in the standard population; however, unlike the general US population, there was a higher incidence in women; mean BMI of women also was higher than that of male patients. A sizeable percentage of Afro-Caribbean patients with MM presented with low levels of monoclonal protein in the presence of multiorgan involvement and damage, suggesting the need for early and aggressive diagnostic testing.

Multiple conformational states of DnaA protein regulate its interaction with DnaA boxes in the initiation of DNA replication.

Science.gov (United States)

Patel, Meera J; Bhatia, Lavesh; Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

2017-09-01

DnaA protein is the initiator of genomic DNA replication in prokaryotes. It binds to specific DNA sequences in the origin of DNA replication and unwinds small AT-rich sequences downstream for the assembly of the replisome. The mechanism of activation of DnaA that enables it to bind and organize the origin DNA and leads to replication initiation remains unclear. In this study, we have developed double-labeled fluorescent DnaA probes to analyze conformational states of DnaA protein upon binding DNA, nucleotide, and Soj sporulation protein using Fluorescence Resonance Energy Transfer (FRET). Our studies demonstrate that DnaA protein undergoes large conformational changes upon binding to substrates and there are multiple distinct conformational states that enable it to initiate DNA replication. DnaA protein adopted a relaxed conformation by expanding ~15Å upon binding ATP and DNA to form the ATP·DnaA·DNA complex. Hydrolysis of bound ATP to ADP led to a contraction of DnaA within the complex. The relaxed conformation of DnaA is likely required for the formation of the multi-protein ATP·DnaA·DNA complex. In the initiation of sporulation, Soj binding to DnaA prevented relaxation of its conformation. Soj·ADP appeared to block the activation of DnaA, suggesting a mechanism for Soj·ADP in switching initiation of DNA replication to sporulation. Our studies demonstrate that multiple conformational states of DnaA protein regulate its binding to DNA in the initiation of DNA replication. Copyright © 2017 Elsevier B.V. All rights reserved.

Stability Properties of Network Diversity Multiple Access with Multiple-Antenna Reception and Imperfect Collision Multiplicity Estimation

Directory of Open Access Journals (Sweden)

Ramiro Samano-Robles

2013-01-01

Full Text Available In NDMA (network diversity multiple access, protocol-controlled retransmissions are used to create a virtual MIMO (multiple-input multiple-output system, where collisions can be resolved via source separation. By using this retransmission diversity approach for collision resolution, NDMA is the family of random access protocols with the highest potential throughput. However, several issues remain open today in the modeling and design of this type of protocol, particularly in terms of dynamic stable performance and backlog delay. This paper attempts to partially fill this gap by proposing a Markov model for the study of the dynamic-stable performance of a symmetrical and non-blind NDMA protocol assisted by a multiple-antenna receiver. The model is useful in the study of stability aspects in terms of the backlog-user distribution and average backlog delay. It also allows for the investigation of the different states of the system and the transition probabilities between them. Unlike previous works, the proposed approach considers the imperfect estimation of the collision multiplicity, which is a crucial process to the performance of NDMA. The results suggest that NDMA improves not only the throughput performance over previous solutions, but also the average number of backlogged users, the average backlog delay and, in general, the stability of random access protocols. It is also shown that when multiuser detection conditions degrade, ALOHA-type backlog retransmission becomes relevant to the stable operation of NDMA.

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations.

Science.gov (United States)

Glover, William J; Mori, Toshifumi; Schuurman, Michael S; Boguslavskiy, Andrey E; Schalk, Oliver; Stolow, Albert; Martínez, Todd J

2018-04-28

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 1 1 B u (ππ*) state and non-adiabatically coupled dark 2 1 A g state of BD. Importantly, AIMS allows for on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 1 1 B u state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1 B u or the dark 2 1 A g state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.

Enhanced population of high-l states due to the interplay between multiple scattering and dynamical screening in ion-solid collisions

Energy Technology Data Exchange (ETDEWEB)

Reinhold, C.O. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6373 (United States); Department of Physics, University of Tennessee, Knoxville, TN 37996-1200 (United States); Arbo, D.G. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6373 (United States); Department of Physics, University of Tennessee, Knoxville, TN 37996-1200 (United States); Instituto de Astronomia y Fisica del Espacio, C.C. 67, Suc. 28, 1428 Buenos Aires (Argentina); Burgdoerfer, J. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6373 (United States); Institute for Theoretical Physics, Vienna University of Technology, A-1040 Vienna (Austria); Gervais, B. [Centre Interdisciplinaire de Recherche Ions Lasers, Laboratoire Mixte, CEA-CNRS-ISMRA, BP 5133, 14070 Caen Cedex 05 (France); Lamour, E. [Centre Interdisciplinaire de Recherche Ions Lasers, Laboratoire Mixte, CEA-CNRS-ISMRA, BP 5133, 14070 Caen Cedex 05 (France); Groupe de Physique des Solides, CNRS UMR 75-88, Universites Paris 6 et Paris 7, 75251 Paris Cedex 05 (France); Vernhet, D.; Rozet, J.P. [Groupe de Physique des Solides, CNRS UMR 75-88, Universites Paris 6 et Paris 7, 75251 Paris Cedex 05 (France)

2000-02-28

We present a study of the sub-shell populations of 13.6 MeV/u Ar{sup 17+} ions after transmission through thin carbon foils. We show that the combined effect of the wake field induced by the ion in the solid and multiple collisions leads to a strongly enhanced population of high angular momentum states. These results explain new experimental data for absolute total line emission intensities. (author). Letter-to-the-editor.

Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells.

Science.gov (United States)

Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S; Chen, Faye H

2012-04-01

Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention.

CARTILAGE OLIGOMERIC MATRIX PROTEIN ENHANCES MATRIX ASSEMBLY DURING CHONDROGENESIS OF HUMAN MESENCHYMAL STEM CELLS

Science.gov (United States)

Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S.; Chen, Faye H.

2011-01-01

Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate-hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. PMID:22095699

Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties.

Science.gov (United States)

Gobec, Martina; Tomašič, Tihomir; Štimac, Adela; Frkanec, Ruža; Trontelj, Jurij; Anderluh, Marko; Mlinarič-Raščan, Irena; Jakopin, Žiga

2018-04-12

Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants, and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis, and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date. Compound 9 augmented pro-inflammatory cytokine release from human peripheral blood mononuclear cells in synergy with lipopolysaccharide. Furthermore, it was able to induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. These findings provide deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines.

Full-potential multiple scattering theory with space-filling cells for bound and continuum states.

Science.gov (United States)

Hatada, Keisuke; Hayakawa, Kuniko; Benfatto, Maurizio; Natoli, Calogero R

2010-05-12

We present a rigorous derivation of a real-space full-potential multiple scattering theory (FP-MST) that is free from the drawbacks that up to now have impaired its development (in particular the need to expand cell shape functions in spherical harmonics and rectangular matrices), valid both for continuum and bound states, under conditions for space partitioning that are not excessively restrictive and easily implemented. In this connection we give a new scheme to generate local basis functions for the truncated potential cells that is simple, fast, efficient, valid for any shape of the cell and reduces to the minimum the number of spherical harmonics in the expansion of the scattering wavefunction. The method also avoids the need for saturating 'internal sums' due to the re-expansion of the spherical Hankel functions around another point in space (usually another cell center). Thus this approach provides a straightforward extension of MST in the muffin-tin (MT) approximation, with only one truncation parameter given by the classical relation l(max) = kR(b), where k is the electron wavevector (either in the excited or ground state of the system under consideration) and R(b) is the radius of the bounding sphere of the scattering cell. Moreover, the scattering path operator of the theory can be found in terms of an absolutely convergent procedure in the l(max) --> ∞ limit. Consequently, this feature provides a firm ground for the use of FP-MST as a viable method for electronic structure calculations and makes possible the computation of x-ray spectroscopies, notably photo-electron diffraction, absorption and anomalous scattering among others, with the ease and versatility of the corresponding MT theory. Some numerical applications of the theory are presented, both for continuum and bound states.

Supplementary Material for: A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein

KAUST Repository

Smirnova, Ekaterina; Kwan, Jamie; Siu, Ryan; Gao, Xin; Zoidl, Georg; Demeler, Borries; Saridakis, Vivian; Donaldson, Logan

2016-01-01

Abstract Background CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions. Results We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size. Conclusions This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses.

Photonic crystals possessing multiple Weyl points and the experimental observation of robust surface states

Science.gov (United States)

Chen, Wen-Jie; Xiao, Meng; Chan, C. T.

2016-01-01

Weyl points, as monopoles of Berry curvature in momentum space, have captured much attention recently in various branches of physics. Realizing topological materials that exhibit such nodal points is challenging and indeed, Weyl points have been found experimentally in transition metal arsenide and phosphide and gyroid photonic crystal whose structure is complex. If realizing even the simplest type of single Weyl nodes with a topological charge of 1 is difficult, then making a real crystal carrying higher topological charges may seem more challenging. Here we design, and fabricate using planar fabrication technology, a photonic crystal possessing single Weyl points (including type-II nodes) and multiple Weyl points with topological charges of 2 and 3. We characterize this photonic crystal and find nontrivial 2D bulk band gaps for a fixed kz and the associated surface modes. The robustness of these surface states against kz-preserving scattering is experimentally observed for the first time. PMID:27703140

The Efficiency of Quantum Identity Testing of Multiple States

OpenAIRE

Kada, Masaru; Nishimura, Harumichi; Yamakami, Tomoyuki

2008-01-01

We examine two quantum operations, the Permutation Test and the Circle Test, which test the identity of n quantum states. These operations naturally extend the well-studied Swap Test on two quantum states. We first show the optimality of the Permutation Test for any input size n as well as the optimality of the Circle Test for three input states. In particular, when n=3, we present a semi-classical protocol, incorporated with the Swap Test, which approximates the Circle Test efficiently. Furt...

Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

DEFF Research Database (Denmark)

Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim

2011-01-01

-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.......048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti...

MANGO: a new approach to multiple sequence alignment.

Science.gov (United States)

Zhang, Zefeng; Lin, Hao; Li, Ming

2007-01-01

Multiple sequence alignment is a classical and challenging task for biological sequence analysis. The problem is NP-hard. The full dynamic programming takes too much time. The progressive alignment heuristics adopted by most state of the art multiple sequence alignment programs suffer from the 'once a gap, always a gap' phenomenon. Is there a radically new way to do multiple sequence alignment? This paper introduces a novel and orthogonal multiple sequence alignment method, using multiple optimized spaced seeds and new algorithms to handle these seeds efficiently. Our new algorithm processes information of all sequences as a whole, avoiding problems caused by the popular progressive approaches. Because the optimized spaced seeds are provably significantly more sensitive than the consecutive k-mers, the new approach promises to be more accurate and reliable. To validate our new approach, we have implemented MANGO: Multiple Alignment with N Gapped Oligos. Experiments were carried out on large 16S RNA benchmarks showing that MANGO compares favorably, in both accuracy and speed, against state-of-art multiple sequence alignment methods, including ClustalW 1.83, MUSCLE 3.6, MAFFT 5.861, Prob-ConsRNA 1.11, Dialign 2.2.1, DIALIGN-T 0.2.1, T-Coffee 4.85, POA 2.0 and Kalign 2.0.

Composite polymer electrolyte containing ionic liquid and functionalized polyhedral oligomeric silsesquioxanes for anhydrous PEM applications.

Science.gov (United States)

Subianto, Surya; Mistry, Mayur K; Choudhury, Namita Roy; Dutta, Naba K; Knott, Robert

2009-06-01

A new type of supported liquid membrane was made by combining an ionic liquid (IL) with a Nafion membrane reinforced with multifunctional polyhedral oligomeric silsesquioxanes (POSSs) using a layer-by-layer strategy for anhydrous proton-exchange membrane (PEM) application. The POSS was functionalized by direct sulfonation, and the sulfonated POSS (S-POSS) was incorporated into Nafion 117 membranes by the infiltration method. The resultant hybrid membrane shows strong ionic interaction between the Nafion matrix and the multifunctional POSS, resulting in increased glass transition temperature and thermal stability at very low loadings of S-POSS (1%). The presence of S-POSS has also improved the proton conductivity especially at low humidities, where it shows a marked increase due to its confinement in the ionic domains and promotes water uptake by capillary condensation. In order to achieve anhydrous conductivity, the IL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMI-BTSI) was incorporated into these membranes to provide proton conduction in the absence of water. Although the incorporation of an IL shows a plasticizing effect on the Nafion membrane, the S-POSS composite membrane with an IL shows a higher modulus at high temperatures compared to Nafion 117 and a Nafion-IL membrane, with significantly higher proton conductivity (5 mS/cm at 150 degrees C with 20% IL). This shows the ability of the multifunctional POSS and IL to work symbiotically to achieve the desirable proton conductivity and mechanical properties of such membranes by enhancing the ionic interaction within the material.

Binding and Oligomerization of Modified and Native Bt Toxins in Resistant and Susceptible Pink Bollworm.

Directory of Open Access Journals (Sweden)

Josue Ocelotl

Full Text Available Insecticidal proteins from Bacillus thuringiensis (Bt are used extensively in sprays and transgenic crops for pest control, but their efficacy is reduced when pests evolve resistance. Better understanding of the mode of action of Bt toxins and the mechanisms of insect resistance is needed to enhance the durability of these important alternatives to conventional insecticides. Mode of action models agree that binding of Bt toxins to midgut proteins such as cadherin is essential for toxicity, but some details remain unresolved, such as the role of toxin oligomers. In this study, we evaluated how Bt toxin Cry1Ac and its genetically engineered counterpart Cry1AcMod interact with brush border membrane vesicles (BBMV from resistant and susceptible larvae of Pectinophora gossypiella (pink bollworm, a global pest of cotton. Compared with Cry1Ac, Cry1AcMod lacks 56 amino acids at the amino-terminus including helix α-1; previous work showed that Cry1AcMod formed oligomers in vitro without cadherin and killed P. gossypiella larvae harboring cadherin mutations linked with >1000-fold resistance to Cry1Ac. Here we found that resistance to Cry1Ac was associated with reduced oligomer formation and insertion. In contrast, Cry1AcMod formed oligomers in BBMV from resistant larvae. These results confirm the role of cadherin in oligomerization of Cry1Ac in susceptible larvae and imply that forming oligomers without cadherin promotes toxicity of Cry1AcMod against resistant P. gossypiella larvae that have cadherin mutations.

Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD 2 in Host Defense during Pneumococcal Pneumonia.

Directory of Open Access Journals (Sweden)

Tijmen J Hommes

Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

Oligomerization of Bacillus subtilis DesR is required for fine tuning regulation of membrane fluidity.

Science.gov (United States)

Najle, Sebastián R; Inda, María E; de Mendoza, Diego; Cybulski, Larisa E

2009-10-01

The DesK-DesR two-component system regulates the order of membrane lipids in the bacterium Bacillus subtilis by controlling the expression of the des gene coding for the delta 5-acyl-lipid desaturase. To activate des transcription, the membrane-bound histidine kinase DesK phosphorylates the response regulator DesR. This covalent modification of the regulatory domain of dimeric DesR promotes, in a cooperative fashion, the hierarchical occupation of two adjacent, non-identical, DesR-P binding sites, so that there is a shift in the equilibrium toward the tetrameric active form of the response regulator. However, the mechanism of regulation of DesR activity by phosphorylation and oligomerization is not well understood. We employed deletion analysis and reporter fusions to study the role of the N-terminal domain on DesR activity. In addition, electromobility shift assays were used to analyze the binding capacity of the transcription factor to deletion mutants of the des promoter. We show that DesR lacking the N-terminal domain is still able to bind to the des promoter. We also demonstrate that if the RA site is moved closer to the -35 region of Pdes, the adjacent site RB is dispensable for activation. Our results indicate that the unphosphorylated regulatory domain of DesR obstructs the access of the recognition helix of DesR to its DNA target. In addition, we present evidence showing that RB is physiologically relevant to control the activation of the des gene when the levels of DesR-P reach a critical threshold.

One-dimensional multiple-well oscillators: A time-dependent

Indian Academy of Sciences (India)

... quantum mechanical multiple-well oscillators. An imaginary-time evolution technique, coupled with the minimization of energy expectation value to reach a global minimum, subject to orthogonality constraint (for excited states) has been employed. Pseudodegeneracy in symmetric, deep multiple-well potentials, probability ...

A Comprehensive Analysis of the Correlations between Resting-State Oscillations in Multiple-Frequency Bands and Big Five Traits.

Science.gov (United States)

Ikeda, Shigeyuki; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Sakaki, Kohei; Nozawa, Takayuki; Yokota, Susumu; Magistro, Daniele; Kawashima, Ryuta

2017-01-01

Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz) of resting-state functional magnetic resonance imaging (fMRI) activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI), and the fractional amplitude of low-frequency fluctuation (fALFF) at four distinct frequency bands (slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz) and slow-2 (0.198-0.25 Hz)). We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands.

Multiple streams approach to tobacco control policymaking in a tobacco-growing state.

Science.gov (United States)

Mamudu, Hadii M; Dadkar, Sumati; Veeranki, Sreenivas P; He, Yi; Barnes, Richard; Glantz, Stanton A

2014-08-01

Smokefree policies (SFPs) have diffused throughout the US and worldwide. However, the development of SFPs in the difficult policy environment of tobacco-producing states and economies worldwide has not been well-explored. In 2007, Tennessee, the third largest tobacco producer in the US, enacted the Non-Smoker Protection Act (NSPA). This study utilizes the multiple streams model to provide understanding of why and how this policy was developed by triangulating interviews with key stakeholders and legislative debates with archival documents. In June 2006, the Governor unexpectedly announced support for SFP, which created a window of opportunity for policy change. The Campaign for Healthy and Responsible Tennessee, a health coalition, seized this opportunity and worked with the administration and the Tennessee Restaurant Association to negotiate a comprehensive SFP, however, a weaker bill was used by the legislative leadership to develop the NSPA. Although the Governor and the Tennessee Restaurant Association's support generated an environment for 100% SFP, health groups did not fully capitalize on this environmental change and settled for a weak policy with several exemptions. This study suggests the importance for proponents of policy change to understand changes in their environment and be willing and able to capitalize on these changes.

Fouling behaviors of polybenzimidazole (PBI)-polyhedral oligomeric silsesquioxane (POSS)/polyacrylonitrile (PAN) hollow fiber membranes for engineering osmosis processes

KAUST Repository

Chen, Sicong; Fu, Xiuzhu; Chung, Neal Tai-Shung

2014-01-01

This paper investigated the individual effects of reverse salt flux and permeate flux on fouling behaviors of as-spun and annealed polybenzimidazole (PBI)-polyhedral oligomeric silsesquioxane (POSS)/polyacrylonitrile (PAN) hollow fiber membranes under forward osmosis (FO) and pressure retarded osmosis (PRO) processes. Two types of membrane fouling had been studied; namely, inorganic fouling (CaSO4·2H2O gypsum scaling) during FO operations and organic fouling (sodium alginate fouling) during PRO operations. It is found that gypsum scaling on the membrane surface may be inhibited and even eliminated with an increase in reverse MgCl2 flux due to competitive formations of MgSO4° and CaSO4·2H2O. In contrast, the increase of reverse NaCl flux exhibits a slight enhancement on alginate fouling in both FO and PRO processes. Comparing to the reverse salt flux, the permeate flux always plays a dominant role in fouling. Therefore, lesser fouling has been observed on the membrane surface under the pressurized PRO process than FO process because the reduced initial flux mitigates the fouling phenomena more significantly than the enhancement caused by an increase in reverse NaCl flux. © 2013 Elsevier B.V.

Fouling behaviors of polybenzimidazole (PBI)-polyhedral oligomeric silsesquioxane (POSS)/polyacrylonitrile (PAN) hollow fiber membranes for engineering osmosis processes

KAUST Repository

Chen, Sicong

2014-02-01

This paper investigated the individual effects of reverse salt flux and permeate flux on fouling behaviors of as-spun and annealed polybenzimidazole (PBI)-polyhedral oligomeric silsesquioxane (POSS)/polyacrylonitrile (PAN) hollow fiber membranes under forward osmosis (FO) and pressure retarded osmosis (PRO) processes. Two types of membrane fouling had been studied; namely, inorganic fouling (CaSO4·2H2O gypsum scaling) during FO operations and organic fouling (sodium alginate fouling) during PRO operations. It is found that gypsum scaling on the membrane surface may be inhibited and even eliminated with an increase in reverse MgCl2 flux due to competitive formations of MgSO4° and CaSO4·2H2O. In contrast, the increase of reverse NaCl flux exhibits a slight enhancement on alginate fouling in both FO and PRO processes. Comparing to the reverse salt flux, the permeate flux always plays a dominant role in fouling. Therefore, lesser fouling has been observed on the membrane surface under the pressurized PRO process than FO process because the reduced initial flux mitigates the fouling phenomena more significantly than the enhancement caused by an increase in reverse NaCl flux. © 2013 Elsevier B.V.

Inhibiting α-synuclein oligomerization by stable cell-penetrating β-synuclein fragments recovers phenotype of Parkinson's disease model flies.

Directory of Open Access Journals (Sweden)

Ronit Shaltiel-Karyo

Full Text Available The intracellular oligomerization of α-synuclein is associated with Parkinson's disease and appears to be an important target for disease-modifying treatment. Yet, to date, there is no specific inhibitor for this aggregation process. Using unbiased systematic peptide array analysis, we identified molecular interaction domains within the β-synuclein polypeptide that specifically binds α-synuclein. Adding such peptide fragments to α-synuclein significantly reduced both amyloid fibrils and soluble oligomer formation in vitro. A retro-inverso analogue of the best peptide inhibitor was designed to develop the identified molecular recognition module into a drug candidate. While this peptide shows indistinguishable activity as compared to the native peptide, it is stable in mouse serum and penetrates α-synuclein over-expressing cells. The interaction interface between the D-amino acid peptide and α-synuclein was mapped by Nuclear Magnetic Resonance spectroscopy. Finally, administering the retro-inverso peptide to a Drosophila model expressing mutant A53T α-synuclein in the nervous system, resulted in a significant recovery of the behavioral abnormalities of the treated flies and in a significant reduction in α-synuclein accumulation in the brains of the flies. The engineered retro-inverso peptide can serve as a lead for developing a novel class of therapeutic agents to treat Parkinson's disease.

Deterministically entangling multiple remote quantum memories inside an optical cavity

Science.gov (United States)

Yan, Zhihui; Liu, Yanhong; Yan, Jieli; Jia, Xiaojun

2018-01-01

Quantum memory for the nonclassical state of light and entanglement among multiple remote quantum nodes hold promise for a large-scale quantum network, however, continuous-variable (CV) memory efficiency and entangled degree are limited due to imperfect implementation. Here we propose a scheme to deterministically entangle multiple distant atomic ensembles based on CV cavity-enhanced quantum memory. The memory efficiency can be improved with the help of cavity-enhanced electromagnetically induced transparency dynamics. A high degree of entanglement among multiple atomic ensembles can be obtained by mapping the quantum state from multiple entangled optical modes into a collection of atomic spin waves inside optical cavities. Besides being of interest in terms of unconditional entanglement among multiple macroscopic objects, our scheme paves the way towards the practical application of quantum networks.

Continued biological investigations of boron-rich oligomeric phosphate diesters (OPDs). Tumor-selective boron agents for BNCT

International Nuclear Information System (INIS)

Lee, Mark W.; Shelly, Kenneth; Kane, Robert R.; Hawthorne, M. Frederick

2006-01-01

Clinical success of Boron Neutron Capture Therapy will rely on the selective intracellular delivery of high concentrations of boron-10 to tumor tissue. In order for a boron agent to facilitate clinical success, the simultaneous needs of obtaining a high tumor dose, high tumor selectivity, and low systemic toxicity must be realized. Boron-rich oligomeric phosphate diesters (OPDs) are a class of highly water-soluble compounds containing up to 40% boron by weight. Previous work in our groups demonstrated that once placed in the cytoplasm of tumor cells, OPDs quickly accumulate within the cell nucleus. The objective of the current study was to determine the biodistribution of seven different free OPDs in BALB/c mice bearing EMT6 tumors. Fructose solutions containing between 1.4 and 6.4 micrograms of boron per gram of tissue were interveinously injected in mice seven to ten days after tumor implantation. At intervals during the study, animals were euthanized and samples of tumor, blood, liver, kidney, brain and skin were collected and analyzed for boron content using ICP-AES. Tumor boron concentrations of between 5 and 29 ppm were achieved and maintained over the 72-hour time course of each experiment. Several OPDs demonstrated high tumor selectivity with one oligomer exhibiting a tumor to blood ratio of 35:1. The apparent toxicity of each oligomer was assessed through animal behavior during the experiment and necropsy of each animal upon sacrifice. (author)

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure*

Science.gov (United States)

Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R.; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

2012-01-01

The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone. PMID:22573329

Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.

Science.gov (United States)

Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

2012-06-29

The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone.

A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

Science.gov (United States)

2013-09-12

performance liquid chroma- tography to greater than 95% purity (Bio-synthesis, Inc., Lewisville, TX). Lyophilized peptides were initially resuspended in...lesser extent RVFV-6sc, were found to precipitate Gc (Figure 5); however, in the presence of the non- ionic detergent Triton-X, which will solubilize...Viral membrane fusion. Nat Struct Mol Biol 15: 690–698. 12. Allison SL, Schalich J, Stiasny K, Mandl CW, Kunz C, et al. (1995) Oligomeric rearrangement

Development of the optical sensor for discriminating isomers of fatty acids based on emissive network polymers composed of polyhedral oligomeric silsesquioxane.

Science.gov (United States)

Narikiyo, Hayato; Kakuta, Takahiro; Matsuyama, Hiroki; Gon, Masayuki; Tanaka, Kazuo; Chujo, Yoshiki

2017-07-01

It was shown that water-soluble network polymers composed of polyhedral oligomeric silsesquioxane (POSS) had hydrophobic spaces inside the network because of strong hydrophobicity of the cubic silica cage. In this study, the water-soluble POSS network polymers connected with triphenylamine derivatives (TPA-POSS) were synthesized, and their functions as a sensor for discriminating the geometric isomers of fatty acids were investigated. Accordingly, in the photoluminescence spectra, different time-courses of intensity and peak wavelengths of the emission bands were detected from the TPA-POSS-containing solution in the presence of cis- or trans-fatty acids during incubation. Furthermore, variable time-dependent changes were obtained by changing coexisting ratios between two geometric isomers. From the mechanistic investigation, it was implied that these changes could be originated from the difference in the degree of interaction between the POSS networks and each fatty acid. Our data could be applicable for constructing a sensing material for generation and proportion of trans-fatty acids in the oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Caught in self-interaction: evolutionary and functional mechanisms of protein homooligomerization

International Nuclear Information System (INIS)

Hashimoto, Kosuke; Nishi, Hafumi; Bryant, Stephen; Panchenko, Anna R

2011-01-01

Many soluble and membrane proteins form homooligomeric complexes in a cell which are responsible for the diversity and specificity of many pathways, may mediate and regulate gene expression, activity of enzymes, ion channels, receptors, and cell adhesion processes. The evolutionary and physical mechanisms of oligomerization are very diverse and its general principles have not yet been formulated. Homooligomeric states may be conserved within certain protein subfamilies and might be important in providing specificity to certain substrates while minimizing interactions with other unwanted partners. Moreover, recent studies have led to a greater awareness that transitions between different oligomeric states may regulate protein activity and provide the switch between different pathways. In this paper we summarize the biological importance of homooligomeric assemblies, physico-chemical properties of their interfaces, experimental and computational methods for their identification and prediction. We particularly focus on homooligomer evolution and describe the mechanisms to develop new specificities through the formation of different homooligomeric complexes. Finally, we discuss the possible role of oligomeric transitions in the regulation of protein activity and compile a set of experimental examples with such regulatory mechanisms

Rise of mean multiplicity depending on transverse momentum

International Nuclear Information System (INIS)

Troshin, S.M.

1977-01-01

Dependence of mean multiplicity on the transversal momentum transfer is studied. In framework of the model in view, based on possible probabilitic interpretation of the unitarity condition, and assuming a weak correlation between the recoil particle momenta in the intermediate n-particle state, it is shown that mean multiplicity increases linearly with rise of the transversal momentum. Behaviour of the mean multiplicity depending on the impact parameter is also studied

State dependent arrival in bulk retrial queueing system with immediate Bernoulli feedback, multiple vacations and threshold

Science.gov (United States)

Niranjan, S. P.; Chandrasekaran, V. M.; Indhira, K.

2017-11-01

The objective of this paper is to analyse state dependent arrival in bulk retrial queueing system with immediate Bernoulli feedback, multiple vacations, threshold and constant retrial policy. Primary customers are arriving into the system in bulk with different arrival rates λ a and λ b . If arriving customers find the server is busy then the entire batch will join to orbit. Customer from orbit request service one by one with constant retrial rate γ. On the other hand if an arrival of customers finds the server is idle then customers will be served in batches according to general bulk service rule. After service completion, customers may request service again with probability δ as feedback or leave from the system with probability 1 - δ. In the service completion epoch, if the orbit size is zero then the server leaves for multiple vacations. The server continues the vacation until the orbit size reaches the value ‘N’ (N > b). At the vacation completion, if the orbit size is ‘N’ then the server becomes ready to provide service for customers from the main pool or from the orbit. For the designed queueing model, probability generating function of the queue size at an arbitrary time will be obtained by using supplementary variable technique. Various performance measures will be derived with suitable numerical illustrations.

Fuzzy multiple attribute decision making methods and applications

CERN Document Server

Chen, Shu-Jen

1992-01-01

This monograph is intended for an advanced undergraduate or graduate course as well as for researchers, who want a compilation of developments in this rapidly growing field of operations research. This is a sequel to our previous works: "Multiple Objective Decision Making--Methods and Applications: A state-of-the-Art Survey" (No.164 of the Lecture Notes); "Multiple Attribute Decision Making--Methods and Applications: A State-of-the-Art Survey" (No.186 of the Lecture Notes); and "Group Decision Making under Multiple Criteria--Methods and Applications" (No.281 of the Lecture Notes). In this monograph, the literature on methods of fuzzy Multiple Attribute Decision Making (MADM) has been reviewed thoroughly and critically, and classified systematically. This study provides readers with a capsule look into the existing methods, their characteristics, and applicability to the analysis of fuzzy MADM problems. The basic concepts and algorithms from the classical MADM methods have been used in the development of the f...

Multiple Intelligences within the Cross-Curricular Approach

Directory of Open Access Journals (Sweden)

Anthoula Vaiou

2010-02-01

Full Text Available The present study was realized in a Greek 6th grade State Primary School class and was based on Howard Gardner’s theory of multiple intelligences, which was first introduced in 1983. More particularly, it was explored to what extent the young learners possess multiple intelligences through the use of a specially-designed questionnaire and a series of interviews. The findings of the above have served as a tool to the construction of a project work based on students’ learning preferences within a cross-curricular framework, easily applicable to the Greek State School curriculum. All learners were activated to participate within a school environment that traditionally promotes linguistic and mathematical skills matching dominant multiple intelligences or a combination of some of them to thematic units already taught by Greek teachers. The suggested project was assessed through observation and student portfolio, showing that the young learners’ multiple intelligences were exploited to a great extent, promoting the learning process satisfactorily. The results of this study can provide a contribution to the literature of multiple intelligences in the Greek reality and suggest a need for further consideration and exploration in the field. Finally, the researcher of this study hopes the present work could function as a springboard for more elaborated studies in the future.

Search for pair production of up-type vector-like quarks and for four-top-quark events in final states with multiple $b$-jets with the ATLAS detector

CERN Document Server

Aaboud, Morad; ATLAS Collaboration; Abbott, Brad; Abdinov, Ovsat; Abeloos, Baptiste; Abidi, Syed Haider; AbouZeid, Ossama; Abraham, Nicola; Abramowicz, Halina; Abreu, Henso; Abulaiti, Yiming; Acharya, Bobby Samir; Adachi, Shunsuke; Adamczyk, Leszek; Adelman, Jahred; Adersberger, Michael; Adye, Tim; Affolder, Tony; Afik, Yoav; Agheorghiesei, Catalin; Aguilar-Saavedra, Juan Antonio; Ahmadov, Faig; Aielli, Giulio; Akatsuka, Shunichi; Åkesson, Torsten Paul Ake; Akilli, Ece; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albicocco, Pietro; Alconada Verzini, Maria Josefina; Alderweireldt, Sara; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Ali, Babar; Aliev, Malik; Alimonti, Gianluca; Alison, John; Alkire, Steven Patrick; Allaire, Corentin; Allbrooke, Benedict; Allen, Benjamin William; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Alshehri, Azzah Aziz; Alstaty, Mahmoud; Alvarez Gonzalez, Barbara; Álvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amaral Coutinho, Yara; Ambroz, Luca; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amoroso, Simone; Amrouche, Cherifa Sabrina; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Angerami, Aaron; Anisenkov, Alexey; Annovi, Alberto; Antel, Claire; Anthony, Matthew; Antonelli, Mario; Antrim, Daniel Joseph; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Araujo Ferraz, Victor; Araujo Pereira, Rodrigo; Arce, Ayana; Ardell, Rose Elisabeth; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Armbruster, Aaron James; Armitage, Lewis James; Arnaez, Olivier; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Artz, Sebastian; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Asimakopoulou, Eleni Myrto; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkin, Ryan Justin; Atkinson, Markus; Atlay, Naim Bora; Augsten, Kamil; Avolio, Giuseppe; Avramidou, Rachel Maria; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baas, Alessandra; Baca, Matthew John; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Bagnaia, Paolo; Bahmani, Marzieh; Bahrasemani, Sina; Bailey, Adam; Baines, John; Bajic, Milena; Baker, Oliver Keith; Bakker, Pepijn Johannes; Bakshi Gupta, Debottam; Baldin, Evgenii; Balek, Petr; Balli, Fabrice; Balunas, William Keaton; Banas, Elzbieta; Bandyopadhyay, Anjishnu; Banerjee, Swagato; Bannoura, Arwa A E; Barak, Liron; Barbe, William Mickael; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisits, Martin-Stefan; Barkeloo, Jason Tyler Colt; Barklow, Timothy; Barlow, Nick; Barnea, Rotem; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska-Blenessy, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barranco Navarro, Laura; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Bates, Richard; Batista, Santiago Juan; Batlamous, Souad; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bauer, Kevin Thomas; Bawa, Harinder Singh; Beacham, James; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Bechtle, Philip; Beck, Hans~Peter; Beck, Helge Christoph; Becker, Kathrin; Becker, Maurice; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bedognetti, Matteo; Bee, Christopher; Beermann, Thomas; Begalli, Marcia; Begel, Michael; Behera, Arabinda; Behr, Janna Katharina; Bell, Andrew Stuart; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Belyaev, Nikita; Benary, Odette; Benchekroun, Driss; Bender, Michael; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez, Jose; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Bergsten, Laura Jean; Beringer, Jürg; Berlendis, Simon; Bernard, Nathan Rogers; Bernardi, Gregorio; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertram, Iain Alexander; Bertsche, Carolyn; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Bethani, Agni; Bethke, Siegfried; Betti, Alessandra; Bevan, Adrian John; Beyer, Julien-christopher; Bianchi, Riccardo-Maria; Biebel, Otmar; Biedermann, Dustin; Bielski, Rafal; Bierwagen, Katharina; Biesuz, Nicolo Vladi; Biglietti, Michela; Billoud, Thomas Remy Victor; Bindi, Marcello; Bingul, Ahmet; Bini, Cesare; Biondi, Silvia; Bisanz, Tobias; Bittrich, Carsten; Bjergaard, David Martin; Black, James; Black, Kevin; Blair, Robert; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blue, Andrew; Blumenschein, Ulrike; Blunier, Sylvain; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boerner, Daniela; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bokan, Petar; Bold, Tomasz; Boldyrev, Alexey; Bolz, Arthur Eugen; Bomben, Marco; Bona, Marcella; Bonilla, Johan Sebastian; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Bortfeldt, Jonathan; Bortoletto, Daniela; Bortolotto, Valerio; Boscherini, Davide; Bosman, Martine; Bossio Sola, Jonathan David; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Boutle, Sarah Kate; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozson, Adam James; Bracinik, Juraj; Brahimi, Nihal; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Braren, Frued; Bratzler, Uwe; Brau, Benjamin; Brau, James; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Brickwedde, Bernard; Briglin, Daniel Lawrence; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brock, Ian; Brock, Raymond; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brost, Elizabeth; Broughton, James; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruni, Alessia; Bruni, Graziano; Bruni, Lucrezia Stella; Bruno, Salvatore; Brunt, Benjamin; Bruschi, Marco; Bruscino, Nello; Bryant, Patrick; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Budagov, Ioulian; Buehrer, Felix; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burch, Tyler James; Burdin, Sergey; Burgard, Carsten Daniel; Burger, Angela Maria; Burghgrave, Blake; Burka, Klaudia; Burke, Stephen; Burmeister, Ingo; Burr, Jonathan Thomas Peter; Büscher, Daniel; Büscher, Volker; Buschmann, Eric; Bussey, Peter; Butler, John; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabras, Grazia; Cabrera Urbán, Susana; Caforio, Davide; Cai, Huacheng; Cairo, Valentina; Cakir, Orhan; Calace, Noemi; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Callea, Giuseppe; Caloba, Luiz; Calvente Lopez, Sergio; Calvet, David; Calvet, Samuel; Calvet, Thomas Philippe; Calvetti, Milene; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminal Armadans, Roger; Camincher, Clement; Campana, Simone; Campanelli, Mario; Camplani, Alessandra; Campoverde, Angel; Canale, Vincenzo; Cano Bret, Marc; Cantero, Josu; Cao, Tingting; Cao, Yumeng; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Carbone, Ryne Michael; Cardarelli, Roberto; Cardillo, Fabio; Carli, Ina; Carli, Tancredi; Carlino, Gianpaolo; Carlson, Benjamin Taylor; Carminati, Leonardo; Carney, Rebecca; Caron, Sascha; Carquin, Edson; Carrá, Sonia; Carrillo-Montoya, German D; Casadei, Diego; Casado, Maria Pilar; Casha, Albert Francis; Casolino, Mirkoantonio; Casper, David William; Castelijn, Remco; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavallaro, Emanuele; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Celebi, Emre; Ceradini, Filippo; Cerda Alberich, Leonor; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chan, Stephen Kam-wah; Chan, Wing Sheung; Chan, Yat Long; Chang, Philip; Chapman, John Derek; Charlton, David; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Che, Siinn; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Cheng; Chen, Chunhui; Chen, Hucheng; Chen, Jing; Chen, Jue; Chen, Shenjian; Chen, Shion; Chen, Xin; Chen, Ye; Chen, Yu-Heng; Cheng, Hok Chuen; Cheng, Huajie; Cheplakov, Alexander; Cheremushkina, Evgeniya; Cherkaoui El Moursli, Rajaa; Cheu, Elliott; Cheung, Kingman; Chevalier, Laurent; Chiarella, Vitaliano; Chiarelli, Giorgio; Chiodini, Gabriele; Chisholm, Andrew; Chitan, Adrian; Chiu, I-huan; Chiu, Yu Him Justin; Chizhov, Mihail; Choi, Kyungeon; Chomont, Arthur Rene; Chouridou, Sofia; Chow, Yun Sang; Christodoulou, Valentinos; Chu, Ming Chung; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Cinca, Diane; Cindro, Vladimir; Cioară, Irina Antonela; Ciocio, Alessandra; Cirotto, Francesco; Citron, Zvi Hirsh; Citterio, Mauro; Clark, Allan G; Clark, Michael; Clark, Philip James; Clarke, Robert; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coimbra, Artur Emanuel; Colasurdo, Luca; Cole, Brian; Colijn, Auke-Pieter; Collot, Johann; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Constantinescu, Serban; Conventi, Francesco; Cooper-Sarkar, Amanda; Cormier, Felix; Cormier, Kyle James Read; Corradi, Massimo; Corrigan, Eric Edward; Corriveau, François; Cortes-Gonzalez, Arely; Costa, María José; Costanzo, Davide; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Crane, Jonathan; Cranmer, Kyle; Crawley, Samuel Joseph; Creager, Rachael; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cueto, Ana; Cuhadar Donszelmann, Tulay; Cukierman, Aviv Ruben; Curatolo, Maria; Cúth, Jakub; Czekierda, Sabina; Czodrowski, Patrick; D'amen, Gabriele; D'Auria, Saverio; D'Eramo, Louis; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dado, Tomas; Dahbi, Salah-eddine; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey; Daneri, Maria Florencia; Dang, Nguyen Phuong; Dann, Nick; Danninger, Matthias; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dartsi, Olympia; Dattagupta, Aparajita; Daubney, Thomas; Davey, Will; David, Claire; Davidek, Tomas; Davis, Douglas; Dawe, Edmund; Dawson, Ian; De, Kaushik; de Asmundis, Riccardo; De Benedetti, Abraham; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Maria, Antonio; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vasconcelos Corga, Kevin; De Vivie De Regie, Jean-Baptiste; Debenedetti, Chiara; Dedovich, Dmitri; Dehghanian, Nooshin; Del Gaudio, Michela; Del Peso, Jose; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Dell'Acqua, Andrea; Dell'Asta, Lidia; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delporte, Charles; Delsart, Pierre-Antoine; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Denisov, Sergey; Denysiuk, Denys; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Dette, Karola; Devesa, Maria Roberta; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Bello, Francesco Armando; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Clemente, William Kennedy; Di Donato, Camilla; Di Girolamo, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Petrillo, Karri Folan; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Dias do Vale, Tiago; Diaz, Marco Aurelio; Dickinson, Jennet; Diehl, Edward; Dietrich, Janet; Díez Cornell, Sergio; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobre, Monica; Dodsworth, David; Doglioni, Caterina; Dolejsi, Jiri; Dolezal, Zdenek; Donadelli, Marisilvia; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dreyer, Etienne; Dreyer, Timo; Dris, Manolis; Du, Yanyan; Duarte-Campderros, Jorge; Dubinin, Filipp; Dubreuil, Arnaud; Duchovni, Ehud; Duckeck, Guenter; Ducourthial, Audrey; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudder, Andreas Christian; Duffield, Emily Marie; Duflot, Laurent; Dührssen, Michael; Dülsen, Carsten; Dumancic, Mirta; Dumitriu, Ana Elena; Duncan, Anna Kathryn; Dunford, Monica; Duperrin, Arnaud; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dutta, Baishali; Duvnjak, Damir; Dyndal, Mateusz; Dziedzic, Bartosz Sebastian; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; El Kosseifi, Rima; Ellajosyula, Venugopal; Ellert, Mattias; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Ennis, Joseph Stanford; Epland, Matthew Berg; Erdmann, Johannes; Ereditato, Antonio; Errede, Steven; Escalier, Marc; Escobar, Carlos; Esposito, Bellisario; Estrada Pastor, Oscar; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Ezzi, Mohammed; Fabbri, Federica; Fabbri, Laura; Fabiani, Veronica; Facini, Gabriel; Faisca Rodrigues Pereira, Rui Miguel; Fakhrutdinov, Rinat; Falciano, Speranza; Falke, Peter Johannes; Falke, Saskia; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farina, Edoardo Maria; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fawcett, William James; Fayard, Louis; Fedin, Oleg; Fedorko, Wojciech; Feickert, Matthew; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Minyu; Fenton, Michael James; Fenyuk, Alexander; Feremenga, Last; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Fiedler, Frank; Filipčič, Andrej; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Flaschel, Nils; Fleck, Ivor; Fleischmann, Philipp; Fletcher, Rob Roy MacGregor; Flick, Tobias; Flierl, Bernhard Matthias; Flores, Lucas Macrorie; Flores Castillo, Luis; Fomin, Nikolai; Forcolin, Giulio Tiziano; Formica, Andrea; Förster, Fabian Alexander; Forti, Alessandra; Foster, Andrew Geoffrey; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; Fressard-Batraneanu, Silvia; Freund, Benjamin; Spolidoro Freund, Werner; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fusayasu, Takahiro; Fuster, Juan; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gach, Grzegorz; Gadatsch, Stefan; Gadomski, Szymon; Gadow, Philipp; Gagliardi, Guido; Gagnon, Louis Guillaume; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gamboa Goni, Rodrigo; Gan, KK; Ganguly, Sanmay; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; García, Carmen; García Navarro, José Enrique; García Pascual, Juan Antonio; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gasnikova, Ksenia; Gaudiello, Andrea; Gaudio, Gabriella; Gavrilenko, Igor; Gavrilyuk, Alexander; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Gee, Norman; Geisen, Jannik; Geisen, Marc; Geisler, Manuel Patrice; Gellerstedt, Karl; Gemme, Claudia; Genest, Marie-Hélène; Geng, Cong; Gentile, Simonetta; Gentsos, Christos; George, Simon; Gerbaudo, Davide; Gessner, Gregor; Ghasemi, Sara; Ghneimat, Mazuza; Giacobbe, Benedetto; Giagu, Stefano; Giangiacomi, Nico; Giannetti, Paola; Gibson, Stephen; Gignac, Matthew; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giraud, Pierre-Francois; Giromini, Paolo; Giugliarelli, Gilberto; Giugni, Danilo; Giuli, Francesco; Giulini, Maddalena; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gkountoumis, Panagiotis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Gama, Rafael; Gonella, Giulia; Gonella, Laura; Gongadze, Alexi; Gonnella, Francesco; Gonski, Julia; González de la Hoz, Santiago; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gottardo, Carlo Alberto; Goudet, Christophe Raymond; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Goy, Corinne; Gozani, Eitan; Grabowska-Bold, Iwona; Gradin, Per Olov Joakim; Graham, Emily Charlotte; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Gratchev, Vadim; Gravila, Paul Mircea; Gray, Chloe; Gray, Heather; Greenwood, Zeno Dixon; Grefe, Christian; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Grevtsov, Kirill; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Groh, Sabrina; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Grummer, Aidan; Guan, Liang; Guan, Wen; Guenther, Jaroslav; Guerguichon, Antinea; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Gugel, Ralf; Gui, Bin; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Guo, Wen; Guo, Yicheng; Guo, Ziyu; Gupta, Ruchi; Gurbuz, Saime; Gustavino, Giuliano; Gutelman, Benjamin Jacque; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Guzik, Marcin Pawel; Gwenlan, Claire; Gwilliam, Carl; Hönle, Andreas; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Hadef, Asma; Hageböck, Stephan; Hagihara, Mutsuto; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamilton, Andrew; Hamity, Guillermo Nicolas; Han, Kunlin; Han, Liang; Han, Shuo; Hanagaki, Kazunori; Hance, Michael; Handl, David Michael; Haney, Bijan; Hankache, Robert; Hanke, Paul; Hansen, Eva; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Harkusha, Siarhei; Harrison, Paul Fraser; Hartmann, Nikolai Marcel; Hasegawa, Yoji; Hasib, Ahmed; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havener, Laura Brittany; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hayden, Daniel; Hayes, Christopher; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Heath, Matthew Peter; Hedberg, Vincent; Heelan, Louise; Heer, Sebastian; Heidegger, Kim Katrin; Heilman, Jesse; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Jochen Jens; Heinrich, Lukas; Heinz, Christian; Hejbal, Jiri; Helary, Louis; Held, Alexander; Hellesund, Simen; Hellman, Sten; Helsens, Clement; Henderson, Robert; Heng, Yang; Henkelmann, Steffen; Henriques Correia, Ana Maria; Herbert, Geoffrey Henry; Herde, Hannah; Herget, Verena; Hernández Jiménez, Yesenia; Herr, Holger; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Herwig, Theodor Christian; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Higashino, Satoshi; Higón-Rodriguez, Emilio; Hildebrand, Kevin; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hils, Maximilian; Hinchliffe, Ian; Hirose, Minoru; Hirschbuehl, Dominic; Hiti, Bojan; Hladik, Ondrej; Hlaluku, Dingane Reward; Hoad, Xanthe; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohn, David; Hohov, Dmytro; Holmes, Tova Ray; Holzbock, Michael; Homann, Michael; Honda, Shunsuke; Honda, Takuya; Hong, Tae Min; Hooberman, Benjamin Henry; Hopkins, Walter; Horii, Yasuyuki; Horn, Philipp; Horton, Arthur James; Horyn, Lesya Anna; Hostachy, Jean-Yves; Hostiuc, Alexandru; Hou, Suen; Hoummada, Abdeslam; Howarth, James; Hoya, Joaquin; Hrabovsky, Miroslav; Hrdinka, Julia; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Qipeng; Hu, Shuyang; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huebner, Michael; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Huhtinen, Mika; Hunter, Robert Francis Holub; Huo, Peng; Hupe, Andre Marc; Huseynov, Nazim; Huston, Joey; Huth, John; Hyneman, Rachel; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idrissi, Zineb; Iengo, Paolo; Ignazzi, Rosanna; Igonkina, Olga; Iguchi, Ryunosuke; Iizawa, Tomoya; Ikegami, Yoichi; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Iltzsche, Franziska; Introzzi, Gianluca; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Isacson, Max Fredrik; Ishijima, Naoki; Ishino, Masaya; Ishitsuka, Masaki; Issever, Cigdem; Istin, Serhat; Ito, Fumiaki; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivina, Anna; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jacka, Petr; Jackson, Paul; Jacobs, Ruth Magdalena; Jain, Vivek; Jäkel, Gunnar; Jakobi, Katharina Bianca; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jamin, David Olivier; Jana, Dilip; Jansky, Roland; Janssen, Jens; Janus, Michel; Janus, Piotr Andrzej; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Javurkova, Martina; Jeanneau, Fabien; Jeanty, Laura; Jejelava, Juansher; Jelinskas, Adomas; Jenni, Peter; Jeong, Jihyun; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Hai; Jiang, Yi; Jiang, Zihao; Jiggins, Stephen; Jimenez Morales, Fabricio Andres; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Jivan, Harshna; Johansson, Per; Johns, Kenneth; Johnson, Christian; Johnson, William Joseph; Jon-And, Kerstin; Jones, Roger; Jones, Samuel David; Jones, Sarah; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Jovicevic, Jelena; Ju, Xiangyang; Junggeburth, Johannes Josef; Juste Rozas, Aurelio; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kaji, Toshiaki; Kajomovitz, Enrique; Kalderon, Charles William; Kaluza, Adam; Kama, Sami; Kamenshchikov, Andrey; Kanjir, Luka; Kano, Yuya; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kaplan, Laser Seymour; Kar, Deepak; Kareem, Mohammad Jawad; Karentzos, Efstathios; Karpov, Sergey; Karpova, Zoya; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kasahara, Kota; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Kato, Chikuma; Katre, Akshay; Katzy, Judith; Kawade, Kentaro; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kay, Ellis; Kazanin, Vassili; Keeler, Richard; Kehoe, Robert; Keller, John; Kellermann, Edgar; Kempster, Jacob Julian; Kendrick, James; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khader, Mazin; Khalil-zada, Farkhad; Khanov, Alexander; Kharlamov, Alexey; Kharlamova, Tatyana; Khodinov, Alexander; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kido, Shogo; Kiehn, Moritz; Kilby, Callum; Kim, Hee Yeun; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; Kirchmeier, David; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kitali, Vincent; Kivernyk, Oleh; Kladiva, Eduard; Klapdor-Kleingrothaus, Thorwald; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klingl, Tobias; Klioutchnikova, Tatiana; Klitzner, Felix Fidelio; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Köhler, Nicolas Maximilian; Koi, Tatsumi; Kolb, Mathis; Koletsou, Iro; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Konya, Balazs; Kopeliansky, Revital; Koperny, Stefan; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotwal, Ashutosh; Koulouris, Aimilianos; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kourlitis, Evangelos; Kouskoura, Vasiliki; Kowalewska, Anna Bozena; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozakai, Chihiro; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitrii; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Krauss, Dominik; Kremer, Jakub Andrzej; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Jiri; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Kruse, Mark; Kubota, Takashi; Kuday, Sinan; Kuechler, Jan Thomas; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Thorsten; Kukhtin, Victor; Kukla, Romain; Kulchitsky, Yuri; Kuleshov, Sergey; Kulinich, Yakov Petrovich; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kupfer, Tobias; Kuprash, Oleg; Kurashige, Hisaya; Kurchaninov, Leonid; Kurochkin, Yurii; Kurth, Matthew Glenn; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; La Ruffa, Francesco; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lack, David Philip John; Lacker, Heiko; Lacour, Didier; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lai, Stanley; Lammers, Sabine; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lanfermann, Marie Christine; Lang, Valerie Susanne; Lange, Jörn Christian; Langenberg, Robert Johannes; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Lapertosa, Alessandro; Laplace, Sandrine; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Lau, Tak Shun; Laudrain, Antoine; Law, Alexander; Laycock, Paul; Lazzaroni, Massimo; Le, Brian; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Quilleuc, Eloi; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne; Lee, Claire Alexandra; Lee, Graham Richard; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Benoit; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehmann Miotto, Giovanna; Leight, William Axel; Leisos, Antonios; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Lerner, Giuseppe; Leroy, Claude; Les, Robert; Lesage, Arthur; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Lewis, Dave; Li, Bing; Li, Changqiao; Li, Haifeng; Li, Liang; Li, Qi; Li, Quanyin; Li, Shu; Li, Xingguo; Li, Yichen; Liang, Zhijun; Liberti, Barbara; Liblong, Aaron; Lie, Ki; Liem, Sebastian; Limosani, Antonio; Lin, Chiao-ying; Lin, Kuan-yu; Lin, Simon; Lin, Tai-Hua; Linck, Rebecca Anne; Lindquist, Brian Edward; Lionti, Anthony; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lister, Alison; Litke, Alan; Little, Jared David; Liu, Bingxuan; Liu, Bo; Liu, Hao; Liu, Hongbin; Liu, Jesse; Liu, Jianbei; Liu, Kun; Liu, Minghui; Liu, Peilian; Liu, Yanlin; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo, Cheuk Yee; Lo Sterzo, Francesco; Lobodzinska, Ewelina Maria; Loch, Peter; Loebinger, Fred; Loesle, Alena; Loew, Kevin Michael; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan David; Long, Robin Eamonn; Longo, Luigi; Looper, Kristina Anne; Lopez, Jorge; Lopez Paz, Ivan; Lopez Solis, Alvaro; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Lösel, Philipp Jonathan; Lou, XinChou; Lou, Xuanhong; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lozano Bahilo, Jose Julio; Lu, Haonan; Lu, Nan; Lu, Yun-Ju; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luedtke, Christian; Luehring, Frederick; Luise, Ilaria; Lukas, Wolfgang; Luminari, Lamberto; Lund-Jensen, Bengt; Lutz, Margaret Susan; Luzi, Pierre Marc; Lynn, David; Lysak, Roman; Lytken, Else; Lyu, Feng; Lyubushkin, Vladimir; Ma, Hong; Ma, Lian Liang; Ma, Yanhui; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Maček, Boštjan; Machado Miguens, Joana; Madaffari, Daniele; Madar, Romain; Mader, Wolfgang; Madsen, Alexander; Madysa, Nico; Maeda, Junpei; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magerl, Veronika; Maidantchik, Carmen; Maier, Thomas; Maio, Amélia; Majersky, Oliver; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Claire; Maltezos, Stavros; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandić, Igor; Maneira, José; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mankinen, Katja Hannele; Mann, Alexander; Manousos, Athanasios; Mansoulie, Bruno; Mansour, Jason Dhia; Mantifel, Rodger; Mantoani, Matteo; Manzoni, Stefano; Marceca, Gino; March, Luis; Marchese, Luigi; Marchiori, Giovanni; Marcisovsky, Michal; Marin Tobon, Cesar Augusto; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marshall, Zach; Martensson, Mikael; Marti-Garcia, Salvador; Martin, Christopher Blake; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martinez Outschoorn, Verena; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Mason, Lara Hannan; Massa, Lorenzo; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Maznas, Ioannis; Mazza, Simone Michele; Mc Fadden, Neil Christopher; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Thomas; McClymont, Laurie; McDonald, Emily; Mcfayden, Josh; Mchedlidze, Gvantsa; McKay, Madalyn; McLean, Kayla; McMahon, Steve; McNamara, Peter Charles; McNicol, Christopher John; McPherson, Robert; Mdhluli, Joyful Elma; Meadows, Zachary Alden; Meehan, Samuel; Megy, Theo; Mehlhase, Sascha; Mehta, Andrew; Meideck, Thomas; Meirose, Bernhard; Melini, Davide; Mellado Garcia, Bruce Rafael; Mellenthin, Johannes Donatus; Melo, Matej; Meloni, Federico; Melzer, Alexander; Menary, Stephen Burns; Meng, Lingxin; Meng, Xiangting; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mergelmeyer, Sebastian; Merlassino, Claudia; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer Zu Theenhausen, Hanno; Miano, Fabrizio; Middleton, Robin; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Millar, Declan Andrew; Miller, David; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Minegishi, Yuji; Ming, Yao; Mir, Lluisa-Maria; Mirto, Alessandro; Mistry, Khilesh; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mizukami, Atsushi; Mjörnmark, Jan-Ulf; Mkrtchyan, Tigran; Mlynarikova, Michaela; Moa, Torbjoern; Mochizuki, Kazuya; Mogg, Philipp; Mohapatra, Soumya; Molander, Simon; Moles-Valls, Regina; Mondragon, Matthew Craig; Mönig, Klaus; Monk, James; Monnier, Emmanuel; Montalbano, Alyssa; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morgenstern, Stefanie; Mori, Daniel; Mori, Tatsuya; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moschovakos, Paris; Mosidze, Maia; Moss, Harry James; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Moyse, Edward; Muanza, Steve; Mueller, Felix; Mueller, James; Mueller, Ralph Soeren Peter; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munoz Sanchez, Francisca Javiela; Murin, Pavel; Murray, Bill; Murrone, Alessia; Muškinja, Miha; Mwewa, Chilufya; Myagkov, Alexey; Myers, John; Myska, Miroslav; Nachman, Benjamin Philip; Nackenhorst, Olaf; Nagai, Koichi; Nagai, Ryo; Nagano, Kunihiro; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Napolitano, Fabrizio; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Narrias Villar, Daniel Isaac; Naryshkin, Iouri; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Michael Edward; Nemecek, Stanislav; Nemethy, Peter; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Newman, Paul; Ng, Tsz Yu; Ng, Sam Yanwing; Nguyen, Hoang Dai Nghia; Nguyen Manh, Tuan; Nibigira, Emery; Nickerson, Richard; Nicolaidou, Rosy; Nielsen, Jason; Nikiforou, Nikiforos; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nishu, Nishu; Nisius, Richard; Nitsche, Isabel; Nitta, Tatsumi; Nobe, Takuya; Noguchi, Yohei; Nomachi, Masaharu; Nomidis, Ioannis; Nomura, Marcelo Ayumu; Nooney, Tamsin; Nordberg, Markus; Norjoharuddeen, Nurfikri; Novak, Tadej; Novgorodova, Olga; Novotny, Radek; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nurse, Emily; Nuti, Francesco; O'Connor, Kelsey; O'Neil, Dugan; O'Rourke, Abigail Alexandra; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okawa, Hideki; Okazaki, Yuta; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Oleiro Seabra, Luis Filipe; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver, Jason; Olsson, Joakim; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onogi, Kouta; Onyisi, Peter; Oppen, Henrik; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orgill, Emily Claire; Orlando, Nicola; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ould-Saada, Farid; Ouraou, Ahmimed; Ouyang, Qun; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Pacheco Rodriguez, Laura; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganini, Michela; Palacino, Gabriel; Palazzo, Serena; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Panagoulias, Ilias; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parida, Bibhuti; Parker, Adam Jackson; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pascuzzi, Vincent; Pasner, Jacob Martin; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Francesca; Pasuwan, Patrawan; Pataraia, Sophio; Pater, Joleen; Pathak, Atanu; Pauly, Thilo; Pearson, Benjamin; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Penc, Ondrej; Peng, Cong; Peng, Haiping; Penwell, John; Peralva, Bernardo; Perego, Marta Maria; Pereira Peixoto, Ana Paula; Perepelitsa, Dennis; Peri, Francesco; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petroff, Pierre; Petrolo, Emilio; Petrov, Mariyan; Petrucci, Fabrizio; Pettersson, Nora Emilia; Peyaud, Alan; Pezoa, Raquel; Pham, Thu; Phillips, Forrest Hays; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Pickering, Mark Andrew; Piegaia, Ricardo; Pilcher, James; Pilkington, Andrew; Pinamonti, Michele; Pinfold, James; Pitt, Michael; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Pluth, Daniel; Podberezko, Pavel; Poettgen, Ruth; Poggi, Riccardo; Poggioli, Luc; Pogrebnyak, Ivan; Pohl, David-leon; Pokharel, Ishan; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Ponomarenko, Daniil; Pontecorvo, Ludovico; Popeneciu, Gabriel Alexandru; Portillo Quintero, Dilia María; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potti, Harish; Poulsen, Trine; Poveda, Joaquin; Pozo Astigarraga, Mikel Eukeni; Pralavorio, Pascal; Prell, Soeren; Price, Darren; Primavera, Margherita; Prince, Sebastien; Proklova, Nadezda; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Puri, Akshat; Puzo, Patrick; Qian, Jianming; Qin, Yang; Quadt, Arnulf; Queitsch-Maitland, Michaela; Qureshi, Anum; Radhakrishnan, Sooraj Krishnan; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Raine, John Andrew; Rajagopalan, Srinivasan; Rashid, Tasneem; Raspopov, Sergii; Ratti, Maria Giulia; Rauch, Daniel; Rauscher, Felix; Rave, Stefan; Ravina, Baptiste; Ravinovich, Ilia; Rawling, Jacob Henry; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Reale, Marilea; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reed, Robert; Reeves, Kendall; Rehnisch, Laura; Reichert, Joseph; Reiss, Andreas; Rembser, Christoph; Ren, Huan; Rescigno, Marco; Resconi, Silvia; Resseguie, Elodie Deborah; Rettie, Sebastien; Reynolds, Elliot; Rezanova, Olga; Reznicek, Pavel; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rifki, Othmane; Rijssenbeek, Michael; Rimoldi, Adele; Rimoldi, Marco; Rinaldi, Lorenzo; Ripellino, Giulia; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rivera Vergara, Juan Cristobal; Rizatdinova, Flera; Rizvi, Eram; Rizzi, Chiara; Roberts, Rhys Thomas; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocco, Elena; Roda, Chiara; Rodina, Yulia; Rodriguez Bosca, Sergi; Rodriguez Perez, Andrea; Rodriguez Rodriguez, Daniel; Rodríguez Vera, Ana María; Roe, Shaun; Rogan, Christopher Sean; Røhne, Ole; Röhrig, Rainer; Roland, Christophe Pol A; Roloff, Jennifer; Romaniouk, Anatoli; Romano, Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosien, Nils-Arne; Rossi, Elvira; Rossi, Leonardo Paolo; Rossini, Lorenzo; Rosten, Jonatan; Rosten, Rachel; Rotaru, Marina; Rothberg, Joseph; Rousseau, David; Roy, Debarati; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Rüttinger, Elias Michael; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryu, Soo; Ryzhov, Andrey; Rzehorz, Gerhard Ferdinand; Sabatini, Paolo; Sabato, Gabriele; Sacerdoti, Sabrina; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saha, Puja; Sahinsoy, Merve; Saimpert, Matthias; Saito, Masahiko; Saito, Tomoyuki; Sakamoto, Hiroshi; Sakharov, Alexander; Salamani, Dalila; Salamanna, Giuseppe; Salazar Loyola, Javier Esteban; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sammel, Dirk; Sampsonidis, Dimitrios; Sampsonidou, Despoina; Sánchez, Javier; Sanchez Pineda, Arturo Rodolfo; Sandaker, Heidi; Sander, Christian Oliver; Sandhoff, Marisa; Sandoval, Carlos; Sankey, Dave; Sannino, Mario; Sano, Yuta; Sansoni, Andrea; Santoni, Claudio; Santos, Helena; Santoyo Castillo, Itzebelt; Sapronov, Andrey; Saraiva, João; Sasaki, Osamu; Sato, Koji; Sauvan, Emmanuel; Savard, Pierre; Savic, Natascha; Sawada, Ryu; Sawyer, Craig; Sawyer, Lee; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Schaarschmidt, Jana; Schacht, Peter; Schachtner, Balthasar Maria; Schaefer, Douglas; Schaefer, Leigh; Schaeffer, Jan; Schaepe, Steffen; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R Dean; Scharmberg, Nicolas; Schegelsky, Valery; Scheirich, Daniel; Schenck, Ferdinand; Schernau, Michael; Schiavi, Carlo; Schier, Sheena; Schildgen, Lara Katharina; Schillaci, Zachary Michael; Schioppa, Enrico Junior; Schioppa, Marco; Schleicher, Katharina; Schlenker, Stefan; Schmidt-Sommerfeld, Korbinian Ralf; Schmieden, Kristof; Schmitt, Christian; Schmitt, Stefan; Schmitz, Simon; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schopf, Elisabeth; Schott, Matthias; Schouwenberg, Jeroen; Schovancova, Jaroslava; Schramm, Steven; Schuh, Natascha; Schulte, Alexandra; Schultz-Coulon, Hans-Christian; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Sciandra, Andrea; Sciolla, Gabriella; Scornajenghi, Matteo; Scuri, Fabrizio; Scutti, Federico; Scyboz, Ludovic Michel; Searcy, Jacob; Sebastiani, Cristiano David; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Semprini-Cesari, Nicola; Senkin, Sergey; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Sessa, Marco; Severini, Horst; Šfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shahinian, Jeffrey David; Shaikh, Nabila Wahab; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Sharma, Abhishek; Sharma, Abhishek; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Shen, Yu-Ting; Sherafati, Nima; Sherman, Alexander David; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shipsey, Ian Peter Joseph; Shirabe, Shohei; Shiyakova, Mariya; Shlomi, Jonathan; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyed Ruhollah; Shope, David Richard; Shrestha, Suyog; Shulga, Evgeny; Sicho, Petr; Sickles, Anne Marie; Sidebo, Per Edvin; Sideras Haddad, Elias; Sidiropoulou, Ourania; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silva Jr, Manuel; Silverstein, Samuel; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Manuel; Sinervo, Pekka; Sinev, Nikolai; Sioli, Maximiliano; Siragusa, Giovanni; Siral, Ismet; Sivoklokov, Serguei; Sjölin, Jörgen; Skinner, Malcolm Bruce; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Slovak, Radim; Smakhtin, Vladimir; Smart, Ben; Smiesko, Juraj; Smirnov, Nikita; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Joshua Wyatt; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snyder, Ian Michael; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffa, Aaron Michael; Soffer, Abner; Søgaard, Andreas; Soh, Dart-yin; Sokhrannyi, Grygorii; Solans Sanchez, Carlos; Solar, Michael; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Son, Hyungsuk; Song, Weimin; Sopczak, Andre; Sopkova, Filomena; Sosa, David; Sotiropoulou, Calliope Louisa; Sottocornola, Simone; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spangenberg, Martin; Spanò, Francesco; Sperlich, Dennis; Spettel, Fabian; Spieker, Thomas Malte; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; Stabile, Alberto; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanitzki, Marcel Michael; Stapf, Birgit Sylvia; Stapnes, Steinar; Starchenko, Evgeny; Stark, Giordon; Stark, Jan; Stark, Simon Holm; Staroba, Pavel; Starovoitov, Pavel; Stärz, Steffen; Staszewski, Rafal; Stegler, Martin; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stevenson, Thomas James; Stewart, Graeme; Stockton, Mark; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Straessner, Arno; Strandberg, Jonas; Strandberg, Sara; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Stupak, John; Styles, Nicholas Adam; Su, Dong; Su, Jun; Suchek, Stanislav; Sugaya, Yorihito; Suk, Michal; Sulin, Vladimir; Sultan, D M S; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Suruliz, Kerim; Suster, Carl; Sutton, Mark; Suzuki, Shota; Svatos, Michal; Swiatlowski, Maximilian; Swift, Stewart Patrick; Sydorenko, Alexander; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Tahirovic, Elvedin; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takasugi, Eric Hayato; Takeda, Kosuke; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tanaka, Junichi; Tanaka, Masahiro; Tanaka, Reisaburo; Tanioka, Ryo; Tannenwald, Benjamin Bordy; Tapia Araya, Sebastian; Tapprogge, Stefan; Tarek Abouelfadl Mohamed, Ahmed; Tarem, Shlomit; Tarna, Grigore; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Aaron; Taylor, Alan James; Taylor, Geoffrey; Taylor, Pierre Thor Elliot; Taylor, Wendy; Tee, Amy Selvi; Teixeira-Dias, Pedro; Temple, Darren; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Thais, Savannah Jennifer; Theveneaux-Pelzer, Timothée; Thiele, Fabian; Thomas, Juergen; Thompson, Paul; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Tian, Yun; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tisserant, Sylvain; Todome, Kazuki; Todorova-Nova, Sharka; Todt, Stefanie; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tolley, Emma; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tong, Baojia(Tony); Tornambe, Peter; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Tosciri, Cecilia; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Treado, Colleen Jennifer; Trefzger, Thomas; Tresoldi, Fabio; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Trofymov, Artur; Troncon, Clara; Trovatelli, Monica; Trovato, Fabrizio; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsai, Fang-ying; Tsang, Ka Wa; Tseng, Jeffrey; Tsiareshka, Pavel; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tu, Yanjun; Tudorache, Alexandra; Tudorache, Valentina; Tulbure, Traian Tiberiu; Tuna, Alexander Naip; Turchikhin, Semen; Turgeman, Daniel; Turk Cakir, Ilkay; Turra, Ruggero; Tuts, Michael; Ucchielli, Giulia; Ueda, Ikuo; Ughetto, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Uno, Kenta; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usui, Junya; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vadla, Knut Oddvar Hoie; Vaidya, Amal; Valderanis, Chrysostomos; Valdes Santurio, Eduardo; Valente, Marco; Valentinetti, Sara; Valero, Alberto; Valéry, Loïc; Vallance, Robert Adam; Vallier, Alexis; Valls Ferrer, Juan Antonio; Van Daalen, Tal Roelof; Van Den Wollenberg, Wouter; van der Graaf, Harry; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vari, Riccardo; Varnes, Erich; Varni, Carlo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vasquez, Jared Gregory; Vasquez, Gerardo; Vazeille, Francois; Vazquez Furelos, David; Vazquez Schroeder, Tamara; Veatch, Jason; Vecchio, Valentina; Veloce, Laurelle Maria; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Venturi, Manuela; Venturi, Nicola; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Ambrosius Thomas; Vermeulen, Jos; Vetterli, Michel; Viaux Maira, Nicolas; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigani, Luigi; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vishwakarma, Akanksha; Vittori, Camilla; Vivarelli, Iacopo; Vlachos, Sotirios; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; von Buddenbrock, Stefan; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Peter; Wagner, Wolfgang; Wagner-Kuhr, Jeannine; Wahlberg, Hernan; Wahrmund, Sebastian; Wakamiya, Kotaro; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wallangen, Veronica; Wang, Ann Miao; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Peilong; Wang, Qing; Wang, Renjie; Wang, Rongkun; Wang, Rui; Wang, Song-Ming; Wang, Tingting; Wang, Wei; Wang, Wenxiao; Wang, Yufeng; Wang, Zirui; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Watkins, Peter; Watson, Alan; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Aaron Foley; Webb, Samuel; Weber, Christian; Weber, Michele; Weber, Sebastian Mario; Weber, Stephen; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weirich, Marcel; Weiser, Christian; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Michael David; Werner, Per; Wessels, Martin; Weston, Thomas; Whalen, Kathleen; Whallon, Nikola Lazar; Wharton, Andrew Mark; White, Aaron; White, Andrew; White, Martin; White, Ryan; Whiteson, Daniel; Whitmore, Ben William; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilk, Fabian; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, John; Wingerter-Seez, Isabelle; Winkels, Emma; Winklmeier, Frank; Winston, Oliver James; Winter, Benedict Tobias; Wittgen, Matthias; Wobisch, Markus; Wolf, Anton; Wolf, Tim Michael Heinz; Wolff, Robert; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Vincent Wai Sum; Woods, Natasha Lee; Worm, Steven; Wosiek, Barbara; Woźniak, Krzysztof; Wraight, Kenneth; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xi, Zhaoxu; Xia, Ligang; Xu, Da; Xu, Hanlin; Xu, Lailin; Xu, Tairan; Xu, Wenhao; Yabsley, Bruce; Yacoob, Sahal; Yajima, Kazuki; Yallup, David; Yamaguchi, Daiki; Yamaguchi, Yohei; Yamamoto, Akira; Yamanaka, Takashi; Yamane, Fumiya; Yamatani, Masahiro; Yamazaki, Tomohiro; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Siqi; Yang, Yi; Yang, Yi-lin; Yang, Zongchang; Yao, Weiming; Yap, Yee Chinn; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yigitbasi, Efe; Yildirim, Eda; Yorita, Kohei; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Yu, Jaehoon; Yu, Jie; Yue, Xiaoguang; Yuen, Stephanie P; Yusuff, Imran; Zabinski, Bartlomiej; Zacharis, Georgios; Zaidan, Remi; Zaitsev, Alexander; Zakharchuk, Nataliia; Zalieckas, Justas; Zambito, Stefano; Zanzi, Daniele; Zeitnitz, Christian; Zemaityte, Gabija; Zeng, Jian Cong; Zeng, Qi; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zgubič, Miha; Zhang, Dengfeng; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Guangyi; Zhang, Huijun; Zhang, Jinlong; Zhang, Lei; Zhang, Liqing; Zhang, Matt; Zhang, Peng; Zhang, Rui; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Yu; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhou, Bing; Zhou, Chen; Zhou, Li; Zhou, Maosen; Zhou, Mingliang; Zhou, Ning; Zhou, You; Zhu, Cheng Guang; Zhu, Heling; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zhulanov, Vladimir; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; Zoch, Knut; Zorbas, Theodore Georgio; Zou, Rui; zur Nedden, Martin; Zwalinski, Lukasz

2018-01-01

A search for pair production of up-type vector-like quarks ($T$) with a significant branching ratio into a top quark and either a Standard Model Higgs boson or a $Z$ boson is presented. The same analysis is also used to search for four-top-quark production in several new physics scenarios. The search is based on a dataset of $pp$ collisions at $\\sqrt{s}=13$ TeV recorded in 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider and corresponds to an integrated luminosity of 36.1 fb$^{-1}$. Data are analysed in the lepton+jets final state, characterised by an isolated electron or muon with high transverse momentum, large missing transverse momentum and multiple jets, as well as the jets+$E_{T}^{miss}$ final state, characterised by multiple jets and large missing transverse momentum. The search exploits the high multiplicity of jets identified as originating from $b$-quarks, and the presence of boosted, hadronically decaying top quarks and Higgs bosons reconstructed as large-radius jets, charac...

Landau levels and shallow donor states in GaAs/AlGaAs multiple quantum wells at mega-gauss magnetic fields

Energy Technology Data Exchange (ETDEWEB)

Zybert, M. [Univ. of Rzeszow, Pigonia (Poland); Marchweka, M. [Univ. of Rzeszow, Pigonia (Poland); Sheregii, E. M. [Center for Microelectronics and Nanotechnology, University of Rzeszow; Rickel, Dwight Gene [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Betts, Jonathan Bobby [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Balakirev, Fedor Fedorovich [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gordon, Michael Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stier, Andreas V. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mielke, Charles H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pfeffer, P. [Polish Academy of Sciences (PAS), Warsaw (Poland); Zawadski, W. [Polish Academy of Sciences (PAS), Warsaw (Poland)

2017-03-06

Landau levels and shallow donor states in multiple GaAs/AlGaAs quantum wells (MQWs) are investigated by means of the cyclotron resonance at mega-gauss magnetic fields. Measurements of magneto-optical transitions were performed in pulsed fields up to 140 T and temperatures from 6 to 300 K. The 14 x 14 P.p band model for GaAs is used to interpret free-electron transitions in a magnetic field. Temperature behavior of the observed resonant structure indicates, in addition to the free-electron Landau states, contributions of magneto-donor states in the GaAs wells and possibly in the AlGaAs barriers. The magneto-donor energies are calculated using a variational procedure suitable for high magnetic fields and accounting for conduction band nonparabolicity in GaAs. It is shown that the above states, including their spin splitting, allow one to interpret the observed mengeto-optical transitions in MQWs in the middle infrared region. Our experimental and theoretical results at very high magnetic fields are consistent with the picture used previously for GaAs/AlGaAs MQWs at lower magnetic fields.

Effect of localization states on the electroluminescence spectral width of blue–green light emitting InGaN/GaN multiple quantum wells

Energy Technology Data Exchange (ETDEWEB)

Liu, Wei [State Key Laboratory on Integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, China and School of Electronic and Electrical Engineering, Chongqing University of Arts and Sciences, Chongqing 402160 (China); Zhao, De Gang, E-mail: dgzhao@red.semi.ac.cn; Jiang, De Sheng; Chen, Ping; Liu, Zong Shun; Zhu, Jian Jun; Li, Xiang; Shi, Ming; Zhao, Dan Mei [State Key Laboratory on Integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); Liu, Jian Ping; Zhang, Shu Ming; Wang, Hui; Yang, Hui [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215125 (China)

2015-11-15

The electroluminescence (EL) spectra of blue–green light emitting InGaN/GaN multiple quantum well (MQW) structures grown via metal-organic chemical vapor deposition are investigated. With increasing In content in InGaN well layers, the peak energy redshifts, the emission intensity reduces and the inhomogeneous broadening of the luminescence band increases. In addition, it is found that the EL spectra shrink with increasing injection current at low excitation condition, which may be ascribed to both Coulomb screening of polarization field and carrier transferring from shallower localization states to the deeper ones, while at high currents the state-filling effect in all localization states may become significant and lead to a broadening of EL spectra. However, surprisingly, for the MQW sample with much higher In content, the EL spectral bandwidth can be almost unchanged with increasing current at the high current range, since a large number of carriers may be captured by the nonradiative recombination centers distributed outside the localized potential traps and the state-filling effect in the localization states is suppressed.

Effect of localization states on the electroluminescence spectral width of blue–green light emitting InGaN/GaN multiple quantum wells

International Nuclear Information System (INIS)

Liu, Wei; Zhao, De Gang; Jiang, De Sheng; Chen, Ping; Liu, Zong Shun; Zhu, Jian Jun; Li, Xiang; Shi, Ming; Zhao, Dan Mei; Liu, Jian Ping; Zhang, Shu Ming; Wang, Hui; Yang, Hui

2015-01-01

The electroluminescence (EL) spectra of blue–green light emitting InGaN/GaN multiple quantum well (MQW) structures grown via metal-organic chemical vapor deposition are investigated. With increasing In content in InGaN well layers, the peak energy redshifts, the emission intensity reduces and the inhomogeneous broadening of the luminescence band increases. In addition, it is found that the EL spectra shrink with increasing injection current at low excitation condition, which may be ascribed to both Coulomb screening of polarization field and carrier transferring from shallower localization states to the deeper ones, while at high currents the state-filling effect in all localization states may become significant and lead to a broadening of EL spectra. However, surprisingly, for the MQW sample with much higher In content, the EL spectral bandwidth can be almost unchanged with increasing current at the high current range, since a large number of carriers may be captured by the nonradiative recombination centers distributed outside the localized potential traps and the state-filling effect in the localization states is suppressed

Cross-cultural generality and specificity in self-regulation: avoidance personal goals and multiple aspects of well-being in the United States and Japan.

Science.gov (United States)

Elliot, Andrew J; Sedikides, Constantine; Murayama, Kou; Tanaka, Ayumi; Thrash, Todd M; Mapes, Rachel R

2012-10-01

The authors examined avoidance personal goals as concurrent (Study 1) and longitudinal (Study 2) predictors of multiple aspects of well-being in the United States and Japan. In both studies, participants adopted more avoidance personal goals in Japan relative to the United States. Both studies also demonstrated that avoidance personal goals were significant negative predictors of the most relevant aspects of well-being in each culture. Specifically, avoidance personal goals were negative predictors of intrapersonal and eudaimonic well-being in the United States and were negative predictors of interpersonal and eudaimonic well-being in Japan. The findings clarify and extend puzzling findings from prior empirical work in this area, and raise provocative possibilities about the nature of avoidance goal pursuit.

Quantum Optical Multiple Scattering

DEFF Research Database (Denmark)

Ott, Johan Raunkjær

. In the first part we use a scattering-matrix formalism combined with results from random-matrix theory to investigate the interference of quantum optical states on a multiple scattering medium. We investigate a single realization of a scattering medium thereby showing that it is possible to create entangled...... states by interference of squeezed beams. Mixing photon states on the single realization also shows that quantum interference naturally arises by interfering quantum states. We further investigate the ensemble averaged transmission properties of the quantized light and see that the induced quantum...... interference survives even after disorder averaging. The quantum interference manifests itself through increased photon correlations. Furthermore, the theoretical description of a measurement procedure is presented. In this work we relate the noise power spectrum of the total transmitted or reflected light...

Pareto-depth for multiple-query image retrieval.

Science.gov (United States)

Hsiao, Ko-Jen; Calder, Jeff; Hero, Alfred O

2015-02-01

Most content-based image retrieval systems consider either one single query, or multiple queries that include the same object or represent the same semantic information. In this paper, we consider the content-based image retrieval problem for multiple query images corresponding to different image semantics. We propose a novel multiple-query information retrieval algorithm that combines the Pareto front method with efficient manifold ranking. We show that our proposed algorithm outperforms state of the art multiple-query retrieval algorithms on real-world image databases. We attribute this performance improvement to concavity properties of the Pareto fronts, and prove a theoretical result that characterizes the asymptotic concavity of the fronts.

Multiple-copy entanglement transformation and entanglement catalysis

International Nuclear Information System (INIS)

Duan Runyao; Feng Yuan; Li Xin; Ying Mingsheng

2005-01-01

We prove that any multiple-copy entanglement transformation [S. Bandyopadhyay, V. Roychowdhury, and U. Sen, Phys. Rev. A 65, 052315 (2002)] can be implemented by a suitable entanglement-assisted local transformation [D. Jonathan and M. B. Plenio, Phys. Rev. Lett. 83, 3566 (1999)]. Furthermore, we show that the combination of multiple-copy entanglement transformation and the entanglement-assisted one is still equivalent to the pure entanglement-assisted one. The mathematical structure of multiple-copy entanglement transformations then is carefully investigated. Many interesting properties of multiple-copy entanglement transformations are presented, which exactly coincide with those satisfied by the entanglement-assisted ones. Most interestingly, we show that an arbitrarily large number of copies of state should be considered in multiple-copy entanglement transformations

Probing membrane protein structure using water polarization transfer solid-state NMR.

Science.gov (United States)

Williams, Jonathan K; Hong, Mei

2014-10-01

Water plays an essential role in the structure and function of proteins, lipid membranes and other biological macromolecules. Solid-state NMR heteronuclear-detected (1)H polarization transfer from water to biomolecules is a versatile approach for studying water-protein, water-membrane, and water-carbohydrate interactions in biology. We review radiofrequency pulse sequences for measuring water polarization transfer to biomolecules, the mechanisms of polarization transfer, and the application of this method to various biological systems. Three polarization transfer mechanisms, chemical exchange, spin diffusion and NOE, manifest themselves at different temperatures, magic-angle-spinning frequencies, and pulse irradiations. Chemical exchange is ubiquitous in all systems examined so far, and spin diffusion plays the key role in polarization transfer within the macromolecule. Tightly bound water molecules with long residence times are rare in proteins at ambient temperature. The water polarization-transfer technique has been used to study the hydration of microcrystalline proteins, lipid membranes, and plant cell wall polysaccharides, and to derive atomic-resolution details of the kinetics and mechanism of ion conduction in channels and pumps. Using this approach, we have measured the water polarization transfer to the transmembrane domain of the influenza M2 protein to obtain information on the structure of this tetrameric proton channel. At short mixing times, the polarization transfer rates are site-specific and depend on the pH, labile protons, sidechain conformation, as well as the radial position of the residues in this four-helix bundle. Despite the multiple dependences, the initial transfer rates reflect the periodic nature of the residue positions from the water-filled pore, thus this technique provides a way of gleaning secondary structure information, helix tilt angle, and the oligomeric structure of membrane proteins. Copyright © 2014 Elsevier Inc. All

How to induce multiple delays in coupled chaotic oscillators?

Energy Technology Data Exchange (ETDEWEB)

Bhowmick, Sourav K. [CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032 (India); Department of Electronics, Asutosh College, Kolkata 700026 (India); Ghosh, Dibakar [Physics and Applied Mathematics Unit, Indian Statistical Institute, Kolkata 700108 (India); Roy, Prodyot K. [Department of Physics, Presidency University, Kolkata 700073 (India); Kurths, Jürgen [Potsdam Institute for Climate Impact Research, 14473 Potsdam (Germany); Institute for Physics, Humboldt University, 12489 Berlin (Germany); Dana, Syamal K. [CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032 (India)

2013-12-15

Lag synchronization is a basic phenomenon in mismatched coupled systems, delay coupled systems, and time-delayed systems. It is characterized by a lag configuration that identifies a unique time shift between all pairs of similar state variables of the coupled systems. In this report, an attempt is made how to induce multiple lag configurations in coupled systems when different pairs of state variables attain different time shift. A design of coupling is presented to realize this multiple lag synchronization. Numerical illustration is given using examples of the Rössler system and the slow-fast Hindmarsh-Rose neuron model. The multiple lag scenario is physically realized in an electronic circuit of two Sprott systems.

High Multiplicity Searches at the LHC Using Jet Masses

Energy Technology Data Exchange (ETDEWEB)

Hook, Anson; /SLAC /Stanford U., Appl. Phys. Dept.; Izaguirre, Eder; /SLAC /Stanford U., Phys. Dept.; Lisanti, Mariangela; /Princeton U.; Wacker, Jay G.; /SLAC /Stanford U., ITP

2012-04-24

This article introduces a new class of searches for physics beyond the Standard Model that improves the sensitivity to signals with high jet multiplicity. The proposed searches gain access to high multiplicity signals by reclustering events into large-radius, or 'fat', jets and by requiring that each event has multiple massive jets. This technique is applied to supersymmetric scenarios in which gluinos are pair-produced and then subsequently decay to final states with either moderate quantities of missing energy or final states without missing energy. In each of these scenarios, the use of jet mass improves the estimated reach in gluino mass by 20% to 50% over current LHC searches.

Recruitment of human aquaporin 3 to internal membranes in the Plasmodium falciparum infected erythrocyte.

Science.gov (United States)

Bietz, Sven; Montilla, Irine; Külzer, Simone; Przyborski, Jude M; Lingelbach, Klaus

2009-09-01

The molecular mechanisms underlying the formation of the parasitophorous vacuolar membrane in Plasmodium falciparum infected erythrocytes are incompletely understood, and the protein composition of this membrane is still enigmatic. Although the differentiated mammalian erythrocyte lacks the machinery required for endocytosis, some reports have described a localisation of host cell membrane proteins at the parasitophorous vacuolar membrane. Aquaporin 3 is an abundant plasma membrane protein of various cells, including mammalian erythrocytes where it is found in distinct oligomeric states. Here we show that human aquaporin 3 is internalized into infected erythrocytes, presumably during or soon after invasion. It is integrated into the PVM where it is organized in novel oligomeric states which are not found in non-infected cells.

Simultaneous qubit-loss-free fusion of three multiple W states

Science.gov (United States)

Wang, Meiyu; Hao, Quanzhi; Yan, Fengli; Gao, Ting

2018-05-01

Qubit-loss-free fusion for two W states introduced by Li K et al (2016 Phys. Rev. A 94 062315) clearly increases the final size of the obtained W state and greatly reduces the number of fusion steps to achieve a W state of a target size. Motivated by this idea, we propose a qubit-loss-free fusion scheme for fusing three polarization entangled W states simultaneously. The elements of a two-outcome positive-operator valued measurement and the appropriate joint unitary operation for realizing a positive-operator valued measurement measurement are given. As an example, with the assistance of weak cross-Kerr nonlinearities, an optical setup for fusing three W states is proposed. We analyze the success probability of the scheme and the resource cost of the present scheme, as compared to previous work.

Mango: multiple alignment with N gapped oligos.

Science.gov (United States)

Zhang, Zefeng; Lin, Hao; Li, Ming

2008-06-01

Multiple sequence alignment is a classical and challenging task. The problem is NP-hard. The full dynamic programming takes too much time. The progressive alignment heuristics adopted by most state-of-the-art works suffer from the "once a gap, always a gap" phenomenon. Is there a radically new way to do multiple sequence alignment? In this paper, we introduce a novel and orthogonal multiple sequence alignment method, using both multiple optimized spaced seeds and new algorithms to handle these seeds efficiently. Our new algorithm processes information of all sequences as a whole and tries to build the alignment vertically, avoiding problems caused by the popular progressive approaches. Because the optimized spaced seeds have proved significantly more sensitive than the consecutive k-mers, the new approach promises to be more accurate and reliable. To validate our new approach, we have implemented MANGO: Multiple Alignment with N Gapped Oligos. Experiments were carried out on large 16S RNA benchmarks, showing that MANGO compares favorably, in both accuracy and speed, against state-of-the-art multiple sequence alignment methods, including ClustalW 1.83, MUSCLE 3.6, MAFFT 5.861, ProbConsRNA 1.11, Dialign 2.2.1, DIALIGN-T 0.2.1, T-Coffee 4.85, POA 2.0, and Kalign 2.0. We have further demonstrated the scalability of MANGO on very large datasets of repeat elements. MANGO can be downloaded at http://www.bioinfo.org.cn/mango/ and is free for academic usage.

Deep convolutional neural network based antenna selection in multiple-input multiple-output system

Science.gov (United States)

Cai, Jiaxin; Li, Yan; Hu, Ying

2018-03-01

Antenna selection of wireless communication system has attracted increasing attention due to the challenge of keeping a balance between communication performance and computational complexity in large-scale Multiple-Input MultipleOutput antenna systems. Recently, deep learning based methods have achieved promising performance for large-scale data processing and analysis in many application fields. This paper is the first attempt to introduce the deep learning technique into the field of Multiple-Input Multiple-Output antenna selection in wireless communications. First, the label of attenuation coefficients channel matrix is generated by minimizing the key performance indicator of training antenna systems. Then, a deep convolutional neural network that explicitly exploits the massive latent cues of attenuation coefficients is learned on the training antenna systems. Finally, we use the adopted deep convolutional neural network to classify the channel matrix labels of test antennas and select the optimal antenna subset. Simulation experimental results demonstrate that our method can achieve better performance than the state-of-the-art baselines for data-driven based wireless antenna selection.

A Comprehensive Analysis of the Correlations between Resting-State Oscillations in Multiple-Frequency Bands and Big Five Traits

Directory of Open Access Journals (Sweden)

Shigeyuki Ikeda

2017-06-01

Full Text Available Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz of resting-state functional magnetic resonance imaging (fMRI activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI, and the fractional amplitude of low-frequency fluctuation (fALFF at four distinct frequency bands (slow-5 (0.01–0.027 Hz, slow-4 (0.027–0.073 Hz, slow-3 (0.073–0.198 Hz and slow-2 (0.198–0.25 Hz. We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands.

Photoisomers of Azobenzene Star with a Flat Core: Theoretical Insights into Multiple States from DFT and MD Perspective.

Science.gov (United States)

Koch, Markus; Saphiannikova, Marina; Santer, Svetlana; Guskova, Olga

2017-09-21

This study focuses on comparing physical properties of photoisomers of an azobenzene star with benzene-1,3,5-tricarboxamide core. Three azobenzene arms of the molecule undergo a reversible trans-cis isomerization upon UV-vis light illumination giving rise to multiple states from the planar all-trans one, via two mixed states to the kinked all-cis isomer. Employing density functional theory, we characterize the structural and photophysical properties of each state indicating a role the planar core plays in the coupling between azobenzene chromophores. To characterize the light-triggered switching of solvophilicity/solvophobicity of the star, the difference in solvation free energy is calculated for the transfer of an azobenzene star from its gas phase to implicit or explicit solvents. For the latter case, classical all-atom molecular dynamics simulations of aqueous solutions of azobenzene star are performed employing the polymer consistent force field to shed light on the thermodynamics of explicit hydration as a function of the isomerization state and on the structuring of water around the star. From the analysis of two contributions to the free energy of hydration, the nonpolar van der Waals and the electrostatic terms, it is concluded that isomerization specificity largely determines the polarity of the molecule and the solute-solvent electrostatic interactions. This convertible hydrophilicity/hydrophobicity together with readjustable occupied volume and the surface area accessible to water, affects the self-assembly/disassembly of the azobenzene star with a flat core triggered by light.

Proteotyping of laboratory-scale biogas plants reveals multiple steady-states in community composition.

Science.gov (United States)

Kohrs, F; Heyer, R; Bissinger, T; Kottler, R; Schallert, K; Püttker, S; Behne, A; Rapp, E; Benndorf, D; Reichl, U

2017-08-01

Complex microbial communities are the functional core of anaerobic digestion processes taking place in biogas plants (BGP). So far, however, a comprehensive characterization of the microbiomes involved in methane formation is technically challenging. As an alternative, enriched communities from laboratory-scale experiments can be investigated that have a reduced number of organisms and are easier to characterize by state of the art mass spectrometric-based (MS) metaproteomic workflows. Six parallel laboratory digesters were inoculated with sludge from a full-scale BGP to study the development of enriched microbial communities under defined conditions. During the first three month of cultivation, all reactors (R1-R6) were functionally comparable regarding biogas productions (375-625 NL L reactor volume -1 d -1 ), methane yields (50-60%), pH values (7.1-7.3), and volatile fatty acids (VFA, 1 gNH 3 L -1 ) showed an increase to pH 7.5-8.0, accumulation of acetate (>10 mM), and decreasing biogas production (<125 NL L reactor volume -1 d -1 ). Tandem MS (MS/MS)-based proteotyping allowed the identification of taxonomic abundances and biological processes. Although all reactors showed similar performances, proteotyping and terminal restriction fragment length polymorphisms (T-RFLP) fingerprinting revealed significant differences in the composition of individual microbial communities, indicating multiple steady-states. Furthermore, cellulolytic enzymes and cellulosomal proteins of Clostridium thermocellum were identified to be specific markers for the thermophilic reactors (R3, R4). Metaproteins found in R3 indicated hydrogenothrophic methanogenesis, whereas metaproteins of acetoclastic methanogenesis were identified in R4. This suggests not only an individual evolution of microbial communities even for the case that BGPs are started at the same initial conditions under well controlled environmental conditions, but also a high compositional variance of microbiomes under

The CoxD protein, a novel AAA+ ATPase involved in metal cluster assembly: hydrolysis of nucleotide-triphosphates and oligomerization.

Directory of Open Access Journals (Sweden)

Tobias Maisel

Full Text Available CoxD of the α-proteobacterium Oligotropha carboxidovorans is a membrane protein which is involved in the posttranslational biosynthesis of the [CuSMoO₂] cluster in the active site of the enzyme CO dehydrogenase. The bacteria synthesize CoxD only in the presence of CO. Recombinant CoxD produced in E. coli K38 pGP1-2/pETMW2 appeared in inclusion bodies from where it was solubilized by urea and refolded by stepwise dilution. Circular dichroism spectroscopy revealed the presence of secondary structural elements in refolded CoxD. CoxD is a P-loop ATPase of the AAA-protein family. Refolded CoxD catalyzed the hydrolysis of MgATP yielding MgADP and inorganic phosphate at a 1∶1∶1 molar ratio. The reaction was inhibited by the slow hydrolysable MgATP-γ-S. GTPase activity of CoxD did not exceed 2% of the ATPase activity. Employing different methods (non linear regression, Hanes and Woolf, Lineweaver-Burk, preparations of CoxD revealed a mean K(M value of 0.69±0.14 mM ATP and an apparent V(max value of 19.3±2.3 nmol ATP hydrolyzed min⁻¹ mg⁻¹. Sucrose density gradient centrifugation and gel filtration showed that refolded CoxD can exist in various multimeric states (2-mer, 4-mer or 6-mer, preferentially as hexamer or dimer. Within weeks the hexamer dissociates into the dimer, a process which can be reversed by MgATP or MgATP-γ-S within hours. Only the hexamers and the dimers exhibited MgATPase activity. Transmission electron microscopy of negatively stained CoxD preparations revealed distinct particles within a size range of 10-16 nm, which further corroborates the oligomeric organization. The 3D structure of CoxD was modeled with the 3D structure of BchI from Rhodobacter capsulatus as template. It has the key elements of an AAA+ domain in the same arrangement and at same positions as in BchI and displays the characteristic inserts of the PS-II-insert clade. Possible functions of CoxD in [CuSMoO₂] cluster assembly are discussed.

The Structure of the Complex between Yeast Frataxin and Ferrochelatase: CHARACTERIZATION AND PRE-STEADY STATE REACTION OF FERROUS IRON DELIVERY AND HEME SYNTHESIS.

Science.gov (United States)

Söderberg, Christopher; Gillam, Mallory E; Ahlgren, Eva-Christina; Hunter, Gregory A; Gakh, Oleksandr; Isaya, Grazia; Ferreira, Gloria C; Al-Karadaghi, Salam

2016-05-27

Frataxin is a mitochondrial iron-binding protein involved in iron storage, detoxification, and delivery for iron sulfur-cluster assembly and heme biosynthesis. The ability of frataxin from different organisms to populate multiple oligomeric states in the presence of metal ions, e.g. Fe(2+) and Co(2+), led to the suggestion that different oligomers contribute to the functions of frataxin. Here we report on the complex between yeast frataxin and ferrochelatase, the terminal enzyme of heme biosynthesis. Protein-protein docking and cross-linking in combination with mass spectroscopic analysis and single-particle reconstruction from negatively stained electron microscopic images were used to verify the Yfh1-ferrochelatase interactions. The model of the complex indicates that at the 2:1 Fe(2+)-to-protein ratio, when Yfh1 populates a trimeric state, there are two interaction interfaces between frataxin and the ferrochelatase dimer. Each interaction site involves one ferrochelatase monomer and one frataxin trimer, with conserved polar and charged amino acids of the two proteins positioned at hydrogen-bonding distances from each other. One of the subunits of the Yfh1 trimer interacts extensively with one subunit of the ferrochelatase dimer, contributing to the stability of the complex, whereas another trimer subunit is positioned for Fe(2+) delivery. Single-turnover stopped-flow kinetics experiments demonstrate that increased rates of heme production result from monomers, dimers, and trimers, indicating that these forms are most efficient in delivering Fe(2+) to ferrochelatase and sustaining porphyrin metalation. Furthermore, they support the proposal that frataxin-mediated delivery of this potentially toxic substrate overcomes formation of reactive oxygen species. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Solid-support Electron Paramagnetic Resonance (EPR) Studies of Aβ40 Monomers Reveal a Structured State with Three Ordered Segments*

Science.gov (United States)

Gu, Lei; Ngo, Sam; Guo, Zhefeng

2012-01-01

Alzheimer disease is associated with the pathological accumulation of amyloid-β peptide (Aβ) in the brain. Soluble Aβ oligomers formed during early aggregation process are believed to be neurotoxins and causative agents in Alzheimer disease. Aβ monomer is the building block for amyloid assemblies. A comprehensive understanding of the structural features of Aβ monomer is crucial for delineating the mechanism of Aβ oligomerization. Here we investigated the structures of Aβ40 monomer using a solid-support approach, in which Aβ40 monomers are tethered on the solid support via an N-terminal His tag to prevent further aggregation. EPR spectra of tethered Aβ40 with spin labels at 18 different positions show that Aβ40 monomers adopt a completely disordered structure under denaturing conditions. Under native conditions, however, EPR spectra suggest that Aβ40 monomers adopt both a disordered state and a structured state. The structured state of Aβ40 monomer has three more ordered segments at 14–18, 29–30, and 38–40. Interactions between these segments may stabilize the structured state, which likely plays an important role in Aβ aggregation. PMID:22277652

First C/sub 4/-functionalisation of condensed tannins. Phlobatannins as prototype of a new class of C-ring isomerised oligomers. Die eerste C/sub 4/-funksionalisering van gekondenseerde tanniene. Flobatanniene as prototipe van 'n nuwe klas van C-ring geisomeriseerde oligomere

Energy Technology Data Exchange (ETDEWEB)

Steenkamp, J A

1986-06-01

This thesis comprises besides the characterisation of new oligomeric flavenoids from the core wood of the indigeneous Colophosphermum mopane, an investigation into the C/sub 4/-functionalisation of flavan-3-ol analogues. The first peltogynoid biflavenoid and prototypes of a new series C-ring isomerised condensed tannins, namely the phlobatannins, were isolated. Besides /sup 1/H- nmr-parameters for structure analysis, the natural phlobatannins were characterised and the unique ring isomerisation was investigated.

Linear systems and multiplicity of ideals

International Nuclear Information System (INIS)

Le Dung Trang

2008-06-01

Using a geometric interpretation of the multiplicity, we give a geometric way to calculate the multiplicity. We consider the particular case of a non-singular complex surface and give an example with a geometric proof of a result. Most of this note is written in the language of complex analytic spaces, but the results can be stated and proved in the case of schemes of finite type over an infinite field with equi-characteristic local rings

Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.

Directory of Open Access Journals (Sweden)

Farah El-Turk

Full Text Available Macrophage Migration Inhibitory Factor (MIF is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G, alanine (L46A and phenylalanine (L46F, and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

Multiplicities and forward-backward correlations in anti pp interactions at 22.4 GeV/c

International Nuclear Information System (INIS)

Boos, E.G.; Samojlov, V.V.; Tashimov, M.A.

1977-01-01

Forward-backward multiplicity correlations in anti pp -interactions at 22.4 GeV/c and multiplicities in a simple icle multiplicity distribution is divided into even and odd components, the probability of producting an odd state is found to be higher than that of producing an even state, which may be interpreted to be due to diffraction forward-backward and to everall multiplicities is discussed

Phase diagrams, thermodynamic properties and sound velocities derived from a multiple Einstein method using vibrational densities of states : an application to MgO–SiO2

NARCIS (Netherlands)

Jacobs, Michael H G; Schmid-Fetzer, Rainer; van den Berg, Arie P.

2017-01-01

In a previous paper, we showed a technique that simplifies Kieffer’s lattice vibrational method by representing the vibrational density of states with multiple Einstein frequencies. Here, we show that this technique can be applied to construct a thermodynamic database that accurately represents

Nucleotide-binding oligomerization domain 2 (NOD2) activation induces apoptosis of human oral squamous cell carcinoma cells.

Science.gov (United States)

Yoon, Hyo-Eun; Ahn, Mee-Young; Kwon, Seong-Min; Kim, Dong-Jae; Lee, Jun; Yoon, Jung-Hoon

2016-04-01

Microbial Pattern-recognition receptors (PRRs), such as nucleotide-binding oligomerization domains (NODs), are essential for mammalian innate immune response. This study was designed to determine the effect of NOD1 and NOD2 agonist on innate immune responses and antitumor activity in oral squamous cell carcinoma (OSCC) cells. NODs expression was examined by RT-PCR, and IL-8 production by NODs agonist was examined by ELISA. Western blot analysis was performed to determine the MAPK activation in response to their agonist. Cell proliferation was determined by MTT assay. Flow cytometry and Western blot analysis were performed to determine the MDP-induced cell death. The levels of NODs were apparently expressed in OSCC cells. NODs agonist, Tri-DAP and MDP, led to the production of IL-8 and MAPK activation. NOD2 agonist, MDP, inhibited the proliferation of YD-10B cells in a dose-dependent manner. Also, the ratio of Annexin V-positive cells and cleaved PARP was increased by MDP treatment in YD-10B cells, suggesting that MDP-induced cell death in YD-10B cells may be owing to apoptosis. Our results indicate that NODs are functionally expressed in OSCC cells and can trigger innate immune responses. In addition, NOD2 agonist inhibited cell proliferation and induced apoptosis. These findings provide the potential value of MDP as novel candidates for antitumor agents of OSCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Search for microscopic black holes in a like-sign dimuon final state using large track multiplicity with the ATLAS detector

OpenAIRE

Aad Georges; others

2013-01-01

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM A search is presented for microscopic black holes in a like-sign dimuon final state in proton–proton collisions at √s = 8 TeV. The data were collected with the ATLAS detector at the Large Hadron Collider in 2012 and correspond to an integrated luminosity of 20.3 fb-1. Using a high track multiplicity ...

Multiple Order Diffractions by laser-Injured Transient Grating in Nematic MBBA Film

International Nuclear Information System (INIS)

Kim, Seong Kyu; Kim, Hack Jin

1999-01-01

The laser-induced transient grating method is applied to study the dynamics of the nematic MBBA film. The nanosecond laser pulses of 355 nm are used to make the transient grating and the cw He-Ne laser of 633 nm is used to probe the dynamics. Strong multiple order diffractions are observed at high nematic temperatures. The reordering process induced by the phototransformed state, which is the locally melted state from the nematic sample, is attributed to the main origin of the multiple order diffractions from the nematic MBBA. The characteristics of the multiple order gratings are discussed with the grating profiles simulated from the multiple diffraction signals

State Complexity of Testing Divisibility

Directory of Open Access Journals (Sweden)

Emilie Charlier

2010-08-01

Full Text Available Under some mild assumptions, we study the state complexity of the trim minimal automaton accepting the greedy representations of the multiples of m >= 2 for a wide class of linear numeration systems. As an example, the number of states of the trim minimal automaton accepting the greedy representations of the multiples of m in the Fibonacci system is exactly 2m^2.

The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

Directory of Open Access Journals (Sweden)

Tintoré M

2016-12-01

Full Text Available Mar Tintoré,1 Maggie Alexander,2 Kathleen Costello,3 Martin Duddy,4 David E Jones,5 Nancy Law,6 Gilmore O’Neill,7 Antonio Uccelli,8 Robert Weissert,9 Sibyl Wray10 1Multiple Sclerosis Centre of Catalonia, Hospital Vall d’Hebron, Barcelona, Spain; 2European Multiple Sclerosis Platform, Brussels, Belgium; 3National Multiple Sclerosis Society, Denver, CO, USA; 4Royal Victoria Infirmary, Newcastle-upon-Tyne, UK; 5Department of Neurology, University of Virginia, Charlottesville, VA, USA; 6Nancy Law Consulting LLC, Parker, CO, USA; 7Biogen, Cambridge, MA, USA; 8Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; 9Department of Neurology, University of Regensburg, Regensburg, Germany; 10Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA Background: Managing multiple sclerosis (MS treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods: A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results: A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT; satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment

Optical transitions involving unconfined energy states in In/sub x/Ga/sub 1-//sub x/As/GaAs multiple quantum wells

International Nuclear Information System (INIS)

Ji, G.; Dobbelaere, W.; Huang, D.; Morkoc, H.

1989-01-01

Optical transitions with energies higher than that of the GaAs band gap in highly strained In/sub x/Ga/sub 1-//sub x/As/GaAs multiple--quantum-well structures have been observed in photoreflectance spectra. In some samples as many as seven such structures were present. We identify them as transitions between the unconfined electron states and the confined heavy-hole states. For energies below the GaAs signal, intense transitions corresponding to such unconfined electron subbands were also observed. The intensity of the transitions involving unconfined electron subbands decreases with increasing well width, but is weakly dependent on the mole fraction x. The transmission coefficients are calculated in order to locate the positions of the unconfined electron subband energies. Good agreement is obtained between the experimental data and the theoretical calculation

Interactive graphical system for small-angle scattering analysis of polydisperse systems

International Nuclear Information System (INIS)

Konarev, P V; Volkov, V V; Svergun, D I

2016-01-01

A program suite for one-dimensional small-angle scattering analysis of polydisperse systems and multiple data sets is presented. The main program, POLYSAS , has a menu-driven graphical user interface calling computational modules from ATSAS package to perform data treatment and analysis. The graphical menu interface allows one to process multiple (time, concentration or temperature-dependent) data sets and interactively change the parameters for the data modelling using sliders. The graphical representation of the data is done via the Winteracter-based program SASPLOT . The package is designed for the analysis of polydisperse systems and mixtures, and permits one to obtain size distributions and evaluate the volume fractions of the components using linear and non-linear fitting algorithms as well as model-independent singular value decomposition. The use of the POLYSAS package is illustrated by the recent examples of its application to study concentration-dependent oligomeric states of proteins and time kinetics of polymer micelles for anticancer drug delivery. (paper)

Multiple Scale Analysis of the Dynamic State Index (DSI)

Science.gov (United States)

Müller, A.; Névir, P.

2016-12-01

The Dynamic State Index (DSI) is a novel parameter that indicates local deviations of the atmospheric flow field from a stationary, inviscid and adiabatic solution of the primitive equations of fluid mechanics. This is in contrast to classical methods, which often diagnose deviations from temporal or spatial mean states. We show some applications of the DSI to atmospheric flow phenomena on different scales. The DSI is derived from the Energy-Vorticity-Theory (EVT) which is based on two global conserved quantities, the total energy and Ertel's potential enstrophy. Locally, these global quantities lead to the Bernoulli function and the PV building together with the potential temperature the DSI.If the Bernoulli function and the PV are balanced, the DSI vanishes and the basic state is obtained. Deviations from the basic state provide an indication of diabatic and non-stationary weather events. Therefore, the DSI offers a tool to diagnose and even prognose different atmospheric events on different scales.On synoptic scale, the DSI can help to diagnose storms and hurricanes, where also the dipole structure of the DSI plays an important role. In the scope of the collaborative research center "Scaling Cascades in Complex Systems" we show high correlations between the DSI and precipitation on convective scale. Moreover, we compare the results with reduced models and different spatial resolutions.

Single site mutations in the hetero-oligomeric Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4 that affect Na+/H+ antiport activity, sodium exclusion, individual Mrp protein levels, or Mrp complex formation.

Science.gov (United States)

Morino, Masato; Natsui, Shinsuke; Ono, Tomohiro; Swartz, Talia H; Krulwich, Terry A; Ito, Masahiro

2010-10-01

Mrp systems are widely distributed and structurally complex cation/proton antiporters. Antiport activity requires hetero-oligomeric complexes of all six or seven hydrophobic Mrp proteins (MrpA-MrpG). Here, a panel of site-directed mutants in conserved or proposed motif residues was made in the Mrp Na(+)(Li(+))/H(+) antiporter from an alkaliphilic Bacillus. The mutant operons were expressed in antiporter-deficient Escherichia coli KNabc and assessed for antiport properties, support of sodium resistance, membrane levels of each Mrp protein, and presence of monomeric and dimeric Mrp complexes. Antiport did not depend on a VFF motif or a conserved tyrosine pair, but a role for a conserved histidine in a potential quinone binding site of MrpA was supported. The importance of several acidic residues for antiport was confirmed, and the importance of additional residues was demonstrated (e.g. three lysine residues conserved across MrpA, MrpD, and membrane-bound respiratory Complex I subunits (NuoL/M/N)). The results extended indications that MrpE is required for normal membrane levels of other Mrp proteins and for complex formation. Moreover, mutations in several other Mrp proteins lead to greatly reduced membrane levels of MrpE. Thus, changes in either of the two Mrp modules, MrpA-MrpD and MrpE-MrpG, influence the other. Two mutants, MrpB-P37G and MrpC-Q70A, showed a normal phenotype but lacked the MrpA-MrpG monomeric complex while retaining the dimeric hetero-oligomeric complex. Finally, MrpG-P81A and MrpG-P81G mutants exhibited no antiport activity but supported sodium resistance and a low [Na(+)](in). Such mutants could be used to screen hypothesized but uncharacterized sodium efflux functions of Mrp apart from Na(+) (Li(+))/H(+) antiport.

Multiple-Father Families and Welfare

Science.gov (United States)

Evenhouse, Eirik; Reilly, Siobhan

2012-01-01

In the United States, multipartnered fertility (MPF) has become commonplace. This study provides the first nationally representative measures of women's MPF, across multiple years, using the U.S. Census Bureau's Surveys of Income and Program Participation. Because welfare rules contain strong incentives for MPF, and because MPF is especially…

Oligomeric models for estimation of polydimethylsiloxane-water partition ratios with COSMO-RS theory: impact of the combinatorial term on absolute error.

Science.gov (United States)

Parnis, J Mark; Mackay, Donald

2017-03-22

A series of 12 oligomeric models for polydimethylsiloxane (PDMS) were evaluated for their effectiveness in estimating the PDMS-water partition ratio, K PDMS-w . Models ranging in size and complexity from the -Si(CH 3 ) 2 -O- model previously published by Goss in 2011 to octadeca-methyloctasiloxane (CH 3 -(Si(CH 3 ) 2 -O-) 8 CH 3 ) were assessed based on their RMS error with 253 experimental measurements of log K PDMS-w from six published works. The lowest RMS error for log K PDMS-w (0.40 in log K) was obtained with the cyclic oligomer, decamethyl-cyclo-penta-siloxane (D5), (-Si(CH 3 ) 2 -O-) 5 , with the mixing-entropy associated combinatorial term included in the chemical potential calculation. The presence or absence of terminal methyl groups on linear oligomer models is shown to have significant impact only for oligomers containing 1 or 2 -Si(CH 3 ) 2 -O- units. Removal of the combinatorial term resulted in a significant increase in the RMS error for most models, with the smallest increase associated with the largest oligomer studied. The importance of inclusion of the combinatorial term in the chemical potential for liquid oligomer models is discussed.

Outcomes of Multiple Listing for Adult Heart Transplantation in the United States: Analysis of OPTN Data From 2000 to 2013.

Science.gov (United States)

Givens, Raymond C; Dardas, Todd; Clerkin, Kevin J; Restaino, Susan; Schulze, P Christian; Mancini, Donna M

2015-12-01

This study sought to assess the association of multiple listing with waitlist outcomes and post-heart transplant (HT) survival. HT candidates in the United States may register at multiple centers. Not all candidates have the resources and mobility needed for multiple listing; thus this policy may advantage wealthier and less sick patients. We identified 33,928 adult candidates for a first single-organ HT between January 1, 2000 and December 31, 2013 in the Organ Procurement and Transplantation Network database. We identified 679 multiple-listed (ML) candidates (2.0%) who were younger (median age, 53 years [interquartile range (IQR): 43 to 60 years] vs. 55 years [IQR: 45 to 61 years]; p < 0.0001), more often white (76.4% vs. 70.7%; p = 0.0010) and privately insured (65.5% vs. 56.3%; p < 0.0001), and lived in zip codes with higher median incomes (US$90,153 [IQR: US$25,471 to US$253,831] vs. US$68,986 [IQR: US$19,471 to US$219,702]; p = 0.0015). Likelihood of ML increased with the primary center's median waiting time. ML candidates had lower initial priority (39.0% 1A or 1B vs. 55.1%; p < 0.0001) and predicted 90-day waitlist mortality (2.9% [IQR: 2.3% to 4.7%] vs. 3.6% [IQR: 2.3% to 6.0]%; p < 0.0001), but were frequently upgraded at secondary centers (58.2% 1A/1B; p < 0.0001 vs. ML primary listing). ML candidates had a higher HT rate (74.4% vs. 70.2%; p = 0.0196) and lower waitlist mortality (8.1% vs. 12.2%; p = 0.0011). Compared with a propensity-matched cohort, the relative ML HT rate was 3.02 (95% confidence interval: 2.59 to 3.52; p < 0.0001). There were no post-HT survival differences. Multiple listing is a rational response to organ shortage but may advantage patients with the means to participate rather than the most medically needy. The multiple-listing policy should be overturned. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Structure–property relationships in hybrid dental nanocomposite resins containing monofunctional and multifunctional polyhedral oligomeric silsesquioxanes

Directory of Open Access Journals (Sweden)

Wang WG

2014-02-01

Full Text Available Weiguo Wang,1,* Xiang Sun,1,* Li Huang,2,* Yu Gao,1 Jinghao Ban,1 Lijuan Shen,1 Jihua Chen1 1Department of Prosthodontics, 2Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China*These authors contributed equally to this workAbstract: Organic-inorganic hybrid materials, such as polyhedral oligomeric silsesquioxanes (POSS, have the potential to improve the mechanical properties of the methacrylate-based composites and resins used in dentistry. In this article, nanocomposites of methacryl isobutyl POSS (MI-POSS [bears only one methacrylate functional group] and methacryl POSS (MA-POSS [bears eight methacrylate functional groups] were investigated to determine the effect of structures on the properties of dental resin. The structures of the POSS-containing networks were determined by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. Monofunctional POSS showed a strong tendency toward aggregation and crystallization, while multifunctional POSS showed higher miscibility with the dimethacrylate monomer. The mechanical properties and wear resistance decreased with increasing amounts of MI-POSS, indicating that the MI-POSS agglomerates act as the mechanical weak point in the dental resins. The addition of small amounts of MA-POSS improved the mechanical and shrinkage properties. However, samples with a higher MA-POSS concentration showed lower flexural strength and flexural modulus, indicating that there is a limited range in which the reinforcement properties of MA-POSS can operate. This concentration dependence is attributed to phase separation at higher concentrations of POSS, which affects the structural integrity, and thus, the mechanical and shrinkage properties of the dental resin. Our results show that resin with 3% MA-POSS is a potential candidate for resin-based dental materials

Measuring multiple residual-stress components using the contour method and multiple cuts

Energy Technology Data Exchange (ETDEWEB)

Prime, Michael B [Los Alamos National Laboratory; Swenson, Hunter [Los Alamos National Laboratory; Pagliaro, Pierluigi [U. PALERMO; Zuccarello, Bernardo [U. PALERMO

2009-01-01

The conventional contour method determines one component of stress over the cross section of a part. The part is cut into two, the contour of the exposed surface is measured, and Bueckner's superposition principle is analytically applied to calculate stresses. In this paper, the contour method is extended to the measurement of multiple stress components by making multiple cuts with subsequent applications of superposition. The theory and limitations are described. The theory is experimentally tested on a 316L stainless steel disk with residual stresses induced by plastically indenting the central portion of the disk. The stress results are validated against independent measurements using neutron diffraction. The theory has implications beyond just multiple cuts. The contour method measurements and calculations for the first cut reveal how the residual stresses have changed throughout the part. Subsequent measurements of partially relaxed stresses by other techniques, such as laboratory x-rays, hole drilling, or neutron or synchrotron diffraction, can be superimposed back to the original state of the body.

Fast Output-sensitive Matrix Multiplication

DEFF Research Database (Denmark)

Jacob, Riko; Stöckel, Morten

2015-01-01

We consider the problem of multiplying two $U \\times U$ matrices $A$ and $C$ of elements from a field $\\F$. We present a new randomized algorithm that can use the known fast square matrix multiplication algorithms to perform fewer arithmetic operations than the current state of the art for output...

Biomedical Ph.D. students enrolled in two elite universities in the United kingdom and the United States report adopting multiple learning relationships.

Science.gov (United States)

Kemp, Matthew W; Lazarus, Benjamin M; Perron, Gabriel G; Hanage, William P; Chapman, Elaine

2014-01-01

The ability to form multiple learning relationships is a key element of the doctoral learning environment in the biomedical sciences. Of these relationships, that between student and supervisor has long been viewed as key. There are, however, limited data to describe the student perspective on what makes this relationship valuable. In the present study, we discuss the findings of semi-structured interviews with biomedical Ph.D. students from the United Kingdom and the United States to: i) determine if the learning relationships identified in an Australian biomedical Ph.D. cohort are also important in a larger international student cohort; and ii) improve our understanding of student perceptions of value in their supervisory relationships. 32 students from two research intensive universities, one in the United Kingdom (n = 17), and one in the United States (n = 15) were recruited to participate in a semi-structured interview. Verbatim transcripts were transcribed, validated and analysed using a Miles and Huberman method for thematic analysis. Students reported that relationships with other Ph.D. students, post-doctoral scientists and supervisors were all essential to their learning. Effective supervisory relationships were perceived as the primary source of high-level project guidance, intellectual support and confidence. Relationships with fellow students were viewed as essential for the provision of empathetic emotional support. Technical learning was facilitated, almost exclusively, by relationships with postdoctoral staff. These data make two important contributions to the scholarship of doctoral education in the biomedical sciences. Firstly, they provide further evidence for the importance of multiple learning relationships in the biomedical doctorate. Secondly, they clarify the form of a 'valued' supervisory relationship from a student perspective. We conclude that biomedical doctoral programs should be designed to contain a minimum level of formalised

Biomedical Ph.D. students enrolled in two elite universities in the United kingdom and the United States report adopting multiple learning relationships.

Directory of Open Access Journals (Sweden)

Matthew W Kemp

Full Text Available The ability to form multiple learning relationships is a key element of the doctoral learning environment in the biomedical sciences. Of these relationships, that between student and supervisor has long been viewed as key. There are, however, limited data to describe the student perspective on what makes this relationship valuable. In the present study, we discuss the findings of semi-structured interviews with biomedical Ph.D. students from the United Kingdom and the United States to: i determine if the learning relationships identified in an Australian biomedical Ph.D. cohort are also important in a larger international student cohort; and ii improve our understanding of student perceptions of value in their supervisory relationships.32 students from two research intensive universities, one in the United Kingdom (n = 17, and one in the United States (n = 15 were recruited to participate in a semi-structured interview. Verbatim transcripts were transcribed, validated and analysed using a Miles and Huberman method for thematic analysis.Students reported that relationships with other Ph.D. students, post-doctoral scientists and supervisors were all essential to their learning. Effective supervisory relationships were perceived as the primary source of high-level project guidance, intellectual support and confidence. Relationships with fellow students were viewed as essential for the provision of empathetic emotional support. Technical learning was facilitated, almost exclusively, by relationships with postdoctoral staff.These data make two important contributions to the scholarship of doctoral education in the biomedical sciences. Firstly, they provide further evidence for the importance of multiple learning relationships in the biomedical doctorate. Secondly, they clarify the form of a 'valued' supervisory relationship from a student perspective. We conclude that biomedical doctoral programs should be designed to contain a minimum level

Development of a polymeric ionic liquid coating for direct-immersion solid-phase microextraction using polyhedral oligomeric silsesquioxane as cross-linker.

Science.gov (United States)

Chen, Chunyan; Liang, Xiaotong; Wang, Jianping; Zou, Ying; Hu, Huiping; Cai, Qingyun; Yao, Shouzhuo

2014-06-27

A novel solid-phase microextraction (SPME) fiber was developed by chemical binding of a crosslinked polymeric ionic liquid (PIL) on the surface of an anodized Ti wire, and was applied in direct-immersion mode for the extraction of perfluorinated compounds (PFCs) from water samples coupled with high performance liquid chromatography-tandem mass spectrometry analysis. The PIL coatings were synthesized by using 1-vinyl-3-hexylimidazolium hexafluorophosphate as monomer and methylacryloyl-substituted polyhedral oligomeric silsesquioxane (POSS) as cross-linker via free radical reaction. The proposed fiber coating exhibited high mechanical stability due to the chemical bonding between the coating and the Ti wire surface. The integration of POSS reagent enhanced the organic solvent resistance of the coating. The parameters affecting the extraction performance of the fiber coating including extraction time, pH of solution, ionic strength and desorption conditions were optimized. The developed PIL-POSS fiber showed good linearity (R<0.998) between 0.1 and 50ngmL(-1) with method detection limits ranging from 0.005 to 0.08ngmL(-1) depending on the analyte, and with relative standard deviation for single-fiber repeatability and fiber-to-fiber reproducibility less than 8.6% and 9.5%, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of valine 106 on structure-function relation of cytosolic human thymidine kinase - Kinetic properties and oligomerization pattern of nine substitution mutants of V106

DEFF Research Database (Denmark)

Frederiksen, Hanne; Berenstein, Dvora; Munch-Petersen, Birgitte

2004-01-01

Information on the regulation and structure-function relation of enzymes involved in DNA precursor synthesis is pivotal, as defects in several of these enzymes have been found to cause depletion or deletion of mitochondrial DNA resulting in severe diseases. Here, the effect of amino acid 106...... and characterized nine mutants of amino acid 106 differing in size, conformation and polarity. According to their oligomerization pattern and thymidine kinetics, the TK1 mutants can be divided into two groups. Group I (V106A, V106I and V106T) behaves like V106WT, in that pre-assay exposure to ATP induces reversible...... transition from a dimer with low catalytic activity to a tetramer with high catalytic activity. Group II (V106G, V106H, V106K, V106L and V106Q) behaves like V106M in that they are permanently high activity tetramers, irrespective of ATP exposure. We conclude that size and conformation of amino acid 106...

Continuous-wave spatial quantum correlations of light induced by multiple scattering

DEFF Research Database (Denmark)

Smolka, Stephan; Ott, Johan Raunkjær; Huck, Alexander

2012-01-01

and reflectance. Utilizing frequency-resolved quantum noise measurements, we observe that the strength of the spatial quantum correlation function can be controlled by changing the quantum state of an incident bright squeezed-light source. Our results are found to be in excellent agreement with the developed......We present theoretical and experimental results on spatial quantum correlations induced by multiple scattering of nonclassical light. A continuous-mode quantum theory is derived that enables determining the spatial quantum correlation function from the fluctuations of the total transmittance...... theory and form a basis for future research on, e. g., quantum interference of multiple quantum states in a multiple scattering medium....

Bioactivity and properties of a dental adhesive functionalized with polyhedral oligomeric silsesquioxanes (POSS) and bioactive glass.

Science.gov (United States)

Rizk, Marta; Hohlfeld, Lisa; Thanh, Loan Tao; Biehl, Ralf; Lühmann, Nicole; Mohn, Dirk; Wiegand, Annette

2017-09-01

This study aimed to analyze the effect of infiltrating a commercial adhesive with nanosized bioactive glass (BG-Bi) particles or methacryl-functionalized polyhedral oligomeric silsesquioxanes (POSS) on material properties and bioactivity. An acetone-based dental adhesive (Solobond Plus adhesive, VOCO GmbH, Cuxhaven, Germany) was infiltrated with nanosized bioactive glass particles (0.1 or 1wt%), or with monofunctional or multifunctional POSS particles (10 or 20wt%). Unfilled adhesive served as control. Dispersion and hydrodynamic radius of the nanoparticles were studied by dynamic light scattering. Set specimens were immersed for 28days in artificial saliva at 37°C, and surfaces were mapped for the formation of calcium phospate (Ca/P) precipitates (scanning electron microscopy/energy-dispersive X-ray spectroscopy). Viscosity (rheometry) and the structural characteristic of the networks were studied, such as degree of conversion (FTIR spectroscopy), sol fraction and water sorption. POSS particles showed a good dispersion of the particles for both types of particles being smaller than 3nm, while the bioactive glass particles had a strong tendency to agglomerate. All nanoparticles induced the formation of Ca/P precipitates. The viscosity of the adhesive was not or only slightly increased by POSS particle addition but strongly increased by the bioactive glass particles. The degree of conversion, water sorption and sol fraction showed a maintained or improved network structure and properties when filled with BG-Bi and multifunctional POSS, however, less polymerization was found when loading a monofunctional POSS. Multifunctional POSS may be incorporated into dental adhesives to provide a bioactive potential without changing material properties adversely. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

New management algorithms in multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per Soelberg

2014-01-01

complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis......PURPOSE OF REVIEW: Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more...

Microglial phagocytosis induced by fibrillar β-amyloid is attenuated by oligomeric β-amyloid: implications for Alzheimer's disease

Directory of Open Access Journals (Sweden)

Lin Nan

2011-06-01

Full Text Available Abstract Background Reactive microglia are associated with β-amyloid (Aβ deposit and clearance in Alzhiemer's Disease (AD. Paradoxically, entocranial resident microglia fail to trigger an effective phagocytic response to clear Aβ deposits although they mainly exist in an "activated" state. Oligomeric Aβ (oAβ, a recent target in the pathogenesis of AD, can induce more potent neurotoxicity when compared with fibrillar Aβ (fAβ. However, the role of the different Aβ forms in microglial phagocytosis, induction of inflammation and oxidation, and subsequent regulation of phagocytic receptor system, remain unclear. Results We demonstrated that Aβ(1-42 fibrils, not Aβ(1-42 oligomers, increased the microglial phagocytosis. Intriguingly, the pretreatment of microglia with oAβ(1-42 not only attenuated fAβ(1-42-triggered classical phagocytic response to fluorescent microspheres but also significantly inhibited phagocytosis of fluorescent labeled fAβ(1-42. Compared with the fAβ(1-42 treatment, the oAβ(1-42 treatment resulted in a rapid and transient increase in interleukin 1β (IL-1β level and produced higher levels of tumor necrosis factor-α (TNF-α, nitric oxide (NO, prostaglandin E2 (PGE2 and intracellular superoxide anion (SOA. The further results demonstrated that microglial phagocytosis was negatively correlated with inflammatory mediators in this process and that the capacity of phagocytosis in fAβ(1-42-induced microglia was decreased by IL-1β, lippolysaccharide (LPS and tert-butyl hydroperoxide (t-BHP. The decreased phagocytosis could be relieved by pyrrolidone dithiocarbamate (PDTC, a nuclear factor-κB (NF-κB inhibitor, and N-acetyl-L-cysteine (NAC, a free radical scavenger. These results suggest that the oAβ-impaired phagocytosis is mediated through inflammation and oxidative stress-mediated mechanism in microglial cells. Furthermore, oAβ(1-42 stimulation reduced the mRNA expression of CD36, integrin β1 (Itgb1, and Ig

Using Bayesian Belief Networks To Assess Volcano State from Multiple Monitoring Timeseries And Other Evidence

Science.gov (United States)

Odbert, Henry; Aspinall, Willy

2013-04-01

When volcanoes exhibit unrest or become eruptively active, science-based decision support invariably is sought by civil authorities. Evidence available to scientists about a volcano's internal state is usually indirect, secondary or very nebulous.Advancement of volcano monitoring technology in recent decades has increased the variety and resolution of multi-parameter timeseries data recorded at volcanoes. Monitoring timeseries may be interpreted in real time by observatory staff and are often later subjected to further analytic scrutiny by the research community at large. With increasing variety and resolution of data, interpreting these multiple strands of parallel, partial evidence has become increasingly complex. In practice, interpretation of many timeseries involves familiarity with the idiosyncracies of the volcano, the monitoring techniques, the configuration of the recording instrumentation, observations from other datasets, and so on. Assimilation of this knowledge is necessary in order to select and apply the appropriate statistical techniques required to extract the required information. Bayesian Belief Networks (BBNs) use probability theory to treat and evaluate uncertainties in a rational and auditable scientific manner, but only to the extent warranted by the strength of the available evidence. The concept is a suitable framework for marshalling multiple observations, model results and interpretations - and associated uncertainties - in a methodical manner. The formulation is usually implemented in graphical form and could be developed as a tool for near real-time, ongoing use in a volcano observatory, for example. We explore the application of BBNs in analysing volcanic timeseries, the certainty with which inferences may be drawn, and how they can be updated dynamically. Such approaches provide a route to developing analytical interface(s) between volcano monitoring analyses and probabilistic hazard analysis. We discuss the use of BBNs in hazard

Goiter and Multiple Food Allergies

Directory of Open Access Journals (Sweden)

Stefanie Leniszewski

2009-01-01

Full Text Available Severe iodine deficiency results in impaired thyroid hormone synthesis and thyroid enlargement. In the United States, adequate iodine intake is a concern for women of childbearing age and pregnant women. Beyond this high risk group iodine deficiency is not considered to be a significant problem. This case report describes a 12-year-old male with severe iodine deficiency disorder (IDD resulting from restricted dietary intake due to multiple food allergies. We describe iodine replacement for this patient and continued monitoring for iodine sufficiency. Children with multiple food allergies, in particular those with restrictions to iodized salt and seafood, should be considered high risk for severe iodine deficiency.

[Delivery in multiple pregnancies].

Science.gov (United States)

Colla, F; D'Addato, F; Grio, R

2001-04-01

A knowledge of clinical physiognomy in pathologies related to multiple births is indispensable for improving maternal and feto-neonatal prognosis. This study is a contribution to the solution of this problem. A meta-analysis of data for multiple births at Department B of the Gynecology and Obstetrics Clinic at the University of Turi during the decade 1989-1998 was carried out, focusing on the arrangement and presentation of fetuses, the various types of birth, the gestational age at which birth occurred, the weight of neonates, neonatal mortality and maternal morbidity. Out of 11,523 births, there were a total of 194 (1.68%) multiple births, including 190 sets of twins and 4 triplets. 154 (79.38%) premature births were reported; 20 occurred 1500 g). The perinatal mortality rate was 3.82%. Maternal complications mainly occurred during the placental state, in the immediate postpartum and in puerperio. The authors feel that a more careful medical and social assistance, preventive hospitalisation, early recognition of the risk, constant monitoring for the optimal timing of birth, and lastly, qualified medical assistance during labour (expert gynecologist, trained obstetric staff) with other medical personnel (anesthetist, neonatal specialist) represent winning strategies to solve the problems arising during multiple pregnancies.

Thrombin generation correlates with disease duration in multiple sclerosis (MS): Novel insights into the MS-associated prothrombotic state.

Science.gov (United States)

Parsons, Martin Em; O'Connell, Karen; Allen, Seamus; Egan, Karl; Szklanna, Paulina B; McGuigan, Christopher; Ní Áinle, Fionnuala; Maguire, Patricia B

2017-01-01

Thrombin is well recognised for its role in the coagulation cascade but it also plays a role in inflammation, with enhanced thrombin generation observed in several inflammatory disorders. Although patients with multiple sclerosis (MS) have a higher incidence of thrombotic disease, thrombin generation has not been studied to date. The aim of this study was to characterise calibrated automated thrombography parameters in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) in comparison to healthy controls (HCs). Calibrated automated thrombography was performed on platelet poor plasma from 15 patients with RRMS, 15 with PPMS and 19 HCs. We found that patients with RRMS generate thrombin at a significantly faster rate than the less inflammatory subtype, PPMS or HCs. In addition, the speed of thrombin generation was significantly correlated with time from clinical diagnosis in both subtypes. However, in RRMS the rate of thrombin generation was increased with increased time from clinical diagnosis, while in PPMS the rate of thrombin generation decreased with increased time from clinical diagnosis. These data likely reflect the differential active proinflammatory states in each MS subtype and provide novel mechanistic insights into the clinically relevant prothrombotic state observed in these patients.

A multiplicity jump trigger using silicon planes

International Nuclear Information System (INIS)

Alexopoulos, T.; Erwin, A.R.

1993-01-01

Since silicon tracking planes are already present in a B decay experiment, it is an attractive idea to use these as part of a multiplicity jump detector. Two average B decays would produce a multiplicity jump of around 10 in the final state. Such a trigger has been tried for a fixed target Charm experiment with disappointing success. The failure was attributed to the difficulty in adequately controlling the gains of a large number of microstrip amplifies

Multiplicity distributions in high-energy neutrino interactions

International Nuclear Information System (INIS)

Chapman, J.W.; Coffin, C.T.; Diamond, R.N.; French, H.; Louis, W.; Roe, B.P.; Seidl, A.A.; Vander Velde, J.C.; Berge, J.P.; Bogert, D.V.; DiBianca, F.A.; Cundy, D.C.; Dunaitsev, A.; Efremenko, V.; Ermolov, P.; Fowler, W.; Hanft, R.; Harigel, G.; Huson, F.R.; Kolganov, V.; Mukhin, A.; Nezrick, F.A.; Rjabov, Y.; Scott, W.G.; Smart, W.

1976-01-01

Results from the Fermilab 15-ft bubble chamber on the charged-particle multiplicity distributions produced in high-energy charged-current neutrino-proton interactions are presented. Comparisons are made to γp, ep, μp, and inclusive pp scattering. The mean hadronic multiplicity appears to depend only on the mass of the excited hadronic state, independent of the mode of excitation. A fit to the neutrino data gives = (1.09+-0.38) +(1.09+-0.03)lnW 2

Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.

Science.gov (United States)

Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

2002-11-01

Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms.

Fabrication of boronate-decorated polyhedral oligomeric silsesquioxanes grafted cotton fiber for the selective enrichment of nucleosides in urine.

Science.gov (United States)

Gao, Li; Wei, Yinmao

2016-06-01

Various cotton fiber based boronate-affinity adsorbents are recently developed for the sample pretreatment of cis-diol-containing biomolecules, but most do not have efficient capacity due to limited binding sites on the surface of cotton fibers. To increase the density of boronate groups on the surface of cotton fiber, polyhedral oligomeric silsesquioxanes were used to modify cotton fiber to provide plentiful reactive sites for subsequent functionalization with 4-formylphenylboronic acid. The new adsorbent showed special recognition ability towards cis-diols and high adsorption capacity (175 μg/g for catechol, 250 μg/g for dopamine, 400 μg/g for adenosine). The in-pipette-tip solid-phase extraction was investigated under different conditions, including pH and ionic strength of solution, adsorbent amount, pipette times, washing solvent, and elution solvent. The in-pipette-tip solid-phase extraction coupled with high-performance liquid chromatography was used to analyze four nucleosides in urine samples. Under the optimal extraction conditions, the detection limits were determined to be between 5.1 and 6.1 ng/mL (S/N  =  3), and the linearity ranged from 20 to 500 ng/mL for these analytes. The accuracy of the analytical method was examined by studying the relative recoveries of analytes in real urine samples with recoveries varying from 83 to 104% (RSD = 3.9-10.2%, n = 3). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.