Single-Cell Detection of Secreted Aβ and sAPPα from Human IPSC-Derived Neurons and Astrocytes.

Science.gov (United States)

Liao, Mei-Chen; Muratore, Christina R; Gierahn, Todd M; Sullivan, Sarah E; Srikanth, Priya; De Jager, Philip L; Love, J Christopher; Young-Pearse, Tracy L

2016-02-03

Secreted factors play a central role in normal and pathological processes in every tissue in the body. The brain is composed of a highly complex milieu of different cell types and few methods exist that can identify which individual cells in a complex mixture are secreting specific analytes. By identifying which cells are responsible, we can better understand neural physiology and pathophysiology, more readily identify the underlying pathways responsible for analyte production, and ultimately use this information to guide the development of novel therapeutic strategies that target the cell types of relevance. We present here a method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells and have applied the method to measure amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα), analytes central to Alzheimer's disease pathogenesis. Through these studies, we have uncovered the dynamic range of secretion profiles of these analytes from single iPSC-derived neuronal and glial cells and have molecularly characterized subpopulations of these cells through immunostaining and gene expression analyses. In examining Aβ and sAPPα secretion from single cells, we were able to identify previously unappreciated complexities in the biology of APP cleavage that could not otherwise have been found by studying averaged responses over pools of cells. This technique can be readily adapted to the detection of other analytes secreted by neural cells, which would have the potential to open new perspectives into human CNS development and dysfunction. We have established a technology that, for the first time, detects secreted analytes from single human neurons and astrocytes. We examine secretion of the Alzheimer's disease-relevant factors amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα) and present novel findings that could not have been observed without a single-cell analytical platform. First, we

Single-ion and single-chain magnetism in triangular spin-chain oxides

Science.gov (United States)

Seikh, Md. Motin; Caignaert, Vincent; Perez, Olivier; Raveau, Bernard; Hardy, Vincent

2017-05-01

S r4 -xC axM n2Co O9 oxides (x =0 and x =2 ) are found to exhibit magnetic responses typical of single-chain magnets (SCMs) and single-ion magnets (SIMs), two features generally investigated in coordination polymers or complexes. The compound x =0 appears to be a genuine SCM, in that blocking effects associated with slow spin dynamics yield remanence and coercivity in the absence of long-range ordering (LRO). In addition, SIM signatures of nearly identical nature are detected in both compounds, coexisting with SCM in x =0 and with LRO in x =2 . It is also observed that a SCM response can be recovered in x =2 after application of magnetic field. These results suggest that purely inorganic systems could play a valuable role in the topical issue of the interplay among SIM, SCM, and LRO phenomena in low-dimensional magnetism.

Elementary excitations in single-chain magnets

Science.gov (United States)

Lutz, Philipp; Aguilà, David; Mondal, Abhishake; Pinkowicz, Dawid; Marx, Raphael; Neugebauer, Petr; Fâk, Björn; Ollivier, Jacques; Clérac, Rodolphe; van Slageren, Joris

2017-09-01

Single-chain magnets (SCMs) are one-dimensional coordination polymers or spin chains that display slow relaxation of the magnetization. Typically their static magnetic properties are described by the Heisenberg model, while the description of their dynamic magnetic properties is based on an Ising-like model. The types of excitations predicted by these models (collective vs localized) are quite different. Therefore we probed the nature of the elementary excitations for two SCMs abbreviated Mn2Ni and Mn2Fe , as well as a mononuclear derivative of the Mn2Fe chain, by means of high-frequency electron paramagnetic resonance spectroscopy (HFEPR) and inelastic neutron scattering (INS). We find that the HFEPR spectra of the chains are clearly distinct from those of the monomer. The momentum transfer dependence of the INS intensity did not reveal significant dispersion, indicating an essentially localized nature of the excitations. At the lowest temperatures these are modified by the occurrence of short-range correlations.

Effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells

International Nuclear Information System (INIS)

Hochberg, Z.; Kuten, A.; Hertz, P.; Tatcher, M.; Kedar, A.; Benderly, A.

1983-01-01

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100 to 1500 rad. Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0 to 300 rad, followed by a decline between 300 to 750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad

Development of two dimensional electrophoresis method using single chain DNA

International Nuclear Information System (INIS)

Ikeda, Junichi; Hidaka, So

1998-01-01

By combining a separation method due to molecular weight and a method to distinguish difference of mono-bases, it was aimed to develop a two dimensional single chain DNA labeled with Radioisotope (RI). From electrophoretic pattern difference of parent and variant strands, it was investigated to isolate the root module implantation control gene. At first, a Single Strand Conformation Polymorphism (SSCP) method using concentration gradient gel was investigated. As a result, it was formed that intervals between double chain and single chain DNAs expanded, but intervals of both single chain DNAs did not expand. On next, combination of non-modified acrylic amide electrophoresis method and Denaturing Gradient-Gel Electrophoresis (DGGE) method was examined. As a result, hybrid DNA developed by two dimensional electrophoresis arranged on two lines. But, among them a band of DNA modified by high concentration of urea could not be found. Therefore, in this fiscal year's experiments, no preferable result could be obtained. By the used method, it was thought to be impossible to detect the differences. (G.K.)

Single-copy entanglement in critical quantum spin chains

International Nuclear Information System (INIS)

Eisert, J.; Cramer, M.

2005-01-01

We consider the single-copy entanglement as a quantity to assess quantum correlations in the ground state in quantum many-body systems. We show for a large class of models that already on the level of single specimens of spin chains, criticality is accompanied with the possibility of distilling a maximally entangled state of arbitrary dimension from a sufficiently large block deterministically, with local operations and classical communication. These analytical results--which refine previous results on the divergence of block entropy as the rate at which maximally entangled pairs can be distilled from many identically prepared chains--are made quantitative for general isotropic translationally invariant spin chains that can be mapped onto a quasifree fermionic system, and for the anisotropic XY model. For the XX model, we provide the asymptotic scaling of ∼(1/6)log 2 (L), and contrast it with the block entropy

Unconventional phase transitions in a constrained single polymer chain

International Nuclear Information System (INIS)

Klushin, L I; Skvortsov, A M

2011-01-01

Phase transitions were recognized among the most fascinating phenomena in physics. Exactly solved models are especially important in the theory of phase transitions. A number of exactly solved models of phase transitions in a single polymer chain are discussed in this review. These are three models demonstrating the second order phase transitions with some unusual features: two-dimensional model of β-structure formation, the model of coil–globule transition and adsorption of a polymer chain grafted on the solid surface. We also discuss models with first order phase transitions in a single macromolecule which admit not only exact analytical solutions for the partition function with explicit finite-size effects but also the non-equilibrium free energy as a function of the order parameter (Landau function) in closed analytical form. One of them is a model of mechanical desorption of a macromolecule, which demonstrates an unusual first order phase transition with phase coexistence within a single chain. Features of first and second order transitions become mixed here due to phase coexistence which is not accompanied by additional interfacial free energy. Apart from that, there exist several single-chain models belonging to the same class (adsorption of a polymer chain tethered near the solid surface or liquid–liquid interface, and escape transition upon compressing a polymer between small pistons) that represent examples of a highly unconventional first order phase transition with several inter-related unusual features: no simultaneous phase coexistence, and hence no phase boundary, non-concave thermodynamic potential and non-equivalence of conjugate ensembles. An analysis of complex zeros of partition functions upon approaching the thermodynamic limit is presented for models with and without phase coexistence. (topical review)

Screened ion-ion interaction in mercury-chain compounds: Single chain

International Nuclear Information System (INIS)

Mohan, M.M.; Griffin, A.

1985-01-01

At room temperature, the mercury chains in Hg/sub 3-delta/AsF 6 exhibit phonons characteristic of a one-dimensional lattice. We calculate the screening of the Hg ion-ion interaction in a single chain by electrons moving in a cylindrical potential of finite radius, within the random-phase approximation. The resulting Bohm-Staver-type expression for the phonon velocity is (Z 2 mN/sub I//MN/sub e/)/sup 1/2/v/sub F/, where Z is the Hg ionic charge and N/sub I/ (N/sub e/) is the number of ions (electrons) per unit length. Use of the Tomonaga-Luttinger solution for the electronic response function (keeping only the small-momentum scattering processes) just renormalizes the Fermi velocity in this expression

Equivalence of chain conformations in the surface region of a polymer melt and a single Gaussian chain under critical conditions.

Science.gov (United States)

Skvortsov, A M; Leermakers, F A M; Fleer, G J

2013-08-07

In the melt polymer conformations are nearly ideal according to Flory's ideality hypothesis. Silberberg generalized this statement for chains in the interfacial region. We check the Silberberg argument by analyzing the conformations of a probe chain end-grafted at a solid surface in a sea of floating free chains of concentration φ by the self-consistent field (SCF) method. Apart from the grafting, probe chain and floating chains are identical. Most of the results were obtained for a standard SCF model with freely jointed chains on a six-choice lattice, where immediate step reversals are allowed. A few data were generated for a five-choice lattice, where such step reversals are forbidden. These coarse-grained models describe the equilibrium properties of flexible atactic polymer chains at the scale of the segment length. The concentration was varied over the whole range from φ = 0 (single grafted chain) to φ = 1 (probe chain in the melt). The number of contacts with the surface, average height of the free end and its dispersion, average loop and train length, tail size distribution, end-point and overall segment distributions were calculated for a grafted probe chain as a function of φ, for several chain lengths and substrate∕polymer interactions, which were varied from strong repulsion to strong adsorption. The computations show that the conformations of the probe chain in the melt do not depend on substrate∕polymer interactions and are very similar to the conformations of a single end-grafted chain under critical conditions, and can thus be described analytically. When the substrate∕polymer interaction is fixed at the value corresponding to critical conditions, all equilibrium properties of a probe chain are independent of φ, over the whole range from a dilute solution to the melt. We believe that the conformations of all flexible chains in the surface region of the melt are close to those of an appropriate single chain in critical conditions, provided

A Strategy for Generating a Broad-Spectrum Monoclonal Antibody and Soluble Single-Chain Variable Fragments against Plant Potyviruses

Science.gov (United States)

Liu, Han-Lin; Lin, Wei-Fang; Hu, Wen-Chi; Lee, Yung-An

2015-01-01

Potyviruses are major pathogens that often cause mixed infection in calla lilies. To reduce the time and cost of virus indexing, a detection method for the simultaneous targeting of multiple potyviruses was developed by generating a broad-spectrum monoclonal antibody (MAb) for detecting the greatest possible number of potyviruses. The conserved 121-amino-acid core regions of the capsid proteins of Dasheen mosaic potyvirus (DsMV), Konjak mosaic potyvirus (KoMV), and Zantedeschia mild mosaic potyvirus (ZaMMV) were sequentially concatenated and expressed as a recombinant protein for immunization. After hybridoma cell fusion and selection, one stable cell line that secreted a group-specific antibody, named C4 MAb, was selected. In the reaction spectrum test, the C4 MAb detected at least 14 potyviruses by indirect enzyme-linked immunosorbent assay (I-ELISA) and Western blot analysis. Furthermore, the variable regions of the heavy (VH) and light (VL) chains of the C4 MAb were separately cloned and constructed as single-chain variable fragments (scFvs) for expression in Escherichia coli. Moreover, the pectate lyase E (PelE) signal peptide of Erwinia chrysanthemi S3-1 was added to promote the secretion of C4 scFvs into the medium. According to Western blot analysis and I-ELISA, the soluble C4 scFv (VL-VH) fragment showed a binding specificity similar to that of the C4 MAb. Our results demonstrate that a recombinant protein derived from fusion of the conserved regions of viral proteins has the potential to produce a broad-spectrum MAb against a large group of viruses and that the PelE signal peptide can improve the secretion of scFvs in E. coli. PMID:26209665

The impact of short chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon

DEFF Research Database (Denmark)

Christiansen, Charlotte Bayer; Gabe, Maria Buur Nordskov; Svendsen, Berit

2018-01-01

chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L-cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects...

Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

Science.gov (United States)

Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

2015-01-01

Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

Effect of chain stiffness on the structure of single-chain polymer nanoparticles

Science.gov (United States)

Moreno, Angel J.; Bacova, Petra; Lo Verso, Federica; Arbe, Arantxa; Colmenero, Juan; Pomposo, José A.

2018-01-01

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by purely intramolecular cross-linking of single polymer chains. By means of computer simulations, we investigate the conformational properties of SCNPs as a function of the bending stiffness of their linear polymer precursors. We investigate a broad range of characteristic ratios from the fully flexible case to those typical of bulky synthetic polymers. Increasing stiffness hinders bonding of groups separated by short contour distances and increases looping over longer distances, leading to more compact nanoparticles with a structure of highly interconnected loops. This feature is reflected in a crossover in the scaling behaviour of several structural observables. The scaling exponents change from those characteristic for Gaussian chains or rings in θ-solvents in the fully flexible limit, to values resembling fractal or ‘crumpled’ globular behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are weakly deformable regions that can be seen as disordered analogues of domains in disordered proteins. Increasing stiffness leads to bigger and less deformable domains. Surprisingly, the scaling behaviour of the domains is in all cases similar to that of Gaussian chains or rings, irrespective of the stiffness and degree of cross-linking. It is the spatial arrangement of the domains which determines the global structure of the SCNP (sparse Gaussian-like object or crumpled globule). Since intramolecular stiffness can be varied through the specific chemistry of the precursor or by introducing bulky side groups in its backbone, our results propose a new strategy to tune the global structure of SCNPs.

Efficient Synthesis of Single-Chain Polymer Nanoparticles via Amide Formation

Directory of Open Access Journals (Sweden)

Ana Sanchez-Sanchez

2015-01-01

Full Text Available Single-chain technology (SCT allows the transformation of individual polymer chains to folded/collapsed unimolecular soft nanoparticles. In this work we contribute to the enlargement of the SCT toolbox by demonstrating the efficient synthesis of single-chain polymer nanoparticles (SCNPs via intrachain amide formation. In particular, we exploit cross-linking between active methylene groups and isocyanate moieties as powerful “click” chemistry driving force for SCNP construction. By employing poly(methyl methacrylate- (PMMA- based copolymers bearing β-ketoester units distributed randomly along the copolymer chains and bifunctional isocyanate cross-linkers, SCNPs were successfully synthesized at r.t. under appropriate reaction conditions. Characterization of the resulting SCNPs was carried out by means of a combination of techniques including size exclusion chromatography (SEC, infrared (IR spectroscopy, proton nuclear magnetic resonance (1H NMR spectroscopy, dynamic light scattering (DLS, and elemental analysis (EA.

Secretive production of long-chain fatty acids, triacylglycerols and n-alkane-2-ones by fermentation processes; Hakkoho ni yoru ekitai nenryo no seisan wa kanoka (shishitsu no bunpi seisan)

Energy Technology Data Exchange (ETDEWEB)

Fukui, S. [University of Fukuyama, Hiroshima (Japan). Faculty of Engineering

1995-10-20

Secretive production of lipids, which are useful source for engine-driving fuel, by microbial process using carbohydrate biomasses as substrate has been investigated in our laboratory. This review consists of four parts concerning breedings and selection of lipid-secretive microorganisms : (1) breedings of long-chain fatty acid-secretive strains from Candida lipolytica L-1 by a step-wise mutagenesis process, (2) selection of a triacylglycerol (TG)-secretive and accumulative yeast strain Trichosporon sp. SH45Y, (3) breedings of mutants, SH45Y-derivatieves, having potent ability to produce TG secretively from glucose, a typical biomass charbohydrate, and (4) selection of microorganisms which produce liquid-n-alkane in culture medium by utilizing long-chain fatty acids and TG; a strain of Penicillium decumbens can produce liquid alkalis with a yield of approximately 60 % in weight from palm kernel oil, a commercial TG. 10 refs., 7 figs., 7 tabs.

Mouse myeloma cells that make short immunoglobulin heavy chains: pleiotropic effects on glycosylation and chain assembly

OpenAIRE

1984-01-01

Two variants in immunoglobulin heavy chain production, derived from the MPC 11 mouse myeloma cell line, make short heavy (H) chains with identical precise deletions of the CH3 domain. The CH3 domain is expressed in the H chain mRNA from both variants. Although in vitro translation of this mRNA produces one H chain species, deleted heavy chains are secreted as heavy-light (HL) and H2L2 moieties in contrast to MPC 11, which secretes only H2L2 . The heavy chains of HL apparently contain more car...

Mechanics of biopolymer materials: Single chains to bulk properties

NARCIS (Netherlands)

Amuasi, H.E.; Storm, C.

2010-01-01

We outline the first stages in the multiscale modeling of biopolymer materials, starting with the statistical mechanics of single stiff chains. In the first coarse graining step, we demonstrate how to integrate out the single polymer degrees of freedom in supramolecular assemblies of such

Mucus glycoprotein secretion by tracheal explants: effects of pollutants

International Nuclear Information System (INIS)

Last, J.A.; Kaizu, T.

1980-01-01

Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with [3H] glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques

Selection rules for single-chain-magnet behaviour in non-collinear Ising systems

International Nuclear Information System (INIS)

Vindigni, Alessandro; Pini, Maria Gloria

2009-01-01

The magnetic behaviour of molecular single-chain magnets is investigated in the framework of a one-dimensional Ising model with single spin-flip Glauber dynamics. Opportune modifications to the original theory are required in order to account for non-collinearity of local anisotropy axes between themselves and with respect to the crystallographic (laboratory) frame. The extension of Glauber's theory to the case of a collinear Ising ferrimagnetic chain is also discussed. Within this formalism, both the dynamics of magnetization reversal in zero field and the response of the system to a weak magnetic field, oscillating in time, are studied. Depending on the experimental geometry, selection rules are found for the occurrence of slow relaxation of the magnetization at low temperatures, as well as for resonant behaviour of the a.c. susceptibility as a function of temperature at low frequencies. The present theory applies successfully to some real systems, namely Mn-, Dy- and Co-based molecular magnetic chains, showing that single-chain-magnet behaviour is not only a feature of collinear ferro- and ferrimagnetic, but also of canted antiferromagnetic chains.

Selection rules for single-chain-magnet behaviour in non-collinear Ising systems

Energy Technology Data Exchange (ETDEWEB)

Vindigni, Alessandro [Laboratorium fuer Festkoerperphysik, ETH Zuerich, CH-8093 Zuerich (Switzerland); Pini, Maria Gloria [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, Via Madonna del Piano 10, I-50019 Sesto Fiorentino (Italy)], E-mail: vindigni@phys.ethz.ch

2009-06-10

The magnetic behaviour of molecular single-chain magnets is investigated in the framework of a one-dimensional Ising model with single spin-flip Glauber dynamics. Opportune modifications to the original theory are required in order to account for non-collinearity of local anisotropy axes between themselves and with respect to the crystallographic (laboratory) frame. The extension of Glauber's theory to the case of a collinear Ising ferrimagnetic chain is also discussed. Within this formalism, both the dynamics of magnetization reversal in zero field and the response of the system to a weak magnetic field, oscillating in time, are studied. Depending on the experimental geometry, selection rules are found for the occurrence of slow relaxation of the magnetization at low temperatures, as well as for resonant behaviour of the a.c. susceptibility as a function of temperature at low frequencies. The present theory applies successfully to some real systems, namely Mn-, Dy- and Co-based molecular magnetic chains, showing that single-chain-magnet behaviour is not only a feature of collinear ferro- and ferrimagnetic, but also of canted antiferromagnetic chains.

Covalent bond force profile and cleavage in a single polymer chain

Science.gov (United States)

Garnier, Lionel; Gauthier-Manuel, Bernard; van der Vegte, Eric W.; Snijders, Jaap; Hadziioannou, Georges

2000-08-01

We present here the measurement of the single-polymer entropic elasticity and the single covalent bond force profile, probed with two types of atomic force microscopes (AFM) on a synthetic polymer molecule: polymethacrylic acid in water. The conventional AFM allowed us to distinguish two types of interactions present in this system when doing force spectroscopic measurements: the first interaction is associated with adsorption sites of the polymer chains onto a bare gold surface, the second interaction is directly correlated to the rupture process of a single covalent bond. All these bridging interactions allowed us to stretch the single polymer chain and to determine the various factors playing a role in the elasticity of these molecules. To obtain a closer insight into the bond rupture process, we moved to a force sensor stable in position when measuring attractive forces. By optimizing the polymer length so as to fulfill the elastic stability conditions, we were able for the first time to map out the entire force profile associated with the cleavage of a single covalent bond. Experimental data coupled with molecular quantum mechanical calculations strongly suggest that the breaking bond is located at one end of the polymer chain.

Exploring single chain amphiphile self-assembly and their possible roles in light transduction

DEFF Research Database (Denmark)

Monnard, Pierre-Alain

2011-01-01

Self-assembled structures of single-chain amphiphiles have been used as hosts for biochemical, and chemical reactions. Their use as models for protocells (i.e., precursors to the first biological cells) has been extensively researched by various groups because the availability of single chain......: the medium composition in terms of ionic strengths and the medium physical parameters, such as temperature, significantly influence the formation of structures, as well as their subsequent stability. In addition, membranes composed of a single amphiphile type seem to be implausible as no potential amphiphile...... source studied to date can supply one single type of amphiphile at concentrations conducive to self-assembly. Mixtures of single-chain amphiphiles were therefore proposed to better model primitive membranes and potentially enhance their structural integrity1-3. Recently, we have established that complex...

Real-time observation of conformational switching in single conjugated polymer chains.

Science.gov (United States)

Tenopala-Carmona, Francisco; Fronk, Stephanie; Bazan, Guillermo C; Samuel, Ifor D W; Penedo, J Carlos

2018-02-01

Conjugated polymers (CPs) are an important class of organic semiconductors that combine novel optoelectronic properties with simple processing from organic solvents. It is important to study CP conformation in solution to understand the physics of these materials and because it affects the properties of solution-processed films. Single-molecule techniques are unique in their ability to extract information on a chain-to-chain basis; however, in the context of CPs, technical challenges have limited their general application to host matrices or semiliquid environments that constrain the conformational dynamics of the polymer. We introduce a conceptually different methodology that enables measurements in organic solvents using the single-end anchoring of polymer chains to avoid diffusion while preserving polymer flexibility. We explore the effect of organic solvents and show that, in addition to chain-to-chain conformational heterogeneity, collapsed and extended polymer segments can coexist within the same chain. The technique enables real-time solvent-exchange measurements, which show that anchored CP chains respond to sudden changes in solvent conditions on a subsecond time scale. Our results give an unprecedented glimpse into the mechanism of solvent-induced reorganization of CPs and can be expected to lead to a new range of techniques to investigate and conformationally manipulate CPs.

Quantum Heisenberg antiferromagnetic chains with exchange and single-ion anisotropies

International Nuclear Information System (INIS)

Peters, D; Selke, W; McCulloch, I P

2010-01-01

Using density matrix renormalization group calculations, ground state properties of the spin-1 Heisenberg chain with exchange and quadratic single-ion anisotropies in an external field are studied, for special choices of the two kinds of anisotropies. In particular, the phase diagram includes antiferromagnetic, spin-liquid (or spin-flop), IS2, and supersolid (or biconical) phases. Especially, new features of the spin-liquid and supersolid phases are discussed. Properties of the quantum chains are compared to those of corresponding classical spin chains.

Sequential Quantum Secret Sharing Using a Single Qudit

Science.gov (United States)

Bai, Chen-Ming; Li, Zhi-Hui; Li, Yong-Ming

2018-05-01

In this paper we propose a novel and efficient quantum secret sharing protocol using d-level single particle, which it can realize a general access structure via the thought of concatenation. In addition, Our scheme includes all advantages of Tavakoli’s scheme [Phys. Rev. A 92 (2015) 030302(R)]. In contrast to Tavakoli’s scheme, the efficiency of our scheme is 1 for the same situation, and the access structure is more general and has advantages in practical significance. Furthermore, we also analyze the security of our scheme in the primary quantum attacks. Sponsored by the National Natural Science Foundation of China under Grant Nos. 61373150 and 61602291, and Industrial Research and Development Project of Science and Technology of Shaanxi Province under Grant No. 2013k0611

Force Spectroscopy of Hyaluronan by AFM; From H-bonded Networks Towards Single Chain Behavior

NARCIS (Netherlands)

Giannotti, M.I.; Rinaudo, Marguerite; Vancso, Gyula J.

2007-01-01

The conformational behavior of hyaluronan (HA) polysaccharide chains in aqueous NaCl solution was characterized directly at the single-molecule level. This comunication reports on one of the first single-chain atomic force microscopy (AFM) experiments performed at variable temperatures,

Production of a phage-displayed single chain variable fragment ...

African Journals Online (AJOL)

Abstract. Purpose: To develop specific single chain variable fragments (scFv) against ... libraries. The binding ability of the selected scFv antibody fragments against the IBDV particles was ..... Hermelink H, Koscielniak E. A human recombinant.

Pressure effects on single chain magnets

Energy Technology Data Exchange (ETDEWEB)

Mito, M. E-mail: mitoh@elcs.kyutech.ac.jp; Shindo, N.; Tajiri, T.; Deguchi, H.; Takagi, S.; Miyasaka, H.; Yamashita, M.; Clerac, R.; Coulon, C

2004-05-01

Pressure effects on a single chain magnet [Mn{sub 2}(saltmen){sub 2}Ni(pao){sub 2}(py){sub 2}](ClO{sub 4}){sub 2} (saltmen{sup 2-}=N,N'-(1,1,2,2-tetramethylethylene)bis(salicylideneiminate), and pao{sup -}=pyridine-2-aldoximate) have been investigated through AC magnetic measurements under pressure (P). The slow relaxation of the magnetization depends on pressure. Both the blocking temperature (T{sub B}) and energy barrier ({delta}) increase by pressurization, and those enhancements saturate at around P=7 kbar.

Stereoelectronic Effect-Induced Conductance Switching in Aromatic Chain Single-Molecule Junctions.

Science.gov (United States)

Xin, Na; Wang, Jinying; Jia, Chuancheng; Liu, Zitong; Zhang, Xisha; Yu, Chenmin; Li, Mingliang; Wang, Shuopei; Gong, Yao; Sun, Hantao; Zhang, Guanxin; Liu, Zhirong; Zhang, Guangyu; Liao, Jianhui; Zhang, Deqing; Guo, Xuefeng

2017-02-08

Biphenyl, as the elementary unit of organic functional materials, has been widely used in electronic and optoelectronic devices. However, over decades little has been fundamentally understood regarding how the intramolecular conformation of biphenyl dynamically affects its transport properties at the single-molecule level. Here, we establish the stereoelectronic effect of biphenyl on its electrical conductance based on the platform of graphene-molecule single-molecule junctions, where a specifically designed hexaphenyl aromatic chain molecule is covalently sandwiched between nanogapped graphene point contacts to create stable single-molecule junctions. Both theoretical and temperature-dependent experimental results consistently demonstrate that phenyl twisting in the aromatic chain molecule produces different microstates with different degrees of conjugation, thus leading to stochastic switching between high- and low-conductance states. These investigations offer new molecular design insights into building functional single-molecule electrical devices.

Earlinet single calculus chain: new products overview

Science.gov (United States)

D'Amico, Giuseppe; Mattis, Ina; Binietoglou, Ioannis; Baars, Holger; Mona, Lucia; Amato, Francesco; Kokkalis, Panos; Rodríguez-Gómez, Alejandro; Soupiona, Ourania; Kalliopi-Artemis, Voudouri

2018-04-01

The Single Calculus Chain (SCC) is an automatic and flexible tool to analyze raw lidar data using EARLINET quality assured retrieval algorithms. It has been already demonstrated the SCC can retrieve reliable aerosol backscatter and extinction coefficient profiles for different lidar systems. In this paper we provide an overview of new SCC products like particle linear depolarization ratio, cloud masking, aerosol layering allowing relevant improvements in the atmospheric aerosol characterization.

Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

Science.gov (United States)

Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

2017-06-01

Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for  85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Effect of single oral dose of tramadol on gastric secretions pH

Directory of Open Access Journals (Sweden)

Khan Mueen Ullah

2015-01-01

Full Text Available Background: Tramadol is an atypical analgesic agent. It has been shown that intramuscular or intravenous injection tramadol is able to inhibit M3 muscarinic receptors. Tramadol is able to mediate smooth muscles contraction and glandular secretions. We have evaluated the effects of single oral dose of tramadol given preoperatively on gastric juices pH in patients electively scheduled for laparoscopic cholecystectomy. Materials and Methods: Sixty adult, American Society of Anesthesiologist I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive either placebo (n = 30 or oral tramadol 50 mg (n = 30. General anesthesia was induced using propofol, fentanyl and cisatracurium. After induction of anesthesia 5 ml of gastric fluid was aspirated through orogastric tube. The gastric fluid pH was measured using pH meter. Result: There was no significant difference in the pH between the groups. Gastric pH of the placebo and tramadol groups was 1.97 versus 1.98 (P = 0.092 respectively. Conclusion: Preoperatively single oral dose of tramadol was unable to elevate the desired level of gastric acid secretions pH (>2.5. This may be due to pharmacokinetic disparity between the analgesic and pH elevating properties of tramadol.

Cloning and expression of recombinant, functional ricin B chain

International Nuclear Information System (INIS)

Chang, M.S.; Russell, D.W.; Uhr, J.W.; Vitetta, E.S.

1987-01-01

The cDNA encoding the B chain of the plant toxin ricin has been cloned and expressed in monkey kidney COS-M6 cells. The recombinant B chain was detected by labeling the transfected cells with [ 35 S]methionine and [ 35 S]-cysteine and demonstrating the secretion of a protein with a M/sub r/ of 30,000-32,000 that was not present in the medium of mock-transfected COS-M6 cells. This protein was specifically immunoprecipitated by an anti-ricin or anti-B-chain antibody and the amount of recombinant B chain secreted by the COS-M6 cells was determined by a radioimmunoassay. Virtually all of the recombinant B chain formed active ricin when mixed with native A chain; it could also bind to the galactose-containing glycoprotein asialofetuin as effectively as native B chain.These results indicate that the vast majority of recombinant B chains secreted into the medium of the COS-M6 cells retain biological function

Molecular dynamics simulation of AFM studies of a single polymer chain

International Nuclear Information System (INIS)

Wang Wenhai; Kistler, Kurt A.; Sadeghipour, Keya; Baran, George

2008-01-01

Single polymer chain force-extension behavior measured by Atomic Force Microscopy (AFM) was interpreted by molecular dynamics (MD) simulation performed by applying a bead-spring (coarse-graining) model in which the bond potential function between adjacent beads is described by a worm-like chain (WLC) model. Simulation results indicate that caution should be applied when interpreting experimental AFM data, because the data vary depending on the point of AFM tip-polymer chain attachment. This approach offers an effective way for eventual analysis of the mechanical behavior of complex polymer networks

Molecular dynamics simulation of AFM studies of a single polymer chain

Energy Technology Data Exchange (ETDEWEB)

Wang Wenhai [Center for Bioengineering and Biomaterials, College of Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122 (United States); Kistler, Kurt A. [Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA 19122 (United States); Sadeghipour, Keya [Center for Bioengineering and Biomaterials, College of Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122 (United States); Baran, George [Center for Bioengineering and Biomaterials, College of Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122 (United States)], E-mail: grbaran@temple.edu

2008-11-24

Single polymer chain force-extension behavior measured by Atomic Force Microscopy (AFM) was interpreted by molecular dynamics (MD) simulation performed by applying a bead-spring (coarse-graining) model in which the bond potential function between adjacent beads is described by a worm-like chain (WLC) model. Simulation results indicate that caution should be applied when interpreting experimental AFM data, because the data vary depending on the point of AFM tip-polymer chain attachment. This approach offers an effective way for eventual analysis of the mechanical behavior of complex polymer networks.

Efficient heterologous expression and secretion in Aspergillus oryzae of a llama variable heavy-chain antibody fragment V(HH) against EGFR.

Science.gov (United States)

Okazaki, Fumiyoshi; Aoki, Jun-ichi; Tabuchi, Soichiro; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko

2012-10-01

We have constructed a filamentous fungus Aspergillus oryzae that secretes a llama variable heavy-chain antibody fragment (V(HH)) that binds specifically to epidermal growth factor receptor (EGFR) in a culture medium. A major improvement in yield was achieved by fusing the V(HH) with a Taka-amylase A signal sequence (sTAA) and a segment of 28 amino acids from the N-terminal region of Rhizopus oryzae lipase (N28). The yields of secreted, immunologically active anti-EGFR V(HH) reached 73.8 mg/1 in a Sakaguchi flask. The V(HH) fragments were released from the sTAA or N28 proteins by an indigenous A. oryzae protease during cultivation. The purified recombinant V(HH) fragment was specifically recognized and could bind to the EGFR with a high affinity.

M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

Directory of Open Access Journals (Sweden)

Linda Cambier

Full Text Available Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.

Single-Molecule Imaging Reveals Topology Dependent Mutual Relaxation of Polymer Chains

KAUST Repository

Abadi, Maram; Serag, Maged F.; Habuchi, Satoshi

2015-01-01

The motion and relaxation of linear and cyclic polymers under entangled conditions are investigated by means of a newly developed single-molecule tracking technique, cumulative-area (CA) tracking. CA tracking enables simultaneous quantitative characterization of the diffusion mode, diffusion rate, and relaxation time that have been impossible with a widely used conventional single-molecule localization and tracking method, by analyzing cumulative areas occupied by the moving molecule. Using the novel approach, we investigate the motion and relaxation of entangled cyclic polymers, which have been an important but poorly understood question. Fluorescently labeled 42 kbp linear or cyclic tracer dsDNAs in concentrated solutions of unlabeled linear or cyclic DNAs are used as model systems. We show that CA tracking can explicitly distinguish topology-dependent diffusion mode, rate, and relaxation time, demonstrating that the method provides an invaluable tool for characterizing topological interaction between the entangled chains. We further demonstrate that the current models proposed for the entanglement between cyclic polymers which are based on cyclic chains moving through an array of fixed obstacles cannot correctly describe the motion of the cyclic chain under the entangled conditions. Our results rather suggest the mutual relaxation of the cyclic chains, which underscore the necessity of developing a new model to describe the motion of cyclic polymer under the entangled conditions based on the mutual interaction of the chains.

Single-Molecule Imaging Reveals Topology Dependent Mutual Relaxation of Polymer Chains

KAUST Repository

Abadi, Maram

2015-08-24

The motion and relaxation of linear and cyclic polymers under entangled conditions are investigated by means of a newly developed single-molecule tracking technique, cumulative-area (CA) tracking. CA tracking enables simultaneous quantitative characterization of the diffusion mode, diffusion rate, and relaxation time that have been impossible with a widely used conventional single-molecule localization and tracking method, by analyzing cumulative areas occupied by the moving molecule. Using the novel approach, we investigate the motion and relaxation of entangled cyclic polymers, which have been an important but poorly understood question. Fluorescently labeled 42 kbp linear or cyclic tracer dsDNAs in concentrated solutions of unlabeled linear or cyclic DNAs are used as model systems. We show that CA tracking can explicitly distinguish topology-dependent diffusion mode, rate, and relaxation time, demonstrating that the method provides an invaluable tool for characterizing topological interaction between the entangled chains. We further demonstrate that the current models proposed for the entanglement between cyclic polymers which are based on cyclic chains moving through an array of fixed obstacles cannot correctly describe the motion of the cyclic chain under the entangled conditions. Our results rather suggest the mutual relaxation of the cyclic chains, which underscore the necessity of developing a new model to describe the motion of cyclic polymer under the entangled conditions based on the mutual interaction of the chains.

Production of a phage-displayed single chain variable fragment ...

African Journals Online (AJOL)

Purpose: To develop specific single chain variable fragments (scFv) against infectious bursal disease virus (IBDV) via phage display technology. Methods: Purified viruses were initially applied for iterative panning rounds of scFv phage display libraries. The binding ability of the selected scFv antibody fragments against the ...

Expression, production and renaturation of a functional single-chain ...

African Journals Online (AJOL)

The single-chain variable antibody fragment (scFv) against human intercellular adhesion molecule-1 (ICAM-1) was expressed at a high level in Escherichia coli as inclusion bodies. We attempted to refold the scFv by ion-exchange chromatography (IEC), dialysis and dilution. The results show that the column ...

Single-Chain Conformation for Interacting Poly(N-isopropylacrylamide in Aqueous Solution

Directory of Open Access Journals (Sweden)

Boualem Hammouda

2015-04-01

Full Text Available The demixing phase behavior of Poly(N-isopropylacrylamide (PNIPAM aqueous solution is investigated using small-angle neutron scattering. This polymer phase separates upon heating and demixes around 32 °C. The pre-transition temperature range is characterized by two scattering modes; a low-Q (large-scale signal and a high-Q dissolved chains signal. In order to get insight into this pre-transition region, especially the origin of the low-Q (large-scale structure, the zero average contrast method is used in order to isolate single-chain conformations even in the demixing polymers transition region. This method consists of measuring deuterated and non-deuterated polymers dissolved in mixtures of deuterated and non-deuterated water for which the polymer scattering length density matches the solvent scattering length density. A fixed 4% polymer mass fraction is used in a contrast variation series where the d-water/h-water fraction is varied in order to determine the match point. The zero average contrast (match point sample displays pure single-chain scattering with no interchain contributions. Our measurements prove that the large scale structure in this polymer solution is due to a transient polymer network formed through hydrophobic segment-segment interactions. Scattering intensity increases when the temperature gets close to the phase boundary. While the apparent radius of gyration increases substantially at the Lower Critical Solution Temperature (LCST transition due to strong interchain correlation, the single-chain true radius of gyration has been found to decrease slightly with temperature when approaching the transition.

Single-molecule study on polymer diffusion in a melt state: Effect of chain topology

KAUST Repository

Habuchi, Satoshi

2013-08-06

We report a new methodology for studying diffusion of individual polymer chains in a melt state, with special emphasis on the effect of chain topology. A perylene diimide fluorophore was incorporated into the linear and cyclic poly(THF)s, and real-time diffusion behavior of individual chains in a melt of linear poly(THF) was measured by means of a single-molecule fluorescence imaging technique. The combination of mean squared displacement (MSD) and cumulative distribution function (CDF) analysis demonstrated the broad distribution of diffusion coefficient of both the linear and cyclic polymer chains in the melt state. This indicates the presence of spatiotemporal heterogeneity of the polymer diffusion which occurs at much larger time and length scales than those expected from the current polymer physics theory. We further demonstrated that the cyclic chains showed marginally slower diffusion in comparison with the linear counterparts, to suggest the effective suppression of the translocation through the threading-entanglement with the linear matrix chains. This coincides with the higher activation energy for the diffusion of the cyclic chains than of the linear chains. These results suggest that the single-molecule imaging technique provides a powerful tool to analyze complicated polymer dynamics and contributes to the molecular level understanding of the chain interaction. © 2013 American Chemical Society.

Single-molecule study on polymer diffusion in a melt state: Effect of chain topology

KAUST Repository

Habuchi, Satoshi; Fujiwara, Susumu; Yamamoto, Takuya; Vá cha, Martin; Tezuka, Yasuyuki

2013-01-01

We report a new methodology for studying diffusion of individual polymer chains in a melt state, with special emphasis on the effect of chain topology. A perylene diimide fluorophore was incorporated into the linear and cyclic poly(THF)s, and real-time diffusion behavior of individual chains in a melt of linear poly(THF) was measured by means of a single-molecule fluorescence imaging technique. The combination of mean squared displacement (MSD) and cumulative distribution function (CDF) analysis demonstrated the broad distribution of diffusion coefficient of both the linear and cyclic polymer chains in the melt state. This indicates the presence of spatiotemporal heterogeneity of the polymer diffusion which occurs at much larger time and length scales than those expected from the current polymer physics theory. We further demonstrated that the cyclic chains showed marginally slower diffusion in comparison with the linear counterparts, to suggest the effective suppression of the translocation through the threading-entanglement with the linear matrix chains. This coincides with the higher activation energy for the diffusion of the cyclic chains than of the linear chains. These results suggest that the single-molecule imaging technique provides a powerful tool to analyze complicated polymer dynamics and contributes to the molecular level understanding of the chain interaction. © 2013 American Chemical Society.

Development of anti-bovine IgA single chain variable fragment and its application in diagnosis of foot-and-mouth disease

Science.gov (United States)

Sridevi, N. V.; Shukra, A. M.; Neelakantam, B.; Anilkumar, J.; Madhanmohan, M.; Rajan, S.; Dev Chandran

2014-01-01

Recombinant antibody fragments like single chain variable fragments (scFvs) represent an attractive yet powerful alternative to immunoglobulins and hold great potential in the development of clinical diagnostic/therapeutic reagents. Structurally, scFvs are the smallest antibody fragments capable of retaining the antigen-binding capacity of whole antibodies and are composed of an immunoglobulin (Ig) variable light (VL) and variable heavy (VH) chain joined by a flexible polypeptide linker. In the present study, we constructed a scFv against bovine IgA from a hybridoma cell line IL-A71 that secretes a monoclonal antibody against bovine IgA using recombinant DNA technology. The scFv was expressed in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC). The binding activity and specificity of the scFv was established by its non-reactivity toward other classes of immunoglobulins as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Kinetic measurement of the scFv indicated that the recombinant antibody fragment had an affinity in picomolar range toward purified IgA. Furthermore, the scFv was used to develop a sensitive ELISA for the detection of foot and mouth disease virus (FMDV) carrier animals. PMID:24678404

Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

Science.gov (United States)

Sreenivas, Suma; Krishnaiah, Sateesh M; Shyam Mohan, Anil H; Mallikarjun, Niveditha; Govindappa, Nagaraja; Chatterjee, Amarnath; Sastry, Kedarnath N

2016-02-01

Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over-expression of Kex2 protease. The enhanced levels of the Kex2 protease was responsible for the processing of the glargine precursor with in the host. Apart from the two-chain glargine product we observed a small proportion of arginine clipped species. This might be due to the clipping of arginine present at the C-terminus of the B-chain as it is exposed upon Kex2 cleavage. The carboxypeptidase precursor Kex1 is known to be responsible for clipping of C-terminal lysine or arginine of the proteins or peptides. In order to address this issue we created a Kex1 knock out in the host using Cre/loxP mechanism of targeted gene deletion. When two-chain glargine was expressed in the Kex1 knock out host of P. pastoris GS115 the C-terminal clipped species reduced by ∼80%. This modification further improved the process by reducing the levels of product related impurities. Copyright © 2015 Elsevier Inc. All rights reserved.

Two-party secret key distribution via a modified quantum secret sharing protocol.

Science.gov (United States)

Grice, W P; Evans, P G; Lawrie, B; Legré, M; Lougovski, P; Ray, W; Williams, B P; Qi, B; Smith, A M

2015-03-23

We present and demonstrate a novel protocol for distributing secret keys between two and only two parties based on N-party single-qubit Quantum Secret Sharing (QSS). We demonstrate our new protocol with N = 3 parties using phase-encoded photons. We show that any two out of N parties can build a secret key based on partial information from each other and with collaboration from the remaining N - 2 parties. Our implementation allows for an accessible transition between N-party QSS and arbitrary two party QKD without modification of hardware. In addition, our approach significantly reduces the number of resources such as single photon detectors, lasers and dark fiber connections needed to implement QKD.

Markov chain analysis of single spin flip Ising simulations

International Nuclear Information System (INIS)

Hennecke, M.

1997-01-01

The Markov processes defined by random and loop-based schemes for single spin flip attempts in Monte Carlo simulations of the 2D Ising model are investigated, by explicitly constructing their transition matrices. Their analysis reveals that loops over all lattice sites using a Metropolis-type single spin flip probability often do not define ergodic Markov chains, and have distorted dynamical properties even if they are ergodic. The transition matrices also enable a comparison of the dynamics of random versus loop spin selection and Glauber versus Metropolis probabilities

Structural and electronic properties of a single C chain doped zigzag BN nanoribbons

International Nuclear Information System (INIS)

Wu, Ping; Wang, Qianwen; Cao, Gengyu; Tang, Fuling; Huang, Min

2014-01-01

The effects of single C-chain on the stability, structural and electronic properties of zigzag BN nanoribbons (ZBNNRs) were investigated by first-principles calculations. C-chain was expected to dope at B-edge for all the ribbon widths N z considered. The band gaps of C-chain doped N z -ZBNNR are narrower than that of perfect ZBNNR due to new localized states induced by C-chain. The band gaps of N z -ZBNNR-C(n) are direct except for the case of C-chain position n=2. Band gaps of BN nanoribbons are tunable by C-chain and its position n, which may endow the potential applications of BNNR in electronics.

Well-defined single-chain polymer nanoparticles via thiol-Michael addition

NARCIS (Netherlands)

Kröger, A. Pia P.; Boonen, Roy J.E.A.; Paulusse, Jos M.J.

2017-01-01

A synthetic strategy has been developed giving facile access to well-defined single-chain polymer nanoparticles (SCNPs) from styrene-, acrylate- and methacrylate-based polymers. Random copolymers (polydispersity indices 1.10–1.15) of methyl (meth)acrylate, benzyl methacrylate or styrene containing

Single-chain statistics and the upper wave-vector cutoff in polymer blends

International Nuclear Information System (INIS)

Holyst, R.; Vilgis, T.A.

1994-01-01

We derive the equation for the single-chain correlation function in polymer blends. The chains in the incompressible blend have a radius of gyration smaller than the radius of gyration for ideal chains. The chains shrink progressively as we approach the critical temperature T c . The correction responsible for shrinking is proportional to 1/ √N , where N is the polymerization index. At T=T c and for N=1000, the size of the chain has been estimated to be 10% smaller than the size of the ideal coil. The estimate relies on the appropriate cutoff. In the limit of N→∞ the chains approach the random walk limit. Additionally, we propose in this paper a self-consistent determination of the radius of gyration and the upper wave-vector cutoff. Our model is free from any divergences such as were encountered in the previous mean-field studies; we make an estimate of the chain size at the true critical temperature and not the mean-field one

CHAINS-PC, Decay Chain Atomic Densities

International Nuclear Information System (INIS)

1994-01-01

1 - Description of program or function: CHAINS computes the atom density of members of a single radioactive decay chain. The linearity of the Bateman equations allows tracing of interconnecting chains by manually accumulating results from separate calculations of single chains. Re-entrant loops can be treated as extensions of a single chain. Losses from the chain are also tallied. 2 - Method of solution: The Bateman equations are solved analytically using double-precision arithmetic. Poles are avoided by small alterations of the loss terms. Multigroup fluxes, cross sections, and self-shielding factors entered as input are used to compute the effective specific reaction rates. The atom densities are computed at any specified times. 3 - Restrictions on the complexity of the problem: Maxima of 100 energy groups, 100 time values, 50 members in a chain

Molecular cloning and expression in mammalian cells of ricin B chain

International Nuclear Information System (INIS)

Chang, M.

1987-01-01

In these studies, the cDNA encoding the B chain of ricin has been cloned and expressed in monkey kidney COS-M6 cells. The recombinant B chain was detected by labeling the transfected cells with 35 S-methionine and 35 S-cysteine and demonstrating secretion of a protein with a Mr of 30-32,000 which was not present in the medium of mock-transfected COS-M6 cells. This protein was specifically immunoprecipitated by an anti-ricin or anti-B chain antibody. The amount of recombinant B chain secreted by the COS-M6 cells was determined by radioimmunoassay to be 1-10 ng/ml of media. Virtually all the recombinant B chain formed active ricin when mixed with native A chain; it could also bind as effectively as native B chain to the galactose-containing glycoprotein, asialofetuin. These results indicate that the vast majority of recombinant B chains secreted into the medium of the COS-M6 cells retain biological function

Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects

NARCIS (Netherlands)

Braat, E. A.; Levi, M. [=Marcel M.; Bos, R.; Haverkate, F.; Lassen, M. R.; de Maat, M. P.; Rijken, D. C.

1999-01-01

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence

Primitive-path statistics of entangled polymers: mapping multi-chain simulations onto single-chain mean-field models

International Nuclear Information System (INIS)

Steenbakkers, Rudi J A; Schieber, Jay D; Tzoumanekas, Christos; Li, Ying; Liu, Wing Kam; Kröger, Martin

2014-01-01

We present a method to map the full equilibrium distribution of the primitive-path (PP) length, obtained from multi-chain simulations of polymer melts, onto a single-chain mean-field ‘target’ model. Most previous works used the Doi–Edwards tube model as a target. However, the average number of monomers per PP segment, obtained from multi-chain PP networks, has consistently shown a discrepancy of a factor of two with respect to tube-model estimates. Part of the problem is that the tube model neglects fluctuations in the lengths of PP segments, the number of entanglements per chain and the distribution of monomers among PP segments, while all these fluctuations are observed in multi-chain simulations. Here we use a recently proposed slip-link model, which includes fluctuations in all these variables as well as in the spatial positions of the entanglements. This turns out to be essential to obtain qualitative and quantitative agreement with the equilibrium PP-length distribution obtained from multi-chain simulations. By fitting this distribution, we are able to determine two of the three parameters of the model, which govern its equilibrium properties. This mapping is executed for four different linear polymers and for different molecular weights. The two parameters are found to depend on chemistry, but not on molecular weight. The model predicts a constant plateau modulus minus a correction inversely proportional to molecular weight. The value for well-entangled chains, with the parameters determined ab initio, lies in the range of experimental data for the materials investigated. (paper)

Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels

Energy Technology Data Exchange (ETDEWEB)

Losa, M. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Magnani, P. [INB-CNR Department of Nuclear Medicine, IRCCS San Raffaele, University of Milan (Italy); Mortini, P. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Persani, L. [Centro Auxologico Italiano IRCCS, University of Milan (Italy); Acerno, S. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Giugni, E. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Songini, C. [INB-CNR Department of Nuclear Medicine, IRCCS San Raffaele, University of Milan (Italy); Fazio, F. [INB-CNR Department of Nuclear Medicine, IRCCS San Raffaele, University of Milan (Italy); Beck-Peccoz, P. [Institute of Endocrine Sciences, Istituto Clinico Humanitas, University of Milan (Italy); Giovanelli, M. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy)

1997-07-01

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of {sup 111}In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 {mu}g octreotide s.c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of {sup 111}In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of {sup 111}In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 {mu}g octreotide s.c. caused a significant reduction in TSH levels from 4.8{+-}1.4 mU/l to a nadir of 3.1{+-}1.1 mU/l after 6 h (P<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that {sup 111}In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance. (orig.). With 1 fig., 1 tab.

Contribution of single amino acid and codon substitutions to the production and secretion of a lipase by Bacillus subtilis.

Science.gov (United States)

Skoczinski, Pia; Volkenborn, Kristina; Fulton, Alexander; Bhadauriya, Anuseema; Nutschel, Christina; Gohlke, Holger; Knapp, Andreas; Jaeger, Karl-Erich

2017-09-25

Bacillus subtilis produces and secretes proteins in amounts of up to 20 g/l under optimal conditions. However, protein production can be challenging if transcription and cotranslational secretion are negatively affected, or the target protein is degraded by extracellular proteases. This study aims at elucidating the influence of a target protein on its own production by a systematic mutational analysis of the homologous B. subtilis model protein lipase A (LipA). We have covered the full natural diversity of single amino acid substitutions at 155 positions of LipA by site saturation mutagenesis excluding only highly conserved residues and qualitatively and quantitatively screened about 30,000 clones for extracellular LipA production. Identified variants with beneficial effects on production were sequenced and analyzed regarding B. subtilis growth behavior, extracellular lipase activity and amount as well as changes in lipase transcript levels. In total, 26 LipA variants were identified showing an up to twofold increase in either amount or activity of extracellular lipase. These variants harbor single amino acid or codon substitutions that did not substantially affect B. subtilis growth. Subsequent exemplary combination of beneficial single amino acid substitutions revealed an additive effect solely at the level of extracellular lipase amount; however, lipase amount and activity could not be increased simultaneously. Single amino acid and codon substitutions can affect LipA secretion and production by B. subtilis. Several codon-related effects were observed that either enhance lipA transcription or promote a more efficient folding of LipA. Single amino acid substitutions could improve LipA production by increasing its secretion or stability in the culture supernatant. Our findings indicate that optimization of the expression system is not sufficient for efficient protein production in B. subtilis. The sequence of the target protein should also be considered as an

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

OpenAIRE

Gracia R.; Marradi M.; Cossío U.; Benito A.; Pérez-San Vicente A.; Gómez-Vallejo V.; Grande H.-J.; Llop J.; and Loinaz I.

2017-01-01

Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and under mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demonstrating their potential use as imaging contrast agents.

Optimization of the crystallizability of a single-chain antibody fragment

Czech Academy of Sciences Publication Activity Database

Škerlová, Jana; Král, Vlastimil; Fábry, Milan; Sedláček, Juraj; Veverka, Václav; Řezáčová, Pavlína

2014-01-01

Roč. 70, č. 12 (2014), s. 1701-1706 ISSN 1744-3091 R&D Projects: GA MŠk(CZ) LK11205 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : single-chain antibody fragment * Thermofluor assay * differential scanning fluorimetry * crystallizability optimization * oligomerization * crystallization Subject RIV: CE - Biochemistry Impact factor: 0.527, year: 2014

Choice between Single and Multiple Reinforcers in Concurrent-Chains Schedules

Science.gov (United States)

Mazur, James E.

2006-01-01

Pigeons responded on concurrent-chains schedules with equal variable-interval schedules as initial links. One terminal link delivered a single reinforcer after a fixed delay, and the other terminal link delivered either three or five reinforcers, each preceded by a fixed delay. Some conditions included a postreinforcer delay after the single…

Stimulation of chymosin secretion by simultaneous expression with chymosin-binding llama single-domain antibody fragments in yeast

NARCIS (Netherlands)

Harmsen, M.M.; Smits, C.B.; Geus, de B.

2002-01-01

We studied the effect of coexpression of chymosin and chymosin-binding llama single-domain antibody fragments (VHHs) on the secretion of chymosin by Saccharomyces cerevisiae cells. A VHH expression library containing chymosin-specific VHHs was obtained by immunization of a llama and coexpressed with

Leg tendon glands in male bumblebees ( Bombus terrestris): structure, secretion chemistry, and possible functions

Science.gov (United States)

Jarau, Stefan; Žáček, Petr; Šobotník, Jan; Vrkoslav, Vladimír; Hadravová, Romana; Coppée, Audrey; Vašíčková, Soňa; Jiroš, Pavel; Valterová, Irena

2012-12-01

Among the large number of exocrine glands described in bees, the tarsal glands were thought to be the source of footprint scent marks. However, recent studies showed that the compounds used for marking by stingless bees are secreted by leg tendon instead of tarsal glands. Here, we report on the structure of leg tendon glands in males of Bombus terrestris, together with a description of the chemical composition of their secretions and respective changes of both during the males' lives. The ultrastructure of leg tendon glands shows that the secretory cells are located in three independent regions, separated from each other by unmodified epidermal cells: in the femur, tibia, and basitarsus. Due to the common site of secretion release, the organ is considered a single secretory gland. The secretion of the leg tendon glands of B. terrestris males differs in its composition from those of workers and queens, in particular by (1) having larger proportions of compounds with longer chain lengths, which we identified as wax esters; and (2) by the lack of certain hydrocarbons (especially long chain dienes). Other differences consist in the distribution of double bond positions in the unsaturated hydrocarbons that are predominantly located at position 9 in males but distributed at seven to nine different positions in the female castes. Double bond positions may change chemical and physical properties of a molecule, which can be recognized by the insects and, thus, may serve to convey specific information. The function of male-specific compounds identified from their tendon glands remains elusive, but several possibilities are discussed.

Strong-coupling behaviour of two t - J chains with interchain single-electron hopping

International Nuclear Information System (INIS)

Zhang Guangming; Feng Shiping; Yu Lu.

1994-01-01

Using the fermion-spin transformation to implement spin-charge separation of constrained electrons, a model of two t - J chains with interchain single-electron hopping is studied by abelian bosonization. After spin-charge decoupling the charge dynamics can be trivially solved, while the spin dynamics is determined by a strong-coupling fixed point where the correlation functions can be calculated explicitly. This is a generalization of the Luther-Emery line for two-coupled t - J chains. The interchain single-electron hopping changes the asymptotic behaviour of the interchain spin-spin correlation functions and the electron Green function, but their exponents are independent of the coupling strength. (author). 25 refs

Dynamical behavior of a single polymer chain under nanometric confinement

Science.gov (United States)

Lagrené, K.; Zanotti, J.-M.; Daoud, M.; Farago, B.; Judeinstein, P.

2010-10-01

We address the dynamical behavior of a single polymer chain under nanometric confinement. We consider a polymer melt made of a mixture of hydrogenated and deuterated high molecular mass Poly(Ethylene Oxide) (PEO). The confining material is a membrane of Anodic Aluminum Oxide (AAO), a macroscopically highly ordered confining system made of parallel cylindrical channels. We use Neutron Spin-Echo (NSE) under the Zero Average Contrast (ZAC) condition to, all at once, i) match the intense porous AAO detrimental elastic SANS (Small Angle Neutron Scattering) contribution to the total intermediate scattering function I(Q,t) and ii) measure the Q dependence of the dynamical modes of a single chain under confinement. The polymer dynamics is probed on an extremely broad spacial ([2.2 10-2 Å-1, 0.2 Å-1]) and temporal ([0.1 ns, 600 ns]) ranges. We do not detect any influence of confinement on the polymer dynamics. This result is discussed in the framework of the debate on the existence of a "corset effect" recently suggested by NMR relaxometry data.

Interfacial free energy governs single polystyrene chain collapse in water and aqueous solutions.

Science.gov (United States)

Li, Isaac T S; Walker, Gilbert C

2010-05-12

The hydrophobic interaction is significantly responsible for driving protein folding and self-assembly. To understand it, the thermodynamics, the role of water structure, the dewetting process surrounding hydrophobes, and related aspects have undergone extensive investigations. Here, we examine the hypothesis that polymer-solvent interfacial free energy is adequate to describe the energetics of the collapse of a hydrophobic homopolymer chain at fixed temperature, which serves as a much simplified model for studying the hydrophobic collapse of a protein. This implies that changes in polymer-solvent interfacial free energy should be directly proportional to the force to extend a collapsed polymer into a bad solvent. To test this hypothesis, we undertook single-molecule force spectroscopy on a collapsed, single, polystyrene chain in water-ethanol and water-salt mixtures where we measured the monomer solvation free energy from an ensemble average conformations. Different proportions within the binary mixture were used to create solvents with different interfacial free energies with polystyrene. In these mixed solvents, we observed a linear correlation between the interfacial free energy and the force required to extend the chain into solution, which is a direct measure of the solvation free energy per monomer on a single chain at room temperature. A simple analytical model compares favorably with the experimental results. This knowledge supports a common assumption that explicit water solvent may not be necessary for cases whose primary concerns are hydrophobic interactions and hydrophobic hydration.

Pricing and ordering policies for price-dependent demand in a supply chain of a single retailer and a single manufacturer

Science.gov (United States)

Kim, Jungkyu; Hong, Yushin; Kim, Taebok

2011-01-01

This article discusses joint pricing and ordering policies for price-dependent demand in a supply chain consisting of a single retailer and a single manufacturer. The retailer places orders for products according to an EOQ policy and the manufacturer produces them on a lot-for-lot basis. Four mechanisms with differing levels of coordination are presented. Mathematical models are formulated and solution procedures are developed to determine the optimal retail prices and order quantities. Through extensive numerical experiments, we analyse and compare the behaviours and characteristics of the proposed mechanisms, and find that enhancing the level of coordination has important benefits for the supply chain.

Enantiopure heterobimetallic single-chain magnets from the chiral Ru(III) building block.

Science.gov (United States)

Ru, Jing; Gao, Feng; Wu, Tao; Yao, Min-Xia; Li, Yi-Zhi; Zuo, Jing-Lin

2014-01-21

A pair of one-dimensional enantiomers based on the versatile chiral dicyanoruthenate(III) building block have been synthesized and they are chiral single-chain magnets with the effective spin-reversal barrier of 28.2 K.

Conformation of Single Pentablock Ionomer Chains in Dilute Solutions

Energy Technology Data Exchange (ETDEWEB)

Aryal, Dipak [Clemson Univ., SC (United States); Perahia, Dvora [Clemson Univ., SC (United States); Grest, Gary S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-04-01

The conformation of single chain pentablock ionomers (A-B-C-B-A) containing randomly sulfonated polystyrene in the center block, tethered to poly-ethylene-r-propylene end-capped by poly-t-butyl styrene is studied in dilute solutions by molecular dynamics simulations. Multi-block copolymers offer a means to tailor several properties into one molecule, taking advantage of their rich phase diagram together with unique properties of specific blocks. For this pentablock the ionic block facilitates transport while the A and B components are incorporated for mechanical stability. The present study investigates the confirmation of a single chain of pentablock ionomer of molecular weight M_w ~ 50,000 g/mol and sulfonated polystyrene of the same molecular weight as that of the center block for six sulfonation fractions f from f=0.0-0.55. For the sulfonated systems Na⁺ counterions are included. Results for the equilibrium conformation of the chains and the three blocks in water and 1:1 mixture of cyclohexane and n-heptane are compared to simulations in implicit poor solvents with dielectric constants ε =1.0 and 77.73. In water, the pentablock is collapsed with sulfonated groups on the outer surface. As the sulfonation fraction f increases, the ionic, center block is increasingly segregated from the hydrophobic regions. In the 1:1 mixture of cyclohexane and heptane both the flexible and end blocks are swollen while the center ionic block is collasped for f>0, while for f=0 all blocks are swollen. In both implicit poor solvents the pentablock is collapsed into a nearly spherical shape for all f. The sodium counterions are dispersed widely throughout the simulation cell for both water and ε =77.73 whereas for ε =1.0 the counterions are largely condensed on the collapsed pentablock.

From single magnetic adatoms on superconductors to coupled spin chains

Science.gov (United States)

Franke, Katharina J.

Magnetic adsorbates on conventional s-wave superconductors lead to exchange interactions that induce Yu-Shiba-Rusinov (YSR) states inside the superconducting energy gap. Here, we employ tunneling spectroscopy at 1.1 K to investigate magnetic atoms and chains on superconducting Pb surfaces. We show that individual Manganese (Mn) atoms give rise to a distinct number of YSR-states. The single-atom junctions are stable over several orders of magnitude in conductance. We identify single-electron tunneling as well as Andreev processes. When the atoms are brought into sufficiently close distance, the Shiba states hybridize, thus giving rise to states with bonding and anti-bonding character. It has been shown that the Pb(110) surface supports the self-assembly of Fe chains, which exhibit fingerprints of Majorana bound states. Using superconducting tips, we resolve a rich subgap structure including peaks at zero energy and low-energy resonances, which overlap with the putative Majorana states. We gratefully acknowledge funding by the Deutsche Forschungsgemeinschaft through collaborative research Grant Sfb 658, and through Grant FR2726/4, as well by the European Research Council through Consolidator Grant NanoSpin.

A Unifying Organ Model of Pancreatic Insulin Secretion.

Directory of Open Access Journals (Sweden)

Andrea De Gaetano

Full Text Available The secretion of insulin by the pancreas has been the object of much attention over the past several decades. Insulin is known to be secreted by pancreatic β-cells in response to hyperglycemia: its blood concentrations however exhibit both high-frequency (period approx. 10 minutes and low-frequency oscillations (period approx. 1.5 hours. Furthermore, characteristic insulin secretory response to challenge maneuvers have been described, such as frequency entrainment upon sinusoidal glycemic stimulation; substantial insulin peaks following minimal glucose administration; progressively strengthened insulin secretion response after repeated administration of the same amount of glucose; insulin and glucose characteristic curves after Intra-Venous administration of glucose boli in healthy and pre-diabetic subjects as well as in Type 2 Diabetes Mellitus. Previous modeling of β-cell physiology has been mainly directed to the intracellular chain of events giving rise to single-cell or cell-cluster hormone release oscillations, but the large size, long period and complex morphology of the diverse responses to whole-body glucose stimuli has not yet been coherently explained. Starting with the seminal work of Grodsky it was hypothesized that the population of pancreatic β-cells, possibly functionally aggregated in islets of Langerhans, could be viewed as a set of independent, similar, but not identical controllers (firing units with distributed functional parameters. The present work shows how a single model based on a population of independent islet controllers can reproduce very closely a diverse array of actually observed experimental results, with the same set of working parameters. The model's success in reproducing a diverse array of experiments implies that, in order to understand the macroscopic behaviour of the endocrine pancreas in regulating glycemia, there is no need to hypothesize intrapancreatic pacemakers, influences between different

Analysis of the paired TCR α- and β-chains of single human T cells.

Directory of Open Access Journals (Sweden)

Song-Min Kim

Full Text Available Analysis of the paired i.e. matching TCR α- and β-chain rearrangements of single human T cells is required for a precise investigation of clonal diversity, tissue distribution and specificity of protective and pathologic T-cell mediated immune responses. Here we describe a multiplex RT-PCR based technology, which for the first time allows for an unbiased analysis of the complete sequences of both α- and β-chains of TCR from single T cells. We validated our technology by the analysis of the pathologic T-cell infiltrates from tissue lesions of two T-cell mediated autoimmune diseases, psoriasis vulgaris (PV and multiple sclerosis (MS. In both disorders we could detect various T cell clones as defined by multiple T cells with identical α- and β-chain rearrangements distributed across the tissue lesions. In PV, single cell TCR analysis of lesional T cells identified clonal CD8(+ T cell expansions that predominated in the epidermis of psoriatic plaques. An MS brain lesion contained two dominant CD8(+ T-cell clones that extended over the white and grey matter and meninges. In both diseases several clonally expanded T cells carried dual TCRs composed of one Vβ and two different Vα-chain rearrangements. These results show that our technology is an efficient instrument to analyse αβ-T cell responses with single cell resolution in man. It should facilitate essential new insights into the mechanisms of protective and pathologic immunity in many human T-cell mediated conditions and allow for resurrecting functional TCRs from any αβ-T cell of choice that can be used for investigating their specificity.

Optical Properties of a Single Carbon Chain-Doped Silicene Nanoribbon

Science.gov (United States)

Lu, Dao-Bang; Song, Yu-Ling; Huang, Xiao-yu; Wang, Chong

2018-05-01

Using first-principles spin polarization density function theory calculations, we have studied the electronic and optical properties of zigzag-edge silicene nanoribbons (ZSiNRs) doped with a single carbon chain. Because of the doped carbon chain, there are several defect states in the band structures of ZSiNRs across the Fermi level, and the ferromagnetic ground state is metallic. The dielectric functions in all three dimensions are completely different from each other, and thus the system exhibits strong optical anisotropism. The carbon chain influenced the dielectric functions most at low energy. The first peak in the E//x direction of the dielectric spectrum exhibits a significant blueshift, and its value has changed as well. The main absorption wavelength depends on the polarization direction of the incident light, but occurs within the UV region for all polarization directions. The peaks of the energy loss spectra correspond to the trailing edges in the reflectivity spectrum, and the highest peak corresponds to a plasmon frequency. Our results could be useful for investigating nanodevices based on silicene nanoribbons.

Sagnac secret sharing over telecom fiber networks.

Science.gov (United States)

Bogdanski, Jan; Ahrens, Johan; Bourennane, Mohamed

2009-01-19

We report the first Sagnac quantum secret sharing (in three-and four-party implementations) over 1550 nm single mode fiber (SMF) networks, using a single qubit protocol with phase encoding. Our secret sharing experiment has been based on a single qubit protocol, which has opened the door to practical secret sharing implementation over fiber telecom channels and in free-space. The previous quantum secret sharing proposals were based on multiparticle entangled states, difficult in the practical implementation and not scalable. Our experimental data in the three-party implementation show stable (in regards to birefringence drift) quantum secret sharing transmissions at the total Sagnac transmission loop distances of 55-75 km with the quantum bit error rates (QBER) of 2.3-2.4% for the mean photon number micro?= 0.1 and 1.7-2.1% for micro= 0.3. In the four-party case we have achieved quantum secret sharing transmissions at the total Sagnac transmission loop distances of 45-55 km with the quantum bit error rates (QBER) of 3.0-3.7% for the mean photon number micro= 0.1 and 1.8-3.0% for micro?= 0.3. The stability of quantum transmission has been achieved thanks to our new concept for compensation of SMF birefringence effects in Sagnac, based on a polarization control system and a polarization insensitive phase modulator. The measurement results have showed feasibility of quantum secret sharing over telecom fiber networks in Sagnac configuration, using standard fiber telecom components.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

Science.gov (United States)

Murphy, P A; Cebula, T A; Windle, B E

1981-10-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of all the forms of endogenous pyrogen. When cells were stimulated in the presence of 3H-labeled amino acids and 14C-labeled glucosamine or glucose, the purified pyrogens were labeled with 3H but not with 14C. Macrophage membrane preparations were made which contained glycosyl transferases and could transfer sugar residues from sugar nucleotides to deglycosylated fetuin. These macrophage membrane preparations did not transfer sugars to the pI 7.3 endogenous pyrogen. Treatment of endogenous pyrogens with neuraminidase or with periodate produced no evidence suggesting that the pyrogens were glycosylated. Last, endogenous pyrogens did not bind to any of four lectins with different carbohydrate specificities. This evidence suggests that the heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylation and must have some other cause.

Spin canting in a Dy-based single-chain magnet with dominant next-nearest-neighbor antiferromagnetic interactions

Science.gov (United States)

Bernot, K.; Luzon, J.; Caneschi, A.; Gatteschi, D.; Sessoli, R.; Bogani, L.; Vindigni, A.; Rettori, A.; Pini, M. G.

2009-04-01

We investigate theoretically and experimentally the static magnetic properties of single crystals of the molecular-based single-chain magnet of formula [Dy(hfac)3NIT(C6H4OPh)]∞ comprising alternating Dy3+ and organic radicals. The magnetic molar susceptibility χM displays a strong angular variation for sample rotations around two directions perpendicular to the chain axis. A peculiar inversion between maxima and minima in the angular dependence of χM occurs on increasing temperature. Using information regarding the monomeric building block as well as an ab initio estimation of the magnetic anisotropy of the Dy3+ ion, this “anisotropy-inversion” phenomenon can be assigned to weak one-dimensional ferromagnetism along the chain axis. This indicates that antiferromagnetic next-nearest-neighbor interactions between Dy3+ ions dominate, despite the large Dy-Dy separation, over the nearest-neighbor interactions between the radicals and the Dy3+ ions. Measurements of the field dependence of the magnetization, both along and perpendicularly to the chain, and of the angular dependence of χM in a strong magnetic field confirm such an interpretation. Transfer-matrix simulations of the experimental measurements are performed using a classical one-dimensional spin model with antiferromagnetic Heisenberg exchange interaction and noncollinear uniaxial single-ion anisotropies favoring a canted antiferromagnetic spin arrangement, with a net magnetic moment along the chain axis. The fine agreement obtained with experimental data provides estimates of the Hamiltonian parameters, essential for further study of the dynamics of rare-earth-based molecular chains.

Alternative types of molecule-decorated atomic chains in Au–CO–Au single-molecule junctions

Directory of Open Access Journals (Sweden)

Zoltán Balogh

2015-06-01

Full Text Available We investigate the formation and evolution of Au–CO single-molecule break junctions. The conductance histogram exhibits two distinct molecular configurations, which are further investigated by a combined statistical analysis. According to conditional histogram and correlation analysis these molecular configurations show strong anticorrelations with each other and with pure Au monoatomic junctions and atomic chains. We identify molecular precursor configurations with somewhat higher conductance, which are formed prior to single-molecule junctions. According to detailed length analysis two distinct types of molecule-affected chain-formation processes are observed, and we compare these results to former theoretical calculations considering bridge- and atop-type molecular configurations where the latter has reduced conductance due to destructive Fano interference.

Nutritional Ingredients Modulate Adipokine Secretion and Inflammation in Human Primary Adipocytes

Science.gov (United States)

Romacho, Tania; Glosse, Philipp; Richter, Isabel; Elsen, Manuela; Schoemaker, Marieke H.; van Tol, Eric A.; Eckel, Jürgen

2015-01-01

Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH) and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH) release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA), and long-chain polyunsaturated fatty acids (LC-PUFAs) on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA). Intracellular adiponectin expression and nuclear factor-κB (NF-κB) activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1) release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH’s effects on adiponectin secretion. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and DHA combined with arachidonic acid (ARA) upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α) induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes. PMID:25629558

Nutritional Ingredients Modulate Adipokine Secretion and Inflammation in Human Primary Adipocytes

Directory of Open Access Journals (Sweden)

Tania Romacho

2015-01-01

Full Text Available Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA, and long-chain polyunsaturated fatty acids (LC-PUFAs on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA. Intracellular adiponectin expression and nuclear factor-κB (NF-κB activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1 release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH’s effects on adiponectin secretion. Eicosapentaenoic acid (EPA, docosahexaenoic acid (DHA, and DHA combined with arachidonic acid (ARA upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes.

Jet and ultrasonic nebulization of single chain urokinase plasminogen activator (scu-PA)

DEFF Research Database (Denmark)

Münster, Anna-Marie; Bendstrup, E; Jensen, J.I.

2000-01-01

locally by nebulization in a recombinant zymogen form as single chain urokinase plasminogen activator (scu-PA). We aimed to characterize the particle size distribution, drug output, and enzymatic activity of scu-PA after nebulization with a Ventstream jet nebulizer (Medic-Aid, Bognor Regis, UK) and a Syst...

Finite-size effects on the static properties of a single-chain magnet

Science.gov (United States)

Bogani, L.; Sessoli, R.; Pini, M. G.; Rettori, A.; Novak, M. A.; Rosa, P.; Massi, M.; Fedi, M. E.; Giuntini, L.; Caneschi, A.; Gatteschi, D.

2005-08-01

We study the role of defects in the “single-chain magnet” CoPhOMe by inserting a controlled number of diamagnetic impurities. The samples are analyzed with unprecedented accuracy with the particle induced x-ray emission technique, and with ac and dc magnetic measurements. In an external applied field the system shows an unexpected behavior, giving rise to a double peak in the susceptibility. The static thermodynamic properties of the randomly diluted Ising chain with alternating g values are then exactly obtained via a transfer matrix approach. These results are compared to the experimental behavior of CoPhOMe, showing qualitative agreement.

From single Debye-Hückel chains to polyelectrolyte solutions: Simulation results

Science.gov (United States)

Kremer, Kurt

1996-03-01

This lecture will present results from simulations of single weakly charged flexible chains, where the electrostatic part of the interaction is modeled by a Debye-Hückel potential,( with U. Micka, IFF, Forschungszentrum Jülich, 52425 Jülich, Germany) as well as simulations of polyelectrolyte solutions, where the counterions are explicitly taken into account( with M. J. Stevens, Sandia Nat. Lab., Albuquerque, NM 87185-1111) ( M. J. Stevens, K. Kremer, JCP 103), 1669 (1995). The first set of the simulations is meant to clear a recent contoversy on the dependency of the persistence length LP on the screening length Γ. While the analytic theories give Lp ~ Γ^x with either x=1 or x=2, the simulations find for all experimentally accessible chain lengths a varying exponent, which is significantly smaller than 1. This causes serious doubts on the applicability of this model for weakly charged polyelectrolytes in general. The second part deals with strongly charged flexible polyelectrolytes in salt free solution. These simulations are performed for multichain systems. The full Coulomb interactions of the monomers and counterions are treated explicitly. Experimental measurements of the osmotic pressure and the structure factor are reproduced and extended. The simulations reveal a new picture of the chain structure based on calculations of the structure factor, persistence length, end-to-end distance, etc. Even at very low density, the chains show significant bending. Furthermore, the chains contract significantly before they start to overlap. We also show that counterion condensation dramatically alters the chain structure, even for a good solvent backbone.

Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity

DEFF Research Database (Denmark)

Barington, T; Juul, Lars; Gyhrs, A

1994-01-01

The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or D...... of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed....

Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate

Directory of Open Access Journals (Sweden)

Ju-Ri Sim

2018-01-01

Full Text Available Short-chain fatty acids (SCFAs, such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP. Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

Conductance of single microRNAs chains related to the autism spectrum disorder

Science.gov (United States)

Oliveira, J. I. N.; Albuquerque, E. L.; Fulco, U. L.; Mauriz, P. W.; Sarmento, R. G.; Caetano, E. W. S.; Freire, V. N.

2014-09-01

The charge transport properties of single-stranded microRNAs (miRNAs) chains associated to autism disorder were investigated. The computations were performed within a tight-binding model, together with a transfer matrix technique, with ionization energies and hopping parameters obtained by quantum chemistry method. Current-voltage (I× V) curves of twelve miRNA chains related to the autism spectrum disorders were calculated and analysed. We have obtained both semiconductor and insulator behavior, and a relationship between the current intensity and the autism-related miRNA bases sequencies, suggesting that a kind of electronic biosensor can be developed to distinguish different profiles of autism disorders.

Creation of Single Chain of Nanoscale Skyrmion Bubbles with Record-high Temperature Stability in a Geometrically Confined Nanostripe

KAUST Repository

Hou, Zhipeng; Zhang, Qiang; Xu, Guizhou; Gong, Chen; Ding, Bei; Wang, Yue; Li, Hang; Liu, Enke; Xu, Feng; Zhang, Hongwei; Yao, Yuan; Wu, Guangheng; Zhang, Xixiang; Wang, Wenhong

2018-01-01

Nanoscale topologically nontrivial spin textures, such as magnetic skyrmions, have been identified as promising candidates for the transport and storage of information for spintronic applications, notably magnetic racetrack memory devices. The design and realization of a single skyrmion chain at room temperature (RT) and above in the low-dimensional nanostructures are of great importance for future practical applications. Here, we report the creation of a single skyrmion bubble chain in a geometrically confined Fe3Sn2 nanostripe with a width comparable to the featured size of a skyrmion bubble. Systematic investigations on the thermal stability have revealed that the single chain of skyrmion bubbles can keep stable at temperatures varying from RT up to a record-high temperature of 630 K. This extreme stability can be ascribed to the weak temperature-dependent magnetic anisotropy and the formation of edge states at the boundaries of the nanostripes. The realization of the highly stable skyrmion bubble chain in a geometrically confined nanostructure is a very important step toward the application of skyrmion-based spintronic devices.

Creation of Single Chain of Nanoscale Skyrmion Bubbles with Record-high Temperature Stability in a Geometrically Confined Nanostripe

KAUST Repository

Hou, Zhipeng

2018-01-04

Nanoscale topologically nontrivial spin textures, such as magnetic skyrmions, have been identified as promising candidates for the transport and storage of information for spintronic applications, notably magnetic racetrack memory devices. The design and realization of a single skyrmion chain at room temperature (RT) and above in the low-dimensional nanostructures are of great importance for future practical applications. Here, we report the creation of a single skyrmion bubble chain in a geometrically confined Fe3Sn2 nanostripe with a width comparable to the featured size of a skyrmion bubble. Systematic investigations on the thermal stability have revealed that the single chain of skyrmion bubbles can keep stable at temperatures varying from RT up to a record-high temperature of 630 K. This extreme stability can be ascribed to the weak temperature-dependent magnetic anisotropy and the formation of edge states at the boundaries of the nanostripes. The realization of the highly stable skyrmion bubble chain in a geometrically confined nanostructure is a very important step toward the application of skyrmion-based spintronic devices.

Single-chain vascular endothelial growth factor variant with antagonist activity

DEFF Research Database (Denmark)

Boesen, Thomas P; Soni, Bobby; Schwartz, Thue W

2002-01-01

receptor molecules and inducing dimerization. By mixing two vascular endothelial growth factor monomers, each with different substitutions, heterodimers with only one active receptor binding site have previously been prepared. These heterodimers bind the receptor molecule but are unable to induce...... dimerization and activation. However, preparation of heterodimers is cumbersome, involving separate expression of different monomers, refolding the mixture, and separating heterodimers from homodimers. Here we show that a fully functional ligand can efficiently be expressed as a single protein chain containing...

The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

International Nuclear Information System (INIS)

Wittel, Uwe A.; Jain, Maneesh; Goel, Apollina; Chauhan, Subhash C.; Colcher, David; Batra, Surinder K.

2005-01-01

Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(Fv) 2 ], noncovalent tetrameric scFv {[sc(Fv) 2 ] 2 } and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(Fv) 2 and [sc(Fv) 2 ] 2 are stable in vivo and have significant potential for diagnostic and therapeutic applications

Surface water retardation around single-chain polymeric nanoparticles: critical for catalytic function?

Science.gov (United States)

Stals, Patrick J M; Cheng, Chi-Yuan; van Beek, Lotte; Wauters, Annelies C; Palmans, Anja R A; Han, Songi; Meijer, E W

2016-03-01

A library of water-soluble dynamic single-chain polymeric nanoparticles (SCPN) was prepared using a controlled radical polymerisation technique followed by the introduction of functional groups, including probes at targeted positions. The combined tools of electron paramagnetic resonance (EPR) and Overhauser dynamic nuclear polarization (ODNP) reveal that these SCPNs have structural and surface hydration properties resembling that of enzymes.

Experimental studies of the dynamic mechanical response of a single polymer chain

DEFF Research Database (Denmark)

Thormann, Esben; Evans, Drew R.; Craig, Vincent S. J.

2006-01-01

The high-frequency and low-amplitude dynamic mechanical response from a single poly(vinyl alcohol) chain was investigated. Modification of a commercial atomic force microscope enabled high-frequency and low-amplitude periodic deformations of polymer chains during extension to be performed...... mechanical response from poly(vinyl alcohol) does not differ from its static response. This result is not unexpected as poly(vinyl alcohol) is a highly flexible polymer with intramolecular relaxation processes taking place on a short time scale. The choice of a polymer with a fast relaxation allows its...... static properties to be recovered from the dynamic measurements and enables the method suggested in this paper for decoupling the polymer response from the hydrodynamic response to be validated....

Noncoordinate expression of J-chain and Blimp-1 define nurse shark plasma cell populations during ontogeny.

Science.gov (United States)

Castro, Caitlin D; Ohta, Yuko; Dooley, Helen; Flajnik, Martin F

2013-11-01

B-lymphocyte-induced maturation protein 1 (Blimp-1) is the master regulator of plasma cell development, controlling genes such as those encoding J-chain and secretory Ig heavy chain. However, some mammalian plasma cells do not express J-chain, and mammalian B1 cells secrete "natural" IgM antibodies without upregulating Blimp-1. While these results have been controversial in mammalian systems, here we describe subsets of normally occurring Blimp-1(-) antibody-secreting cells in nurse sharks, found in lymphoid tissues at all ontogenic stages. Sharks naturally produce large amounts of both pentameric (classically "19S") and monomeric (classically "7S") IgM, the latter an indicator of adaptive immunity. Consistent with the mammalian paradigm, shark Blimp-1 is expressed in splenic 7S IgM-secreting cells, though rarely detected in the J-chain(+) cells producing 19S IgM. Although IgM transcript levels are lower in J-chain(+) cells, these cells nevertheless secrete 19S IgM in the absence of Blimp-1, as demonstrated by ELISPOT and metabolic labeling. Additionally, cells in the shark BM equivalent (epigonal) are Blimp-1(-). Our data suggest that, in sharks, 19S-secreting cells and other secreting memory B cells in the epigonal are maintained for long periods without Blimp-1, but like in mammals, Blimp-1 is required for terminating the B-cell program following an adaptive immune response in the spleen. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes

Science.gov (United States)

Raithel, Dominic; Simine, Lena; Pickel, Sebastian; Schötz, Konstantin; Panzer, Fabian; Baderschneider, Sebastian; Schiefer, Daniel; Lohwasser, Ruth; Köhler, Jürgen; Thelakkat, Mukundan; Sommer, Michael; Köhler, Anna; Rossky, Peter J.; Hildner, Richard

2018-03-01

The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (˜2,000 cm‑1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron‑hole polarization.

Acetate stimulates secretion in the rabbit mandibular gland

DEFF Research Database (Denmark)

Novak, I; Young, J A

1989-01-01

In isolated perfused rabbit mandibular glands undergoing stimulation with 0.8 microM acetylcholine, replacement of HCO3- with acetate (25 mM) increased fluid secretion by more than 100%. Other short-chain fatty acids, except for propionate, had a similar effect. We focused our further studies...

Non-coordinate expression of J-chain and Blimp-1 define nurse shark plasma cell populations during ontogeny

Science.gov (United States)

Castro, Caitlin D.; Ohta, Yuko; Dooley, Helen; Flajnik, Martin F.

2014-01-01

Summary Blimp-1 is the master regulator of plasma cell development, controlling genes such as J-chain and secretory Ig heavy chain. However, some mammalian plasma cells do not express J-chain, and mammalian B1 cells secrete “natural” IgM antibodies without upregulating Blimp-1. While these results have been controversial in mammalian systems, here we describe subsets of normally occurring Blimp-1- antibody secreting cells in nurse sharks, found in lymphoid tissues at all ontogenic stages. Sharks naturally produce large amounts of both pentameric (classically ‘19S’) and monomeric (classically ‘7S’) IgM, the latter an indicator of adaptive immunity. Consistent with the mammalian paradigm, shark Blimp-1 is expressed in splenic 7S IgM-secreting cells, though rarely detected in the J-chain+ cells producing 19S IgM. Although IgM transcript levels are lower in J-chain+ cells, these cells nevertheless secrete 19S IgM in the absence of Blimp-1, as demonstrated by ELISPOT and metabolic labeling. Additionally, cells in the shark bone marrow equivalent (epigonal) are Blimp-1-. Our data suggest that, in sharks, 19S-secreting cells and other secreting memory B cells in the epigonal can be maintained for long periods without Blimp-1, but like in mammals, Blimp-1 is required for terminating the B cell program following an adaptive immune response in the spleen. PMID:23897025

Single step, pH induced gold nanoparticle chain formation in lecithin/water system.

Science.gov (United States)

Sharma, Damyanti

2013-07-01

Gold nanoparticle (AuNP) chains have been formed by a single step method in a lecithin/water system where lecithin itself plays the role of a reductant and a template for AuNP chain formation. Two preparative strategies were explored: (1) evaporating lecithin solution with aqueous gold chloride (HAuCl4) at different pHs and (2) dispersing lecithin vesicles in aqueous HAuCl4 solutions of various pHs in the range of 2.5-11.3. In method 1, at initial pH 2.5, 20-50 nm AuNPs are found attached to lecithin vesicles. When pH is raised to 5.5 there are no vesicles present and 20 nm monodisperse particles are found aggregating. Chain formation of fine nanoparticles (3-5 nm) is observed from neutral to basic pH, between 6.5-10.3 The chains formed are hundreds of nanometers to micrometer long and are usually 2-3 nanoparticles wide. On further increasing pH to 11.3, particles form disk-like or raft-like structures. When method (ii) was used a little chain formation was observed. Most of the nanoparticles formed were found either sitting together as raft like structures or scattered on lecithin structures. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhanced detection of single-cell-secreted proteins using a fluorescent immunoassay on the protein-G-terminated glass substrate

Directory of Open Access Journals (Sweden)

Jeong Y

2015-11-01

Full Text Available Yoon Jeong,1,2 Kwan Hong Lee,1,2 Hansoo Park,3 Jonghoon Choi1,2 1Department of Bionano Technology, Graduate School, Hanyang University, Seoul, 2Department of Bionano Engineering, Hanyang University ERICA, Ansan, 3School of Integrative Engineering, Chung-Ang University, Seoul, South Korea Abstract: We present an evaluation of protein-G-terminated glass slides that may contain a suitable substrate for aligning the orientation of antibodies to obtain better binding moiety to the target antigen. The results of the protein-G-terminated slides were compared with those obtained with epoxy-based slides to evaluate signal enhancement for human immunoglobulin G (IgG targets, and an increase in the average fluorescence intensity was observed for the lowest measurable amount of IgG target in the assay using protein-G-terminated slides. Applying this strategy for signal amplification to single-cell assays improves the limits of detection for human IgG protein and cytokines (interleukin-2 and interferon-γ captured from hybridomas. Our data indicate that protein-G-terminated slides have a higher binding capacity for antigens and have better spot-to-spot consistency than that of traditional epoxy-based slides. These properties would be beneficial in the detection of fine amounts of single-cell-secreted proteins, which may provide key insights into cell–cell communication and immune responses. Keywords: microwell array, antibody’s orientation, single cell analysis, secreted cytokine, protein-G-terminated surface

Regulated Mucin Secretion from Airway Epithelial Cells

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Kenneth Bruce Adler

2013-09-01

Full Text Available Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3x10^6 D per monomer whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ~1 um in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among MARCKS, cysteine string protein (CSP, HSP70 and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG. Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to phospholipase C by Gq, resulting in the

Kinetic analysis of a monoclonal therapeutic antibody and its single-chain homolog by surface plasmon resonance.

Science.gov (United States)

Patel, Rekha; Andrien, Bruce A

2010-01-01

Monoclonal antibodies (mAbs) and antibody fragments have become an emerging class of therapeutics since 1986. Their versatility enables them to be engineered for optimal efficiency and decreased immunogenicity, and the path to market has been set by recent regulatory approvals. One of the initial criteria for success of any protein or antibody therapeutic is to understand its binding characteristics to the target antigen. Surface plasmon resonance (SPR) has been widely used and is an important tool for ligand-antigen binding characterization. In this work, the binding kinetics of a recombinant mAb and its single-chain antibody homolog, single-chain variable fragment (scFv), was analyzed by SPR. These two proteins target the same antigen. The binding kinetics of the mAb (bivalent antibody) and scFv (monovalent scFv) for this antigen was analyzed along with an assessment of the thermodynamics of the binding interactions. Alternative binding configurations were investigated to evaluate potential experimental bias because theoretically experimental binding configuration should have no impact on binding kinetics. Self-association binding kinetics in the proteins' respective formulation solutions and antigen epitope mapping were also evaluated. Functional characterization of monoclonal and single-chain antibodies has become just as important as structural characterization in the biotechnology field.

Efficient sampling of reversible cross-linking polymers: Self-assembly of single-chain polymeric nanoparticles

Science.gov (United States)

Oyarzún, Bernardo; Mognetti, Bortolo Matteo

2018-03-01

We present a new simulation technique to study systems of polymers functionalized by reactive sites that bind/unbind forming reversible linkages. Functionalized polymers feature self-assembly and responsive properties that are unmatched by the systems lacking selective interactions. The scales at which the functional properties of these materials emerge are difficult to model, especially in the reversible regime where such properties result from many binding/unbinding events. This difficulty is related to large entropic barriers associated with the formation of intra-molecular loops. In this work, we present a simulation scheme that sidesteps configurational costs by dedicated Monte Carlo moves capable of binding/unbinding reactive sites in a single step. Cross-linking reactions are implemented by trial moves that reconstruct chain sections attempting, at the same time, a dimerization reaction between pairs of reactive sites. The model is parametrized by the reaction equilibrium constant of the reactive species free in solution. This quantity can be obtained by means of experiments or atomistic/quantum simulations. We use the proposed methodology to study the self-assembly of single-chain polymeric nanoparticles, starting from flexible precursors carrying regularly or randomly distributed reactive sites. We focus on understanding differences in the morphology of chain nanoparticles when linkages are reversible as compared to the well-studied case of irreversible reactions. Intriguingly, we find that the size of regularly functionalized chains, in good solvent conditions, is non-monotonous as a function of the degree of functionalization. We clarify how this result follows from excluded volume interactions and is peculiar of reversible linkages and regular functionalizations.

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

Science.gov (United States)

di Maso, N. A.; Caiozzo, V. J.; Baldwin, K. M.

2000-01-01

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

Construction and Self-Assembly of Single-Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water.

Science.gov (United States)

Zhu, Zhengguang; Xu, Na; Yu, Qiuping; Guo, Lei; Cao, Hui; Lu, Xinhua; Cai, Yuanli

2015-08-01

Simultaneous coordination-association and electrostatic-repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self-assembly of artificial aqueous polymer single-chain nanoparticles (SCNPs). Herein, the construction and self-assembly of dative-bonded aqueous SCNPs are reported via simultaneous coordination-association and electrostatic-repulsion interactions within single chains of histamine-based hydrophilic block copolymer. The electrostatic-repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II)-coordination leads to the intramolecular association and single-chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative-bonded block and steric shielding of nonionic water-soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media-sensitive phase-transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme-inspired smart aqueous catalysts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mediating Dynamic Supply Chain Formation by Collaborative Single Machine Earliness/Tardiness Agents in Supply Mesh

Directory of Open Access Journals (Sweden)

Hang Yang

2014-01-01

Full Text Available Nowadays, a trend of forming dynamic supply chains with different trading partners over different e-marketplaces has emerged. These supply chains, which are called “supply mesh,” generally refer to heterogeneous electronic marketplaces in which dynamic supply chains, as per project (often make-to-order, are formed across different parties. Conceptually, in a supply mesh a dynamic supply chain is formed vertically, mediating several companies for a project. Companies that are on the same level horizontally are either competitors or cohorts. A complex scenario such as this makes it challenging to find the right group of members for a dynamic supply chain. Earlier on, a multiagent model called the collaborative single machine earliness/tardiness (CSET model was proposed for the optimal formation of make-to-order supply chains. This paper contributes the particular agent designs, for enabling the mediation of CSET in a supply mesh, and the possibilities are discussed. It is demonstrated via a computer simulation, based on samples from the U.S. textile industry, that by using intelligent agents under the CSET model it is possible to automatically find an ideal group of trading partners from a supply mesh.

Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction.

Science.gov (United States)

Abdeldaim, Guma M K; Strålin, Kristoffer; Kirsebom, Leif A; Olcén, Per; Blomberg, Jonas; Herrmann, Björn

2009-08-01

A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 10(4) DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.

Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia.

Science.gov (United States)

Abdeldaim, Guma M K; Strålin, Kristoffer; Olcén, Per; Blomberg, Jonas; Mölling, Paula; Herrmann, Björn

2013-06-01

A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions. Copyright © 2013 Elsevier Inc. All rights reserved.

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

International Nuclear Information System (INIS)

Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

2015-01-01

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm 2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

2015-08-14

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen

International Nuclear Information System (INIS)

Collier, I.E.; Wilhelm, S.M.; Eisen, A.Z.

1988-01-01

H-ras transformed human bronchial epithelial cells (TBE-1) secrete a single major extracellular matrix metalloprotease which is not found in the normal parental cells. The enzyme is secreted in a latent form which can be activated to catalyze the cleavage of the basement membrane macromolecule type IV collagen. The substrates in their order of preference are: gelatin, type IV collagen, type V collagen, fibronectin, and type VII collagen; but the enzyme does not cleave the interstitial collagens or laminin. This protease is identical to gelatinase isolated from normal human skin explants, normal human skin fibroblasts, and SV40-transformed human lung fibroblasts. Based on this ability to initiate the degradation of type IV collagen in a pepsin-resistant portion of the molecule, it will be referred to as type IV collagenase. This enzyme is most likely the human analog of type IV collagenase detected in several rodent tumors. Type IV collagenase consists of three domains. Type IV collagenase represents the third member of a newly recognized gene family coding for secreted extracellular matrix metalloproteases, which includes interstitial fibroblast collagenase and stromelysin

First-order reversal curves of single domain particles: diluted random assemblages and chains

Science.gov (United States)

Egli, R.

2009-04-01

Exact magnetic models can be used to calculate first-order reversal curves (FORC) of single domain (SD) particle assemblages, as shown by Newell [2005] for the case of isolated Stoner-Wohlfarth particles. After overcoming experimental difficulties, a FORC diagram sharing many similarities to Newell's model has been measured on a lake sediment sample (see A.P. Chen et al., "Quantification of magnetofossils using first-order reversal curves", EGU General Assembly 2009, Abstracts Vol. 11, EGU2009-10719). This sample contains abundant magnetofossils, as shown by coercivity analysis and electron microscopy, therefore suggesting that well dispersed, intact magnetosome chains are the main SD carriers. Subtle differences between the reversible and the irreversible contributions of the measured FORC distribution suggest that magnetosome chains might not be correctly described by the Stoner-Wohlfarth model. To better understand the hysteresis properties of such chains, a simple magnetic model has been implemented, taking dipole-dipole interactions between particles within the same chain into account. The model results depend on the magnetosome elongation, the number of magnetosomes in a chain, and the gap between them. If the chain axis is subparallel to the applied field, the magnetic moment reverses by a pseudo-fanning mode, which is replaced by a pseudo-coherent rotation mode at greater angles. These reversal modes are intrinsically different from coherent rotation assumed Stoner-Wohlfarth model, resulting in FORC diagrams with a smaller reversible component. On the other hand, isolated authigenic SD particles can precipitate in the sediment matrix, as it might occur for pedogenic magnetite. In this case, an assembly of randomly located particles provides a possible model for the resulting FORC diagram. If the concentration of the particles is small, each particle is affected by a random interaction field whose statistical distribution can be calculated from first

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Science.gov (United States)

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

2016-01-01

Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

Quantum phase transitions driven by rhombic-type single-ion anisotropy in the S =1 Haldane chain

Science.gov (United States)

Tzeng, Yu-Chin; Onishi, Hiroaki; Okubo, Tsuyoshi; Kao, Ying-Jer

2017-08-01

The spin-1 Haldane chain is an example of the symmetry-protected-topological (SPT) phase in one dimension. Experimental realization of the spin chain materials usually involves both the uniaxial-type, D (Sz)2 , and the rhombic-type, E [(Sx)2-(Sy)2] , single-ion anisotropies. Here, we provide a precise ground-state phase diagram for a spin-1 Haldane chain with these single-ion anisotropies. Using quantum numbers, we find that the Z2 symmetry breaking phase can be characterized by double degeneracy in the entanglement spectrum. Topological quantum phase transitions take place on particular paths in the phase diagram, from the Haldane phase to the large-Ex, large-Ey, or large-D phases. The topological critical points are determined by the level spectroscopy method with a newly developed parity technique in the density matrix renormalization group [Phys. Rev. B 86, 024403 (2012), 10.1103/PhysRevB.86.024403], and the Haldane-large-D critical point is obtained with an unprecedented precision, (D/J ) c=0.9684713 (1 ) . Close to this critical point, a small rhombic single-ion anisotropy |E |/J ≪1 can destroy the Haldane phase and bring the system into a y -Néel phase. We propose that the compound [Ni (HF2) (3-Clpy ) 4] BF4 is a candidate system to search for the y -Néel phase.

Magnetic properties of CsCrCl/sub 3/, an antiferromagnetic chain compound with single-ion anisotropy

Energy Technology Data Exchange (ETDEWEB)

Day, P; Gregson, A K; Leech, D H [Oxford Univ. (UK). Inorganic Chemistry Lab.; Hutchings, M T [UKAEA Atomic Energy Research Establishment, Harwell. Materials Physics Div.; Rainford, B D [Imperial Coll. of Science and Technology, London (UK). Dept. of Physics

1979-01-01

The magnetic structure and excitations of the linear chain hexagonal perovskite salt CsCrCl/sub 3/ have been studied by susceptibility, powder and single crystal neutron diffraction, and coherent inelastic neutron scattering. Below the Neel temperature, Tsub(N) = 16 K, the spins lie in the basal plane with antiferromagnetic ordering along the c-axis chains. At 4.5 K there is strong dispersion of the spin-wave energy along c but no measurable dispersion perpendicular to c.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

Science.gov (United States)

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and

Identification of the chain-dispersing peptidoglycan hydrolase LytB of Streptococcus gordonii.

Directory of Open Access Journals (Sweden)

Riccardo Arrigucci

Full Text Available Bacterial cell division ends with the separation of the daughter cells, a process that requires peptidoglycan hydrolases (PGHs. Bacteria lacking cell separating PGHs are impaired in cell separation with the formation of long chains or clusters. We identified a gene in Streptococcus gordonii encoding for a putative glucosaminidase (lytB. The lytB isogenic mutant grew in long bacterial chains and resulted in impaired biofilm formation. Purified recombinant LytB showed a murolytic activity on Micrococcus lysodeikticus cell suspension and was able to disperse the long chains of the mutant, restoring the wild type diplococci/short chain phenotype. LytB protein was localized only in culture supernatant cell fraction of S. gordonii, and co-cultures of wild type and lytB mutant showed a significant reduction of bacterial chain length, indicating that LytB is a secreted enzyme. Our results demonstrate that LytB is a secreted peptidoglycan hydrolase required for S. gordonii cell separation.

The marine bacteria Shewanella frigidimarina NCIMB400 upregulates the type VI secretion system during early biofilm formation.

Science.gov (United States)

Linares, Denis; Jean, Natacha; Van Overtvelt, Perrine; Ouidir, Tassadit; Hardouin, Julie; Blache, Yves; Molmeret, Maëlle

2016-02-01

Shewanella sp. are facultative anaerobic Gram-negative bacteria, extensively studied for their electron transfer ability. Shewanella frigidimarina has been detected and isolated from marine environments, and in particular, from biofilms. However, its ability to adhere to surfaces and form a biofilm is poorly understood. In this study, we show that the ability to adhere and to form a biofilm of S. frigidimarina NCIMB400 is significantly higher than that of Shewanella oneidensis in our conditions. We also show that this strain forms a biofilm in artificial seawater, whereas in Luria-Bertani, this capacity is reduced. To identify proteins involved in early biofilm formation, a proteomic analysis of sessile versus planktonic membrane-enriched fractions allowed the identification of several components of the same type VI secretion system gene cluster: putative Hcp1 and ImpB proteins as well as a forkhead-associated domain-containing protein. The upregulation of Hcp1 a marker of active translocation has been confirmed using quantitative reverse transcription polymerase chain reaction. Our data demonstrated the presence of a single and complete type VI secretion system in S. frigidimarina NCIMB400 genome, upregulated in sessile compared with planktonic conditions. The fact that three proteins including the secreted protein Hcp1 have been identified may suggest that this type VI secretion system is functional. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

Directory of Open Access Journals (Sweden)

Oliinyk O. S.

2014-02-01

Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

Monte Carlo simulated dynamical magnetization of single-chain magnets

Energy Technology Data Exchange (ETDEWEB)

Li, Jun; Liu, Bang-Gui, E-mail: bgliu@iphy.ac.cn

2015-03-15

Here, a dynamical Monte-Carlo (DMC) method is used to study temperature-dependent dynamical magnetization of famous Mn{sub 2}Ni system as typical example of single-chain magnets with strong magnetic anisotropy. Simulated magnetization curves are in good agreement with experimental results under typical temperatures and sweeping rates, and simulated coercive fields as functions of temperature are also consistent with experimental curves. Further analysis indicates that the magnetization reversal is determined by both thermal-activated effects and quantum spin tunnelings. These can help explore basic properties and applications of such important magnetic systems. - Highlights: • Monte Carlo simulated magnetization curves are in good agreement with experimental results. • Simulated coercive fields as functions of temperature are consistent with experimental results. • The magnetization reversal is understood in terms of the Monte Carlo simulations.

The exact solution of the Ising quantum chain with alternating single and sector defects

International Nuclear Information System (INIS)

Zhang Degang; Li Bozang; Li Yun

1992-10-01

The Ising quantum chain with alternating single and sector defects is solved exactly by using the technique of Lieb, Schultz and Mattis. The energy spectrum of this model is shown to have a tower structure if and only if these defects constitute a commensurate configuration. This means that conformal invariance is preserved under these circumstances. (author). 13 refs

Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.

Science.gov (United States)

Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S

2014-01-01

Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A uranium-based UO_2"+-Mn"2"+ single-chain magnet assembled trough cation-cation interactions

International Nuclear Information System (INIS)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella; Caciuffo, Roberto; Colineau, Eric; Tuna, Floriana; Magnani, Nicola; Geyer, Arnaud de

2014-01-01

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]_n, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO_2(salen)py][Cp"*_2Co] (Cp"*=pentamethylcyclopentadienyl) with Cd(NO_3)_2 or Mn(NO_3)_2 in pyridine. The infinite UMn chain displays a high relaxation barrier of 134±0.8 K (93±0.5 cm"-"1), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T<6 K, with an impressive coercive field of 3.4 T at 2 K.

Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

OpenAIRE

Matsukizono, Miho; Kamegawa, Mariko; Tanaka, Koichi; Kohra, Shinya; Arizono, Koji; Hamazoe, Yuta; Sugimura, Kazuhisa

2013-01-01

An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv) clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg) but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competi...

J chain in the nurse shark: implications for function in a lower vertebrate.

Science.gov (United States)

Hohman, Valerie S; Stewart, Sue E; Rumfelt, Lynn L; Greenberg, Andrew S; Avila, David W; Flajnik, Martin F; Steiner, Lisa A

2003-06-15

J chain is a small polypeptide covalently attached to polymeric IgA and IgM. In humans and mice, it plays a role in binding Ig to the polymeric Ig receptor for transport into secretions. The putative orthologue of mammalian J chain has been identified in the nurse shark by sequence analysis of cDNA and the polypeptide isolated from IgM. Conservation with J chains from other species is relatively poor, especially in the carboxyl-terminal portion, and, unlike other J chains, the shark protein is not acidic. The only highly conserved segment in all known J chains is a block of residues surrounding an N-linked glycosylation site. Of the eight half-cystine residues that are conserved in mammalian J chains, three are lacking in the nurse shark, including two in the carboxyl-terminal segment that have been reported to be required for binding of human J chain-containing IgA to secretory component. Taken together with these data, the relative abundance of J chain transcripts in the spleen and their absence in the spiral valve (intestine) suggest that J chain in nurse sharks may not have a role in Ig secretion. Analysis of J chain sequences in diverse species is in agreement with accepted phylogenetic relationships, with the exception of the earthworm, suggesting that the reported presence of J chain in invertebrates should be reassessed.

Secretion of Bacterial Lipoproteins: Through the Cytoplasmic Membrane, the Periplasm and Beyond

Science.gov (United States)

Zückert, Wolfram R.

2014-01-01

Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., grampositive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporterlike LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the “+2 rule”. Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

Binding of human beta 2-microglobulin to murine EL4 thymoma cells upregulates MHC class I heavy-chain epitopes, inhibits IL-2 secretion and induces resistance to killing by natural killer cells

DEFF Research Database (Denmark)

Claësson, M H; Nissen, Mogens Holst

1994-01-01

line (ABLS-8), X63 B-lymphoma cells and YAC cells did not bind h beta 2m. In two of the T lymphomas, EL4 and BW5147, binding of h beta 2m led to an increase in major histocompatibility complex class I (MHC-I) heavy-chain epitope expression as measured by anti-H-2K/D antibody binding and FACS analysis....... EL4 cells which had bound h beta 2m decreased their rate of constitutive IL-2 secretion and became resistant to activated natural killer (NK) cell killing. The present data suggest the binding of h beta 2m to mouse T cells leads to conformational changes of MHC-I heavy chains which influence both...

Secretion of bacterial lipoproteins: through the cytoplasmic membrane, the periplasm and beyond.

Science.gov (United States)

Zückert, Wolfram R

2014-08-01

Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., gram-positive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporter-like LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the "+2 rule". Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

Targeting nanodisks via a single chain variable antibody - Apolipoprotein chimera

International Nuclear Information System (INIS)

Iovannisci, David M.; Beckstead, Jennifer A.; Ryan, Robert O.

2009-01-01

Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that α-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

Bubble dynamics and bubble-induced turbulence of a single-bubble chain

Science.gov (United States)

Lee, Joohyoung; Park, Hyungmin

2016-11-01

In the present study, the bubble dynamics and liquid-phase turbulence induced by a chain of bubbles injected from a single nozzle have been experimentally investigated. Using a high-speed two-phase particle image velociemtry, measurements on the bubbles and liquid-phase velocity field are conducted in a transparent tank filled with water, while varying the bubble release frequency from 0.1 to 35 Hz. The tested bubble size ranges between 2.0-3.2 mm, and the corresponding bubble Reynolds number is 590-1100, indicating that it belongs to the regime of path instability. As the release frequency increases, it is found that the global shape of bubble dispersion can be classified into two regimes: from asymmetric (regular) to axisymmetric (irregular). In particular, at higher frequency, the wake vortices of leading bubbles cause an irregular behaviour of the following bubble. For the liquid phase, it is found that a specific trend on the bubble-induced turbulence appears in a strong relation to the above bubble dynamics. Considering this, we try to provide a theoretical model to estimate the liquid-phase turbulence induced by a chain of bubbles. Supported by a Grant funded by Samsung Electronics, Korea.

A Single-Chain Photoswitchable CRISPR-Cas9 Architecture for Light-Inducible Gene Editing and Transcription.

Science.gov (United States)

Zhou, Xin X; Zou, Xinzhi; Chung, Hokyung K; Gao, Yuchen; Liu, Yanxia; Qi, Lei S; Lin, Michael Z

2018-02-16

Optical control of CRISPR-Cas9-derived proteins would be useful for restricting gene editing or transcriptional regulation to desired times and places. Optical control of Cas9 functions has been achieved with photouncageable unnatural amino acids or by using light-induced protein interactions to reconstitute Cas9-mediated functions from two polypeptides. However, these methods have only been applied to one Cas9 species and have not been used for optical control of different perturbations at two genes. Here, we use photodissociable dimeric fluorescent protein domains to engineer single-chain photoswitchable Cas9 (ps-Cas9) proteins in which the DNA-binding cleft is occluded at baseline and opened upon illumination. This design successfully controlled different species and functional variants of Cas9, mediated transcriptional activation more robustly than previous optogenetic methods, and enabled light-induced transcription of one gene and editing of another in the same cells. Thus, a single-chain photoswitchable architecture provides a general method to control a variety of Cas9-mediated functions.

A uranium-based UO_2"+-Mn"2"+ single-chain magnet assembled trough cation-cation interactions

International Nuclear Information System (INIS)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella; Caciuffo, Roberto; Colineau, Eric; Tuna, Floriana; Magnani, Nicola; Geyer, Arnaud de

2014-01-01

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]_n, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO_2(salen)py][Cp*_2Co] (Cp*=pentamethylcyclopentadienyl) with Cd(NO_3)_2 or Mn(NO_3)_2 in pyridine. The infinite UMn chain displays a high relaxation barrier of 134 ±0.8 K (93 ±0.5 cm"-"1), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T <6 K, with an impressive coercive field of 3.4 T at 2 K. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Purification, crystallization, X-ray diffraction analysis and phasing of an engineered single-chain PvuII restriction endonuclease

International Nuclear Information System (INIS)

Meramveliotaki, Chrysi; Kotsifaki, Dina; Androulaki, Maria; Hountas, Athanasios; Eliopoulos, Elias; Kokkinidis, Michael

2007-01-01

PvuII is the first type II restriction endonuclease to be converted from its wild-type homodimeric form into an enzymatically active single-chain variant. The enzyme was crystallized and phasing was successfully performed by molecular replacement. The restriction endonuclease PvuII from Proteus vulgaris has been converted from its wild-type homodimeric form into the enzymatically active single-chain variant scPvuII by tandemly joining the two subunits through the peptide linker Gly-Ser-Gly-Gly. scPvuII, which is suitable for the development of programmed restriction endonucleases for highly specific DNA cleavage, was purified and crystallized. The crystals diffract to a resolution of 2.35 Å and belong to space group P4 2 , with unit-cell parameters a = b = 101.92, c = 100.28 Å and two molecules per asymmetric unit. Phasing was successfully performed by molecular replacement

No Effect of the Transforming Growth Factor {beta}1 Promoter Polymorphism C-509T on TGFB1 Gene Expression, Protein Secretion, or Cellular Radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Reuther, Sebastian; Metzke, Elisabeth [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Bonin, Michael [Department of Medical Genetics, University of Tuebingen (Germany); Petersen, Cordula [Clinic of Radiotherapy and Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Dikomey, Ekkehard, E-mail: dikomey@uke.de [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Raabe, Annette [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany)

2013-02-01

Purpose: To study whether the promoter polymorphism (C-509T) affects transforming growth factor {beta}1 gene (TGFB1) expression, protein secretion, and/or cellular radiosensitivity for both human lymphocytes and fibroblasts. Methods and Materials: Experiments were performed with lymphocytes taken either from 124 breast cancer patients or 59 pairs of normal monozygotic twins. We used 15 normal human primary fibroblast strains as controls. The C-509T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism or TaqMan single nucleotide polymorphism (SNP) genotyping assay. The cellular radiosensitivity of lymphocytes was measured by G0/1 assay and that of fibroblasts by colony assay. The amount of extracellular TGFB1 protein was determined by enzyme-linked immunosorbent assay, and TGFB1 expression was assessed via microarray analysis or reverse transcription-polymerase chain reaction. Results: The C-509T genotype was found not to be associated with cellular radiosensitivity, neither for lymphocytes (breast cancer patients, P=.811; healthy donors, P=.181) nor for fibroblasts (P=.589). Both TGFB1 expression and TGFB1 protein secretion showed considerable variation, which, however, did not depend on the C-509T genotype (protein secretion: P=.879; gene expression: lymphocytes, P=.134, fibroblasts, P=.605). There was also no general correlation between TGFB1 expression and cellular radiosensitivity (lymphocytes, P=.632; fibroblasts, P=.573). Conclusion: Our data indicate that any association between the SNP C-509T of TGFB1 and risk of normal tissue toxicity cannot be ascribed to a functional consequence of this SNP, either on the level of gene expression, protein secretion, or cellular radiosensitivity.

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

DEFF Research Database (Denmark)

Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

2017-01-01

in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance....... These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging....

Bordetella pertussis diagnosed by polymerase chain reaction

DEFF Research Database (Denmark)

Birkebaek, N H; Heron, I; Skjødt, K

1994-01-01

The object of this work was to test the polymerase chain reaction (PCR) for demonstration of Bordetella pertussis (BP) in nasopharyngeal secretions. The method was applied to patients with recently diagnosed pertussis, as verified by BP culture. In order to test the sensitivity and specificity...... in 25 patients in whose nasopharyngeal secretions BP had been demonstrated after 4-7 days of culture. The detection limit of PCR in aqueous solution was 1-2 BP bacteria per reaction tube. PCR was 100% specific for BP, showing no response with other Bordetella species or other bacteria known to colonize...

Adsorption of a single polymer chain on a surface: effects of the potential range.

Science.gov (United States)

Klushin, Leonid I; Polotsky, Alexey A; Hsu, Hsiao-Ping; Markelov, Denis A; Binder, Kurt; Skvortsov, Alexander M

2013-02-01

We investigate the effects of the range of adsorption potential on the equilibrium behavior of a single polymer chain end-attached to a solid surface. The exact analytical theory for ideal lattice chains interacting with a planar surface via a box potential of depth U and width W is presented and compared to continuum model results and to Monte Carlo (MC) simulations using the pruned-enriched Rosenbluth method for self-avoiding chains on a simple cubic lattice. We show that the critical value U(c) corresponding to the adsorption transition scales as W(-1/ν), where the exponent ν=1/2 for ideal chains and ν≈3/5 for self-avoiding walks. Lattice corrections for finite W are incorporated in the analytical prediction of the ideal chain theory U(c)≈(π(2)/24)(W+1/2)(-2) and in the best-fit equation for the MC simulation data U(c)=0.585(W+1/2)(-5/3). Tail, loop, and train distributions at the critical point are evaluated by MC simulations for 1≤W≤10 and compared to analytical results for ideal chains and with scaling theory predictions. The behavior of a self-avoiding chain is remarkably close to that of an ideal chain in several aspects. We demonstrate that the bound fraction θ and the related properties of finite ideal and self-avoiding chains can be presented in a universal reduced form: θ(N,U,W)=θ(NU(c),U/U(c)). By utilizing precise estimations of the critical points we investigate the chain length dependence of the ratio of the normal and lateral components of the gyration radius. Contrary to common expectations this ratio attains a limiting universal value /=0.320±0.003 only at N~5000. Finite-N corrections for this ratio turn out to be of the opposite sign for W=1 and for W≥2. We also study the N dependence of the apparent crossover exponent φ(eff)(N). Strong corrections to scaling of order N(-0.5) are observed, and the extrapolated value φ=0.483±0.003 is found for all values of W. The strong correction to scaling effects found here explain why

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Matzuk, M.M.; Krieger, M.; Corless, C.L.; Boime, I.

1987-01-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common α subunit but differ in their hormone-specific β-subunits. The β subunit of hCG (hCGβ) is unique among the β subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCGβ gene alone or together with the hCGα gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results reveal that hCGβ can be secreted normally in the absence of its O-linked oligosaccharides. hCGβ devoid of O-linked carbohydrate can also combine efficiently with hCGα and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCGβ O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG

Effects of X-irradiation on gonadotropin secretion in rat anterior pituitary cells

International Nuclear Information System (INIS)

Li Xinmin; Liu Shuzheng

1988-01-01

The dispersed rat anterior pituitary cells cultured in 3 days was exposed to single doses of X-irradiation in the range of 0.5-8.0 Gy. LH and FSH contents in both the supernatant and the cells were measured. The LH secretion was significantly increased at the doses greater than 0.5 Gy and FSH secretion was also significantly enhanced at the dose of 4.0 Gy. The cellular contents of both LH and FSH remained near the control levels. It is concluded that gonadotropin secretion can be stimulated by single doses of X-rays in the range of 0.5-8.0 Gy

The Smart Grid - A saucerful of secrets?

International Nuclear Information System (INIS)

Wissner, Matthias

2011-01-01

To many, a lot of secrets are at the bottom of the often-cited catchphrase 'Smart Grid'. This article gives an overview of the options that information and communication technology (ICT) offers for the restructuring and modernisation of the German power system, in particular with a view towards its development into a Smart Grid and thus tries to reveal these secrets. After a short outline on the development of ICT in terms of technology types and their availability, the further analysis highlights upcoming challenges in all parts of the power value chain and possible solutions for these challenges through the intensified usage of ICT applications. They are examined with regard to their effectiveness and efficiency in the fields of generation, transmission, distribution and supply. Finally, potential obstacles that may defer the introduction of ICT into the power system are shown. The analysis suggests that if certain hurdles are taken, the huge potential of ICT can create additional value in various fields of the whole power value chain. This ranges from increased energy efficiency and the more sophisticated integration of decentralised (renewable) energy plants to a higher security of supply and more efficient organisation of market processes. The results are true for the German power market but can in many areas also be transferred to other industrialised nations with liberalised power markets.

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction.

Science.gov (United States)

Brownfoot, Fiona C; Hastie, Roxanne; Hannan, Natalie J; Cannon, Ping; Tuohey, Laura; Parry, Laura J; Senadheera, Sevvandi; Illanes, Sebastian E; Kaitu'u-Lino, Tu'uhevaha J; Tong, Stephen

2016-03-01

Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and soluble endoglin into the maternal circulation. This causes widespread endothelial dysfunction that manifests clinically as hypertension and multisystem organ injury. Recently, small molecule inhibitors of hypoxic inducible factor 1α have been found to reduce soluble fms-like tyrosine kinase 1 and soluble endoglin secretion. However, their safety profile in pregnancy is unknown. Metformin is safe in pregnancy and is also reported to inhibit hypoxic inducible factor 1α by reducing mitochondrial electron transport chain activity. The purposes of this study were to determine (1) the effects of metformin on placental soluble fms-like tyrosine kinase 1 and soluble endoglin secretion, (2) to investigate whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion are regulated through the mitochondrial electron transport chain, and (3) to examine its effects on endothelial dysfunction, maternal blood vessel vasodilation, and angiogenesis. We performed functional (in vitro and ex vivo) experiments using primary human tissues to examine the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from placenta, endothelial cells, and placental villous explants. We used succinate, mitochondrial complex II substrate, to examine whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion were mediated through the mitochondria. We also isolated mitochondria from preterm preeclamptic placentas and gestationally matched control subjects and measured mitochondrial electron transport chain activity using kinetic spectrophotometric assays. Endothelial cells or whole maternal vessels were incubated with metformin to determine whether it rescued endothelial dysfunction induced by either tumor necrosis factor-α (to endothelial cells) or placenta villous

Comparison of the Effect of Pre-operative Single Oral Dose of Tramadol and Famotidine on Gastric Secretions pH and Volume in Patients Scheduled for Laparoscopic Cholecystectomy

International Nuclear Information System (INIS)

Khan, M. U.; Aqil, M.; Hussain, A.; Zahrani, T. A.; Hillis, M.

2015-01-01

Objective: To evaluate and compare the effects of pre-operative single oral dose of tramadol and famotidine on gastric secretions pH and volume in patients electively scheduled for laparoscopic cholecystectomy. Study Design: Randomized control trial. Place and Duration of Study: Department of Anaesthesia, King Saud University Riyadh, Saudi Arabia, from August 2011 to June 2013. Methodology: Ninety adult, ASA-I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive pre-operatively either placebo (Group-C, n=30), oral tramadol 100 mg (Group-T, n=30) or famotidine 40 mg (Group-F, n=30). After induction of general anaesthesia, gastric fluid was aspirated through orogastric tube. The gastric secretions volume and pH was measured using pH meter. Results:There was no statistically difference between groups in age, weight and gender. The gastric secretions mean pH was 2.06 ± 0.22,2.04 ± 0.20, 5.79 ± 0.77 and volume was 0.59 ± 0.17, 0.59 ± 0.14 and 0.28 ± 0.16 ml/kg in Group-C, Group-T and Group-F respectively. There was a significant statistical difference in the mean pH values between Group-C vs. Group-F (p greater than 0.001) and Group-Tvs. Group-F (p greater than 0.001). Statistically significant difference was also found in the mean gastric secretions volume between Group - C vs. Group-F (p greater than 0.001) and Group-Tvs. Group-F (p greater than 0.001). There was no significant difference in the mean gastric fluid pH values (p=0.99) and mean gastric secretions volume (p=0.99) between Group-Tand Group-C. Conclusion:As compared to famotidine, pre-operative single oral dose of tramadol was unable to elevate the desired level of gastric fluid pH (less than 2.5) and decrease in gastric secretions volume (greater than 0.4ml/kg). (author)

Early recognition is important when multiple magnets masquerade as a single chain after foreign body ingestion

Directory of Open Access Journals (Sweden)

Auriel August

2016-10-01

Full Text Available Ingestions of multiple magnets can lead to serious damage to the gastrointestinal tract. Moreover, these foreign bodies can take deceptive shapes such as single chains which may mislead clinicians. We report the case of a ten-year-old boy who swallowed 33 magnets, the most yet reported, which took on the appearance of a single loop in the stomach, while actually being located in the stomach, small bowel, and colon. Early recognition and prompt intervention are necessary to avoid complications of this foreign body misadventure.

Phase transitions of single polymer chains and of polymer solutions: insights from Monte Carlo simulations

International Nuclear Information System (INIS)

Binder, K; Paul, W; Strauch, T; Rampf, F; Ivanov, V; Luettmer-Strathmann, J

2008-01-01

The statistical mechanics of flexible and semiflexible macromolecules is distinct from that of small molecule systems, since the thermodynamic limit can also be approached when the number of (effective) monomers of a single chain (realizable by a polymer solution in the dilute limit) is approaching infinity. One can introduce effective attractive interactions into a simulation model for a single chain such that a swollen coil contracts when the temperature is reduced, until excluded volume interactions are effectively canceled by attractive forces, and the chain conformation becomes almost Gaussian at the theta point. This state corresponds to a tricritical point, as the renormalization group theory shows. Below the theta temperature a fluid globule is predicted (at nonzero concentration then phase separation between dilute and semidilute solutions occurs), while at still lower temperature a transition to a solid phase (crystal or glass) occurs. Monte Carlo simulations have shown, however, that the fluid globule phase may become suppressed, when the range of the effective attractive forces becomes too short, with the result that a direct (ultimately first-order) transition from the swollen coil to the solid occurs. This behavior is analogous to the behavior of colloidal particles with a very short range of attractive forces, where liquid-vapor-type phase separation may be suppressed. Analogous first-order transitions from swollen coils to dense rodlike or toroidal structures occur for semiflexible polymers. Finally, the modifications of the behavior discussed when the polymers are adsorbed at surfaces are also mentioned, and possible relations to wetting behavior of polymer solutions are addressed.

First principles studies of the electronic properties and catalytic activity of single-walled carbon nanotube doped with Pt clusters and chains

International Nuclear Information System (INIS)

Hayes, Kayla E.; Lee, Hee-Seung

2012-01-01

Highlights: ► Electronic and magnetic properties of (5, 5)-SWNT doped with Pt clusters and chains. ► Pt-doping can change metallic (5, 5)-SWNT to semiconducting CNT. ► Oxygen adsorption on Pt-doped (5, 5)-SWNT is barrierless process. ► Pt-doping reduces the activation barrier of oxygen dissociation reaction. ► Adsorbed oxygen has 2 O 2 - – character. - Abstract: We report the results of density functional theory calculations on the electronic structures, geometrical parameters, and magnetic properties of a wide variety of Pt clusters/chains adsorbed on metallic (5,5) single-walled carbon nanotube (SWNT). It was found that the electronic band structures of Pt/CNT systems are very sensitive to the small changes in the geometries of Pt clusters and chains. In some cases, metallic (5, 5)-SWNT becomes a small-gap semiconducting nanotube with adsorbed Pt clusters and chains. We also investigated the dissociation of molecular oxygen on the (5, 5)-SWNT doped with a single Pt atom via the nudged elastic band (NEB) method. The NEB results showed that the activation barrier is lowered even with a single Pt atom compared to that of pristine SWNT. It was found that the electronic structure of molecular oxygen adsorbed on Pt-doped CNT resembles that of 2 O 2 - , which should facilitate the dissociation process.

Optimal Decisions in a Single-Period Supply Chain with Price-Sensitive Random Demand under a Buy-Back Contract

Directory of Open Access Journals (Sweden)

Feng Wang

2014-01-01

Full Text Available This paper studies a single-period supply chain with a buy-back contract under a Stackelberg game model, in which the supplier (leader decides on the wholesale price, and the retailer (follower responds to determine the retail price and the order quantity. We analytically investigate the decentralized retailer’s optimal decision. Our results demonstrate that the retailer has a unique optimal simultaneous decision on the retail price and the order quantity, under a mild restriction on the demand distribution. Moreover, as it can be shown that the decentralized supply chain facing price-sensitive random demand cannot be coordinated with buy-back contract, we propose a scheme for the system to achieve Pareto-improvement. Theoretical analysis suggests that there exists a unique Pareto-equilibrium for the supply chain. In particular, when the Pareto-equilibrium is reached, the supply chain is coordinated. Numerical experiments confirm our results.

Conformation of single block copolymer chain in two-dimensional microphase-separated structure studied by scanning near-field optical microscopy.

Science.gov (United States)

Sekine, Ryojun; Aoki, Hiroyuki; Ito, Shinzaburo

2009-05-21

The localization and orientation of the symmetric diblock copolymer chain in a quasi-two-dimensional microphase-separated structure were studied by scanning near-field optical microscopy (SNOM). In the monolayer of poly(isobutyl methacrylate)-block-poly(octadecyl methacrylate) (PiBMA-b-PODMA), the individual PiBMA subchains were directly observed by SNOM, and the center of mass (CM) and orientational angle relative to the phase interface were examined at the single chain level. It was found that the position of the CM and the orientation of the PiBMA subchain in the lamellar structure were dependent on the curvature of the PiBMA/PODMA interface. As the interface was bent toward the objective chain, the block chain preferred the CM position closer to the domain center, and the conformation was strongly oriented perpendicularly to the domain interface. With increase of the curvature, the steric hindrance among the block chain increases, resulting in the stretched conformation.

DIFFERENTIAL HEPATIC PROCESSING AND BILIARY-SECRETION OF HEADGROUP AND ACYL CHAINS OF LIPOSOMAL PHOSPHATIDYLCHOLINES

NARCIS (Netherlands)

VERKADE, HJ; DERKSEN, JTP; GERDING, A; SCHERPHOF, GL; VONK, RJ; KUIPERS, F

1991-01-01

To investigate the contribution of plasma-derived phosphatidylcholine (PC) to bile PC, the hepatic processing and biliary secretion of liposome-associated PC was studied in rats. For this purpose, small unilamellar vesicles (SUV), containing trace amounts of

Secret-Key-Aided Scheme for Securing Untrusted DF Relaying Networks

KAUST Repository

Shafie, Ahmed El

2017-06-12

This paper proposes a new scheme to secure the transmissions in an untrusted decode-and-forward (DF) relaying network. A legitimate source node, Alice, sends her data to a legitimate destination node, Bob, with the aid of an untrusted DF relay node, Charlie. To secure the transmissions from Charlie during relaying time slots, each data codeword is secured using a secret-key codeword that has been previously shared between Alice and Bob during the perfectly secured time slots (i.e., when the channel secrecy rate is positive). The secret-key bits exchanged between Alice and Bob are stored in a finite-length buffer and are used to secure data transmission whenever needed. We model the secret-key buffer as a queueing system and analyze its Markov chain. Our numerical results show the gains of our proposed scheme relative to benchmarks. Moreover, the proposed scheme achieves an upper bound on the secure throughput.

Secret-Key-Aided Scheme for Securing Untrusted DF Relaying Networks

KAUST Repository

Shafie, Ahmed El; Salem, Ahmed Sultan; Mabrouk, Asma; Tourki, Kamel; Al-Dhahir, Naofal

2017-01-01

This paper proposes a new scheme to secure the transmissions in an untrusted decode-and-forward (DF) relaying network. A legitimate source node, Alice, sends her data to a legitimate destination node, Bob, with the aid of an untrusted DF relay node, Charlie. To secure the transmissions from Charlie during relaying time slots, each data codeword is secured using a secret-key codeword that has been previously shared between Alice and Bob during the perfectly secured time slots (i.e., when the channel secrecy rate is positive). The secret-key bits exchanged between Alice and Bob are stored in a finite-length buffer and are used to secure data transmission whenever needed. We model the secret-key buffer as a queueing system and analyze its Markov chain. Our numerical results show the gains of our proposed scheme relative to benchmarks. Moreover, the proposed scheme achieves an upper bound on the secure throughput.

Electrical contacts to nanorod networks at different length scales: From macroscale ensembles to single nanorod chains

KAUST Repository

Lavieville, Romain; Zhang, Yang; Di Fabrizio, Enzo M.; Krahne, Roman

2013-01-01

The nature of metal-semiconductor interfaces at the nanoscale is an important issue in micro- and nanoelectronic engineering. The study of charge transport through chains of CdSe semiconductor nanorods linked by Au particles represents an ideal model system for this matter, because the metal semiconductor interface is an intrinsic feature of the nanosystem. Here we show the controlled fabrication of all-inorganic hybrid metal-semiconductor networks with different size, in which the semiconductor nanorods are linked by Au domains at their tips. We demonstrate different approaches to selectively contact the networks and single nanorod chains with planar electrodes, and we investigate their charge transport at room temperature. © 2013 Elsevier B.V. All rights reserved.

Electrical contacts to nanorod networks at different length scales: From macroscale ensembles to single nanorod chains

KAUST Repository

Lavieville, Romain

2013-11-01

The nature of metal-semiconductor interfaces at the nanoscale is an important issue in micro- and nanoelectronic engineering. The study of charge transport through chains of CdSe semiconductor nanorods linked by Au particles represents an ideal model system for this matter, because the metal semiconductor interface is an intrinsic feature of the nanosystem. Here we show the controlled fabrication of all-inorganic hybrid metal-semiconductor networks with different size, in which the semiconductor nanorods are linked by Au domains at their tips. We demonstrate different approaches to selectively contact the networks and single nanorod chains with planar electrodes, and we investigate their charge transport at room temperature. © 2013 Elsevier B.V. All rights reserved.

Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection

International Nuclear Information System (INIS)

Wang, Lin-Xu; Mellon, Michael; Bowder, Dane; Quinn, Meghan; Shea, Danielle; Wood, Charles; Xiang, Shi-Hua

2015-01-01

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from Neisseria gonorrhoeae, which enabled surface display of the antibody molecule. Our results indicate that the scFv-VRC01 antibody molecule was displayed on the surface of the bacteria as demonstrated by flow cytometry and immunofluorescence microscopy. The engineered bacteria can capture HIV-1 particles via surface-binding and inhibit HIV-1 infection in cell culture. - Highlights: • Designed single-chain VRC01 antibody was demonstrated to bind HIV-1 envelope gp120. • Single-chain VRC01 antibody was successfully displayed on the surface of E. coli. • Engineered bacteria can absorb HIV-1 particles and prevent HIV-1 infection in cell culture

End-anchored polymers in good solvents from the single chain limit to high anchoring densities.

Science.gov (United States)

Whitmore, Mark D; Grest, Gary S; Douglas, Jack F; Kent, Michael S; Suo, Tongchuan

2016-11-07

An increasing number of applications utilize grafted polymer layers to alter the interfacial properties of solid substrates, motivating refinement in our theoretical understanding of such layers. To assess existing theoretical models of them, we have investigated end-anchored polymer layers over a wide range of grafting densities, σ, ranging from a single chain to high anchoring density limits, chain lengths ranging over two orders of magnitude, for very good and marginally good solvent conditions. We compare Monte Carlo and molecular dynamics simulations, numerical self-consistent field calculations, and experimental measurements of the average layer thickness, h, with renormalization group theory, the Alexander-de Gennes mushroom theory, and the classical brush theory. Our simulations clearly indicate that appreciable inter-chain interactions exist at all simulated areal anchoring densities so that there is no mushroom regime in which the layer thickness is independent of σ. Moreover, we find that there is no high coverage regime in which h follows the predicted scaling, h ∼ Nσ 1/3 , for classical polymer brushes either. Given that no completely adequate analytic theory seems to exist that spans wide ranges of N and σ, we applied scaling arguments for h as a function of a suitably defined reduced anchoring density, defined in terms of the solution radius of gyration of the polymer chains and N. We find that such a scaling approach enables a smooth, unified description of h in very good solvents over the full range of anchoring density and chain lengths, although this type of data reduction does not apply to marginal solvent quality conditions.

Effective single chain antibody (scFv) concentrations in vivo via adenoviral vector mediated expression of secretory scFv

NARCIS (Netherlands)

Arafat, WO; Gomez-Navarro, J; Buchsbaum, DJ; Xiang, J; Casado, E; Barker, SD; Mahasreshti, PJ; Haisma, HJ; Barnes, MN; Siegal, GP; Alvarez, RD; Hemminki, A; Nettelbeck, DM; Curiel, DT

Single chain antibodies (scFv) represent powerful interventional agents for the achievement of targeted therapeutics. The practical utility of these agents have been limited, however, by difficulties related to production of recombinant scFv and the achievement of effective and sustained levels of

Unbiased analysis of TCRα/β chains at the single-cell level in human CD8+ T-cell subsets.

Science.gov (United States)

Sun, Xiaoming; Saito, Masumichi; Sato, Yoshinori; Chikata, Takayuki; Naruto, Takuya; Ozawa, Tatsuhiko; Kobayashi, Eiji; Kishi, Hiroyuki; Muraguchi, Atsushi; Takiguchi, Masafumi

2012-01-01

T-cell receptor (TCR) α/β chains are expressed on the surface of CD8(+) T-cells and have been implicated in antigen recognition, activation, and proliferation. However, the methods for characterization of human TCRα/β chains have not been well established largely because of the complexity of their structures owing to the extensive genetic rearrangements that they undergo. Here we report the development of an integrated 5'-RACE and multiplex PCR method to amplify the full-length transcripts of TCRα/β at the single-cell level in human CD8(+) subsets, including naive, central memory, early effector memory, late effector memory, and effector phenotypic cells. Using this method, with an approximately 47% and 62% of PCR success rate for TCRα and for TCRβ chains, respectively, we were able to analyze more than 1,000 reads of transcripts of each TCR chain. Our comprehensive analysis revealed the following: (1) chimeric rearrangements of TCRδ-α, (2) control of TCRα/β transcription with multiple transcriptional initiation sites, (3) altered utilization of TCRα/β chains in CD8(+) subsets, and (4) strong association between the clonal size of TCRα/β chains and the effector phenotype of CD8(+) T-cells. Based on these findings, we conclude that our method is a useful tool to identify the dynamics of the TCRα/β repertoire, and provides new insights into the study of human TCRα/β chains.

Evidence for single-chain magnet behavior in a Mn(III)-Ni(II) chain designed with high spin magnetic units: a route to high temperature metastable magnets.

Science.gov (United States)

Clérac, Rodolphe; Miyasaka, Hitoshi; Yamashita, Masahiro; Coulon, Claude

2002-10-30

We herein present the synthesis, crystal structure, and magnetic properties of a new heterometallic chain of MnIII and NiII ions, [Mn2(saltmen)2Ni(pao)2(py)2](ClO4)2 (1) (saltmen2- = N,N'-(1,1,2,2-tetramethylethylene) bis(salicylideneiminate) and pao- = pyridine-2-aldoximate). The crystal structure of 1 was investigated by X-ray crystallographic analysis: compound 1 crystallized in monoclinic, space group C2/c (No. 15) with a = 21.140(3) A, b = 15.975(1) A, c = 18.6212(4) A, beta = 98.0586(4) degrees , V = 6226.5(7) A3, and Z = 4. This compound consists of two fragments, the out-of-plane dimer [Mn2(saltmen)2]2+ as a coordination acceptor building block and the neutral mononuclear unit [Ni(pao)2(py)2] as a coordination donor building block, forming an alternating chain having the repeating unit [-Mn-(O)2-Mn-ON-Ni-NO-]n. In the crystal structure, each chain is well separated with a minimum intermetallic distance between Mn and Ni ions of 10.39 A and with the absence of interchain pi overlaps between organic ligands. These features ensure a good magnetic isolation of the chains. The dc and ac magnetic measurements were performed on both the polycrystalline sample and the aligned single crystals of 1. Above 30 K, the magnetic susceptibility of this one-dimensional compound was successfully described in a mean field approximation as an assembly of trimers (Mn...Ni...Mn) with a NiII...MnIII antiferromagnetic interaction (J = -21 K) connected through a ferromagnetic MnIII...MnIII interaction (J'). However, the mean field theory fails to describe the magnetic behavior below 30 K emphasizing the one-dimensional magnetic character of the title compound. Between 5 and 15 K, the susceptibility in the chain direction was fitted to a one-dimensional Ising model leading to the same value of J'. Hysteresis loops are observed below 3.5 K, indicating a magnet-type behavior. In the same range of temperature, combined ac and dc measurements show a slow relaxation of the magnetization

Open Secrets

OpenAIRE

Madison, Michael

2017-01-01

The law of trade secrets is often conceptualized in bilateral terms, as creating and enforcing rights between trade secret owners, on the one hand, and misappropriators on the other hand. This paper, a chapter in a forthcoming collection on the law of trade secrets, argues that trade secrets and the law that guards them can serve structural and insitutional roles as well. Somewhat surprisingly, given the law’s focus on secrecy, among the institutional products of trade secrets law are commons...

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

Directory of Open Access Journals (Sweden)

Renzhi Wang

2016-09-01

Full Text Available Adrenocorticotrophin (ACTH-secreting pituitary adenoma, also known as Cushing disease (CD, is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT. We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1, collagen type I α 1 chain (COL1A1, 5′-nucleotidase ecto (NT5E, HtrA serine peptidase 1 (HTRA1 and angiopoietin 1 (ANGPT1 and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

Contaminant transport in fractured porous media: analytical solution for a two-member decay chain in a single fracture

International Nuclear Information System (INIS)

Sudicky, E.A.; Frind, E.O.

1984-01-01

An analytical solution is presented for the problem of radionuclide chain decay during transport through a discrete fracture situated in a porous rock matrix. The solution takes into account advection along the fracture, molecular diffusion from the fracture to the porous matrix, adsorption on the fracture face, adsorption in the rock matrix, and radioactive decay. The solution for the daughter product is in the form of a double integral which is evaluated by Gauss-Legendre quadrature. Results show that the daughter product tends to advance ahead of the parent nuclide even when the half-life of the parent is larger. This is attributed to the effect of chain decay in the matrix, which tends to reduce the diffusive loss of the daughter along the fracture. The examples also demonstrate that neglecting the parent nuclide and modeling its daughter as a single species can result in significant overestimation of arrival times at some point along the fracture. Although the analytical solution is restricted to a two-member chain for practical reasons, it represents a more realistic description of nuclide transport along a fracture than available single-species models. The solution may be of use for application to other contaminants undergoing different types of first-order transformation reactions

Ground-state phase diagram of an (S, S') = (1, 2) spin-alternating chain with competing single-ion anisotropies

International Nuclear Information System (INIS)

Tonegawa, T; Okamoto, K; Sakai, T; Kaburagi, M

2009-01-01

Employing various numerical methods, we determine the ground-state phase diagram of an (S, S') = (1, 2) spin-alternating chain with antiferromagnetic nearest-neighboring exchange interactions and uniaxial single-ion anisotropies. The resulting phase diagram consists of eight kinds of phases including two phases which accompany the spontaneous breaking of the translational symmetry and a ferrimagnetic phase in which the ground-state magnetization varies continuously with the uniaxial single-ion anisotropy constants for the S=1 and S =2 spins. The appearance of these three phases is attributed to the competition between the uniaxial single-ion anisotropies of both spins.

Association between very long chain fatty acids in the meibomian gland and dry eye resulting from n-3 fatty acid deficiency.

Science.gov (United States)

Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru

2015-06-01

In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function. Copyright © 2015 Elsevier Ltd. All rights reserved.

The normally expressed kappa immunoglobulin light chain gene repertoire and somatic mutations studied by single-sided specific polymerase chain reaction (PCR); frequent occurrence of features often assigned to autoimmunity

DEFF Research Database (Denmark)

Juul, L; Hougs, L; Andersen, V

1997-01-01

The expressed human kappa light chain gene repertoire utilized by healthy individuals was studied by two different single-sided specific PCR techniques to avoid bias for certain V genes. A total of 103 rearranged kappa sequences from peripheral blood mononuclear cells from healthy individuals were...

A conceptual framework for economic optimization of single hazard surveillance in livestock production chains.

Science.gov (United States)

Guo, Xuezhen; Claassen, G D H; Oude Lansink, A G J M; Saatkamp, H W

2014-06-01

Economic analysis of hazard surveillance in livestock production chains is essential for surveillance organizations (such as food safety authorities) when making scientifically based decisions on optimization of resource allocation. To enable this, quantitative decision support tools are required at two levels of analysis: (1) single-hazard surveillance system and (2) surveillance portfolio. This paper addresses the first level by presenting a conceptual approach for the economic analysis of single-hazard surveillance systems. The concept includes objective and subjective aspects of single-hazard surveillance system analysis: (1) a simulation part to derive an efficient set of surveillance setups based on the technical surveillance performance parameters (TSPPs) and the corresponding surveillance costs, i.e., objective analysis, and (2) a multi-criteria decision making model to evaluate the impacts of the hazard surveillance, i.e., subjective analysis. The conceptual approach was checked for (1) conceptual validity and (2) data validity. Issues regarding the practical use of the approach, particularly the data requirement, were discussed. We concluded that the conceptual approach is scientifically credible for economic analysis of single-hazard surveillance systems and that the practicability of the approach depends on data availability. Copyright © 2014 Elsevier B.V. All rights reserved.

A single-chain variable fragment intrabody prevents intracellular polymerization of Z α1-antitrypsin while allowing its antiproteinase activity.

Science.gov (United States)

Ordóñez, Adriana; Pérez, Juan; Tan, Lu; Dickens, Jennifer A; Motamedi-Shad, Neda; Irving, James A; Haq, Imran; Ekeowa, Ugo; Marciniak, Stefan J; Miranda, Elena; Lomas, David A

2015-06-01

Mutant Z α1-antitrypsin (E342K) accumulates as polymers within the endoplasmic reticulum (ER) of hepatocytes predisposing to liver disease, whereas low levels of circulating Z α1-antitrypsin lead to emphysema by loss of inhibition of neutrophil elastase. The ideal therapy should prevent polymer formation while preserving inhibitory activity. Here we used mAb technology to identify interactors with Z α1-antitrypsin that comply with both requirements. We report the generation of an mAb (4B12) that blocked α1-antitrypsin polymerization in vitro at a 1:1 molar ratio, causing a small increase of the stoichiometry of inhibition for neutrophil elastase. A single-chain variable fragment (scFv) intrabody was generated based on the sequence of mAb4B12. The expression of scFv4B12 within the ER (scFv4B12KDEL) and along the secretory pathway (scFv4B12) reduced the intracellular polymerization of Z α1-antitrypsin by 60%. The scFv4B12 intrabody also increased the secretion of Z α1-antitrypsin that retained inhibitory activity against neutrophil elastase. MAb4B12 recognized a discontinuous epitope probably located in the region of helices A/C/G/H/I and seems to act by altering protein dynamics rather than binding preferentially to the native state. This novel approach could reveal new target sites for small-molecule intervention that may block the transition to aberrant polymers without compromising the inhibitory activity of Z α1-antitrypsin. © FASEB.

Unbiased analysis of TCRα/β chains at the single-cell level in human CD8+ T-cell subsets.

Directory of Open Access Journals (Sweden)

Xiaoming Sun

Full Text Available T-cell receptor (TCR α/β chains are expressed on the surface of CD8(+ T-cells and have been implicated in antigen recognition, activation, and proliferation. However, the methods for characterization of human TCRα/β chains have not been well established largely because of the complexity of their structures owing to the extensive genetic rearrangements that they undergo. Here we report the development of an integrated 5'-RACE and multiplex PCR method to amplify the full-length transcripts of TCRα/β at the single-cell level in human CD8(+ subsets, including naive, central memory, early effector memory, late effector memory, and effector phenotypic cells. Using this method, with an approximately 47% and 62% of PCR success rate for TCRα and for TCRβ chains, respectively, we were able to analyze more than 1,000 reads of transcripts of each TCR chain. Our comprehensive analysis revealed the following: (1 chimeric rearrangements of TCRδ-α, (2 control of TCRα/β transcription with multiple transcriptional initiation sites, (3 altered utilization of TCRα/β chains in CD8(+ subsets, and (4 strong association between the clonal size of TCRα/β chains and the effector phenotype of CD8(+ T-cells. Based on these findings, we conclude that our method is a useful tool to identify the dynamics of the TCRα/β repertoire, and provides new insights into the study of human TCRα/β chains.

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

Science.gov (United States)

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

2015-01-01

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

Development of coordination system model on single-supplier multi-buyer for multi-item supply chain with probabilistic demand

Science.gov (United States)

Olivia, G.; Santoso, A.; Prayogo, D. N.

2017-11-01

Nowadays, the level of competition between supply chains is getting tighter and a good coordination system between supply chains members is very crucial in solving the issue. This paper focused on a model development of coordination system between single supplier and buyers in a supply chain as a solution. Proposed optimization model was designed to determine the optimal number of deliveries from a supplier to buyers in order to minimize the total cost over a planning horizon. Components of the total supply chain cost consist of transportation costs, handling costs of supplier and buyers and also stock out costs. In the proposed optimization model, the supplier can supply various types of items to retailers whose item demand patterns are probabilistic. Sensitivity analysis of the proposed model was conducted to test the effect of changes in transport costs, handling costs and production capacities of the supplier. The results of the sensitivity analysis showed a significant influence on the changes in the transportation cost, handling costs and production capacity to the decisions of the optimal numbers of product delivery for each item to the buyers.

Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain

OpenAIRE

Nandi, Sayan; Akhter, Mohammed P.; Seifert, Mark F.; Dai, Xu-Ming; Stanley, E. Richard

2006-01-01

The primary macrophage growth factor, colony-stimulating factor-1 (CSF-1), is homodimeric and exists in 3 biologically active isoforms: a membrane-spanning, cell-surface glycoprotein (csCSF-1) and secreted glycoprotein (sgCSF-1) and proteoglycan (spCSF-1) isoforms. To investigate the in vivo role of the chondroitin sulfate glycosaminoglycan (GAG) chain of spCSF-1, we created mice that exclusively express, in a normal tissue-specific and developmental manner, either the secreted precursor of s...

Accelerating the coupled-cluster singles and doubles method using the chain-of-sphere approximation

Science.gov (United States)

Dutta, Achintya Kumar; Neese, Frank; Izsák, Róbert

2018-06-01

In this paper, we present a chain-of-sphere implementation of the external exchange term, the computational bottleneck of coupled-cluster calculations at the singles and doubles level. This implementation is compared to standard molecular orbital, atomic orbital and resolution of identity implementations of the same term within the ORCA package and turns out to be the most efficient one for larger molecules, with a better accuracy than the resolution-of-identity approximation. Furthermore, it becomes possible to perform a canonical CC calculation on a tetramer of nucleobases in 17 days, 20 hours.

Oxygenation decreases elastin secretion from rat ductus arteriosus smooth muscle cells.

Science.gov (United States)

Kawakami, Shoji; Minamisawa, Susumu

2015-08-01

The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The oxygen concentration in the blood rises after birth, and in the DA this increase in oxygen concentration causes functional closure, which is induced by smooth muscle contraction. Previous studies have demonstrated that hypoxia and/or oxygenation affect vascular remodeling of various vessels. Therefore, we hypothesized that the rise in oxygen concentration would affect the vascular structure of the DA due to production of proteins secreted from DA smooth muscle cells (SMC). Liquid chromatography-tandem mass spectrometry was used to comprehensively investigate the secreted proteins in the supernatant of rat DA SMC harvested under hypoxic conditions (1% oxygen) or under normoxic conditions (21% oxygen). We found that the rise in oxygen concentration reduced the secretion of elastin from DA SMC. On reverse transcription-polymerase chain reaction, the expression of elastin mRNA was not significantly changed in DA SMC from hypoxic to normoxic conditions. Given that elastin forms internal elastic lamina and elastic fibers in the vascular muscle layers, and that a rise in oxygen concentration reduced the secretion of elastin, this suggests that the rise in blood oxygen concentration after birth reduces the secretion of elastin, and therefore may play a role in DA structural remodeling after birth. © 2015 Japan Pediatric Society.

Single-chain magnet features in 1D [MnR4TPP][TCNE] compounds

International Nuclear Information System (INIS)

Balanda, Maria; Tomkowicz, Zbigniew; Rams, Michal; Haase, Wolfgang

2011-01-01

Molecular chains of antiferrimagnetically coupled Mn III -ion (S = 2) and TCNE (tetracyanoethylene) radical moments (s = 1/2 ) show different behaviour depending on group R substituted to TPP (tetraphenylporphyrin) and on the substitution site. The compound with R = F in Ortho position is a Single-Chain Magnet (SCM) with blocking temperature T b = 6.6K, while that with R = F in Meta position shows both blocking (T b = 5.4 K) and magnetic ordering transition (T c = 10 K). For bulky groups R = OC n H 2n+1 , the magnetically ordered phase is observed (T c ∼ 22 K), which does not however prevent slow relaxation at T c of 2 T at 2.3 K is like that of SCM. The frequency dependent AC susceptibility in the superimposed DC field reveals common features of all systems. The energy of intrachain ferromagnetic coupling between effective spin units 3/2, relevant at low temperatures, is determined for all compounds and the interchain dipolar coupling is estimated. It is concluded that slow relaxation is inherent for all quasi one-dimensional compounds and for the magnetically ordered ones shows up in the high enough magnetic field.

Intestinal absorption and secretion of 65Zn in the rat

International Nuclear Information System (INIS)

Methfessel, A.H.; Spencer, H.

1974-01-01

A single dose of 65 Zn Cl 2 was given by intubation to the intact rat or was instilled into the lumen of ligated intestinal sacs to determine the absorption, or injected intravenously via the tail vein to determine intestinal secretion of 65 Zn. Results indicated that the small intestine plays a major role in the absorption and secretion of zinc and that aging decreases the absorption of zinc for the duodenum of the rat

Bioaccumulation and Toxicity of Single-Walled Carbon Nanotubes to Benthic Organisms at the Base of the Marine Food Chain

Science.gov (United States)

As the use of single-walled carbon nanotubes (SWNTs) increases over time, so does the potential for environmental release. This research aimed to determine the toxicity, bioavailability, and bioaccumulation of SWNTs in marine benthic organisms at the base of the food chain. The t...

An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells

Science.gov (United States)

Knies, Diana; Klobuch, Sebastian; Xue, Shao-An; Birtel, Matthias; Echchannaoui, Hakim; Yildiz, Oezlem; Omokoko, Tana; Guillaume, Philippe; Romero, Pedro; Stauss, Hans; Sahin, Ugur; Herr, Wolfgang; Theobald, Matthias; Thomas, Simone; Voss, Ralf-Holger

2016-01-01

Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells. PMID:27028870

EARLINET Single Calculus Chain - overview on methodology and strategy

Science.gov (United States)

D'Amico, G.; Amodeo, A.; Baars, H.; Binietoglou, I.; Freudenthaler, V.; Mattis, I.; Wandinger, U.; Pappalardo, G.

2015-11-01

In this paper we describe the EARLINET Single Calculus Chain (SCC), a tool for the automatic analysis of lidar measurements. The development of this tool started in the framework of EARLINET-ASOS (European Aerosol Research Lidar Network - Advanced Sustainable Observation System); it was extended within ACTRIS (Aerosol, Clouds and Trace gases Research InfraStructure Network), and it is continuing within ACTRIS-2. The main idea was to develop a data processing chain that allows all EARLINET stations to retrieve, in a fully automatic way, the aerosol backscatter and extinction profiles starting from the raw lidar data of the lidar systems they operate. The calculus subsystem of the SCC is composed of two modules: a pre-processor module which handles the raw lidar data and corrects them for instrumental effects and an optical processing module for the retrieval of aerosol optical products from the pre-processed data. All input parameters needed to perform the lidar analysis are stored in a database to keep track of all changes which may occur for any EARLINET lidar system over the time. The two calculus modules are coordinated and synchronized by an additional module (daemon) which makes the whole analysis process fully automatic. The end user can interact with the SCC via a user-friendly web interface. All SCC modules are developed using open-source and freely available software packages. The final products retrieved by the SCC fulfill all requirements of the EARLINET quality assurance programs on both instrumental and algorithm levels. Moreover, the manpower needed to provide aerosol optical products is greatly reduced and thus the near-real-time availability of lidar data is improved. The high-quality of the SCC products is proven by the good agreement between the SCC analysis, and the corresponding independent manual retrievals. Finally, the ability of the SCC to provide high-quality aerosol optical products is demonstrated for an EARLINET intense observation

Finite-size effects on the dynamic susceptibility of CoPhOMe single-chain molecular magnets in presence of a static magnetic field

Science.gov (United States)

Pini, M. G.; Rettori, A.; Bogani, L.; Lascialfari, A.; Mariani, M.; Caneschi, A.; Sessoli, R.

2011-09-01

The static and dynamic properties of the single-chain molecular magnet Co(hfac)2NITPhOMe (CoPhOMe) (hfac = hexafluoroacetylacetonate, NITPhOMe = 4'-methoxy-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) are investigated in the framework of the Ising model with Glauber dynamics, in order to take into account both the effect of an applied magnetic field and a finite size of the chains. For static fields of moderate intensity and short chain lengths, the approximation of a monoexponential decay of the magnetization fluctuations is found to be valid at low temperatures; for strong fields and long chains, a multiexponential decay should rather be assumed. The effect of an oscillating magnetic field, with intensity much smaller than that of the static one, is included in the theory in order to obtain the dynamic susceptibility χ(ω). We find that, for an open chain with N spins, χ(ω) can be written as a weighted sum of N frequency contributions, with a sum rule relating the frequency weights to the static susceptibility of the chain. Very good agreement is found between the theoretical dynamic susceptibility and the ac susceptibility measured in moderate static fields (Hdc≤2 kOe), where the approximation of a single dominating frequency for each segment length turns out to be valid. For static fields in this range, data for the relaxation time, τ versus Hdc, of the magnetization of CoPhOMe at low temperature are also qualitatively reproduced by theory, provided that finite-size effects are included.

On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

Directory of Open Access Journals (Sweden)

Wang Daoshun

2010-01-01

Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

Authentication Without Secrets

Energy Technology Data Exchange (ETDEWEB)

Pierson, Lyndon G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robertson, Perry J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-11-01

This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

Novel insulin from the bullfrog: its structure and function in protein secretion by hepatocytes

International Nuclear Information System (INIS)

Hulsebus, J.J.

1987-01-01

Bullfrog insulin was extracted and purified from the pancreas of Rana catesbeiana adults using gel filtration and reverse phase high performance liquid chromatography. Amino acid analysis of bullfrog insulin revealed 52 amino acids instead of the most common number of 51. The most unique features of bullfrog insulin is a two amino acid extension on the amino terminus (A1) of the A chain. This is the only insulin to date that has an extension at this position. Bullfrog and porcine insulin increase protein secretion from bullfrog adult and three developmental stages of tadpole hepatocytes in a totally defined, serum-free culture system. The hormone slightly stimulates protein secretion by premetamorphic and early prometamorphic tadpoles. Late prometamorphic tadpoles respond to bullfrog and porcine insulin with higher concentrations of secreted protein than either of the two previous developmental stages. Insulin treated adult hepatocytes secrete significantly higher concentrations of protein than any of the tadpole stages. 35 S-methionine and 35 S-cysteine were added to the culture medium for twelve hours. Proteins secreted into the medium were separated using SDS polyacrylamide linear gradient gels. Densitometer scans of autoradiograms did not show an increases in any specific proteins, but did show a generalized increase in all secreted proteins for both adults, and tadpoles

Structure predictions of two Bauhinia variegata lectins reveal patterns of C-terminal properties in single chain legume lectins.

Science.gov (United States)

Moreira, Gustavo M S G; Conceição, Fabricio R; McBride, Alan J A; Pinto, Luciano da S

2013-01-01

Bauhinia variegata lectins (BVL-I and BVL-II) are single chain lectins isolated from the plant Bauhinia variegata. Single chain lectins undergo post-translational processing on its N-terminal and C-terminal regions, which determines their physiological targeting, carbohydrate binding activity and pattern of quaternary association. These two lectins are isoforms, BVL-I being highly glycosylated, and thus far, it has not been possible to determine their structures. The present study used prediction and validation algorithms to elucidate the likely structures of BVL-I and -II. The program Bhageerath-H was chosen from among three different structure prediction programs due to its better overall reliability. In order to predict the C-terminal region cleavage sites, other lectins known to have this modification were analysed and three rules were created: (1) the first amino acid of the excised peptide is small or hydrophobic; (2) the cleavage occurs after an acid, polar, or hydrophobic residue, but not after a basic one; and (3) the cleavage spot is located 5-8 residues after a conserved Leu amino acid. These rules predicted that BVL-I and -II would have fifteen C-terminal residues cleaved, and this was confirmed experimentally by Edman degradation sequencing of BVL-I. Furthermore, the C-terminal analyses predicted that only BVL-II underwent α-helical folding in this region, similar to that seen in SBA and DBL. Conversely, BVL-I and -II contained four conserved regions of a GS-I association, providing evidence of a previously undescribed X4+unusual oligomerisation between the truncated BVL-I and the intact BVL-II. This is the first report on the structural analysis of lectins from Bauhinia spp. and therefore is important for the characterisation C-terminal cleavage and patterns of quaternary association of single chain lectins.

Direct demonstration of macula densa-mediated renin secretion

DEFF Research Database (Denmark)

Skøtt, O; Briggs, J P

1987-01-01

An in vitro method has been used to examine whether secretion of renin from the juxtaglomerular apparatus is affected by changes in the sodium chloride concentration of the tubular fluid at the macula densa. Single juxtaglomerular apparatuses were microdissected from rabbits and the tubule segmen...

IG and TR single chain fragment variable (scFv) sequence analysis: a new advanced functionality of IMGT/V-QUEST and IMGT/HighV-QUEST.

Science.gov (United States)

Giudicelli, Véronique; Duroux, Patrice; Kossida, Sofia; Lefranc, Marie-Paule

2017-06-26

IMGT®, the international ImMunoGeneTics information system® ( http://www.imgt.org ), was created in 1989 in Montpellier, France (CNRS and Montpellier University) to manage the huge and complex diversity of the antigen receptors, and is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. Immunoglobulins (IG) or antibodies and T cell receptors (TR) are managed and described in the IMGT® databases and tools at the level of receptor, chain and domain. The analysis of the IG and TR variable (V) domain rearranged nucleotide sequences is performed by IMGT/V-QUEST (online since 1997, 50 sequences per batch) and, for next generation sequencing (NGS), by IMGT/HighV-QUEST, the high throughput version of IMGT/V-QUEST (portal begun in 2010, 500,000 sequences per batch). In vitro combinatorial libraries of engineered antibody single chain Fragment variable (scFv) which mimic the in vivo natural diversity of the immune adaptive responses are extensively screened for the discovery of novel antigen binding specificities. However the analysis of NGS full length scFv (~850 bp) represents a challenge as they contain two V domains connected by a linker and there is no tool for the analysis of two V domains in a single chain. The functionality "Analyis of single chain Fragment variable (scFv)" has been implemented in IMGT/V-QUEST and, for NGS, in IMGT/HighV-QUEST for the analysis of the two V domains of IG and TR scFv. It proceeds in five steps: search for a first closest V-REGION, full characterization of the first V-(D)-J-REGION, then search for a second V-REGION and full characterization of the second V-(D)-J-REGION, and finally linker delimitation. For each sequence or NGS read, positions of the 5'V-DOMAIN, linker and 3'V-DOMAIN in the scFv are provided in the 'V-orientated' sense. Each V-DOMAIN is fully characterized (gene identification, sequence description, junction analysis, characterization of mutations and amino

Combined action of the major secreted exo- and endopolygalacturonases is required for full virulence of Fusarium oxysporum.

Science.gov (United States)

Bravo Ruiz, Gustavo; Di Pietro, Antonio; Roncero, M Isabel G

2016-04-01

The genome of the tomato pathogen Fusarium oxysporum f. sp. lycopersici encodes eight different polygalacturonases (PGs): four endoPGs and four exoPGs. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed that endoPGs pg1 and pg5 and exoPGs pgx4 and pgx6 are expressed at significant levels during growth on citrus pectin, polygalacturonic acid or the monomer galacturonic acid, as well as during the infection of tomato plants. The remaining PG genes exhibit low expression levels under all the conditions tested. Secreted PG activity was decreased significantly during growth on pectin in the single deletion mutants lacking either pg1 or pgx6, as well as in the double mutant. Although the single deletion mutants did not display a significant virulence reduction on tomato plants, the Δpg1Δpgx6 double mutant was significantly attenuated in virulence. The combined action of exoPGs and endoPGs is thus essential for plant infection by the vascular wilt fungus F. oxysporum. © 2015 BSPP and John Wiley & Sons Ltd.

A uranium-based UO{sub 2}{sup +}-Mn{sup 2+} single-chain magnet assembled trough cation-cation interactions

Energy Technology Data Exchange (ETDEWEB)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella [CEA-Grenoble (France). Lab. de Reconnaissance Ionique et Chimie de Coordination; Caciuffo, Roberto; Colineau, Eric [European Commission, Karlsruhe (Germany). Inst. for Transuranium Elements; Tuna, Floriana [Manchester Univ. (United Kingdom). School of Chemistry; Magnani, Nicola [KIT Karlsruhe (Germany). Inst. of Nanotechnology; Geyer, Arnaud de [CEA-Grenoble (France). Service General des Rayons X

2014-01-13

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]{sub n}, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO{sub 2}(salen)py][Cp{sup *}{sub 2}Co] (Cp{sup *}=pentamethylcyclopentadienyl) with Cd(NO{sub 3}){sub 2} or Mn(NO{sub 3}){sub 2} in pyridine. The infinite UMn chain displays a high relaxation barrier of 134±0.8 K (93±0.5 cm{sup -1}), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T<6 K, with an impressive coercive field of 3.4 T at 2 K.

A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

Science.gov (United States)

Ji, Xiaonan; Shen, Yanli; Sun, Hao; Gao, Xiangdong

2016-08-01

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity

Directory of Open Access Journals (Sweden)

Masanori Matsui

2014-01-01

Full Text Available We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.

Direct visualization of secretion from single bovine adrenal chromaffin cells by laser-induced native fluorescence imaging microscopy

Energy Technology Data Exchange (ETDEWEB)

Tong, W.; Yeung, E.S. [Ames Laboratory---USDOE and Department of Chemistry, Iowa State University, Ames, Iowa 50011 (United States)

1998-03-01

Direct visualization of the secretion process of individual bovine adrenal chromaffin cells was achieved with laser-induced native fluorescence imaging microscopy. By monitoring the native fluorescence of catecholamines excited by the 275 nm laser line with an intensified charge-coupled-device (CCD) camera, we obtained good temporal and spatial resolution simultaneously without using additional fluorescent probes. Large variations were found among individual cells in terms of the amounts of catecholamines secreted and the rates of secretion. Different regions of a cell also behave differently during the secretion process. However, the degree of this local heterogeneity is smaller than in neurons and neuralgia. The influence of deep-ultraviolet (UV) laser excitation on cells is also discussed. This quantitative imaging technique provides a useful noninvasive approach for the study of dynamic cellular changes and the understanding of the molecular mechanisms of secretory processes. {copyright} {ital 1998} {ital Society for Applied Spectroscopy}

Digestive physiology of the pig symposium: secretion of gastrointestinal hormones and eating control.

Science.gov (United States)

Steinert, R E; Feinle-Bisset, C; Geary, N; Beglinger, C

2013-05-01

Nutrient ingestion triggers numerous changes in gastrointestinal (GI) peptide hormone secretion that affect appetite and eating. Evidence for these effects comes from research in laboratory animals, healthy humans, and, increasingly, obese patients after Roux-en-Y gastric bypass (RYGB) surgery, which has marked effects on GI hormone function and is currently the most effective therapy for morbid obesity. Increases in cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine (PYY) and decreases in ghrelin secretion after meals are triggered by changes in the nutrient content of the intestine. One apparent physiological function of each is to initiate a reflex-like feedback control of eating. Here we briefly review this function, with an emphasis on the controls of their secretion. Each is secreted from enteroendocrine cells that are directly or indirectly affected by caloric load, macronutrient composition, and other characteristics of ingested food such as fatty acid chain length. In addition, digestive hydrolysis is a critical mechanism that controls their secretion. Although there are relatively few data in agricultural animals, the generally consistent results across widely divergent mammals suggests that most of the processes described are also likely to be relevant to GI hormone functions and eating in agricultural animals.

Noncoherent capacity of secret-key agreement with public discussion

KAUST Repository

Agrawal, Anurag

2011-09-01

We study the noncoherent capacity of secret-key agreement with public discussion over independent identically distributed (i.i.d.) Rayleigh fading wireless channels, where neither the sender nor the receivers have access to instantaneous channel state information (CSI). We present two results. At high signal-to-noise ratio (SNR), the secret-key capacity is bounded in SNR, regardless of the number of antennas at each terminal. Second, for a system with a single antenna at both the legitimate and the eavesdropper terminals and an arbitrary number of transmit antennas, the secret-key capacity-achieving input distribution is discrete, with a finite number of mass points. Numerically we observe that at low SNR, the capacity achieving distribution has two mass points with one of them at the origin. © 2011 IEEE.

Noncoherent capacity of secret-key agreement with public discussion

KAUST Repository

Agrawal, Anurag; Rezki, Zouheir; Khisti, Ashish J.; Alouini, Mohamed-Slim

2011-01-01

We study the noncoherent capacity of secret-key agreement with public discussion over independent identically distributed (i.i.d.) Rayleigh fading wireless channels, where neither the sender nor the receivers have access to instantaneous channel state information (CSI). We present two results. At high signal-to-noise ratio (SNR), the secret-key capacity is bounded in SNR, regardless of the number of antennas at each terminal. Second, for a system with a single antenna at both the legitimate and the eavesdropper terminals and an arbitrary number of transmit antennas, the secret-key capacity-achieving input distribution is discrete, with a finite number of mass points. Numerically we observe that at low SNR, the capacity achieving distribution has two mass points with one of them at the origin. © 2011 IEEE.

Straight and branched-chain fatty acids in preorbital glands of sika deer, Cervus nippon.

Science.gov (United States)

Wood, William F

2004-02-01

Using GC-MS analysis, 11 major volatile compounds were found in the preorbital gland secretion from a female sika deer, Cervus nippon. These compounds are the C14 through C18 straight-chain fatty acids, (ZZ)-9,12-octadecadienoic acid, 12-methyltridecanoic acid, 13-methyltetradecanoic acid, 14-methylpentadecanoic acid, 14-methylhexadecanoic acid, and 15-methylhexadecanoic acid. The five branched-chain acids make up over 29% of the volatiles in the gland. This is the first time branched-chain carboxylic acids have been reported from ungulate preorbital glands.

Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders

DEFF Research Database (Denmark)

Klitgaard, H; Zhou, M.-Y.; Richter, Erik

1990-01-01

The myosin heavy chain (MHC) composition of single fibres from m. biceps brachii of young sedentary men (28 +/- 0.4 years, mean +/- SE, n = 4) and male body builders (25 +/- 2.0 years, n = 4) was analysed with a sensitive one-dimensional electrophoretic technique. Compared with sedentary men...... expression of MHC isoforms within histochemical type II fibres of human skeletal muscle with body building. Furthermore, in human skeletal muscle differences in expression of MHC isoforms may not always be reflected in the traditional histochemical classification of types I, IIa, IIb and IIc fibres....

Quantum phase transitions in spin-1 X X Z chains with rhombic single-ion anisotropy

Science.gov (United States)

Ren, Jie; Wang, Yimin; You, Wen-Long

2018-04-01

We explore numerically the inverse participation ratios in the ground state of one-dimensional spin-1 X X Z chains with the rhombic single-ion anisotropy. By employing the techniques of density-matrix renormalization group, effects of the rhombic single-ion anisotropy on various information theoretical measures are investigated, such as the fidelity susceptibility, the quantum coherence, and the entanglement entropy. Their relations with the quantum phase transitions are also analyzed. The phase transitions from the Y -Néel phase to the large-Ex or the Haldane phase can be well characterized by the fidelity susceptibility. The second-order derivative of the ground-state energy indicates all the transitions are of second order. We also find that the quantum coherence, the entanglement entropy, the Schmidt gap, and the inverse participation ratios can be used to detect the critical points of quantum phase transitions. Results drawn from these quantum information observables agree well with each other. Finally we provide a ground-state phase diagram as functions of the exchange anisotropy Δ and the rhombic single-ion anisotropy E .

Charge distribution in an two-chain dual model

International Nuclear Information System (INIS)

Fialkowski, K.; Kotanski, A.

1983-01-01

Charge distributions in the multiple production processes are analysed using the dual chain model. A parametrisation of charge distributions for single dual chains based on the νp and anti vp data is proposed. The rapidity charge distributions are then calculated for pp and anti pp collisions and compared with the previous calculations based on the recursive cascade model of single chains. The results differ at the SPS collider energies and in the energy dependence of the net forward charge supplying the useful tests of the dual chain model. (orig.)

Realities of Supply Chain Collaboration

NARCIS (Netherlands)

Kampstra, R.P.; Ashayeri, J.; Gattorna, J.

2006-01-01

Successful supply chain collaboration (SCC) practices are rather exceptional, yet collaboration is believed to be the single most pressing need in supply chain management.In this paper we discuss the realities of SCC, present prerequisites for the collaboration process, indicate where the process

Chain formation of metal atoms

DEFF Research Database (Denmark)

Bahn, Sune Rastad; Jacobsen, Karsten Wedel

2001-01-01

The possibility of formation of single-atomic chains by manipulation of nanocontacts is studied for a selection of metals (Ni, Pd, Pt, Cu, Ag, Au). Molecular dynamics simulations show that the tendency for chain formation is strongest for Au and Pt. Density functional theory calculations indicate...... that the metals which form chains exhibit pronounced many-atom interactions with strong bonding in low coordinated systems....

Phase transitions in single macromolecules: Loop-stretch transition versus loop adsorption transition in end-grafted polymer chains

Science.gov (United States)

Zhang, Shuangshuang; Qi, Shuanhu; Klushin, Leonid I.; Skvortsov, Alexander M.; Yan, Dadong; Schmid, Friederike

2018-01-01

We use Brownian dynamics simulations and analytical theory to compare two prominent types of single molecule transitions. One is the adsorption transition of a loop (a chain with two ends bound to an attractive substrate) driven by an attraction parameter ɛ and the other is the loop-stretch transition in a chain with one end attached to a repulsive substrate, driven by an external end-force F applied to the free end. Specifically, we compare the behavior of the respective order parameters of the transitions, i.e., the mean number of surface contacts in the case of the adsorption transition and the mean position of the chain end in the case of the loop-stretch transition. Close to the transition points, both the static behavior and the dynamic behavior of chains with different length N are very well described by a scaling ansatz with the scaling parameters (ɛ - ɛ*)Nϕ (adsorption transition) and (F - F*)Nν (loop-stretch transition), respectively, where ϕ is the crossover exponent of the adsorption transition and ν is the Flory exponent. We show that both the loop-stretch and the loop adsorption transitions provide an exceptional opportunity to construct explicit analytical expressions for the crossover functions which perfectly describe all simulation results on static properties in the finite-size scaling regime. Explicit crossover functions are based on the ansatz for the analytical form of the order parameter distributions at the respective transition points. In contrast to the close similarity in equilibrium static behavior, the dynamic relaxation at the two transitions shows qualitative differences, especially in the strongly ordered regimes. This is attributed to the fact that the surface contact dynamics in a strongly adsorbed chain is governed by local processes, whereas the end height relaxation of a strongly stretched chain involves the full spectrum of Rouse modes.

Structural requirement of carboxyl-terminal globular domains of laminin alpha 3 chain for promotion of rapid cell adhesion and migration by laminin-5.

Science.gov (United States)

Hirosaki, T; Mizushima, H; Tsubota, Y; Moriyama, K; Miyazaki, K

2000-07-21

The basement membrane protein laminin-5, a heterotrimer of laminin alpha3, beta3, and gamma2 chains, potently promotes cellular adhesion and motility. It has been supposed that the carboxyl-terminal globular region of the alpha3 chain consisting of five distinct domains (G1 to G5) is important for its interaction with integrins. To clarify the function of each G domain, we transfected cDNAs for the full-length (wild type (WT)) and five deletion derivatives (DeltaGs) of the alpha3 chain into human fibrosarcoma cell line HT1080, which expressed and secreted the laminin beta3 and gamma2 chains but not the alpha3 chain. The transfectants with the alpha3 chain cDNAs lacking G5 (DeltaG(5)), G4-5 (DeltaG(4-5)), G3-5 (DeltaG(3-5)), and G2-5 (DeltaG(2-5)) secreted laminin-5 variants at levels comparable to that with WT cDNA. However, the transfectant with the cDNA without any G domains (DeltaG(1-5)) secreted little laminin-5, suggesting that the G domains are essential for the efficient assembly and secretion of the heterotrimer alpha3beta3gamma2. The transfectants with WT, DeltaG(5), and DeltaG(4-5) cDNAs survived in serum-free medium longer than those with DeltaG(3-5), DeltaG(2-5), and DeltaG(1-5) cDNAs. The transfectants with WT, DeltaG(5), and DeltaG(4-5) cDNAs secreted apparently the same size of laminin-5, which lacked G4 and G5 due to proteolytic cleavage between G3 and G4, and these laminin-5 forms potently promoted integrin alpha(3)beta(1)-dependent cell adhesion and migration. However, the laminin-5 forms of DeltaG(3-5) and DeltaG(2-5) hardly promoted the cell adhesion and motility. These findings demonstrate that the G3 domain, but not the G4 and G5 domains, of the alpha3 chain is essential for the potent promotion of cell adhesion and motility by laminin-5.

Non-coherent capacity of secret-key agreement with public discussion

KAUST Repository

Agrawal, Anurag

2011-06-01

We study the Rayleigh fading non-coherent capacity of secret-key agreement with public discussion, where neither the sender nor the receivers have access to instantaneous channel state information (CSI) of any channel. We present two results. At high Signal-to-Noise Ratio (SNR), the secret-key capacity is bounded in SNR, regardless of the number of antennas at each terminal. Second, for a system with a single antenna at both the legitimate and the eavesdropper terminals and an arbitrary number of transmit antennas, the secret-key capacity-achieving input distribution is discrete, with a finite number of mass points. Numerically we observe that at low-SNR, the capacity achieving distribution has two mass points with one of them at the origin. © 2011 IEEE.

Non-coherent capacity of secret-key agreement with public discussion

KAUST Repository

Agrawal, Anurag; Rezki, Zouheir; Khisti, Ashish J.; Alouini, Mohamed-Slim

2011-01-01

We study the Rayleigh fading non-coherent capacity of secret-key agreement with public discussion, where neither the sender nor the receivers have access to instantaneous channel state information (CSI) of any channel. We present two results. At high Signal-to-Noise Ratio (SNR), the secret-key capacity is bounded in SNR, regardless of the number of antennas at each terminal. Second, for a system with a single antenna at both the legitimate and the eavesdropper terminals and an arbitrary number of transmit antennas, the secret-key capacity-achieving input distribution is discrete, with a finite number of mass points. Numerically we observe that at low-SNR, the capacity achieving distribution has two mass points with one of them at the origin. © 2011 IEEE.

Quantum communication and state transfer in spin chains

International Nuclear Information System (INIS)

Van der Jeugt, Joris

2011-01-01

We investigate the time evolution of a single spin excitation state in certain linear spin chains, as a model for quantum communication. We consider first the simplest possible spin chain, where the spin chain data (the nearest neighbour interaction strengths and the magnetic field strengths) are constant throughout the chain. The time evolution of a single spin state is determined, and this time evolution is illustrated by means of an animation. Some years ago it was discovered that when the spin chain data are of a special form so-called perfect state transfer takes place. These special spin chain data can be linked to the Jacobi matrix entries of Krawtchouk polynomials or dual Hahn polynomials. We discuss here the case related to Krawtchouk polynomials, and illustrate the possibility of perfect state transfer by an animation showing the time evolution of the spin chain from an initial single spin state. Very recently, these ideas were extended to discrete orthogonal polynomials of q-hypergeometric type. Here, a remarkable result is a new analytic model where perfect state transfer is achieved: this is when the spin chain data are related to the Jacobi matrix of q-Krawtchouk polynomials. This case is discussed here, and again illustrated by means of an animation.

Exactly solved mixed spin-(1,1/2) Ising–Heisenberg diamond chain with a single-ion anisotropy

International Nuclear Information System (INIS)

Lisnyi, Bohdan; Strečka, Jozef

2015-01-01

The mixed spin-(1,1/2) Ising–Heisenberg diamond chain with a single-ion anisotropy is exactly solved through the generalized decoration–iteration transformation and the transfer-matrix method. The decoration–iteration transformation is first used for establishing a rigorous mapping equivalence with the corresponding spin-1 Blume–Emery–Griffiths chain, which is subsequently exactly treated within the transfer-matrix technique. Apart from three classical ground states the model exhibits three striking quantum ground states in which a singlet-dimer state of the interstitial Heisenberg spins is accompanied either with a frustrated state or a polarized state or a non-magnetic state of the nodal Ising spins. It is evidenced that two magnetization plateaus at zero and/or one-half of the saturation magnetization may appear in low-temperature magnetization curves. The specific heat may display remarkable temperature dependences with up to three and four distinct round maxima in a zero and non-zero magnetic field, respectively. - Highlights: • Mixed spin-(1,1/2) Ising–Heisenberg diamond chain is exactly solved. • Quantum ground states with a singlet-dimer state of the Heisenberg spins are found. • Magnetization curve displays intermediate plateaus at zero and half of full magnetization. • Thermal dependences of specific heat may display up to four distinct peaks

Ground state properties of a spin chain within Heisenberg model with a single lacking spin site

International Nuclear Information System (INIS)

Mebrouki, M.

2011-01-01

The ground state and first excited state energies of an antiferromagnetic spin-1/2 chain with and without a single lacking spin site are computed using exact diagonalization method, within the Heisenberg model. In order to keep both parts of a spin chain with a lacking site connected, next nearest neighbors interactions are then introduced. Also, the Density Matrix Renormalization Group (DMRG) method is used, to investigate ground state energies of large system sizes; which permits us to inquire about the effect of large system sizes on energies. Other quantum quantities such as fidelity and correlation functions are also studied and compared in both cases. - Research highlights: → In this paper we compute ground state and first excited state energies of a spin chain with and without a lacking spin site. The next nearest neighbors are introduced with the antiferromagnetic Heisenberg spin-half. → Exact diagonalization is used for small systems, where DMRG method is used to compute energies for large systems. Other quantities like quantum fidelity and correlation are also computed. → Results are presented in figures with comments. → E 0 /N is computed in a function of N for several values of J 2 and for both systems. First excited energies are also investigated.

Observation of a commensurate array of flux chains in tilted flux lattices in Bi-Sr-Ca-Cu-O single crystals

International Nuclear Information System (INIS)

Bolle, C.A.; Gammel, P.L.; Grier, D.G.; Murray, C.A.; Bishop, D.J.; Mitzi, D.B.; Kapitulnik, A.

1991-01-01

We report the observation of a novel flux-lattice structure, a commensurate array of flux-line chains. Our experiments consist of the magnetic decoration of the flux lattices in single crystals of Ba-Sr-Ca-Cu-O where the magnetic field is applied at an angle with respect to the conducting planes. For a narrow range of angles, the equilibrium structure is one with uniformly spaced chains with a higher line density of vortices than the background lattice. Our observations are in qualitative agreement with theories which suggest that, in strongly anisotropic materials the vortices develop an attractive interaction in tilted magnetic fields

Calculation of single chain cellulose elasticity using fully atomistic modeling

Science.gov (United States)

Xiawa Wu; Robert J. Moon; Ashlie Martini

2011-01-01

Cellulose nanocrystals, a potential base material for green nanocomposites, are ordered bundles of cellulose chains. The properties of these chains have been studied for many years using atomic-scale modeling. However, model predictions are difficult to interpret because of the significant dependence of predicted properties on model details. The goal of this study is...

Excitation of random intense single-cycle light-pulse chains in optical fiber

International Nuclear Information System (INIS)

Ding, Y C; Zhang, F L; Gao, J B; Chen, Z Y; Lin, C Y; Yu, M Y

2014-01-01

Excitation of intense periodic single-cycle light pulses in a stochastic background arising from continuous wave stimulated Brillouin scattering (SBS) in a long optical fiber with weak optical feedback is found experimentally and modeled theoretically. Such intense light-pulse chains occur randomly and the optical feedback is a requirement for their excitation. The probability of these forms, among the large number of experimental output signals with identifiable waveforms, appearing is only about 3%, with the remainder exhibiting regular SBS characteristics. It is also found that pulses with low period numbers appear more frequently and the probability distribution for their occurrence in terms of the pulse power is roughly L-shaped, like that for rogue waves. The results from a three-wave-coupling model for SBS including feedback phase control agree well qualitatively with the observed phenomena. (paper)

Secretory signal peptide modification for optimized antibody-fragment expression-secretion in Leishmania tarentolae

Directory of Open Access Journals (Sweden)

Klatt Stephan

2012-07-01

Full Text Available Abstract Background Secretory signal peptides (SPs are well-known sequence motifs targeting proteins for translocation across the endoplasmic reticulum membrane. After passing through the secretory pathway, most proteins are secreted to the environment. Here, we describe the modification of an expression vector containing the SP from secreted acid phosphatase 1 (SAP1 of Leishmania mexicana for optimized protein expression-secretion in the eukaryotic parasite Leishmania tarentolae with regard to recombinant antibody fragments. For experimental design the online tool SignalP was used, which predicts the presence and location of SPs and their cleavage sites in polypeptides. To evaluate the signal peptide cleavage site as well as changes of expression, SPs were N-terminally linked to single-chain Fragment variables (scFv’s. The ability of L. tarentolae to express complex eukaryotic proteins with highly diverse post-translational modifications and its easy bacteria-like handling, makes the parasite a promising expression system for secretory proteins. Results We generated four vectors with different SP-sequence modifications based on in-silico analyses with SignalP in respect to cleavage probability and location, named pLTEX-2 to pLTEX-5. To evaluate their functionality, we cloned four individual scFv-fragments into the vectors and transfected all 16 constructs into L. tarentolae. Independently from the expressed scFv, pLTEX-5 derived constructs showed the highest expression rate, followed by pLTEX-4 and pLTEX-2, whereas only low amounts of protein could be obtained from pLTEX-3 clones, indicating dysfunction of the SP. Next, we analysed the SP cleavage sites by Edman degradation. For pLTEX-2, -4, and -5 derived scFv’s, the results corresponded to in-silico predictions, whereas pLTEX-3 derived scFv’s contained one additional amino-acid (AA. Conclusions The obtained results demonstrate the importance of SP-sequence optimization for efficient

A uranium-based UO{sub 2}{sup +}-Mn{sup 2+} single-chain magnet assembled trough cation-cation interactions

Energy Technology Data Exchange (ETDEWEB)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella [Laboratoire de Reconnaissance Ionique et Chimie de Coordination, SCIB, UMR-E3 CEA-UJF, INAC, CEA-Grenoble (France); Caciuffo, Roberto; Colineau, Eric [European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe (Germany); Tuna, Floriana [EPSRC UK EPR Facility, School of Chemistry and Photon Science Institute, The University of Manchester (United Kingdom); Magnani, Nicola [Institute of Nanotechnology, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Geyer, Arnaud de [Service General des Rayons X, SP2M, INAC, CEA-Grenoble (France)

2014-01-13

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]{sub n}, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO{sub 2}(salen)py][Cp*{sub 2}Co] (Cp*=pentamethylcyclopentadienyl) with Cd(NO{sub 3}){sub 2} or Mn(NO{sub 3}){sub 2} in pyridine. The infinite UMn chain displays a high relaxation barrier of 134 ±0.8 K (93 ±0.5 cm{sup -1}), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T <6 K, with an impressive coercive field of 3.4 T at 2 K. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Development of a single-chain variable fragment-alkaline phosphatase fusion protein and a sensitive direct competitive chemiluminescent enzyme immunoassay for detection of ractopamine in pork

Energy Technology Data Exchange (ETDEWEB)

Dong Jiexian; Li Zhenfeng; Lei Hongtao; Sun Yuanming [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China); Ducancel, Frederic [CEA, iBiTec-S, Service de Pharmacologie et d' Immnoanalyse (SPI), CEA Saclay, F-91191 Gif sur Yvette (France); Xu Zhenlin [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China); Boulain, Jean-Claude [CEA, iBiTec-S, Service de Pharmacologie et d' Immnoanalyse (SPI), CEA Saclay, F-91191 Gif sur Yvette (France); Yang Jinyi; Shen Yudong [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China); Wang Hong, E-mail: gzwhongd@63.com [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China)

2012-07-29

Graphical abstract: Detection model of dc-CLEIA based on anti-RAC scFv-AP fusion protein. Highlights: Black-Right-Pointing-Pointer The scFv-AP fusion protein against ractopamine (RAC) was produced. Black-Right-Pointing-Pointer A dc-CLEIA for RAC was developed based on the purified scFv-AP fusion protein. Black-Right-Pointing-Pointer The sensitivity of dc-CLEIA was 10 times as sensitive as dc-ELISA for RAC. Black-Right-Pointing-Pointer Recovery tests from pork samples were studied. Black-Right-Pointing-Pointer Good accuracy was obtained. - Abstract: A rapid, sensitive chemiluminescent enzyme immunoassay (CLEIA) for ractopamine (RAC) based on a single-chain variable fragment (scFv)-alkaline phosphatase (AP) fusion protein was developed. The scFv gene was prepared by cloning the heavy- and light-chain variable region genes (V{sub H} and V{sub L}) from hybridoma cell line AC2, which secretes antibodies against RAC, and assembling V{sub H} and V{sub L} genes with a linker by means of splicing overlap extension polymerase chain reaction. The resulting scFv gene was inserted into the expression vector pLIP6/GN containing AP to produce the fusion protein in Escherichia coli strain BL21. The purified scFv-AP fusion protein was used to develop a direct competitive CLEIA (dcCLEIA) protocol for detection of RAC. The average concentration required for 50% inhibition of binding and the limit of detection of the assay were 0.25 {+-} 0.03 and 0.02 {+-} 0.004 ng mL{sup -1}, respectively, and the linear response range extended from 0.05 to 1.45 ng mL{sup -1}. The assay was 10 times as sensitive as the corresponding enzyme-linked immunosorbent assay based on the same fusion protein. Cross-reactivity studies showed that the fusion protein did not cross react with RAC analogs. DcCLEIA was used to analyze RAC spiked pork samples, and the validation was confirmed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The results showed a good correlation between

Expression and characterization of recombinant single-chain salmon class I MHC fused with beta2-microglobulin with biological activity

DEFF Research Database (Denmark)

Zhao, Heng; Stet, René J M; Skjødt, Karsten

2008-01-01

Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa beta2-microglobulin (beta2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable ...... MHC class I molecules with biological activity. We report here the use of a bacterial expression system to produce the recombinant single-chain MHC molecules based on a specific allele Sasa-UBA*0301. This particular allele was selected because previous work has shown its association...... antibodies were successfully produced against both the MHC class I heavy chain and beta(2)m, and showed binding to the recombinant molecule. The recombinant complex Sasabeta2mUBA*0301 was expressed and isolated; the production was scaled up by adjusting to its optimal conditions. Subsequently......, the recombinant proteins were purified by affinity chromatography using mAb against beta2m and alpha3. Eluates were analyzed by Western blot and refolded by the removal of denaturant. The correct folding was confirmed by measuring its binding capacity against mAb produced to recognize the native form of MHC...

LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

Directory of Open Access Journals (Sweden)

Matson Jyl S

2008-02-01

Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

Arachnids secrete a fluid over their adhesive pads.

Directory of Open Access Journals (Sweden)

Anne M Peattie

Full Text Available BACKGROUND: Many arachnids possess adhesive pads on their feet that help them climb smooth surfaces and capture prey. Spider and gecko adhesives have converged on a branched, hairy structure, which theoretically allows them to adhere solely by dry (solid-solid intermolecular interactions. Indeed, the consensus in the literature is that spiders and their smooth-padded relatives, the solifugids, adhere without the aid of a secretion. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the adhesive contact zone of living spiders, solifugids and mites using interference reflection microscopy, which allows the detection of thin liquid films. Like insects, all the arachnids we studied left behind hydrophobic fluid footprints on glass (mean refractive index: 1.48-1.50; contact angle: 3.7-11.2°. Fluid was not always secreted continuously, suggesting that pads can function in both wet and dry modes. We measured the attachment forces of single adhesive setae from tarantulas (Grammostola rosea by attaching them to a bending beam with a known spring constant and filming the resulting deflection. Individual spider setae showed a lower static friction at rest (26%±2.8 SE of the peak friction than single gecko setae (Thecadactylus rapicauda; 96%±1.7 SE. This may be explained by the fact that spider setae continued to release fluid after isolation from the animal, lubricating the contact zone. SIGNIFICANCE: This finding implies that tarsal secretions occur within all major groups of terrestrial arthropods with adhesive pads. The presence of liquid in an adhesive contact zone has important consequences for attachment performance, improving adhesion to rough surfaces and introducing rate-dependent effects. Our results leave geckos and anoles as the only known representatives of truly dry adhesive pads in nature. Engineers seeking biological inspiration for synthetic adhesives should consider whether model species with fluid secretions are appropriate to their

Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

Science.gov (United States)

Chen, Chien-Chang; Liu, Chong-An

2013-01-01

A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places

Science.gov (United States)

Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth

2014-01-01

In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…

Effects of dietary biotin supplementation on glucagon production, secretion, and action.

Science.gov (United States)

Lazo-de-la-Vega-Monroy, Maria-Luisa; Larrieta, Elena; Tixi-Verdugo, Wilma; Ramírez-Mondragón, Rafael; Hernández-Araiza, Ileana; German, Michael S; Fernandez-Mejia, Cristina

Despite increasing evidence that pharmacologic concentrations of biotin modify glucose metabolism, to our knowledge there have not been any studies addressing the effects of biotin supplementation on glucagon production and secretion, considering glucagon is one of the major hormones in maintaining glucose homeostasis. The aim of this study was to investigate the effects of dietary biotin supplementation on glucagon expression, secretion, and action. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for 8 wk postweaning. Glucagon gene mRNA expression was measured by the real-time polymerase chain reaction. Glucagon secretion was assessed in isolated islets and by glucagon concentration in plasma. Glucagon action was evaluated by glucagon tolerance tests, phosphoenolpyruvate carboxykinase (Pck1) mRNA expression, and glycogen degradation. Compared with the control group, glucagon mRNA and secretion were increased from the islets of the biotin-supplemented group. Fasting plasma glucagon levels were higher, but no differences between the groups were observed in nonfasting glucagon levels. Despite the elevated fasting glucagon levels, no differences were found in fasting blood glucose concentrations, fasting/fasting-refeeding glucagon tolerance tests, glycogen content and degradation, or mRNA expression of the hepatic gluconeogenic rate-limiting enzyme, Pck1. These results demonstrated that dietary biotin supplementation increased glucagon expression and secretion without affecting fasting blood glucose concentrations or glucagon tolerance and provided new insights into the effect of biotin supplementation on glucagon production and action. Copyright © 2017 Elsevier Inc. All rights reserved.

Ability of multicellular salt glands in Tamarix species to secrete Na+ and K+ selectively.

Science.gov (United States)

Ma, Haiyan; Tian, Changyan; Feng, Gu; Yuan, Junfeng

2011-03-01

The present study aimed to determine the mechanism of cation-selective secretion by multicellular salt glands. Using a hydroponic culture system, the secretion and accumulation of Na(+) and K(+) in Tamarix ramosissima and T. laxa under different salt stresses (NaCl, KCl and NaCl+KCl) were studied. Additionally, the effects of salt gland inhibitors (orthovanadate, Ba(2+), ouabain, tetraethylammonium (TEA) and verapamil) on Na(+) and K(+) secretion and accumulation were examined. Treatment with NaCl (at 0-200 mmol L(-1) levels) significantly increased Na(+) secretion, whereas KCl treatment (at 0-200 mmol L(-1) levels) significantly increased K(+) secretion. The ratio of secretion to accumulation of Na(+) was higher than that of K(+). The changes in Na(+) and K(+) secretion differed after adding different ions into the single-salt solutions. Addition of NaCl to the KCl solution (at 100 mmol L(-1) level, respectively) led to a significant decrease in K(+) secretion rate, whereas addition of KCl to the NaCl solution (at 100 mmol L(-1) level, respectively) had little impact on the Na(+) secretion rate. These results indicated that Na+ secretion in Tamarix was highly selective. In addition, Na(+) secretion was significantly inhibited by orthovanadate, ouabain, TEA and verapamil, and K(+) secretion was significantly inhibited by ouabain, TEA and verapamil. The different impacts of orthovanadate on Na(+) and K(+) secretion might be the primary cause for the different Na(+) and K(+) secretion abilities of multicellular salt glands in Tamarix.

Leucine metabolism in regulation of insulin secretion from pancreatic beta cells

OpenAIRE

Yang, Jichun; Chi, Yujing; Burkhardt, Brant R.; Guan, Youfei; Wolf, Bryan A

2010-01-01

Leucine, a the branched-chain amino acids that must be supplied in daily diet, plays an important role in controlling protein synthesis and regulating cell metabolism in various cell types. In pancreatic β cells, leucine acutely stimulates insulin secretion by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. Leucine has also been shown to regulate gene transcription and protein synthesis in pancreatic islet β cells via both mTOR-dep...

Crystallization and preliminary crystallographic studies of the single-chain variable fragment of antibody chA21 in complex with an N-terminal fragment of ErbB2

International Nuclear Information System (INIS)

Liu, Yang; Zhou, Huihao; Zhu, Juanjuan; Gao, Yongxiang; Niu, Liwen; Liu, Jing; Teng, Maikun

2009-01-01

An antibody–antigen complex consisting of a single-chain variable fragment of the potential therapeutic antibody chA21 and an N-terminal fragment (residues 1–192) of the human ErbB2 extracellular domain was expressed, purified and crystallized. X-ray diffraction data were collected to 2.45 Å resolution. ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes abnormality and disorder in cell signalling and leads to cell transformation. Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was developed. Here, an antibody–antigen complex consisting of the single-chain variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1–192, named EP I) of the ErbB2 extracellular domain was crystallized using the sitting-drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45 Å resolution from a single flash-cooled crystal; the crystal belonged to space group P2 1 2 1 2 1

Salmonella-secreted Virulence Factors

Energy Technology Data Exchange (ETDEWEB)

Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

2011-05-01

In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

Cell surface expression of single chain antibodies with applications to imaging of gene expression in vivo

International Nuclear Information System (INIS)

Northrop, Jeffrey P.; Bednarski, Mark; Li, King C.; Barbieri, Susan O.; Lu, Amy T.; Nguyen, Dee; Varadarajan, John; Osen, Maureen; Star-Lack, Josh

2003-01-01

Imaging of gene expression in vivo has many potential uses for biomedical research and drug discovery, ranging from the study of gene regulation and cancer to the non-invasive assessment of gene therapies. To streamline the development of imaging marker gene technologies for nuclear medicine, we propose a new approach to the design of reporter/probe pairs wherein the reporter is a cell surface-expressed single chain antibody variable fragment that has been raised against a low molecular weight imaging probe with optimized pharmacokinetic properties. Proof of concept of the approach was achieved using a single chain antibody variable fragment that binds with high affinity to fluorescein and an imaging probe consisting of fluorescein isothiocyanate coupled to the chelator diethylene triamine penta-acetic acid labeled with the gamma-emitter 111 In. We demonstrate specific high-affinity binding of this probe to the cell surface-expressed reporter in vitro and assess the in vivo biodistribution of the probe both in wild-type mice and in mice harboring tumor xenografts expressing the reporter. Specific uptake of the probe by, and in vivo imaging of, tumors expressing the reporter are shown. Since ScFvs with high affinities can be raised to almost any protein or small molecule, the proposed methodology may offer a new flexibility in the design of imaging tracer/reporter pairs wherein both probe pharmacokinetics and binding affinities can be readily optimized. (orig.)

Single-chain magnet features in 1D [MnR{sub 4}TPP][TCNE] compounds

Energy Technology Data Exchange (ETDEWEB)

Balanda, Maria [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow (Poland); Tomkowicz, Zbigniew; Rams, Michal [Institute of Physics, Jagiellonian University, Reymonta 4, 30-059 Krakow (Poland); Haase, Wolfgang, E-mail: Maria.Balanda@ifj.edu.pl [Institute of Physical Chemistry, Darmstadt University of Technology, 64287 Darmstadt (Germany)

2011-07-06

Molecular chains of antiferrimagnetically coupled Mn{sup III}-ion (S = 2) and TCNE (tetracyanoethylene) radical moments (s = 1/2 ) show different behaviour depending on group R substituted to TPP (tetraphenylporphyrin) and on the substitution site. The compound with R = F in Ortho position is a Single-Chain Magnet (SCM) with blocking temperature T{sub b} = 6.6K, while that with R = F in Meta position shows both blocking (T{sub b} = 5.4 K) and magnetic ordering transition (T{sub c} = 10 K). For bulky groups R = OC{sub n}H{sub 2n+1}, the magnetically ordered phase is observed (T{sub c} {approx} 22 K), which does not however prevent slow relaxation at T <8 K. Magnetic hysteresis with coercive field H{sub c} of 2 T at 2.3 K is like that of SCM. The frequency dependent AC susceptibility in the superimposed DC field reveals common features of all systems. The energy of intrachain ferromagnetic coupling between effective spin units 3/2, relevant at low temperatures, is determined for all compounds and the interchain dipolar coupling is estimated. It is concluded that slow relaxation is inherent for all quasi one-dimensional compounds and for the magnetically ordered ones shows up in the high enough magnetic field.

Meaningful Share Generation for Increased Number of Secrets in Visual Secret-Sharing Scheme

Directory of Open Access Journals (Sweden)

Mustafa Ulutas

2010-01-01

Full Text Available This paper presents a new scheme for hiding two halftone secret images into two meaningful shares created from halftone cover images. Meaningful shares are more desirable than noise-like (meaningless shares in Visual Secret Sharing because they look natural and do not attract eavesdroppers' attention. Previous works in the field focus on either increasing number of secrets or creating meaningful shares for one secret image. The method outlined in this paper both increases the number of secrets and creates meaningful shares at the same time. While the contrast ratio of shares is equal to that of Extended Visual Cryptography, two secrets are encoded into two shares as opposed to one secret in the Extended Visual Cryptography. Any two natural-looking images can be used as cover unlike the Halftone Visual Cryptography method where one cover should be the negative of the other cover image and can only encode one secret. Effectiveness of the proposed method is verified by an experiment.

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma.

Science.gov (United States)

Zhang, Jianhua; Liu, Shanhong; Shang, Zhigang; Shi, Li; Yun, Jun

2012-08-22

We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=ABn-ABO2+CDn-CDO2+BCn-BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.

Consistency of the single calculus chain for climatological studies using long-term measurements from thessaloniki lidar station

Science.gov (United States)

Siomos, Nikolaos; Voudouri, Kalliopi A.; Filioglou, Maria; Giannakaki, Eleni; Amiridis, Vasilis; D'Amico, Giuseppe; Balis, Dimitris S.

2018-04-01

The long term analysis of 15 years of lidar data derived from a Raman lidar at Thessaloniki is presented here. All measurements have been processed with the latest version 4 of the EARLINET Single Calculus Chain algorithm and are compared with the results from the current operational retrieval algorithm. In this paper we investigate the consistency between the EARLINET database and SCC for the case of Thessaloniki and we identify the issues to be considered when switching from current operations to SCC.

Expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori

NARCIS (Netherlands)

Joosten, V.; Gouka, R.J.; Hondel, C.A.M.J.J. van den; Verrips, C.T.; Lokman, B.C.

2005-01-01

We report the expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori. Fragments encoding VHHs were cloned in a suitable Aspergillus expression vector and transformants secreting VHH fragments were analysed for integrated gene copy-numbers, mRNA

Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

Directory of Open Access Journals (Sweden)

Tanya L Poshusta

Full Text Available BACKGROUND: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL, each patient has a unique monoclonal immunoglobulin light chain (LC that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels of circulating immunoglobulin free light chain varies greatly, but even patients with very low levels can have very advanced amyloid deposition. CONCLUSIONS: Our results show that in specific secondary structure elements, there are significant differences in the number of non-conservative mutations between normal and AL sequences. AL sequences from patients with different levels of secreted light chain have distinct differences in the location of non-conservative mutations, suggesting that for patients with very low levels of light chains and advanced amyloid deposition, the location of non-conservative mutations rather than the amount of free light chain in circulation may determine the amyloidogenic propensity of light chains.

Secret sharing via quantum entanglement

International Nuclear Information System (INIS)

Hillery, M.; Buzek, V.

1999-01-01

Secret sharing is a procedure for splitting a message into several parts so that no single part is sufficient to read the message, but the entire set is. This procedure can be implemented using either GHZ states or two-particle entangled states. In the quantum case the presence of an eavesdropper will introduce errors so that her presence can be detected. We also discuss how quantum information can be split into parts so that the message can be reconstructed from a sufficiently large subset of the parts. (Authors)

Formation and properties of metal-oxygen atomic chains

DEFF Research Database (Denmark)

Thijssen, W.H.A.; Strange, Mikkel; de Brugh, J.M.J.A.

2008-01-01

of longer atomic chains. The mechanical and electrical properties of these diatomic chains have been investigated by determining local vibration modes of the chain and by measuring the dependence of the average chain-conductance on the length of the chain. Additionally, we have performed calculations......Suspended chains consisting of single noble metal and oxygen atoms have been formed. We provide evidence that oxygen can react with and be incorporated into metallic one-dimensional atomic chains. Oxygen incorporation reinforces the linear bonds in the chain, which facilitates the creation...

A family of rare-earth-based single chain magnets: playing with anisotropy.

Science.gov (United States)

Bernot, Kevin; Bogani, Lapo; Caneschi, Andrea; Gatteschi, Dante; Sessoli, Roberta

2006-06-21

The first family of rare-earth-based single chain magnets is presented. Compounds of general formula [M(hfac)3(NITPhOPh)], where M = Eu, Gd, Tb, Dy, Ho, Er, or Yb, and PhOPh is the nitronyl-nitroxide radical (2,4'-benzoxo-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), have been structurally characterized and found to be isostructural. The characterization of both static and dynamic magnetic properties of the whole family is reported. Dy, Tb, and Ho compounds display slow relaxation of the magnetization, and ac susceptibility shows a thermally activated regime with energy barriers of 69, 45, and 34 K for Dy, Tb, and Ho compounds, respectively, while only a frequency-dependent susceptibility is observed for Er below 2.0 K. In Gd and Yb derivatives, antiferromagnetic interactions dominate. The pre-exponential factors differ by about 4 orders of magnitude. Finite size effects, due to naturally occurring defects, affect the static and dynamic properties of the compounds differently.

Comparison of reverse transcription-quantitative polymerase chain reaction methods and platforms for single cell gene expression analysis.

Science.gov (United States)

Fox, Bridget C; Devonshire, Alison S; Baradez, Marc-Olivier; Marshall, Damian; Foy, Carole A

2012-08-15

Single cell gene expression analysis can provide insights into development and disease progression by profiling individual cellular responses as opposed to reporting the global average of a population. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the "gold standard" for the quantification of gene expression levels; however, the technical performance of kits and platforms aimed at single cell analysis has not been fully defined in terms of sensitivity and assay comparability. We compared three kits using purification columns (PicoPure) or direct lysis (CellsDirect and Cells-to-CT) combined with a one- or two-step RT-qPCR approach using dilutions of cells and RNA standards to the single cell level. Single cell-level messenger RNA (mRNA) analysis was possible using all three methods, although the precision, linearity, and effect of lysis buffer and cell background differed depending on the approach used. The impact of using a microfluidic qPCR platform versus a standard instrument was investigated for potential variability introduced by preamplification of template or scaling down of the qPCR to nanoliter volumes using laser-dissected single cell samples. The two approaches were found to be comparable. These studies show that accurate gene expression analysis is achievable at the single cell level and highlight the importance of well-validated experimental procedures for low-level mRNA analysis. Copyright © 2012 Elsevier Inc. All rights reserved.

Bowman-Birk inhibitor-like protein is secreted by sprouted pea seeds in response to induced colonization by enteropathogenic Escherichia coli.

Science.gov (United States)

Anuradha, Ravi; Raveendran, Muthuraj; Babu, Subramanian

2013-11-01

The interaction between the clinical isolate of enteropathogenic Escherichia coli (EPEC) SBANU8 and pea sprouts was compared with avirulent K 12. E. coli. This was carried out by repeated co-incubation with pea sprouts for 5 days, and the protein profile of the culture supernatant was analyzed by single and two-dimensional electrophoresis. Mass spectrometry analysis led to the identification of two serine protease inhibitors including a Bowman-Birk-type protein secreted by pea sprouts in response to clinical isolate. Expression of the E. coli intimin gene involved in animal host colonization and virulence was studied by reverse transcription polymerase chain reaction. Expression of this gene was high in SBANU8 when co-incubated with pea sprouts. The present study gives baseline data on the molecular level interactions of EPEC and pea sprouts, which are needed to design the outbreak control strategies.

Analysis of chemical profiles of insect adhesion secretions by gas chromatography–mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Reitz, Manuela [Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen (Germany); Gerhardt, Heike [Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen (Germany); Schmitt, Christian; Betz, Oliver [Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen (Germany); Albert, Klaus, E-mail: klaus.albert@uni-tuebingen.de [Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen (Germany); Lämmerhofer, Michael, E-mail: michael.laemmerhofer@uni-tuebingen.de [Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen (Germany)

2015-01-07

Highlights: • Adhesion secretions of desert locust analyzed by GC–MS. • Insect secretions are composed of apolar and polar constituents. • Sampling simplified with contact SPME as compared to solvent sampling. • Thin-film SPME-GC–MS revealed complex alkane patterns for insect secretions. • Differences in tarsal (feet) secretions and samples from tibiae (upper legs) identified. - Abstract: This article reports on the chemical analysis of molecular profiles of tarsal secretions of the desert locust Schistocerca gregaria (Forsskål, 1775) by gas chromatography hyphenated with quadrupol mass spectrometry (GC–MS) as well as {sup 1}H-nuclear magnetic resonance ({sup 1}H NMR) spectroscopy. Special focus of this study was to elaborate on sampling methods which enable selective microscale extraction of insect secretions in a spatially controlled manner, in particular tarsal adhesive secretions and secretions located on cuticle surfaces at the tibia. Various solvent sampling procedures and contact solid-phase microextraction (SPME) methods were compared in terms of comprehensiveness and extraction efficiencies as measured by signal intensities in GC–MS. Solvent sampling with water as extraction solvent gave access to the elucidation of chemical profiles of polar compound classes such as amino acids and carbohydrates, but is extremely tedious. Contact SPME on the other hand can be regarded as a simplified and more elegant alternative, in particular for the lipophilic compound fraction. Many proteinogenic amino acids and ornithine as well as carbohydrate monomers arabinose, xylose, glucose, and galactose were detected in tarsal secretions after acid hydrolysis of aqueous extracts. Qualitatively similar but quantitatively significantly different molecular profiles were found for the lipid fraction which contained mainly n-alkanes and internally branched monomethyl-, dimethyl-, and trimethyl-alkanes in the C23–C49 range as well as long chain fatty acids and

Analysis of chemical profiles of insect adhesion secretions by gas chromatography–mass spectrometry

International Nuclear Information System (INIS)

Reitz, Manuela; Gerhardt, Heike; Schmitt, Christian; Betz, Oliver; Albert, Klaus; Lämmerhofer, Michael

2015-01-01

Highlights: • Adhesion secretions of desert locust analyzed by GC–MS. • Insect secretions are composed of apolar and polar constituents. • Sampling simplified with contact SPME as compared to solvent sampling. • Thin-film SPME-GC–MS revealed complex alkane patterns for insect secretions. • Differences in tarsal (feet) secretions and samples from tibiae (upper legs) identified. - Abstract: This article reports on the chemical analysis of molecular profiles of tarsal secretions of the desert locust Schistocerca gregaria (Forsskål, 1775) by gas chromatography hyphenated with quadrupol mass spectrometry (GC–MS) as well as 1 H-nuclear magnetic resonance ( 1 H NMR) spectroscopy. Special focus of this study was to elaborate on sampling methods which enable selective microscale extraction of insect secretions in a spatially controlled manner, in particular tarsal adhesive secretions and secretions located on cuticle surfaces at the tibia. Various solvent sampling procedures and contact solid-phase microextraction (SPME) methods were compared in terms of comprehensiveness and extraction efficiencies as measured by signal intensities in GC–MS. Solvent sampling with water as extraction solvent gave access to the elucidation of chemical profiles of polar compound classes such as amino acids and carbohydrates, but is extremely tedious. Contact SPME on the other hand can be regarded as a simplified and more elegant alternative, in particular for the lipophilic compound fraction. Many proteinogenic amino acids and ornithine as well as carbohydrate monomers arabinose, xylose, glucose, and galactose were detected in tarsal secretions after acid hydrolysis of aqueous extracts. Qualitatively similar but quantitatively significantly different molecular profiles were found for the lipid fraction which contained mainly n-alkanes and internally branched monomethyl-, dimethyl-, and trimethyl-alkanes in the C23–C49 range as well as long chain fatty acids and aldehydes

Expression and purification of a novel therapeutic single-chain variable fragment antibody against BNP from inclusion bodies of Escherichia coli.

Science.gov (United States)

Bu, Dawei; Zhou, Yuwei; Tang, Jian; Jing, Fang; Zhang, Wei

2013-12-01

Abnormal brain natriuretic peptide (BNP) secretion is regarded as the dominating mechanism of cerebral salt wasting syndrome (CSW), which results from a renal loss of sodium and water during intracranial disease leading to hyponatremia. Scale preparation of therapeutic single-chain variable fragment (scFv) that can neutralize elevated circulating BNP may have potential value for clinical use. In this report, we used a recently isolated humanized anti-BNP scFv fragment (3C1) as model antibody (Ab) to evaluate the potential of scale production of this therapeutic protein. The truncated gene encoding for scFv fragment cloned in pET22b (+) was mainly overexpressed as inclusion bodies in Escherichia coli (E. coli) Rosetta (DE3) pLysS cells. The insoluble fragment was solubilized and purified by Ni-NTA agarose resin under denaturation conditions, and recovered via an effective refolding buffer containing 50 mM Tris-HCl, pH 8.0, 0.15 M NaCl, 1 mM EDTA, 0.5 M arginine, 2 mM GSH, 1 mM GSSG, and 5% glycerol. The refolded scFv fragment was concentrated by PEG20000, and dialyzed in PBS (containing 5% glycerol, pH 7.4). The final yield was approximately 10.2 mg active scFv fragment per liter of culture (3.4 g wet weight cells). The scFv fragment was more than 95% pure assessed by SDS-PAGE assay. Recombinant scFv fragment with His tag displayed its immunoreactivity with anti-His tag Ab by western blotting. ELISA showed the scFv fragment specifically bound to BNP, and it displayed similar activity as the traditional anti-BNP monoclonal Ab (mAb). Thus, the current strategy allows convenient small-scale production of this therapeutic protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

DEFF Research Database (Denmark)

Schmidt, P T; Hansen, L; Hilsted, L

2004-01-01

BACKGROUND: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin....... METHODS: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. RESULTS: CCK infusion...... at 10(-9) M and 10(-8) M decreased gastrin output to 70.5% +/- 7.6% (n = 8) and 76.3% +/- 3.6% (n = 7) of basal output, respectively. CCK at 10(-10) M had no effect (n = 6). Somatostatin secretion was dose-dependently increased by CCK infusion and increased to 268 +/- 38.2% (n = 7) of basal secretion...

Supply Chain Management in Albania: An Empirical Study

OpenAIRE

Alma Spaho, Thoma Mitre

2012-01-01

Supply chain management in Albania has received little attention in the recent literature. Many companies now realize that actions taken by one member of the chain can influence the profitability of all others in the chain. Companies are increasingly thinking in terms of competing as part of a supply chain against other supply chains, rather than as a single firm against other individual firms. The aim of the paper is to investigate the current situation of supply chain management in Albania ...

Dynamic quantum secret sharing

International Nuclear Information System (INIS)

Jia, Heng-Yue; Wen, Qiao-Yan; Gao, Fei; Qin, Su-Juan; Guo, Fen-Zhuo

2012-01-01

In this Letter we consider quantum secret sharing (QSS) between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications. -- Highlights: ► We consider quantum secret sharing between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). ► In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. ► Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. ► Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. ► Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications.

Quantum gates controlled by spin chain soliton excitations

Energy Technology Data Exchange (ETDEWEB)

Cuccoli, Alessandro, E-mail: cuccoli@fi.infn.it [Dipartimento di Fisica e Astronomia, Università di Firenze, I-50019 Sesto Fiorentino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Firenze, I-50019 Sesto Fiorentino (Italy); Nuzzi, Davide [Dipartimento di Fisica e Astronomia, Università di Firenze, I-50019 Sesto Fiorentino (Italy); Vaia, Ruggero [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, I-50019 Sesto Fiorentino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Firenze, I-50019 Sesto Fiorentino (Italy); Verrucchi, Paola [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, I-50019 Sesto Fiorentino (Italy); Dipartimento di Fisica e Astronomia, Università di Firenze, I-50019 Sesto Fiorentino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Firenze, I-50019 Sesto Fiorentino (Italy)

2014-05-07

Propagation of soliton-like excitations along spin chains has been proposed as a possible way for transmitting both classical and quantum information between two distant parties with negligible dispersion and dissipation. In this work, a somewhat different use of solitons is considered. Solitons propagating along a spin chain realize an effective magnetic field, well localized in space and time, which can be exploited as a means to manipulate the state of an external spin (i.e., a qubit) that is weakly coupled to the chain. We have investigated different couplings between the qubit and the chain, as well as different soliton shapes, according to a Heisenberg chain model. It is found that symmetry properties strongly affect the effectiveness of the proposed scheme, and the most suitable setups for implementing single qubit quantum gates are singled out.

Oxygen vacancy chain and conductive filament formation in hafnia

Science.gov (United States)

Xue, Kan-Hao; Miao, Xiang-Shui

2018-04-01

The stability and aggregation mechanisms of oxygen vacancy chains are studied for hafnia using self-energy corrected density functional theory. While oxygen vacancies tend not to align along the c-axis of monoclinic HfO2, oxygen vacancy chains along a-axis and b-axis are energetically favorable, with cohesive energies of 0.05 eV and 0.03 eV per vacancy, respectively. Nevertheless, with an increase of the cross section area, intensive oxygen vacancy chains become much more stable in hafnia, which yields phase separation into Hf-clusters and HfO2. Compared with disperse single vacancy chains, intensive oxygen vacancy chains made of 4, 6, and 8 single vacancy chains are energetically more favorable by 0.17, 0.20, and 0.30 eV per oxygen vacancy, respectively. On the other hand, while a single oxygen vacancy chain exhibits a tiny electronic energy gap of around 0.5 eV, metallic conduction emerges for the intensive vacancy chain made of 8 single vacancy chains, which possesses a filament cross section area of ˜0.4 nm2. This sets a lower area limit for Hf-cluster filaments from metallic conduction point of view, but in real hafnia resistive RAM devices the cross section area of the filaments can generally be much larger (>5 nm2) for the sake of energy minimization. Our work sets up a bridge between oxygen vacancy ordering and phase separation in hafnia, and shows a clear trend of filament stabilization with larger dimensions. The results could explain the threshold switching phenomenon in hafnia when a small AFM tip was used as the top electrode, as well as the undesired multimode operation in resistive RAM cells with 3 nm-thick hafnia.

An ATP sensitive light addressable biosensor for extracellular monitoring of single taste receptor cell.

Science.gov (United States)

Wu, Chunsheng; Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping

2012-12-01

Adenosine triphosphate (ATP) is considered as the key neurotransmitter in taste buds for taste signal transmission and processing. Measurements of ATP secreted from single taste receptor cell (TRC) with high sensitivity and specificity are essential for investigating mechanisms underlying taste cell-to-cell communications. In this study, we presented an aptamer-based biosensor for the detection of ATP locally secreted from single TRC. ATP sensitive DNA aptamer was used as recognition element and its DNA competitor was served as signal transduction element that was covalently immobilized on the surface of light addressable potentiometric sensor (LAPS). Due to the light addressable capability of LAPS, local ATP secretion from single TRC can be detected by monitoring the working potential shifts of LAPS. The results show this biosensor can detect ATP with high sensitivity and specificity. It is demonstrated this biosensor can effectively detect the local ATP secretion from single TRC responding to tastant mixture. This biosensor could provide a promising new tool for the research of taste cell-to-cell communications as well as for the detection of local ATP secretion from other types of ATP secreting individual cells.

Glycopattern analysis of acidic secretion in the intestine of the red-eared slender turtle; Trachemys scripta elegans (Testudines: Emydidae).

Science.gov (United States)

Scillitani, Giovanni; Mentino, Donatella; Mastrodonato, Maria

2017-10-01

The secretion of the goblet cells in the intestine of Trachemys scripta elegans was studied in situ by histochemical methods to analyze the diversity of sugar chains, with particular regard to the acidic glycans. Conventional histochemical stains (Periodic acid-Schiff, Alcian Blue pH 2.5, High Iron Diamine) and binding with ten FITC-labelled lectins combined with chemical and enzymatic pre-treatments were used to characterize the oligosaccharidic chains. The intestine can be divided into three regions, i.e. a duodenum, a small intestine and a large intestine. Goblet cells were observed in all the three tracts and presented an acidic secretion. WGA, LFA, PNA and SBA binding was observed only after desulfation. Glycans secreted by the three tracts consist mainly of sulfosialomucins with 1,2-linked fucose, mannosylated, glucosaminylated and subterminal galactosyl/galactosaminylated residuals. Differences among tracts are quantitative rather than qualitative, with sulfated, galactosaminylated and glycosaminylated residuals increasing from duodenum to large intestine, and galactosylated and fucosylated residuals showing an opposite trend. Variation is observed also between apices and bases of villi in both duodenum and small intestine, where sulphation decreases from the base to the apex and glycosylation shows an opposite trend. Functional implication of these findings is discussed in a comparative context. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stimulated polarization wave process in spin 3/2 chains

International Nuclear Information System (INIS)

Furman, G. B.

2007-01-01

Stimulated wave of polarization, triggered by a flip of a single spin, presents a simple model of quantum amplification. Recently, it has been demonstrated that, in an idealized one-dimensional Ising spin 1/2 chain with nearest-neighbor interactions and realistic spin 1/2 chain including the natural dipole-dipole interactions, irradiated by a weak resonant transverse field, a wave of flipped spins can be triggered by a single spin flip. Here we focuse on control of polarization wave in chain of spin 3/2, where the nuclear quadrupole interaction is dominant. Results of simulations for 1D spin chains and rings with up to five spins are presented.

Direct observation of the discrete energy spectrum of two lanthanide-based single-chain magnets by far-infrared spectroscopy

Science.gov (United States)

Haas, Sabrina; Heintze, Eric; Zapf, Sina; Gorshunov, Boris; Dressel, Martin; Bogani, Lapo

2014-05-01

The far-infrared optical transmission has been studied for two lanthanide-based single-chain magnets DyPhOPh and TbPhOPh in the frequency range between 3 and 80 cm-1. The spectra were acquired at temperatures between 2 and 80 K and magnetic fields up to 6 T. Based on their magnetic field dependence in DyPhOPh two of the observed absorption lines are identified as transitions inside the crystal field split Dy3+ ground multiplet 6H15/2, coupled to the neighboring spins. In TbPhOPh one transition was observed inside the crystal-field-split Tb3+ ground multiplet 7F6. The results allow a spectroscopic investigation of the role of single-ion anisotropy and exchange in Glauber dynamics.

Quantitative measurement of zinc secretion from pancreatic islets with high temporal resolution using droplet-based microfluidics.

Science.gov (United States)

Easley, Christopher J; Rocheleau, Jonathan V; Head, W Steven; Piston, David W

2009-11-01

We assayed glucose-stimulated insulin secretion (GSIS) from live, murine islets of Langerhans in microfluidic devices by the downstream formation of aqueous droplets. Zinc ions, which are cosecreted with insulin from beta-cells, were quantitatively measured from single islets with high temporal resolution using a fluorescent indicator, FluoZin-3. Real-time storage of secretions into droplets (volume of 0.470 +/- 0.009 nL) effectively preserves the temporal chemical information, allowing reconstruction of the secretory time record. The use of passive flow control within the device removes the need for syringe pumps, requiring only a single hand-held syringe. Under stimulatory glucose levels (11 mM), bursts of zinc as high as approximately 800 fg islet(-1) min(-1) were measured. Treatment with diazoxide effectively blocked zinc secretion, as expected. High temporal resolution reveals two major classes of oscillations in secreted zinc, with predominate periods at approximately 20-40 s and approximately 5-10 min. The more rapid oscillation periods match closely with those of intraislet calcium oscillations, while the slower oscillations are consistent with insulin pulses typically measured in bulk islet experiments or in the bloodstream. This droplet sampling technique should be widely applicable to time-resolved cellular secretion measurements, either in real-time or for postprocessing.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

Science.gov (United States)

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins.

Science.gov (United States)

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. © 2011 American Institute of Physics

Determination of backbone chain direction of PDA using FFM

Science.gov (United States)

Jo, Sadaharu; Okamoto, Kentaro; Takenaga, Mitsuru

2010-01-01

The effect of backbone chains on friction force was investigated on both Langmuir-Blodgett (LB) films of 10,12-heptacosadiynoic acid and the (0 1 0) surfaces of single crystals of 2,4-hexadiene-1,6-diol using friction force microscopy (FFM). It was observed that friction force decreased when the scanning direction was parallel to the [0 0 1] direction in both samples. Moreover, friction force decreased when the scanning direction was parallel to the crystallographic [1 0 2], [1 0 1], [1 0 0] and [1 0 1¯] directions in only the single crystals. For the LB films, the [0 0 1] direction corresponds to the backbone chain direction of 10,12-heptacosadiynoic acid. For the single crystals, both the [0 0 1] and [1 0 1] directions correspond to the backbone chain direction, and the [1 0 2], [1 0 0] and [1 0 1¯] directions correspond to the low-index crystallographic direction. In both the LB films and single crystals, the friction force was minimized when the directions of scanning and the backbone chain were parallel.

Role of single-point mutations and deletions on transition temperatures in ideal proteinogenic heteropolymer chains in the gas phase.

Science.gov (United States)

Olivares-Quiroz, L

2016-07-01

A coarse-grained statistical mechanics-based model for ideal heteropolymer proteinogenic chains of non-interacting residues is presented in terms of the size K of the chain and the set of helical propensities [Formula: see text] associated with each residue j along the chain. For this model, we provide an algorithm to compute the degeneracy tensor [Formula: see text] associated with energy level [Formula: see text] where [Formula: see text] is the number of residues with a native contact in a given conformation. From these results, we calculate the equilibrium partition function [Formula: see text] and characteristic temperature [Formula: see text] at which a transition from a low to a high entropy states is observed. The formalism is applied to analyze the effect on characteristic temperatures [Formula: see text] of single-point mutations and deletions of specific amino acids [Formula: see text] along the chain. Two probe systems are considered. First, we address the case of a random heteropolymer of size K and given helical propensities [Formula: see text] on a conformational phase space. Second, we focus our attention to a particular set of neuropentapeptides, [Met-5] and [Leu-5] enkephalins whose thermodynamic stability is a key feature on their coupling to [Formula: see text] and [Formula: see text] receptors and the triggering of biochemical responses.

An extended chain Ising model and its Glauber dynamics

International Nuclear Information System (INIS)

Zhao Xing-Yu; Fan Xiao-Hui; Huang Yi-Neng; Huang Xin-Ru

2012-01-01

It was first proposed that an extended chain Ising (ECI) model contains the Ising chain model, single spin double-well potentials and a pure phonon heat bath of a specific energy exchange with the spins. The extension method is easy to apply to high dimensional cases. Then the single spin-flip probability (rate) of the ECI model is deduced based on the Boltzmann principle and general statistical principles of independent events and the model is simplified to an extended chain Glauber—Ising (ECGI) model. Moreover, the relaxation dynamics of the ECGI model were simulated by the Monte Carlo method and a comparison with the predictions of the special chain Glauber—Ising (SCGI) model was presented. It was found that the results of the two models are consistent with each other when the Ising chain length is large enough and temperature is relative low, which is the most valuable case of the model applications. These show that the ECI model will provide a firm physical base for the widely used single spin-flip rate proposed by Glauber and a possible route to obtain the single spin-flip rate of other form and even the multi-spin-flip rate. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Reaction pathway towards formation of cobalt single chain magnets and nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Balaji, G.; Desilva, Rohini M.; Palshin, V. [Center for Advanced Microstructures and Devices, Louisiana State University, 6980 Jefferson Highway, Baton Rouge, LA 70806 (United States); Desilva, N. [Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803 (United States); Palmer, G. [Department of Biochemistry and Cell Biology, Rice University, MS 140, 6100 Main street, Houston, TX 77251 (United States); Kumar, Challa S.S.R., E-mail: ckumar1@lsu.ed [Center for Advanced Microstructures and Devices, Louisiana State University, 6980 Jefferson Highway, Baton Rouge, LA 70806 (United States)

2010-03-15

With the advent of molecular magnets the quest for suitable high density magnetic storage materials has fuelled further research in this area. Here in this report, we present a detailed mechanistic investigation of thermal decomposition of cyclopentadienyl cobalt [CoCp(CO){sub 2}] precursor where Cp is the cyclopentadienyl moiety. The reaction revealed the formation of cobalt nanoparticles (Co-NPs) through an isolable reaction intermediate characterized as a Single Chain Magnet (SCM), [Co(Cp){sub 2}]{sub 2}CoCl{sub 4} (1). The SQUID magnetic measurements showed the presence of very strong antiferromagnetic interactions between Co{sup 2+} ions. The zero-field cooled (ZFC) and field cooled (FC) magnetization curves branch out below 5 K and there is evidence for frequency dependent complex susceptibility along with a maximum observed around 2.5 K. The optical studies indicated that the Co{sup 2+} d-d transition is influenced by the polarity of the solvents. The cobalt nanoparticles (Co-NPs) were obtained, either directly from 1 or from its precursor. They are spherical in shape with a mean size 15 nm, have fcc crystal structure and were found to be ferromagnetic at room temperature.

Solvable single-species aggregation-annihilation model for chain-shaped cluster growth

International Nuclear Information System (INIS)

Ke Jianhong; Lin Zhenquan; Zheng Yizhuang; Chen Xiaoshuang; Lu Wei

2007-01-01

We propose a single-species aggregation-annihilation model, in which an aggregation reaction between two clusters produces an active cluster and an annihilation reaction produces an inert one. By means of the mean-field rate equation, we respectively investigate the kinetic scaling behaviours of three distinct systems. The results exhibit that: (i) for the general aggregation-annihilation system, the size distribution of active clusters consistently approaches the conventional scaling form; (ii) for the system with the self-degeneration of the cluster's activities, it takes the modified scaling form; and (iii) for the system with the self-closing of active clusters, it does not scale. Moreover, the size distribution of inert clusters with small size takes a power-law form, while that of large inert clusters obeys the scaling law. The results also show that all active clusters will eventually transform into inert ones and the inert clusters of any size can be produced by such an aggregation-annihilation process. This model can be used to mimic the chain-shaped cluster growth and can provide some useful predictions for the kinetic behaviour of the system

A discrete particle swarm optimization algorithm with local search for a production-based two-echelon single-vendor multiple-buyer supply chain

Science.gov (United States)

Seifbarghy, Mehdi; Kalani, Masoud Mirzaei; Hemmati, Mojtaba

2016-03-01

This paper formulates a two-echelon single-producer multi-buyer supply chain model, while a single product is produced and transported to the buyers by the producer. The producer and the buyers apply vendor-managed inventory mode of operation. It is assumed that the producer applies economic production quantity policy, which implies a constant production rate at the producer. The operational parameters of each buyer are sales quantity, sales price and production rate. Channel profit of the supply chain and contract price between the producer and each buyer is determined based on the values of the operational parameters. Since the model belongs to nonlinear integer programs, we use a discrete particle swarm optimization algorithm (DPSO) to solve the addressed problem; however, the performance of the DPSO is compared utilizing two well-known heuristics, namely genetic algorithm and simulated annealing. A number of examples are provided to verify the model and assess the performance of the proposed heuristics. Experimental results indicate that DPSO outperforms the rival heuristics, with respect to some comparison metrics.

Intramolecular structures in a single copolymer chain consisting of flexible and semiflexible blocks: Monte Carlo simulation of a lattice model

International Nuclear Information System (INIS)

Martemyanova, Julia A; Ivanov, Victor A; Paul, Wolfgang

2014-01-01

We study conformational properties of a single multiblock copolymer chain consisting of flexible and semiflexible blocks. Monomer units of different blocks are equivalent in the sense of the volume interaction potential, but the intramolecular bending potential between successive bonds along the chain is different. We consider a single flexible-semiflexible regular multiblock copolymer chain with equal content of flexible and semiflexible units and vary the length of the blocks and the stiffness parameter. We perform flat histogram type Monte Carlo simulations based on the Wang-Landau approach and employ the bond fluctuation lattice model. We present here our data on different non-trivial globular morphologies which we have obtained in our model for different values of the block length and the stiffness parameter. We demonstrate that the collapse can occur in one or in two stages depending on the values of both these parameters and discuss the role of the inhomogeneity of intraglobular distributions of monomer units of both flexible and semiflexible blocks. For short block length and/or large stiffness the collapse occurs in two stages, because it goes through intermediate (meta-)stable structures, like a dumbbell shaped conformation. In such conformations the semiflexible blocks form a cylinder-like core, and the flexible blocks form two domains at both ends of such a cylinder. For long block length and/or small stiffness the collapse occurs in one stage, and in typical conformations the flexible blocks form a spherical core of a globule while the semiflexible blocks are located on the surface and wrap around this core.

Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines

International Nuclear Information System (INIS)

Bronzert, D.A.; Pantazis, P.; Antoniades, H.N.; Kasid, A.; Davidson, N.; Dickson, R.B.; Lippman, M.E.

1987-01-01

The authors report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or competence activity that is capable of inducing incorporation of [ 3 H] thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (95 0 C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO 4 /polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO 4 /polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth

Identification and characterization of human polyserase-3, a novel protein with tandem serine-protease domains in the same polypeptide chain

Directory of Open Access Journals (Sweden)

Garabaya Cecilia

2006-03-01

Full Text Available Abstract Background We have previously described the identification and characterization of polyserase-1 and polyserase-2, two human serine proteases containing three different catalytic domains within the same polypeptide chain. Polyserase-1 shows a complex organization and it is synthesized as a membrane-bound protein which can generate three independent serine protease domains as a consequence of post-translational processing events. The two first domains are enzymatically active. By contrast, polyserase-2 is an extracellular glycosylated protein whose three protease domains remain embedded in the same chain, and only the first domain possesses catalytic activity. Results Following our interest in the study of the human degradome, we have cloned a human liver cDNA encoding polyserase-3, a new protease with tandem serine protease domains in the same polypeptide chain. Comparative analysis of polyserase-3 with the two human polyserases described to date, revealed that this novel polyprotein is more closely related to polyserase-2 than to polyserase-1. Thus, polyserase-3 is a secreted protein such as polyserase-2, but lacks additional domains like the type II transmembrane motif and the low-density lipoprotein receptor module present in the membrane-anchored polyserase-1. Moreover, analysis of post-translational mechanisms operating in polyserase-3 maturation showed that its two protease domains remain as integral parts of the same polypeptide chain. This situation is similar to that observed in polyserase-2, but distinct from polyserase-1 whose protease domains are proteolytically released from the original chain to generate independent units. Immunolocalization studies indicated that polyserase-3 is secreted as a non-glycosylated protein, thus being also distinct from polyserase-2, which is a heavily glycosylated protein. Enzymatic assays indicated that recombinant polyserase-3 degrades the α-chain of fibrinogen as well as pro

Hydrogel Tethering Enhances Interdomain Stabilization of Single-Chain Antibodies

Energy Technology Data Exchange (ETDEWEB)

Xiong, Yijia [Department; Ford, Nicole R. [Marine; Hecht, Karen A. [Marine; Roesijadi, Guritno [Marine; Department; Squier, Thomas C. [Department

2017-10-12

Self-assembly of recombinant proteins within the biosilica of living diatoms represents a means to construct functional materials in a reproducible and scalable manner that enable applications that harness the inherent specificities of proteins to sense and respond to environmental cues. Here we describe the use of a silaffin-derived lysine-rich 39 amino-acid targeting sequence (Sil3T8) to direct a single chain fragment variable (scFv) antibody or an enhanced green fluorescent protein (EGFP) to assemble within the biosilica frustule, resulting in abundances in excess of 200,000 proteins per frustule. The fluorescence of either a derivative of trinitrotoluene (TNT) bound to the scFv or the endogenous fluorescence of EGFP was used to monitor pro-tein conformational dynamics, accessibility to external quenchers, binding affinity, and conformational stability. We find that proteins within isolated frustules undergo isotropic rotational motions with two-fold increases in rotational correlation times, which are indicative of weak macromolecular associations within the biosilica. Solvent accessibilities and high-affinity (pM) binding are comparable to those in solution. In contrast to solution conditions, scFv antibod-ies within the biosilica matrix retain their binding affinity in the presence of chaotropic agents (i.e., 8 M urea). These results argue that dramatic increases in protein conforma-tional stability within the biosilica frustule matrices arise through molecular crowding, acting to retain native protein folds and associated functionality to allow the utility of engineered proteins under a range of harsh environmental conditions associated with environmental sensing and industrial catalytic transformations.

Mesoscale simulation of semiflexible chains. I. Endpoint distribution and chain dynamics

Science.gov (United States)

Groot, Robert D.

2013-06-01

The endpoint distribution and dynamics of semiflexible fibers are studied by numerical simulation. A brief overview is given over the analytical theory of flexible and semiflexible polymers. In particular, a closed expression is given for the relaxation spectrum of wormlike chains, which determines polymer diffusion and rheology. Next a simulation model for wormlike chains with full hydrodynamic interaction is described, and relations for the bending and torsion modulus are given. Two methods are introduced to include torsion stiffness into the model. The model is validated by simulating single chains in a heat bath, and comparing the endpoint distribution of the chains with established Monte Carlo results. It is concluded that torsion stiffness leads to a slightly shorter effective persistence length for a given bending stiffness. To further validate the simulation model, polymer diffusion is studied for fixed persistence length and varying polymer length N. The diffusion constant shows crossover from Rouse (D ∝ N-1) to reptation behaviour (D ∝ N-2). The terminal relaxation time obtained from the monomer displacement is consistent with the theory of wormlike chains. The probability for chain crossing has also been studied. This probability is so low that it does not influence the present results.

Cooperation and profit allocation in distribution chains

NARCIS (Netherlands)

Guardiola, L.A.; Meca, A.; Timmer, Judith B.

2005-01-01

We study the coordination of actions and the allocation of profit in distribution chains under decentralized control. We consider distribution chains in which a single supplier supplies goods for replenishment of stocks of several retailers who, in turn, sell these goods to their own separate

Impact of charge carrier injection on single-chain photophysics of conjugated polymers

Energy Technology Data Exchange (ETDEWEB)

Hofmann, Felix J.; Vogelsang, Jan, E-mail: jan.vogelsang@physik.uni-regensburg.de; Lupton, John M. [Institut für Experimentelle und Angewandte Physik, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg (Germany)

2016-06-27

Charges in conjugated polymer materials have a strong impact on the photophysics and their interaction with the primary excited state species has to be taken into account in understanding device properties. Here, we employ single-molecule spectroscopy to unravel the influence of charges on several photoluminescence (PL) observables. The charges are injected either stochastically by a photochemical process or deterministically in a hole-injection sandwich device configuration. We find that upon charge injection, besides a blue-shift of the PL emission and a shortening of the PL lifetime due to quenching and blocking of the lowest-energy chromophores, the non-classical photon arrival time distribution of the multichromophoric chain is modified towards a more classical distribution. Surprisingly, the fidelity of photon antibunching deteriorates upon charging, whereas one would actually expect the opposite: the number of chromophores to be reduced. A qualitative model is presented to explain the observed PL changes. The results are of interest to developing a microscopic understanding of the intrinsic charge-exciton quenching interaction in devices.

Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

Energy Technology Data Exchange (ETDEWEB)

Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Wang, Zai [Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Li, Jian; Cai, Jian-Ping [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [School of Biomedical Sciences and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Pokfulam (Hong Kong); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China); Zhang, Tie-Mei, E-mail: tmzhang126@126.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China)

2016-08-05

Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Cui, Ju; Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan; Wang, Zai; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

2016-01-01

Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

Supply Chain Coordination under Trade Credit and Quantity Discount with Sales Effort Effects

Directory of Open Access Journals (Sweden)

Zhihong Wang

2018-01-01

Full Text Available The purpose of this paper is to investigate the role of trade credit and quantity discount in supply chain coordination when the sales effort effect on market demand is considered. In this paper, we consider a two-echelon supply chain consisting of a single retailer ordering a single product from a single manufacturer. Market demand is stochastic and is influenced by retailer sales effort. We formulate an analytical model based on a single trade credit and find that the single trade credit cannot achieve the perfect coordination of the supply chain. Then, we develop a hybrid quantitative analytical model for supply chain coordination by coherently integrating incentives of trade credit and quantity discount with sales effort effects. The results demonstrate that, providing that the discount rate satisfies certain conditions, the proposed hybrid model combining trade credit and quantity discount will be able to effectively coordinate the supply chain by motivating retailers to exert their sales effort and increase product order quantity. Furthermore, the hybrid quantitative analytical model can provide great flexibility in coordinating the supply chain to achieve an optimal situation through the adjustment of relevant parameters to resolve conflict of interests from different supply chain members. Numerical examples are provided to demonstrate the effectiveness of the hybrid model.

A single-chain fusion molecule consisting of peptide, major histocompatibility gene complex class I heavy chain and beta2-microglobulin can fold partially correctly, but binds peptide inefficiently

DEFF Research Database (Denmark)

Sylvester-Hvid, C; Buus, S

1999-01-01

of a recombinant murine MHC-I molecule, which could be produced in large amounts in bacteria. The recombinant MHC-I protein was expressed as a single molecule (PepSc) consisting of the antigenic peptide linked to the MHC-I heavy chain and further linked to human beta2-microglobulin (hbeta2m). The PepSc molecule...... electrophoresis (SDS-PAGE). Serological analysis revealed the presence of some, but not all, MHC-I-specific epitopes. Biochemically, PepSc could bind peptide, however, rather ineffectively. We suggest that a partially correctly refolded MHC-I has been obtained....

Quantum strongly secure ramp secret sharing

DEFF Research Database (Denmark)

Zhang, Paul; Matsumoto, Rytaro Yamashita

2015-01-01

Quantum secret sharing is a scheme for encoding a quantum state (the secret) into multiple shares and distributing them among several participants. If a sufficient number of shares are put together, then the secret can be fully reconstructed. If an insufficient number of shares are put together...... however, no information about the secret can be revealed. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an unqualified set, that cannot fully reconstruct the secret. By allowing this, the size of a share can be drastically reduced....... This paper introduces a quantum analog of classical strong security in ramp secret sharing schemes. While the ramp secret sharing scheme still leaks partial information about the secret to unqualified sets of participants, the strong security condition ensures that qudits with critical information can...

Partnering for change in chains : on the capacity of partnerships to promote sustainable change in global agricultural commodity chains

OpenAIRE

Bitzer, V.C.

2011-01-01

Partnerships mirror the changing nature of the relationships among state, business and civil society organizations, and are often considered as innovative mechanisms to overcome single actor failure in the context of globalization. This thesis analyzes the capacity of partnerships to promote sustainable change in global agricultural commodity chains, using the global coffee, cotton and cocoa chains as main fields of application for the empirical analyses. All three chains are characterized by...

Controlling Chain Conformations of High-k Fluoropolymer Dielectrics to Enhance Charge Mobilities in Rubrene Single-Crystal Field-Effect Transistors.

Science.gov (United States)

Adhikari, Jwala M; Gadinski, Matthew R; Li, Qi; Sun, Kaige G; Reyes-Martinez, Marcos A; Iagodkine, Elissei; Briseno, Alejandro L; Jackson, Thomas N; Wang, Qing; Gomez, Enrique D

2016-12-01

A novel photopatternable high-k fluoropolymer, poly(vinylidene fluoride-bromotrifluoroethylene) P(VDF-BTFE), with a dielectric constant (k) between 8 and 11 is demonstrated in thin-film transistors. Crosslinking P(VDF-BTFE) reduces energetic disorder at the dielectric-semiconductor interface by controlling the chain conformations of P(VDF-BTFE), thereby leading to approximately a threefold enhancement in the charge mobility of rubrene single-crystal field-effect transistors. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic secrets in communication security

CERN Document Server

Xiao, Sheng; Towsley, Donald

2013-01-01

Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

Sodium arsenite impairs insulin secretion and transcription in pancreatic β-cells

International Nuclear Information System (INIS)

Diaz-Villasenor, Andrea; Sanchez-Soto, M. Carmen; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia; Hiriart, Marcia

2006-01-01

Human studies have shown that chronic inorganic arsenic (iAs) exposure is associated with a high prevalence and incidence of type 2 diabetes. However, the mechanism(s) underlying this effect are not well understood, and practically, there is no information available on the effects of arsenic on pancreatic β-cells functions. Thus, since insulin secreted by the pancreas plays a crucial role in maintaining glucose homeostasis, our aim was to determine if sodium arsenite impairs insulin secretion and mRNA expression in single adult rat pancreatic β-cells. Cells were treated with 0.5, 1, 2, 5 and 10 μM sodium arsenite and incubated for 72 and 144 h. The highest dose tested (10 μM) decreased β-cell viability, by 33% and 83%, respectively. Insulin secretion and mRNA expression were evaluated in the presence of 1 and 5 μM sodium arsenite. Basal insulin secretion, in 5.6 mM glucose, was not significantly affected by 1 or 5 μM treatment for 72 h, but basal secretion was reduced when cells were exposed to 5 μM sodium arsenite for 144 h. On the other hand, insulin secretion in response to 15.6 mM glucose decreased with sodium arsenite in a dose-dependent manner in such a way that cells were no longer able to distinguish between different glucose concentrations. We also showed a significant decrease in insulin mRNA expression of cells exposed to 5 μM sodium arsenite during 72 h. Our data suggest that arsenic may contribute to the development of diabetes mellitus by impairing pancreatic β-cell functions, particularly insulin synthesis and secretion

Phase-coexistence simulations of fluid mixtures by the Markov Chain Monte Carlo method using single-particle models

KAUST Repository

Li, Jun

2013-09-01

We present a single-particle Lennard-Jones (L-J) model for CO2 and N2. Simplified L-J models for other small polyatomic molecules can be obtained following the methodology described herein. The phase-coexistence diagrams of single-component systems computed using the proposed single-particle models for CO2 and N2 agree well with experimental data over a wide range of temperatures. These diagrams are computed using the Markov Chain Monte Carlo method based on the Gibbs-NVT ensemble. This good agreement validates the proposed simplified models. That is, with properly selected parameters, the single-particle models have similar accuracy in predicting gas-phase properties as more complex, state-of-the-art molecular models. To further test these single-particle models, three binary mixtures of CH4, CO2 and N2 are studied using a Gibbs-NPT ensemble. These results are compared against experimental data over a wide range of pressures. The single-particle model has similar accuracy in the gas phase as traditional models although its deviation in the liquid phase is greater. Since the single-particle model reduces the particle number and avoids the time-consuming Ewald summation used to evaluate Coulomb interactions, the proposed model improves the computational efficiency significantly, particularly in the case of high liquid density where the acceptance rate of the particle-swap trial move increases. We compare, at constant temperature and pressure, the Gibbs-NPT and Gibbs-NVT ensembles to analyze their performance differences and results consistency. As theoretically predicted, the agreement between the simulations implies that Gibbs-NVT can be used to validate Gibbs-NPT predictions when experimental data is not available. © 2013 Elsevier Inc.

Regulation of ghrelin secretion and action.

Science.gov (United States)

Camiña, Jesus P; Carreira, Marcos C; Micic, Dragan; Pombo, Manuel; Kelestimur, Fahrettin; Dieguez, Carlos; Casanueva, Felipe F

2003-10-01

The pulsatile release of growth hormone (GH) from anterior pituitary gland is regulated by the interplay of at least two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. Furthermore, release of GH in vivo may also be controlled by a third type of receptor, the growth hormone secretagogue receptor, a G-protein-coupled receptor, called GHS receptor type 1a (GHSR1a), which was identified in the pituitary and the hypothalamus in humans using a nonpeptidyl growth hormone secretagogue (MK-0677). Ghrelin, the endogenous ligand for the GHS-R1a, is a 28-amino-acid peptide isolated from human stomach that is modified by a straight chain octanoyl group covalently linked to Ser3, which is essential for its endocrine activity. This hormone, predominantly expressed and secreted by the stomach, has a dual action on GH secretion and food intake, showing interdependency between these actions. The finding that fasting and food intake, respectively, increase and decrease the secretion of ghrelin suggests that this hormone may be the bridge connecting somatic growth and body composition with energy metabolism, and appears to play a role in the alteration of energy homeostasis and body weight in pathophysiological states such as hypothyroidism and hyperthyroidism. Despite this, little is known about the intracellular signaling through which ghrelin exerts its regulatory actions. Activation of intracellular calcium mobilization is one of the earliest known cellular signals elicited by ghrelin. In HEK- 293 cells expressing the GHS-R1a, ghrelin induces a biphasic cytosolic calcium elevation characterized by a spike phase of the response, which reflects Ins(1,4,5)P3- dependent calcium mobilization of intracellular stores, and a sustained phase of the response, which is due to calcium influx across the plasma membrane triggered by aperture of capacitative calcium channels

Equivalence of chain conformations in the surface region of a polymer melt and a single Gaussian chain nder critical conditions

NARCIS (Netherlands)

Skvortsov, A.M.; Leermakers, F.A.M.; Fleer, G.J.

2013-01-01

In the melt polymer conformations are nearly ideal according to Flory's ideality hypothesis. Silberberg generalized this statement for chains in the interfacial region. We check the Silberberg argument by analyzing the conformations of a probe chain end-grafted at a solid surface in a sea of

Investigations of model polymers: Dynamics of melts and statics of a long chain in a dilute melt of shorter chains

International Nuclear Information System (INIS)

Bishop, M.; Ceperley, D.; Frisch, H.L.; Kalos, M.H.

1982-01-01

We report additional results on a simple model of polymers, namely the diffusion in concentrated polymer systems and the static properties of one long chain in a dilute melt of shorter chains. It is found, for the polymer sizes and time scales amenable to our computer calculations, that there is as yet no evidence for a ''reptation'' regime in a melt. There is some indication of reptation in the case of a single chain moving through fixed obstacles. No statistically significant effect of the change, from excluded volume behavior of the long chain to ideal behavior as the shorter chains grow, is observed

Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine

DEFF Research Database (Denmark)

Christensen, Louise Wulff; Kuhre, Rune Ehrenreich; Janus, Charlotte

2015-01-01

-protein-cou- pled receptor, FFAR1 (previously GPR40), expressed on L cells and activated by long-chain fatty acids (LCFAs) is a potential target. A link between FFAR1 activation and GLP-1 secretion has been demonstrated in cellular models and small-molecule FFAR1 agonists have been developed. In this study, we exam......- ined the effect of FFAR1 activation on GLP-1 secretion using isolated, per- fused small intestines from rats, a physiologically relevant model allowing distinction between direct and indirect effects of FFAR1 activation. The endogenous FFAR1 ligand, linoleic acid (LA), and four synthetic FFAR1 ago...

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

Energy Technology Data Exchange (ETDEWEB)

Lee, Je Min, E-mail: jemin@knu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of); Department of Horticultural Science, Kyungpook National University, Daegu (Korea, Republic of); Lee, Sang-Jik [Biotechnology Institute, Nongwoo Bio Co, Ltd, Yeoju (Korea, Republic of); Department of Plant Biology, Cornell University, Ithaca, NY (United States); Rose, Jocelyn K.C. [Department of Plant Biology, Cornell University, Ithaca, NY (United States); Yeam, Inhwa [Department of Horticulture and Breeding, Andong National University, Andong (Korea, Republic of); Kim, Byung-Dong [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of)

2014-04-18

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

International Nuclear Information System (INIS)

Lee, Je Min; Lee, Sang-Jik; Rose, Jocelyn K.C.; Yeam, Inhwa; Kim, Byung-Dong

2014-01-01

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening

Immunoglobins in mammary secretions

DEFF Research Database (Denmark)

Hurley, W L; Theil, Peter Kappel

2013-01-01

Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells

International Nuclear Information System (INIS)

Majesky, M.W.; Benditt, E.P.; Schwartz, S.M.

1988-01-01

Cultured arterial smooth muscle cells (SMC) can produce platelet-derived growth factor (PDGF)-like molecules. This property raises the possibility that SMC-derived PDGFs function as autocrine/paracrine regulators in the formation and maintenance of the artery wall. In this study the authors have asked if levels of mRNAs directing synthesis of PDFG are modulated in aortic SMC during postnatal development. The authors report here that genes encoding PDGF A- and B-chain precursors are expressed at similar low levels in intact aortas from newborn and adult rats. Marked differences in regulation of transcript abundance of these genes were revealed when aortic SMC were grown in cell culture. PDGF B-chain transcripts accumulated in passaged newborn rat SMC but not adult rat SMC, whereas PDGF A-chain RNA was found in comparable amounts in SMC from both age groups. Similarly, SMC from newborn rats secreted at least 60-fold more PDGF-like activity into conditioned medium than did adult rat SMC. These results show that PDGF A- and B-chain genes are transcribed in the normal rat aorta and provide evidence for age-related change in the control of PDGF B-chain gene expression in aortic SMC. Independent regulation of transcript levels in cultured SMC leaves open the possibility that PDGFs of different composition (AA, AB, BB) play different roles in normal function of the artery wall

Research on manufacturing service behavior modeling based on block chain theory

Science.gov (United States)

Zhao, Gang; Zhang, Guangli; Liu, Ming; Yu, Shuqin; Liu, Yali; Zhang, Xu

2018-04-01

According to the attribute characteristics of processing craft, the manufacturing service behavior is divided into service attribute, basic attribute, process attribute, resource attribute. The attribute information model of manufacturing service is established. The manufacturing service behavior information is successfully divided into public and private domain. Additionally, the block chain technology is introduced, and the information model of manufacturing service based on block chain principle is established, which solves the problem of sharing and secreting information of processing behavior, and ensures that data is not tampered with. Based on the key pairing verification relationship, the selective publishing mechanism for manufacturing information is established, achieving the traceability of product data, guarantying the quality of processing quality.

Detector-device-independent quantum secret sharing with source flaws.

Science.gov (United States)

Yang, Xiuqing; Wei, Kejin; Ma, Haiqiang; Liu, Hongwei; Yin, Zhenqiang; Cao, Zhu; Wu, Lingan

2018-04-10

Measurement-device-independent entanglement witness (MDI-EW) plays an important role for detecting entanglement with untrusted measurement device. We present a double blinding-attack on a quantum secret sharing (QSS) protocol based on GHZ state. Using the MDI-EW method, we propose a QSS protocol against all detector side-channels. We allow source flaws in practical QSS system, so that Charlie can securely distribute a key between the two agents Alice and Bob over long distances. Our protocol provides condition on the extracted key rate for the secret against both external eavesdropper and arbitrary dishonest participants. A tight bound for collective attacks can provide good bounds on the practical QSS with source flaws. Then we show through numerical simulations that using single-photon source a secure QSS over 136 km can be achieved.

Matroids and quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Sarvepalli, Pradeep; Raussendorf, Robert

2010-01-01

A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previous work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.

Extracellular secretion of recombinant proteins

Science.gov (United States)

Linger, Jeffrey G.; Darzins, Aldis

2014-07-22

Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

The relationship between the connecting peptide of recombined single chain insulin and its biological function

Institute of Scientific and Technical Information of China (English)

HUANG; Yiding; (

2001-01-01

［1］Straus, D. S., Growth-stimulatory of insulin in vitro and in vivo, Endocr. Rev., 1984, 5(2): 356-369.［2］Svenningsen, A. F., Kanje, M., Insulin and the insulin-like growth factors I and II are mitogenic to cultured rat sciatic nerve segments and stimulate [3H] thuymidine incorporation through their respective receptors, Glia, 1996, 18(1): 68-72.［3］Ogihara, S., Yamada, M., Saito, T. et al., Insulin potentiates mitogenic effect of epidermal growth factor on cultured guinea pig gastric mucous cells, Am. J. Physiol., 1996, 271(1 Pt 1): G104-121.［4］Steiner, D. F., Oyer, P. E., The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma, Proc. Nalt. Acad. Sci. USA, 1967, 57(2): 473-480.［5］King, G. L., Kahn, C. R., The growth-promoting effects of insulin, in Growth and Maturation Factors(ed. Guroff, G.), New York: John Wiley & Sons, 1984, 223-265.［6］Peavy, D. E., Brunner, M. R., Duckworth, W. C. et al., Receptor binding and biological potency of several split forms (conversion intermediates) of human proinsulin, Studies in cultured IM-9 lymphocytes and in vivo and in vitro in rats, J. Biol. Chem., 1985, 260: 13989-13994.［7］Derewenda, U., Derewenda, Z., Dodson, E. J. et al., X-ray analysis of the single chain B29-A1 peptide-linked insulin molecule. A completely inactive analogue, J. Mol. Biol., 1991, 220: 425-433.［8］Hua, Q. X., Shoelson, S. E., Kochoyan, M. et al., Receptor binding redefined by a structural switch in a mutant human insulin, Nature, 1991, 354: 238-241.［9］Hua, Q. X., Gozani, S. N., Chance, R. E. et al., Structure of a protein in a kinetic trap, Nat. Struc. Boil, 1995, 2: 129-138.［10］Kristensen, C., Andersen, A. S., Hach, M., A single-chain insulin-like growth factor I/insulin hybrid binds with high affinity to the insulin receptor, Biochem. J., 1995, 305: 981-986.［11］Humbel, R. E., Insulin-like growth factors I and II, Euro. J. Biochem., 1990, 190: 445-462.［12］Cooke, R. M

A single-supply, high rate, small size and cheap electronic chain for 3He neutron counters

International Nuclear Information System (INIS)

Boffa, A.; Fazzi, A.; Pirovano, C.; Varoli, V.

1996-01-01

The paper describes a complete counting chain (charge preamplifier, shaping amplifier and threshold discriminator) devoted to 3 He neutron detectors. Since it is characterized by single supply operation, high counting rate, small size and low cost, it is well suited for high efficiency neutron well detectors where a large number (10 - 100) of counting tubes are used. Such detectors are commonly used for verification of Plutonium stocks. The preamplifier adopts an innovative circuit with the gate of the input JFET floating and a DC feedback loop that stabilizes the output voltage acting on the input cascode second transistor. Static and dynamic analysis, including the effects of the detector bias network, is reported. The shaping amplifier transfer function is a fifth order approximation of the gaussian response. All the complex pole pairs are realized with a single fourth order Voltage Controlled Voltage Source cell thus minimizing component count. Experimental signals and spectra, obtained with shaping time constants in the 1 μs - 100 ns range, are reported and discussed

Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

Science.gov (United States)

Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

2015-12-01

Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

Primitive chain network simulations of probe rheology.

Science.gov (United States)

Masubuchi, Yuichi; Amamoto, Yoshifumi; Pandey, Ankita; Liu, Cheng-Yang

2017-09-27

Probe rheology experiments, in which the dynamics of a small amount of probe chains dissolved in immobile matrix chains is discussed, have been performed for the development of molecular theories for entangled polymer dynamics. Although probe chain dynamics in probe rheology is considered hypothetically as single chain dynamics in fixed tube-shaped confinement, it has not been fully elucidated. For instance, the end-to-end relaxation of probe chains is slower than that for monodisperse melts, unlike the conventional molecular theories. In this study, the viscoelastic and dielectric relaxations of probe chains were calculated by primitive chain network simulations. The simulations semi-quantitatively reproduced the dielectric relaxation, which reflects the effect of constraint release on the end-to-end relaxation. Fair agreement was also obtained for the viscoelastic relaxation time. However, the viscoelastic relaxation intensity was underestimated, possibly due to some flaws in the model for the inter-chain cross-correlations between probe and matrix chains.

Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases.

Science.gov (United States)

Yamada, Shozo; Fukuhara, Noriaki; Horiguchi, Kentaro; Yamaguchi-Okada, Mitsuo; Nishioka, Hiroshi; Takeshita, Akira; Takeuchi, Yasuhiro; Ito, Junko; Inoshita, Naoko

2014-12-01

The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical

Production and properties of monoclonal antibodies to human blood coagulation factor VII and factor VIIa

International Nuclear Information System (INIS)

Mann, P.; Nesbitt, J.A.; Ge, M.; Kisiel, W.

1986-01-01

Human factor VII is a trace vitamin K-dependent protein that circulates in blood as a single-chain precursor to a serine protease. Upon activation, two-chain factor VIIa activates factor x in the presence of tissue factor and calcium. Purified preparations of single-chain (SC) human factor VII and two-chain (TC) factor VIIa were utilized to immunize Balb/c mice. Spleen cells from these immunized mice were fused to a non-secreting NS-1 derivative of X63-Ag8 myeloma cells and grown in selective medium. Analysis of culture supernatants by EIA revealed several hybridomas that were secreting IgG specific for Sc-factor VII and TC-factor VIIa. In addition, several hybridomas secreted IgG that reacted equally well with factor VII and factor VIIa. One of the latter McAb (A-29) reacted with the heavy chain of factor VIIa and the intact factor VII molecule equally as judged by Western blotting. A-29 was produced in ascites fluid, purified and coupled to activated CH-Sepharose. Application of one liter of normal human plasma to 10 ml of this immunoadsorbent column, elution of factor VII and subsequent Western blot using 125 I-rabbit anti-human factor VII indicated a single species of factor VII(M/sub r/ = 50 KDa) in normal plasma. These specific factor VII/VIIa McAbs may prove useful in the analysis of these factors, and in the separation of SC-factor VII from TC-factor VIIa

Pituitary-hormone secretion by thyrotropinomas.

Science.gov (United States)

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M; Biermasz, Nienke R; Smit, Jan W; Frolich, Marijke; Keenan, Daniel M; Veldhuis, Johannes D; Romijn, Johannes A

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

Semiquantum secret sharing using entangled states

International Nuclear Information System (INIS)

Li Qin; Chan, W. H.; Long Dongyang

2010-01-01

Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but one of them cannot. The presented protocols are also shown to be secure against eavesdropping.

Probabilistic Infinite Secret Sharing

OpenAIRE

Csirmaz, László

2013-01-01

The study of probabilistic secret sharing schemes using arbitrary probability spaces and possibly infinite number of participants lets us investigate abstract properties of such schemes. It highlights important properties, explains why certain definitions work better than others, connects this topic to other branches of mathematics, and might yield new design paradigms. A probabilistic secret sharing scheme is a joint probability distribution of the shares and the secret together with a colle...

Block copolymer systems: from single chain to self-assembled nanostructures.

Science.gov (United States)

Giacomelli, Cristiano; Schmidt, Vanessa; Aissou, Karim; Borsali, Redouane

2010-10-19

Recent advances in the field of macromolecular engineering applied to the fabrication of nanostructured materials using block copolymer chains as elementary building blocks are described in this feature article. By highlighting some of our work in the area and accounting for the contribution of other groups, we discuss the relationship between the physical-chemical properties of copolymer chains and the characteristics of nano-objects originating from their self-assembly in solution and in bulk, with emphasis on convenient strategies that allow for the control of composition, functionality, and topology at different levels of sophistication. In the case of micellar nanoparticles in solution, in particular, we present approaches leading to morphology selection via macromolecular architectural design, the functionalization of external solvent-philic shells with biomolecules (polysaccharides and proteins), and the maximization of micelle loading capacity by the suitable choice of solvent-phobic polymer segments. The fabrication of nanomaterials mediated by thin block copolymer films is also discussed. In this case, we emphasize the development of novel polymer chain manipulation strategies that ultimately allow for the preparation of precisely positioned nanodomains with a reduced number of defects via block-selective chemical reactivity. The challenges facing the soft matter community, the urgent demand to convert huge public and private investments into consumer products, and future possible directions in the field are also considered herein.

Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

Directory of Open Access Journals (Sweden)

Kazuhisa Sugimura

2013-02-01

Full Text Available An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competitive ELISA with M86 and morphine-C-Tg in the absence or presence of varying doses of free morphine and related compounds. IC50 values for opium, morphine, codeine, and heroin were 257 ng/mL, 36.4, 7.3, and 7.4 nM, respectively. Ketamine and cocaine exhibited no competitive binding activity to M86. Thus, we established a phage library-derived scFv, M86, which recognized not only free morphine and codeine as opium components but also heroin. This characteristic of M86 may be useful for developing therapeutic reagents for opiate addiction and as a free morphine-specific antibody probe.

Effect of chain stiffness on the structure of single-chain polymer nanoparticles

DEFF Research Database (Denmark)

Moreno, Angel J; Bacova, Petra; Lo Verso, Federica

2018-01-01

of the domains is in all cases similar to that of Gaussian chains or rings, irrespective of the stiffness and degree of cross-linking. It is the spatial arrangement of the domains which determines the global structure of the SCNP (sparse Gaussian-like object or crumpled globule). Since intramolecular stiffness...... or 'crumpled' globular behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are weakly deformable regions that can be seen as disordered analogues of domains in disordered proteins. Increasing stiffness leads to bigger and less deformable domains. Surprisingly, the scaling behaviour...... can be varied through the specific chemistry of the precursor or by introducing bulky side groups in its backbone, our results propose a new strategy to tune the global structure of SCNPs. ....

Mechanism of Action of Secreted Newt Anterior Gradient Protein.

Directory of Open Access Journals (Sweden)

Kathrin S Grassme

Full Text Available Anterior gradient (AG proteins have a thioredoxin fold and are targeted to the secretory pathway where they may act in the ER, as well as after secretion into the extracellular space. A newt member of the family (nAG was previously identified as interacting with the GPI-anchored salamander-specific three-finger protein called Prod1. Expression of nAG has been implicated in the nerve dependence of limb regeneration in salamanders, and nAG acted as a growth factor for cultured newt limb blastemal (progenitor cells, but the mechanism of action was not understood. Here we show that addition of a peptide antibody to Prod1 specifically inhibit the proliferation of blastema cells, suggesting that Prod1 acts as a cell surface receptor for secreted nAG, leading to S phase entry. Mutation of the single cysteine residue in the canonical active site of nAG to alanine or serine leads to protein degradation, but addition of residues at the C terminus stabilises the secreted protein. The mutation of the cysteine residue led to no detectable activity on S phase entry in cultured newt limb blastemal cells. In addition, our phylogenetic analyses have identified a new Caudata AG protein called AG4. A comparison of the AG proteins in a cell culture assay indicates that nAG secretion is significantly higher than AGR2 or AG4, suggesting that this property may vary in different members of the family.

Heavy chain only antibodies

DEFF Research Database (Denmark)

Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud

2013-01-01

Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

RSA-Based Secret Handshakes

OpenAIRE

Vergnaud , Damien

2006-01-01

A secret handshake mechanism allows two entities, members of a same group, to authenticate each other secretly. This primitive was introduced recently by Balfanz, Durfee, Shankar, Smetters, Staddon and Wong and, so far, all the schemes proposed are based on discrete log systems. This paper proposes three new secret handshake protocols secure against active impersonator and detector adversaries. Inspired by two RSA-based key agreement protocols introduced by Okamoto and Tanaka in 1989 and Gira...

High-dimensional quantum key distribution with the entangled single-photon-added coherent state

Energy Technology Data Exchange (ETDEWEB)

Wang, Yang [Zhengzhou Information Science and Technology Institute, Zhengzhou, 450001 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Bao, Wan-Su, E-mail: 2010thzz@sina.com [Zhengzhou Information Science and Technology Institute, Zhengzhou, 450001 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Bao, Hai-Ze; Zhou, Chun; Jiang, Mu-Sheng; Li, Hong-Wei [Zhengzhou Information Science and Technology Institute, Zhengzhou, 450001 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China)

2017-04-25

High-dimensional quantum key distribution (HD-QKD) can generate more secure bits for one detection event so that it can achieve long distance key distribution with a high secret key capacity. In this Letter, we present a decoy state HD-QKD scheme with the entangled single-photon-added coherent state (ESPACS) source. We present two tight formulas to estimate the single-photon fraction of postselected events and Eve's Holevo information and derive lower bounds on the secret key capacity and the secret key rate of our protocol. We also present finite-key analysis for our protocol by using the Chernoff bound. Our numerical results show that our protocol using one decoy state can perform better than that of previous HD-QKD protocol with the spontaneous parametric down conversion (SPDC) using two decoy states. Moreover, when considering finite resources, the advantage is more obvious. - Highlights: • Implement the single-photon-added coherent state source into the high-dimensional quantum key distribution. • Enhance both the secret key capacity and the secret key rate compared with previous schemes. • Show an excellent performance in view of statistical fluctuations.

High-dimensional quantum key distribution with the entangled single-photon-added coherent state

International Nuclear Information System (INIS)

Wang, Yang; Bao, Wan-Su; Bao, Hai-Ze; Zhou, Chun; Jiang, Mu-Sheng; Li, Hong-Wei

2017-01-01

High-dimensional quantum key distribution (HD-QKD) can generate more secure bits for one detection event so that it can achieve long distance key distribution with a high secret key capacity. In this Letter, we present a decoy state HD-QKD scheme with the entangled single-photon-added coherent state (ESPACS) source. We present two tight formulas to estimate the single-photon fraction of postselected events and Eve's Holevo information and derive lower bounds on the secret key capacity and the secret key rate of our protocol. We also present finite-key analysis for our protocol by using the Chernoff bound. Our numerical results show that our protocol using one decoy state can perform better than that of previous HD-QKD protocol with the spontaneous parametric down conversion (SPDC) using two decoy states. Moreover, when considering finite resources, the advantage is more obvious. - Highlights: • Implement the single-photon-added coherent state source into the high-dimensional quantum key distribution. • Enhance both the secret key capacity and the secret key rate compared with previous schemes. • Show an excellent performance in view of statistical fluctuations.

Effect of single physical exercise at 35% VO2 max. intensity on secretion activity of pancreas β-cells and 125J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus

International Nuclear Information System (INIS)

Szczesniak, L.; Rychlewski, T.; Banaszak, F.; Kasprzak, Z.; Walczak, M.

1994-01-01

In this report we showed research results of effect of single physical exercise on cycloergometer at 35% VO 2 max. intensity on 125 J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus, secreting and non-secreting endogenous insulin. Insulin secretion was evaluated by measurement of C-peptide by Biodet test (Serono) of sensitivity threshold at 0.3 μg/ml. We indicated in children non-secreting endogenous insulin (n=32) there is statistically essential lower 125 J-insulin binding with erythrocyte receptor in comparison to children group with C-peptide. Physical exercise on cycloergometer at 35% VO 2 max. intensity caused different reaction in range of physiological indices, like acid-base parameters, level of glucose and 125 J-insulin binding and degradation. In children devoid of endogenous insulin we indicated statistically nonessential changes in 125 J-insulin degradation by non-impaired erythrocytes and by hemolizate, as well. 125 J-insulin binding after physical exercise increased in both groups, though change amplitude was different. Obtained research results allowed us to conclude, in children with I-type diabetes, that in dependence of impairment degree of pancreas βcells sensitivity of insulin receptor and/or number of receptors on erythrocyte surface is different

Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery.

Science.gov (United States)

Zhou, Li; Wang, Hsuan-Yao; Tong, Shanshan; Okamoto, Curtis T; Shen, Wei-Chiang; Zaro, Jennica L

2017-02-01

Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc) 2 ), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc) 2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc) 2 -mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc) 2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human α2-HS-glycoprotein: the A and B chains with a connecting sequence are encoded by a single mRNA transcript

International Nuclear Information System (INIS)

Lee, C.C.; Bowman, B.H.; Yang, F.

1987-01-01

The α 2 -HS-glycoprotein (AHSG) is a plasma protein reported to play roles in bone mineralization and in the immune response. It is composed of two subunits, the A and B chains. Recombinant plasmids containing human cDNA AHSG have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. The cDNA clones containing AHSG inserts span approximately 1.5 kilobase pairs and include the entire AHSG coding sequence, demonstrating that the A and B chains are encoded by a single mRNA transcript. The cDNA sequence predicts an 18-amino-acid signal peptide, followed by the A-chain sequence of AHSG. A heretofore unseen connecting sequence of 40 amino acids was deduced between the A- and B-chain sequences. The connecting sequence demonstrates the unique amino acid doublets and collagen triplets found in the A and B chains; it is not homologous with other reported amino acid sequences. The connecting sequence may be cleaved in a posttranslational step by limited proteolysis before mature AHSG is released into the circulation or may vary in its presence because of alternative processing. The AHSG cDNA was utilized for mapping the AHSG gene to the 3q21→qter region of human chromosome 3. The availability of the AHSG cDNA clone will facilitate the analysis of its genetic control and gene expression during development and bone formation

Efficient multiparty quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Xiao Li; Deng Fuguo; Long Guilu; Pan Jianwei

2004-01-01

In this work, we generalize the quantum-secret-sharing scheme of Hillery, Buzek, and Berthiaume [Phys. Rev. A 59, 1829 (1999)] into arbitrary multiparties. Explicit expressions for the shared secret bit is given. It is shown that in the Hillery-Buzek-Berthiaume quantum-secret-sharing scheme the secret information is shared in the parity of binary strings formed by the measured outcomes of the participants. In addition, we have increased the efficiency of the quantum-secret-sharing scheme by generalizing two techniques from quantum key distribution. The favored-measuring-basis quantum-secret-sharing scheme is developed from the Lo-Chau-Ardehali technique [H. K. Lo, H. F. Chau, and M. Ardehali, e-print quant-ph/0011056] where all the participants choose their measuring-basis asymmetrically, and the measuring-basis-encrypted quantum-secret-sharing scheme is developed from the Hwang-Koh-Han technique [W. Y. Hwang, I. G. Koh, and Y. D. Han, Phys. Lett. A 244, 489 (1998)] where all participants choose their measuring basis according to a control key. Both schemes are asymptotically 100% in efficiency, hence nearly all the Greenberger-Horne-Zeilinger states in a quantum-secret-sharing process are used to generate shared secret information

Anti-Human Endoglin (hCD105) Immunotoxin-Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1.

Science.gov (United States)

Barriuso, Begoña; Antolín, Pilar; Arias, F Javier; Girotti, Alessandra; Jiménez, Pilar; Cordoba-Diaz, Manuel; Cordoba-Diaz, Damián; Girbés, Tomás

2016-06-10

Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT)-containing recombinant musarmin 1 (single chain ribosome-inactivating proteins) linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10(-10) to 10(-9) M.

Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

International Nuclear Information System (INIS)

Batzri, S.; Catravas, G.

1988-01-01

We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig

Finite-temperature dynamic structure factor of the spin-1 XXZ chain with single-ion anisotropy

Science.gov (United States)

Lange, Florian; Ejima, Satoshi; Fehske, Holger

2018-02-01

Improving matrix-product state techniques based on the purification of the density matrix, we are able to accurately calculate the finite-temperature dynamic response of the infinite spin-1 XXZ chain with single-ion anisotropy in the Haldane, large-D , and antiferromagnetic phases. Distinct thermally activated scattering processes make a significant contribution to the spectral weight in all cases. In the Haldane phase, intraband magnon scattering is prominent, and the on-site anisotropy causes the magnon to split into singlet and doublet branches. In the large-D phase response, the intraband signal is separated from an exciton-antiexciton continuum. In the antiferromagnetic phase, holons are the lowest-lying excitations, with a gap that closes at the transition to the Haldane state. At finite temperatures, scattering between domain-wall excitations becomes especially important and strongly enhances the spectral weight for momentum transfer π .

Scattering of waves by impurities in precompressed granular chains.

Science.gov (United States)

Martínez, Alejandro J; Yasuda, Hiromi; Kim, Eunho; Kevrekidis, P G; Porter, Mason A; Yang, Jinkyu

2016-05-01

We study scattering of waves by impurities in strongly precompressed granular chains. We explore the linear scattering of plane waves and identify a closed-form expression for the reflection and transmission coefficients for the scattering of the waves from both a single impurity and a double impurity. For single-impurity chains, we show that, within the transmission band of the host granular chain, high-frequency waves are strongly attenuated (such that the transmission coefficient vanishes as the wavenumber k→±π), whereas low-frequency waves are well-transmitted through the impurity. For double-impurity chains, we identify a resonance-enabling full transmission at a particular frequency-in a manner that is analogous to the Ramsauer-Townsend (RT) resonance from quantum physics. We also demonstrate that one can tune the frequency of the RT resonance to any value in the pass band of the host chain. We corroborate our theoretical predictions both numerically and experimentally, and we directly observe almost complete transmission for frequencies close to the RT resonance frequency. Finally, we show how this RT resonance can lead to the existence of reflectionless modes in granular chains (including disordered ones) with multiple double impurities.

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

Science.gov (United States)

Lakshmanan, J; Landel, C P

1986-07-01

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

Sweet Tetra-Trophic Interactions: Multiple Evolution of Nectar Secretion, a Defensive Extended Phenotype in Cynipid Gall Wasps.

Science.gov (United States)

Nicholls, James A; Melika, George; Stone, Graham N

2017-01-01

Many herbivores employ reward-based mutualisms with ants to gain protection from natural enemies. We examine the evolutionary dynamics of a tetra-trophic interaction in which gall wasp herbivores induce their host oaks to produce nectar-secreting galls, which attract ants that provide protection from parasitoids. We show that, consistent with other gall defensive traits, nectar secretion has evolved repeatedly across the oak gall wasp tribe and also within a single genus (Disholcaspis) that includes many nectar-inducing species. Once evolved, nectar secretion is never lost in Disholcaspis, consistent with high defensive value of this trait. We also show that evolution of nectar secretion is correlated with a transition from solitary to aggregated oviposition, resulting in clustered nectar-secreting galls, which produce a resource that ants can more easily monopolize. Such clustering is commonly seen in ant guard mutualisms. We suggest that correlated evolution between maternal oviposition and larval nectar induction traits has enhanced the effectiveness of this gall defense strategy.

Lean in the supply chain : research and practice

OpenAIRE

Ugochukwu, Paschal

2012-01-01

Lean is a management philosophy that enhances customer value through waste elimination and continuous improvement in a system by applying lean principles, practices, and techniques. The focus on lean implementations and research had been typically a single company without extension to the entire supply chain. When the concept of lean is implemented across the entire supply chain, however, it is referred to as lean supply chain. The purpose of this thesis is to create a structure from theory a...

Slow magnetic relaxation in a cobalt magnetic chain.

Science.gov (United States)

Yang, Chen-I; Chuang, Po-Hsiang; Lu, Kuang-Lieh

2011-04-21

A homospin ladder-like chain, [Co(Hdhq)(OAc)](n) (1; H(2)dhq = 2,3-dihydroxyquinoxaline), shows a single-chain-magnet-like (SCM-like) behavior with the characteristics of frequency dependence of the out-of-phase component in alternating current (ac) magnetic susceptibilities and hysteresis loops. © The Royal Society of Chemistry 2011

Secretion management in the mechanically ventilated patient.

Science.gov (United States)

Branson, Richard D

2007-10-01

Secretion management in the mechanically ventilated patient includes routine methods for maintaining mucociliary function, as well as techniques for secretion removal. Humidification, mobilization of the patient, and airway suctioning are all routine procedures for managing secretions in the ventilated patient. Early ambulation of the post-surgical patient and routine turning of the ventilated patient are common secretion-management techniques that have little supporting evidence of efficacy. Humidification is a standard of care and a requisite for secretion management. Both active and passive humidification can be used. The humidifier selected and the level of humidification required depend on the patient's condition and the expected duration of intubation. In patients with thick, copious secretions, heated humidification is superior to a heat and moisture exchanger. Airway suctioning is the most important secretion removal technique. Open-circuit and closed-circuit suctioning have similar efficacy. Instilling saline prior to suctioning, to thin the secretions or stimulate a cough, is not supported by the literature. Adequate humidification and as-needed suctioning are the foundation of secretion management in the mechanically ventilated patient. Intermittent therapy for secretion removal includes techniques either to simulate a cough, to mechanically loosen secretions, or both. Patient positioning for secretion drainage is also widely used. Percussion and postural drainage have been widely employed for mechanically ventilated patients but have not been shown to reduce ventilator-associated pneumonia or atelectasis. Manual hyperinflation and insufflation-exsufflation, which attempt to improve secretion removal by simulating a cough, have been described in mechanically ventilated patients, but neither has been studied sufficiently to support routine use. Continuous lateral rotation with a specialized bed reduces atelectasis in some patients, but has not been shown

Supply Chain Simulation using Business Process Modeling in Service Oriented Architecture

OpenAIRE

Taejong Yoo

2015-01-01

For supply chain optimization, as a key determinant of strategic resources mobility along the value-added chain, simulation is widely used to test the impact on supply chain performance for the strategic level decisions, such as the number of plants, the modes of transport, or the relocation of warehouses. Traditionally, a single centralized model that encompasses multiple participants in the supply chain is built when optimization of the supply chain through simulation is required. However, ...

Stabilization of bacterially expressed erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites.

Science.gov (United States)

Hoffmann, E; Streichert, K; Nischan, N; Seitz, C; Brunner, T; Schwagerus, S; Hackenberger, C P R; Rubini, M

2016-05-24

The covalent attachment of polyethylene glycol (PEG) to therapeutic proteins can improve their physicochemical properties. In this work we utilized the non-natural amino acid p-azidophenylalanine (pAzF) in combination with the chemoselective Staudinger-phosphite reaction to install branched PEG chains to recombinant unglycosylated erythropoietin (EPO) at each single naturally occurring glycosylation site. PEGylation with two short 750 or 2000 Da PEG units at positions 24, 38, or 83 significantly decreased unspecific aggregation and proteolytic degradation while biological activity in vitro was preserved or even increased in comparison to full-glycosylated EPO. This site-specific bioconjugation approach permits to analyse the impact of PEGylation at single positions. These results represent an important step towards the engineering of site-specifically modified EPO variants from bacterial expression with increased therapeutic efficacy.

Supply chain oriented performance measurement for automotive spare parts

NARCIS (Netherlands)

de Leeuw, S.L.J.M.; Beekman, L.

2008-01-01

Literature provides a number of conceptual frameworks and discussions on performance measurement in supply chains. However, most of these frameworks focus on a single link of a supply chain. Furthermore, there is a lack of empirical analysis and case studies on performance metrics and measurements

Incretin secretion: direct mechanisms

DEFF Research Database (Denmark)

Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

2014-01-01

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

Nonlinear tearing mode and vortex chains

International Nuclear Information System (INIS)

Jovanovic, D.; Vranjes, J.

1996-01-01

We study the nonlinear stage of a tearing mode, whose island width exceeds the tearing layer thickness, and the wavelength is of the order of collisionless skin depth. A coherent solution is found in the form of a moving vortex chain. It is the result of a self-organization process, which adjusts the profile of the sheared poloidal magnetic field and excites a localized perpendicular sheared plasma flow, consisting of three counterstreaming jets. A numerical solution shows a twin chain of plasma vortices, coupled with a single chain of magnetic islands, whose width is of the order of collisionless skin depth. Adiabatic evolution of the vortex chain in the presence of small viscosity reveals its finite lifetime. The chain destruction may occur either directly, or through a sequence of bifurcations (corresponding to abrupt changes of the vortex chain parameters) to magnetic field stochastization within a layer of the collisionless skin depth scale, which occurs before the magnetic island overlapping takes place. This provides a new mechanism for the anomalous transport. (orig.)

Anti-Human Endoglin (hCD105 Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

Directory of Open Access Journals (Sweden)

Begoña Barriuso

2016-06-01

Full Text Available Endoglin (CD105 is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio propionate (SPDP. The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.

Efficacy of continuous versus intermittent subglottic secretion drainage in preventing ventilator-associated pneumonia in patients requiring mechanical ventilation: A single-center randomized controlled trial.

Science.gov (United States)

Fujimoto, Hiroko; Yamaguchi, Osamu; Hayami, Hajime; Shimosaka, Mika; Tsuboi, Sayaka; Sato, Mitsunori; Takebayashi, Shigeo; Morita, Satoshi; Saito, Mari; Goto, Takahisa; Kurahashi, Kiyoyasu

2018-03-23

Aspiration of subglottic secretion is a widely used intervention to prevent ventilator-associated pneumonia (VAP). This study aimed to compare the efficacy of continuous and intermittent subglottic secretion drainage (SSD) in preventing VAP. A single-center randomized controlled trial was conducted on adult postoperative patients who were expected to undergo mechanical ventilation for more than 48 hours. Primary outcome measure was incidence of VAP and secondary outcome measures were length of mechanical ventilation and intensive-care unit (ICU) stay. Fifty-nine patients received continuous SSD, while 60 patients received intermittent SSD. Of these 119 patients, 88 (74%) were excluded and 15 and 16 patients were allocated to receive continuous and intermittent SSD, respectively. VAP was detected in 4 (26.7%) and 7 (43.8%) patients in the continuous and intermittent groups, respectively, (p=0.320). The length of mechanical ventilation was significantly shorter (p=0.034) in the continuous group (99.5±47.1 h) than in the intermittent group (159.9±94.5 h). The length of ICU stay was also shorter (p=0.0097) in the continuous group (6.3±2.1 days) than the intermittent group (9.8±4.8 days). Although continuous SSD did not reduce the incidence of VAP, it reduced the length of mechanical ventilation and ICU stay when compared to intermittent SSD.

Dynamics of Cancer Cell near Collagen Fiber Chain

Science.gov (United States)

Kim, Jihan; Sun, Bo

Cell migration is an integrated process that is important in life. Migration is essential for embryonic development as well as homeostatic processes such as wound healing and immune responses. When cell migrates through connective extracellular matrix (ECM), it applies cellular traction force to ECM and senses the rigidity of their local environment. We used human breast cancer cell (MDA-MB-231) which is highly invasive and applies strong traction force to ECM. As cancer cell applies traction force to type I collage-based ECM, it deforms collagen fibers near the surface. Patterns of deforming collagen fibers are significantly different with pairs of cancer cells compared to a single cancer cell. While a pair of cancer cells within 60 um creates aligned collagen fiber chains between them permanently, a single cancer cell does not form any fiber chains. In this experiment we measured a cellular response and an interaction between a pair of cells through the chain. Finally, we analyzed correlation of directions between cancer cell migration and the collagen chain alignment.

Electronic properties of linear carbon chains: Resolving the controversy

International Nuclear Information System (INIS)

Al-Backri, Amaal; Zólyomi, Viktor; Lambert, Colin J.

2014-01-01

Literature values for the energy gap of long one-dimensional carbon chains vary from as little as 0.2 eV to more than 4 eV. To resolve this discrepancy, we use the GW many-body approach to calculate the band gap E g of an infinite carbon chain. We also compute the energy dependence of the attenuation coefficient β governing the decay with chain length of the electrical conductance of long chains and compare this with recent experimental measurements of the single-molecule conductance of end-capped carbon chains. For long chains, we find E g = 2.16 eV and an upper bound for β of 0.21 Å −1

Nonlinear secret image sharing scheme.

Science.gov (United States)

Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

2014-01-01

Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively.

Single-chain-in-mean-field simulations of weak polyelectrolyte brushes

Science.gov (United States)

Léonforte, F.; Welling, U.; Müller, M.

2016-12-01

Structural properties of brushes which are composed of weak acidic and basic polyelectrolytes are studied in the framework of a particle-based approach that implicitly accounts for the solvent quality. Using a semi-grandcanonical partition function in the framework of the Single-Chain-in-Mean-Field (SCMF) algorithm, the weak polyelectrolyte is conceived as a supramolecular mixture of polymers in different dissociation states, which are explicitly treated in the partition function and sampled by the SCMF procedure. One obtains a local expression for the equilibrium acid-base reaction responsible for the regulation of the charged groups that is also incorporated to the SCMF sampling. Coupled to a simultaneous treatment of the electrostatics, the approach is shown to capture the main features of weak polyelectrolyte brushes as a function of the bulk pH in the solution, the salt concentration, and the grafting density. Results are compared to experimental and theoretical works from the literature using coarse-grained representations of poly(acrylic acid) (PAA) and poly(2-vinyl pyridine) (P2VP) polymer-based brushes. As the Born self-energy of ions can be straightforwardly included in the numerical approach, we also study its effect on the local charge regulation mechanism of the brush. We find that its effect becomes significant when the brush is dense and exposed to high salt concentrations. The numerical methodology is then applied (1) to the study of the kinetics of collapse/swelling of a P2VP brush and (2) to the ability of an applied voltage to induce collapse/swelling of a PAA brush in a pH range close to the pKa value of the polymer.

Qing-Hua Granule induces GLP-1 secretion via bitter taste receptor in db/db mice.

Science.gov (United States)

Li, Junyan; Xu, Jie; Hou, Ruifang; Jin, Xin; Wang, Jingyi; Yang, Na; Yang, Li; Liu, Li; Tao, Feng; Lu, Hao

2017-05-01

Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks. GLP-1 secretion was evaluated. The bitter receptor signaling pathway, which regulates GLP-1 secretion, including TAS2R5 (a subtype of TAS2R), α-gustducin (Gαgust), 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase beta-2 (PLCβ2), transient receptor potential cation channel subfamily M member 5 (TRPM5), was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). The biochemical observations of ileum and pancreas tissue were detected histopathologically. Acquity Ultra Performance LCTM - Micromass ZQ 2000 (UPLC-MS) was used for the phytochemical analysis. QHG exhibited significant and dose-dependent effect on GLP-1 secretion in db/db mice, along with significant up-regulation of TAS2R5 mRNA level and activation of TAS2R pathway (p<0.05). In addition, QHG improved the histopathological structure of ileum and pancreatic tissue. Seventeen compounds were identified in QHG. In conclusion, QHG induces GLP-1 secretion in db/db mice, most likely through the bitter taste receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment

Science.gov (United States)

Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes

2013-01-01

It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…

On alternative approach for verifiable secret sharing

OpenAIRE

Kulesza, Kamil; Kotulski, Zbigniew; Pieprzyk, Joseph

2002-01-01

Secret sharing allows split/distributed control over the secret (e.g. master key). Verifiable secret sharing (VSS) is the secret sharing extended by verification capacity. Usually verification comes at the price. We propose "free lunch", the approach that allows to overcome this inconvenience.

Trade Secrets in Life Science and Pharmaceutical Companies

Science.gov (United States)

Nealey, Tara; Daignault, Ronald M.; Cai, Yu

2015-01-01

Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through “improper means” is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today’s interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees’ careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. PMID:25414378

Trade secrets in life science and pharmaceutical companies.

Science.gov (United States)

Nealey, Tara; Daignault, Ronald M; Cai, Yu

2014-11-20

Trade secret protection arises under state common law and state statutes. In general, a trade secret is information that is not generally known to the public and is maintained as a secret, and it provides a competitive advantage or economic benefit to the trade secret holder. Trade secrets can be worth tens or hundreds of millions of dollars, and damage awards in trade secret litigation have been high; often, there is a lot at stake. Obtaining a trade secret through "improper means" is misappropriation. If the alleged trade secret, however, was developed independently, known publicly, or not maintained as a secret, then those defenses may successfully overcome a claim for trade secret misappropriation. With today's interconnectedness in the biotechnology and pharmaceutical fields, more collaborations, joint ventures, and outsourcing arrangements among firms, and increased mobility of employees' careers, life science companies need to not only understand how to protect their trade secrets, but also know how to defend against a claim for trade secret theft. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Characterising pharmacological ligands to study the long chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4

DEFF Research Database (Denmark)

Milligan, G; Alvarez-Curto, E; Watterson, K R

2015-01-01

The G protein-coupled receptors FFA1 (previously designated GPR40) and FFA4 (previously GPR120) are both activated by saturated and unsaturated longer-chain free fatty acids. With expression patterns and functions anticipated to directly or indirectly promote insulin secretion, provide homeostati...

Revenue-Sharing Contract Models for Logistics Service Supply Chains with Mass Customization Service

Directory of Open Access Journals (Sweden)

Weihua Liu

2015-01-01

Full Text Available The revenue-sharing contract is one of the most important supply chain coordination contracts; it has been applied in various supply chains. However, studies related to service supply chains with mass customization (MC are lacking. Considering the equity of benefit distribution between the members of service supply chains, in this paper, we designed two revenue-sharing contracts. The first contract for the maximum equity of a single logistics service integrator (LSI and single functional logistics service provider (FLSP in a two-echelon logistics service supply chain was designed by introducing the fair entropy function (“one to one” model. Furthermore, the method is extended to a more complex supply chain, which consists of a single LSI and multiple FLSPs. A new contract was designed not only for considering the equity of an LSI and each FLSP but also for the equity between each FLSP (“one to N” model. The “one to one” model in three-echelon LSSC is also provided. The result exemplifies that, whether in the “one to one” model or “one to N” model, there exists a best interval of customized level when the revenue-sharing coefficient reaches its maximum.

Visualization and characterization of individual type III protein secretion machines in live bacteria.

Science.gov (United States)

Zhang, Yongdeng; Lara-Tejero, María; Bewersdorf, Jörg; Galán, Jorge E

2017-06-06

Type III protein secretion machines have evolved to deliver bacterially encoded effector proteins into eukaryotic cells. Although electron microscopy has provided a detailed view of these machines in isolation or fixed samples, little is known about their organization in live bacteria. Here we report the visualization and characterization of the Salmonella type III secretion machine in live bacteria by 2D and 3D single-molecule switching superresolution microscopy. This approach provided access to transient components of this machine, which previously could not be analyzed. We determined the subcellular distribution of individual machines, the stoichiometry of the different components of this machine in situ, and the spatial distribution of the substrates of this machine before secretion. Furthermore, by visualizing this machine in Salmonella mutants we obtained major insights into the machine's assembly. This study bridges a major resolution gap in the visualization of this nanomachine and may serve as a paradigm for the examination of other bacterially encoded molecular machines.

Novel short chain fatty acids restore chloride secretion in cystic fibrosis

International Nuclear Information System (INIS)

Nguyen, Toan D.; Kim, Ug-Sung; Perrine, Susan P.

2006-01-01

Phenylalanine deletion at position 508 of the cystic fibrosis transmembrane conductance regulator (ΔF508-CFTR), the most common mutation in cystic fibrosis (CF), causes a misfolded protein exhibiting partial chloride conductance and impaired trafficking to the plasma membrane. 4-Phenylbutyrate corrects defective ΔF508-CFTR trafficking in vitro, but is not clinically efficacious. From a panel of short chain fatty acid derivatives, we showed that 2,2-dimethyl-butyrate (ST20) and α-methylhydrocinnamic acid (ST7), exhibiting high oral bioavailability and sustained plasma levels, correct the ΔF508-CFTR defect. Pre-incubation (≥6 h) of CF IB3-1 airway cells with ≥1 mM ST7 or ST20 restored the ability of 100 μM forskolin to stimulate an 125 I - efflux. This efflux was fully inhibited by NPPB, DPC, or glibenclamide, suggesting mediation through CFTR. Partial inhibition by DIDS suggests possible contribution from an additional Cl - channel regulated by CFTR. Thus, ST7 and ST20 offer treatment potential for CF caused by the ΔF508 mutation

The Evaluation of Simulation Games Applicablity for Better Understanding Supply Chain Principles

OpenAIRE

Blaženka Kneževiæ

2008-01-01

In order to achieve competitive advantage, each company has to determine its strategic position in relation to its suppliers and buyers, and to realize how behavior of supply chain participants influence on overall supply chain functionality. Supply chains with high level of synchronization of activities from producer to consumer, at a long-time run, will achieve high business result for single participant, and for entire chain. Supply chain synchronization is complex and expensive process. T...

Size, shape, and diffusivity of a single Debye-Hückel polyelectrolyte chain in solution

Science.gov (United States)

Soysa, W. Chamath; Dünweg, B.; Prakash, J. Ravi

2015-08-01

Brownian dynamics simulations of a coarse-grained bead-spring chain model, with Debye-Hückel electrostatic interactions between the beads, are used to determine the root-mean-square end-to-end vector, the radius of gyration, and various shape functions (defined in terms of eigenvalues of the radius of gyration tensor) of a weakly charged polyelectrolyte chain in solution, in the limit of low polymer concentration. The long-time diffusivity is calculated from the mean square displacement of the centre of mass of the chain, with hydrodynamic interactions taken into account through the incorporation of the Rotne-Prager-Yamakawa tensor. Simulation results are interpreted in the light of the Odjik, Skolnick, Fixman, Khokhlov, and Khachaturian blob scaling theory (Everaers et al., Eur. Phys. J. E 8, 3 (2002)) which predicts that all solution properties are determined by just two scaling variables—the number of electrostatic blobs X and the reduced Debye screening length, Y. We identify three broad regimes, the ideal chain regime at small values of Y, the blob-pole regime at large values of Y, and the crossover regime at intermediate values of Y, within which the mean size, shape, and diffusivity exhibit characteristic behaviours. In particular, when simulation results are recast in terms of blob scaling variables, universal behaviour independent of the choice of bead-spring chain parameters, and the number of blobs X, is observed in the ideal chain regime and in much of the crossover regime, while the existence of logarithmic corrections to scaling in the blob-pole regime leads to non-universal behaviour.

5 CFR 1312.27 - Top secret control.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Top secret control. 1312.27 Section 1312... Classified Information § 1312.27 Top secret control. The EOP Security Officer serves as the Top Secret... Top Secret material. The ATSCOs will be responsible for the accountability and custodianship of Top...

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

Science.gov (United States)

Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

Secretion Trap Tagging of Secreted and Membrane-Spanning Proteins Using Arabidopsis Gene Traps

Science.gov (United States)

Andrew T. Groover; Joseph R. Fontana; Juana M. Arroyo; Cristina Yordan; W. Richard McCombie; Robert A. Martienssen

2003-01-01

Secreted and membrane-spanning proteins play fundamental roles in plant development but pose challenges for genetic identification and characterization. We describe a "secretion trap" screen for gene trap insertions in genes encoding proteins routed through the secretory pathway. The gene trap transposon encodes a ß-glucuronidase reporter enzyme...

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

Science.gov (United States)

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

2001-02-01

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

Market orientation seen in a value chain perspective

DEFF Research Database (Denmark)

Sonne, Anne-Mette; Stacey, Julia; Grunert, Klaus G.

2002-01-01

Market orientation is regarded as a prerequisite for a company's ability to create customer value and higher profits. Market orientation is usually regarded as something, which characterises a company. However, companies are part of value chains, and a lot of competition taking place...... in international markets is between the different value chains rather than between the individual companies. This is the reason why it makes more sense to look at the degree of market orientation in a complete value chain rather than the degree of market orientation of a single company....

On the Wrapping of Polyglycolide, Poly(Ethylene Oxide), and Polyketone Polymer Chains Around Single-Walled Carbon Nanotubes Using Molecular Dynamics Simulations

Science.gov (United States)

Rouhi, S.; Alizadeh, Y.; Ansari, R.

2015-02-01

By using molecular dynamics simulations, the interaction between a single-walled carbon nanotube and three different polymers has been studied in this work. The effects of various parameters such as the nanotube geometry and temperature on the interaction energy and radius of gyration of polymers have been explored. By studying the snapshots of polymers along the single-walled carbon nanotube, it has been shown that 50 ps can be considered as a suitable time after which the shape of polymer chains around the nanotube remains almost unchanged. It is revealed that the effect of temperature on the interaction energy and radius of gyration of polymers in the range of 250 to 500 K is not significant Also, it is shown that the interaction energy depends on the nanotube diameter.

Linear-after-the-exponential polymerase chain reaction and allied technologies. Real-time detection strategies for rapid, reliable diagnosis from single cells.

Science.gov (United States)

Pierce, Kenneth E; Wangh, Lawrence J

2007-01-01

Accurate detection of gene sequences in single cells is the ultimate challenge to polymerase chain reaction (PCR) sensitivity. Unfortunately, commonly used conventional and real-time PCR techniques are often too unreliable at that level to provide the accuracy needed for clinical diagnosis. Here we provide details of linear-after-the-exponential-PCR (LATE-PCR), a method similar to asymmetric PCR in the use of primers at different concentrations, but with novel design criteria to ensure high efficiency and specificity. Compared with conventional PCR, LATE-PCR increases the signal strength and allele discrimination capability of oligonucleotide probes such as molecular beacons and reduces variability among replicate samples. The analysis of real-time kinetics of LATE-PCR signals provides a means for improving the accuracy of single cell genetic diagnosis.

22 CFR 1421.15 - Secret ballot.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Secret ballot. 1421.15 Section 1421.15 Foreign Relations FOREIGN SERVICE LABOR RELATIONS BOARD; FEDERAL LABOR RELATIONS AUTHORITY; GENERAL COUNSEL OF THE... THIS SUBCHAPTER § 1421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine...

Stability of llama heavy chain antibody fragments under extreme conditions

NARCIS (Netherlands)

Dolk, E.

2004-01-01

Camelids have next to their normal antibodies, a unique subset of antibodies lacking light chains. The resulting single binding domain, VHH, of these heavy chain antibodies consequently have unique properties. A high stability is one of these properties, which was investigated in this thesis. The

Single Chain Antibody Fragment against Venom from the Snake Daboia russelii formosensis

Directory of Open Access Journals (Sweden)

Chi-Hsin Lee

2017-10-01

Full Text Available Russell’s vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs containing 3.4 × 107 and 5.5 × 107 transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

Single Chain Antibody Fragment against Venom from the Snake Daboia russelii formosensis.

Science.gov (United States)

Lee, Chi-Hsin; Lee, Yu-Ching; Lee, Yueh-Lun; Leu, Sy-Jye; Lin, Liang-Tzung; Chen, Chi-Ching; Chiang, Jen-Ron; Mwale, Pharaoh Fellow; Tsai, Bor-Yu; Hung, Ching-Sheng; Yang, Yi-Yuan

2017-10-27

Russell's vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF) venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY) antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs) containing 3.4 × 10⁷ and 5.5 × 10⁷ transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

A Novel Algorithm for the Generation of Distinct Kinematic Chain

Science.gov (United States)

Medapati, Sreenivasa Reddy; Kuchibhotla, Mallikarjuna Rao; Annambhotla, Balaji Srinivasa Rao

2016-07-01

Generation of distinct kinematic chains is an important topic in the design of mechanisms for various industrial applications i.e., robotic manipulator, tractor, crane etc. Many researchers have intently focused on this area and explained various processes of generating distinct kinematic chains which are laborious and complex. It is desirable to enumerate the kinematic chains systematically to know the inherent characteristics of a chain related to its structure so that all the distinct chains can be analyzed in depth, prior to the selection of a chain for a purpose. This paper proposes a novel and simple method with set of rules defined to eliminate isomorphic kinematic chains generating distinct kinematic chains. Also, this method simplifies the process of generating distinct kinematic chains even at higher levels i.e., 10-link, 11-link with single and multiple degree of freedom.

Multiple impacts in dissipative granular chains

CERN Document Server

Nguyen, Ngoc Son

2014-01-01

The extension of collision models for single impacts between two bodies, to the case of multiple impacts (which take place when several collisions occur at the same time in a multibody system) is a challenge in Solid Mechanics, due to the complexity of such phenomena, even in the frictionless case. This monograph aims at presenting the main multiple collision rules proposed in the literature. Such collisions typically occur in granular materials, the simplest of which are made of chains of aligned balls. These chains are used throughout the book to analyze various multiple impact rules which extend the classical Newton (kinematic restitution), Poisson (kinetic restitution) and Darboux-Keller (energetic or kinetic restitution) approaches for impact modelling. The shock dynamics in various types of chains of aligned balls (monodisperse, tapered, decorated, stepped chains) is carefully studied and shown to depend on several parameters: restitution coefficients, contact stiffness ratios, elasticity coefficients (...

Alternative protein secretion: The Mam1 ABC transporter supports secretion of M-factor linked GFP in fission yeast

International Nuclear Information System (INIS)

Kjaerulff, Soren; Mueller, Sven; Jensen, Martin Roland

2005-01-01

To examine whether the fission yeast Mam1 ABC transporter can be used for secretion of heterologous proteins, thereby bypassing the classical secretion pathway, we have analyzed chimeric forms of the M-factor precursor. It was demonstrated that GFP can be exported when fused to both the amino-terminal prosequence from mfm1 and a CaaX motif. This secretion was dependent on the Mam1 transporter and not the classical secretion pathway. The secretion efficiency of GFP, however, was relatively low and most of the reporter protein was trapped in the vacuolar membranes. Our findings suggest that the Mam1 ABC protein is a promiscuous peptide transporter that can accommodate globular proteins of a relatively large size. Furthermore, our results help in defining the sequences required for processing and secretion of natural M-factor

29 CFR 401.11 - Secret ballot.

Science.gov (United States)

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Secret ballot. 401.11 Section 401.11 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS MEANING OF TERMS USED IN THIS SUBCHAPTER § 401.11 Secret ballot. Secret ballot means the expression by...

The gonococcal genetic island and type IV secretion in the pathogenic Neisseria

Directory of Open Access Journals (Sweden)

Meghan E Ramsey

2011-04-01

Full Text Available Eighty percent of Neisseria gonorrhoeae strains and some Neisseria meningitidis strains encode a 57 kb gonococcal genetic island (GGI. The GGI was horizontally acquired and is inserted in the chromosome at the replication terminus. The GGI is flanked by direct repeats, and site-specific recombination at these sites results in excision of the GGI and may be responsible for its original acquisition. Although the role of the GGI in N. meningitidis is unclear, the GGI in N. gonorrhoeae encodes a type IV secretion system (T4SS. Type IV secretion systems are versatile multi-protein complexes and include both conjugation systems as well as effector systems that translocate either proteins or DNA-protein complexes. In N. gonorrhoeae, the T4SS secretes single-stranded chromosomal DNA into the extracellular milieu in a contact-independent manner. Importantly, the DNA secreted through the T4SS is effective in natural transformation and therefore contributes to the spread of genetic information through Neisseria populations. Mutagenesis experiments have identified genes for DNA secretion including those encoding putative structural components of the apparatus, peptidoglycanases which may act in assembly, and relaxosome components for processing the DNA and delivering it to the apparatus. The T4SS may also play a role in infection by N. gonorrhoeae. During intracellular infection, N. gonorrhoeae requires the Ton complex for iron acquisition and survival. However, N. gonorrhoeae strains that do not express the Ton complex can survive intracellularly if they express structural components of the T4SS. These data provide evidence that the T4SS is expressed during intracellular infection and suggest that the T4SS may provide an advantage for intracellular survival. Here we review our current understanding of how the GGI and type IV secretion affect natural transformation and pathogenesis in N. gonorrhoeae and N. meningitidis.

Newton's Cradle and Entanglement Transport in a Flexible Rydberg Chain

International Nuclear Information System (INIS)

Wuester, S.; Ates, C.; Eisfeld, A.; Rost, J. M.

2010-01-01

In a regular, flexible chain of Rydberg atoms, a single electronic excitation localizes on two atoms that are in closer mutual proximity than all others. We show how the interplay between excitonic and atomic motion causes electronic excitation and diatomic proximity to propagate through the Rydberg chain as a combined pulse. In this manner entanglement is transferred adiabatically along the chain, reminiscent of momentum transfer in Newton's cradle.

29 CFR 1202.4 - Secret ballot.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Secret ballot. 1202.4 Section 1202.4 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.4 Secret ballot. In conducting such investigation, the Board is authorized to take a secret ballot of the employees involved, or...

The Secret of Future Victories

Science.gov (United States)

1992-02-01

Copy S of 320 copies AD--A25 0 718 IDA PAPER P-265 3 THE SECRET OF FUTURE VICTORIES Paul F. Gormnan General, USA (Retired) DTIC 05M February 1992 NAY...TYPE AND DATES COVERED IFebruary 1992 Final--June 1991-January 1992 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS The Secret of Future Victories C -MDA...8 2N0-102 IDA PAPER P-2653 THE SECRET OF FUTURE VICTORIES Paul F. Gorman General. LUSA (Retired) February 1992 Approved for public release

Current Therapies That Modify Glucagon Secretion

DEFF Research Database (Denmark)

Grøndahl, Magnus F.; Keating, Damien J.; Vilsbøll, Tina

2017-01-01

and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs. Recent Findings: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon...... may be involved in the drugs’ efficacy and safety profiles. Based on these findings, modulation of glucagon secretion seems to play a hitherto underestimated role in the efficacy and safety of several glucose-lowering drugs. Summary: Numerous drugs currently available to diabetologists are capable...... of altering glucagon secretion: metformin, sulfonylurea compounds, insulin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors and amylin mimetics. Their diverse effects on glucagon secretion are of importance for their individual efficacy...

Characterization of a secreted Chlamydia protease

DEFF Research Database (Denmark)

Shaw, A.C.; Vandahl, B.B.; Larsen, M.R.

2002-01-01

Chlamydiae are obligate intracellular bacteria that are important human pathogens. The Chlamydia genomes contain orthologues to secretion apparatus proteins from other intracellular bacteria, but only a few secreted proteins have been identified. Most likely, effector proteins are secreted in order...... to promote infection. Effector proteins cannot be identified by motif or similarity searches. As a new strategy for identification of secreted proteins we have compared 2D-PAGE profiles of [35S]-labelled Chlamydia proteins from whole lysates of infected cells to 2D-PAGE profiles of proteins from purified...... Chlamydia. Several secretion candidates from Chlamydia trachomatis D and Chlamydia pneumoniae were detected by this method. Two protein spots were identified among the candidates. These represent fragments of the 'chlamydial protease- or proteasome-like activity factor' (CPAF) and were clearly present in 2D...

EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

Directory of Open Access Journals (Sweden)

Ya. S. Onokhina

2013-01-01

Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

Equilibrium and stochastic resonance in finite chains of noisy bistable elements

International Nuclear Information System (INIS)

Morillo, Manuel; Gomez-Ordonez, Jose; Casado, Jose Manuel

2010-01-01

Graphical abstract: We analyze the dependence of the equilibrium distribution of a collective variable of a chain on relevant parameters including the chain size and its connectivity. We also analyze the stochastic resonance effect of the same variable. - Abstract: Using numerical simulations, we analyze equilibrium properties of finite chains of coupled noisy bistable units and their response to weak time periodic forces. Finite chains with global as well as local (nearest neighbors) coupling are considered. We focus on the study of a collective variable defined as the arithmetic mean of the variables characterizing each element of the chain. By contrast with the case of infinite size chains, where the coexistence of several equilibrium distributions for the same values of parameters is possible, for finite chains just a single equilibrium distribution exists for given values of the parameters. We demonstrate that, regardless of the chain connectivity, there exist transition lines separating regions in parameter space where the equilibrium distribution function is either monomodal or multimodal. The location of the transition line depends on the chain connectivity and the size of the system. For driven chains, the response of the system shows stochastic resonant effects. For the two types of chains considered, both the power spectral amplification and the signal-to-noise ratio of the collective variable are analyzed as the noise strength, the coupling parameter and the number of bistable units in the system are varied. Compared with the effects observed in single unit systems, the collective variable shows a strong enhancement of the stochastic resonance effects.

5 CFR 2421.15 - Secret ballot.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Secret ballot. 2421.15 Section 2421.15... FEDERAL LABOR RELATIONS AUTHORITY MEANING OF TERMS AS USED IN THIS SUBCHAPTER § 2421.15 Secret ballot. Secret ballot means the expression by ballot, voting machine or otherwise, but in no event by proxy, of a...

29 CFR 452.97 - Secret ballot.

Science.gov (United States)

2010-07-01

... 29 Labor 2 2010-07-01 2010-07-01 false Secret ballot. 452.97 Section 452.97 Labor Regulations... OF 1959 Election Procedures; Rights of Members § 452.97 Secret ballot. (a) A prime requisite of elections regulated by title IV is that they be held by secret ballot among the members or in appropriate...

Linear-chain assemblies of iron oxide nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Dhak, Prasanta; Kim, Min-Kwan; Lee, Jae Hyeok; Kim, Miyoung; Kim, Sang-Koog, E-mail: sangkoog@snu.ac.kr

2017-07-01

Highlights: • Hydrothermal synthesis of pure phase 200 nm Fe{sub 3}O{sub 4} nanoparticles. • Studies of linear-chain assemblies of iron oxide nanosphere by FESEM. • Micromagnetic simulations showed the presence of 3D vortex states. • The B.E. for different numbers of particles in linear chain assemblies were calculated. - Abstract: We synthesized iron oxide nanoparticles using a simple hydrothermal approach and found several types of segments of their linear-chain self-assemblies as observed by field emission scanning electron microscopy. X-ray diffraction and transmission electron microscopy measurements confirm a well-defined single-phase FCC structure. Vibrating sample magnetometry measurements exhibit a ferromagnetic behavior. Micromagnetic numerical simulations show magnetic vortex states in the nanosphere model. Also, calculations of binding energies for different numbers of particles in the linear-chain assemblies explain a possible mechanism responsible for the self-assemblies of segments of the linear chains of nanoparticles. This work offers a step towards linear-chain self-assemblies of iron oxide nanoparticles and the effect of magnetic vortex states in individual nanoparticles on their binding energy.

Secretive eating among youth with overweight or obesity.

Science.gov (United States)

Kass, Andrea E; Wilfley, Denise E; Eddy, Kamryn T; Boutelle, Kerri N; Zucker, Nancy; Peterson, Carol B; Le Grange, Daniel; Celio-Doyle, Angela; Goldschmidt, Andrea B

2017-07-01

Secretive eating, characterized by eating privately to conceal being seen, may reflect eating- and/or body-related shame, be associated with depression, and correlate with binge eating, which predicts weight gain and eating disorder onset. Increasing understanding of secretive eating in youth may improve weight status and reduce eating disorder risk. This study evaluated the prevalence and correlates of secretive eating in youth with overweight or obesity. Youth (N = 577) presented to five research/clinical institutions. Using a cross-sectional design, secretive eating was evaluated in relation to eating-related and general psychopathology via linear and logistic regression analyses. Secretive eating was endorsed by 111 youth, who were, on average, older than youth who denied secretive eating (mean age = 12.07 ± 2.83 versus 10.97 ± 2.31). Controlling for study site and age, youth who endorsed secretive eating had higher eating-related psychopathology and were more likely to endorse loss of control eating and purging than their counterparts who did not endorse secretive eating. Groups did not differ in excessive exercise or behavioral problems. Dietary restraint and purging were elevated among adolescents (≥13y) but not children (<13y) who endorsed secretive eating; depression was elevated among children, but not adolescents, who endorsed secretive eating. Secretive eating may portend heightened risk for eating disorders, and correlates of secretive eating may differ across pediatric development. Screening for secretive eating may inform identification of problematic eating behaviors, and understanding factors motivating secretive eating may improve intervention tailoring. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cutting Food Waste through Cooperation along the Food Supply Chain

Directory of Open Access Journals (Sweden)

Christine Göbel

2015-01-01

Full Text Available Food produced but not used for human consumption is a waste of natural resources. In order to prevent and reduce food waste, the main causes have to be identified systematically along the food supply chain (FSC. The aim of this study is (1 to shed light on the causes and effects of food waste through the analysis of 44 qualitative expert interviews examining the processes and intermediaries along the German food chain and (2 to find methods to reduce it. Results indicate that food waste occurs at all stages in the food chain. Thus, there is no single culprit to be blamed. Besides, the identified reasons for food waste differ between product groups; not a single solution can cause notable change. Furthermore, the analysis demonstrates that the causes and effects of food waste are to be found at different stages of the value chain. Hence, it is of high importance to improve communication and to raise a new appreciation for food among all stakeholders of the food supply chain in order to develop a more sustainable food system. Information on the topic of food waste needs to be shared among all actors of the supply chain. They need to share responsibility and work together to reduce food waste.

Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

International Nuclear Information System (INIS)

Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El

2016-01-01

To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma

Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi Young; Kim, Jin Hee; Oh, Young Kee; Kim, El [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

2016-06-15

To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma.

Extracellular secretion of a recombinant therapeutic peptide by Bacillus halodurans utilizing a modified flagellin type III secretion system

CSIR Research Space (South Africa)

Berger, E

2011-08-01

Full Text Available further 3.5-fold increase in the secretion of recombinant peptide fusions. Conclusions: The type III flagellar secretion system of B. halodurans has been shown to successfully secrete a therapeutic peptide as a heterologous flagellin fusion. Improvements...

Pituitary-hormone secretion by thyrotropinomas

NARCIS (Netherlands)

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading

General model of phospholipid bilayers in fluid phase within the single chain mean field theory

Energy Technology Data Exchange (ETDEWEB)

Guo, Yachong; Baulin, Vladimir A. [Departament d’Enginyeria Química, Universitat Rovira i Virgili, Av. dels Paisos Catalans 26, 43007 Tarragona (Spain); Pogodin, Sergey [Institute of Chemical Research of Catalonia, ICIQ, Av. Paisos Catalans 16, 43007 Tarragona (Spain)

2014-05-07

Coarse-grained model for saturated phospholipids: 1,2-didecanoyl-sn-glycero-3-phosphocholine (DCPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and unsaturated phospholipids: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2- dioleoyl-sn-glycero-3-phosphocholine (DOPC) is introduced within the single chain mean field theory. A single set of parameters adjusted for DMPC bilayers gives an adequate description of equilibrium and mechanical properties of a range of saturated lipid molecules that differ only in length of their hydrophobic tails and unsaturated (POPC, DOPC) phospholipids which have double bonds in the tails. A double bond is modeled with a fixed angle of 120°, while the rest of the parameters are kept the same as saturated lipids. The thickness of the bilayer and its hydrophobic core, the compressibility, and the equilibrium area per lipid correspond to experimentally measured values for each lipid, changing linearly with the length of the tail. The model for unsaturated phospholipids also fetches main thermodynamical properties of the bilayers. This model is used for an accurate estimation of the free energies of the compressed or stretched bilayers in stacks or multilayers and gives reasonable estimates for free energies. The proposed model may further be used for studies of mixtures of lipids, small molecule inclusions, interactions of bilayers with embedded proteins.

Hafnium carbide nanocrystal chains for field emitters

International Nuclear Information System (INIS)

Tian, Song; Li, Hejun; Zhang, Yulei; Ren, Jincui; Qiang, Xinfa; Zhang, Shouyang

2014-01-01

A hafnium carbide (HfC) nanostructure, i.e., HfC nanocrystal chain, was synthesized by a chemical vapor deposition (CVD) method. X-ray diffractometer, field-emission scanning electron microscope, transmission electron microscope, and energy-dispersive X-ray spectrometer were employed to characterize the product. The synthesized one-dimensional (1D) nanostructures with many faceted octahedral nanocrystals possess diameters of tens of nanometers to 500 nm and lengths of a few microns. The chain-like structures possess a single crystalline structure and preferential growth direction along the [1 0 0] crystal orientation. The growth of the chains occurred through the vapor–liquid–solid process along with a negative-feedback mechanism. The field emission (FE) properties of the HfC nanocrystal chains as the cold cathode emitters were examined. The HfC nanocrystal chains display good FE properties with a low turn-on field of about 3.9 V μm −1 and a high field enhancement factor of 2157, implying potential applications in vacuum microelectronics.

Normal and abnormal secretion by haemopoietic cells

Science.gov (United States)

STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

2001-01-01

The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

Some Economics of Trade Secret Law

OpenAIRE

David D. Friedman; William M. Landes; Richard A. Posner

1991-01-01

Despite the practical importance of trade secrets to the business community, the law of trade secrets is a neglected orphan in economic analysis. This paper sketches an approach to the economics of trade secret law that connects it more closely both to other areas of intellectual property and to broader issues in the positive economic theory of the common law.

Effect of inhibition of microsomal Ca(2+)-ATPase on cytoplasmic calcium and enzyme secretion in pancreatic acini.

Science.gov (United States)

Metz, D C; Pradhan, T K; Mrozinski, J E; Jensen, R T; Turner, R J; Patto, R J; Gardner, J D

1994-01-13

We used thapsigargin (TG), 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ) and cyclopiazonic acid (CPA), each of which inhibits microsomal Ca(2+)-ATPase, to evaluate the effects of this inhibition on cytoplasmic free calcium ([Ca2+]i) and secretagogue-stimulated enzyme secretion in rat pancreatic acini. Using single-cell microspectrofluorimetry of fura-2-loaded acini we found that all three agents caused a sustained increase in [Ca2+]i by mobilizing calcium from inositol-(1,4,5)-trisphosphate-sensitive intracellular calcium stores and by promoting influx of extracellular calcium. Concentrations of all three agents that increased [Ca2+]i potentiated the stimulation of enzyme secretion caused by secretagogues that activate adenylate cyclase but inhibited the stimulation of enzyme secretion caused by secretagogues that activate phospholipase C. With BHQ, potentiation of adenylate cyclase-mediated enzyme secretion occurred immediately whereas inhibition of phospholipase C-mediated enzyme secretion occurred only after several min of incubation. In addition, the effects of BHQ and CPA on both [Ca2+]i and secretagogue-stimulated enzyme secretion were reversed completely by washing whereas the actions of TG could not be reversed by washing. Concentrations of BHQ in excess of those that caused maximal changes in [Ca2+]i inhibited all modes of stimulated enzyme secretion by a mechanism that was apparently unrelated to changes in [Ca2+]i. Finally, in contrast to the findings with TG and BHQ, CPA inhibited bombesin-stimulated enzyme secretion over a range of concentrations that was at least 10-fold lower than the range of concentrations over which CPA potentiated VIP-stimulated enzyme secretion.

Simulation of Lean Principles Impact in a Multi-Product Supply Chain

OpenAIRE

Matteo, Rossini; Alberto, Portioli Staudacher

2015-01-01

The market competition is moving from the single firm to the whole supply chain because of increasing competition and growing need for operational efficiencies and customer orientation. Supply chain management allows companies to look beyond their organizational boundaries to develop and leverage resources and capabilities of their supply chain partners. This creates competitive advantages in the marketplace and because of this SCM has acquired strategic importance. Lean ...

Structural organization of the needle complex of the type III secretion apparatus of Shigella flexneri

NARCIS (Netherlands)

Sani, Musa; Allaoui, Abdelmounaaïm; Fusetti, Fabrizia; Oostergetel, Gert T.; Keegstra, Wilko; Boekema, Egbert J.

2007-01-01

The secretion apparatus known as the needle complex (NC) from the bacterium Shigella flexneri was studied by single particle electron microscopy. The isolated intact NC appears in projection to be composed of a basal body consisting of seven rings and a protruding needle appendage. A comparison of

The Evolution of the Secreted Regulatory Protein Progranulin.

Science.gov (United States)

Palfree, Roger G E; Bennett, Hugh P J; Bateman, Andrew

2015-01-01

Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide

Physiology of bile secretion.

Science.gov (United States)

Esteller, Alejandro

2008-10-07

The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

Antiretroviral procurement and supply chain management.

Science.gov (United States)

Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

2014-01-01

Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products.

Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells.

Directory of Open Access Journals (Sweden)

Tina Zavašnik-Bergant

Full Text Available Dendritic cells (DC play a pivotal role as antigen presenting cells (APC and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70 during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii.

Conformational explosion: Understanding the complexity of short chain para-dialkylbenzene potential energy surfaces

Science.gov (United States)

Mishra, Piyush; Hewett, Daniel M.; Zwier, Timothy S.

2018-05-01

The single-conformation ultraviolet and infrared spectroscopy of three short-chain para-dialkylbenzenes (para-diethylbenzene, para-dipropylbenzene, and para-dibutylbenzene) is reported for the jet-cooled, isolated molecules. The present study builds off previous work on single-chain n-alkylbenzenes, where an anharmonic local mode Hamiltonian method was developed to account for stretch-bend Fermi resonance in the alkyl CH stretch region [D. P. Tabor et al., J. Chem. Phys. 144, 224310 (2016)]. The jet-cooled molecules are interrogated using laser-induced fluorescence (LIF) excitation, fluorescence dip infrared spectroscopy, and dispersed fluorescence. The LIF spectra in the S1 ← S0 origin region show a dramatic increase in the number of resolved transitions with increasing length of the alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an "egg carton" shaped potential energy surface. A combination of electronic frequency shift and alkyl CH stretch infrared spectra is used to generate a consistent set of conformational assignments. Using these experimental techniques in conjunction with computational methods, subsets of origin transitions in the LIF excitation spectrum can be classified into different conformational families. Two conformations are resolved in para-diethylbenzene, seven in para-dipropylbenzene, and about nineteen in para-dibutylbenzene. These chains are largely independent of each other as there are no new single-chain conformations induced by the presence of a second chain. A cursory LIF excitation scan of para-dioctylbenzene shows a broad congested spectrum at frequencies consistent with interactions of alkyl chains with the phenyl π cloud.

Unconventional Pathways of Secretion Contribute to Inflammation

Directory of Open Access Journals (Sweden)

Michael J. D. Daniels

2017-01-01

Full Text Available In the conventional pathway of protein secretion, leader sequence-containing proteins leave the cell following processing through the endoplasmic reticulum (ER and Golgi body. However, leaderless proteins also enter the extracellular space through mechanisms collectively known as unconventional secretion. Unconventionally secreted proteins often have vital roles in cell and organism function such as inflammation. Amongst the best-studied inflammatory unconventionally secreted proteins are interleukin (IL-1β, IL-1α, IL-33 and high-mobility group box 1 (HMGB1. In this review we discuss the current understanding of the unconventional secretion of these proteins and highlight future areas of research such as the role of nuclear localisation.

Proton pump inhibitors inhibit pancreatic secretion

DEFF Research Database (Denmark)

Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

2015-01-01

+/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

Hoopoes color their eggs with antimicrobial uropygial secretions

Science.gov (United States)

Soler, Juan J.; Martín-Vivaldi, M.; Peralta-Sánchez, J. M.; Arco, L.; Juárez-García-Pelayo, N.

2014-09-01

Uropygial gland secretions are used as cosmetics by some species of birds to color and enhance properties of feathers and teguments, which may signal individual quality. Uropygial secretions also reach eggshells during incubation and, therefore, may influence the coloration of birds' eggs, a trait that has attracted the attention of evolutionary biologists for more than one century. The color of hoopoe eggs typically changes along incubation, from bluish-gray to greenish-brown. Here, we test experimentally the hypothesis that dark uropygial secretion of females is responsible for such drastic color change. Moreover, since uropygial secretion of hoopoes has antimicrobial properties, we also explore the association between color and antimicrobial activity of the uropygial secretion of females. We found that eggs stayed bluish-gray in nests where female access to the uropygial secretion was experimentally blocked. Furthermore, experimental eggs that were maintained in incubators and manually smeared with uropygial secretion experienced similar color changes that naturally incubated eggs did, while control eggs that were not in contact with the secretions did not experience such color changes. All these results strongly support the hypothesis that female hoopoes use their uropygial gland secretion to color the eggs. Moreover, saturation of the uropygial secretion was associated with antimicrobial activity against Bacillus licheniformis. Given the known antimicrobial potential of uropygial secretions of birds, this finding opens the possibility that in scenarios of sexual selection, hoopoes in particular and birds in general signal antimicrobial properties of their uropygial secretion by mean of changes in egg coloration along incubation.

Gut microbiota–derived short-chain fatty acids and kidney diseases

Directory of Open Access Journals (Sweden)

Li L

2017-12-01

Full Text Available Lingzhi Li, Liang Ma, Ping Fu Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China Abstract: Gut microbiota and its metabolites play pivotal roles in host physiology and pathology. Short-chain fatty acids (SCFAs, as a group of metabolites, exert positive regulatory effects on energy metabolism, hormone secretion, immune inflammation, hypertension, and cancer. The functions of SCFAs are related to their activation of transmembrane G protein-coupled receptors and their inhibition of histone acetylation. Though controversial, growing evidence suggests that SCFAs, which regulate inflammation, oxidative stress, and fibrosis, have been involved in kidney disease through the activation of the gut–kidney axis; however, the molecular relationship among gut microbiota–derived metabolites, signaling pathways, and kidney disease remains to be elucidated. This review will provide an overview of the physiology and functions of SCFAs in kidney disease. Keywords: gut microbiome, short-chain fatty acids, kidney diseases, gut–kidney axis

Grazer-induced chain lenght plasticity reduces grazing risk in a marine diatom

DEFF Research Database (Denmark)

Bergkvist, Johanna; Thor, Peter; Jakobsen, Hans Henrik

2012-01-01

. marinoi was exposed to chemical cues from caged A. tonsa without physical contact with the responding cells. The reductions in chain length significantly reduced copepod grazing; grazing rates on chains (four cells or more) were several times higher compared to that of single cells. This suggests...... that chain length plasticity is a means for S. marinoi to reduce copepod grazing. In contrast, chain length was not suppressed in cultures exposed to the microzooplankton grazer Gyrodinium dominans. Size-selective predation may have played a key role in the evolution of chain formation and chain length...... plasticity in diatoms...

Semisynthetic protein nanoreactor for single-molecule chemistry

OpenAIRE

Lee, Joongoo; Bayley, Hagan

2015-01-01

The modulation of ionic current flowing through an individual protein pore provides information at the single-molecule level about chemical reactions occurring within the pore. However, chemistry investigated in this way has been largely confined to the reactions of thiolates, presented by the side chains of cysteine residues. The introduction of unnatural amino acids would provide a large variety of reactive side chains with which additional single-molecule chemistry could be investigated. H...

Anomalous conductance oscillations and half-metallicity in atomic Ag-O chains

DEFF Research Database (Denmark)

Strange, Mikkel; Thygesen, Kristian Sommer; Sethna, James P

2008-01-01

. The conductances of the chains exhibit weak even-odd oscillations around an anomalously low value of 0.1G(0) (G(0) = 2e(2)/h) which coincide with the averaged experimental conductance in the long chain limit. The unusual conductance properties are explained in terms of a resonating-chain model, which takes...... the reflection probability and phase shift of a single bulk-chain interface as the only input. The model also explains the conductance oscillations for other metallic chains.......Using spin density functional theory, we study the electronic and magnetic properties of atomically thin, suspended chains containing silver and oxygen atoms in an alternating sequence. Chains longer than 4 atoms develop a half-metallic ground state implying fully spin-polarized charge carriers...

Robust Multiparty Quantum Secret Key Sharing Over Two Collective-Noise Channels via Three-Photon Mixed States

International Nuclear Information System (INIS)

Wang Zhangyin; Yuan Hao; Gao Gan; Shi Shouhua

2006-01-01

We present a robust (n,n)-threshold scheme for multiparty quantum secret sharing of key over two collective-noise channels (i.e., the collective dephasing channel and the collective rotating channel) via three-photon mixed states. In our scheme, only if all the sharers collaborate together can they establish a joint key with the message sender and extract the secret message from the sender's encrypted message. This scheme can be implemented using only a Bell singlet, a one-qubit state and polarization identification of single photon, so it is completely feasible according to the present-day technique.

The role of jasmonates in floral nectar secretion.

Directory of Open Access Journals (Sweden)

Venkatesan Radhika

Full Text Available Plants produce nectar in their flowers as a reward for their pollinators and most of our crops depend on insect pollination, but little is known on the physiological control of nectar secretion. Jasmonates are well-known for their effects on senescence, the development and opening of flowers and on plant defences such as extrafloral nectar. Their role in floral nectar secretion has, however, not been explored so far. We investigated whether jasmonates have an influence on floral nectar secretion in oil-seed rape, Brassica napus. The floral tissues of this plant produced jasmonic acid (JA endogenously, and JA concentrations peaked shortly before nectar secretion was highest. Exogenous application of JA to flowers induced nectar secretion, which was suppressed by treatment with phenidone, an inhibitor of JA synthesis. This effect could be reversed by additional application of JA. Jasmonoyl-isoleucine and its structural mimic coronalon also increased nectar secretion. Herbivory or addition of JA to the leaves did not have an effect on floral nectar secretion, demonstrating a functional separation of systemic defence signalling from reproductive nectar secretion. Jasmonates, which have been intensively studied in the context of herbivore defences and flower development, have a profound effect on floral nectar secretion and, thus, pollination efficiency in B. napus. Our results link floral nectar secretion to jasmonate signalling and thereby integrate the floral nectar secretion into the complex network of oxylipid-mediated developmental processes of plants.

Chained learning architectures in a simple closed-loop behavioural context

DEFF Research Database (Denmark)

Kulvicius, Tomas; Porr, Bernd; Wörgötter, Florentin

2007-01-01

are very simple and consist of single learning unit. The current study is trying to solve this problem focusing on chained learning architectures in a simple closed-loop behavioural context. METHODS: We applied temporal sequence learning (Porr B and Wörgötter F 2006) in a closed-loop behavioural system...... where a driving robot learns to follow a line. Here for the first time we introduced two types of chained learning architectures named linear chain and honeycomb chain. We analyzed such architectures in an open and closed-loop context and compared them to the simple learning unit. CONCLUSIONS...

Secretome analysis of Aspergillus fumigatus reveals Asp-hemolysin as a major secreted protein.

Science.gov (United States)

Wartenberg, Dirk; Lapp, Katrin; Jacobsen, Ilse D; Dahse, Hans-Martin; Kniemeyer, Olaf; Heinekamp, Thorsten; Brakhage, Axel A

2011-11-01

Surface-associated and secreted proteins represent primarily exposed components of Aspergillus fumigatus during host infection. Several secreted proteins are known to be involved in defense mechanisms or immune evasion, thus, probably contributing to pathogenicity. Furthermore, several secreted antigens were identified as possible biomarkers for the verification of diseases caused by Aspergillus species. Nevertheless, there is only limited knowledge about the composition of the secretome and about molecular functions of particular proteins. To identify secreted proteins potentially essential for virulence, the core secretome of A. fumigatus grown in minimal medium was determined. Two-dimensional gel electrophoretic separation and subsequent MALDI-TOF-MS/MS analyses resulted in the identification of 64 different proteins. Additionally, secretome analyses of A. fumigatus utilizing elastin, collagen or keratin as main carbon and nitrogen source were performed. Thereby, the alkaline serine protease Alp1 was identified as the most abundant protein and hence presumably represents an important protease during host infection. Interestingly, the Asp-hemolysin (Asp-HS), which belongs to the protein family of aegerolysins and which was often suggested to be involved in fungal virulence, was present in the secretome under all growth conditions tested. In addition, a second, non-secreted protein with an aegerolysin domain annotated as Asp-hemolysin-like (HS-like) protein can be found to be encoded in the genome of A. fumigatus. Generation and analysis of Asp-HS and HS-like deletion strains revealed no differences in phenotype compared to the corresponding wild-type strain. Furthermore, hemolysis and cytotoxicity was not altered in both single-deletion and double-deletion mutants lacking both aegerolysin genes. All mutant strains showed no attenuation in virulence in a mouse infection model for invasive pulmonary aspergillosis. Overall, this study provides a comprehensive

Channel characteristics and coordination in three-echelon dual-channel supply chain

Science.gov (United States)

Saha, Subrata

2016-02-01

We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.

Secret-key expansion from covert communication

Science.gov (United States)

Arrazola, Juan Miguel; Amiri, Ryan

2018-02-01

Covert communication allows the transmission of messages in such a way that it is not possible for adversaries to detect that the communication is occurring. This provides protection in situations where knowledge that two parties are talking to each other may be incriminating to them. In this work, we study how covert communication can be used for a different purpose: secret key expansion. First, we show that any message transmitted in a secure covert protocol is also secret and therefore unknown to an adversary. We then propose a covert communication protocol where the amount of key consumed in the protocol is smaller than the transmitted key, thus leading to secure secret key expansion. We derive precise conditions for secret key expansion to occur, showing that it is possible when there are sufficiently low levels of noise for a given security level. We conclude by examining how secret key expansion from covert communication can be performed in a computational security model.

Atrazine analysis using an amperometric immunosensor based on single-chain antibody fragments and regeneration-free multi-calibrant measurement

International Nuclear Information System (INIS)

Grennan, Kathleen; Strachan, Gillian; Porter, Andrew J.; Killard, Anthony J.; Smyth, Malcolm R.

2003-01-01

This work describes the development of an electrochemical immunosensor for the analysis of atrazine using recombinant single-chain antibody (scAb) fragments. The sensors are based on carbon paste screen-printed electrodes incorporating the conducting polymer polyaniline (PANI)/poly(vinylsulphonic acid) (PVSA), which enables direct mediatorless coupling to take place between the redox centres of antigen-labelled horseradish peroxidase (HRP) and the electrode surface. Competitive immunoassays can be performed in real-time using this separation-free system. Analytical measurements based on the pseudo-linear relationship between the slope of a real-time amperometric signal and the concentration of analyte, yield a novel immunosensor set-up capable of regenerationless amperometric analysis. Multiple, sequential measurements of standards and samples can be performed on a single scAb-modified surface in a matter of minutes. No separation of bound and unbound species was necessary prior to detection. The system is capable of measuring atrazine to a detection limit of 0.1 ppb (0.1 μg l -1 ). This system offers the potential for rapid, cost-effective immunosensing for the analysis of samples of environmental, medical and pharmaceutical significance

Magnetic hysteresis and domain wall dynamics in single chain magnets with antiferromagnetic interchain coupling

Energy Technology Data Exchange (ETDEWEB)

Bukharov, A A; Ovchinnikov, A S; Baranov, N V [Department of Physics, Ural State University, Ekaterinburg, 620083 (Russian Federation); Inoue, K [Institute for Advanced Materials Research, Hiroshima University, Hiroshima (Japan)

2010-11-03

Using Monte Carlo simulations we investigate magnetic hysteresis in two- and three-dimensional systems of weakly antiferromagnetically coupled spin chains based on a scenario of domain wall (kink) motion within the chains. By adapting the model of walkers to simulate the domain wall dynamics and using the Ising-like dipole-dipole model, we study the effects of interchain coupling, temperature and anisotropy axis direction on hysteresis curves.

Generation of high-affinity, internalizing anti-FGFR2 single-chain variable antibody fragment fused with Fc for targeting gastrointestinal cancers.

Science.gov (United States)

Borek, Aleksandra; Sokolowska-Wedzina, Aleksandra; Chodaczek, Grzegorz; Otlewski, Jacek

2018-01-01

Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2). The binders were selected from the human single chain variable fragment scFv phage display libraries Tomlinson I + J and showed high specificity and binding affinity towards human FGFR2 with nanomolar KD values. To improve the affinity of the best binder selected, scFvF7, we reformatted it to a bivalent diabody format, or fused it with the Fc region (scFvF7-Fc). The scFvF7-Fc antibody construct presented the highest affinity for FGFR2, with a KD of 0.76 nM, and was selectively internalized into cancer cells overexpressing FGFR2, Snu-16 and NCI-H716. Finally, we prepared a conjugate of scFvF7-Fc with the cytotoxic drug monomethyl-auristatin E (MMAE) and evaluated its cytotoxicity. The conjugate delivered MMAE selectively to FGFR2-positive tumor cells. These results indicate that scFvF7-Fc-vcMMAE is a highly potent molecule for the treatment of cancers with FGFR2 overexpression.

Pancreatic bicarbonate secretion involves two proton pumps

DEFF Research Database (Denmark)

Novak, Ivana; Wang, Jing; Henriksen, Katrine L.

2011-01-01

Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium expres...

Gastric secretion elicited by conditioning in rats.

Science.gov (United States)

Caboclo, José Liberato Ferreira; Cury, Francico de Assis; Borin, Aldenis Albanese; Caboclo, Luís Otávio Sales Ferreira; Ribeiro, Maria Fernanda Sales Caboclo; de Freitas, Pedro José; Andersson, Sven

2009-01-01

To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

Price competition and equilibrium analysis in multiple hybrid channel supply chain

Science.gov (United States)

Kuang, Guihua; Wang, Aihu; Sha, Jin

2017-06-01

The amazing boom of Internet and logistics industry prompts more and more enterprises to sell commodity through multiple channels. Such market conditions make the participants of multiple hybrid channel supply chain compete each other in traditional and direct channel at the same time. This paper builds a two-echelon supply chain model with a single manufacturer and a single retailer who both can choose different channel or channel combination for their own sales, then, discusses the price competition and calculates the equilibrium price under different sales channel selection combinations. Our analysis shows that no matter the manufacturer and retailer choose same or different channel price to compete, the equilibrium price does not necessarily exist the equilibrium price in the multiple hybrid channel supply chain and wholesale price change is not always able to coordinate supply chain completely. We also present the sufficient and necessary conditions for the existence of equilibrium price and coordination wholesale price.

GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

Energy Technology Data Exchange (ETDEWEB)

Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin, E-mail: hjjang@khu.ac.kr

2015-12-04

Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

International Nuclear Information System (INIS)

Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin

2015-01-01

Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

Mammalian protein secretion without signal peptide removal. Biosynthesis of plasminogen activator inhibitor-2 in U-937 cells

International Nuclear Information System (INIS)

Ye, R.D.; Wun, T.C.; Sadler, J.E.

1988-01-01

Plasminogen activator inhibitor-2 (PAI-2) is a serine protease inhibitor that regulates plasmin generation by inhibiting urokinase and tissue plasminogen activator. The primary structure of PAI-2 suggests that it may be secreted without cleavage of a single peptide. To confirm this hypothesis we have studied the glycosylation and secretion of PAI-2 in human monocytic U-937 cells by metabolic labeling, immunoprecipitation, glycosidase digestion, and protein sequencing. PAI-2 is variably glycosylated on asparagine residues to yield intracellular intermediates with zero, one, two, or three high mannose-type oligosaccharide units. Secretion of the N-glycosylated species began by 1 h of chase and the secreted molecules contained both complex-type N-linked and O-linked oligosaccharides. Enzymatically deglycosylated PAI-2 had an electrophoretic mobility identical to that of the nonglycosylated precursor and also to that of PAI-2 synthesized in vitro in a rabbit reticulocyte lysate from synthetic mRNA derived from full length PAI-2 cDNA. The amino-terminal protein sequence of secreted PAI-2 began with the initiator methionine residue. These results indicate that PAI-2 is glycosylated and secreted efficiently without the cleavage of a signal peptide. PAI-2 shares this property with its nearest homologue in the serine protease inhibitor family, chicken ovalbumin, and appears to be the first well characterized example of this phenomenon among natural mammalian proteins

Air Force UAV’s: The Secret History

Science.gov (United States)

2010-07-01

iA Mitchell Institute Study i Air Force UAVs The Secret History A Mitchell Institute Study July 2010 By Thomas P. Ehrhard Report Documentation Page...DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Air Force UAVs The Secret History 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c... The Secret History 2 Air Force UAVs: The Secret History2 air Force uaVs: The secret history Has any airplane in the past decade captured the public

A quantum secret-sharing protocol with fairness

International Nuclear Information System (INIS)

Liu, Feng; Qin, Su-Juan; Wen, Qiao-Yan

2014-01-01

A quantum secret-sharing (QSS) protocol consists of two main phases, called sharing and reconstruction. In the first phase, the dealer selects a secret, divides it into several shares, and sends each participant its share securely with a quantum channel. In the second phase, the participants run an interactive protocol in order to reconstruct the secret. If the participants can communicate via a broadcast channel, they can show their shares and learn the secrets simultaneously. So what happens if the channel is not simultaneous? In this paper, we propose a QSS protocol with cheaters by using partially and maximally entangled states. A secure and fair reconstruction mechanism is designed, in a way that each participant can learn or cannot learn the secret simultaneously. (papers)

The conversion of BTEX compounds by single and defined mixed cultures to medium-chain-length polyhydroxyalkanoate.

Science.gov (United States)

Nikodinovic, Jasmina; Kenny, Shane T; Babu, Ramesh P; Woods, Trevor; Blau, Werner J; O'Connor, Kevin E

2008-09-01

Here, we report the use of petrochemical aromatic hydrocarbons as a feedstock for the biotechnological conversion into valuable biodegradable plastic polymers--polyhydroxyalkanoates (PHAs). We assessed the ability of the known Pseudomonas putida species that are able to utilize benzene, toluene, ethylbenzene, p-xylene (BTEX) compounds as a sole carbon and energy source for their ability to produce PHA from the single substrates. P. putida F1 is able to accumulate medium-chain-length (mcl) PHA when supplied with toluene, benzene, or ethylbenzene. P. putida mt-2 accumulates mcl-PHA when supplied with toluene or p-xylene. The highest level of PHA accumulated by cultures in shake flask was 26% cell dry weight for P. putida mt-2 supplied with p-xylene. A synthetic mixture of benzene, toluene, ethylbenzene, p-xylene, and styrene (BTEXS) which mimics the aromatic fraction of mixed plastic pyrolysis oil was supplied to a defined mixed culture of P. putida F1, mt-2, and CA-3 in the shake flasks and fermentation experiments. PHA was accumulated to 24% and to 36% of the cell dry weight of the shake flask and fermentation grown cultures respectively. In addition a three-fold higher cell density was achieved with the mixed culture grown in the bioreactor compared to shake flask experiments. A run in the 5-l fermentor resulted in the utilization of 59.6 g (67.5 ml) of the BTEXS mixture and the production of 6 g of mcl-PHA. The monomer composition of PHA accumulated by the mixed culture was the same as that accumulated by single strains supplied with single substrates with 3-hydroxydecanoic acid occurring as the predominant monomer. The purified polymer was partially crystalline with an average molecular weight of 86.9 kDa. It has a thermal degradation temperature of 350 degrees C and a glass transition temperature of -48.5 degrees C.

Integrable spin chain in superconformal Chern-Simons theory

International Nuclear Information System (INIS)

Bak, Dongsu; Rey, Soo-Jong

2008-01-01

N = 6 superconformal Chern-Simons theory was proposed as gauge theory dual to Type IIA string theory on AdS 4 x CP 3 . We study integrability of the theory from conformal dimension spectrum of single trace operators at planar limit. At strong 't Hooft coupling, the spectrum is obtained from excitation energy of free superstring on OSp(6|4; R)/SO(3, 1) x SU(3) x U(1) supercoset. We recall that the worldsheet theory is integrable classically by utilizing well-known results concerning sigma model on symmetric space. With R-symmetry group SU(4), we also solve relevant Yang-Baxter equation for a spin chain system associated with the single trace operators. From the solution, we construct alternating spin chain Hamiltonian involving three-site interactions between 4 and 4-bar . At weak 't Hooft coupling, we study gauge theory perturbatively, and calculate action of dilatation operator to single trace operators up to two loops. To ensure consistency, we computed all relevant Feynman diagrams contributing to the dilatation opeator. We find that resulting spin chain Hamiltonian matches with the Hamiltonian derived from Yang-Baxter equation. We further study new issues arising from the shortest gauge invariant operators TrY I Y † J = (15, 1). We observe that 'wrapping interactions' are present, compute the true spectrum and find that the spectrum agrees with prediction from supersymmetry. We also find that scaling dimension computed naively from alternating spin chain Hamiltonian coincides with the true spectrum. We solve Bethe ansatz equations for small number of excitations, and find indications of correlation between excitations of 4's and 4-bar 's and of nonexistence of mesonic (44-bar ) bound-state.

Trade secrets protection mode of nuclear power plant

International Nuclear Information System (INIS)

Zeng Bin

2015-01-01

The paper analyzes the legal environment in which nuclear power enterprises are stayed, and mainly discusses the business secret protection modes of China's nuclear power enterprises. It is expected to provide a revelation and help for these enterprises to protect their business secrets. Firstly, the paper briefly expounds the legal basis of business secret protection and China's legalization status in this regard. Then it mainly puts forward the business secret management framework and postulations for nuclear power enterprises, and key points in application and protection of nuclear power business secret. (author)

Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the African Hyperoliid Frog, Kassina senegalensis.

Science.gov (United States)

Du, Qiang; Wang, Hui; Ma, Chengbang; Wu, Yue; Xi, Xinping; Zhou, Mei; Chen, Tianbao; Shaw, Chris; Wang, Lei

2017-07-19

The defensive skin secretions of amphibians continue to be an excellent source of novel biologically-active peptides. Here we report the identification and pharmacological activity of a novel C-terminally amided myotropic octapeptide from the skin secretion of the African hyperoliid frog, Kassina senegalensis . The 8-amino acid peptide has the following primary structure: WMSLGWSL-amide and has a molecular mass of 978 Da. The primary structure and organisation of the biosynthetic precursor of WL-8 amide was successfully deduced from cloned skin secretion-derived cDNA. The open-reading frame encoded a single copy of WL-8, located at the C-terminus. Synthetic WL-8 amide was found to cause relaxation of rat tail artery smooth muscle with an EC 50 of 25.98 nM. This peptide is unique in terms of its primary structure and is unlike any other peptide previously isolated from an amphibian source which has been archived in the NCBI database. WL-8 amide thus represents the prototype of a novel family of myotropic peptide from amphibian defensive skin secretions.

Lamellar granule secretion starts before the establishment of tight junction barrier for paracellular tracers in mammalian epidermis.

Directory of Open Access Journals (Sweden)

Akemi Ishida-Yamamoto

Full Text Available Defects in epidermal barrier function and/or vesicular transport underlie severe skin diseases including ichthyosis and atopic dermatitis. Tight junctions (TJs form a single layered network in simple epithelia. TJs are important for both barrier functions and vesicular transport. Epidermis is stratified epithelia and lamellar granules (LGs are secreted from the stratum granulosum (SG in a sequential manner. Previously, continuous TJs and paracellular permeability barriers were found in the second layer (SG2 of SG in mice, but their fate and correlation with LG secretion have been poorly understood. We studied epidermal TJ-related structures in humans and in mice and found occludin/ZO-1 immunoreactive multilayered networks spanning the first layer of SG (SG1 and SG2. Paracellular penetration tracer passed through some TJs in SG2, but not in SG1. LG secretion into the paracellular tracer positive spaces started below the level of TJs of SG1. Our study suggests that LG-secretion starts before the establishment of TJ barrier in the mammalian epidermis.

Supply Chain Contracts in Fashion Department Stores: Coordination and Risk Analysis

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Bin Shen

2014-01-01

Full Text Available In the fashion industry, department stores normally trade with suppliers of national brands by markdown contract whilst developing private labels with cooperated designers by profit sharing contract. Motivated by this real industrial practice, we study a single-supplier single-retailer two-echelon fashion supply chain selling a short-life fashion product of either a national brand or a private label. The supplier refers to the national/designer brand owner and the retailer refers to the department store. We investigate the supply chain coordination issue and examine the supply chain agents’ performances under the mentioned two contracts. We find the analytical evidence that there is a similar relative risk performance but different absolute risk performances between the national brand and the private label. This finding provides an important implication in strategic interaction for the risk-averse department stores in product assortment and brand management. Furthermore, we explore the impact of sales effort on the supply chain system and find that the supply chain is able to achieve coordination if and only if the supplier (i.e., the national brand or the private label is willing to share the cost of the sales effort.

Coordinating a Supply Chain with Price and Advertisement Dependent Stochastic Demand

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Li, Liying; Wang, Yong; Yan, Xiaoming

2013-01-01

This paper investigates pricing and ordering as well as advertising coordination issues in a single-manufacturer single-retailer supply chain, where the manufacturer sells a newsvendor-type product through the retailer who faces a stochastic demand depending on both retail price and advertising expenditure. Under the assumption that the market demand has a multiplicative functional form, the Stackelberg and cooperative game models are developed, and the closed form solution to each model is provided as well. Comparisons and insights are presented. We show that a properly designed revenue-cost-sharing contract can achieve supply chain coordination and lead to a Pareto improving win-win situation for channel members. We also discuss the allocation of the extra joint profit according to individual supply chain members' risk preferences and negotiating powers. PMID:24453832

Coordinating a Supply Chain with Price and Advertisement Dependent Stochastic Demand

Directory of Open Access Journals (Sweden)

Liying Li

2013-01-01

Full Text Available This paper investigates pricing and ordering as well as advertising coordination issues in a single-manufacturer single-retailer supply chain, where the manufacturer sells a newsvendor-type product through the retailer who faces a stochastic demand depending on both retail price and advertising expenditure. Under the assumption that the market demand has a multiplicative functional form, the Stackelberg and cooperative game models are developed, and the closed form solution to each model is provided as well. Comparisons and insights are presented. We show that a properly designed revenue-cost-sharing contract can achieve supply chain coordination and lead to a Pareto improving win-win situation for channel members. We also discuss the allocation of the extra joint profit according to individual supply chain members’ risk preferences and negotiating powers.

Coordinating a supply chain with price and advertisement dependent stochastic demand.

Science.gov (United States)

Li, Liying; Wang, Yong; Yan, Xiaoming

2013-01-01

This paper investigates pricing and ordering as well as advertising coordination issues in a single-manufacturer single-retailer supply chain, where the manufacturer sells a newsvendor-type product through the retailer who faces a stochastic demand depending on both retail price and advertising expenditure. Under the assumption that the market demand has a multiplicative functional form, the Stackelberg and cooperative game models are developed, and the closed form solution to each model is provided as well. Comparisons and insights are presented. We show that a properly designed revenue-cost-sharing contract can achieve supply chain coordination and lead to a Pareto improving win-win situation for channel members. We also discuss the allocation of the extra joint profit according to individual supply chain members' risk preferences and negotiating powers.

A time-dependent density functional theory investigation of plasmon resonances of linear Au atomic chains

International Nuclear Information System (INIS)

Liu Dan-Dan; Zhang Hong

2011-01-01

We report theoretical studies on the plasmon resonances in linear Au atomic chains by using ab initio time-dependent density functional theory. The dipole responses are investigated each as a function of chain length. They converge into a single resonance in the longitudinal mode but split into two transverse modes. As the chain length increases, the longitudinal plasmon mode is redshifted in energy while the transverse modes shift in the opposite direction (blueshifts). In addition, the energy gap between the two transverse modes reduces with chain length increasing. We find that there are unique characteristics, different from those of other metallic chains. These characteristics are crucial to atomic-scale engineering of single-molecule sensing, optical spectroscopy, and so on. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Ionizing radiation in secret services' conspirative actions

International Nuclear Information System (INIS)

Vogel, H.; Lotz, P.; Vogel, B.

2007-01-01

Introduction: The death of Litvinenko has been reported by the media. It has raised the question whether this case had been unique. The fall of the wall has allowed a glimpse in the planning and comporting of a secret service. Material and method: Documents of the secret service of the former German democratic republic (GDR), books of defectors, and media reports about secret service actions with radiating substances have been analyzed. Results: Since decades, secret services have been using radioactive nuclides and radiation for their tasks. Several killings with radiation have been reported. A complicated logistic had been developed. Conclusion: Only singular cases of the employment of radiating substances have become known. It is probable that the majority rests unknown. Government support seems necessary in secret services' conspirative actions with radiating substance

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

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Bat-Chen eAmit-Cohen

2013-07-01

Full Text Available Tumor macrophages are generally considered to be alternatively/M2 activated to induce secretion of pro-angiogenic factors such as VEGF and MMPs. EMMPRIN (CD147, basigin is overexpressed in many tumor types, and has been shown to induce fibroblasts and endothelial cell expression of MMPs and VEGF. We first show that tumor cell interactions with macrophages resulted in increased expression of EMMPRIN and induction of MMP-9 and VEGF. Human A498 renal carcinoma or MCF-7 breast carcinoma cell lines were co-cultured with the U937 monocytic-like cell line in the presence of TNFalpha (1 ng/ml. Membranal EMMPRIN expression was increased in the co-cultures (by 3-4 folds, p<0.01, as was the secretion of MMP-9 and VEGF (by 2-5 folds for both MMP-9 and VEGF, p<0.01, relative to the single cultures with TNFalpha. Investigating the regulatory mechanisms, we show that EMMPRIN was post-translationally regulated by miR-146a, as no change was observed in the tumoral expression of EMMPRIN mRNA during co-culture, expression of miR-146a was increased and its neutralization by its antagomir inhibited EMMPRIN expression. The secretion of EMMPRIN was also enhanced (by 2-3 folds, p<0.05, only in the A498 co-culture via shedding off of the membranal protein by a serine protease that is yet to be identified, as demonstrated by the use of wide range protease inhibitors. Finally, soluble EMMPRIN enhanced monocytic secretion of MMP-9 and VEGF, as inhibition of its expression levels by neutralizing anti-EMMPRIN or siRNA in the tumor cells lead to subsequent decreased induction of these two pro-angiogenic proteins. These results reveal a mechanism whereby tumor cell-macrophage interactions promote angiogenesis via an EMMPRIN-mediated pathway.

Understanding for convergence monitoring for probabilistic risk assessment based on Markov Chain Monte Carlo Simulation

International Nuclear Information System (INIS)

Kim, Joo Yeon; Jang, Han Ki; Jang, Sol Ah; Park, Tae Jin

2014-01-01

There is a question that the simulation actually leads to draws from its target distribution and the most basic one is whether such Markov chains can always be constructed and all chain values sampled from them. The problem to be solved is the determination of how large this iteration should be to achieve the target distribution. This problem can be answered as convergence monitoring. In this paper, two widely used methods, such as autocorrelation and potential scale reduction factor (PSRF) in MCMC are characterized. There is no general agreement on the subject of the convergence. Although it is generally agreed that running n parallel chains in practice is computationally inefficient and unnecessary, running multiple parallel chains is generally applied for the convergence monitoring due to easy implementation. The main debate is the number of parallel chains needed. If the convergence properties of the chain are well understood then clearly a single chain suffices. Therefore, autocorrelation using single chain and multiple parallel ones are tried and their results then compared with each other in this study. And, the following question is answered from the two convergence results: Have the Markov chain realizations for achieved the target distribution?

Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement.

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Kravchenko-Balasha, Nataly; Shin, Young Shik; Sutherland, Alex; Levine, R D; Heath, James R

2016-05-17

Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell-cell signaling can depend on cell-cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell-cell signaling that induces a directed cell-cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell-cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell-cell distances. We show that glioblastoma cell-cell movement can be described as Brownian motion biased by cell-cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation.

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Ghoraie, Laleh Soltan; Burkowski, Forbes; Li, Shuai Cheng; Zhu, Mu

2014-01-01

Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.

Regulation of glucagon secretion by incretins

DEFF Research Database (Denmark)

Holst, Jens Juul; Christensen, M; Lund, A

2011-01-01

Glucagon secretion plays an essential role in the regulation of hepatic glucose production, and elevated fasting and postprandial plasma glucagon concentrations in patients with type 2 diabetes (T2DM) contribute to their hyperglycaemia. The reason for the hyperglucagonaemia is unclear, but recent...... studies have shown lack of suppression after oral but preserved suppression after isoglycaemic intravenous glucose, pointing to factors from the gut. Gastrointestinal hormones that are secreted in response to oral glucose include glucagon-like peptide-1 (GLP-1) that strongly inhibits glucagon secretion......, and GLP-2 and GIP, both of which stimulate secretion. When the three hormones are given together on top of isoglycaemic intravenous glucose, glucagon suppression is delayed in a manner similar to that observed after oral glucose. Studies with the GLP-1 receptor antagonist, exendin 9-39, suggest...

Role of adipose secreted factors and kisspeptin in the metabolic control of gonadotropin secretion and puberty

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Factors secreted by adipose tissue continue to be discovered. Evidence indicates a strong link between neural influences and adipocyte expression and secretion of a wide array of cytokines, neurotrophic factors, growth factors, binding proteins, and neuropeptides. These “adipokines” are linked to im...

Burkholderia cenocepacia type VI secretion system mediates escape of type II secreted proteins into the cytoplasm of infected macrophages.

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Roberto Rosales-Reyes

Full Text Available Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (BcCVs resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1β secretion and pyroptosis. Moreover, IL-1β secretion by B. cenocepacia-infected macrophages is suppressed in deletion mutants unable to produce functional Type VI, Type IV, and Type 2 secretion systems (SS. We provide evidence that the T6SS mediates the disruption of the BcCV membrane, which allows the escape of proteins secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for efficient IL-1β secretion in a T6SS dependent manner. ZmpA and ZmpB are also required for the maturation arrest of the BcCVs and bacterial intra-macrophage survival in a T6SS-independent fashion. Our results uncover a novel mechanism for inflammasome activation that involves cooperation between two bacterial secretory pathways, and an unanticipated role for T2SS-secreted proteins in intracellular bacterial survival.

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP-BM5 Retrovirus Infection

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Maria C. Lopez

2005-01-01

Full Text Available In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7+ cells and an increase in the percentage of IL-16+ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-Υ secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-Υ secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4+CD8- or CD4- CD8+ cells was due to accumulation of both immature (CD3- and mature (CD3+ single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection.

Contracts and Information Structure in a Supply Chain with Operations and Marketing Interaction

DEFF Research Database (Denmark)

El Ouardighi, F.; Erickson, G.; Grass, D.

2016-01-01

and the consumer price. The state of the game is summarized in the firms' backlogs and the manufacturer's advertising goodwill. Depending on whether the supply chain members have and share state information, they may either make decisions contingent on the current state of the game (feedback Nash strategy......The objective of the paper is to study how wholesale price and revenue sharing contracts affect operations and marketing decisions in a supply chain under different dynamic informational structures. We suggest a differential game model of a supply chain consisting of a manufacturer and a single...... retailer that agree on the contract parameters at the outset of the game. The model includes key operational and marketing activities related to a single product in the supply chain. The manufacturer sets a production rate and the rate of advertising efforts while the retailer chooses a purchase rate...

Visualization of glucagon secretion from pancreatic α cells by bioluminescence video microscopy: Identification of secretion sites in the intercellular contact regions

International Nuclear Information System (INIS)

Yokawa, Satoru; Suzuki, Takahiro; Inouye, Satoshi; Inoh, Yoshikazu; Suzuki, Ryo; Kanamori, Takao; Furuno, Tadahide; Hirashima, Naohide

2017-01-01

We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion. From immunochemical analyses, PGCG-GLase stably expressed in clonal αTC1.6 cells was correctly processed and released by secretory granules. Luminescence signals of the secreted PGCG-GLase from the stable cells were visualized by video-rate bioluminescence microscopy. The video images showed an increase in glucagon secretion from clustered cells in response to stimulation by KCl. The secretory events were observed frequently at the intercellular contact regions. Thus, the localization and frequency of glucagon secretion might be regulated by cell-cell adhesion. - Highlights: • The fused protein of proglucagon to Gaussia luciferase was used as a reporter. • The fusion protein was highly expressed using a preferred human-codon optimized gene. • Glucagon secretion stimulated by depolarization was determined by luminescence. • Glucagon secretion in α cells was visualized by bioluminescence imaging. • Glucagon secretion sites were localized in the intercellular contact regions.

29 CFR 1903.9 - Trade secrets.

Science.gov (United States)

2010-07-01

... INSPECTIONS, CITATIONS AND PROPOSED PENALTIES § 1903.9 Trade secrets. (a) Section 15 of the Act provides: “All... concerns or relates to the trade secrets, processes, operations, style of work, or apparatus, or to the...

Air Force UAVs: The Secret History

Science.gov (United States)

2010-07-01

iA Mitchell Institute Study i Air Force UAVs The Secret History A Mitchell Institute Study July 2010 By Thomas P. Ehrhard Report Documentation Page...DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Air Force UAVs The Secret History 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...opening phases of Operation Enduring Freedom in Afghanistan. By Thomas P. Ehrhard a miTchEll insTiTuTE sTudy July 2010 Air Force UAVs The Secret History

Single-polymer dynamics under constraints: scaling theory and computer experiment

International Nuclear Information System (INIS)

Milchev, Andrey

2011-01-01

The relaxation, diffusion and translocation dynamics of single linear polymer chains in confinement is briefly reviewed with emphasis on the comparison between theoretical scaling predictions and observations from experiment or, most frequently, from computer simulations. Besides cylindrical, spherical and slit-like constraints, related problems such as the chain dynamics in a random medium and the translocation dynamics through a nanopore are also considered. Another particular kind of confinement is imposed by polymer adsorption on attractive surfaces or selective interfaces-a short overview of single-chain dynamics is also contained in this survey. While both theory and numerical experiments consider predominantly coarse-grained models of self-avoiding linear chain molecules with typically Rouse dynamics, we also note some recent studies which examine the impact of hydrodynamic interactions on polymer dynamics in confinement. In all of the aforementioned cases we focus mainly on the consequences of imposed geometric restrictions on single-chain dynamics and try to check our degree of understanding by assessing the agreement between theoretical predictions and observations. (topical review)

Half the entanglement in critical systems is distillable from a single specimen

International Nuclear Information System (INIS)

Orus, R.; Latorre, J. I.; Eisert, J.; Cramer, M.

2006-01-01

We establish a quantitative relationship between the entanglement content of a single quantum chain at a critical point and the corresponding entropy of entanglement. We find that, surprisingly, the leading critical scaling of the single-copy entanglement with respect to any bipartitioning is exactly one-half of the entropy of entanglement, in a general setting of conformal field theory and quasifree systems. Conformal symmetry imposes that the single-copy entanglement scales as E 1 (ρ L )=(c/6)ln L-(c/6)(π 2 /ln L)+O(1/L), where L is the number of constituents in a block of an infinite chain and c denotes the central charge. This shows that from a single specimen of a critical chain, already half the entanglement can be distilled compared to the rate that is asymptotically available. The result is substantiated by a quantitative analysis for all translationally invariant quantum spin chains corresponding to all isotropic quasifree fermionic models. An example of the XY spin chain shows that away from criticality the above relation is maintained only near the quantum phase transition

THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

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Dusik eKim

2014-06-01

Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

The ESX system in Bacillus subtilis mediates protein secretion.

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Laura A Huppert

Full Text Available Esat-6 protein secretion systems (ESX or Ess are required for the virulence of several human pathogens, most notably Mycobacterium tuberculosis and Staphylococcus aureus. These secretion systems are defined by a conserved FtsK/SpoIIIE family ATPase and one or more WXG100 family secreted substrates. Gene clusters coding for ESX systems have been identified amongst many organisms including the highly tractable model system, Bacillus subtilis. In this study, we demonstrate that the B. subtilis yuk/yue locus codes for a nonessential ESX secretion system. We develop a functional secretion assay to demonstrate that each of the locus gene products is specifically required for secretion of the WXG100 virulence factor homolog, YukE. We then employ an unbiased approach to search for additional secreted substrates. By quantitative profiling of culture supernatants, we find that YukE may be the sole substrate that depends on the FtsK/SpoIIIE family ATPase for secretion. We discuss potential functional implications for secretion of a unique substrate.

Hyperthyroidism caused by an ectopic thyrotropin-secreting tumor of the nasopharynx: a case report and review of the literature.

Science.gov (United States)

Tong, Anli; Xia, Weibo; Qi, Fang; Jin, Zimeng; Yang, Di; Zhang, Zhuhua; Li, Fang; Xing, Xiaoping; Lian, Xiaolan

2013-09-01

Ectopic thyrotropin (TSH)-secreting tumors are extremely rare. To our knowledge, only three cases have previously been reported so far, but the tumors were not studied ultrastructurally and in vitro. We present a case that was extensively examined to gain deeper insights in terms of the histopathological features and hormonal secretion profile of the tumor. A 49-year-old female complained of nasal obstruction for 15 years and thyrotoxicosis for one and a half years. Except for a high basal TSH with concomitantly elevated free tri-iodothyronine (FT3) and free thyroxine (FT4) levels, her pituitary hormone profile yielded normal results. Magnetic resonance imaging revealed a 2 cm × 2 cm mass in the nasopharynx, which showed an increased tracer uptake on octreotide scintigraphy. Preoperative treatment with octreotide effectively reduced serum TSH, FT3, and FT4 to normal levels. The mass was endoscopically removed via an endonasal approach. Immunophenotyping and hormone determination of cultured cells confirmed that the mass was a plurihormonal TSH-/growth hormone (GH)-/prolactin (PRL)-producing adenoma. Co-expression of TSH and GH was found in most cells. Electron microscopy showed that the adenoma was formed by a single cell type, with secretory granules of small size. In vitro studies demonstrated that octreotide reduced both TSH and GH secretion. We report an ectopic TSH-secreting tumor, which had plurihormonal secretion in vitro, including TSH, GH, and PRL. Histologically, it mimicked a TSH-secreting pituitary adenoma. Octreotide was useful in the diagnosis and treatment of this ectopic TSH-secreting tumor. Ectopic TSH-secreting tumors are extremely rare. In terms of hormone secretion profile, histological characteristics, and response to octreotide, they are similar to pituitary TSH-secreting adenomas, suggesting that they are of identical cell origin.

Extrafloral nectar secretion from wounds of Solanum dulcamara.

Science.gov (United States)

Lortzing, Tobias; Calf, Onno W; Böhlke, Marlene; Schwachtje, Jens; Kopka, Joachim; Geuß, Daniel; Kosanke, Susanne; van Dam, Nicole M; Steppuhn, Anke

2016-04-25

Plants usually close wounds rapidly to prevent infections and the loss of valuable resources such as assimilates(1). However, herbivore-inflicted wounds on the bittersweet nightshade Solanum dulcamara appear not to close completely and produce sugary wound secretions visible as droplets. Many plants across the plant kingdom secrete sugary nectar from extrafloral nectaries(2) to attract natural enemies of herbivores for indirect defence(3,4). As ants forage on wound edges of S. dulcamara in the field, we hypothesized that wound secretions are a form of extrafloral nectar (EFN). We show that, unlike EFN from known nectaries, wound secretions are neither associated with any specific structure nor restricted to certain locations. However, similar to EFN, they are jasmonate-inducible and the plant controls their chemical composition. Wound secretions are attractive for ants, and application of wound secretion mimics increases ant attraction and reduces herbivory on S. dulcamara plants in a natural population. In greenhouse experiments, we reveal that ants can defend S. dulcamara from two of its native herbivores, slugs and flea beetle larvae. Since nectar is defined by its ecological function as a sugary secretion involved in interactions with animals(5), such 'plant bleeding' could be a primitive mode of nectar secretion exemplifying an evolutionary origin of structured extrafloral nectaries.

Incretin hormone secretion over the day

DEFF Research Database (Denmark)

Ahren, B; Carr, RD; Deacon, Carolyn F.

2010-01-01

The two incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are key factors in the regulation of islet function and glucose metabolism, and incretin-based therapy for type 2 diabetes has gained considerable interest during recent years. Regulat......The two incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are key factors in the regulation of islet function and glucose metabolism, and incretin-based therapy for type 2 diabetes has gained considerable interest during recent years....... Regulation of incretin hormone secretion is less well characterized. The main stimulus for incretin hormone secretion is presence of nutrients in the intestinal lumen, and carbohydrate, fat as well as protein all have the capacity to stimulate GIP and GLP-1 secretion. More recently, it has been established...... that a diurnal regulation exists with incretin hormone secretion to an identical meal being greater when the meal is served in the morning compared to in the afternoon. Finally, whether incretin hormone secretion is altered in disease states is an area with, so far, controversial results in different studies...

Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment

International Nuclear Information System (INIS)