Sample records for surface governing ligand

  1. An Extended Surface Loop on Toxoplasma gondii Apical Membrane Antigen 1 (AMA1 Governs Ligand Binding Selectivity.

    Directory of Open Access Journals (Sweden)

    Michelle L Parker

    Full Text Available Apicomplexan parasites are the causative agents of globally prevalent diseases including malaria and toxoplasmosis. These obligate intracellular pathogens have evolved a sophisticated host cell invasion strategy that relies on a parasite-host cell junction anchored by interactions between apical membrane antigens (AMAs on the parasite surface and rhoptry neck 2 (RON2 proteins discharged from the parasite and embedded in the host cell membrane. Key to formation of the AMA1-RON2 complex is displacement of an extended surface loop on AMA1 called the DII loop. While conformational flexibility of the DII loop is required to expose the mature RON2 binding groove, a definitive role of this substructure has not been elucidated. To establish a role of the DII loop in Toxoplasma gondii AMA1, we engineered a form of the protein where the mobile portion of the loop was replaced with a short Gly-Ser linker (TgAMA1ΔDIIloop. Isothermal titration calorimetry measurements with a panel of RON2 peptides revealed an influential role for the DII loop in governing selectivity. Most notably, an Eimeria tenella RON2 (EtRON2 peptide that showed only weak binding to TgAMA1 bound with high affinity to TgAMA1ΔDIIloop. To define the molecular basis for the differential binding, we determined the crystal structure of TgAMA1ΔDIIloop in complex with the EtRON2 peptide. When analyzed in the context of existing AMA1-RON2 structures, spatially distinct anchor points in the AMA1 groove were identified that, when engaged, appear to provide the necessary traction to outcompete the DII loop. Collectively, these data support a model where the AMA1 DII loop serves as a structural gatekeeper to selectively filter out ligands otherwise capable of binding with high affinity in the AMA1 apical groove. These data also highlight the importance of considering the functional implications of the DII loop in the ongoing development of therapeutic intervention strategies targeting the AMA1-RON

  2. Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions

    KAUST Repository

    Bealing, Clive R.


    Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind to the nanocrystal surface in the form of lead oleate. The Wulff construction predicts the thermodynamic equilibrium shape of the PbSe nanocrystals. The equilibrium shape is a function of the ligand surface coverage, which can be controlled by changing the concentration of oleic acid during synthesis. The different binding energy of the ligand on the {100} and {111} facets results in different equilibrium ligand coverages on the facets, and a transition in the equilibrium shape from octahedral to cubic is predicted when increasing the ligand concentration during synthesis. © 2012 American Chemical Society.

  3. Reaction chemistry and ligand exchange at cadmium selenide nanocrystal surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Jonathan; Park, Jungwon; Trudeau, Paul-Emile; Alivisatos, A. Paul


    Chemical modification of nanocrystal surfaces is fundamentally important to their assembly, their implementation in biology and medicine, and greatly impacts their electrical and optical properties. However, it remains a major challenge owing to a lack of analytical tools to directly determine nanoparticle surface structure. Early nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) studies of CdSe nanocrystals prepared in tri-n-octylphosphine oxide (1) and tri-n-octylphosphine (2), suggested these coordinating solvents are datively bound to the particle surface. However, assigning the broad NMR resonances of surface-bound ligands is complicated by significant concentrations of phosphorus-containing impurities in commercial sources of 1, and XPS provides only limited information about the nature of the phosphorus containing molecules in the sample. More recent reports have shown the surface ligands of CdSe nanocrystals prepared in technical grade 1, and in the presence of alkylphosphonic acids, include phosphonic and phosphinic acids. These studies do not, however, distinguish whether these ligands are bound datively, as neutral, L-type ligands, or by X-type interaction of an anionic phosphonate/phosphinate moiety with a surface Cd{sup 2+} ion. Answering this question would help clarify why ligand exchange with such particles does not proceed generally as expected based on a L-type ligand model. By using reagents with reactive silicon-chalcogen and silicon-chlorine bonds to cleave the ligands from the nanocrystal surface, we show that our CdSe and CdSe/ZnS core-shell nanocrystal surfaces are likely terminated by X-type binding of alkylphosphonate ligands to a layer of Cd{sup 2+}/Zn{sup 2+} ions, rather than by dative interactions. Further, we provide spectroscopic evidence that 1 and 2 are not coordinated to our purified nanocrystals.

  4. Decoding of lipoprotein-receptor interactions: properties of ligand binding modules governing interactions with apolipoprotein E. (United States)

    Guttman, Miklos; Prieto, J Helena; Croy, Johnny E; Komives, Elizabeth A


    Clusters of complement-type ligand binding repeats in the LDL receptor family are thought to mediate the interactions between these receptors and their various ligands. Apolipoprotein E, a key ligand for cholesterol homeostasis, has been shown to interact with LDLR, LRP, and VLDLR, through these clusters. LDLR and VLDLR each contain a single ligand binding repeat cluster, whereas LRP contains three large clusters of ligand binding repeats, each with ligand binding functions. We show that within sLRP3 the three-repeat subcluster CR16-18 recapitulated ligand binding to the isolated receptor binding portion of ApoE (residues 130-149). Binding experiments with LA3-5 of LDLR and CR16-18 showed that a conserved W25/D30 pair appears to be critical for high-affinity binding to ApoE(130-149). The triple repeat LA3-5 showed the expected interaction with ApoE(1-191).DMPC, but surprisingly CR16-18 did not interact with this form of ApoE. To understand these differences in ApoE binding affinity, we introduced mutations of conserved residues from LA5 into CR18 and produced a CR16-18 variant capable of binding ApoE(1-191).DMPC. This change cannot fully be accounted for by the interaction with the proposed ApoE receptor binding region; therefore, we speculate that LA5 is recognizing a distinct epitope on ApoE that may only exist in the lipid-bound form. The combination of avidity effects with this distinct recognition process likely governs the ApoE-LDL receptor interaction.

  5. Coupling of Ligands to the Liposome Surface by Click Chemistry. (United States)

    Spanedda, Maria Vittoria; De Giorgi, Marcella; Hassane, Fatouma Saïd; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît


    Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.

  6. Switching of bacterial adhesion to a glycosylated surface by reversible reorientation of the carbohydrate ligand

    DEFF Research Database (Denmark)

    Weber, Theresa; Chrasekaran, Vijayan; Stamer, Insa


    The surface recognition in many biological systems is guided by the interaction of carbohydrate-specific proteins (lectins) with carbohydrate epitopes (ligands) located within the unordered glycoconjugate layer (glycocalyx) of cells. Thus, for recognition, the respective ligand has to reorient...

  7. Microporous Cyclic Titanium-Oxo Clusters with Labile Surface Ligands. (United States)

    Zhao, Chaowei; Han, Ying-Zi; Dai, Shuqi; Chen, Xumao; Yan, Juanzhu; Zhang, Weijie; Su, Haifeng; Lin, Shuichao; Tang, Zichao; Teo, Boon K; Zheng, Nanfeng


    By using ethylene glycol and monocarboxylic acid as surface ligands, a series of cyclic Ti-oxo clusters (CTOC) with permanent microporosity are successfully synthesized. With a cyclic {Ti32 O16 } backbone made of eight connected Ti4 tetrahedral cages that are arranged in a zigzag fashion, the clusters have a "donut" shape with an inner diameter of 8.3 Å, outer diameter of 26.9 Å and height of 10.4 Å. While both inner and outer walls of the "donut" clusters are modified by double-deprotonated ethylene glycolates, their upper and lower surfaces are bound by carboxylates and mono-deprotonated ethylene glycolates. The clusters are readily packed into one-dimensional tubes which are further arranged in two different modes into crystalline microporous solids with surface areas over 660 m2  g-1 , depending on the surface carboxylates. The solid with olefin-bearing carboxylates exhibits a superior CO2 adsorption capacity of 40 cm3  g-1 at 273 K under 1 atm. Moreover, the mono-deprotonated ethylene glycolates on the clusters are demonstrated to be highly exchangeable by other alcohols, providing a nice platform for creating microporous solids or films with a wide variety of surface functionalities. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Effects of sulfate ligand on uranyl carbonato surface species on ferrihydrite surfaces (United States)

    Arai, Yuji; Fuller, C.C.


    Understanding uranium (U) sorption processes in permeable reactive barriers (PRB) are critical in modeling reactive transport for evaluating PRB performance at the Fry Canyon demonstration site in Utah, USA. To gain insight into the U sequestration mechanism in the amorphous ferric oxyhydroxide (AFO)-coated gravel PRB, U(VI) sorption processes on ferrihydrite surfaces were studied in 0.01 M Na2SO4 solutions to simulate the major chemical composition of U-contaminatedgroundwater (i.e., [SO42-]~13 mM L-1) at the site. Uranyl sorption was greater at pH 7.5 than that at pH 4 in both air- and 2% pCO2-equilibrated systems. While there were negligible effects of sulfate ligands on the pH-dependent U(VI) sorption (analysis showed sulfate ligand associated U(VI) surface species at the ferrihydrite–water interface. In air-equilibrated systems, binary and mono-sulfate U(VI) ternary surface species co-existed at pH 5.43. At pH 6.55–7.83, a mixture of mono-sulfate and bis-carbonato U(VI) ternary surface species became more important. At 2% pCO2, there was no contribution of sulfate ligands on the U(VI) ternary surface species. Instead, a mixture of bis-carbonato inner-sphere (38%) and tris-carbonato outer-sphere U(VI) ternary surface species (62%) was found at pH 7.62. The study suggests that the competitive ligand (bicarbonate and sulfate) coordination on U(VI) surface species might be important in evaluating the U solid-state speciation in the AFO PRB at the study site where pCO2 fluctuates between 1 and 2 pCO2%.

  9. Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

    KAUST Repository

    Choi, Joshua J.


    The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

  10. Polysulfide ligand exchange on zinc sulfide nanocrystal surfaces for improved film formation

    Energy Technology Data Exchange (ETDEWEB)

    Herron, Steven M. [Department of Chemistry, Stanford University, Stanford, CA 94305 (United States); Lawal, Qudus O. [Department of Chemical Engineering, Stanford University, Stanford, CA 94305 (United States); Bent, Stacey F., E-mail: [Department of Chemical Engineering, Stanford University, Stanford, CA 94305 (United States)


    Graphical abstract: - Highlights: • Ammonium polysulfides are prepared in aprotic solvents. • Native ligands on surfaces of colloidal ZnS nanocrystals are efficiently exchanged with polysulfides. • Ligand exchange improves crystallinity and composition in annealed ZnS thin films. • Polysulfide nanocrystal inks increase mass retention from 62% to 88%. - Abstract: The physical and chemical properties of nanocrystals can be modified by changing the ligands attached at their surfaces. A ligand exchange procedure with ammonium polysulfides has been developed to replace the native ligands on cubic zinc sulfide nanocrystals. Several mixtures of polysulfides in formamide and other solvents were prepared with different average chain lengths and used to achieve high yield ligand exchange, as confirmed by UV–vis spectroscopy, infrared spectroscopy and X-ray photoelectron spectroscopy. The results show that polysulfide content can be increased with longer surface ligands and that the exchange process yields compositionally pure surfaces before and after high temperature anneals. X-ray diffraction and scanning electron microscopy show that, when annealed in nitrogen at 525 °C, polysulfide ligands lead to average crystal sizes 2–3 times larger than in the un-exchanged control sample. The ligand exchange procedure itself does not alter nanocrystal size. Nanocrystal inks prepared from the exchanged samples form thin films that exhibit superior grain growth, morphology, mass retention, and composition compared to the un-exchanged material. Overall, polysulfide species are demonstrated as alternative ligands for the surfaces of metal chalcogenide nanocrystals which, when incorporated in an efficient ligand-exchange procedure, can improve the quality of ZnS nanocrystal inks.

  11. Surface-Bound Ligands Modulate Chemoselectivity and Activity of a Bimetallic Nanoparticle Catalyst

    KAUST Repository

    Vu, Khanh B.


    "Naked" metal nanoparticles (NPs) are thermodynamically and kinetically unstable in solution. Ligands, surfactants, or polymers, which adsorb at a particle\\'s surface, can be used to stabilize NPs; however, such a mode of stabilization is undesirable for catalytic applications because the adsorbates block the surface active sites. The catalytic activity and the stability of NPs are usually inversely correlated. Here, we describe an example of a bimetallic (PtFe) NP catalyst stabilized by carboxylate surface ligands that bind preferentially to one of the metals (Fe). NPs stabilized by fluorous ligands were found to be remarkably competent in catalyzing the hydrogenation of cinnamaldehyde; NPs stabilized by hydrocarbon ligands were significantly less active. The chain length of the fluorous ligands played a key role in determining the chemoselectivity of the FePt NP catalysts. (Chemical Presented). © 2015 American Chemical Society.

  12. Group IV nanocrystals with ion-exchangeable surface ligands and methods of making the same

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler, Lance M.; Nichols, Asa W.; Chernomordik, Boris D.; Anderson, Nicholas C.; Beard, Matthew C.; Neale, Nathan R.


    Methods are described that include reacting a starting nanocrystal that includes a starting nanocrystal core and a covalently bound surface species to create an ion-exchangeable (IE) nanocrystal that includes a surface charge and a first ion-exchangeable (IE) surface ligand ionically bound to the surface charge, where the starting nanocrystal core includes a group IV element.

  13. Internalization and trafficking of cell surface proteoglycans and proteoglycan-binding ligands. (United States)

    Payne, Christine K; Jones, Sara A; Chen, Chen; Zhuang, Xiaowei


    Using multicolor live cell imaging in combination with biochemical assays, we have investigated an endocytic pathway mediated by cell surface proteoglycans, primary receptors for many cationic ligands. We have characterized this pathway for a variety of proteoglycan-binding ligands including cationic polymers, lipids and polypeptides. Following clathrin- and caveolin-independent, but flotillin- and dynamin-dependent internalization, proteoglycan-bound ligands associate with flotillin-1-positive vesicles and are efficiently trafficked to late endosomes. The route to late endosomes differs considerably from that following clathrin-mediated endocytosis. The proteoglycan-dependent pathway to late endosomes does not require microtubule-dependent transport or phosphatidyl-inositol-3-OH kinase-dependent sorting from early endosomes. The pathway taken by these ligands is identical to that taken by an antibody against heparan sulfate proteoglycans, suggesting that this mechanism may be used generally by cell surface proteoglycans and proteoglycan-binding ligands that lack secondary receptors.

  14. Antibody-ligand interactions for hydrophobic charge-induction chromatography: a surface plasmon resonance study. (United States)

    Cheng, Fang; Li, Ming-Yang; Wang, Han-Qi; Lin, Dong-Qiang; Qu, Jing-Ping


    This article describes the use of surface plasmon resonance (SPR) spectroscopy to study antibody-ligand interactions for hydrophobic charge-induction chromatography (HCIC) and its versatility in investigating the surface and solution factors affecting the interactions. Two density model surfaces presenting the HCIC ligand (mercapto-ethyl-pyridine, MEP) were prepared on Au using a self-assembly technique. The surface chemistry and structure, ionization, and protein binding of such model surfaces were characterized by X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure (NEXAFS), contact-angle titration, and SPR, respectively. The influences of the surface and solution factors, e.g., ligand density, salt concentration, and solution pH, on protein adsorption were determined by SPR. Our results showed that ligand density affects both equilibrium and dynamic aspects of the interactions. Specifically, a dense ligand leads to an increase in binding strength, rapid adsorption, slow desorption, and low specificity. In addition, both hydrophobic interactions and hydrogen bonding contribute significantly to the protein adsorption at neutral pH, while the electrostatic repulsion is overwhelmed under acidic conditions. The hydrophobic interaction at a high concentration of lyotropic salt would cause drastic conformational changes in the adsorbed protein. Combined with the self-assembly technique, SPR proves to be a powerful tool for studying the interactions between an antibody and a chromatographic ligand.

  15. Effects of surface ligands and solvents on quantum dot photostability under pulsed UV laser irradiation (United States)

    Krivenkov, Victor A.; Samokhvalov, Pavel S.; Linkov, Pavel A.; Prokhorov, Sergey D.; Martynov, Igor L.; Chistyakov, Alexander A.; Nabiev, Igor


    The organic ligands passivating the surface of semiconductor quantum dots (QDs) and the solvents used strongly determine the photostability of QD solutions. Highly purified QD solutions in chloroform have been shown to photodegrade upon pulsed ultraviolet (UV) irradiation, irrespectively of the type of surface ligand. However, the photostability of QDs dissolved in n-octane, a more photochemically inert solvent, strongly depends on the ligands passivating their surface. In n-octane, hexadecylamine-coated QDs are completely stable and display no photochemical response to pulsed UV laser irradiation. In solutions of octanethiol-capped QDs, the photoluminescence intensity slightly decreases under irradiation. QDs coated with trioctylphosphine oxide exhibit a more complex pattern of photobleaching, which depends on the initial value of fluorescence quantum yield of QDs. This complex pattern may be accounted for by two competing processes: (1) ligand photodesorption accompanied by photobleaching due to specific alignment of the band levels of QDs and highest occupied molecular orbital of the ligand and (2) photoinduced decrease in the population of trapping states. Furthermore, practically no thermodynamic degradation of QD solutions has been observed for the micromolar QD concentration used in the study, in contrast to lower concentrations, thus confirming the photoinduced origin of the changes caused by UV irradiation. Obtained results show that the photostability of QDs may be strongly increased by careful selection of the ligands passivating their surface and the solvents used in the experiments.

  16. Doping Control Via Molecularly Engineered Surface Ligand Coordination

    KAUST Repository

    Yuan, Mingjian


    A means to control the net doping of a CQD solid is identified via the design of the bidentate ligand crosslinking the material. The strategy does not rely on implementing different atmospheres at different steps in device processing, but instead is a robust strategy implemented in a single processing ambient. We achieve an order of magnitude difference in doping that allows us to build a graded photovoltaic device and maintain high current and voltage at maximum power-point conditions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Impact of Different Surface Ligands on the Optical Properties of PbS Quantum Dot Solids. (United States)

    Xu, Fan; Gerlein, Luis Felipe; Ma, Xin; Haughn, Chelsea R; Doty, Matthew F; Cloutier, Sylvain G


    The engineering of quantum dot solids with low defect concentrations and efficient carrier transport through a ligand strategy is crucial to achieve efficient quantum dot (QD) optoelectronic devices. Here, we study the consequences of various surface ligand treatments on the light emission properties of PbS quantum dot films using 1,3-benzenedithiol (1,3-BDT), 1,2-ethanedithiol (EDT), mercaptocarboxylic acids (MPA) and ammonium sulfide ((NH4)2S). We first investigate the influence of different ligand treatments on the inter-dot separation, which mainly determines the conductivity of the QD films. Then, through a combination of photoluminescence and transient photoluminescence characterization, we demonstrate that the radiative and non-radiative recombination mechanisms in the quantum dot films depend critically on the length and chemical structure of the surface ligands.

  18. Impact of Different Surface Ligands on the Optical Properties of PbS Quantum Dot Solids

    Directory of Open Access Journals (Sweden)

    Fan Xu


    Full Text Available The engineering of quantum dot solids with low defect concentrations and efficient carrier transport through a ligand strategy is crucial to achieve efficient quantum dot (QD optoelectronic devices. Here, we study the consequences of various surface ligand treatments on the light emission properties of PbS quantum dot films using 1,3-benzenedithiol (1,3-BDT, 1,2-ethanedithiol (EDT, mercaptocarboxylic acids (MPA and ammonium sulfide ((NH42S. We first investigate the influence of different ligand treatments on the inter-dot separation, which mainly determines the conductivity of the QD films. Then, through a combination of photoluminescence and transient photoluminescence characterization, we demonstrate that the radiative and non-radiative recombination mechanisms in the quantum dot films depend critically on the length and chemical structure of the surface ligands.

  19. Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display (United States)

    Nair, Pradeep M.; Flores, Heather; Gogineni, Alvin; Marsters, Scot; Lawrence, David A.; Kelley, Robert F.; Ngu, Hai; Sagolla, Meredith; Komuves, Laszlo; Bourgon, Richard; Settleman, Jeffrey; Ashkenazi, Avi


    TNF superfamily death ligands are expressed on the surface of immune cells and can trigger apoptosis in susceptible cancer cells by engaging cognate death receptors. A recombinant soluble protein comprising the ectodomain of Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has shown remarkable preclinical anticancer activity but lacked broad efficacy in patients, possibly owing to insufficient exposure or potency. We observed that antibody cross-linking substantially enhanced cytotoxicity of soluble Apo2L/TRAIL against diverse cancer cell lines. Presentation of the ligand on glass-supported lipid bilayers enhanced its ability to drive receptor microclustering and apoptotic signaling. Furthermore, covalent surface attachment of Apo2L/TRAIL onto liposomes—synthetic lipid-bilayer nanospheres—similarly augmented activity. In vivo, liposome-displayed Apo2L/TRAIL achieved markedly better exposure and antitumor activity. Thus, covalent synthetic-membrane attachment of a cell-surface ligand enhances efficacy, increasing therapeutic potential. These findings have translational implications for liposomal approaches as well as for Apo2L/TRAIL and other clinically relevant TNF ligands. PMID:25902490

  20. Including surface ligand effects in continuum elastic models of nanocrystal vibrations (United States)

    Lee, Elizabeth M. Y.; Mork, A. Jolene; Willard, Adam P.; Tisdale, William A.


    The measured low frequency vibrational energies of some quantum dots (QDs) deviate from the predictions of traditional elastic continuum models. Recent experiments have revealed that these deviations can be tuned by changing the ligands that passivate the QD surface. This observation has led to speculation that these deviations are due to a mass-loading effect of the surface ligands. In this article, we address this speculation by formulating a continuum elastic theory that includes the dynamical loading by elastic surface ligands. We demonstrate that this model is capable of accurately reproducing the l = 0 phonon energy across a variety of different QD samples, including cores with different ligand identities and epitaxially grown CdSe/CdS core/shell heterostructures. We highlight that our model performs well even in the small QD regime, where traditional elastic continuum models are especially prone to failure. Furthermore, we show that our model combined with Raman measurements can be used to infer the elastic properties of surface bound ligands, such as sound velocities and elastic moduli, that are otherwise challenging to measure.

  1. Vesicular stomatitis virus infection promotes immune evasion by preventing NKG2D-ligand surface expression.

    Directory of Open Access Journals (Sweden)

    Helle Jensen

    Full Text Available Vesicular stomatitis virus (VSV has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection leads to a robust induction of MICA mRNA expression, however the subsequent surface expression is potently hindered. Thus, VSV lines up with human cytomegalovirus (HCMV and adenovirus, which actively subvert the immune system by negatively affecting NKG2D-ligand surface expression. VSV infection caused an active suppression of NKG2D-ligand surface expression, affecting both endogenous and histone deacetylase (HDAC-inhibitor induced MICA, MICB and ULBP-2 expression. The classical immune escape mechanism of VSV (i.e., the M protein blockade of nucleocytoplasmic mRNA transport was not involved, as the VSV mutant strain, VSV(ΔM51, which possess a defective M protein, prevented MICA surface expression similarly to wild-type VSV. The VSV mediated down modulation of NKG2D-ligand expression did not involve apoptosis. Constitutive expression of MICA bypassed the escape mechanism, suggesting that VSV affect NKG2D-ligand expression at an early post-transcriptional level. Our results show that VSV possess an escape mechanism, which could affect the immune recognition of VSV infected cancer cells. This may also have implications for immune recognition of cancer cells after combined treatment with VSV and chemotherapeutic drugs.

  2. Sulfur ligand mediated electrochemistry of gold surfaces and nanoparticles: what, how, and why

    DEFF Research Database (Denmark)

    Chi, Qijin; Ford, Michael J.; Halder, Arnab


    . This review considers the diversity of known atomic structures for gold-sulfur interfaces, how these structures facilitate a diversity of mechanisms in electrochemical applications, and why this is possible based on recent advances in the basic understanding of the electronic structure of gold-sulfur bonds......Gold surfaces are widely used in electrochemistry whilst gold nanoparticles have very many uses, with both the surfaces and the particles often being protected by sulfur-bound organic ligands. The ligands not only provide chemical stability but also directly participate in many desired processes...

  3. Functionalization of Cadmium Selenide Quantum Dots with Poly(ethylene glycol): Ligand Exchange, Surface Coverage, and Dispersion Stability. (United States)

    Wenger, Whitney Nowak; Bates, Frank S; Aydil, Eray S


    Semiconductor quantum dots synthesized using rapid mixing of precursors by injection into a hot solution of solvents and surfactants have surface ligands that sterically stabilize the dispersions in nonpolar solvents. Often, these ligands are exchanged to disperse the quantum dots in polar solvents, but quantitative studies of quantum dot surfaces before and after ligand exchange are scarce. We studied exchanging trioctylphosphine (TOP) and trioctylphosphine oxide (TOPO) ligands on as-synthesized CdSe quantum dots dispersed in hexane with a 2000 g/mol thiolated poly(ethylene glycol) (PEG) polymer. Using infrared spectroscopy we quantify the absolute surface concentration of TOP/TOPO and PEG ligands per unit area before and after ligand exchange. While 50-85% of the TOP/TOPO ligands are removed upon ligand exchange, only a few are replaced with PEG. Surprisingly, the remaining TOP/TOPO ligands outnumber the PEG ligands, but these few PEG ligands are sufficient to disperse the quantum dots in polar solvents such as chloroform, tetrahydrofuran, and water. Moreover, as-synthesized quantum dots once easily dispersed in hexane are no longer dispersible in nonpolar solvents after ligand exchange. A subtle coverage-dependent balance between attractive PEG-solvent interactions and repulsive TOP/TOPO-solvent interactions determines the dispersion stability.

  4. Spectroscopic Studies of Metal-Ligand-Surface Interactions (United States)


    2 ions ( aquo complex ) were more highly ordered around the metal cation than in the case of the Ca-X and Na-X samples. It has long been recognized...influence the adsorption and transformation of organic-surface complexes . To accomplish these goals, a four-pronged program of research was carried out...SPECTROSCOPY OF MATRIX-ISOLATED COMPLEXES OF HYDRAZINE AND AMMONIA WITH THE NEUTRAL TRANSITION METALS, Cu AND Fe......... 90 A.* INTRODUCTION

  5. A Bifunctional Spin Label for Ligand Recognition on Surfaces


    Hollas, Michael A.; Webb, Simon J.; Flitsch, Sabine L.; Fielding, Alistair J.


    Abstract In?situ monitoring of biomolecular recognition, especially at surfaces, still presents a significant technical challenge. Electron paramagnetic resonance (EPR) of biomolecules spin?labeled with nitroxides can offer uniquely sensitive and selective insights into these processes, but new spin?labeling strategies are needed. The synthesis and study of a bromoacrylaldehyde spin label (BASL), which features two attachment points with orthogonal reactivity is reported. The first examples o...

  6. Ligand effects on nitrate reduction by zero-valent iron: Role of surface complexation. (United States)

    Song, Xiaojie; Chen, Zhihao; Wang, Xiaomeng; Zhang, Shujuan


    Surface passivation is a key limiting factor in the application of zero-valent iron (ZVI) for water remediation. Addition of ligands is a useful approach to overcome this issue. In this work, a small amount of acetylacetone (AA) (0.5 mM) was found highly efficient to enhance the reduction of nitrate by ZVI at near neutral conditions (pH 6.0) with the formation of considerable black coating on ZVI. At an initial nitrate concentration of 20 mg N/L, the pseudo first-order reduction rate constant of nitrate in the ZVI-AA-NO3- system was 0.0991 h-1, which was 52 times higher than that in the ZVI-NO3- system. Under otherwise identical conditions, the other five ligands, including EDTA, formate, acetate, oxalate, and phosphate, had negligible effects. Based on the pKa values of these ligands and the final species of iron, the ligand effects on nitrate reduction by ZVI were summarized from three aspects: (1) the ability to offer potentially dissociable protons from the ligands; (2) the complexation ability to eliminate iron (hydr)oxide precipitates from the surface of ZVI; and (3) the ability to lower down the redox potentials of iron species. The good performance of AA in these three aspects makes it advantage over the other ligands. A cycle test up to six runs demonstrates that AA could continuously take effect in the ZVI system. The results here point out the potential of AA as an effective ligand in ZVI system for enhanced contaminant transformation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effects of surface ligands on the uptake and transport of gold nanoparticles in rice and tomato. (United States)

    Li, Hongying; Ye, Xinxin; Guo, Xisheng; Geng, Zhigang; Wang, Guozhong


    Nanotechnology is advancing rapidly and substantial amounts of nanomaterials are released into the environment. Plants are an essential base component of the ecological environment and play a critical role in the fate and transport of nanomaterials in the environment through plant uptake and bioaccumulation. In this study, plant uptake of gold nanoparticles (GNPs) functionalized with three types of short ligands [cysteamine (CA), cysteine (CYS) and thioglycolic acid (TGA)] and of nearly identical hydrodynamic size (8-12nm) was investigated in the major crops rice (Oryza sativa L.) and tomato (Solanum lycopersicum). Uptake and translocation of GNPs not only depended on particle surface charge, but were also related to the species of ligand on the GNPs. The negatively charged GNPs capped with the CYS ligand (GNP-CYS) were more efficiently absorbed in roots and transferred to shoots (including stems and leaves) than that of GNPs capped with CA and TGA. The absorption process of GNPs involved a combination of both clathrin-dependent and -independent mechanisms. The endocytosis of GNPs was strongly inhibited by wortmannin, suggesting that clathrin-independent endocytosis was an important pathway of nanoparticle internalization in plants. Competition experiments with a free ligand (CYS) showed that the CYS ligand probably facilitated the endocytosis process of GNPs and increased the internalization of GNP-CYS in plants. The results will aid understanding of the mechanisms of nanoparticle uptake and translocation in plants. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Exhaustive comparison and classification of ligand-binding surfaces in proteins (United States)

    Murakami, Yoichi; Kinoshita, Kengo; Kinjo, Akira R; Nakamura, Haruki


    Many proteins function by interacting with other small molecules (ligands). Identification of ligand-binding sites (LBS) in proteins can therefore help to infer their molecular functions. A comprehensive comparison among local structures of LBSs was previously performed, in order to understand their relationships and to classify their structural motifs. However, similar exhaustive comparison among local surfaces of LBSs (patches) has never been performed, due to computational complexity. To enhance our understanding of LBSs, it is worth performing such comparisons among patches and classifying them based on similarities of their surface configurations and electrostatic potentials. In this study, we first developed a rapid method to compare two patches. We then clustered patches corresponding to the same PDB chemical component identifier for a ligand, and selected a representative patch from each cluster. We subsequently exhaustively as compared the representative patches and clustered them using similarity score, PatSim. Finally, the resultant PatSim scores were compared with similarities of atomic structures of the LBSs and those of the ligand-binding protein sequences and functions. Consequently, we classified the patches into ∼2000 well-characterized clusters. We found that about 63% of these clusters are used in identical protein folds, although about 25% of the clusters are conserved in distantly related proteins and even in proteins with cross-fold similarity. Furthermore, we showed that patches with higher PatSim score have potential to be involved in similar biological processes. PMID:23934772

  9. PL-PatchSurfer: A Novel Molecular Local Surface-Based Method for Exploring Protein-Ligand Interactions

    Directory of Open Access Journals (Sweden)

    Bingjie Hu


    Full Text Available Structure-based computational methods have been widely used in exploring protein-ligand interactions, including predicting the binding ligands of a given protein based on their structural complementarity. Compared to other protein and ligand representations, the advantages of a surface representation include reduced sensitivity to subtle changes in the pocket and ligand conformation and fast search speed. Here we developed a novel method named PL-PatchSurfer (Protein-Ligand PatchSurfer. PL-PatchSurfer represents the protein binding pocket and the ligand molecular surface as a combination of segmented surface patches. Each patch is characterized by its geometrical shape and the electrostatic potential, which are represented using the 3D Zernike descriptor (3DZD. We first tested PL-PatchSurfer on binding ligand prediction and found it outperformed the pocket-similarity based ligand prediction program. We then optimized the search algorithm of PL-PatchSurfer using the PDBbind dataset. Finally, we explored the utility of applying PL-PatchSurfer to a larger and more diverse dataset and showed that PL-PatchSurfer was able to provide a high early enrichment for most of the targets. To the best of our knowledge, PL-PatchSurfer is the first surface patch-based method that treats ligand complementarity at protein binding sites. We believe that using a surface patch approach to better understand protein-ligand interactions has the potential to significantly enhance the design of new ligands for a wide array of drug-targets.

  10. Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

    Energy Technology Data Exchange (ETDEWEB)

    Bokoch, Michael P.; Zou, Yaozhong; Rasmussen, Søren G.F.; Liu, Corey W.; Nygaard, Rie; Rosenbaum, Daniel M.; Fung, Juan José; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Puglisi, Joseph D.; Weis, William I.; Pardo, Leonardo; Prosser, R. Scott; Mueller, Luciano; Kobilka, Brian K. (Stanford-MED); (Toronto); (BMS); (UAB, Spain)


    G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the {beta}{sub 2} adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.

  11. Surface-ligand effect on radiosensitization of ultrasmall luminescent gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Xingya Jiang


    Full Text Available Gold nanoparticles (AuNPs could serve as potential radiotherapy sensitizers because of their exceptional biocompatibility and high-Z material nature; however, since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries, whether surface ligands can affect their radiosensitization has seldom been investigated in the radiosensitization of AuNPs. By conducting head-to-head comparison on radiosensitization of two kinds of ultrasmall (∼2nm near-infrared (NIR emitting AuNPs that are coated with zwitterionic glutathione and neutral polyethylene glycol (PEG ligands, respectively, we found that zwitterionic glutathione coated AuNPs (GS-AuNPs can reduce survival rates of MCF-7 cells under irradiation of clinically used megavoltage photon beam at low dosage of ∼2.25Gy. On the other hand, PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation, clearly indicating the key role of surface chemistry in radiosensitization of AuNPs. More detailed studies suggested that such difference was independent of cellular uptake and its efficiency, but might be related to the ligand-induced difference in photoelectron generation and/or interactions between AuNPs and X-ray triggered reactive oxygen species (ROS.

  12. Tuning optoelectronic properties of small semiconductor nanocrystals through surface ligand chemistry (United States)

    Lawrence, Katie N.

    Semiconductor nanocrystals (SNCs) are a class of material with one dimension organic solvents therefore limiting their applicability. In addition, use of insulating ligands hinder SNCs' transport properties and thus their potential application in solid state devices. Appropriate choice of surface ligation can provide 1) solubility, 2) stability, and 3) facilitate exciton delocalization. In this dissertation, the effects of appropriate surface ligation on strongly quantum confined ultrasmall SNCs was investigated. Due to their high surface to volume ratio, we are able to highly control their optical and electronic properties through surface ligand modification. Throughout this dissertation, we utilized a variety of ligands (e.g. oleylamine, cadmium benzoate, and PEGn-thiolate) in order to change the solubility of the SNC as well as investigate their optical and electronic properties. First delocalization of the excitonic wave function 1) into the ligand monolayer using metal carboxylates and 2) beyond the ligand monolayer to provide strong inter-SNC electronic coupling using poly(ethylene) glycol (PEG)-thiolate was explored. Passivation of the Se sites of metal chalcogenide SNCs by metal carboxylates provided a two-fold outcome: (1) facilitating the delocalization of exciton wave functions into ligand monolayers (through appropriate symmetry matching and energy alignment) and (2) increasing fluorescence quantum yield (through passivation of midgap trap states). An ˜240 meV red-shift in absorbance was observed upon addition of Cd(O2CPh)2, as well as a ˜260 meV shift in emission with an increase in PL-QY to 73%. Through a series of control experiments, as well as full reversibility of our system, we were able to conclude that the observed bathochromic shifts were the sole consequence of delocalization, not a change in size or relaxation of the inorganic core, as previously reported. Furthermore, the outstanding increase in PL-QY was found to be a product of both

  13. LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation

    Directory of Open Access Journals (Sweden)

    Schroeder Michael


    Full Text Available Abstract Background Identifying pockets on protein surfaces is of great importance for many structure-based drug design applications and protein-ligand docking algorithms. Over the last ten years, many geometric methods for the prediction of ligand-binding sites have been developed. Results We present LIGSITEcsc, an extension and implementation of the LIGSITE algorithm. LIGSITEcsc is based on the notion of surface-solvent-surface events and the degree of conservation of the involved surface residues. We compare our algorithm to four other approaches, LIGSITE, CAST, PASS, and SURFNET, and evaluate all on a dataset of 48 unbound/bound structures and 210 bound-structures. LIGSITEcsc performs slightly better than the other tools and achieves a success rate of 71% and 75%, respectively. Conclusion The use of the Connolly surface leads to slight improvements, the prediction re-ranking by conservation to significant improvements of the binding site predictions. A web server for LIGSITEcsc and its source code is available at

  14. Predicting Ligand Binding Sites on Protein Surfaces by 3-Dimensional Probability Density Distributions of Interacting Atoms (United States)

    Jian, Jhih-Wei; Elumalai, Pavadai; Pitti, Thejkiran; Wu, Chih Yuan; Tsai, Keng-Chang; Chang, Jeng-Yih; Peng, Hung-Pin; Yang, An-Suei


    Predicting ligand binding sites (LBSs) on protein structures, which are obtained either from experimental or computational methods, is a useful first step in functional annotation or structure-based drug design for the protein structures. In this work, the structure-based machine learning algorithm ISMBLab-LIG was developed to predict LBSs on protein surfaces with input attributes derived from the three-dimensional probability density maps of interacting atoms, which were reconstructed on the query protein surfaces and were relatively insensitive to local conformational variations of the tentative ligand binding sites. The prediction accuracy of the ISMBLab-LIG predictors is comparable to that of the best LBS predictors benchmarked on several well-established testing datasets. More importantly, the ISMBLab-LIG algorithm has substantial tolerance to the prediction uncertainties of computationally derived protein structure models. As such, the method is particularly useful for predicting LBSs not only on experimental protein structures without known LBS templates in the database but also on computationally predicted model protein structures with structural uncertainties in the tentative ligand binding sites. PMID:27513851

  15. Cell-surface nucleolin acts as a central mediator for carcinogenic, anti-carcinogenic, and disease-related ligands. (United States)

    Fujiki, Hirota; Watanabe, Tatsuro; Suganuma, Masami


    Cell-surface nucleolin in human gastric cancer cell lines is a receptor for TNF-α-inducing protein (Tipα) of Helicobacter pylori. The binding complex of nucleolin and Tipα is internalized into the cells and then induces tumor progression of human gastric cancer. Surface nucleolin is also a receptor of human immunodeficiency virus-1, and the anti-HIV pseudopeptide (HB-19) showed anti-carcinogenic activity in vivo. Surface nucleolin has dual functions depending on the ligands: In order to understand the mechanisms of surface nucleolin, it is necessary to review surface nucleolin and its relation to carcinogenic ligands and anti-carcinogenic ligands. Other ligands can be grouped among disease-related ligands, which is an important new topic for the prevention of various ailments. This paper mainly deals with two ligands of surface nucleolin, Tipα and pseudopeptide HB-19. The binding complex of nucleolin and Tipα induces expression of TNF-α and chemokine genes and activates NF-κB in gastric cancer cells of humans and mice. However, when human gastric cancer cell line MKN-1 was transfected with nucleolin-targeted siRNA, the result was inhibition of cell migration and elongation induced by Tipα. The amount of surface nucleolin was reduced in membrane fraction of the nucleolin knockdown MKN-1 cells, but the amount of nucleolin in the cytosol or nuclear fractions of the cells did not change. The results indicate that surface nucleolin acts as a carcinogenic mediator for Tipα of H. pylori. In contrast, both the viral external envelop glycoprotein gp120 of HIV and the anti-HIV pseudopeptide HB-19 bind to surface nucleolin. Through this binding, treatment with HB-19 inhibited tumor development in human breast cancer cell line MDA-MB-231 and rhabdoid tumor cell line derived from Wilms's tumor in xenograft nude mouse models. The results show that surface nucleolin acts as an anti-carcinogenic mediator for HB-19. Based on these discrete functions of surface nucleolin

  16. Surface modified fluorescent quantum dots with neurotransmitter ligands for potential targeting of cell signaling applications. (United States)

    Mansur, Alexandra A P; Saliba, Juliana B; Mansur, Herman S


    The possibility of combining nanotechnology with nanomedicine opens a broad field of research which may truly revolutionize our society. The neural system plays a crucial role in the human body, and most related diseases can dramatically change the quality of life. Thus, the present study reports a novel approach for using neurotransmitters as ligands in the synthesis of surface-modified fluorescent nanocrystals for potential use in cell labeling applications. Briefly, CdS quantum dots (QDs) were prepared using L-glutamic and L-aspartic as surface capping agents via a one-step chemical processing method, which resulted in stable aqueous colloidal systems at room temperature and ambient pressure. UV-visible spectroscopy, photoluminescence spectroscopy (PL), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM) were used to characterize the synthesis and relative stability of peptide-capped CdS nanocrystals. The results demonstrate that both ligands were effective in nucleating and stabilizing CdS quantum dots in colloidal aqueous suspensions, with an estimated dimension below 3.3 nm and with fluorescence activity. Thus, novel nanohybrids were developed based on QDs bioconjugated to surface-active neurotransmitter moieties suitable for investigation as potential biomarkers in cell targeting and signaling applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The FcεRI Signaling Cascade and Integrin Trafficking Converge at Patterned Ligand Surfaces. (United States)

    Wakefield, Devin L; Holowka, David; Baird, Barbara


    We examined the spatial targeting of early and downstream signaling mediated by the IgE receptor (FcεRI) in RBL mast cells utilizing surface-patterned 2,4 dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge-concentrated for DNP-BSA. These distributions of IgE-FcεRI propagate to the spatial recruitment of early signaling proteins, including spleen tyrosine kinase (Syk), linker for activation of T cells (LAT), and activated phospholipase C gamma 1 (PLCγ1), which all localize with engaged receptors. We found stimulated polymerization of F-actin is not required for Syk recruitment but is progressively involved in the recruitment of LAT and PLCγ1. We further found β1- and β3-integrins colocalize with IgE-FcεRI at patterned ligand surfaces as cells spread. This recruitment corresponds to directed exocytosis of recycling endosomes (REs) containing these integrins and their fibronectin ligand. Together, our results show targeting of signaling components, including integrins, to regions of clustered IgE-FcεRI in processes that depend on stimulated actin polymerization and outward trafficking of REs. © 2017 by The American Society for Cell Biology.

  18. Superparamagnetic Ironoxide Nanoparticles via Ligand Exchange Reactions: Organic 1,2-Diols as Versatile Building Blocks for Surface Engineering

    Directory of Open Access Journals (Sweden)

    Wolfgang H. Binder


    Full Text Available A method for the preparation of ligand-covered superparamagnetic iron oxide nanoparticles via exchange reactions is described. 1,2-diol-ligands are used to provide a stable binding of the terminally modified organic ligands onto the surface of γ-Fe2O3-nanoparticles (r∼4 nm. The 1,2-diol-ligands are equipped with variable terminal functional groups (i.e., hydrogen bonding moieties, azido- bromo-, fluorescent moieties and can be easily prepared via osmium tetroxide-catalyzed 1,2-dihydroxylation reactions of the corresponding terminal alkenes. Starting from octylamine-covered γ-Fe2O3-nanoparticles, ligand exchange was effected at 50∘C over 24–48 hours, whereupon complete ligand exchange is taking place as proven by thermogravimetric (TGA- and IR-spectroscopic measurements. A detailed kinetic analysis of the ligand exchange reaction was performed via TGA analysis, demonstrating a complete ligand exchange after 24 hours. The method offers a simple approach for the generation of various γ-Fe2O3-nanoparticles with functional organic shells in a one-step procedure.

  19. Surface ligand dependent toxicity of zinc oxide nanoparticles in HepG2 cell model (United States)

    Bartczak, D.; Baradez, M.-O.; Merson, S.; Goenaga-Infante, H.; Marshall, D.


    Physicochemical properties of nanoparticles (NP) strongly affect their influence on cell behaviour, but can be significantly distorted by interactions with the proteins present in biological solutions. In this study we show how different surface functionalities of zinc oxide (ZnO) NP lead to changes in the size distribution and dissolution of the NP in serum containing cell culture media and how this impacts on NP toxicity. NPs capped with weakly bound large proteins undergo substantial transformations due to the exchange of the original surface ligands to the components of the cell culture media. Conversely, NP capped with a tight monolayer of small organic molecules or with covalently conjugated proteins show significantly higher stability. These differences in ligand exchange also affect the toxicity of the NP to the HepG2 liver cell model, with the NP capped with small organic molecules being more toxic than those capped with large proteins. This study highlights the importance of characterising NPs in biological media and the effect the media has during in-vitro analysis.

  20. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations (United States)

    Pedro, Liliana; Van Voorhis, Wesley C.; Quinn, Ronald J.


    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase ( PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.

  1. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations. (United States)

    Pedro, Liliana; Van Voorhis, Wesley C; Quinn, Ronald J


    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase (PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each. Graphical Abstract ᅟ.

  2. Ligand-Exchange Dynamics on Gold Nanocrystals: Direct Monitoring of Nanoscale Polyvinylpyrrolidone-Thiol Domain Surface Morphology. (United States)

    Zhang, Shuaidi; Kim, Sunghan; Tsukruk, Vladimir V


    We report direct high-resolution monitoring of an evolving mixed nanodomain surface morphology during thiol adsorption on polyvinylpyrrolidone (PVP)-stabilized single crystal gold nanocrystals. The thiol adsorption and replacement dynamics are much more complex than a simple complete substitution of the initial polymer ligand. We observed that during ligand exchange with linear thiol, the nanocrystal surface evolved from an initial 1 nm uniform PVP coating into a remarkably stable network of globular PVP domains 20-100 nm in size and ∼4 nm in height surrounded by thiol self-assembled monolayers. The final stability of such a mixed thiol-PVP surface morphology can possibly be attributed to the interfacial energy reduction from partially solvophilic surfaces and the entropic gain from mixed ligand surface layers. The ligand-exchange dynamics and the unusual equilibrium morphology revealed here provide important insights into both displacement dynamics of surface-bound molecules and the nanoscale peculiarities of surface functionalization of colloidal metal substrates.

  3. Surface ligand controls silver ion release of nanosilver and its antibacterial activity against Escherichia coli. (United States)

    Long, Yan-Min; Hu, Li-Gang; Yan, Xue-Ting; Zhao, Xing-Chen; Zhou, Qun-Fang; Cai, Yong; Jiang, Gui-Bin


    Understanding the mechanism of nanosilver-dependent antibacterial activity against microorganisms helps optimize the design and usage of the related nanomaterials. In this study, we prepared four kinds of 10 nm-sized silver nanoparticles (AgNPs) with dictated surface chemistry by capping different ligands, including citrate, mercaptopropionic acid, mercaptohexanoic acid, and mercaptopropionic sulfonic acid. Their surface-dependent chemistry and antibacterial activities were investigated. Owing to the weak bond to surface Ag, short carbon chain, and low silver ion attraction, citrate-coated AgNPs caused the highest silver ion release and the strongest antibacterial activity against Escherichia coli, when compared to the other tested AgNPs. The study on the underlying antibacterial mechanisms indicated that cellular membrane uptake of Ag, NAD+/NADH ratio increase, and intracellular reactive oxygen species (ROS) generation were significantly induced in both AgNP and silver ion exposure groups. The released silver ions from AgNPs inside cells through a Trojan-horse-type mechanism were suggested to interact with respiratory chain proteins on the membrane, interrupt intracellular O2 reduction, and induce ROS production. The further oxidative damages of lipid peroxidation and membrane breakdown caused the lethal effect on E. coli. Altogether, this study demonstrated that AgNPs exerted antibacterial activity through the release of silver ions and the subsequent induction of intracellular ROS generation by interacting with the cell membrane. The findings are helpful in guiding the controllable synthesis through the regulation of surface coating for medical care purpose.

  4. Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles. (United States)

    Galaski, Johanna; Ahmad, Fareed; Tibroni, Nadine; Pujol, Francois M; Müller, Birthe; Schmidt, Reinhold E; Fackler, Oliver T


    HIV-1 Vpu and Nef proteins downregulate cell surface levels of natural killer (NK) cell ligands but functional consequences of individual downregulation events are unclear. We tested how well-conserved NK cell ligand downregulation is among Vpu and Nef variants isolated from chronic HIV patients. Proviral vpu and nef sequences were amplified from 27 chronic HIV patients, subcloned, and tested for their ability to downregulate cell surface receptors. Cell surface downregulation of CD4, CD317/tetherin, and major histocompatibility complex class 1 that exert biological functions other than NK cell activation were well conserved among patient-derived Vpu and Nef variants. Among NK cell ligands, NK-T-B-antigen, poliovirus receptor, and UL16-binding protein were identified as main targets for Vpu and Nef, the downregulation of which by at least 1 viral protein was highly conserved. NK cell ligands displayed specific sensitivity to Vpu (NK-T-B-antigen) or Nef (poliovirus receptor), and downregulation of cell surface UL16-binding protein was identified as a novel and highly conserved activity of HIV-1 Vpu but not Nef. The conservation of downregulation of major NK cell ligands by either HIV-1 Vpu or Nef suggests an important pathophysiological role of this activity, which may impact the acute but not the chronic phase of HIV infection.

  5. Quantified Binding Scale of Competing Ligands at the Surface of Gold Nanoparticles: The Role of Entropy and Intermolecular Forces. (United States)

    Goldmann, Claire; Ribot, François; Peiretti, Leonardo F; Quaino, Paola; Tielens, Frederik; Sanchez, Clément; Chanéac, Corinne; Portehault, David


    A basic understanding of the driving forces for the formation of multiligand coronas or self-assembled monolayers over metal nanoparticles is mandatory to control and predict the properties of ligand-protected nanoparticles. Herein, 1 H nuclear magnetic resonance experiments and advanced density functional theory (DFT) modeling are combined to highlight the key parameters defining the efficiency of ligand exchange on dispersed gold nanoparticles. The compositions of the surface and of the liquid reaction medium are quantitatively correlated for bifunctional gold nanoparticles protected by a range of competing thiols, including an alkylthiol, arylthiols of varying chain length, thiols functionalized by ethyleneglycol units, and amide groups. These partitions are used to build scales that quantify the ability of a ligand to exchange dodecanethiol. Such scales can be used to target a specific surface composition by choosing the right exchange conditions (ligand ratio, concentrations, and particle size). In the specific case of arylthiols, the exchange ability scale is exploited with the help of DFT modeling to unveil the roles of intermolecular forces and entropic effects in driving ligand exchange. It is finally suggested that similar considerations may apply to other ligands and to direct biligand synthesis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Role of strain and ligand effects in the modification of the electronic and chemical properties of bimetallic surfaces

    DEFF Research Database (Denmark)

    Kitchin, J.R.; Nørskov, Jens Kehlet; Barteau, M.A.


    Periodic density functional calculations are used to illustrate how the combination of strain and ligand effects modify the electronic and surface chemical properties of Ni, Pd, and Pt monolayers supported on other transition metals. Strain and the ligand effects are shown to change the width...... of the surface d band, which subsequently moves up or down in energy to maintain a constant band filling. Chemical properties such as the dissociative adsorption energy of hydrogen are controlled by changes induced in the average energy of the d band by modification of the d-band width....

  7. Human Cancer Antigen Globo H Is a Cell-Surface Ligand for Human Ribonuclease 1. (United States)

    Eller, Chelcie H; Chao, Tzu-Yuan; Singarapu, Kiran K; Ouerfelli, Ouathek; Yang, Guangbin; Markley, John L; Danishefsky, Samuel J; Raines, Ronald T


    Pancreatic-type ribonucleases are secretory enzymes that catalyze the cleavage of RNA. Recent efforts have endowed the homologues from cow (RNase A) and human (RNase 1) with toxicity for cancer cells, leading to a clinical trial. The basis for the selective toxicity of ribonuclease variants for cancerous versus noncancerous cells has, however, been unclear. A screen for RNase A ligands in an array of mammalian cell-surface glycans revealed strong affinity for a hexasaccharide, Globo H, that is a tumor-associated antigen and the basis for a vaccine in clinical trials. The affinity of RNase A and RNase 1 for immobilized Globo H is in the low micromolar-high nanomolar range. Moreover, reducing the display of Globo H on the surface of human breast adenocarcinoma cells with a small-molecule inhibitor of biosynthesis or a monoclonal antibody antagonist decreases the toxicity of an RNase 1 variant. Finally, heteronuclear single quantum coherence (HSQC) NMR spectroscopy showed that RNase 1 interacts with Globo H by using residues that are distal from the enzymic active site. The discovery that a systemic human ribonuclease binds to a moiety displayed on human cancer cells links two clinical paradigms and suggests a mechanism for innate resistance to cancer.

  8. Catalyst-Free Conjugation and In Situ Quantification of Nanoparticle Ligand Surface Density Using Fluorogenic Cu-Free Click Chemistry

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming; Sun, Honghao; Berg, Rolf Henrik


    A highly efficient method for functionalizing nanoparticles and directly quantifying conjugation efficiency and ligand surface density has been developed. Attachment of 3-azido-modifed RGD-peptides to PEGylated liposomes was achieved by using Cu-free click conditions. Upon coupling a fluorophore...

  9. Surface integrity governs the proteome of hypomineralized enamel. (United States)

    Mangum, J E; Crombie, F A; Kilpatrick, N; Manton, D J; Hubbard, M J


    Growing interest in the treatment and prevention of Molar/Incisor Hypomineralization (MIH) warrants investigation into the protein composition of hypomineralized enamel. Hypothesizing abnormality akin to amelogenesis imperfecta, we profiled proteins in hypomineralized enamel from human permanent first molars using a biochemical approach. Hypomineralized enamel was found to have from 3- to 15-fold higher protein content than normal, but a near-normal level of residual amelogenins. This distinguished MIH from hypomaturation defects with high residual amelogenins (amelogenesis imperfecta, fluorosis) and so typified it as a hypocalcification defect. Second, hypomineralized enamel was found to have accumulated various proteins from oral fluid and blood, with differential incorporation depending on integrity of the enamel surface. Pathogenically, these results point to a pre-eruptive disturbance of mineralization involving albumin and, in cases with post-eruptive breakdown, subsequent protein adsorption on the exposed hydroxyapatite matrix. These insights into the pathogenesis and properties of hypomineralized enamel hold significance for prevention and treatment of MIH.

  10. Surface chemistry governs cellular tropism of nanoparticles in the brain (United States)

    Song, Eric; Gaudin, Alice; King, Amanda R.; Seo, Young-Eun; Suh, Hee-Won; Deng, Yang; Cui, Jiajia; Tietjen, Gregory T.; Huttner, Anita; Saltzman, W. Mark


    Nanoparticles are of long-standing interest for the treatment of neurological diseases such as glioblastoma. Most past work focused on methods to introduce nanoparticles into the brain, suggesting that reaching the brain interstitium will be sufficient to ensure therapeutic efficacy. However, optimized nanoparticle design for drug delivery to the central nervous system is limited by our understanding of their cellular deposition in the brain. Here, we investigated the cellular fate of poly(lactic acid) nanoparticles presenting different surface chemistries, after administration by convection-enhanced delivery. We demonstrate that nanoparticles with `stealth' properties mostly avoid internalization by all cell types, but internalization can be enhanced by functionalization with bio-adhesive end-groups. We also show that association rates measured in cultured cells predict the extent of internalization of nanoparticles in cell populations. Finally, evaluating therapeutic efficacy in an orthotopic model of glioblastoma highlights the need to balance significant uptake without inducing adverse toxicity.

  11. Affinity Interaction between Hexamer Peptide Ligand HWRGWV and Immunoglobulin G Studied by Quartz Crystal Microbalance and Surface Plasmon Resonance (United States)

    Shen, Fei

    Immunoglobulins (Ig), also referred to as antibodies, act as protective agents against pathogens trying to invade an organism. Human immunoglobulin G (hIgG), as the most prominent immunoglobulin presented in serum and other human fluids, has broad applications in fields like immunotherapy and clinical diagnostics. Staphylococcus aureus Protein A and Streptococcus Protein G are the most common affinity ligands for IgG purifaction and detection. However, drawbacks associated with these two protein ligands have motivated searches for alternative affinity ligands. The hexamer peptide ligand HWRGWV identified from a one-bead-one-peptide combinatorial library synthesized on chromatography resins has demonstrated high affinity and specificity to the Fc fragment of hIgG. A chromatography resin with HWRGWV can purify human IgG (hIgG) from complete minimum essential medium (cMEM) with purities and yields as high as 95%, which are comparable to using Protein A as affinity ligand (4). As a short peptide ligand, HWRGWV can be produced at relatively low costs under good manufacturing practices (GMP) conditions, it is highly robust, less immunogenic and allows for milder elution conditions for the bound antibody (3, 5). Although this short peptide ligand has exhibited promising properties for IgG capture and purification, limited information is available on the intrinsic mechanisms of affinity interaction between the peptide ligand and target protein. In this study, the affinity interaction between hIgG and peptide ligand immobilized on solid surfaces was studied by quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). Compared with previous methods employed for the peptide characterization, QCM and SPR can provide direct measurements of equilibrium adsorption isotherms and rates of adsorption, allowing a complete kinetic and thermodynamics analyses of the ligand-target interactions. New methods were developed to modify gold and silica surfaces of QCM and SPR

  12. Surface plasmon resonance spectroscopy for characterisation of membrane protein-ligand interactions and its potential for drug discovery. (United States)

    Patching, Simon G


    Surface plasmon resonance (SPR) spectroscopy is a rapidly developing technique for the study of ligand binding interactions with membrane proteins, which are the major molecular targets for validated drugs and for current and foreseeable drug discovery. SPR is label-free and capable of measuring real-time quantitative binding affinities and kinetics for membrane proteins interacting with ligand molecules using relatively small quantities of materials and has potential to be medium-throughput. The conventional SPR technique requires one binding component to be immobilised on a sensor chip whilst the other binding component in solution is flowed over the sensor surface; a binding interaction is detected using an optical method that measures small changes in refractive index at the sensor surface. This review first describes the basic SPR experiment and the challenges that have to be considered for performing SPR experiments that measure membrane protein-ligand binding interactions, most importantly having the membrane protein in a lipid or detergent environment that retains its native structure and activity. It then describes a wide-range of membrane protein systems for which ligand binding interactions have been characterised using SPR, including the major drug targets G protein-coupled receptors, and how challenges have been overcome for achieving this. Finally it describes some recent advances in SPR-based technology and future potential of the technique to screen ligand binding in the discovery of drugs. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. The effect of geometrical presentation of multimodal cation-exchange ligands on selective recognition of hydrophobic regions on protein surfaces. (United States)

    Woo, James; Parimal, Siddharth; Brown, Matthew R; Heden, Ryan; Cramer, Steven M


    The effects of spatial organization of hydrophobic and charged moieties on multimodal (MM) cation-exchange ligands were examined by studying protein retention behavior on two commercial chromatographic media, Capto™ MMC and Nuvia™ cPrime™. Proteins with extended regions of surface-exposed aliphatic residues were found to have enhanced retention on the Capto MMC system as compared to the Nuvia cPrime resin. The results further indicated that while the Nuvia cPrime ligand had a strong preference for interactions with aromatic groups, the Capto MMC ligand appeared to interact with both aliphatic and aromatic clusters on the protein surfaces. These observations were formalized into a new set of protein surface property descriptors, which quantified the local distribution of electrostatic and hydrophobic potentials as well as distinguishing between aromatic and aliphatic properties. Using these descriptors, high-performing quantitative structure-activity relationship (QSAR) models (R(2)>0.88) were generated for both the Capto MMC and Nuvia cPrime datasets at pH 5 and pH 6. Descriptors of electrostatic properties were generally common across the four models; however both Capto MMC models included descriptors that quantified regions of aliphatic-based hydrophobicity in addition to aromatic descriptors. Retention was generally reduced by lowering the ligand densities on both MM resins. Notably, elution order was largely unaffected by the change in surface density, but smaller and more aliphatic proteins tended to be more affected by this drop in ligand density. This suggests that modulating the exposure, shape and density of the hydrophobic moieties in multimodal chromatographic systems can alter the preference for surface exposed aliphatic or aromatic residues, thus providing an additional dimension for modulating the selectivity of MM protein separation systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. 2-deoxy D-glucose prevents cell surface expression of NKG2D ligands through inhibition of N-linked glycosylation

    DEFF Research Database (Denmark)

    Andresen, Lars; Skovbakke, Sarah Line; Persson, Gry


    NKG2D ligand surface expression is important for immune recognition of stressed and neotransformed cells. In this study, we show that surface expression of MICA/B and other NKG2D ligands is dependent on N-linked glycosylation. The inhibitor of glycolysis and N-linked glycosylation, 2-deoxy...

  15. Chemogenomic analysis of G-protein coupled receptors and their ligands deciphers locks and keys governing diverse aspects of signalling.

    Directory of Open Access Journals (Sweden)

    Jörg D Wichard

    Full Text Available Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic or inhibitory (antagonistic ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences.

  16. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Monine, Michael [Los Alamos National Laboratory; Posner, Richard [TRANSLATION GENOMICS RESAEARCH INSTITUTE; Savage, Paul [BYU; Faeder, James [UNIV OF PITTSBURGH; Hlavacek, William S [UNM


    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  17. A chelating dendritic ligand capped quantum dot: preparation, surface passivation, bioconjugation and specific DNA detection (United States)

    Zhou, Dejian; Li, Yang; Hall, Elizabeth A. H.; Abell, Chris; Klenerman, David


    Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has stronger fluorescence than that capped by a monodendate single-chain thiol, 3-mercapto-propionic acid (MPA-QD). In addition, the fluorescence of the CDL-QD can be enhanced by 2.5-fold by treatments with Zn2+ or S2- ions, presumably due to effective passivation of the surface defects. This level of fluorescence enhancement obtained for the CDL-QD is much greater than that for the MPA-QD. Further, by coupling a short single-stranded DNA target to the QD via the CDL carboxylic acidgroup, a functional QD-DNA conjugate that can resist non-specific adsorption and hybridize quickly to its complementary DNAprobe has been obtained. This functional QD-DNA conjugate is suitable for specific quantification of short, labelled complementary probes at the low DNAprobe:QD copy numbers via a QD-sensitised dyefluorescence resonance energy transfer (FRET) response with 500 pM sensitivity on a conventional fluorimeter.Herein we report the synthesis of a new chelating dendritic ligand (CDL) and its use in the preparation a compact, stable and water-soluble quantum dot (QD), and further development of specific DNA sensor. The CDL, which contains a chelative dihydrolipoic acid moiety for strong QD surface anchoring and four dendritic carboxylic acidgroups, provides a stable, compact and entangled hydrophilic coating around the QD that significantly increases the stability of the resulting water-soluble QD. A CDL-capped CdSe/ZnS core/shell QD (CDL-QD) has

  18. Regulation of NKG2D-ligand cell surface expression by intracellular calcium after HDAC-inhibitor treatment

    DEFF Research Database (Denmark)

    Jensen, Helle; Hagemann-Jensen, Michael Henrik; Lauridsen, Felicia Kathrine Bratt


    cell surface expression on melanoma cells and Jurkat T-cells. A NKG2D-dependent cytolytic assay and staining with a recombinant NKG2D-Fc fusion protein showed that calcium chelation impaired the functional ability of NKG2D-ligands induced by HDAC-inhibitor treatment. The HDAC-inhibitor induced cell......-cells. We further show that secretion and cell surface binding of the calcium-regulating protein galectin-1 is enhanced upon HDAC-inhibitor treatment of melanoma cells. However, binding of galectin-1 to cell surface glycoproteins was not critical for constitutive or HDAC-inhibitor induced MICA/B and ULBP2...

  19. Rapid Buffer and Ligand Screening for Affinity Chromatography by Multiplexed Surface Plasmon Resonance Imaging

    NARCIS (Netherlands)

    Geuijen, K.P.M.; Wijk-Basten, van Danielle E.J.W.; Egging, Davis F.; Schasfoort, Richard B.M.; Eppink, M.H.M.


    Protein purifications are often based on the principle of affinity chromatography, where the protein of interest selectively binds to an immobilized ligand. The development of affinity purification requires selecting proper wash and elution conditions. In recent years, miniaturization of the

  20. Synthesis of Janus-like gold nanoparticles with hydrophilic/hydrophobic faces by surface ligand exchange and their self-assemblies in water. (United States)

    Iida, Ryo; Kawamura, Hitoshi; Niikura, Kenichi; Kimura, Takashi; Sekiguchi, Shota; Joti, Yasumasa; Bessho, Yoshitaka; Mitomo, Hideyuki; Nishino, Yoshinori; Ijiro, Kuniharu


    This study aims at the synthesis of Janus gold nanoparticles (Janus GNPs) with hydrophilic/hydrophobic faces by a simple ligand exchange reaction in an homogeneous system and at the elucidation of the self-assembled structures of the Janus GNPs in water. As hydrophilic surface ligands, we synthesized hexaethylene glycol (E6)-terminated thiolate ligands with C3, C7, or C11 alkyl chains, referred to as E6C3, E6C7, and E6C11, respectively. As a hydrophobic ligand, a butyl-headed thiolate ligand C4-E6C11, in which a C4 alkyl was introduced on the E6C11 terminus, was synthesized. The degree of segregation between the two ligands on the GNPs (5 nm in diameter) was examined by matrix-assisted laser desorption/ionization time-of fright mass spectrometry (MALDI-TOF MS) analysis. We found that the choice of immobilization methods, one-step or two-step addition of the two ligands to the GNP solution, crucially affects the degree of segregation. The two-step addition of a hydrophilic ligand (E6C3) followed by a hydrophobic ligand (C4-E6C11) produced a large degree of segregation on the GNPs, providing Janus-like GNPs. When dispersed in water, these Janus-like GNPs formed assemblies of ∼160 nm in diameter, whereas Domain GNPs, in which the two ligands formed partial domains on the surface, were precipitated even when the molar ratio of the hydrophilic ligand and the hydrophobic ligand on the surface of the NPs was almost 1:1. The assembled structure of the Janus-like GNPs in water was directly observed by pulsed coherent X-ray solution scattering using an X-ray free-electron laser, revealing irregular spherical structures with uneven surfaces.

  1. Reduced curvature of ligand-binding domain free-energy surface underlies partial agonism at NMDA receptors. (United States)

    Dai, Jian; Zhou, Huan-Xiang


    NMDA receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. Partial agonists elicit submaximal channel activation, but crystal structures of the ligand-binding domains (LBDs) bound with partial and full agonists show little difference. To uncover the molecular mechanism for partial agonism, here we computed the free-energy surfaces of the GluN1 (an obligatory subunit of NMDA receptors) LBD bound with a variety of ligands. The free-energy minima are similarly positioned for full and partial agonists, but the curvatures are significantly reduced in the latter case, indicating higher probabilities for sampling conformations with a not fully closed domain cleft. The free-energy surfaces for antagonists have both shifted minima and further reduced curvatures. Reduced curvature of free-energy surface appears to explain well the partial agonism at NMDA receptors and may present a unique paradigm in producing graded responses for receptors in general. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Photochemical cycling of iron in the surface ocean mediated by microbial iron(III)-binding ligands (United States)

    Barbeau, K.; Rue, E. L.; Bruland, K. W.; Butler, A.


    Iron is a limiting nutrient for primary production in large areas of the oceans. Dissolved iron(III) in the upper oceans occurs almost entirely in the form of complexes with strong organic ligands presumed to be of biological origin. Although the importance of organic ligands to aquatic iron cycling is becoming clear, the mechanism by which they are involved in this process remains uncertain. Here we report observations of photochemical reactions involving Fe(III) bound to siderophores-high-affinity iron(III) ligands produced by bacteria to facilitate iron acquisition. We show that photolysis of Fe(III)-siderophore complexes leads to the formation of lower-affinity Fe(III) ligands and the reduction of Fe(III), increasing the availability of siderophore-bound iron for uptake by planktonic assemblages. These photochemical reactions are mediated by the α-hydroxy acid moiety, a group which has generally been found to be present in the marine siderophores that have been characterized. We suggest that Fe(III)-binding ligands can enhance the photolytic production of reactive iron species in the euphotic zone and so influence iron availability in aquatic systems.

  3. Optimum design of amphiphilic polymers bearing hydrophobic groups for both cell surface ligand presentation and intercellular cross-linking. (United States)

    Takeo, Masafumi; Li, Cuicui; Matsuda, Masayoshi; Nagai, Hiroko; Hatanaka, Wataru; Yamamoto, Tatsuhiro; Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki


    Amphiphilic polymers bearing hydrophobic alkyl groups are expected to be applicable for both ligand presentation on the cell surface and intercellular crosslinking. To explore the optimum design for each application, we synthesized eight different acyl-modified dextrans with varying molecular weight, alkyl length, and alkyl modification degree. We found that the behenate-modified polymers retained on the cell surface longer than the palmitate-modified ones. Since the polymers were also modified with biotin, streptavidin can be presented on the cell surface through biotin-streptavidin recognition. The duration of streptavidin on the cell surface is longer in the behenate-modified polymer than the palmitate-modified one. As for the intercellular crosslinking, the palmitate-modified polymers were more efficient than the behenate-modified polymers. The findings in this research will be helpful to design the acyl-modified polymers for the cell surface engineering.

  4. Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

    DEFF Research Database (Denmark)

    Jensen, Helle; Andresen, Lars; Nielsen, Jens


    Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection......D-ligand expression at an early post-transcriptional level. Our results show that VSV possess an escape mechanism, which could affect the immune recognition of VSV infected cancer cells. This may also have implications for immune recognition of cancer cells after combined treatment with VSV...

  5. Surface engineering of SPIONs: role of phosphonate ligand multivalency in tailoring their efficacy (United States)

    Lam, Tina; Avti, Pramod K.; Pouliot, Philippe; Tardif, Jean-Claude; Rhéaume, Éric; Lesage, Frederic; Kakkar, Ashok


    We report the design of scaffolds containing mono-, bis-, and tris-phosphonate coordinating groups, and a polyethylene glycol chain, for stabilizing superparamagnetic iron oxide nanoparticles (SPIONs), using simple and versatile chemistry. We demonstrate that the number of anchoring phosphonate sites on the ligand influence the colloidal stability, magnetic and biological properties of SPIONs, and the latter do not solely depend on attaching moieties that can enhance their aqueous dispersion. These parameters can be tailored by the number of conjugation sites on the ligand, as evidenced from dynamic light scattering at various salt concentrations, magnetic relaxivities and cell viability studies.

  6. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Behrendt, N; Ploug, M; Patthy, L


    with the internal repeats of u-PAR constitute the extracellular part of Ly-6 antigens and of the squid glycoprotein Sgp-2. Like u-PAR, these proteins are attached to the membrane by a glycosyl-phosphatidylinositol anchor. The hydrophilic, ligand-binding u-PAR domain identified in the present study has potential...

  7. Topological defects govern crack front motion and facet formation on broken surfaces (United States)

    Kolvin, Itamar; Cohen, Gil; Fineberg, Jay


    Cracks develop intricate patterns on the surfaces that they create. As faceted fracture surfaces are commonly formed by slow tensile cracks in both crystalline and amorphous materials, facet formation and structure cannot reflect microscopic order. Although fracture mechanics predict that slow crack fronts should be straight and form mirror-like surfaces, facet-forming fronts propagate simultaneously within different planes separated by steps. Here we show that these steps are topological defects of crack fronts and that crack front separation into disconnected overlapping segments provides the condition for step stability. Real-time imaging of propagating crack fronts combined with surface measurements shows that crack dynamics are governed by localized steps that drift at a constant angle to the local front propagation direction while their increased dissipation couples to long-ranged elasticity to determine front shapes. We study how three-dimensional topology couples to two-dimensional fracture dynamics to provide a fundamental picture of how patterned surfaces are generated.

  8. Surface polyPEGylation of Eu3+ doped luminescent hydroxyapatite nanorods through the combination of ligand exchange and metal free surface initiated atom transfer radical polymerization (United States)

    Zeng, Guangjian; Liu, Meiying; Heng, Chunning; Huang, Qiang; Mao, Liucheng; Huang, Hongye; Hui, Junfeng; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen


    The Eu3+ doped luminescent hydroxyapatite (HAp) nanorods with uniform size and morphology can be synthesized by hydrothermal route. However, these HAp nanorods are coated by hydrophobic oleylamine, which makes them difficult to be dispersed in aqueous solution and impede their biomedical applications. In this work, Eu3+ doped luminescent polymers functionalized HAp nanorods were prepared through the combination of ligand exchange reaction and metal free surface initiated atom transfer radical polymerization (ATRP) method. In this procedure, the amino group functionalized HAp nanorods were first prepared by ligand exchange reaction using adenosine monophosphate (AMP) as ligand. Then the Br-containing initiators (HAp-Br) were introduced onto the surface of HAp-AMP nanorods through the amidation reaction. Finally, polymers functionalized HAp nanorods were prepared by metal free ATRP method using poly(ethylene glycol) methacrylate (PEGMA) as monomer and 10-phenylphenothiazine (PTH) as organic photocatalyst. The properties of these obtained HAp nanocomposites (HAP-polyPEGMA nanorods) were characterized by means of transmission electron microscopy, Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis in detail. The cell imaging of these HAP-polyPEGMA nanorods was examined using laser scanning confocal microscope to evaluate their biomedical applications. We demonstrated for the first time that hydrophobic luminescent HAp nanorods can be functionalized with polyPEGMA through the combination of ligand exchange reaction and metal free surface initiated ATRP. As compared with the traditional ATRP, the metal free ATRP can overcome the toxic and fluorescence quenching effects of metal catalysts such as copper ions. More importantly, the strategy described in this work should also be utilized for fabrications of many other luminescent polymer nanocomposites due to its good monomer adoptability.

  9. Surface polyPEGylation of Eu{sup 3+} doped luminescent hydroxyapatite nanorods through the combination of ligand exchange and metal free surface initiated atom transfer radical polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Guangjian; Liu, Meiying [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Heng, Chunning [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an 710069 (China); Huang, Qiang; Mao, Liucheng; Huang, Hongye [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Hui, Junfeng [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an 710069 (China); Deng, Fengjie, E-mail: [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Zhang, Xiaoyong, E-mail: [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: [Department of Chemistry and The Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)


    Highlights: • Surface modification of HAp nanorods through the combination of ligand exchange reaction and metal free SI-ATRP. • HAp-polyPEGMA displayed high water dispersibility, good biocompatibility and biological imaging capability. • Metal free ATRP can overcome the toxic and fluorescence quenching effects of metal catalysts of conventional ATRP. - Abstract: The Eu{sup 3+} doped luminescent hydroxyapatite (HAp) nanorods with uniform size and morphology can be synthesized by hydrothermal route. However, these HAp nanorods are coated by hydrophobic oleylamine, which makes them difficult to be dispersed in aqueous solution and impede their biomedical applications. In this work, Eu{sup 3+} doped luminescent polymers functionalized HAp nanorods were prepared through the combination of ligand exchange reaction and metal free surface initiated atom transfer radical polymerization (ATRP) method. In this procedure, the amino group functionalized HAp nanorods were first prepared by ligand exchange reaction using adenosine monophosphate (AMP) as ligand. Then the Br-containing initiators (HAp-Br) were introduced onto the surface of HAp-AMP nanorods through the amidation reaction. Finally, polymers functionalized HAp nanorods were prepared by metal free ATRP method using poly(ethylene glycol) methacrylate (PEGMA) as monomer and 10-phenylphenothiazine (PTH) as organic photocatalyst. The properties of these obtained HAp nanocomposites (HAP-polyPEGMA nanorods) were characterized by means of transmission electron microscopy, Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis in detail. The cell imaging of these HAP-polyPEGMA nanorods was examined using laser scanning confocal microscope to evaluate their biomedical applications. We demonstrated for the first time that hydrophobic luminescent HAp nanorods can be functionalized with polyPEGMA through the combination of ligand exchange reaction and metal free surface

  10. CO2 activation through silylimido and silylamido zirconium hydrides supported on N-donor chelating SBA15 surface ligand

    KAUST Repository

    Pasha, Fahran Ahmad


    Density functional theory calculations and 2D 1H-13C HETCOR solid state NMR spectroscopy prove that CO2 can probe, by its own reactivity, different types of N-donor surface ligands on SBA15-supported ZrIV hydrides: [(≡Si-O-)(≡Si-N=)[Zr]H] and [(≡Si-NH-)(≡Si-X-)[Zr]H2] (X = O or NH). Moreover, [(≡Si-O-)(≡Si-N=)[Zr]H] activates CO2 more efficiently than the other complexes and leads to a carbimato Zr formate.

  11. Surface functionalization of semiconductor and oxide nanocrystals with small inorganic oxoanions (PO4(3-), MoO4(2-)) and polyoxometalate ligands. (United States)

    Huang, Jing; Liu, Wenyong; Dolzhnikov, Dmitriy S; Protesescu, Loredana; Kovalenko, Maksym V; Koo, Bonil; Chattopadhyay, Soma; Shenchenko, Elena V; Talapin, Dmitri V


    In this work, we study the functionalization of the nanocrystal (NC) surface with inorganic oxo ligands, which bring a new set of functionalities to all-inorganic colloidal nanomaterials. We show that simple inorganic oxoanions, such as PO4(3-) and MoO4(2-), exhibit strong binding affinity to the surface of various II-VI and III-V semiconductor and metal oxide NCs. ζ-Potential titration offered a useful tool to differentiate the binding affinities of inorganic ligands toward different NCs. Direct comparison of the binding affinity of oxo and chalcogenidometallate ligands revealed that the former ligands form a stronger bond with oxide NCs (e.g., Fe2O3, ZnO, and TiO2), while the latter prefer binding to metal chalcogenide NCs (e.g., CdSe). The binding between NCs and oxo ligands strengthens when moving from small oxoanions to polyoxometallates (POMs). We also show that small oxo ligands and POMs make it possible to tailor NC properties. For example, we observed improved stability upon Li(+)-ion intercalation into the films of Fe2O3 hollow NCs when capped with MoO4(2-) ligands. We also observed lower overpotential and enhanced exchange current density for water oxidation using Fe2O3 NCs capped with [P2Mo18O62](6-) ligands and even more so for [{Ru4O4(OH)2(H2O)4}(γ-SiW10O36)2] with POM as the capping ligand.

  12. Analysis of the surface density and reactivity of perfluorophenylazide and the impact on ligand immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Zorn, Gilad, E-mail:; Castner, David G. [National ESCA and Surface Analysis Center for Biomedical Problems, Departments of Bioengineering and Chemical Engineering, University of Washington, Box 351653, Seattle, Washington 98195-1653 (United States); Tyagi, Anuradha; Wang, Xin; Wang, Hui; Yan, Mingdi, E-mail: [Department of Chemistry, Portland State University, Portland, Oregon 97207-0751 (United States)


    Perfluorophenylazide (PFPA) chemistry is a novel method for tailoring the surface properties of solid surfaces and nanoparticles. It is general and versatile, and has proven to be an efficient way to immobilize graphene, proteins, carbohydrates, and synthetic polymers. The main thrust of this work is to provide a detailed investigation on the chemical composition and surface density of the PFPA tailored surface. Specifically, gold surfaces were treated with PFPA-derivatized (11-mercaptoundecyl)tetra(ethylene glycol) (PFPA-MUTEG) mixed with 2-[2-(2-mercaptoethoxy)ethoxy]ethanol (MDEG) at varying solution mole ratios. Complementary analytical techniques were employed to characterize the resulting films including Fourier transform infrared spectroscopy to detect fingerprints of the PFPA group, x-ray photoelectron spectroscopy and ellipsometry to study the homogeneity and uniformity of the films, and near edge x-ray absorption fine structures to study the electronic and chemical structure of the PFPA groups. Results from these studies show that the films prepared from 90:10 and 80:20 PFPA-MUTEG/MDEG mixed solutions exhibited the highest surface density of PFPA and the most homogeneous coverage on the surface. A functional assay using surface plasmon resonance with carbohydrates covalently immobilized onto the PFPA-modified surfaces showed the highest binding affinity for lectin on the PFPA-MUTEG/MDEG film prepared from a 90:10 solution.

  13. Interactions between a receptor tyrosine phosphatase and a cell surface ligand regulate axon guidance and glial-neuronal communication. (United States)

    Lee, Hyung-Kook Peter; Cording, Amy; Vielmetter, Jost; Zinn, Kai


    We developed a screening method for orphan receptor ligands, in which cell-surface proteins are expressed in Drosophila embryos from GAL4-dependent insertion lines and ligand candidates identified by the presence of ectopic staining with receptor fusion proteins. Stranded at second (Sas) binds to the receptor tyrosine phosphatase Ptp10D in embryos and in vitro. Sas and Ptp10D can interact in trans when expressed in cultured cells. Interactions between Sas and Ptp10D on longitudinal axons are required to prevent them from abnormally crossing the midline. Sas is expressed on both neurons and glia, whereas Ptp10D is restricted to CNS axons. We conducted epistasis experiments by overexpressing Sas in glia and examining how the resulting phenotypes are changed by removal of Ptp10D from neurons. We find that neuronal Ptp10D restrains signaling by overexpressed glial Sas, which would otherwise produce strong glial and axonal phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Testing the Coulomb/Accessible Surface Area solvent model for protein stability, ligand binding, and protein design

    Directory of Open Access Journals (Sweden)

    Bathelt Christine


    Full Text Available Abstract Background Protein structure prediction and computational protein design require efficient yet sufficiently accurate descriptions of aqueous solvent. We continue to evaluate the performance of the Coulomb/Accessible Surface Area (CASA implicit solvent model, in combination with the Charmm19 molecular mechanics force field. We test a set of model parameters optimized earlier, and we also carry out a new optimization in this work, using as a target a set of experimental stability changes for single point mutations of various proteins and peptides. The optimization procedure is general, and could be used with other force fields. The computation of stability changes requires a model for the unfolded state of the protein. In our approach, this state is represented by tripeptide structures of the sequence Ala-X-Ala for each amino acid type X. We followed an iterative optimization scheme which, at each cycle, optimizes the solvation parameters and a set of tripeptide structures for the unfolded state. This protocol uses a set of 140 experimental stability mutations and a large set of tripeptide conformations to find the best tripeptide structures and solvation parameters. Results Using the optimized parameters, we obtain a mean unsigned error of 2.28 kcal/mol for the stability mutations. The performance of the CASA model is assessed by two further applications: (i calculation of protein-ligand binding affinities and (ii computational protein design. For these two applications, the previous parameters and the ones optimized here give a similar performance. For ligand binding, we obtain reasonable agreement with a set of 55 experimental mutation data, with a mean unsigned error of 1.76 kcal/mol with the new parameters and 1.47 kcal/mol with the earlier ones. We show that the optimized CASA model is not inferior to the Generalized Born/Surface Area (GB/SA model for the prediction of these binding affinities. Likewise, the new parameters perform

  15. Equilibrium binding studies of mono, di and triisocyanide ligands on Au powder surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Ontko, Alyn [Iowa State Univ., Ames, IA (United States)


    The author`s group has previously shown that isocyanides are readily adsorbed from solutions to Au powder and bind to the Au surface in an end-on fashion through the terminal carbon. Later work demonstrated that the equilibrium constants for the reversible adsorption of electronically inequivalent isocyanides could be obtained using the Langmuir isotherm technique. This dissertation describes two projects completed which complement the initial findings of this group. Initially, several alkylisocyanides were synthesized to examine the effect of tail length on Au powder adsorption. It was observed that the length of the alkyl chain affected not only the Au surface binding affinity, but also the rate of surface saturation and saturation coverage values. Direct competition studies were also studied using a 13C-labeled isocyanide. These studies demonstrated the stabilization afforded by substrate-substrate packing forces in SAM`s formed by the longer chain isocyanides. In a second study, di and triisocyanides were synthesized to determine the effect that the length of the connecting link and the number of isocyanide groups (as points of attachment) have on Au adsorption stability. The work in this area describes the binding modes, relative binding affinities and surface coverage values for a series of flexible alkyl and xylyldiisocyanides on Au powder surfaces. This report contains only the introductory material, and general summary. Two chapters have been processed separately. 56 refs.

  16. Surface hydrophilicity of PLGA fibers governs in vitro mineralization and osteogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Minnah; Arora, Aditya; Katti, Dhirendra S., E-mail:


    Interfacial properties of biomaterials play an important role in governing their interaction with biological microenvironments. This work investigates the role of surface hydrophilicity of electrospun poly(lactide-co-glycolide) (PLGA) fibers in determining their biological response. For this, PLGA is blended with varying amounts of Pluronic®F-108 and electrospun to fabricate microfibers with varying surface hydrophilicity. The results of mineralization study in simulated body fluid (SBF) demonstrate a significant enhancement in mineralization with an increase in surface hydrophilicity. While presence of serum proteins in SBF reduces absolute mineral content, mineralization continues to be higher on samples with higher surface hydrophilicity. The results from in vitro cell culture studies demonstrate a marked improvement in mesenchymal stem cell —adhesion, elongation, proliferation, infiltration, osteogenic differentiation and matrix mineralization on hydrophilized fibers. Therefore, hydrophilized PLGA fibers are advantageous both in terms of mineralization and elicitation of favorable cell response. Since most of the polymeric materials being used in orthopedics are hydrophobic in nature, the results from this study have strong implications in the future design of interfaces of such hydrophobic materials. In addition, the work proposes a facile method for the modification of electrospun fibers of hydrophobic polymers by blending with a poloxamer for improved bone tissue regeneration. - Highlights: • Surface hydrophilicity of PLGA modulated by blending with Pluronic F-108. • Hydrophilized fibers support better in vitro mineralization. • Mineralization trends retained in the presence of adsorbed serum proteins. • Hydrophilized fibers promote better cell adhesion and proliferation. • Hydrophilized fibers also enable better osteogenic differentiation.

  17. Mechanochemical transformation of an organic ligand on mineral surfaces: The efficiency of birnessite in catechol degradation

    Energy Technology Data Exchange (ETDEWEB)

    Di Leo, Paola, E-mail: [Consiglio Nazionale delle Ricerche - Istituto di Metodologie per l' Analisi Ambientale, C.da S. Loja, Zona Industriale, 85050 Tito Scalo (PZ) (Italy); Pizzigallo, Maria Donata Rosa [Dipartimento di Biologia e Chimica Agroforestale e Ambientale, Universita di Bari Aldo Moro, Via Amendola 165/a, 70126 Bari (Italy); Ancona, Valeria [Consiglio Nazionale delle Ricerche - Istituto di Ricerca sulle Acque, Via F. De Blasio 5, 70132 Bari (Italy); Di Benedetto, Francesco [Dipartimento di Chimica, Universita di Firenze, Via della Lastruccia, 3, 50019 Sesto Fiorentino (Italy); Mesto, Ernesto; Schingaro, Emanuela; Ventruti, Gennaro [Dipartimento di Scienze della Terra e Geoambientali, Universita di Bari Aldo Moro, Via Orabona, 4, 70125 Bari (Italy)


    Graphical abstract: . The efficiency of mechanochemical treatments in degrading CAT molecules in presence of the highly reactive phyllomanganate birnessite, and without using organic solvents, has been demonstrated in the present study. Integrating information from different techniques on solid let it possible to get a comprehensive picture of the most reliable reaction mechanism of degradation of CAT molecules onto KBi surfaces, thus allowing the individuation of specific sites in the synthesized oxides on which catechol molecules were preferentially adsorbed, and thus degraded. The degradation mechanism mainly occurs via a redox reaction. It implies the formation of a surface bidentate inner-sphere complex between the phenolic group of the organic molecules and the Mn(IV) from the birnessite structure. Structural changes occur on the MnO{sub 6} layers of birnessite as due to the mechanically induced surface reactions: reduction of Mn(IV), consequent formation of Mn(III) and new vacancies, and free Mn{sup 2+} ions production. The extent of the mechanochemical degradation of CAT onto birnessite surfaces is higher. This is a consequence of the two phenolic groups of catechol that easily reacts. Highlights: Black-Right-Pointing-Pointer A basic insight at molecular scale of the mechanically induced transformations of CAT onto birnessite is obtained. Black-Right-Pointing-Pointer The abiotic degradative mechanisms of CAT onto birnessite is provided. Black-Right-Pointing-Pointer The mechanically induced degradation of CAT mainly occurs via a redox reaction. Black-Right-Pointing-Pointer Mechanochemistry improves the efficiency of birnessite to degrade CAT. Black-Right-Pointing-Pointer The mechanochemical technique offer potentials in remediating contaminated sites. - Abstract: The aim of this work is to investigate the efficiency of the phyllomanganate birnessite in degrading catechol after mechanochemical treatments. A synthesized birnessite and the organic molecule were

  18. Improvement of Ligand Affinity and Thermodynamic Properties by NMR-Based Evaluation of Local Dynamics and Surface Complementarity in the Receptor-Bound State. (United States)

    Mizukoshi, Yumiko; Takeuchi, Koh; Arutaki, Misa; Tokunaga, Yuji; Takizawa, Takeshi; Hanzawa, Hiroyuki; Shimada, Ichio


    The thermodynamic properties of a ligand in the bound state affect its binding specificity. Strict binding specificity can be achieved by introducing multiple spatially defined interactions, such as hydrogen bonds and van der Waals interactions, into the ligand-receptor interface. These introduced interactions are characterized by restricted local dynamics and improved surface complementarity in the bound state. In this study, we experimentally evaluated the local dynamics and the surface complementarity of weak-affinity ligands in the receptor-bound state by forbidden coherence transfer analysis in free-bound exchange systems (Ex-FCT), using the interaction between a ligand, a myocyte-enhancer factor 2A (MEF2A) docking peptide, and a receptor, p38α, as a model system. The Ex-FCT analyses successfully provided information for the rational design of a ligand with higher affinity and preferable thermodynamic properties for p38α. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Extracellular Polymeric Substances Govern the Surface Charge of Biogenic Elemental Selenium Nanoparticles

    KAUST Repository

    Jain, Rohan


    © 2014 American Chemical Society. The origin of the organic layer covering colloidal biogenic elemental selenium nanoparticles (BioSeNPs) is not known, particularly in the case when they are synthesized by complex microbial communities. This study investigated the presence of extracellular polymeric substances (EPS) on BioSeNPs. The role of EPS in capping the extracellularly available BioSeNPs was also examined. Fourier transform infrared (FT-IR) spectroscopy and colorimetric measurements confirmed the presence of functional groups characteristic of proteins and carbohydrates on the BioSeNPs, suggesting the presence of EPS. Chemical synthesis of elemental selenium nanoparticles in the presence of EPS, extracted from selenite fed anaerobic granular sludge, yielded stable colloidal spherical selenium nanoparticles. Furthermore, extracted EPS, BioSeNPs, and chemically synthesized EPS-capped selenium nanoparticles had similar surface properties, as shown by ζ-potential versus pH profiles and isoelectric point measurements. This study shows that the EPS of anaerobic granular sludge form the organic layer present on the BioSeNPs synthesized by these granules. The EPS also govern the surface charge of these BioSeNPs, thereby contributing to their colloidal properties, hence affecting their fate in the environment and the efficiency of bioremediation technologies.

  20. Atomic models for anionic ligand passivation of cation-rich surfaces of IV-VI, II-VI, and III-V colloidal quantum dots. (United States)

    Ko, Jae-Hyeon; Yoo, Dongsuk; Kim, Yong-Hyun


    We formulated atomic models of cation-rich surfaces passivated with anionic ligands for IV-VI, II-VI, and III-V colloidal quantum dots, employing electron counting models and quantum mechanical calculations. We found that the fractional dangling bonds of cation-rich (100) and (111) surfaces could be greatly stabilized by dimerization-anion passivation and amine-anion co-passivation.

  1. Bipodal surface organometallic complexes with surface N-donor ligands and application to the catalytic cleavage of C-H and C-C bonds in n -Butane

    KAUST Repository

    Bendjeriou-Sedjerari, Anissa


    We present a new generation of "true vicinal" functions well-distributed on the inner surface of SBA15: [(Sî - Si-NH 2)(≡Si-OH)] (1) and [(≡Si-NH2)2] (2). From these amine-modified SBA15s, two new well-defined surface organometallic species [(≡Si-NH-)(≡Si-O-)]Zr(CH2tBu) 2 (3) and [(≡Si-NH-)2]Zr(CH2tBu) 2 (4) have been obtained by reaction with Zr(CH2tBu) 4. The surfaces were characterized with 2D multiple-quantum 1H-1H NMR and infrared spectroscopies. Energy-filtered transmission electron microscopy (EFTEM), mass balance, and elemental analysis unambiguously proved that Zr(CH2tBu)4 reacts with these vicinal amine-modified surfaces to give mainly bipodal bis(neopentyl)zirconium complexes (3) and (4), uniformly distributed in the channels of SBA15. (3) and (4) react with hydrogen to give the homologous hydrides (5) and (6). Hydrogenolysis of n-butane catalyzed by these hydrides was carried out at low temperature (100 C) and low pressure (1 atm). While (6) exhibits a bis(silylamido)zirconium bishydride, [(≡Si-NH-)2]Zr(H) 2 (6a) (60%), and a bis(silylamido)silyloxozirconium monohydride, [(≡Si-NH-)2(≡Si-O-)]ZrH (6b) (40%), (5) displays a new surface organometallic complex characterized by an 1H NMR signal at 14.46 ppm. The latter is assigned to a (silylimido)(silyloxo)zirconium monohydride, [(≡Si-Nî)(≡Si-O-)]ZrH (5b) (30%), coexistent with a (silylamido)(silyloxo)zirconium bishydride, [(≡Si-NH-)(≡Si-O-)] Zr(H)2 (5a) (45%), and a silylamidobis(silyloxo)zirconium monohydride, [(≡Si-NH-)(≡Si-O-)2]ZrH (5c) (25%). Surprisingly, nitrogen surface ligands possess catalytic properties already encountered with silicon oxide surfaces, but interestingly, catalyst (5) with chelating [N,O] shows better activity than (6) with chelating [N,N]. © 2013 American Chemical Society.

  2. Structures of SdrD from Staphylococcus aureus reveal the molecular mechanism of how the cell surface receptors recognize their ligands. (United States)

    Wang, Xiao; Ge, Jingpeng; Liu, Bao; Hu, Yulin; Yang, Maojun


    Staphylococcus aureus is the most important Gram-positive colonizer of human skin and nasal passage, causing high morbidity and mortality. SD-repeat containing protein D (SdrD), an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family surface protein, plays an important role in S. aureus adhesion and pathogenesis, while its binding target and molecular mechanism remain largely unknown. Here we solved the crystal structures of SdrD N2-N3 domain and N2-N3-B1 domain. Through structural analysis and comparisons, we characterized the ligand binding site of SdrD, and proposed a featured sequence motif of its potential ligands. In addition, the structures revealed for the first time the interactions between B1 domain and N2-N3 domain among B domain-containing MSCRAMMs. Our results may help in understanding the roles SdrD plays in S. aureus adhesion and shed light on the development of novel antibiotics.

  3. Interdomain electron transfer in cellobiose dehydrogenase is governed by surface electrostatics. (United States)

    Kadek, Alan; Kavan, Daniel; Marcoux, Julien; Stojko, Johann; Felice, Alfons K G; Cianférani, Sarah; Ludwig, Roland; Halada, Petr; Man, Petr


    Cellobiose dehydrogenase (CDH) is a fungal extracellular oxidoreductase which fuels lytic polysaccharide monooxygenase with electrons during cellulose degradation. Interdomain electron transfer between the flavin and cytochrome domain in CDH, preceding the electron flow to lytic polysaccharide monooxygenase, is known to be pH dependent, but the exact mechanism of this regulation has not been experimentally proven so far. To investigate the structural aspects underlying the domain interaction in CDH, hydrogen/deuterium exchange (HDX-MS) with improved proteolytic setup (combination of nepenthesin-1 with rhizopuspepsin), native mass spectrometry with ion mobility and electrostatics calculations were used. HDX-MS revealed pH-dependent changes in solvent accessibility and hydrogen bonding at the interdomain interface. Electrostatics calculations identified these differences to result from charge neutralization by protonation and together with ion mobility pointed at higher electrostatic repulsion between CDH domains at neutral pH. In addition, we uncovered extensive O-glycosylation in the linker region and identified the long-unknown exact cleavage point in papain-mediated domain separation. Transition of CDH between its inactive (open) and interdomain electron transfer-capable (closed) state is shown to be governed by changes in the protein surface electrostatics at the domain interface. Our study confirms that the interdomain electrostatic repulsion is the key factor modulating the functioning of CDH. The results presented in this paper provide experimental evidence for the role of charge repulsion in the interdomain electron transfer in cellobiose dehydrogenases, which is relevant for exploiting their biotechnological potential in biosensors and biofuel cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The human NKG2D ligand ULBP2 can be expressed at the cell surface with or without a GPI anchor and both forms can activate NK cells


    Fernández-Messina, Lola; Ashiru, Omodele; Agüera-González, Sonia; Reyburn, Hugh T.; Valés-Gómez, Mar


    The activating immune receptor NKG2D binds to several stress-induced ligands that are structurally different. MHC-class-I-related chain (MIC) A/B molecules have a transmembrane domain, whereas most UL16 binding proteins (ULBPs) are glycosylphosphatidylinositol (GPI)-linked molecules. The significance of this variability in membrane anchors is unclear. Here, we demonstrate that ULBP2, but not ULBP1 or ULBP3, can reach the cell surface without the GPI modification. Several proteins are expresse...

  5. The Effect of Nitrogen Surface Ligands on Propane Metathesis: Design and Characterizations of N-modified SBA15-Supported Schrock-type Tungsten Alkylidyne

    KAUST Repository

    Eid, Ahmed A.


    Catalysis, which is primarily a molecular phenomenon, is an important field of chemistry because it requires the chemical conversion of molecules into other molecules. It also has an effect on many fields, including, but not limited to, industry, environment and life Science[1]. Surface Organometallic Chemistry is an effective methodology for Catalysis as it imports the concept and mechanism of organometallic chemistry, to surface science and heterogeneous catalysis. So, it bridges the gap between homogenous and heterogeneous catalysis[1]. The aim of the present research work is to study the effect of Nitrogen surface ligands on the activity of Alkane, Propane in particular, metathesis. Our approach is based on the preparation of selectively well-defined group (VI) transition metal complexes supported onto mesoporous materials, SBA15 and bearing amido and/or imido ligands. We choose nitrogen ligands because, according to the literature, they showed in some cases better catalytic properties in homogenous catalysis in comparison with their oxygen counterparts[2]. The first section covers the modification of a highly dehydroxylated SBA15 surface using a controlled ammonia treatment. These will result in the preparation of two kind of Nitrogen surface ligands: -\\tOne with vicinal silylamine/silanol, (≡SiNH2)(≡SiOH), noted [N,O]SBA15 and, -\\tAnother\\tone\\twith\\tvicinal\\tbis-silylamine moieties (≡SiNH2)2, noted [N,N]SBA15[3]. The second section covers the reaction of Schrock type Tungsten Carbyne [W(≡C- tBu)(CH2-tBu)3] with those N-surface ligands and their characterizations by FT-IR, multiple quantum solid state NMR (1H, 13C), elemental analysis and gas phase analysis. The third section covers the generation of the active site, tungsten hydride species. Their performance toward propane metathesis reaction using the dynamic reactor technique PID compared toward previous well-known catalysts supported on silica oxide or mesoporous materials[4]. A fairly good

  6. Hexanedioic acid mediated surface-ligand-exchange process for transferring NaYF4:Yb/Er (or Yb/Tm) up-converting nanoparticles from hydrophobic to hydrophilic

    NARCIS (Netherlands)

    Zhang, Q.; Song, K.; Zhao, J.; Kong, X.; Sun, Y.; Liu, X.; Zhang, Y.; Zeng, Q.; Zhang, H.


    Water-soluble and carboxyl-functionalized up-converting rare-earth nanoparticles (UCNPs) are obtained via an efficient surface-ligand-exchange procedure. Hexanedioic acid molecules are employed to replace the original hydrophobic ligands in diethylene glycol solvent at high temperature. Various

  7. Aerosol surface area concentration: a governing factor in new particle formation in Beijing

    Directory of Open Access Journals (Sweden)

    R. Cai


    Full Text Available The predominating role of aerosol Fuchs surface area, AFuchs, in determining the occurrence of new particle formation (NPF events in Beijing was elucidated in this study. The analysis was based on a field campaign from 12 March to 6 April 2016 in Beijing, during which aerosol size distributions down to  ∼  1 nm and sulfuric acid concentrations were simultaneously monitored. The 26 days were classified into 11 typical NPF days, 2 undefined days, and 13 non-event days. A dimensionless factor, LΓ, characterized by the relative ratio of the coagulation scavenging rate over the condensational growth rate (Kuang et al., 2010, was applied in this work to reveal the governing factors for NPF events in Beijing. The three parameters determining LΓ are sulfuric acid concentration, the growth enhancement factor characterized by contribution of other gaseous precursors to particle growth, Γ, and AFuchs. Different from other atmospheric environments, such as in Boulder and Hyytiälä, the daily-maximum sulfuric acid concentration and Γ in Beijing varied in a narrow range with geometric standard deviations of 1.40 and 1.31, respectively. A positive correlation between the estimated new particle formation rate, J1.5, and sulfuric acid concentration was found with a mean fitted exponent of 2.4. However, the maximum sulfuric acid concentrations on NPF days were not significantly higher (even lower, sometimes than those on non-event days, indicating that the abundance of sulfuric acid in Beijing was high enough to initiate nucleation, but may not necessarily lead to NPF events. Instead, AFuchs in Beijing varied greatly among days with a geometric standard deviation of 2.56, whereas the variabilities of AFuchs in Tecamac, Atlanta, and Boulder were reported to be much smaller. In addition, there was a good correlation between AFuchs and LΓ in Beijing (R2 = 0.88. Therefore, it was AFuchs that fundamentally determined the occurrence of NPF events

  8. Aerosol surface area concentration: a governing factor in new particle formation in Beijing (United States)

    Cai, Runlong; Yang, Dongsen; Fu, Yueyun; Wang, Xing; Li, Xiaoxiao; Ma, Yan; Hao, Jiming; Zheng, Jun; Jiang, Jingkun


    The predominating role of aerosol Fuchs surface area, AFuchs, in determining the occurrence of new particle formation (NPF) events in Beijing was elucidated in this study. The analysis was based on a field campaign from 12 March to 6 April 2016 in Beijing, during which aerosol size distributions down to ˜ 1 nm and sulfuric acid concentrations were simultaneously monitored. The 26 days were classified into 11 typical NPF days, 2 undefined days, and 13 non-event days. A dimensionless factor, LΓ, characterized by the relative ratio of the coagulation scavenging rate over the condensational growth rate (Kuang et al., 2010), was applied in this work to reveal the governing factors for NPF events in Beijing. The three parameters determining LΓ are sulfuric acid concentration, the growth enhancement factor characterized by contribution of other gaseous precursors to particle growth, Γ, and AFuchs. Different from other atmospheric environments, such as in Boulder and Hyytiälä, the daily-maximum sulfuric acid concentration and Γ in Beijing varied in a narrow range with geometric standard deviations of 1.40 and 1.31, respectively. A positive correlation between the estimated new particle formation rate, J1.5, and sulfuric acid concentration was found with a mean fitted exponent of 2.4. However, the maximum sulfuric acid concentrations on NPF days were not significantly higher (even lower, sometimes) than those on non-event days, indicating that the abundance of sulfuric acid in Beijing was high enough to initiate nucleation, but may not necessarily lead to NPF events. Instead, AFuchs in Beijing varied greatly among days with a geometric standard deviation of 2.56, whereas the variabilities of AFuchs in Tecamac, Atlanta, and Boulder were reported to be much smaller. In addition, there was a good correlation between AFuchs and LΓ in Beijing (R2 = 0.88). Therefore, it was AFuchs that fundamentally determined the occurrence of NPF events. Among 11 observed NPF events, 10

  9. Effects of charge and surface ligand properties of nanoparticles on oxidative stress and gene expression within the gut of Daphnia magna

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez, Gustavo A.; Lohse, Samuel E.; Torelli, Marco; Murphy, Catherine; Hamers, Robert J.; Orr, Galya; Klaper, Rebecca D.


    Concern has been raised regarding the current and future release of engineered nanomaterials into aquatic environments from industry and other sources. However, not all nanomaterials may cause an environ-mental impact and identifying which nanomaterials may be of greatest concern has been difficult. It is thought that the surface groups of a functionalized nanoparticles (NPs) may play a significant role in determining their interactions with aquatic organisms, but the way in which surface properties of NPs impact their toxicity in whole organisms has been minimally explored. A major point of interaction of NPs with aquatic organisms is in the gastrointestinal tract as they ingest particulates from the water column or from the sediment. The main goal of this study was to use model gold NP (AuNPs) to evaluate the potential effects of the different surfaces groups on NPs on the gut of an aquatic model organism, Daphnia magna. In this study, we exposed daphnids to a range of AuNPs concentrations and assessed the impact of AuNP exposure in the daphnid gut by measuring reactive oxygen species (ROS) production and expression of genes associated with oxidative stress and general cellular stress: glutathione S-transferase(gst), catalase (cat), heat shock protein 70 (hsp70), and metallothionein1 (mt1). We found ROS formation and gene expression were impacted by both charge and the specific surface ligand used. We detected some degree of ROS production in all NP exposures, but positively charged AuNPs induced a greater ROS response. Similarly, we observed that, compared to controls, both positively charged AuNPs and only one negatively AuNP impacted expression of genes associated with cellular stress. Finally, ligand-AuNP exposures showed a different toxicity and gene expression profile than the ligand alone, indicating a NP specific effect.

  10. Surface anisotropy of iron oxide nanoparticles and slabs from first principles: Influence of coatings and ligands as a test of the Heisenberg model

    Energy Technology Data Exchange (ETDEWEB)

    Brymora, Katarzyna; Calvayrac, Florent, E-mail:


    Highlights: • A new method is given to extract surface anisotropies from ab initio calculations. • Heisenberg model for magnetic clusters and surfaces is validated in simple cases. • Ligands, metallic clusters, or coatings degrade the validity of the Heisenberg model. • Values for surface anisotropies, volume anisotropies, exchange constants are computed. • Results are in agreement with experimental data, previous theoretical findings. - Abstract: We performed ab initio computations of the magnetic properties of simple iron oxide clusters and slabs. We considered an iron oxide cluster functionalized by a molecule or glued to a gold cluster of the same size. We also considered a magnetite slab coated by cobalt oxide or a mixture of iron oxide and cobalt oxide. The changes in magnetic behavior were explored using constrained magnetic calculations. A possible value for the surface anisotropy was estimated from the fit of a classical Heisenberg model on ab initio results. The value was found to be compatible with estimations obtained by other means, or inferred from experimental results. The addition of a ligand, coating, or of a metallic nanoparticle to the systems degraded the quality of the description by the Heisenberg Hamiltonian. Proposing a change in the anisotropies allowing for the proportion of each transition atom we could get a much better description of the magnetism of series of hybrid cobalt and iron oxide systems.

  11. Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor (United States)

    Orgovan, Norbert; Peter, Beatrix; Bősze, Szilvia; Ramsden, Jeremy J.; Szabó, Bálint; Horvath, Robert


    A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (vRGD) of integrin ligand RGD-motifs. vRGD was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 +/- 243 μm-2 (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels.

  12. Intracellular dynamics of sst5 receptors in transfected COS-7 cells: maintenance of cell surface receptors during ligand-induced endocytosis. (United States)

    Stroh, T; Jackson, A C; Sarret, P; Dal Farra, C; Vincent, J P; Kreienkamp, H J; Mazella, J; Beaudet, A


    Internalization of G protein-coupled receptors is crucial for resensitization of phosphorylation-desensitized receptors, but also for their long term desensitization through sequestration. To elucidate the mechanisms regulating cell surface availability of the somatostatin (SRIF) receptor subtype sst5, we characterized its internalization properties in transfected COS-7 cells using biochemical, confocal microscopic, and electron microscopic techniques. Our results demonstrated rapid and efficient sequestration of specifically bound [125I]Tyr0-D-Trp8-SRIF (up to 45% of bound radioactivity). Combined immunocytochemical detection of sst5 and visualization of a fluorescent SRIF analog by confocal microscopy revealed that whereas the internalized ligand progressively clustered toward the cell center with time, immunoreactive receptors remained predominantly associated with the plasma membrane. The preservation of cell surface receptors was confirmed by binding experiments on whole cells revealing a lack of saturability of [125I]Tyr0-D-Trp8-SRIF binding at 37 C. Binding was rendered saturable by the drug monensin, showing that receptor recycling played a key role in the preservation of cell surface receptors. Electron microscopy demonstrated that in addition to receptor recycling, internalization of receptor-ligand complexes triggered a massive recruitment of sst5 receptor molecules from intracellular stores to the membrane. This combination of recycling and recruitment of spare receptors may protect sst5 from long term down-regulation through sequestration and, therefore, facilitate extended SRIF signaling.

  13. Controlled immobilization of His-tagged proteins for protein-ligand interaction experiments using Ni²⁺-NTA layer on glass surfaces. (United States)

    Cherkouk, Charaf; Rebohle, Lars; Lenk, Jens; Keller, Adrian; Ou, Xin; Laube, Markus; Neuber, Christin; Haase-Kohn, Cathleen; Skorupa, Wolfgang; Pietzsch, Jens


    Gold surfaces functionalized with nickel-nitrilotriacetic acid (Ni²⁺-NTA) as self-assembled monolayers (SAM) to immobilize histidine (His)-tagged biomolecules are broadly reported in the literature. However, the increasing demand of using microfluidic systems and biosensors takes more and more advantage on silicon technology which provides dedicated glass surfaces and substantially allows cost and resource savings. Here we present a novel method for the controlled oriented immobilization of His-tagged proteins on glass surfaces functionalized with a Ni²⁺-NTA layer. Exemplarily, the protein pattern morphology after immobilization on the Ni²⁺-NTA layer of His6-tagged soluble receptor for advanced glycation endproducts (sRAGE) was investigated and compared to non-oriented immobilization of sRAGE on amino SAM by using scanning electron microscopy (SEM). Moreover, we demonstrated interaction of immobilized sRAGE with three structurally different ligands, S100A12, S100A4, and glycated low density lipoproteins (glycLDL), by means of peak-force tapping atomic force microscopy (PF-AFM). We showed a clear discrimination of different protein-ligand orientations by differential height measurements.

  14. The Role of Surface-Capping Ligands in Photoexcited Electron Transfer Between CdS Nanorods and [FeFe] Hydrogenase and the Subsequent H 2 Generation

    Energy Technology Data Exchange (ETDEWEB)

    Wilker, Molly B.; Utterback, James K.; Greene, Sophie; Brown, Katherine A.; Mulder, David W.; King, Paul W.; Dukovic, Gordana


    Complexes of CdS nanorods and [FeFe] hydrogenase from Clostridium acetobutylicum have been shown to photochemically produce H2. This study examines the role of the ligands that passivate the nanocrystal surfaces in the electron transfer from photoexcited CdS to hydrogenase and the H2 generation that follows. We functionalized CdS nanorods with a series of mercaptocarboxylate surface-capping ligands of varying lengths and measured their photoexcited electron relaxation by transient absorption (TA) spectroscopy before and after hydrogenase adsorption. Rate constants for electron transfer from the nanocrystals to the enzyme, extracted by modeling of TA kinetics, decrease exponentially with ligand length, suggesting that the ligand layer acts as a barrier to charge transfer and controls the degree of electronic coupling. Relative light-driven H2 production efficiencies follow the relative quantum efficiencies of electron transfer, revealing the critical role of surface-capping ligands in determining the photochemical activity of these nanocrystal-enzyme complexes. Our results suggest that the H2 production in this system could be maximized with a choice of a surface-capping ligand that decreases the distance between the nanocrystal surface and the electron injection site of the enzyme.

  15. Surface thermodynamics and adhesion forces governing bacterial transmission in contact lens related microbial keratitis

    NARCIS (Netherlands)

    Qu, Wenwen; Busscher, Henk J.; Hooymans, Johanna M. M.; van der Mei, Henny C.


    Contact lens induced microbial keratitis results from bacterial transmission from one surface to another. We investigated the adhesion forces of Pseudomonas aeruginosa, Staphylococci and Serratia to different contact lenses, lens cases and corneal surfaces using AFM, and applied a Weibull analysis

  16. Mobility of the Arg-Gly-Asp ligand on the outermost surface of biomaterials suppresses integrin-mediated mechanotransduction and subsequent cell functions. (United States)

    Kakinoki, Sachiro; Seo, Ji-Hun; Inoue, Yuuki; Ishihara, Kazuhiko; Yui, Nobuhiko; Yamaoka, Tetsuji


    Mechanotransduction in the regulation of cellular responses has been previously studied using elastic hydrogels. Because cells interact only with the surface of biomaterials, we are focusing on the molecular mobility at the outermost surface of biomaterials. In this study, surfaces with the mobile Arg-Gly-Asp-Ser (RGDS) peptide have been constructed. Cell culture substrates were coated with ABA-type block copolymers composed of poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) segments (A) and a polyrotaxane (PRX) unit with RGDS bound to α-cyclodextrin (B). Adhesion, morphological changes and actin filament formation of human umbilical vein endothelial cells were reduced on the surfaces containing mobile PRX-RGDS in comparison to the immobile RGDS surfaces constructed from random copolymers with RGDS side groups (Prop-andom-RGDS). In the neurite outgrowth assay using rat adrenal pheochromocytoma cells (PC12), only ∼20% of adherent PC12 cells had neurites on PRX-RGDS surfaces, but more than 50% did on the Random-RGDS surface. The beating colony of dimethyl-sulfoxide-treated mouse embryonic carcinoma cells (P19CL6) were found 10 and 14 days after induction on PRX-RGDS and Random-RGDS surfaces, respectively. After 22 days, the beating colony disappeared on PRX-RGDS surfaces, but many colonies remained on Random-RGDS surfaces. These data suggest that the molecular mobility of the cell-binding ligand on the outermost surface of materials effectively suppresses the actin filament formation and differentiation of these functional cell lines, and may be used as a culture substrate for immature stem cells or progenitor cells. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. The Phenomena of Spreading of Hydrotalcite Sol on A Porous Silica Surface Governed by Marangoni Effect

    Directory of Open Access Journals (Sweden)

    Z. Helwani


    Full Text Available Wetting phenomena plays a crucial role in a wide range of technological applications. Spreading of liquids on solids involving phase change is encountered in many areas ranging from biological systems to industrial applications such as coatings, printing, painting and spraying. The fundamental study on wetting of membrane precursors namely hydrotalcite sols on a porous silica surface with different types of precursor material was successfully carried out. Relationship between the contact angle of a hydrotalcite droplet on silica surface and the Marangoni effect was also investigated. The presence of PVA in hydrotalcite sols was found to influence the rheological properties of the sols significantly, resulting in higher viscosity and ultimately leading to lower contact angle on solid surfaces. The degree of hydrotalcite's philicity on a substrate was improved by the addition of PVA solution. In this study, the spreading of a liquid droplet on a solid surface controlled by a surface tension gradient, due to Marangoni effect was found to drive better spreading of the liquid droplet. Marangoni Number, Ma was found to be proportionally related with the surface tension of the sols but inversely proportional to contact angles of the sols. Marangoni forces that decreased the contact angle, promoted spreading of hydrotalcite droplets on the selected glass substrates. Keywords: contact angle, hydrotalcite, marangoni effect, spreading, wetting evolution

  18. CSF-1 receptor signalling is governed by pre-requisite EHD1 mediated receptor display on the macrophage cell surface. (United States)

    Cypher, Luke R; Bielecki, Timothy Alan; Huang, Lu; An, Wei; Iseka, Fany; Tom, Eric; Storck, Matthew D; Hoppe, Adam D; Band, Vimla; Band, Hamid


    Colony stimulating factor-1 receptor (CSF-1R), a receptor tyrosine kinase (RTK), is the master regulator of macrophage biology. CSF-1 can bind CSF-1R resulting in receptor activation and signalling essential for macrophage functions such as proliferation, differentiation, survival, polarization, phagocytosis, cytokine secretion, and motility. CSF-1R activation can only occur after the receptor is presented on the macrophage cell surface. This process is reliant upon the underlying macrophage receptor trafficking machinery. However, the mechanistic details governing this process are incompletely understood. C-terminal Eps15 Homology Domain-containing (EHD) proteins have recently emerged as key regulators of receptor trafficking but have not yet been studied in the context of macrophage CSF-1R signalling. In this manuscript, we utilize primary bone-marrow derived macrophages (BMDMs) to reveal a novel function of EHD1 as a regulator of CSF-1R abundance on the cell surface. We report that EHD1-knockout (EHD1-KO) macrophages cell surface and total CSF-1R levels are significantly decreased. The decline in CSF-1R levels corresponds with reduced downstream macrophage functions such as cell proliferation, migration, and spreading. In EHD1-KO macrophages, transport of newly synthesized CSF-1R to the macrophage cell surface was reduced and was associated with the shunting of the receptor to the lysosome, which resulted in receptor degradation. These findings reveal a novel and functionally important role for EHD1 in governing CSF-1R signalling via regulation of anterograde transport of CSF-1R to the macrophage cell surface. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Ligands Binding to Cell Surface Ganglioside GD2 Cause Src-Dependent Activation of N-Methyl-D-Aspartate Receptor Signaling and Changes in Cellular Morphology.

    Directory of Open Access Journals (Sweden)

    Wenyong Tong

    Full Text Available Ganglioside GD2 is a plasma membrane glycosphinogolipid. In healthy adults it is expressed at low levels, but it is over-expressed in many cancers. For cancer therapy, GD2 is targeted with anti-GD2 monoclonal antibodies (mAbs, and one adverse side effect is severe visceral pain. Pain is not neuropathic, cannot be blocked with morphine, and stops on discontinuation of mAb therapy. Here, we provide evidence that ligand binding to cell surface GD2 induces rapid and transient activation of Src-family kinases, followed by Src-dependent phosphorylation of NMDA-receptor NR2B subunits selectively, activation of Ca++ fluxes, production of cAMP, and changes in cellular morphology. These GD2-ligand activated signals differ in kinetics and in pharmacology from activation of the same signals in the same cells by BDNF, the growth factor agonist of the TrkB receptor, suggesting biological specificity. Hence, cell surface GD2 regulates pathways that can be associated with neoplasia and with morphine-intractable pain; and this can explain why expression of GD2 correlates with these two pathologies.

  20. Attributing seasonal pH variability in surface ocean waters to governing factors

    NARCIS (Netherlands)

    Hagens, M.; Middelburg, J.J.


    On-going ocean acidification and increasing availability of high-frequency pH data have stimulated interest to understand seasonal pH dynamics in surface waters. Here we show that it is possible to accurately reproduce observed pH values by combining seasonal changes in temperature (T), dissolved

  1. The use of surface immobilization of P-selectin glycoprotein ligand-1 on mesenchymal stem cells to facilitate selectin mediated cell tethering and rolling (United States)

    Lo, Chi Y.; Antonopoulos, Aristotelis; Dell, Anne; Haslam, Stuart M.; Lee, Techung; Neelamegham, Sriram


    Mesenchymal stem/stromal cells (MSCs) are an important candidate for cell-based therapy since they can be easily isolated and expanded, secrete beneficial paracrine factors, and differentiate into multiple lineages. Since the endothelium at sites of injury and inflammation often express adhesion molecules belonging to the selectin family, methods to endow MSCs with selectin-ligands can enhance the efficacy of cell delivery and tissue engraftment. Here, we describe a construct 19Fc[FUT7+], where the first 19 amino acids of the pan-selectin ligand PSGL-1 (P-selectin glycoprotein ligand-1) was fused to a human IgG1. When expressed in HEK293T cells over-expressing the α(1,3)fucosyltransferase FUT7, 19Fc[FUT7+] is decorated by a core-2 sialyl Lewis-X sialofucosylated O-glycan. The non-covalent coupling of this protein onto MSC surface using palmitated protein G (PPG) enhanced cell binding to E- and P-selectin under hydrodynamic shear, without altering MSC multipotency. MSCs functionalized with 19Fc[FUT7+] were captured/tethered onto stimulated endothelial cell monolayers at wall shear stresses up to 4 dyn/cm2. Once captured, the cells rolled robustly up to the highest shear stress tested, 10 dyn/cm2. Unlike previous work where MSCs could only be captured onto selectin-bearing substrates at low or no-flow conditions, the current work presents a ‘glycan engineering’ strategy to enable leukocyte-like capture and rolling. PMID:23891082

  2. Nanohole-based surface plasmon resonance instruments with improved spectral resolution quantify a broad range of antibody-ligand binding kinetics. (United States)

    Im, Hyungsoon; Sutherland, Jamie N; Maynard, Jennifer A; Oh, Sang-Hyun


    We demonstrate an affordable low-noise surface plasmon resonance (SPR) instrument based on extraordinary optical transmission (EOT) in metallic nanohole arrays and quantify a broad range of antibody-ligand binding kinetics with equilibrium dissociation constants ranging from 200 pM to 40 nM. This nanohole-based SPR instrument is straightforward to construct, align, and operate, since it is built around a standard microscope and a portable fiber-optic spectrometer. The measured refractive index resolution of this platform is 3.1 × 10(-6) without on-chip cooling, which is among the lowest reported for SPR sensors based on EOT. This is accomplished via rapid full-spectrum acquisition in 10 ms followed by frame averaging of the EOT spectra, which is made possible by the production of template-stripped gold nanohole arrays with homogeneous optical properties over centimeter-sized areas. Sequential SPR measurements are performed using a 12-channel microfluidic flow cell after optimizing surface modification protocols and antibody injection conditions to minimize mass-transport artifacts. The immobilization of a model ligand, the protective antigen of anthrax on the gold surface, is monitored in real-time with a signal-to-noise ratio of ~860. Subsequently, real-time binding kinetic curves were measured quantitatively between the antigen and a panel of small, 25 kDa single-chain antibodies at concentrations down to 1 nM. These results indicate that nanohole-based SPR instruments have potential for quantitative antibody screening and as a general-purpose platform for integrating SPR sensors with other bioanalytical tools.

  3. Poly(styrene-divinylbenzene) beads surface functionalized with di-block polymer grafting and multi-modal ligand attachment: performance of reversibly immobilized lipase in ester synthesis. (United States)

    Bayramoglu, Gulay; Karagoz, Bunyamin; Altintas, Begum; Arica, M Yakup; Bicak, Niyazi


    Fibrous poly(styrene-b-glycidylmethacrylate) brushes were grafted on poly(styrene-divinylbenzene) (P(S-DVB)) beads using surface-initiated atom transfer radical polymerization. Tetraethyldiethylenetriamine (TEDETA) ligand was incorporated on P(GMA) block. The ligand attached beads were used for reversible immobilization of lipase. The influences of pH, ionic strength, and initial lipase concentration on the immobilization capacities of the beads have been investigated. Lipase adsorption capacity of the beads was about 78.1 mg/g beads at pH 6.0. The Km value for immobilized lipase was about 2.1-fold higher than that of free enzyme. The thermal, and storage stability of the immobilized lipase also was increased compared to the native lipase. It was observed that the same support enzyme could be repeatedly used for immobilization of lipase after regeneration without significant loss in adsorption capacity or enzyme activity. A lipase from Mucor miehei immobilized on styrene-divinylbenzene copolymer was used to catalyze the direct esterification of butyl alcohol and butyric acid.

  4. Effects of the capping ligands, linkers and oxide surface on the electron injection mechanism of copper sulfide quantum dot-sensitized solar cells. (United States)

    Suárez, Javier Amaya; Plata, Jose J; Márquez, Antonio M; Sanz, Javier Fdez


    Quantum dot-sensitized solar cells, QDSCs, are a clean and effective alternative to fossil fuels to reduce CO2 emissions. However, the different components that constitute the QDSCs and the difficulty of isolating experimentally their effects on the performance of the whole system slow down the development of more efficient devices. In this work, DFT calculations are combined with a bottom-up approach to differentiate the effect of each component on the electronic structure and absorption spectra. First, Cu2S QDs were built including a U parameter to effectively describe the localization of electrons. The effect of capping agents is addressed using ligands with different electron-donating/withdrawing groups. The role of linkers and their adsorption on the oxide surface are also examined. Finally, we propose a main indirect electron injection mechanism based on the position of the peaks of the spectra.

  5. Molecular recognition by a polymorphic cell surface receptor governs cooperative behaviors in bacteria.

    Directory of Open Access Journals (Sweden)

    Darshankumar T Pathak


    Full Text Available Cell-cell recognition is a fundamental process that allows cells to coordinate multicellular behaviors. Some microbes, such as myxobacteria, build multicellular fruiting bodies from free-living cells. However, how bacterial cells recognize each other by contact is poorly understood. Here we show that myxobacteria engage in recognition through interactions between TraA cell surface receptors, which leads to the fusion and exchange of outer membrane (OM components. OM exchange is shown to be selective among 17 environmental isolates, as exchange partners parsed into five major recognition groups. TraA is the determinant of molecular specificity because: (i exchange partners correlated with sequence conservation within its polymorphic PA14-like domain and (ii traA allele replacements predictably changed partner specificity. Swapping traA alleles also reprogrammed social interactions among strains, including the regulation of motility and conferred immunity from inter-strain killing. We suggest that TraA helps guide the transition of single cells into a coherent bacterial community, by a proposed mechanism that is analogous to mitochondrial fusion and fission cycling that mixes contents to establish a homogenous population. In evolutionary terms, traA functions as a rare greenbeard gene that recognizes others that bear the same allele to confer beneficial treatment.

  6. Human and pneumococcal cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins are both ligands of human C1q protein. (United States)

    Terrasse, Rémi; Tacnet-Delorme, Pascale; Moriscot, Christine; Pérard, Julien; Schoehn, Guy; Vernet, Thierry; Thielens, Nicole M; Di Guilmi, Anne Marie; Frachet, Philippe


    C1q, a key component of the classical complement pathway, is a major player in the response to microbial infection and has been shown to detect noxious altered-self substances such as apoptotic cells. In this work, using complementary experimental approaches, we identified the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a C1q partner when exposed at the surface of human pathogenic bacteria Streptococcus pneumoniae and human apoptotic cells. The membrane-associated GAPDH on HeLa cells bound the globular regions of C1q as demonstrated by pulldown and cell surface co-localization experiments. Pneumococcal strains deficient in surface-exposed GAPDH harbored a decreased level of C1q recognition when compared with the wild-type strains. Both recombinant human and pneumococcal GAPDHs interacted avidly with C1q as measured by surface plasmon resonance experiments (K(D) = 0.34-2.17 nm). In addition, GAPDH-C1q complexes were observed by transmission electron microscopy after cross-linking. The purified pneumococcal GAPDH protein activated C1 in an in vitro assay unlike the human form. Deposition of C1q, C3b, and C4b from human serum at the surface of pneumococcal cells was dependent on the presence of surface-exposed GAPDH. This ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response.

  7. Tungsten(VI) Carbyne/Bis(carbene) Tautomerization Enabled by N-Donor SBA15 Surface Ligands: A Solid-State NMR and DFT Study

    KAUST Repository

    Bendjeriou-Sedjerari, Anissa


    Designing supported well-defined bis(carbene) complexes remains a key challenge in heterogeneous catalysis. The reaction of W(CtBu)(CH(2)tBu)(3) with amine-modified mesoporous SBA15 silica, which has vicinal silanol/silylamine pairs [(SiOH)(SiNH2)], leads to [(SiNH2-)(SiO-)W(CHtBu)(CH(2)tBu)(2)] and [(SiNH2-)(SiO-)W(=CHtBu)(2)(CH(2)tBu). Variable temperature, H-1-H-1 2D double-quantum, H-1-C-13 HETCOR, and HETCOR with spin diffusion solid-state NMR spectroscopy demonstrate tautomerization between the alkyl alkylidyne and the bis(alkylidene) on the SBA15 surface. Such equilibrium is possible through the coordination of W to the surface [(Si-OH)(Si-NH2)] groups, which act as a [N,O] pincer ligand. DFT calculations provide a rationalization for the surface-complex tautomerization and support the experimental results. This direct observation of such a process shows the strong similarity between molecular mechanisms in homogeneous and heterogeneous catalysis. In propane metathesis (at 150 degrees C), the tungsten bis(carbene) tautomer is favorable, with a turnover number (TON) of 262. It is the highest TON among all the tungsten alkyl-supported catalysts.

  8. Combined use of immunocytochemical techniques and ligand-gold complexes for investigation of platelet membrane responses to surface activation. (United States)

    Escolar, G; White, J G


    Exposure of blood platelets to foreign surfaces results in dramatic changes in physical appearance and conversion from a non-sticky to an adhesive state. Membrane glycoproteins and cytoskeletal assembly play a pivotal role in these interactions. Cytochemical techniques commonly applied for demonstration of macromolecules in tissues have been used for the localization of target glycoproteins on spread cells. The present review examines different experimental strategies and immunocytochemical techniques that can be combined to better understand the organization of platelet receptors during surface activation. Glycoprotein IIb-IIIa (GPIIb-IIIa) was localized by immunocytochemical techniques on fixed, surface-activated platelets. The distribution of functional fibrinogen receptors expressed on GPIIb-IIIa was revealed by incubation of fixed platelets with fibrinogen-gold conjugates (Fgn/Au). The movement of receptor complexes was investigated in additional experiments in which surface-activated platelets were interacted with Fgn/Au and then fixed at different periods. The overall impression of these observations suggests that fibrinogen receptors on surface-activated platelets do not redistribute spontaneously and that particulates (gold particles), rather than fibrinogen, may trigger the movement. These results are presented in detail and their significance discussed in the light of current theory. Applications and limitations of such techniques are also discussed.

  9. Writing on Nanocrystals: Patterning Colloidal Inorganic Nanocrystal Films through Irradiation-Induced Chemical Transformations of Surface Ligands. (United States)

    Palazon, Francisco; Prato, Mirko; Manna, Liberato


    In the past couple of decades, colloidal inorganic nanocrystals (NCs) and, more specifically, semiconductor quantum dots (QDs) have emerged as crucial materials for the development of nanoscience and nanotechnology, with applications in very diverse areas such as optoelectronics and biotechnology. Films made of inorganic NCs deposited on a substrate can be patterned by e-beam lithography, altering the structure of their capping ligands and thus allowing exposed areas to remain on the substrate while non-exposed areas are redispersed in a solvent, as in a standard lift-off process. This methodology can be described as a "direct" lithography process, since the exposure is performed directly on the material of interest, in contrast with conventional lithography which uses a polymeric resist as a mask for subsequent material deposition (or etching). A few reports from the late 1990s and early 2000s used such direct lithography to fabricate electrical wires from metallic NCs. However, the poor conductivity obtained through this process hindered the widespread use of the technique. In the early 2010s, the same method was used to define fluorescent patterns on QD films, allowing for further applications in biosensing. For the past 2-3 years, direct lithography on NC films with e-beams and X-rays has gone through an important development as it has been demonstrated that it can tune further transformations on the NCs, leading to more complex patternings and opening a whole new set of possible applications. This Perspective summarizes the findings of the past 20 years on direct lithography on NC films with a focus on the latest developments on QDs from 2014 and provides different potential future outcomes of this promising technique.

  10. Fine-tuning pore size by shifting coordination sites of ligands and surface polarization of metal-organic frameworks to sharply enhance the selectivity for CO2. (United States)

    Du, Liting; Lu, Zhiyong; Zheng, Kaiyuan; Wang, Junyi; Zheng, Xin; Pan, Yi; You, Xiaozeng; Bai, Junfeng


    Based upon the (3,6)-connected metal-organic framework {Cu(L1)·2H(2)O·1.5DMF}(∞) (L1 = 5-(pyridin-4-yl)isophthalic acid) (SYSU, for Sun Yat-Sen University), iso-reticular {Cu(L2)·DMF}(∞) (L2 = 5-(pyridin-3-yl)isophthalic acid) (NJU-Bai7; NJU-Bai for Nanjing University Bai group) and {Cu(L3)·DMF·H(2)O}(∞) (L3 = 5-(pyrimidin-5-yl)isophthalic acid) (NJU-Bai8) were designed by shifting the coordination sites of ligands to fine-tune pore size and polarizing the inner surface with uncoordinated nitrogen atoms, respectively, with almost no changes in surface area or porosity. Compared with those of the prototype SYSU, both the adsorption enthalpy and selectivity of CO(2) for NJU-Bai7 and NJU-Bai8 have been greatly enhanced, which makes NJU-Bai7 and NJU-Bai8 good candidates for postcombustion CO(2) capture. Notably, the CO(2) adsorption enthalpy of NJU-Bai7 is the highest reported so far among the MOFs without any polarizing functional groups or open metal sites. Meanwhile, NJU-Bai8 exhibits high uptake of CO(2) and good CO(2)/CH(4) selectivity at high pressure, which are quite valuable characteristics in the purification of natural gases.

  11. A Hirshfeld surface analysis, crystal structure and spectroscopic properties of new Zn(II) complex with N-aminoethylpiperazine ligand (United States)

    El Glaoui, Maroua; El Glaoui, Maher; Jelsch, Christian; Aubert, Emmanuel; Lefebvre, Frédéric; Ben Nasr, Chérif


    A new organic-inorganic hybrid material, 1-amonioethylpiperazine-1, 4-diium tetrachloridozincate(II) chloride, (C6H18N3)[ZnCl4]Cl, has been synthesized and characterized by various physicochemical techniques including UV-visible absorption, Infra-Red (IR), Raman and NMR spectroscopies. The compound crystallizes in the monoclinic system and P21 space group with Z = 2 and the following unit cell dimensions: a = 7.1728 (6), b = 12.4160 (11), c = 8.0278 (7) Å, β = 97.513 (1)°, V = 708.80 (11) Å3. In this structure, the Zn2+ ion, surrounded by four chlorides, adopts a distorted tetrahedral coordination geometry. The structure of this compound consists of monomeric 1-amonioethylpiperazine-1, 4-diium trications and monomeric [ZnCl4]2- and Cl- anions. These entities are interconnected by means of hydrogen bonding contacts [Nsbnd H⋯Cl, Csbnd H⋯Cl], forming a three-dimensional network. Intermolecular interactions were investigated by Hirshfeld surfaces. More than three quarters of the interaction surface in the crystal packing is constituted by attractive and favored H⋯Cl hydrogen bonds. The 13C and 15N CP-MAS NMR spectra are discussed and the vibrational absorption bands were identified by infrared and Raman spectroscopy.

  12. Crystal structure, Hirshfeld surfaces and DNA cleavage investigation of two copper(II) complexes containing polypyridine and salicylide ligands. (United States)

    Luo, Yang-Hui; Sun, Bai-Wang


    Two copper complexes 1 [Cu2(phen)2(salicylaldehyde)2(ClO4)2] and 2 [Cu2 (2,2'-dipyridyl)2(salicylaldehyde)2(ClO4)2] have been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. These two complexes were display binuclear structure with Cu(II) ions in distorted octahedral environment but antipodal orientation of the binuclear units between them. Molecular Hirshfeld surfaces revealed that the crystal structures of 1 and 2 were supported mainly by H-H, C-H⋯π, π⋯π (C-C), and C-H⋯O intermolecular interactions. DNA cleavage experiments of complexes 1 and 2 revealed that these complexes can intercalation with DNA. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Cell surface-bound TIMP3 induces apoptosis in mesenchymal Cal78 cells through ligand-independent activation of death receptor signaling and blockade of survival pathways.

    Directory of Open Access Journals (Sweden)

    Christina Koers-Wunrau

    Full Text Available BACKGROUND: The matrix metalloproteinases (MMPs and their endogenous regulators, the tissue inhibitor of metalloproteinases (TIMPs 1-4 are responsible for the physiological remodeling of the extracellular matrix (ECM. Among all TIMPs, TIMP3 appears to play a unique role since TIMP3 is a secreted protein and, unlike the other TIMP family members, is tightly bound to the ECM. Moreover TIMP3 has been shown to be able to induce apoptotic cell death. As little is known about the underlying mechanisms, we set out to investigate the pro-apoptotic effect of TIMP3 in human mesenchymal cells. METHODOLOGY/PRINCIPAL FINDINGS: Lentiviral overexpression of TIMP3 in mesenchymal cells led to a strong dose-dependent induction of ligand-independent apoptosis as reflected by a five-fold increase in caspase 3 and 7 activity compared to control (pLenti6/V5-GW/lacZ or uninfected cells, whereas exogenous TIMP3 failed to induce apoptosis. Concordantly, increased cleavage of death substrate PARP and the caspases 3 and 7 was observed in TIMP3 overexpressing cultures. Notably, activation of caspase-8 but not caspase-9 was observed in TIMP3-overexpressing cells, indicating a death receptor-dependent mechanism. Moreover, overexpression of TIMP3 led to a further induction of apoptosis after stimulation with TNF-alpha, FasL and TRAIL. Most interestingly, TIMP3-overexpression was associated with a decrease in phosphorylation of cRaf, extracellular signal-regulated protein kinase (Erk1/2, ribosomal S6 kinase (RSK1 and Akt and serum deprivation of TIMP3-overexpressing cells resulted in a distinct enhancement of apoptosis, pointing to an impaired signaling of serum-derived survival factors. Finally, heparinase treatment of heparan sulfate proteoglycans led to the release of TIMP3 from the surface of overexpressing cells and to a significant decrease in apoptosis indicating that the binding of TIMP3 is necessary for apoptosis induction. CONCLUSION: The results demonstrate that

  14. Surface Functionalization of Magnetic Iron Oxide Nanoparticles for MRI Applications – Effect of Anchoring Group and Ligand Exchange Protocol (United States)

    Smolensky, Eric D.; Park, Hee-Yun E.; Berquó, Thelma S.; Pierre, Valérie C.


    Hydrophobic magnetite nanoparticles synthesized from thermal decomposition of iron salts must be rendered hydrophilic for their application as MRI contrast agents. This process requires refunctionalizing the surface of the nanoparticles with a hydrophilic organic coating such as polyethylene glycol. Two parameters were found to influence the magnetic behavior and relaxivity of the resulting hydrophilic iron oxide nanoparticles: the functionality of the anchoring group and the protocol followed for the functionalization. Nanoparticles coated with PEGs via a catecholate-type anchoring moiety maintain the saturation magnetization and relaxivity of the hydrophobic magnetite precursor. Other anchoring functionalities, such as phosphonate, carboxylate, and dopamine decrease the magnetization and relaxivity of the contrast agent. The protocol for functionalizing the nanoparticles also influences the magnetic behavior of the material. Nanoparticles refunctionalized according to a direct biphasic protocol exhibit higher relaxivity than those refunctionalized according to a two-step procedure which first involves stripping the nanoparticles. This research presents the first systematic study of both the binding moiety and the functionalization protocol on the relaxivity and magnetization of water-soluble coated iron oxide nanoparticles used as MRI contrast agents. PMID:21861279

  15. Crystal and geometry-optimized structure, Hirshfeld surface analysis and physicochemical studies of a new Co(II) complex with the ligand 2-amino-6-methoxypyrimidine (United States)

    Nbili, W.; Soudani, S.; Kaabi, K.; Wojtaś, M.; Ferretti, V.; Lefebvre, F.; Jelsch, C.; Ben Nasr, C.


    The crystal structure of the new complex [Co(C5H7N3O)2(H2O)4](NO3)2ṡ4H2O synthesized in aqueous solution has been determined by single crystal X-ray diffraction. The compound crystallizes in the triclinic space group P 1 bar with lattice parameters: a = 7.3056(2), b = 8.4065(2), c = 10.4724(3) Å, α = 103.9470(19), β = 105.6600(14), γ = 91.1350(18)°, V = 598.54(3) Å3 and Z = 1. The Co(II) central ion is in a slightly distorted octahedral coordination geometry formed by two nitrogen atoms of two 2-amino-6-methoxypyrimidine ligands and four oxygen atoms of coordinated water molecules. The crystal packing is stabilized by intermolecular Osbnd H⋯O, Nsbnd H⋯O and Csbnd H⋯O hydrogen bonds which link the molecules into a three-dimensional network. Intermolecular interactions were investigated by Hirshfeld surfaces. Electronic properties such as HOMO and LUMO energies were derived. The vibrational absorption bands were identified by infrared spectroscopy. The compound was characterized by thermal analysis to determine its thermal behavior with respect to temperature.

  16. A Hirshfeld surface analysis, synthesis, structure and characterization of a new Ni(II) diamagnetic complex with the bidentate ligand homopiperazine (United States)

    Klai, Kacem; Kaabi, Kamel; Jelsch, Christian; Wenger, Emmanuel; Lefebvre, Frédéric; Ben Nasr, Cherif


    A new Ni(II) complex with the bidentate ligand homopiperazine, [Ni(C5H12N2)2](CH3COO)2.4H2O, has been prepared and characterized by single crystal X-ray diffraction, elemental analysis and IR spectroscopy. The basic coordination patterns of the homopiperazine coordinated metal cations are slightly distorted square planar. In the atomic arrangement, the cationic complexes [Ni(C5H12N2)2]2+ are interconnected by the CH3COO-anions via Nsbnd H⋯O and Csbnd H⋯O hydrogen bonds to form layers parallel to the (a, b) plane. These layers are connected by hydrogen bonds generated with water molecules to build a three dimensional network. The charge density of the compound could be refined from X-ray diffraction data measured at cryogenic temperature. Intermolecular interactions were investigated by Hirshfeld surfaces. The title compound is diamagnetic as confirmed by theoretical calculations, allowing its 13C and 15N solid-state NMR spectra to be recorded. Absorption bands were identified by infrared spectroscopy. Electronic properties such as HOMO and LUMO energies were also obtained.

  17. Cell-surface trafficking and release of flt3 ligand from T lymphocytes is induced by common cytokine receptor gamma-chain signaling and inhibited by cyclosporin A. (United States)

    Chklovskaia, E; Nissen, C; Landmann, L; Rahner, C; Pfister, O; Wodnar-Filipowicz, A


    The flt3 ligand (FL) is a growth and differentiation factor for primitive hematopoietic precursors, dendritic cells, and natural killer cells. Human T lymphocytes express FL constitutively, but the cytokine is retained intracellularly within the Golgi complex. FL is mobilized from the cytoplasmic stores and its serum levels are massively increased during the period of bone marrow aplasia after stem cell transplantation (SCT). Signals that trigger the release of FL by T cells remain unknown. This study shows that interleukin (IL)-2, IL-4, IL-7, and IL-15, acting through a common receptor gamma chain (gammac), but not cytokines interacting with other receptor families, are efficient inducers of cell surface expression of membrane-bound FL (mFL) and secretion of soluble FL (sFL) by human peripheral blood T lymphocytes. The gammac-mediated signaling up-regulated FL in a T-cell receptor-independent manner. IL-2 and IL-7 stimulated both FL messenger RNA (mRNA) expression and translocation of FL protein to the cell surface. Cyclosporin A (CsA) inhibited gammac-mediated trafficking of FL at the level of transition from the Golgi to the trans-Golgi network. Accordingly, serum levels of sFL and expression of mFL by T cells of CsA-treated recipients of stem cell allografts were reduced approximately 2-fold (P <.01) compared to patients receiving autologous grafts. The conclusion is that FL expression is controlled by gammac receptor signaling and that CsA interferes with FL release by T cells. The link between gammac-dependent T-cell activation and FL expression might be important for T-cell effector functions in graft acceptance and antitumor immunity after SCT.

  18. Identification of a ligand for tumor necrosis factor receptor from Chinese herbs by combination of surface plasmon resonance biosensor and UPLC-MS. (United States)

    Cao, Yan; Li, Ying-Hua; Lv, Di-Ya; Chen, Xiao-Fei; Chen, Lang-Dong; Zhu, Zhen-Yu; Chai, Yi-Feng; Zhang, Jun-Ping


    Identification of bioactive compounds directly from complex herbal extracts is a key issue in the study of Chinese herbs. The present study describes the establishment and application of a sensitive, efficient, and convenient method based on surface plasmon resonance (SPR) biosensors for screening active ingredients targeting tumor necrosis factor receptor type 1 (TNF-R1) from Chinese herbs. Concentration-adjusted herbal extracts were subjected to SPR binding assay, and a remarkable response signal was observed in Rheum officinale extract. Then, the TNF-R1-bound ingredients were recovered, enriched, and analyzed by UPLC-QTOF/MS. As a result, physcion-8-O-β-D-monoglucoside (PMG) was identified as a bioactive compound, and the affinity constant of PMG to TNF-R1 was determined by SPR affinity analysis (K D  = 376 nM). Pharmacological assays revealed that PMG inhibited TNF-α-induced cytotoxicity and apoptosis in L929 cells via TNF-R1. Although PMG was a trace component in the chemical constituents of the R. officinale extract, it had considerable anti-inflammatory activities. It was found for the first time that PMG was a ligand for TNF receptor from herbal medicines. The proposed SPR-based screening method may prove to be an effective solution to analyzing bioactive components of Chinese herbs and other complex drug systems. Graphical abstract Scheme of the method based on SPR biosensor for screening and recovering active ingredients from complex herbal extracts and UPLC-MS for identifying them. Scheme of the method based on SPR biosensor for screening and recovering active ingredients from complex herbal extracts and UPLC-MS for identifying them.

  19. Ligand-Mediated Coating of Liposomes with Human Serum Albumin. (United States)

    Sato, Hikari; Nakhaei, Elnaz; Kawano, Takahito; Murata, Masaharu; Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki


    Coating liposome surfaces with human serum albumin (HSA) can improve the colloidal stability and prevent opsonization. HSA coating via specific binding with alkyl ligands is promising because although the ligand-mediated coating is relatively stable it can spontaneously exchange with fresh HSA. However, to achieve surface coating with HSA, multiple hydrophobic ligands must be exposed to an aqueous medium prior to binding with HSA. This presents a challenge, as hydrophobic ligands tend to be buried in the liposomal membrane. Here we present the first HSA modification of liposome surfaces via alkyl ligands. We found that a relatively short alkyl ligand, or a long alkyl ligand with a terminal carboxylate, could be exposed on the liposome surface without causing aggregation of the liposomes and these ligands could subsequently bind HSA. The resulting HSA-coated liposomes were as inert as conventional PEGylated liposomes in terms of macrophage recognition.

  20. Study of the role of the ligands coordinated at the surface of pure Wuestite nanoparticles prepared following a room temperature organometallic method: Evidence of ferromagnetic - in shell- and antiferromagnetic - in core magnetic behaviors

    Energy Technology Data Exchange (ETDEWEB)

    Glaria, Arnaud [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Kahn, Myrtil L., E-mail: [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Chaudret, Bruno [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Universite de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Lecante, Pierre; Casanove, Marie-Jose [CNRS, CEMES (Centre d' Elaboration des Materiaux et d' Etudes Structurales), 29 rue Jeanne Marvig, BP 4347, 31055 Toulouse Cedex (France); Barbara, Bernard, E-mail: [Institut Louis Neel, CNRS, 25 Av. des martyrs, BP 166, 38042 Grenoble Cedex 09 (France)


    Highlights: {yields} Pure Wuestite (Fe{sub 1-y}O) nanoparticles synthesized by organometallic chemistry. {yields} The influence of the surface ligands on the magnetic properties. {yields} Ferromagnetic core-antiferromagnetic shell magnetic nanoparticles. - Abstract: Wuestite particles (Fe{sub 1-y}O) are synthesized using controlled hydrolysis at room temperature of [Fe(N(SiMe{sub 3}){sub 2}){sub 2}] and stabilized by amine ligands. This method leads to 5 nm pure wuestite particles. This phase is clearly identified by transmission electron microscopy and wide angle X-ray scattering. Distortion in the crystallographic structure has been demonstrated. Particular attention is paid on the Fe(III) formation. Moreover, a combination of Moessbauer spectroscopy and SQuID measurements, revealed that the particles are composed of an antiferromagnetic core surrounded by a ferromagnetic shell. According to the Neel theory, the Fe(III) and Fe(II) ions present in the particles are ferromagnetically coupled and the proportion of Fe(III) ions varies from 3.9 to 7.1% as a function of the amine ligand.

  1. The structure and function of the urokinase receptor, a membrane protein governing plasminogen activation on the cell surface

    DEFF Research Database (Denmark)

    Behrendt, N; Rønne, E; Danø, K


    PA receptor, uPAR, is a cell-surface protein which plays an important role in the localization and regulation of these processes. In the present article a number of established conclusions concerning the structure and function of uPAR are presented, and in addition various models are discussed which might...... with the continuous identification of inhibitory reagents, this knowledge should open the possibility to interfere with the resulting, degradative events....

  2. Interactive governance

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob; Peters, B. Guy

    Governance has become one of the most commonly used concepts in contemporary political science. It is, however, often used to mean a variety of different things. This book helps to clarify this conceptual muddle by concentrating on one variety of governance-interactive governance. The authors argue...... that although the state may remain important for many aspects of governing, interactions between state and society represent an important, and perhaps increasingly important, dimension of governance. These interactions may be with social actors such as networks, with market actors or with other governments......, but all these forms represent means of governing involving mixtures of state action with the actions of other entities.This book explores thoroughly this meaning of governance, and links it to broader questions of governance. In the process of explicating this dimension of governance the authors also...

  3. Characterization of Ligand-Induced Endocytosis of EGF-Receptors

    National Research Council Canada - National Science Library

    Schmid, Sandra


    Under the auspices of this training Fellowship (May 9, 1994-November 9, 1997) I have undertaken studies on the molecular mechanisms that govern ligand-induced endocytosis of epidermal growth factor receptors (EGFR...

  4. Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments (United States)

    Richter, David; Moraga, Ignacio; Winkelmann, Hauke; Birkholz, Oliver; Wilmes, Stephan; Schulte, Markos; Kraich, Michael; Kenneweg, Hella; Beutel, Oliver; Selenschik, Philipp; Paterok, Dirk; Gavutis, Martynas; Schmidt, Thomas; Garcia, K. Christopher; Müller, Thomas D.; Piehler, Jacob


    The spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand-receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization. Single molecule localization microscopy at physiological cell surface expression levels, however, reveals efficient ligand-induced receptor dimerization by all ligands, largely independent of receptor binding affinities, in line with the similar STAT6 activation potencies observed for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic trapping of receptor dimers in actin-dependent microcompartments sustains robust receptor dimerization and signalling.

  5. Ligand Interface Chemistry of Lead Chalcogenide Nanocrystals (United States)

    Liu, Kun; Bealing, Clive; Hennig, Richard; Hennig Group Team


    Lead chalcogenides nanocrystals (NCs) have shown promise in photovoltaic applications. Surface chemistry is one of the most important, yet least understood aspects of NC synthesis and functionalization controlling their properties. For example, an incomplete surface passivation could create trap states that enhance undesired exciton recombination. Clever choices of ligands ensure that neighboring NCs are electronically coupled while maintaining their quantum size effects. These two barriers limiting performance of NC solar cells illustrate the importance of fundamental studies for the interaction between ligands and NC surfaces. We use density functional theory to determine the binding sites and energies of ligands commonly used in NC synthesis and functionalization. Specifically we study amine-, carboxyl-, and thiol-ligands on different PbSe and PbS surfaces. For methylamine ligands we find a similar binding energy on the (100) and (111) facet while carboxylic acid ligands strongly prefer the (111) facet leading to different effective NC shapes. This work was supported in part by Award No. KUS-C1-018-02, made by King Abdullah University of Science and Technology (KAUST) and by the Energy Materials Center at Cornell (EMC2) funded by the U.S. Department of Energy under Award Number DE-SC0001086

  6. Interactive Governance

    DEFF Research Database (Denmark)

    Bang, Henrik


    Governance analysis has exploded in recent years, and it has become nearly impossible to tell what difference the concept and practice of governance makes from those of government and state. In addition governance analysis has been placed more and more in the shadow of the new institutionalisms and...... and growth. However, interactive governance is not a property or effect of institutions; nor does it apply solely to those individuals who seek success above everything else. It is connective more than individualistic or collectivistic in nature; and it manifests a governability capacity which...

  7. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

    Andersen, P S; Menné, C; Mariuzza, R A


    To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affinity...... determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

  8. A Candida albicans regulator of disseminated infection operates primarily as a repressor and governs cell surface remodeling. (United States)

    Böhm, Lena; Muralidhara, Prathibha; Pérez, J Christian


    Virulence traits are often controlled by transcription regulators, i.e. sequence-specific DNA-binding proteins. The regulators that sustain microbial proliferation in the host typically work by promoting the expression of the genes that mediate such traits. Here, we report a singular example in the human fungal pathogen Candida albicans in which a transcription regulator functions by repressing the expression of virulence genes, yet its overall role is to promote virulence. We explain this apparent paradox by establishing that a major function of this protein, Zcf21p, is to set a default state of low expression of multiple cell wall components which include virulence determinants. These components comprise GPI-anchored proteins, adhesins and enzymes that synthesize cell wall sugar decorations. Deletion or overexpression of ZCF21 results in cell wall structure modifications that influence recognition and elimination of the fungus by macrophages. By leveling off the expression of adhesins, ZCF21 also prevents C. albicans self-aggregation. Balancing the expression of cell wall components - virulence determinants included - is, therefore, critical for C. albicans to assemble a cell surface configuration that is suitable to colonize mammalian tissues and evade immune surveillance. © 2015 John Wiley & Sons Ltd.

  9. Electronic Government

    DEFF Research Database (Denmark)

    Wimmer, Maria A.; Traunmüller, Roland; Grönlund, Åke

    This book constitutes the refereed proceedings of the 4th International Conference on Electronic Government, EGOV 2005, held in Copenhagen, Denmark, in August 2005. The 30 revised papers presented were carefully reviewed and selected from numerous submissions, and assess the state-of-the-art in e-government/e-governance...

  10. A conserved WW domain-like motif regulates invariant chain-dependent cell-surface transport of the NKG2D ligand ULBP2

    DEFF Research Database (Denmark)

    Uhlenbrock, Franziska Katharina; van Andel, Esther; Andresen, Lars


    surface expression of wt ULBP2 while Trp-mutants could not be expressed, proposing that this Trp-motif is required for an Ii-dependent cell-surface transport of ULBP2. Aberrant soluble ULBP2 is immunosuppressive. Thus, targeting a distinct protein module on the ULBP2 sequence could counteract...

  11. Ligand-modified metal clusters for gas separation and purification (United States)

    Okrut, Alexander; Ouyang, Xiaoying; Runnebaum, Ron; Gates, Bruce C.; Katz, Alexander


    Provided is an organic ligand-bound metal surface that selects one gaseous species over another. The species can be closely sized molecular species having less than 1 Angstrom difference in kinetic diameter. In one embodiment, the species comprise carbon monoxide and ethylene. Such organic ligand-bound metal surfaces can be successfully used in gas phase separations or purifications, sensing, and in catalysis.

  12. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Menard, Claude


    Plural governance is a form of governance where a firm both makes and buys similar goods or services. Despite a widespread use of plural governance there are no transaction cost models of how plural governance affects performance. This paper reviews the literature about plural forms and proposes...... a model relating transaction cost and resource-based variables to the cost of the plural form. The model is then used to analyze when the plural form is efficient compared to alternative governance structures. We also use the model to discuss the strength of three plural form synergies....

  13. Program governance

    CERN Document Server

    Khan, Muhammad Ehsan


    FOUNDATION OF GOVERNANCEGovernanceDefining GovernanceGovernance at Multiple LevelsSummaryReferencesTransaction Cost EconomicsTransactions-Core Elements and Attributes     Behavioral Assumptions     Governance Structure AttributesHazards of Concern     Incomplete Contracting     Bilateral Dependency and Fundamental Transformation     Adaptation or MaladaptationLinking Governance, Governance Structures, and ContractsThe Impact of Asset Specificity and Behavioral Assumptions on ContractsAp

  14. Intramolecular Electron Transfer at Metal Surfaces. I. Relative Energetics of Some Corresponding Outer- and Inner-Sphere Pathways Involving Halide and Pseudohalide Bridging Ligands. (United States)


    product, whose reoxidation is thermodynamically unfavorable except 21 at extremely positive electrode potentials. The values of k between replicate...5Br, and Co(NH3 )5 NCS at platinum and gold surfaces in contact with •.4 * . . . . . 6 0.1 M NaClO4 + 5 mM HClO4 ; Table II gives corresponding data...alterations in AG* The latter may arise from variations in the "surface thermodynamic " term 44 13 11- RT(lnK - InKs) as well as in AG* . If the surface binding

  15. Receptor sequestration in response to β-arrestin-2 phosphorylation by ERK1/2 governs steady-state levels of GPCR cell-surface expression. (United States)

    Paradis, Justine S; Ly, Stevenson; Blondel-Tepaz, Élodie; Galan, Jacob A; Beautrait, Alexandre; Scott, Mark G H; Enslen, Hervé; Marullo, Stefano; Roux, Philippe P; Bouvier, Michel


    MAPKs are activated in response to G protein-coupled receptor (GPCR) stimulation and play essential roles in regulating cellular processes downstream of these receptors. However, very little is known about the reciprocal effect of MAPK activation on GPCRs. To investigate possible crosstalk between the MAPK and GPCRs, we assessed the effect of ERK1/2 on the activity of several GPCR family members. We found that ERK1/2 activation leads to a reduction in the steady-state cell-surface expression of many GPCRs because of their intracellular sequestration. This subcellular redistribution resulted in a global dampening of cell responsiveness, as illustrated by reduced ligand-mediated G-protein activation and second-messenger generation as well as blunted GPCR kinases and β-arrestin recruitment. This ERK1/2-mediated regulatory process was observed for GPCRs that can interact with β-arrestins, such as type-2 vasopressin, type-1 angiotensin, and CXC type-4 chemokine receptors, but not for the prostaglandin F receptor that cannot interact with β-arrestin, implicating this scaffolding protein in the receptor's subcellular redistribution. Complementation experiments in mouse embryonic fibroblasts lacking β-arrestins combined with in vitro kinase assays revealed that β-arrestin-2 phosphorylation on Ser14 and Thr276 is essential for the ERK1/2-promoted GPCR sequestration. This previously unidentified regulatory mechanism was observed after constitutive activation as well as after receptor tyrosine kinase- or GPCR-mediated activation of ERK1/2, suggesting that it is a central node in the tonic regulation of cell responsiveness to GPCR stimulation, acting both as an effector and a negative regulator.

  16. Synthesis and crystal structure of copper (II) uracil ternary polymeric complex with 1,10-phenanthroline along with the Hirshfeld surface analysis of the metal binding sites for the uracil ligand (United States)

    Patil, Yogesh Prakash; Nethaji, Munirathinam


    The study of models for "metal-enzyme-substrate" interaction has been a proactive area of research owing to its biological and pharmacological importance. In this regard the ternary copper uracil complex with 1,10-phenanthroline represents metal-enzyme-substrate system for DNA binding enzymes. The synthesis of the complex, followed by slow evaporation of the reaction mixture forms two concomitant solvatomorph crystals viz., {[Cu(phen)(μ-ura)(H2O)]n·H2O (1a)} and {[Cu(phen)(μ-ura)(H2O)]n·CH3OH (1b)}. Both complexes are structurally characterized, while elemental analysis, IR and EPR spectra were recorded for 1b (major product). In both complexes, uracil coordinates uniquely via N1 and N3 nitrogen atom acting as a bidentate bridging ligand forming a 1-D polymer. The two solvatomorphs were quantitatively analyzed for the differences with the aid of Hirshfeld surface analysis.

  17. Copper(II) and zinc(II) ion binding properties of a MAP type branched ligand with histidines as surface functionalities. (United States)

    Kolozsi, András; Vosekalna, Ilze; Martinek, Tamás; Larsen, Erik; Gyurcsik, Béla


    A novel branched peptide type ligand consisting of three lysines as branching units and four histidines as functional groups has been designed and prepared by solid phase peptide synthesis. The N-terminal histidines offer eight primary protonation/metal ion binding sites: four amino and four imidazole groups, capable of binding up to two metal ions. We examined the protonation equilibria, and the complex formation processes with copper(II) and zinc(II) ions in c(M):c(L) = 1:1 and 2:1 initial concentration ratio in aqueous solutions. The composition, speciation and the solution structure of the complexes have been determined by combined pH-potentiometric titrations, visible absorption, circular dichroism and NMR spectroscopy. In the case of both metal ions, mono- and dimetallic complexes formed with bis-histamine type coordination as the main species. While above pH 8 the precipitation of a neutral complex was observed for both metal ions, in the copper(II) containing systems it dissolved in alkaline solutions (pH > 11.0). The resulting complex in an equimolar system displays deprotonated amide-nitrogen coordination, with fused five-membered chelate rings around the metal ion in [CuLH(-3)](-). At the same time, only one copper(II) is able to coordinate in the same manner in the [Cu(2)LH(-5)](-) species. The second metal ion is probably surrounded by two amide nitrogens and two others either from amino or imidazole donor groups.

  18. Role of surface passivating ligand and growth temperature on the size quantization effects of colloidal hybrid (MEH-PPV/P3HT:PbSe) nanocomposites (United States)

    Sharma, Shailesh N.; Mehta, Aarti; Kumar, Umesh; Chand, S.


    In this work, it has been demonstrated that a systematic combination of the reaction and growth conditions allows the possibility to produce high quality PbSe nanocrystals over a broad range of diameters with narrow size distributions without resorting to any size selective precipitation techniques. Effect of capping agents and critical growth parameters such as injection and growth temperature on the morphology of PbSe nanocrystallites is analyzed and discussed in terms of Efros'effective mass approximation theory and Wang's hyperbolic band model respectively. It is found that a hyperbolic Wang's band model is sufficiently accurate to explain the size quantization effects of PbSe nanocrystals. The capping agent/ligand (tri-n-octylphosphine and oleic acid mixture) helps to control the grain growth of the nanocrystals during its formation and increases the dispersibility of the nanocrystals in conducting polymer matrices viz. poly[2-methoxy, 5-(2-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) and poly(3-hexylthiophene) (P3HT) for its application in photovoltaics.

  19. Ligand mediated evolution of size dependent magnetism in cobalt nanoclusters. (United States)

    Hartmann, Michael J; Millstone, Jill E; Häkkinen, Hannu


    We use density functional theory to model the impact of a ligand shell on the magnetic properties of CoN (15 ≤ N ≤ 55) nanoclusters. We study three different ligand shells on each nanocluster core size, each known to have different electronic interactions with the surface: pure Cl ligand shells (X-type), pure PH3 ligand shells (L-type), and two component ligand shells with mixtures of Cl and PH3 ligands. The simulations show that the identity, arrangement, and total coverage of the ligand shell controls the distribution of local magnetic moments across the CoN core. On the surface of an unpassivated CoN nanocluster, the Co-Co coordination number (CN) is known to determine the local magnetic moments. Upon the introduction of a ligand, the Co-Co CN remains important, however the nature of the metal-ligand bond changes the extent to which increasing Co-Co CN quenches magnetism. Further, we identify an additional and significant long-range impact on local magnetic moments (LMM) from the PH3 ligand shells. Thus, we establish important design principles of magnetic nanoclusters, where ligand shell chemistry mediates the distribution of LMMs across a CoNLM nanocluster, allowing a route to rational design of specific magnetic properties.

  20. Electronic Government

    DEFF Research Database (Denmark)

    Wimmer, Maria A.; Traunmüller, Roland; Grönlund, Åke

    This book constitutes the refereed proceedings of the 4th International Conference on Electronic Government, EGOV 2005, held in Copenhagen, Denmark, in August 2005. The 30 revised papers presented were carefully reviewed and selected from numerous submissions, and assess the state-of-the-art in e......-government/e-governance and provide guidance for research, development and application of this emerging field. The papers are arranged in topical sections on challenges, performance, strategy, knowledge, and technology....

  1. Surface chemical modification of nanocrystals (United States)

    Helms, Brett Anthony; Milliron, Delia Jane; Rosen, Evelyn Louise; Buonsanti, Raffaella; Llordes, Anna


    Nanocrystals comprising organic ligands at surfaces of the plurality of nanocrystals are provided. The organic ligands are removed from the surfaces of the nanocrystals using a solution comprising a trialkyloxonium salt in a polar aprotic solvent. The removal of the organic ligands causes the nanocrystals to become naked nanocrystals with cationic surfaces.

  2. Controlling Signal Transduction with Synthetic Ligands (United States)

    Spencer, David M.; Wandless, Thomas J.; Schreiber, Stuart L.; Crabtree, Gerald R.


    Dimerization and oligomerization are general biological control mechanisms contributing to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. Cell permeable, synthetic ligands were devised that can be used to control the intracellular oligomerization of specific proteins. To demonstrate their utility, these ligands were used to reduce intracellular oligomerization of cell surface receptors that lacked their transmembrane and extracellular regions but contained intracellular signaling domains. Addition of these ligands to cells in culture resulted in signal transmission and specific target gene activation. Monomeric forms of the ligands blocked the pathway. This method of ligandregulated activation and termination of signaling pathways has the potential to be applied wherever precise control of a signal transduction pathway is desired.

  3. Unraveling the core-shell structure of ligand-capped Sn/SnOx nanoparticles by surface-enhanced nuclear magnetic resonance, Mössbauer, and X-ray absorption spectroscopies. (United States)

    Protesescu, Loredana; Rossini, Aaron J; Kriegner, Dominik; Valla, Maxence; de Kergommeaux, Antoine; Walter, Marc; Kravchyk, Kostiantyn V; Nachtegaal, Maarten; Stangl, Julian; Malaman, Bernard; Reiss, Peter; Lesage, Anne; Emsley, Lyndon; Copéret, Christophe; Kovalenko, Maksym V


    A particularly difficult challenge in the chemistry of nanomaterials is the detailed structural and chemical analysis of multicomponent nano-objects. This is especially true for the determination of spatially resolved information. In this study, we demonstrate that dynamic nuclear polarization surface-enhanced solid-state NMR spectroscopy (DNP-SENS), which provides selective and enhanced NMR signal collection from the (near) surface regions of a sample, can be used to resolve the core-shell structure of a nanoparticle. Li-ion anode materials, monodisperse 10-20 nm large tin nanoparticles covered with a ∼3 nm thick layer of native oxides, were used in this case study. DNP-SENS selectively enhanced the weak 119Sn NMR signal of the amorphous surface SnO2 layer. Mössbauer and X-ray absorption spectroscopies identified a subsurface SnO phase and quantified the atomic fractions of both oxides. Finally, temperature-dependent X-ray diffraction measurements were used to probe the metallic β-Sn core and indicated that even after 8 months of storage at 255 K there are no signs of conversion of the metallic β-Sn core into a brittle semiconducting α-phase, a phase transition which normally occurs in bulk tin at 286 K (13 °C). Taken together, these results indicate that Sn/SnOx nanoparticles have core/shell1/shell2 structure of Sn/SnO/SnO2 phases. The study suggests that DNP-SENS experiments can be carried on many types of uniform colloidal nanomaterials containing NMR-active nuclei, in the presence of either hydrophilic (ion-capped surfaces) or hydrophobic (capping ligands with long hydrocarbon chains) surface functionalities.

  4. Corporate Governance


    International Finance Corporation; UN Global Compact


    Corporate citizenship - a commitment to ethical behavior in business strategy, operations, and culture - has been on the periphery of corporate governance and board leadership, linked mainly to corporate reputation. However, in today’s globalized and interconnected world, investors, creditors, and other stakeholders have come to recognize that environmental, social, and governance responsi...

  5. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

    Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)


    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  6. Chlorodiethylaluminum supported on silica: A dinuclear aluminum surface species with bridging μ2-Cl-ligand as a highly efficient co-catalyst for the Ni-catalyzed dimerization of ethene

    KAUST Repository

    Kermagoret, Anthony


    Silica-supported chloro alkyl aluminum co-catalysts (DEAC@support) were prepared via Surface Organometallic Chemistry by contacting diethylaluminum chloride (DEAC) and high specific surface silica materials, i.e. SBA-15, MCM-41, and Aerosil SiO2. Such systems efficiently activate NiCl 2(PBu3)2 for catalytic ethene dimerization, with turnover frequency (TOF) reaching up to 498,000 molC2H4/ (molNi h) for DEAC@MCM-41. A detailed analysis of the DEAC@SBA-15 co-catalyst structure by solid-state aluminum-27 NMR at high-field (17.6 T and 20.0 T) and ultrafast spinning rates allows to detect six sites, characterized by a distribution of quadrupolar interaction principal values CQ and isotropic chemical shifts δiso. Identification of the corresponding Al-grafted structures was possible by comparison of the experimental NMR signatures with these calculated by DFT on a wide range of models for the aluminum species (mono- versus di-nuclear, mono- versus bis-grafted with bridging Cl or ethyl). Most of the sites were identified as dinuclear species with retention of the structure of DEAC, namely with the presence of μ2-Cl-ligands between two aluminum, and this probably explains the high catalytic performance of this silica-supported co-catalysts. © 2014 Elsevier Inc. All rights reserved.

  7. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

    Hay, B. [Pacific Northwest Lab., Richland, WA (United States)


    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used tin applications for the cost-effective removal of specific radionuclides from nuclear waste streams.

  8. Government Organizations

    DEFF Research Database (Denmark)

    Krause Hansen, Hans; Salskov-Iversen, Dorte


    This entry is concerned with demonstrating the increasingly important interface between government organization and communication. Government organization can be approached in terms of state centrism, where the emphasis is on government organization understood as state authority and power......, with clearly defined boundaries between the public and private; and in terms of polycentrism, where power and authority are seen as dispersed among state and nonstate organizations, including business and civil society organizations. Globalization and new media technologies imply changes in the relationship...... between power, communication, and organizational forms, and suggest the usefulness of viewing government organization in terms of polycentrism, highlighting communication and organizing processes in a wider perspective. The entry focuses particularly on two major strands of literature: deliberative...

  9. Corporate Governance


    Mostepaniuk, Alla


    The purpose of this study is to analyze and understand the recently introduced form of managementof a company limited by shares. The Law no. 441/2006, which fundamentally amended Company Law,created this form of controlling the company, the corporate governance, but the legislation does not explicitlydefine what it wants to achieve through this instrument. This topic is recent in research as the theme ofgerman-roman commercial law systems (in French corporate governance system was introduced ...

  10. Organizational governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Klein, Peter G.

    This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory, and the ......This chapter reviews and discusses rational-choice approaches to organizational governance. These approaches are found primarily in organizational economics (virtually no rational-choice organizational sociology exists), particularly in transaction cost economics, principal-agent theory...

  11. Dengue virus induces expression of CXC chemokine ligand 10/IFN-gamma-inducible protein 10, which competitively inhibits viral binding to cell surface heparan sulfate. (United States)

    Chen, Jia-Perng; Lu, Hsin-Lin; Lai, Szu-Liang; Campanella, Gabriele S; Sung, Jui-Ming; Lu, Mei-Yi; Wu-Hsieh, Betty A; Lin, Yi-Ling; Lane, Thomas E; Luster, Andrew D; Liao, Fang


    Dengue virus is an arthropod-borne flavivirus that causes a mild febrile illness, dengue fever, or a potentially fatal syndrome, dengue hemorrhagic fever/dengue shock syndrome. Chemokines primarily orchestrate leukocyte recruitment to the areas of viral infection, which makes them critical mediators of immune and inflammatory responses. In the present study, we investigated the induction and function of chemokines in mice early after infection with dengue virus in vivo. We found that CXCL10/IFN-gamma-inducible protein 10 (IP-10) expression was rapidly and transiently induced in liver following infection. The expressed CXCL10/IP-10 likely mediates the recruitment of activated NK cells, given that anti-CXCL10/IP-10-treated mice showed diminished NK cell infiltration and reduced hepatic expression of effector molecules in activated NK cells after dengue virus infection. Of particular interest, we found that CXCL10/IP-10 also was able to inhibit viral binding to target cells in vitro. Further investigation revealed that various CXCL10/IP-10 mutants, in which the residues that mediate the interaction between the chemokine and heparan sulfate were substituted, failed to exert the inhibitory effect on dengue binding, which suggests that CXCL10/IP-10 competes with dengue virus for binding to heparan sulfate on the cell surface. Moreover, subsequent plaque assays showed that this inhibition of dengue binding blocked viral uptake and replication. The inhibitory effect of CXCL10/IP-10 on the binding of dengue virus to cells may represent a novel contribution of this chemokine to the host defense against viral infection.

  12. The extracellular matrix, p53 and estrogen compete to regulate cell-surface Fas/Apo-1 suicide receptor expression in proliferating embryonic cerebral cortical precursors, and reciprocally, Fas-ligand modifies estrogen control of cell-cycle proteins

    Directory of Open Access Journals (Sweden)

    Newman Joseph M


    Full Text Available Abstract Background Apoptosis is important for normal cerebral cortical development. We previously showed that the Fas suicide receptor was expressed within the developing cerebral cortex, and that in vitro Fas activation resulted in caspase-dependent death. Alterations in cell-surface Fas expression may significantly influence cortical development. Therefore, in the following studies, we sought to identify developmentally relevant cell biological processes that regulate cell-surface Fas expression and reciprocal consequences of Fas receptor activation. Results Flow-cytometric analyses identified two distinct neural sub-populations that expressed Fas on their cell surface at high (FasHi or moderate (FasMod levels. The anti-apoptotic protein FLIP further delineated a subset of Fas-expressing cells with potential apoptosis-resistance. FasMod precursors were mainly in G0, while FasHi precursors were largely apoptotic. However, birth-date analysis indicated that neuroblasts express the highest levels of cell-surface Fas at the end of S-phase, or after their final round of mitosis, suggesting that Fas expression is induced at cell cycle checkpoints or during interkinetic nuclear movements. FasHi expression was associated with loss of cell-matrix adhesion and anoikis. Activation of the transcription factor p53 was associated with induction of Fas expression, while the gonadal hormone estrogen antagonistically suppressed cell-surface Fas expression. Estrogen also induced entry into S-phase and decreased the number of Fas-expressing neuroblasts that were apoptotic. Concurrent exposure to estrogen and to soluble Fas-ligand (sFasL suppressed p21/waf-1 and PCNA. In contrast, estrogen and sFasL, individually and together, induced cyclin-A expression, suggesting activation of compensatory survival mechanisms. Conclusions Embryonic cortical neuronal precursors are intrinsically heterogeneous with respect to Fas suicide-sensitivity. Competing intrinsic (p53

  13. Stakeholder Governance

    DEFF Research Database (Denmark)

    Flak, Leif Skiftenes; Rose, Jeremy


    The e-government field, like most young fields, lacks a strong body of well-developed theory. One strategy for coping with theoretical immaturity is to import and adapt theories from other, more mature fields. This study reviews Stakeholder Theory (ST) and investigates its potential in relation...... to e-Government. Originally a management theory, stakeholder theory advocates addressing the concerns of all stakeholders in a firm, as opposed to concentration on the interests of senior managers and stockholders. Apart from the original profit focus, there is no serious conceptual mismatch between...... stakeholder theory and government’s objective of providing policy and services for citizens and organizations – society’s stakeholders. Potential problems with adapting a management theory to a government setting are discussed. The paper further discusses how information technology impacts a stakeholder model...

  14. Increased accuracy of ligand sensing by receptor internalization (United States)

    Aquino, Gerardo; Endres, Robert G.


    Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as the overcounting of the same ligand molecules is reduced. Here we show, by extending simple ligand-receptor models to out-of-equilibrium thermodynamics, that internalization increases the accuracy with which cells can measure ligand concentrations in the external environment. Comparison with experimental rates of real receptors demonstrates that our model has indeed biological significance.

  15. Is governance, gross domestic product, inequality, population size or country surface area associated with coverage and equity of health interventions? Ecological analyses of cross-sectional surveys from 80 countries. (United States)

    Wehrmeister, Fernando C; da Silva, Inácio Crochemore M; Barros, Aluisio J D; Victora, Cesar G


    To assess associations between national characteristics, including governance indicators, with a proxy for universal health coverage in reproductive, maternal, newborn and child health (RMNCH). Ecological analysis based on data from national standardised cross-sectional surveys. Low-income and middle-income countries with a Demographic and Health Survey or a Multiple Indicator Cluster Survey since 2005. 1 246 710 mothers and 2 129 212 children from 80 national surveys. Gross domestic product (GDP), country surface area, population, Gini index and six governance indicators (control of corruption, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and voice and accountability). Levels and inequality in the composite coverage index (CCI), a weighted average of eight RMNCH interventions. Relative and absolute inequalities were measured through the concentration index (CIX) and slope index of inequality (SII) for CCI, respectively. The average values of CCI (70.5% (SD=13.3)), CIX (5.3 (SD=5.1)) and mean slope index (19.8 (SD=14.7)) were calculated. In the unadjusted analysis, all governance variables and GDP were positively associated with the CCI and negatively with inequalities. Country surface showed inverse associations with both inequality indices. After adjustment, among the governance indicators, only political stability and absence of violence was directly related to CCI (β=6.3; 95% CI 3.6 to 9.1; pgovernance indicators were found in the poorest wealth quintile. Similar patterns were observed for GDP. Country surface area was inversely related to inequalities on CCI. Levels and equity in RMNCH interventions are positively associated with political stability and absence of violence, and with GDP, and inversely associated with country surface area.

  16. Corporate Governance

    International Development Research Centre (IDRC) Digital Library (Canada)

    the developing world, adhere to good governance practices, and uphold the public interest. The IDRC Act specifies that at least 11 of the Governors must have experience in international development or a background in the natural or social sciences, or in tech- nology. These stipulations are reflected in a profile of skills.

  17. Electronic Government

    DEFF Research Database (Denmark)

    Wimmer, Maria A.; Traunmüller, Roland; Grönlund, Åke

    This book constitutes the refereed proceedings of the 4th International Conference on Electronic Government, EGOV 2005, held in Copenhagen, Denmark, in August 2005. The 30 revised papers presented were carefully reviewed and selected from numerous submissions, and assess the state-of-the-art in e...

  18. Amino acid ionic liquids as chiral ligands in ligand-exchange chiral separations. (United States)

    Liu, Qian; Wu, Kangkang; Tang, Fei; Yao, Lihua; Yang, Fei; Nie, Zhou; Yao, Shouzhuo


    Recently, amino acid ionic liquids (AAILs) have attracted much research interest. In this paper, we present the first application of AAILs in chiral separation based on the chiral ligand exchange principle. By using 1-alkyl-3-methylimidazolium L-proline (L-Pro) as a chiral ligand coordinated with copper(II), four pairs of underivatized amino acid enantiomers-dl-phenylalanine (dl-Phe), dl-histidine (dl-His), dl-tryptophane (dl-Trp), and dl-tyrosine (dl-Tyr)-were successfully separated in two major chiral separation techniques, HPLC and capillary electrophoresis (CE), with higher enantioselectivity than conventionally used amino acid ligands (resolution (R(s))=3.26-10.81 for HPLC; R(s)=1.34-4.27 for CE). Interestingly, increasing the alkyl chain length of the AAIL cation remarkably enhanced the enantioselectivity. It was inferred that the alkylmethylimidazolium cations and L-Pro form ion pairs on the surface of the stationary phase or on the inner surface of the capillary. The ternary copper complexes with L-Pro are consequently attached to the support surface, thus inducing an ion-exchange type of retention for the dl-enantiomers. Therefore, the AAIL cation plays an essential role in the separation. This work demonstrates that AAILs are good alternatives to conventional amino acid ligands for ligand-exchange-based chiral separation. It also reveals the tremendous application potential of this new type of task-specific ILs.

  19. A Langmuir study of novel Schiff Base ligand for ion sensor application

    African Journals Online (AJOL)

    Two novel Schiff Base ligands are used in this work. These amphiphilic ligands were being chosen because of the suitability in forming Langmuir film by using Langmuir-Blodgett (LB) technique. Characterizations of these ligands were carried out through LB technique to obtain the surface pressure-mean molecular area ...

  20. Mobilizing Government

    DEFF Research Database (Denmark)

    Wang, Cancan; Medaglia, Rony; Jensen, Tina Blegind


    The nature of inter-organizational collaboration between government and other stakeholders is rapidly changing with the introduction of open social media (OSM) platforms. Characterized by a high degree of informality as well as a blurred personal/professional nature, OSM can potentially introduce...... in China. Drawing on the framework of the theory of temporary organizations, we analyze data from interviews and participant observations to single out the characteristics of inter-organizational collaboration afforded by OSM. The findings outline the features of collaboration practices afforded by OSM...... changes and tensions in the well-established routines of the public sector. This paper aims at shedding light on such changes, presenting findings from a study on the use of an OSM platform, WeChat, in an interorganizational collaboration project between government, university, and industry stakeholders...

  1. Sterically demanding iminopyridine ligands

    NARCIS (Netherlands)

    Irrgang, Torsten; Keller, Sandra; Maisel, Heidi; Kretschmer, Winfried; Kempe, Rhett

    Two sterically demanding iminopyridine ligands, (2,6-diisopropylphenyl)[6-(2,4,6-triisopropylphenyl)pyridin-2-ylmeth- ylene]amine and (2,6-diisopropylphenyl)]6-(2,6-dimethylphenyl)pyridin-2-ylmethylene]amine, were prepared by a two-step process: first, condensation of 6-bromopyridine-2-carbaldehyde

  2. Plural Governance

    DEFF Research Database (Denmark)

    Mols, Niels Peter; Hansen, Jesper Rosenberg; Villadsen, Anders Ryom

    We suggest that both making and buying the same product or service has several effects on market performance. A model is developed and tested by use of 170 answers gathered from the Danish municipalities. The results support the hypotheses that both making and buying: (1) moderates the negative r...... on how the plurality is measured. The results indicate that internal production may facilitate effective governance of the relationships with suppliers. Implications for research on firm boundaries and for practice are also discussed....

  3. School governance


    Monique Turkenburg


    Original title: De school bestuurd. Until now, little was known about school boards in primary and secondary schools. This study presents a national overview of the way in which these school boards interpret and fulfil their role. More and different demands have been placed on school boards in recent years, for example with regard to transparency of governance and public accountability. In a national survey of school boards, the Netherlands Institute for Social Research/SCP explored what they...

  4. Metal-ligand cooperation at tethered pi-ligands

    NARCIS (Netherlands)

    Verhoeven, Dide G. A.; Moret, Marc-Etienne


    Metal–ligand cooperativity in homogeneous catalysis is emerging as a powerful tool for the design of efficient transition-metal catalysts. This perspective highlights recent advances in the use of neutral π-coordinating ligands, tethered to a transition-metal center by other donor ligands, as

  5. Ligand Exchange Kinetics of Environmentally Relevant Metals

    Energy Technology Data Exchange (ETDEWEB)

    Panasci, Adele Frances [Univ. of California, Davis, CA (United States)


    The interactions of ground water with minerals and contaminants are of broad interest for geochemists but are not well understood. Experiments on the molecular scale can determine reaction parameters (i.e. rates of ligand exchange, activation entropy, activation entropy, and activation volume) that can be used in computations to gain insight into reactions that occur in natural groundwaters. Experiments to determine the rate of isotopic ligand exchange for three environmentally relevant metals, rhodium (Rh), iron (Fe), and neptunium (Np), are described. Many environmental transformations of metals (e.g. reduction) in soil occur at trivalent centers, Fe(III) in particular. Contaminant ions absorb to mineral surfaces via ligand exchange, and the reversal of this reaction can be dangerous, releasing contaminants into the environment. Ferric iron is difficult to study spectroscopically because most of its complexes are paramagnetic and are generally reactive toward ligand exchange; therefore, Rh(III), which is diamagnetic and less reactive, was used to study substitution reactions that are analogous to those that occur on mineral oxide surfaces. Studies on both Np(V) and Np(VI) are important in their own right, as 237Np is a radioactive transuranic element with a half-life of 2 million years.

  6. Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition.

    Directory of Open Access Journals (Sweden)

    Matthew W Parker

    Full Text Available Neuropilin (Nrp receptors function as essential cell surface receptors for the Vascular Endothelial Growth Factor (VEGF family of proangiogenic cytokines and the semaphorin 3 (Sema3 family of axon guidance molecules. There are two Nrp homologues, Nrp1 and Nrp2, which bind to both overlapping and distinct members of the VEGF and Sema3 family of molecules. Nrp1 specifically binds the VEGF-A(164/5 isoform, which is essential for developmental angiogenesis. We demonstrate that VEGF-A specific binding is governed by Nrp1 residues in the b1 coagulation factor domain surrounding the invariant Nrp C-terminal arginine binding pocket. Further, we show that Sema3F does not display the Nrp-specific binding to the b1 domain seen with VEGF-A. Engineered soluble Nrp receptor fragments that selectively sequester ligands from the active signaling complex are an attractive modality for selectively blocking the angiogenic and chemorepulsive functions of Nrp ligands. Utilizing the information on Nrp ligand binding specificity, we demonstrate Nrp constructs that specifically sequester Sema3 in the presence of VEGF-A. This establishes that unique mechanisms are used by Nrp receptors to mediate specific ligand binding and that these differences can be exploited to engineer soluble Nrp receptors with specificity for Sema3.

  7. Approaching Moisture Recycling Governance (United States)

    Keys, Patrick; Wang-Erlandsson, Lan; Gordon, Line; Galaz, Victor; Ebbesson, Jonas


    The spatial and temporal dynamics of water resources are a continuous challenge for effective and sustainable national and international governance. Despite the surface watershed being the typical unit of water management, recent advances in hydrology have revealed 'atmospheric watersheds' - otherwise known as precipitationsheds. Also, recent research has demonstrated that water flowing within a precipitationshed may be modified by land-use change in one location, while the effect of this modification could be felt in a different province, nation, or continent. Notwithstanding these insights, the major legal and institutional implications of modifying moisture recycling have remained unexplored. In this presentation, we examine potential approaches to moisture recycling governance. We first identify a set of international study regions, and then develop a typology of moisture recycling relationships within these regions ranging from bilateral moisture exchange to more complex networks. This enables us to classify different types of legal and institutional governance principles. Likewise, we relate the moisture recycling types to existing land and water governance frameworks and management practices. The complexity of moisture recycling means institutional fit will be difficult to generalize for all moisture recycling relationships, but our typology allows the identification of characteristics that make effective governance of these normally ignored water flows more tenable.

  8. Governing Warfare

    DEFF Research Database (Denmark)

    Harste, Gorm

    its origins in a - some say 1st - generation of warfare, where armies were concentrated and could be controlled by political masters who were also acclaimed as warfare "geniuses". With subsequent generations of warfare, however, the control of war cannot be replaced by a control of military...... administration. While organisation systems continue to make some kind of political control possible, this is not the case in relation to wars. The organisation system is the in-between that should mediatise politics and war but is not functionally equivalent to just and unjust wars. The paper investigates...... the risks of lacking unity and displays the organisational trap to the fatal political myth of controlled warfare: Does it come from the military organisation system itself, from political ideologies of goal-rational governance, or from the chameleonic logic of wars?  ...

  9. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders


    Abstract: Most people agree that our world faces daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel...... dominant perspectives in challenge perception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping...... of engineering education and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter...

  10. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders


    Most people agree that our world face daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel dominant...... perspectives in challenge per-ception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping of engineering education...... and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter strives to elicit the bodies...

  11. Internet Governance

    Directory of Open Access Journals (Sweden)

    Pedro Veiga


    Full Text Available It has now become quite obvious that the Internet has brought significant changes to our society and a break on how we lived before its emergence. It is still too early to assess the impact on society of the new services at our disposal, such as the capacity to communicate faster and cheaper on a global scale, access information and, perhaps more importantly, to produce and disseminate information in a way that is accessible to all.It is clear that the advent of the Information Society implies changes in our society that constitute a point of no return. However, contrary to what happened when we entered the Industrial Age about three centuries ago, when the changing process was slow and led by older individuals, these days the entrance into the Information Society is taking place rapidly and the decisive players are younger people. The global nature of the Internet, the possibility of producing and distributing any type of content in digital form at almost zero cost, as well as the vast number of people who use the web, have highlighted the need for new forms of intervention in a sector where there are many types of players. It is in this context that the problem of Internet Governance becomes a very current issue, inasmuch as one feels the need to guarantee a diversity of rights and duties, which may appear difficult to reconcile.This paper presents a brief overview of the main players and initiatives which, in the field of Internet Governance, have tried to contribute to turning this network into a factor for social development and democraticity on a global scale.

  12. A General Strategy for Ligand Exchange on Upconversion Nanoparticles. (United States)

    Kong, Wei; Sun, Tianying; Chen, Bing; Chen, Xian; Ai, Fujin; Zhu, Xiaoyue; Li, Mingyu; Zhang, Wenjun; Zhu, Guangyu; Wang, Feng


    Lanthanide-doped upconversion nanoparticles with a suitable surface coating are appealing for biomedical applications. Because high-quality upconversion nanoparticles are typically prepared in an organic solvent and passivated by hydrophobic oleate ligands, a convenient and reliable method for the surface modification of upconversion nanoparticles is thus highly desired to satisfy downstream biological investigations. In this work, we describe a facile and versatile strategy for displacing native oleate ligands on upconversion nanoparticles with a diversity of hydrophilic molecules. The ligand-exchange procedure involves the removal of original oleate ligands followed by the attachment of new ligands in a separate step. The successful coating of relevant ligands was confirmed by Fourier transform infrared spectroscopy, thermogravimetry analysis, and ζ-potential measurement. The surface-modified nanoparticles display high stability and good biocompatibility, as revealed by electron microscopy, photoluminescence spectroscopy, and cytotoxicity assessment. Our study demonstrates that functional biomolecules such as biotin can be directly immobilized on the nanoparticle surface using this approach for the quick and effective detection of streptavidin.

  13. Virtually Bare Nanocrystal Surfaces - Significantly Enhanced Electrical Transport in CuInSe2 and CuIn(1-x)Ga(x)Se2 Thin Films upon Ligand Exchange with Thermally Degradable 1-Ethyl-5-thiotetrazole


    Lauth, Jannika; Marbach, Jakob; Meyer, Andreas; Dogan, Sedat; Klinke, Christian; Kornowski, Andreas; Weller, Horst


    We present a facile and safe ligand exchange method for readily synthesized CuInSe2 (CIS) and CuIn(1-x)Ga(x)Se2 (CIGS) nanocrystals (NCs) from oleylamine to 1-ethyl-5-thiotetrazole which preserves the colloidal stability of the chalcopyrite structure. 1-ethyl-5-thiotetrazole as thermally degradable ligand is adapted for the first time for trigonal pyramidal CIS NCs (18 nm), elongated CIS NCs (9 nm) and CIGS NCs (6 nm). The exchanged NC solutions are spin-coated onto Si/SiO2 substrates with pr...

  14. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea


    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA.......g., IC(50) = 300 microM for (2R,4S)-4-methyl-AA (5d)]. The two unsaturated analogs (S)- (7a) and (R)-(E)-Delta(4)-5-methyl-AA (7b) turned out to be a weak AMPA receptor agonist and a weak mixed NMDA/AMPA receptor antagonist, respectively....

  15. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian


    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... polyamines are known to modulate the function of these receptors in vivo. In this study, recent developments in the medicinal chemistry of polyamine-based ligands are given, particularly focusing on the use of solid-phase synthesis (SPS) as a tool for the facile generation of libraries of polyamine toxin...

  16. The relative importance of topography and RGD ligand density for endothelial cell adhesion.

    Directory of Open Access Journals (Sweden)

    Guillaume Le Saux

    Full Text Available The morphology and function of endothelial cells depends on the physical and chemical characteristics of the extracellular environment. Here, we designed silicon surfaces on which topographical features and surface densities of the integrin binding peptide arginine-glycine-aspartic acid (RGD could be independently controlled. We used these surfaces to investigate the relative importance of the surface chemistry of ligand presentation versus surface topography in endothelial cell adhesion. We compared cell adhesion, spreading and migration on surfaces with nano- to micro-scaled pyramids and average densities of 6×10(2-6×10(11 RGD/mm(2. We found that fewer cells adhered onto rough than flat surfaces and that the optimal average RGD density for cell adhesion was 6×10(5 RGD/mm(2 on flat surfaces and substrata with nano-scaled roughness. Only on surfaces with micro-scaled pyramids did the topography hinder cell migration and a lower average RGD density was optimal for adhesion. In contrast, cell spreading was greatest on surfaces with 6×10(8 RGD/mm(2 irrespectively of presence of feature and their size. In summary, our data suggest that the size of pyramids predominately control the number of endothelial cells that adhere to the substratum but the average RGD density governs the degree of cell spreading and length of focal adhesion within adherent cells. The data points towards a two-step model of cell adhesion: the initial contact of cells with a substratum may be guided by the topography while the engagement of cell surface receptors is predominately controlled by the surface chemistry.

  17. Metal-ligand cooperation at tethered π-ligands. (United States)

    Verhoeven, Dide G A; Moret, Marc-Etienne


    Metal-ligand cooperativity in homogeneous catalysis is emerging as a powerful tool for the design of efficient transition-metal catalysts. This perspective highlights recent advances in the use of neutral π-coordinating ligands, tethered to a transition-metal center by other donor ligands, as cooperative reaction centers. The state-of-the-art organometallic complexes, including π-coordinating ligands originating from C[double bond, length as m-dash]C, C[double bond, length as m-dash]E (E = O, N) and boron containing moieties, are described here, with special attention on their specific reactivity. Geometric and electronic aspects of ligand design and their influence on the coordination mode and reactivity of the π-system are discussed.

  18. Hydrogeochemical processes governing the origin, transport and fate of major and trace elements from mine wastes and mineralized rock to surface waters (United States)

    Nordstrom, D. Kirk


    The formation of acid mine drainage from metals extraction or natural acid rock drainage and its mixing with surface waters is a complex process that depends on petrology and mineralogy, structural geology, geomorphology, surface-water hydrology, hydrogeology, climatology, microbiology, chemistry, and mining and mineral processing history. The concentrations of metals, metalloids, acidity, alkalinity, Cl-, F- and SO42- found in receiving streams, rivers, and lakes are affected by all of these factors and their interactions. Remediation of mine sites is an engineering concern but to design a remediation plan without understanding the hydrogeochemical processes of contaminant mobilization can lead to ineffective and excessively costly remediation. Furthermore, remediation needs a goal commensurate with natural background conditions rather than water-quality standards that might bear little relation to conditions of a highly mineralized terrain. This paper reviews hydrogeochemical generalizations, primarily from US Geological Survey research, that enhance our understanding of the origin, transport, and fate of contaminants released from mined and mineralized areas.

  19. Metal speciation dynamics in dispersions of soft colloidal ligand particles under steady-state laminar flow condition. (United States)

    Duval, Jérôme F L; Qian, Shizhi


    A theory is presented for metal speciation dynamics in a swarm of soft, spherical core-hell colloidal ligand particles under steady-state laminar flow condition. Mass transfer and subsequent complexation of metal species within the reactive, permeable particle shell are governed by the interplay between (i) convective-diffusion of free metal ions M within and around the shell where ligands L are distributed, and (ii) kinetics of ML complex formation/dissociation in the shell. The local concentrations of metal M and complex ML are determined by the convective-diffusion equations with appropriate chemical source term and full account of radial and angular concentration polarization contributions. The steady-state flow field is determined from the solution of Navier-tokes equation including convective acceleration term for the fluid external to the particle, and from Brinkman equation for the internal fluid flow. The confined location of ligands within the particle shell leads to ML formation/dissociation rate constants (denoted as ka* and kd*, respectively) that differ significantly from their counterparts (ka and kd) defined for homogeneous ligand distribution throughout the solution. The relationship between ka,d* and ka,d is derived from the numerical evaluation of the spatial, time-dependent distributions of free and bound metal within and/or outside the particle. The dramatic dependence of ka,d* on hydrodynamic particle softness, Péclet number, soft surface layer thickness, and particle radius are analyzed in the steady-state nonequilibrium chemical regime within the context of dynamic features for colloidal complexes. The analysis covers the limiting cases of hydrodynamically impermeable, hard particles where binding sites are located at the very surface of the particle core (e.g., functionalized latex colloids) and free draining, polymeric ligand particles devoid of a hard core (e.g., porous gel particles). The formalism further applies to any values of the

  20. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond


    are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

  1. Iron-binding ligands in the southern California Current System: mechanistic studies

    Directory of Open Access Journals (Sweden)

    Randelle M Bundy


    Full Text Available The distributions of dissolved iron and organic iron-binding ligands were examined in water column profiles and deckboard incubation experiments in the southern California Current System (sCCS along a transition from coastal to semi-oligotrophic waters. Analysis of the iron-binding ligand pool by competitive ligand exchange-adsorptive cathodic stripping voltammetry (CLE-ACSV using multiple analytical windows (MAWs revealed three classes of iron-binding ligands present throughout the water column (L1-L3, whose distributions closely matched those of dissolved iron and nitrate. Despite significant biogeochemical gradients, ligand profiles were similar between stations, with surface minima in strong ligands (L1 and L2, and relatively constant concentrations of weaker ligands (L3 down to 500 m. A phytoplankton grow-out incubation, initiated from an iron-limited water mass, showed dynamic temporal cycling of iron-binding ligands. A biological iron model was able to capture the patterns of the strong ligands in the grow-out incubation relatively well with only the microbial community as a biological source. An experiment focused on remineralization of particulate organic matter showed production of both strong and weak iron-binding ligands by the heterotrophic community, supporting a mechanism for in-situ production of both strong and weak iron-binding ligands in the subsurface water column. Photochemical experiments showed a variable influence of sunlight on the degradation of natural iron-binding ligands, providing some evidence to explain differences in surface ligand concentrations between stations. Patterns in ligand distributions between profiles and in the incubation experiments were primarily related to macronutrient concentrations, suggesting microbial remineralization processes might dominate on longer time-scales over short-term changes associated with photochemistry or phytoplankton growth.

  2. Substrate Coupling Strength of Integrin-Binding Ligands Modulates Adhesion, Spreading, and Differentiation of Human Mesenchymal Stem Cells. (United States)

    Choi, Chun Kit K; Xu, Yang J; Wang, Ben; Zhu, Meiling; Zhang, Li; Bian, Liming


    Substrate stiffness has been shown to regulate the differentiation fate of human mesenchymal stem cells (hMSCs). hMSCs sense and respond to substrate rigidity by exerting traction forces upon the binding between integrins and integrin-specific ligands present on the substrate surface. However, in previous studies, integrin-specific ligands such as Arg-Gly-Asp (RGD) peptides are always grafted to the substrate by a permanent covalent bond. Whether the coupling strength of integrin-specific ligands on substrate will influence cell behaviors has not been explored. In this work, we have developed a facile platform to investigate the effects of varied coupling strength between the RGD peptide and the glass substrate on stem cell behaviors. Glass coverslips are decorated with positive charges by silanization using (3-aminopropyl) triethoxysilane (APTES) to immobilize negatively charged citrate-capped gold nanoparticles (cit-AuNPs) solely via electrostatic interactions. The monolayer of electrostatically immobilized cit-AuNPs is further conjugated with the thiolated RGD peptides through the sulfur-gold bond. The substrate coupling strength of the RGD peptides, which is dependent on the electrostatic interactions between the APTES-treated glass substrate and the cit-AuNPs, is simply tuned by changing the APTES dosage and, hence, the resultant positive charge density on the surface. A total of 0.5% and 12.5% of APTES are used to fabricate low-coupling-strength surfaces (namely, LCS0.5 and LCS12.5), whereas 25% and 50% of APTES are used to fabricate high-coupling-strength surfaces (namely, HCS25 and HCS50). Fluorescence microscopy shows that hMSCs spread well and form stable actin filamentous structure on HCS surfaces but not on LCS surfaces. Remarkably, hMSCs exhibit enhanced osteogenesis on HCS surfaces as revealed by the immunostaining results of multiple early osteogenic markers. These differential behaviors may be governed by Yes-associated protein (YAP), a

  3. Engineering governance: introducing a governance meta framework.

    NARCIS (Netherlands)

    Brand, N.; Beens, B.; Vuuregge, E.; Batenburg, R.


    There is a need for a framework that depicts strategic choices within an organisation with regard to potential governance structures. The governance meta framework provides the necessary structure in the current developments of governance. Performance as well as conformance are embedded in this

  4. Government and governance strategies in medical tourism

    NARCIS (Netherlands)

    Ormond, M.E.; Mainil, T.


    This chapter provides an overview of current government and governance strategies relative to medical tourism development and management around the world. Most studies on medical tourism have privileged national governments as key actors in medical tourism regulation and, in some cases, even

  5. Two novel mixed-ligand complexes containing organosulfonate ligands. (United States)

    Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun


    The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

  6. Distinct Iron-binding Ligands in the Upper Water Column at Station ALOHA (United States)

    Bundy, R.; Boiteau, R.; Repeta, D.


    The distribution and chemical properties of iron-binding organic ligands at station ALOHA were examined using a combination of solid phase extraction (SPE) followed by high pressure liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). HPLC-ICPMS ligand measurements were complemented by competitive ligand exchange adsorptive cathodic stripping voltammetry (CLE-ACSV) analysis using salicylaldoxime as the added ligand. By HPLC-ICPMS, we find enhanced concentrations of distinct naturally-occurring polar iron-binding ligands present at the surface and in the chlorophyll maximum. Lower concentrations were found in the subsurface, where a suite of non-polar ligands was detected. Siderophores were present at the deepest depths sampled at station ALOHA, down to 400m. Incubation studies provided evidence for the production of iron-binding ligands associated with nutrient amended phytoplankton growth in surface waters, and as a result of microbial particle remineralization in the subsurface water column. Ligands classes identified via SPE were then compared to CLE-ACSV ligand measurements, as well as the conditional stability constants measured from model polar and non-polar siderophores, yielding insight to the sources of iron-binding ligands throughout the water column at station ALOHA.

  7. The metalloprotease SepA governs processing of accumulation-associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis. (United States)

    Paharik, Alexandra E; Kotasinska, Marta; Both, Anna; Hoang, Tra-My N; Büttner, Henning; Roy, Paroma; Fey, Paul D; Horswill, Alexander R; Rohde, Holger


    The otherwise harmless skin inhabitant Staphylococcus epidermidis is a major cause of healthcare-associated medical device infections. The species' selective pathogenic potential depends on its production of surface adherent biofilms. The Cell wall-anchored protein Aap promotes biofilm formation in S. epidermidis, independently from the polysaccharide intercellular adhesin PIA. Aap requires proteolytic cleavage to act as an intercellular adhesin. Whether and which staphylococcal proteases account for Aap processing is yet unknown. Here, evidence is provided that in PIA-negative S. epidermidis 1457Δica, the metalloprotease SepA is required for Aap-dependent S. epidermidis biofilm formation in static and dynamic biofilm models. qRT-PCR and protease activity assays demonstrated that under standard growth conditions, sepA is repressed by the global regulator SarA. Inactivation of sarA increased SepA production, and in turn augmented biofilm formation. Genetic and biochemical analyses demonstrated that SepA-related induction of biofilm accumulation resulted from enhanced Aap processing. Studies using recombinant proteins demonstrated that SepA is able to cleave the A domain of Aap at residue 335 and between the A and B domains at residue 601. This study identifies the mechanism behind Aap-mediated biofilm maturation, and also demonstrates a novel role for a secreted staphylococcal protease as a requirement for the development of a biofilm. © 2016 John Wiley & Sons Ltd.

  8. Developing digital forensic governance

    CSIR Research Space (South Africa)

    Grobler, M


    Full Text Available This paper presents a Digital Forensic (DF) governance framework and its mapping on the SANS ISO/IEC 38500:2009 Corporate governance of information technology structure. DF governance assists organisations in guiding the management team...

  9. Why Governments Intervene

    DEFF Research Database (Denmark)

    Knudsen, Jette Steen; Brown, Dana


    Why are national governments increasingly adopting policies on corporate social responsibility (CSR)? Government CSR policies have been explained either as a means of substituting or supporting (mirroring) domestic political-economic institutions and policies, or as a means for government...

  10. Voluntary Environmental Governance Arrangements

    NARCIS (Netherlands)

    van der Heijden, J.


    Voluntary environmental governance arrangements have focal attention in studies on environmental policy, regulation and governance. The four major debates in the contemporary literature on voluntary environmental governance arrangements are studied. The literature falls short of sufficiently

  11. Correcting ligands, metabolites, and pathways

    NARCIS (Netherlands)

    Ott, M.A.; Vriend, G.


    BACKGROUND: A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases,

  12. FAS Ligand Triggers Pulmonary Silicosis (United States)

    Borges, Valéria M.; Falcão, Haroldo; Leite-Júnior, José H.; Alvim, Luciana; Teixeira, Gerlinde P.; Russo, Momtchilo; Nóbrega, Alberto F.; Lopes, Marcela F.; Rocco, Patricia M.; Davidson, Wendy F.; Linden, Rafael; Yagita, Hideo; Zin, Walter A.; DosReis, George A.


    We investigated the role of Fas ligand in murine silicosis. Wild-type mice instilled with silica developed severe pulmonary inflammation, with local production of tumor necrosis factor (TNF)-α, and interstitial neutrophil and macrophage infiltration in the lungs. Strikingly, Fas ligand–deficient generalized lymphoproliferative disease mutant (gld) mice did not develop silicosis. The gld mice had markedly reduced neutrophil extravasation into bronchoalveolar space, and did not show increased TNF-α production, nor pulmonary inflammation. Bone marrow chimeras and local adoptive transfer demonstrated that wild-type, but not Fas ligand–deficient lung macrophages recruit neutrophils and initiate silicosis. Silica induced Fas ligand expression in lung macrophages in vitro and in vivo, and promoted Fas ligand–dependent macrophage apoptosis. Administration of neutralizing anti-Fas ligand antibody in vivo blocked induction of silicosis. Thus, Fas ligand plays a central role in induction of pulmonary silicosis. PMID:11457890

  13. E-Government Dimension


    Rosiyadi, Didi; Suryana, Nana; Cahyana, Ade; Nuryani, Nuryani


    Makalah ini mengemukakan E-Government Dimension yang merupakan salah satu hasil TahapanPengumpulan Data, dimana tahapan ini adalah bagian dari penelitian kompetitif di Lembaga Ilmu PengetahuanIndonesia 2007 yang sekarang sedang dilakukan. Data E-Government Dimension ini didapatkan dari berbagaisumber yang meliputi E-Government beberapa Negara di dunia, E-Government yang dibangun oleh beberapapenyedia aplikasi E-Government. E-Government Dimension terdiri dari tiga dimensi yaitu DemocraticDimen...

  14. VT Certified Local Governments (United States)

    Vermont Center for Geographic Information — Vermont established its Certified Local Government (CLG) program in 1985 to better help local governments integrate historic preservation concerns with planning and...

  15. Size and ligand effects on the electrochemical and spectroelectrochemical responses of CdSe nanocrystals

    NARCIS (Netherlands)

    Querner, Claudia; Reiss, Peter; Sadki, Said; Zagorska, Malgorzata; Pron, Adam


    The electrochemical properties of CdSe quantum dots with electrochemically inactive surface ligands (TOPO) have been investigated in comparison with the analogous nanocrystals containing electrochemically active oligoaniline ligands. The TOPO-capped nanocrystals have been studied in a wide size

  16. Water-soluble diphosphadiazacyclooctanes as ligands for aqueous organometallic catalysis

    KAUST Repository

    Boulanger, Jérôme


    Two new water-soluble diphosphacyclooctanes been synthesized and characterized by NMR and surface tension measurements. Both phosphanes proved to coordinate rhodium in a very selective way as well-defined bidentates were obtained. When used in Rh-catalyzed hydroformylation of terminal alkenes, both ligands positively impacted the reaction chemoselectivity. © 2012 Elsevier B.V.

  17. Data governance implementation concept


    Ullrichová, Jana


    This master´s thesis discusses concept of implementation for data governance. The theoretical part of this thesis is about data governance. It explains why data are important for company, describes definitoons of data governance, its history, its components, its principles and processes and fitting in company. Theoretical part is amended with examples of data governance failures and banking specifics. The main goal of this thesis is to create a concept for implementing data governance and its...

  18. Leisure, Government and Governance: A Swedish Perspective (United States)

    Lindstrom, Lisbeth


    The leisure sector has witnessed a tremendous expansion since 1960. The purpose of this article is to analyse the decisions and goals of Swedish government policy during the period 1962 to 2005. The empirical analysis covers government Propositions and governmental investigations. The fields covered are sports, culture, exercise, tourism and…

  19. Why mercury prefers soft ligands

    Energy Technology Data Exchange (ETDEWEB)

    Riccardi, Demian M [ORNL; Guo, Hao-Bo [ORNL; Gu, Baohua [ORNL; Parks, Jerry M [ORNL; Summers, Anne [University of Georgia, Athens, GA; Miller, S [University of California, San Francisco; Liang, Liyuan [ORNL; Smith, Jeremy C [ORNL


    Mercury (Hg) is a major global pollutant arising from both natural and anthropogenic sources. Defining the factors that determine the relative affinities of different ligands for the mercuric ion, Hg2+, is critical to understanding its speciation, transformation, and bioaccumulation in the environment. Here, we use quantum chemistry to dissect the relative binding free energies for a series of inorganic anion complexes of Hg2+. Comparison of Hg2+ ligand interactions in the gaseous and aqueous phases shows that differences in interactions with a few, local water molecules led to a clear periodic trend within the chalcogenide and halide groups and resulted in the well-known experimentally observed preference of Hg2+ for soft ligands such as thiols. Our approach establishes a basis for understanding Hg speciation in the biosphere.

  20. Surfactant Ligand Removal and Rational Fabrication of Inorganically Connected Quantum Dots

    KAUST Repository

    Zhang, Haitao


    A novel method is reported to create inorganically connected nanocrystal (NC) assemblies for both II-VI and IV-VI semiconductors by removing surfactant ligands using (NH 4) 2S. This surface modification process differs from ligand exchange methods in that no new surfactant ligands are introduced and the post-treated NC surfaces are nearly bare. The detailed mechanism study shows that the high reactivity between (NH 4) 2S and metal-surfactant ligand complexes enables the complete removal of surfactant ligands in seconds and converts the NC metal-rich shells into metal sulfides. The post-treated NCs are connected through metal-sulfide bonding and form a larger NCs film assembly, while still maintaining quantum confinement. Such "connected but confined" NC assemblies are promising new materials for electronic and optoelectronic devices. © 2011 American Chemical Society.

  1. Heteromultivalent ligand-decoration for actively targeted nanomedicine. (United States)

    Modery-Pawlowski, Christa L; Gupta, Anirban Sen


    Active targeting has become an important component of nanomedicine design where nanovehicles are surface-decorated with cell receptor-specific or disease matrix-specific ligands to enable site-selective binding, retention and delivery of theranostic cargo. In this context, there have been numerous reports regarding surface-modification of nanovehicles with antibodies, antibody fragments, carbohydrates, aptamers and peptides as targeting ligands. However, majority of these reports have focused on using a single type of targeting moiety on the vehicle surface. In any disease development and progression, multiple receptors and proteins are often spatio-temporally upregulated simultaneously and heterogeneously. Rationalizing from this, a significant advantage can be envisioned in targeting multiple entities simultaneously using vehicle co-decoration with multiple types of ligands, to enhance binding activity and targeting specificity. To this end, we present a comprehensive up-to-date review on research endeavors in heteromultivalent ligand-modification of nanovehicles and provide a mechanistic rationale as well as an insightful discussion of this promising area, including findings from our own research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Ligand-dependent exciton dynamics and photovoltaic properties of PbS quantum dot heterojunction solar cells. (United States)

    Chang, Jin; Ogomi, Yuhei; Ding, Chao; Zhang, Yao Hong; Toyoda, Taro; Hayase, Shuzi; Katayama, Kenji; Shen, Qing


    The surface chemistry of colloidal quantum dots (QDs) plays an important role in determining the photoelectric properties of QD films and the corresponding quantum dot heterojunction solar cells (QDHSCs). To investigate the effects of the ligand structure on the photovoltaic performance and exciton dynamics of QDHSCs, PbS QDHSCs were fabricated by the solid state ligand exchange method with mercaptoalkanoic acid as the cross-linking ligand. Temperature-dependent photoluminescence and ultrafast transient absorption spectra show that the electronic coupling and charge transfer rate within QD ensembles were monotonically enhanced as the ligand length decreased. However, in practical QDHSCs, the second shortest ligand 3-mercaptopropionic acid (MPA) showed higher power conversion efficiency than the shortest ligand thioglycolic acid (TGA). This could be attributed to the difference in their surface trap states, supported by thermally stimulated current measurements. Moreover, compared with the non-conjugated ligand MPA, the conjugated ligand 4-mercaptobenzoic acid (MBA) introduces less trap states and has a similar charge transfer rate in QD ensembles, but has poor photovoltaic properties. This unexpected result could be contributed by the QD-ligand orbital mixing, leading to the charge transfer from QDs to ligands instead of charge transfer between adjacent QDs. This work highlights the significant effects of ligand structures on the photovoltaic properties and exciton dynamics of QDHSCs, which would shed light on the further development of QD-based photoelectric devices.

  3. Ligand-based virtual screening under partial shape constraints (United States)

    von Behren, Mathias M.; Rarey, Matthias


    Ligand-based virtual screening has proven to be a viable technology during the search for new lead structures in drug discovery. Despite the rapidly increasing number of published methods, meaningful shape matching as well as ligand and target flexibility still remain open challenges. In this work, we analyze the influence of knowledge-based sterical constraints on the performance of the recently published ligand-based virtual screening method mRAISE. We introduce the concept of partial shape matching enabling a more differentiated view on chemical structure. The new method is integrated into the LBVS tool mRAISE providing multiple options for such constraints. The applied constraints can either be derived automatically from a protein-ligand complex structure or by manual selection of ligand atoms. In this way, the descriptor directly encodes the fit of a ligand into the binding site. Furthermore, the conservation of close contacts between the binding site surface and the query ligand can be enforced. We validated our new method on the DUD and DUD-E datasets. Although the statistical performance remains on the same level, detailed analysis reveal that for certain and especially very flexible targets a significant improvement can be achieved. This is further highlighted looking at the quality of calculated molecular alignments using the recently introduced mRAISE dataset. The new partial shape constraints improved the overall quality of molecular alignments especially for difficult targets with highly flexible or different sized molecules. The software tool mRAISE is freely available on Linux operating systems for evaluation purposes and academic use (see

  4. Ligand-based virtual screening under partial shape constraints. (United States)

    von Behren, Mathias M; Rarey, Matthias


    Ligand-based virtual screening has proven to be a viable technology during the search for new lead structures in drug discovery. Despite the rapidly increasing number of published methods, meaningful shape matching as well as ligand and target flexibility still remain open challenges. In this work, we analyze the influence of knowledge-based sterical constraints on the performance of the recently published ligand-based virtual screening method mRAISE. We introduce the concept of partial shape matching enabling a more differentiated view on chemical structure. The new method is integrated into the LBVS tool mRAISE providing multiple options for such constraints. The applied constraints can either be derived automatically from a protein-ligand complex structure or by manual selection of ligand atoms. In this way, the descriptor directly encodes the fit of a ligand into the binding site. Furthermore, the conservation of close contacts between the binding site surface and the query ligand can be enforced. We validated our new method on the DUD and DUD-E datasets. Although the statistical performance remains on the same level, detailed analysis reveal that for certain and especially very flexible targets a significant improvement can be achieved. This is further highlighted looking at the quality of calculated molecular alignments using the recently introduced mRAISE dataset. The new partial shape constraints improved the overall quality of molecular alignments especially for difficult targets with highly flexible or different sized molecules. The software tool mRAISE is freely available on Linux operating systems for evaluation purposes and academic use (see ).

  5. The thermodynamic principles of ligand binding in chromatography and biology

    DEFF Research Database (Denmark)

    Mollerup, Jørgen


    In chromatography, macromolecules do not adsorb in the traditional sense of the word but bind to ligands that are covalently bonded to the surface of the porous bead. Therefore, the adsorption must be modelled as a process where protein molecules bind to the immobilised ligands. The paper discusses...... but it is also observed in chromatography due to protein-protein interactions. Retention measurements on P-lactoglobulin A demonstrate this. A discussion of salt effects on hydrophobic interactions in precipitation and chromatography of proteins concludes the paper. (c) 2007 Elsevier B.V. All rights reserved....... the general thermodynamic principles of ligand binding. Models of the multi-component adsorption in ion-exchange and hydrophobic chromatography, HIC and RPLC, are developed. The parameters in the models have a well-defined physical significance. The models are compared to the Langmuir model...

  6. cAMP-Induced Desensitization of Surface cAMP Receptors in Dictyostelium : Different Second Messengers Mediate Receptor Phosphorylation, Loss of Ligand Binding, Degradation of Receptor, and Reduction of Receptor mRNA Levels

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Wang, Mei; Bominaar, Anthony A.; Devreotes, Peter N.; Schaap, Pauline

    Surface cAMP receptors on Dictyostelium cells are linked to several second messenger systems and mediate multiple physiological responses, including chemotaxis and differentiation. Activation of the receptor also triggers events which desensitize signal transduction. These events include the

  7. Rosetta Ligand docking with flexible XML protocols. (United States)

    Lemmon, Gordon; Meiler, Jens


    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  8. Forms of global governence

    Directory of Open Access Journals (Sweden)

    Maxim V. Kharkevich


    Full Text Available Global governance as a concept defines the meaning of contemporary world politics both as a discipline and as reality. Interdependent and globalized world requires governance, and a global government has not been formed yet. The theoretical possibility of global governance without global government is proved and justified. The purpose of this article is to analytically identify possible forms of global governance. Three such forms of global governance are identified: hierarchical, market and network. In a hierarchy the governance is due to the asymmetry of power between the parties. Market control happens via anonymous pricing mechanism. Network, in contrast to the market is characterized by a closer value link between the actors, but unlike the hierarchical relationship actors are free to leave the network. Global governance takes three forms and is being implemented by different actors. To determine the most efficient form of global governance is impossible. Efficiency depends on the match between a form and an object of government. It should be noted that meta governance is likely to remain a monopoly of institutionally strong states in global governance.

  9. Surface treatment of nanocrystal quantum dots after film deposition (United States)

    Sykora, Milan; Koposov, Alexey; Fuke, Nobuhiro


    Provided are methods of surface treatment of nanocrystal quantum dots after film deposition so as to exchange the native ligands of the quantum dots for exchange ligands that result in improvement in charge extraction from the nanocrystals.

  10. Langmuir-Blodgett monolayers of InP quantum dots with short chain ligands. (United States)

    Lambert, K; Wittebrood, L; Moreels, I; Deresmes, D; Grandidier, B; Hens, Z


    We demonstrate the organization of nearly monodisperse colloidal InP quantum dots at the air/water interface in Langmuir monolayers. The organization of the particles is monitored in situ by surface pressure-surface area measurements and ex situ by AFM measurements on films transferred to mica by Langmuir-Blodgett deposition. The influence of different ligands on the quality of the monolayer formed has been studied. We show that densely packed monolayers with little holes can be formed using short chain ligands like pyridine and pentamethylene sulfide. The advantage of using short chain ligands for electron tunneling to or from the quantum dots is demonstrated using scanning tunneling spectroscopy.

  11. The selenium metabolite methylselenol regulates the expression of ligands that trigger immune activation through the lymphocyte receptor NKG2D

    DEFF Research Database (Denmark)

    Hagemann-Jensen, Michael Henrik; Uhlenbrock, Franziska Katharina; Kehlet, Stephanie


    : Increased formation of reactive oxygen species (ROS), induction of DNA damage, triggering of apoptosis and the inhibition of angiogenesis. Here, we revealed that CH3SeH modulates cell surface expression of NKG2D ligands. The expression of NKG2D ligands is induced by stress-associated pathways, which occur...... ligands. A balanced cell-surface expression of NKG2D ligands is considered as an innate barrier against tumor development. Our work therefore indicates that the application of selenium compounds, which are metabolized to CH3SeH, could improve NKG2D-based immune therapy....


    African Journals Online (AJOL)



    Jun 30, 2010 ... ion. This brings about repulsion between the adsorbent and positively charged ion and consequently a reduction in the amount of heavy metal adsorbed at lower pH. (Lee, 1999). The effectiveness of the anionic ligands in the removal of heavy metal ions from aqueous solution seems to be low for the EDTA.

  13. Government and Business

    DEFF Research Database (Denmark)

    Campbell, John L.


    There is a vast literature about the relationships between government and business in advanced capitalist societies.......There is a vast literature about the relationships between government and business in advanced capitalist societies....

  14. Transformative environmental governance (United States)

    Chaffin, Brian C.; Garmestani, Ahjond S.; Gunderson, Lance H.; Harm Benson, Melinda; Angeler, David G.; Arnold, Craig Anthony (Tony); Cosens, Barbara; Kundis Craig, Robin; Ruhl, J.B.; Allen, Craig R.


    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to alternative, more desirable, or more functional regimes by altering the structures and processes that define the system. Transformative governance is rooted in ecological theories to explain cross-scale dynamics in complex systems, as well as social theories of change, innovation, and technological transformation. Similar to adaptive governance, transformative governance involves a broad set of governance components, but requires additional capacity to foster new social-ecological regimes including increased risk tolerance, significant systemic investment, and restructured economies and power relations. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds.

  15. Nordic Corporate Governance Revisited

    DEFF Research Database (Denmark)

    Thomsen, Steen


    This paper reviews the key elements of the Nordic governance model, which include a distinct legal system, high governance ratings and low levels of corruption. Other characteristics include concentrated ownership, foundation ownership, semi two-tier board structures, employee representation...

  16. Project governance: selected South African government experiments

    Directory of Open Access Journals (Sweden)

    G. van der Walt


    Full Text Available Some form of accountability and power structure binds all organisations. Such structures are typically referred to as the “governance” structure of the organisation. In organisations that have relatively mature project applications and methodologies in place, governance mechanisms are established on more permanent bases. With its focus on performance, results and outcomes, project governance establishes decision-making structures, as well as accountability and responsibility mechanisms in public institutions to oversee projects. As government institutions increasingly place emphasis on project applications for policy implementation and service delivery initiatives, mechanisms or structures should be established to facilitate clear interfaces between the permanent organisation and the temporary project organisation. Such mechanisms or structures should enhance the governance of projects, that is, the strategic alignment of projects, the decentralisation of decision- making powers, rapid resource allocation, and the participation of external stakeholders. The purpose of this article is to explore the concept “project governance”, and to highlight examples of project governance as applied in selected government departments in provincial and national spheres. This would enable the establishment of best practice examples and assist to develop benchmarks for effective project applications for service delivery improvement.

  17. Tourism and Governance

    DEFF Research Database (Denmark)

    Dredge, Dianne


    This chapter discusses tourism education for sustainability with a particular focus on the challenges and opportunities associated with preparing students to work within complex tourism governance settings. It takes the position that the development of tourism within a sustainability framework...... and contemporary knowledge and understandings of governance; competencies for tourism governance for sustainability; and ethical action-oriented practice....

  18. Transformative environmental governance (United States)

    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to ...

  19. Government failure : four types

    NARCIS (Netherlands)

    Dolfsma, W.A.

    Economists tend to see the market as a default option for social order and a role for government only when markets fail. Developing a convincing analysis of the role of government in economic processes, however, needs to start by considering government failure in its own terms. Drawing on insights

  20. Global water governance

    NARCIS (Netherlands)

    Gupta, J.; Falkner, R.


    Although (fresh) water challenges are primarily local in nature, globalization has led to feedback effects that make many water challenges global in nature. This chapter examines global water governance. It discusses four phases of water governance, argues that water governance is dispersed and

  1. Size and ligand effects on the electrochemical and spectroelectrochemical responses of CdSe nanocrystals. (United States)

    Querner, Claudia; Reiss, Peter; Sadki, Said; Zagorska, Malgorzata; Pron, Adam


    The electrochemical properties of CdSe quantum dots with electrochemically inactive surface ligands (TOPO) have been investigated in comparison with the analogous nanocrystals containing electrochemically active oligoaniline ligands. The TOPO-capped nanocrystals have been studied in a wide size range (from 3 to 6.5 nm) with the goal to amplify the influence of the quantum confinement effect on the electrochemical response. The determined HOMO and LUMO levels have been found in good agreement with the ones obtained from photoluminescence studies and those predicted theoretically. Ligand exchange with aniline tetramer significantly influences the voltammetric peaks associated with the HOMO oxidation and the LUMO reduction of the quantum dots, which are shifted to higher and lower potentials, respectively. These shifts are interpreted in terms of the positive ligand charging which precedes the oxidation of the nanocrystals and the insulating nature of the ligand in the case of the nanocrystal reduction. The ligand-nanocrystal interactions have also been studied by UV-Vis-NIR and Raman spectroelectrochemistry in comparison with a specially prepared model compound which, apart from the anchoring function is identical to the grafted oligoaniline ligand. Both spectroelectrochemical techniques clearly indicate the same nature of the oxidation/reduction pathway for both the model compound and the grafted ligand. The influence of the grafting is manifested by a shift in the onset of the ligand oxidation as compared to the case of the "free" model compound. Since both components (ligands and nanocrystals) mutually influence their electrochemical and spectroelectrochemical properties, the newly developed system can be considered as a true molecular hybrid. Such hybrids are of interest because the potential zone of the ligand electroactivity is well separated from that of the nanocrystals and, as a result, the organic part can be electrochemically switched between the

  2. Negotiating Collaborative Governance Designs

    DEFF Research Database (Denmark)

    Plotnikof, Mie


    the meaning negotiations of local designs, discursive tensions and resistance generate changes in the organizing. The article shows that a discursive approach offers concepts valuable for refining the understanding of the emergence of collaborative governance in practice, and proposes approaching this process...... as organizing accomplished through and complicated by endemic meaning negotiations and change....... governance designs emerge and change. The findings of a case study of local governments' efforts to innovate quality management in education through collaborative governance suggest that such form of governance is continuingly negotiated in communication during both design and implementation phases. Through...

  3. Colloidal-quantum-dot photovoltaics using atomic-ligand passivation

    KAUST Repository

    Tang, Jiang


    Colloidal-quantum-dot (CQD) optoelectronics offer a compelling combination of solution processing and spectral tunability through quantum size effects. So far, CQD solar cells have relied on the use of organic ligands to passivate the surface of the semiconductor nanoparticles. Although inorganic metal chalcogenide ligands have led to record electronic transport parameters in CQD films, no photovoltaic device has been reported based on such compounds. Here we establish an atomic ligand strategy that makes use of monovalent halide anions to enhance electronic transport and successfully passivate surface defects in PbS CQD films. Both time-resolved infrared spectroscopy and transient device characterization indicate that the scheme leads to a shallower trap state distribution than the best organic ligands. Solar cells fabricated following this strategy show up to 6% solar AM1.5G power-conversion efficiency. The CQD films are deposited at room temperature and under ambient atmosphere, rendering the process amenable to low-cost, roll-by-roll fabrication. © 2011 Macmillan Publishers Limited. All rights reserved.

  4. Selective Electrocatalytic Activity of Ligand Stabilized Copper Oxide Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kauffman, Douglas R; Ohodnicki, Paul R; Kail, Brian W; Matranga, Christopher


    Ligand stabilization can influence the surface chemistry of Cu oxide nanoparticles (NPs) and provide unique product distributions for electrocatalytic methanol (MeOH) oxidation and CO{sub 2} reduction reactions. Oleic acid (OA) stabilized Cu{sub 2}O and CuO NPs promote the MeOH oxidation reaction with 88% and 99.97% selective HCOH formation, respectively. Alternatively, CO{sub 2} is the only reaction product detected for bulk Cu oxides and Cu oxide NPs with no ligands or weakly interacting ligands. We also demonstrate that OA stabilized Cu oxide NPs can reduce CO{sub 2} into CO with a {approx}1.7-fold increase in CO/H{sub 2} production ratios compared to bulk Cu oxides. The OA stabilized Cu oxide NPs also show 7.6 and 9.1-fold increases in CO/H{sub 2} production ratios compared to weakly stabilized and non-stabilized Cu oxide NPs, respectively. Our data illustrates that the presence and type of surface ligand can substantially influence the catalytic product selectivity of Cu oxide NPs.

  5. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui


    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  6. An efficient computational method for calculating ligand binding affinities.

    Directory of Open Access Journals (Sweden)

    Atsushi Suenaga

    Full Text Available Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, the docking scores are not sufficiently precise to represent the protein-ligand binding affinity. Here, we developed an efficient computational method for calculating protein-ligand binding affinity, which is based on molecular mechanics generalized Born/surface area (MM-GBSA calculations and Jarzynski identity. Jarzynski identity is an exact relation between free energy differences and the work done through non-equilibrium process, and MM-GBSA is a semimacroscopic approach to calculate the potential energy. To calculate the work distribution when a ligand is pulled out of its binding site, multiple protein-ligand conformations are randomly generated as an alternative to performing an explicit single-molecule pulling simulation. We assessed the new method, multiple random conformation/MM-GBSA (MRC-MMGBSA, by evaluating ligand-binding affinities (scores for four target proteins, and comparing these scores with experimental data. The calculated scores were qualitatively in good agreement with the experimental binding affinities, and the optimal docking structure could be determined by ranking the scores of the multiple docking poses obtained by the molecular docking process. Furthermore, the scores showed a strong linear response to experimental binding free energies, so that the free energy difference of the ligand binding (ΔΔG could be calculated by linear scaling of the scores. The error of calculated ΔΔG was within ≈ ± 1.5 kcal.mol(-1 of the experimental values. Particularly, in the case of flexible target proteins, the MRC-MMGBSA scores were more effective in ranking ligands than those generated by the MM-GBSA method using a single protein-ligand conformation. The results suggest that, owing to its lower computational costs and greater accuracy, the MRC-MMGBSA offers efficient means to rank the ligands, in

  7. Governance and organizational theory

    Directory of Open Access Journals (Sweden)

    Carlos E. Quintero Castellanos


    Full Text Available The objective of this essay is to propose a way to link the theoretical body that has been weaved around governance and organizational theory. For this, a critical exposition is done about what is the theoretical core of governance, the opportunity areas are identified for the link of this theory with organizational theory. The essay concludes with a proposal for the organizational analysis of administrations in governance. The essay addresses with five sections. The first one is the introduction. In the second one, I present a synthesis of the governance in its current use. In the next one are presented the work lines of the good governance. In the fourth part, I show the organizational and managerial limits in the governance theory. The last part develops the harmonization proposal for the governance and organizational theories.

  8. Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery. (United States)

    Ji, Hong-Fang; Kong, De-Xin; Shen, Liang; Chen, Ling-Ling; Ma, Bin-Guang; Zhang, Hong-Yu


    Extant life depends greatly on the binding of small molecules (such as ligands) with macromolecules (such as proteins), and one ligand can bind multiple proteins. However, little is known about the global patterns of ligand-protein mapping. By examining 2,186 well-defined small-molecule ligands and thousands of protein domains derived from a database of druggable binding sites, we show that a few ligands bind tens of protein domains or folds, whereas most ligands bind only one, which indicates that ligand-protein mapping follows a power law. Through assigning the protein-binding orders (early or late) for bio-ligands, we demonstrate that the preferential attachment principle still holds for the power-law relation between ligands and proteins. We also found that polar molecular surface area, H-bond acceptor counts, H-bond donor counts and partition coefficient are potential factors to discriminate ligands from ordinary molecules and to differentiate super ligands (shared by three or more folds) from others. These findings have significant implications for evolution and drug discovery. First, the chronology of ligand-protein binding can be inferred by the power-law feature of ligand-protein mapping. Some nucleotide-containing ligands, such as ATP, ADP, GDP, NAD, FAD, dihydro-nicotinamide-adenine-dinucleotide phosphate (NDP), nicotinamide-adenine-dinucleotide phosphate (NAP), flavin mononucleotide (FMN) and AMP, are found to be the earliest cofactors bound to proteins, agreeing with the current understanding of evolutionary history. Second, the finding that about 30% of ligands are shared by two or more domains will help with drug discovery, such as in finding new functions from old drugs, developing promiscuous drugs and depending more on natural products.

  9. ALX receptor ligands define a biochemical endotype for severe asthma (United States)

    Ricklefs, Isabell; Barkas, Ioanna; Duvall, Melody G.; Grossman, Nicole L.; Israel, Elliot; Bleecker, Eugene R.; Castro, Mario; Erzurum, Serpil C.; Fahy, John V.; Gaston, Benjamin M.; Denlinger, Loren C.; Mauger, David T.; Wenzel, Sally E.; Comhair, Suzy A.; Coverstone, Andrea M.; Fajt, Merritt L.; Hastie, Annette T.; Johansson, Mats W.; Peters, Michael C.; Phillips, Brenda R.; Levy, Bruce D.


    BACKGROUND. In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). METHODS. ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47]). RESULTS. Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4. CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. TRIAL REGISTRATION. Severe Asthma Research Program-3 (SARP-3; NCT01606826) FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology. PMID:28724795

  10. Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

    Directory of Open Access Journals (Sweden)

    Aaron Clapp


    Full Text Available Luminescent colloidal quantum dots (QDs possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands.

  11. Governance or Governing – the Missing Link?

    Directory of Open Access Journals (Sweden)

    Luminiţa Maria Crăciun


    Full Text Available Governance and governing are two distinct concepts, but they intertwine. “Good governing” exercises good influence on development. “Good governance” supposes first a relationship of power focused on a series of reforms structured at three levels: the political – administrative level, the economic level, and the level of civil society. As this dimension is difficult to measure, the qualitative evaluation of the governing act raised the interest of the World Bank researchers, who elaborated and monitored the dynamics of a set of indicators, which includes six major dimensions of the governing. A retrospective concerning the image of governing in Romania during the period from 1996 to 2005 suggests a modest increase of the score: from -0.138 (1996 to 0.008 (2002; that was partially achieved based on the voice and responsibility index and on the political stability index, not on those that measure more directly the administrative performance or the integrity of the governing act. For a comparative study, we chose seven countries for the purposes of analysis (two new European Union member states: Romania and Bulgaria; two older member countries of the European Union: Slovenia and Latvia; three non-member states: Moldova, Ukraine, and Georgia, which reveal the quality of the governing from a comparative perspective. Corruption control completes the image created by the analyzed indicators. The mere formal accomplishment of commitments made in the pre-accession activity, doubled by recent internal evolutions, bring doubts about the credibility of the anticorruption reforms, as Romania continues to be considered the country with the highest CPI in the European Union. The pessimism of public opinion and the fact that only 34% of the Romanian people consider that the level of corruption will decrease in the following three years constitutes an alarm signal addressed to the governance, in view of the real reformation of the administration system

  12. Passivating ligand and solvent contributions to the electronic properties of semiconductor nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, S.; Crotty, A.; Kilina, S.; Ivanov, I.; Tretiak, S


    We examine in detail the impact of passivating ligands (i.e., amines, phosphines, phosphine oxides and pyridines) on the electronic and optical spectra of Cd{sub 33}Se{sub 33} quantum dots (QDs) using density functional theory (DFT) and time-dependent DFT (TDDFT) quantum-chemical methodologies. Most ligand orbitals are found deep inside in the valence and conduction bands of the QD, with pyridine being an exception by introducing new states close to the conduction band edge. Importantly, all ligands contribute states which are highly delocalized over both the QD surface and ligands, forming hybridized orbitals rather than ligand-localized trap states. In contrast, the states close to the band gap are delocalized over the QD atoms only and define the lower energy absorption spectra. The random detachment of one of ligands from the QD surface results in the appearance of a highly localized unoccupied state inside the energy gap of the QD. Such changes in the electronic structure are correlated with the respective QD-ligand binding energy and steric ligand-ligand interactions. Polar solvent significantly reduces both effects leading to delocalization and stabilization of the surface states. Thus, trap and surface states are substantially eliminated by the solvent. Polar solvent also blue-shifts (e.g., 0.3-0.4 eV in acetonitrile) the calculated absorption spectra. This shift increases with an increase of the dielectric constant of the solvent. We also found that the approximate single-particle Kohn-Sham (KS) approach is adequate for calculating the absorption spectra of the ligated QDs. Besides a systematic blue-shift, the KS spectra are in very good agreement with their respective counterparts calculated with the more accurate TDDFT method.

  13. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli


    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.


    African Journals Online (AJOL)

    KEY WORDS: Supramolecular architecture, Hirschfeld surface analysis, Magnetism. INTRODUCTION. Coordination polymers (CPs) have attracted intense attention in recent years ... The hydrogen atoms of organic ligands were placed in calculated positions and refined using a riding on attached atoms with isotropic.

  15. Civil Society and Governance

    DEFF Research Database (Denmark)

    Hulgård, Lars

    An illustration of how important the relationship is between civil society anbd governance. A short historic journey with four snapshots of times and situations that have provided interesting evidence about the connection between civil society and governance. My goal for the short historic journey...... is to make clear and hopefully even verify that providing knowledge about the impact of civil society and citizens’ participation on governance is one of the most urgent research tasks in the current period of time....

  16. Energy Efficiency Governance: Handbook

    Energy Technology Data Exchange (ETDEWEB)



    This handbook has been written to assist EE practitioners, government officials and stakeholders to establish effective EE governance structures for their country. The handbook provides readers with relevant information in an accessible format that will help develop comprehensive and effective governance mechanisms. For each of the specific topics dealt with (see Figure 1 in the Handbook), the IEA offers guidelines for addressing issues, or directs readers to examples of how such issues have been dealt with by specific countries.

  17. Internet Governance: An Introduction


    Arthur J. Cordell; Prabir K. Neogi


    Internet Governance: An Introduction offers a complete guide to the “ins and outs” of Internet governance. Drawing on a range of international authors Internet Governance is best suited for those seeking an overview of the range of issues involved as the Internet becomes increasingly important to bu siness and to society in general, affecting the daily lives of millions of people around the world.

  18. Exploring Knowledge Governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahoney, Joseph T

    Knowledge governance is characterized as a distinctive research subject, the understanding of which cuts across diverse fields in management. In particular, it represents an intersection of knowledge management, strategic management, and theories of the firm. Knowledge governance considers how...... deployment of governance mechanisms influences knowledge processes: sharing, retaining, and creating knowledge. We survey the papers in this volume of the special issue, and discuss the remaining research challenges....

  19. Gobernanza Versus Gobierno Governance Versus Government

    Directory of Open Access Journals (Sweden)

    Dany-Robert Dufour


    Full Text Available El desplazamiento del término moderno de gobierno por el postmoderno de gobernanza, pone de manifiesto un nuevo lenguaje postmoderno en el que se deja entrever que ambas nociones, gobierno y gobernanza, tienden a oponerse. La gobernanza corporativa designa la toma del poder del capitalismo financiero sobre el capitalismo industrial, que no es otra cosa que, por un lado, propender por la rentabilidad máxima para los accionistas, valorizar todo en el mercado sin consideraciones morales, obligar a los actores a la búsqueda de riesgo permanente y flexibilizar las relaciones jerárquicas en la Administración de la empresa; y por el otro, la marginación de la clase obrera. La gobernanza ha llegado a los asuntos políticos convirtiéndose en modelo de gestión pública por excelencia, ella trata que el gobierno reducido a su mínima expresión guie a una sociedad civil que adquiere un papel importante en la creación y seguimiento de las diferentes políticas, es decir, que el gobierno adquiere una forma flexible de regulación, es allá donde la gobernanza política nos conduce, a la supuesta autorregulación de los intereses privados que sumados pasan a configurar el interés general. En realidad se trata de una nueva forma de dominación marcada por un desvanecimiento político, donde la sociedad civil juega en contra del Estado. La gobernanza le está tendiendo una temible trampa a la democracia, en tanto se presenta como una ampliación de la democracia materializada en una mejor participación de la sociedad civil, destruyendo la persona pública que se forma por la unión de todos los otros y convirtiéndola en representante de intereses particulares.The displacement of the modern term of government for the postmodern one of governance, reveals a new postmodern language in which one is left to guess that both notions, government and governance, tend to be opposed. Corporate governance signifies the seizure of power of financial capitalism

  20. E-Government Partnerships Across Levels of Government


    Charbit, Claire; Michalun, Varinia


    E-government Partnerships across Levels of Government, is an overview of the challenges and approaches to creating a collaborative and cooperative partnership across levels of government for e-government development and implementation.

  1. Organic ligand-induced dissolution kinetics of antimony trioxide. (United States)

    Hu, Xingyun; He, Mengchang


    The influence of low-molecular-weight dissolved organic matter (LMWDOM) on the dissolution rate of Sb2O3 was investigated. Some representative LMWDOMs with carboxyl, hydroxyl, hydrosulfuryl and amidogen groups occurring naturally in the solution were chosen, namely oxalic acid, citric acid, tartaric acid, EDTA, salicylic acid, phthalandione, glycine, thiolactic acid, xylitol, glucose and catechol. These LMWDOMs were dissolved in inert buffers at pH=3.7, 6.6 and 8.6 and added to powdered Sb2O3 in a stirred, thermostatted reactor (25°C). The addition of EDTA, tartaric acid, thiolactic acid, citric acid and oxalic acid solutions at pH3.7 and catechol at pH8.6 increased the rate of release of antimony. In the 10mmol/L thiolactic acid solution, up to 97% by mass of the antimony was released after 120min reaction. There was no effect on the dissolution of Sb2O3 for the other ligands. A weak correlation between dissolution rate with the dissociation constant of ligands and the stability of the dissolved complex was also found. All the results showed that the extent of the promoting effect of ligands on the dissolution of Sb2O3 was not determined by the stability of the dissolved complex, but by the dissociation constant of ligands and detachment rate of surface chelates from the mineral surface. This study can not only help in further understanding the effect of individual low-molecular-weight organic ligands, but also provides a reference to deduce the effect of natural organic matters with oxygen-bearing functional groups on the dissolution of antimony oxide minerals. Copyright © 2016. Published by Elsevier B.V.

  2. Evaluation of Receptor-Ligand Mechanisms of Dual-Targeted Particles to an Inflamed Endothelium. (United States)

    Fromen, Catherine A; Fish, Margaret B; Zimmerman, Anthony; Adili, Reheman; Holinstat, Michael; Eniola-Adefeso, Omolola


    Vascular-targeted carriers (VTCs) are designed as leukocyte mimics, decorated with ligands that target leukocyte adhesion molecules (LAMs) and facilitate adhesion to diseased endothelium. VTCs require different design considerations than other targeted particle therapies; adhesion of VTCs in regions with dynamic blood flow requires multiple ligand-receptor (LR) pairs that provide particle adhesion and disease specificity. Despite the ultimate goal of leukocyte mimicry, the specificity of multiple LAM-targeted VTCs remains poorly understood, especially in physiological environments. Here, we investigate particle binding to an inflamed mesentery via intravital microscopy using a series of particles with well-controlled ligand properties. We find that the total number of sites of a single ligand can drive particle adhesion to the endothelium, however, combining ligands that target multiple LR pairs provides a more effective approach. Combining sites of sialyl Lewis A (sLeA) and anti-intercellular adhesion molecule-1 (aICAM), two adhesive molecules, resulted in ~3-7-fold increase of adherent particles at the endothelium over single-ligand particles. At a constant total ligand density, a particle with a ratio of 75% sLeA: 25% aICAM resulted in more than 3-fold increase over all over other ligand ratios tested in our in vivo model. Combined with in vitro and in silico data, we find the best dual-ligand design of a particle is heavily dependent on the surface expression of the endothelial cells, producing better adhesion with more particle ligand for the lesser-expressed receptor. These results establish the importance of considering LR-kinetics in intelligent VTC ligand design for future therapeutics.

  3. Understanding ligand effects in gold clusters using mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Grant E.; Laskin, Julia


    This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because “each-atom-counts” toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation of numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted that may be compared with the results of high-level theoretical calculations. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well

  4. Understanding ligand effects in gold clusters using mass spectrometry. (United States)

    Johnson, Grant E; Laskin, Julia


    This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because "each-atom-counts" toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation of numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well-defined surfaces may be explored using ion soft landing (SL) in a custom

  5. Force loading explains spatial sensing of ligands by cells (United States)

    Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere


    Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin–ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin–ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow

  6. Increased Accuracy of Ligand Sensing by Receptor Internalization and Lateral Receptor Diffusion (United States)

    Aquino, Gerardo; Endres, Robert


    Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as overcounting of the same ligand molecules is reduced. A similar role may be played by receptor diffusion om the cell membrane. Fast, lateral receptor diffusion is known to be relevant in neurotransmission initiated by release of neurotransmitter glutamate in the synaptic cleft between neurons. By binding ligand and removal by diffusion from the region of release of the neurotransmitter, diffusing receptors can be reasonably expected to reduce the local overcounting of the same ligand molecules in the region of signaling. By extending simple ligand-receptor models to out-of-equilibrium thermodynamics, we show that both receptor internalization and lateral diffusion increase the accuracy with which cells can measure ligand concentrations in the external environment. We confirm this with our model and give quantitative predictions for experimental parameters values. We give quantitative predictions, which compare favorably to experimental data of real receptors.

  7. Revealing sources and chemical identity of iron ligands across the California Current System (United States)

    Boiteau, R.; Repeta, D.; Fitzsimmons, J. N.; Parker, C.; Twining, B. S.; Baines, S.


    The California Current System is one of the most productive regions of the ocean, fueled by the upwelling of nutrient rich water. Differences in the supply of micronutrient iron to surface waters along the coast lead to a mosaic of iron-replete and iron-limited conditions across the region, affecting primary production and community composition. Most of the iron in this region is supplied by upwelling of iron from the benthic boundary layer that is complexed by strong organic ligands. However, the source, identity, and bioavailability of these ligands are unknown. Here, we used novel hyphenated chromatography mass spectrometry approaches to structurally characterize organic ligands across the region. With these methods, iron ligands are detected with liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICPMS), and then their mass and fragmentation spectra are determined by high resolution electrospray ionization mass spectrometry (LC-ESIMS). Iron isotopic exchange was used to compare the relative binding strengths of different ligands. Our survey revealed a broad range of ligands from multiple sources. Benthic boundary layers and anoxic sediments were sources of structurally amorphous weak ligands, likely organic degradation products, as well as siderophores, strong iron binding molecules that facilitate iron acquisition. In the euphotic zone, marine microbes and zooplankton grazing produced a wide distribution of other compounds that included known and novel siderophores. This work demonstrates that the chemical nature of ligands from different sources varies substantially and has important implications for iron biogeochemical cycling and availability to members of the microbial community.

  8. Effect of cleaning agents and additives on Protein A ligand degradation and chromatography performance. (United States)

    Yang, Lihua; Harding, Jason D; Ivanov, Alexander V; Ramasubramanyan, Natarajan; Dong, Diane D


    Protein A chromatography, employing the recombinant Protein A ligand, is widely used as a capture step for antibody and Fc-fusion proteins manufacture. Protein A ligands in these matrices are susceptible to degradation/loss when exposed to cleaning agents such as sodium hydroxide, resulting in loss of capacity on reuse. In this study, MabSelect Protein A ligand and MabSelect SuRe Protein A ligand were chosen to evaluate the impact of alkaline cleaning solutions on the ligands and the packed columns. The Protein A ligands alone and the Protein A columns were incubated or cycled in different concentrations of sodium hydroxide solutions with and without additives, respectively. Ligand integrity (degradation) and ligand function (binding affinity) were studied using SDS-PAGE and customized Biacore technology, surface plasma resonance (SPR) and were successfully correlated with column performance measurement in terms of static binding capacity (SBC), dynamic binding capacity (DBC) and recovery as a function of exposure to cleaning agents with and without additives. The findings and the methodology presented in this study are not only able to determine appropriate cleaning conditions for Protein A chromatography, but also provided tools to enable systematic and rapid study of the cleaning solutions and conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Emergence of On-Surface Magnetochemistry


    Ballav, Nirmalya; Waeckerlin, Christian; Siewert, Dorota; Oppeneer, Peter M.; Jung, Thomas A.


    The control of exchange coupling across the molecule–substrate interface is a key feature in molecular spintronics. This Perspective reviews the emerging field of on-surface magnetochemistry, where coordination chemistry is applied to surface-supported metal porphyrins and metal phthalocyanines to control their magnetic properties. The particularities of the surface as a multiatomic ligand or “surface ligand” are introduced. The asymmetry involved in the action of a chemical ligand and a surf...

  10. Effects of ligand binding strength and facet coverage on the morphology of nanocrystal superlattices (United States)

    Bealing, Clive; Hennig, Richard


    Nanocrystals (NCs) of lead-salt have been proposed for a number of photovoltaic applications. These NCs consist of an inorganic core, in the rock salt structure, whose surface is usually passivated by oleate ligands. The self-assembly of NCs from colloidal solutions into mesoscale superlattices provides a path to materials with tunable electronic, physical and chemical properties that are promising for applications. The self-assembly is controlled by the NC shape and by ligand-mediated interactions between NCs; to understand this, it is necessary to know the effect of the ligands on the surface energies, as well as the relative coverage of the different facets. Our density functional calculations of the binding energies of carboxylic acid-based ligands on PbSe and PbS show that the ligands exhibit a strong energetic preference to particular facets. The results suggest that the transformation of the NC superlattice structure from fcc to bcc in aged NC assemblies is caused by the preferential detachment of ligands from particular facets, leading to anisotropic ligand coverage. Combined with the experimental results, our calculations present a potential route to greater control over the morphology of the NC superlattice assembly. This work was supported by Award No. KUS-C1-018-02, made by King Abdullah University of Science and Technology (KAUST).

  11. Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering. (United States)

    Yu, Chao; Sonnen, Andreas F-P; George, Roger; Dessailly, Benoit H; Stagg, Loren J; Evans, Edward J; Orengo, Christine A; Stuart, David I; Ladbury, John E; Ikemizu, Shinji; Gilbert, Robert J C; Davis, Simon J


    The inhibitory T-cell surface-expressed receptor, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which belongs to the class of cell surface proteins phosphorylated by extrinsic tyrosine kinases that also includes antigen receptors, binds the related ligands, B7-1 and B7-2, expressed on antigen-presenting cells. Conformational changes are commonly invoked to explain ligand-induced "triggering" of this class of receptors. Crystal structures of ligand-bound CTLA-4 have been reported, but not the apo form, precluding analysis of the structural changes accompanying ligand binding. The 1.8-Å resolution structure of an apo human CTLA-4 homodimer emphasizes the shared evolutionary history of the CTLA-4/CD28 subgroup of the immunoglobulin superfamily and the antigen receptors. The ligand-bound and unbound forms of both CTLA-4 and B7-1 are remarkably similar, in marked contrast to B7-2, whose binding to CTLA-4 has elements of induced fit. Isothermal titration calorimetry reveals that ligand binding by CTLA-4 is enthalpically driven and accompanied by unfavorable entropic changes. The similarity of the thermodynamic parameters determined for the interactions of CTLA-4 with B7-1 and B7-2 suggests that the binding is not highly specific, but the conformational changes observed for B7-2 binding suggest some level of selectivity. The new structure establishes that rigid-body ligand interactions are capable of triggering CTLA-4 phosphorylation by extrinsic kinase(s).

  12. 3 CFR - Government Contracting (United States)


    ... contract oversight could reduce such sums significantly. Government outsourcing for services also raises... commercial services used by the Government, such as transportation, food, and maintenance. Office of... governmental functions. Agencies and departments must operate under clear rules prescribing when outsourcing is...

  13. Human-centred Governance

    DEFF Research Database (Denmark)

    Bason, Christian


    Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

  14. Partnerships and Governance

    DEFF Research Database (Denmark)

    Damgaard, Bodil

    Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark.......Three models of cooperation are outlined and their consequences for governance discussed, using case studies of local multisectoral collaboration on labour market related social policy - active social policy - in Denmark....

  15. Educational Governance in Denmark (United States)

    Moos, Lejf


    Denmark has entered global competition by expanding collaboration with European countries, which is profoundly impacting the public sector and school governance. Relations between the state and institutions are transforming from traditional democratic, public-sector models of governance into new forms characterized as corporate and market-driven…

  16. Enforcement and Corporate Governance


    Berglöf, Erik; Claessens, Stijn


    Enforcement more than regulations, laws-on-the-books, or voluntary codes is key to effective corporate governance, at least in transition and developing countries. Corporate governance and enforcement mechanisms are intimately linked as they affect firms' ability to commit to their stakeholders, in particular to external investors. The authors provide a framework for understanding these li...

  17. Using IT Governance (United States)

    Brobst, Jan; Council, Chip


    The discussion in this article is intended to provide an examination of why top management, IT management, and internal auditors should be interested in IT governance. Some aspects of IT management will be described including implementation, auditing, availability, security, and alignment. One governance framework, COBIT, will be utilized as a…

  18. Governing through standards

    DEFF Research Database (Denmark)

    Brøgger, Katja

    This abstract adresses the ways in which new education standards have become integral to new modes of education governance. The paper explores the role of standards for accelerating the shift from national to transnational governance in higher education. Drawing on the case of higher education...

  19. Benefit from the Government

    NARCIS (Netherlands)

    Evert Pommer; Jedid-Jah Jonker


    Original title: Profijt van de overheid. Income levels are determined to a considerable extent by the government, which exerts an influence through social security and taxation. The traditional purchasing power tables are a reflection of this. However, the influence of the government goes

  20. Negotiating Collaborative Governance Designs

    DEFF Research Database (Denmark)

    Plotnikof, Mie


    This chapter addresses the design and implementation issues of collaborative governance, a public management practice aimed at involving stakeholders in problem-solving and public innovation.......This chapter addresses the design and implementation issues of collaborative governance, a public management practice aimed at involving stakeholders in problem-solving and public innovation....

  1. Hard and Soft Governance

    DEFF Research Database (Denmark)

    Moos, Lejf


    The governance and leadership at transnational, national and school level seem to be converging into a number of isomorphic forms as we see a tendency towards substituting 'hard' forms of governance, that are legally binding, with 'soft' forms based on persuasion and advice. This article analyses...

  2. Innovation in City Governments

    DEFF Research Database (Denmark)

    Lewis, Jenny M; Ricard, Lykke Margot; Klijn, Erik Hans

    Innovation has become an important focus for governments around the world over the last decade, with greater pressure on governments to do more with less, and expanding community expectations. Some are now calling this ‘social innovation’ – innovation that is related to creating new services......, are related to the innovations introduced by these cities. The volume maps and analyses the social networks of the three cities and examines boundary spanning within and outside of the cities. It also examines what leadership qualities are important for innovation. Innovation in City Governments: Structures...... that have value for stakeholders (such as citizens) in terms of the social and political outcomes they produce. Innovation in City Governments: Structures, Networks, and Leadership establishes an analytical framework of innovation capacity based on three dimensions: Structure - national governance...

  3. The Knowledge Governance Approach

    DEFF Research Database (Denmark)

    Foss, Nicolai J.

    An attempt is made to characterize a `knowledge governance approach' as a distinctive, emerging field that cuts across the fields of knowledge management, organisation studies, strategy and human resource management. Knowledge governance is taken up with how the deployment of administrative...... apparatus influences knowledge processes, such as sharing, retaining and creating knowledge. It insists on clear behavioural foundations, adopts an economizing perspective and examines efficient alignment between knowledge transactions with diverse characteristics and governance structures and mechanisms...... with diverse capabilities of handling these transactions. Various open research issues that a knowledge governance approach may illuminate are sketched. Although knowledge governance draws clear inspiration from organizational economics and `rational' organization theory, it recognizes that knowledge...

  4. Energy Efficiency Governance

    Energy Technology Data Exchange (ETDEWEB)



    The purpose of this report is to help EE practitioners, government officials and stakeholders to establish the most effective EE governance structures, given their specific country context. It also aims to provide readers with relevant and accessible information to support the development of comprehensive and effective governance mechanisms. The International Energy Agency (IEA) conducted a global review of many elements of EE governance,including legal frameworks, institutional frameworks, funding mechanisms, co-ordination mechanisms and accountability arrangements, such as evaluation and oversight. The research tools included a survey of over 500 EE experts in 110 countries, follow-up interviews of over 120 experts in 27 countries and extensive desk study and literature searches on good EE governance.

  5. Making Government Liquid

    DEFF Research Database (Denmark)

    du Gay, Paul; Millo, Yuval; Tuck, Penelope


    The financialised character of contemporary rationalities of public governance has been the subject of increased attention within a range of disciplinary and interdisciplinary fields. With this paper we propose a particular analytical framework, focused on the notion of 'governance devices......', for understanding the processes that underpin financialised governance and, more fundamentally, maintain the connections between markets and politics. Deploying three distinct cases, we indicate that these devices transcend divisions between the actor and the device and create a diff erent form of agency......- an assemblage. We argue that understanding such assemblages-their emergence, activity, and, frequently, their failures-opens a window on analysing the nature of contemporary forms of financialised governance as a technosocial system. In so doing we suggest that the governance devices approach can off er a way...

  6. Governance, Trust and Taxes

    DEFF Research Database (Denmark)

    Weihe, Guri; Joensen, E. Juanna Schröter

    This paper examines the role of social capital (trust) vis-à-vis the propensity of a country to be a tax haven. The empirical analysis corroborates that better governed countries have a higher ceteris paribus probability to be tax havens. However, social capital counteracts the effect of governance...... quality. This effect is so strong that the partial effect of governance quality is reversed for countries with the trust index in the top quartile – making these high trust countries less likely to be tax havens – even as governance quality is increased. Thus it is crucial to consider the interaction...... between institutions and social capital, since the same governance institutions have a different impact on the tax haven propensity for countries with different social capital....

  7. Privacy and Open Government

    Directory of Open Access Journals (Sweden)

    Teresa Scassa


    Full Text Available The public-oriented goals of the open government movement promise increased transparency and accountability of governments, enhanced citizen engagement and participation, improved service delivery, economic development and the stimulation of innovation. In part, these goals are to be achieved by making more and more government information public in reusable formats and under open licences. This paper identifies three broad privacy challenges raised by open government. The first is how to balance privacy with transparency and accountability in the context of “public” personal information. The second challenge flows from the disruption of traditional approaches to privacy based on a collapse of the distinctions between public and private sector actors. The third challenge is that of the potential for open government data—even if anonymized—to contribute to the big data environment in which citizens and their activities are increasingly monitored and profiled.

  8. Four logics of governance

    DEFF Research Database (Denmark)

    Friche, Nanna; Normann Andersen, Vibeke

    and well-being of students enrolled in the VETs must be strengthened. We focus on target 1, 2 and 4. The reform is being implemented in a field of VET that can be characterized by four logics of governance. Firstly, a governance logic characterized by institutional independence of vocational colleges...... combined with state funding through a taximeter scheme (pay per student). Secondly, party governance system involving labor market partners at both national and local level formalized through a national Council for Vocational Training and 50 local trade committees as well as local education committees...... at each college. The third governance logic is based on a decentralized quality management system at each college. Each college has set up its own system of quality developments and quality assurances. The fourth governance logic is performance management conducted by the national level towards...

  9. A new corporate governance

    Directory of Open Access Journals (Sweden)

    Ion Bucur


    Full Text Available The issue of corporate governance has become increasingly important as globalisation has begun to accelerate and the economic and financial turmoil have intensified. Post-crisis context has imposed the need to expand the prospects for analysis over governance and companies, as well as the need to identify new ways of administration and resource management. From this perspective, the author aims to highlight the conditions, factors and events that have generated profound changes within the business environment, while the analysis is focusing on contemporary changes in the systems of corporate governance and economic mutations, especially in terms of the companies. The establishment of new governance rules is demanding a theoretical approach based on new methodological requirements which are needed to reform theoretical foundations and to promote creative and effective shapes and governance systems.

  10. Post-colonial governance through securitization?

    DEFF Research Database (Denmark)

    Rasmussen, Rasmus Kjærgaard; Merkelsen, Henrik


    This article combines the securitization approach with theory of risk and narratological methodology in the analysis of the Danish-Greenlandic government debates about potential uranium exploitation. The authors conclude that the securitization controversy visible at the surface level of policy...... documents reflects an identity struggle at the deeper narrative level closely related to the understanding of national identity politics. These underlying stakes are brought to the fore when securitization is used as a governance technique....

  11. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  12. The architecture of ligand attachment to nanocarriers controls their specific interaction with target cells


    Sawant, Rupa R.; Sawant, Rishikesh M.; Kale, Amit A.; Torchilin, Vladimir P.


    Surface architecture of pharmaceutical nanocarriers (using polymeric micelles as an example) and the length of the spacer group through which specific ligand is attached to the carrier surface determine the interaction of ligand-bearing nanocarrier with cells. We have prepared surface-modified polyethyleneglycol–phosphatidylethanolamine (PEG–PE) micelles containing TATp attached to PEG–PE with a PEG block longer or shorter (TATp–PEG1000–PE or TATp–PEG3400–PE) than the PEG block in the main mi...

  13. Transnational Governance and Constitutionalism

    DEFF Research Database (Denmark)

    Joerges, Christian; Sand, Inger-Johanne; Teubner, Gunther

    The term transnational governance designates untraditional types of international and regional collaboration among both public and private actors. These legally-structured or less formal arrangements link economic, scientific and technological spheres with political and legal processes. They are ......The term transnational governance designates untraditional types of international and regional collaboration among both public and private actors. These legally-structured or less formal arrangements link economic, scientific and technological spheres with political and legal processes....... They are challenging the type of governance which constitutional states were supposed to represent and ensure. They also provoke old questions: Who bears the responsibility for governance without a government? Can accountability be ensured? The term 'constitutionalism' is still widely identified with statal form...... of democratic governance. The book refers to this term as a yardstick to which then contributors feel committed even where they plead for a reconceptualisation of constitutionalism or a discussion of its functional equivalents. 'Transnational governance' is neither public nor private, nor purely international...

  14. Ligand functionality as a versatile tool to control the assembly behavior of preformed titania nanocrystals. (United States)

    Polleux, Julien; Pinna, Nicola; Antonietti, Markus; Hess, Christian; Wild, Ute; Schlögl, Robert; Niederberger, Markus


    Nanoparticle powders composed of surface-functionalized anatase crystals with diameters of about 3 nm self-organize into different structures upon redispersion in water. The assembly is directed by a small amount of a low-molecular-weight functional ligand (the "assembler") adsorbed on the surface of the nanoparticles. The ligand functionality determines the anisotropy of the resulting structures. Multidentate ligands, such as trizma ((HOCH(2))(3)CNH(2)) and serinol ((HOCH(2))(2)CNH(2)), with a chargeable terminal group preferentially induce the formation of anisotropic nanostructures several hundreds of nanometers in total length, whereas all the other investigated ligands (ethanolamine H(2)N(CH(2))(2)OH, glycine hydroxamate H(2)NCH(2)CONHOH, dopamine (OH)(2)C(6)H(3)(CH(2))(2)NH(3)Cl, tris (HOCH(2))(3)CCH(3)) mainly lead to uncontrolled agglomeration. Experimental data suggests that the anisotropic assembly is a consequence of the water-promoted desorption of the organic ligands from the {001} faces of the crystalline building blocks together with the dissociative adsorption of water on these crystal faces. Both processes induce the preferred attachment of the titania nanoparticles along the [001] direction. The use of polydentate and charged ligands to functionalize the surface of nanoparticles thus provides a versatile tool to control their arrangement on the nanoscale.

  15. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara


    in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs......” in their communication efforts, and that they face a daily professional challenge as they attempt to promote the European Parliament and its activities to the news media in a way that will not compromise their credibility as government sources. The study provides new insights into communicative aspects of EU governance...

  16. Ambidextrous IT Governance

    DEFF Research Database (Denmark)

    Andersen, Peter; Svejvig, Per; Tordrup Heeager, Lise


    Through a case study at a global technology company, we investigate how organizations can adapt their IT governance approach to the information system at hand. This is done by considering the degree of information system integration and whether the system is related to supporting operational...... efficiency (exploitation) or innovation (exploration). Based on the findings of the case study, we introduce the concept of ambidextrous IT governance to describe how IT governance can be adapted to fit the dual needs of both exploration and exploitation through the use of IS....

  17. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel


    G protein-coupled receptors (GPCRs) belong to a large superfamily of membrane receptors mediating a variety of physiological functions. As such they are attractive targets for drug therapy. However, it remains a challenge to develop subtype selective GPCR ligands due to the high conservation...... sites. Computational studies on ligand binding to GPCRs have revealed transient, low-affinity binding sites, termed metastable binding sites. Metastable binding sites may provide a new source of allosteric binding sites that could be exploited in the design of bitopic ligands. Unlike the bitopic ligands...

  18. Clinical Use of PPARγ Ligands in Cancer

    Directory of Open Access Journals (Sweden)

    Jennifer L. Hatton


    Full Text Available The role of PPARγ in adipocyte differentiation has fueled intense interest in the function of this steroid nuclear receptor for regulation of malignant cell growth and differentiation. Given the antiproliferative and differentiating effects of PPARγ ligands on liposarcoma cells, investigation of PPARγ expression and ligand activation in other solid tumors such as breast, colon, and prostate cancers ensued. The anticancer effects of PPARγ ligands in cell culture and rodent models of a multitude of tumor types suggest broad applicability of these agents to cancer therapy. This review focuses on the clinical use of PPARγ ligands, specifically the thiazolidinediones, for the treatment and prevention of cancer.

  19. Fibronectin and avidin-biotin as a heterogeneous ligand system for enhanced endothelial cell adhesion. (United States)

    Bhat, V D; Truskey, G A; Reichert, W M


    A preadsorbed layer of "heterogeneous" integrin-dependent and -independent protein was used to enhance initial integrin-mediated endothelial cell attachment and spreading. Glass substrates were treated with fibronectin (Fn) and avidin coupled through adsorbed biotinylated bovine serum albumin (b-BSA). The slides then were seeded with biotinylated BAEC. Control "homogeneous" surfaces were slides adsorbed with either Fn or avidin coupled to b-BSA. The cells were incubated for 0.5 h in serum-containing media and exposed to a range of shear stresses in a laminar flow variable-height flow chamber. The critical shear stress to detach 50% of the seeded cells on the heterogeneous ligand surface was significantly greater than for either of the control homogeneous ligand systems (p < 0.001). Cellular spreading during the initial period of 0-2 h also was higher (p < 0.05) on the heterogeneous ligand-treated surface than on the surface of either of the homogeneous controls. The close contact area of the cell membrane with the substrate 1 h after seeding in serum-containing media was measured using TIRFM. Cells attached onto the heterogeneous ligand-treated surfaces had a significantly (p < 0.01) higher area of close contact with the substrate, which is consistent with a greater degree of attachment and spreading. The results indicate that the combination of integrin-dependent and -independent adhesion systems using heterogeneous ligands further enhances initial endothelial cell attachment and spreading.

  20. Explicit all-atom modeling of realistically sized ligand-capped nanocrystals

    KAUST Repository

    Kaushik, Ananth P.


    We present a study of an explicit all-atom representation of nanocrystals of experimentally relevant sizes (up to 6 nm), capped with alkyl chain ligands, in vacuum. We employ all-atom molecular dynamics simulation methods in concert with a well-tested intermolecular potential model, MM3 (molecular mechanics 3), for the studies presented here. These studies include determining the preferred conformation of an isolated single nanocrystal (NC), pairs of isolated NCs, and (presaging studies of superlattice arrays) unit cells of NC superlattices. We observe that very small NCs (3 nm) behave differently in a superlattice as compared to larger NCs (6 nm and above) due to the conformations adopted by the capping ligands on the NC surface. Short ligands adopt a uniform distribution of orientational preferences, including some that lie against the face of the nanocrystal. In contrast, longer ligands prefer to interdigitate. We also study the effect of changing ligand length and ligand coverage on the NCs on the preferred ligand configurations. Since explicit all-atom modeling constrains the maximum system size that can be studied, we discuss issues related to coarse-graining the representation of the ligands, including a comparison of two commonly used coarse-grained models. We find that care has to be exercised in the choice of coarse-grained model. The data provided by these realistically sized ligand-capped NCs, determined using explicit all-atom models, should serve as a reference standard for future models of coarse-graining ligands using united atom models, especially for self-assembly processes. © 2012 American Institute of Physics.

  1. Remote Control of Multimodal Nanoscale Ligand Oscillations Regulates Stem Cell Adhesion and Differentiation. (United States)

    Kang, Heemin; Wong, Dexter Siu Hong; Yan, Xiaohui; Jung, Hee Joon; Kim, Sungkyu; Lin, Sien; Wei, Kongchang; Li, Gang; Dravid, Vinayak P; Bian, Liming


    Cellular adhesion is regulated by the dynamic ligation process of surface receptors, such as integrin, to adhesive motifs, such as Arg-Gly-Asp (RGD). Remote control of adhesive ligand presentation using external stimuli is an appealing strategy for the temporal regulation of cell-implant interactions in vivo and was recently demonstrated using photochemical reaction. However, the limited tissue penetration of light potentially hampers the widespread applications of this method in vivo. Here, we present a strategy for modulating the nanoscale oscillations of an integrin ligand simply and solely by adjusting the frequency of an oscillating magnetic field to regulate the adhesion and differentiation of stem cells. A superparamagnetic iron oxide nanoparticle (SPION) was conjugated with the RGD ligand and anchored to a glass substrate by a long flexible poly(ethylene glycol) linker to allow the oscillatory motion of the ligand to be magnetically tuned. In situ magnetic scanning transmission electron microscopy and atomic force microscopy imaging confirmed the nanoscale motion of the substrate-tethered RGD-grafted SPION. Our findings show that ligand oscillations under a low oscillation frequency (0.1 Hz) of the magnetic field promoted integrin-ligand binding and the formation and maturation of focal adhesions and therefore the substrate adhesion of stem cells, while ligands oscillating under high frequency (2 Hz) inhibited integrin ligation and stem cell adhesion, both in vitro and in vivo. Temporal switching of the multimodal ligand oscillations between low- and high-frequency modes reversibly regulated stem cell adhesion. The ligand oscillations further induced the stem cell differentiation and mechanosensing in the same frequency-dependent manner. Our study demonstrates a noninvasive, penetrative, and tunable approach to regulate cellular responses to biomaterials in vivo. Our work not only provides additional insight into the design considerations of biomaterials to

  2. Measuring the Valence of Nanocrystal Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Jonathan Scharle [Columbia Univ., New York, NY (United States)


    The goal of this project is to understand and control the interplay between nanocrystal stoichiometry, surface ligand binding and exchange, and the optoelectronic properties of semiconductor nanocrystals in solution and in thin solid films. We pursued three research directions with this goal in mind: 1) We characterized nanocrystal stoichiometry and its influence on the binding of L-type and X-type ligands, including the thermodynamics of binding and the kinetics of ligand exchange. 2) We developed a quantitative understanding of the relationship between surface ligand passivation and photoluminescence quantum yield. 3) We developed methods to replace the organic ligands on the nanocrystal with halide ligands and controllably deposit these nanocrystals into thin films, where electrical measurements were used to investigate the electrical transport and internanocrystal electronic coupling.

  3. Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

    Energy Technology Data Exchange (ETDEWEB)

    Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J


    Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH{sub 2}-PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH{sub 2}-PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His{sub 6}-tagged protein molecules to AFM tips via noncovalent NTA-Ni{sup 2+}-His{sub 6} bridges. The new crosslinker was applied to link a recombinant His{sub 6}-tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin {beta}1 was studied in detail by SMRFM, using the new crosslinker to link His{sub 6}-tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557].

  4. Cold pressure welding - the mechanisms governing bonding

    DEFF Research Database (Denmark)

    Bay, Niels


    Investigations of the bonding surface in scanning electron microscope after fracture confirm the mechanisms of bond formation in cold pressure welding to be: fracture of work-hardened surface layer, surface expansion increasing the area of virgin surface, extrusion of virgin material through cracks...... of the original surface layer, and establishment of real contact and bonding between virgin material. This implies that normal pressure as well as surface expansion are basic parameters governing the bond strength. Experimental investigations of pressure welding Al-Al under plane strain compression in a specially...... developed equipment allowing independent variation of normal pressure and surface expansion confirm this. Based upon a slip-line analysis of the extrusion through cracks of the surface layer and upon the establishment of real contact between virgin material, a theory for the bond strength as a function...

  5. Lean Government Methods Guide (United States)

    This Guide focuses primarily on Lean production, which is an organizational improvement philosophy and set of methods that originated in manufacturing but has been expanded to government and service sectors.

  6. Codes of Good Governance

    DEFF Research Database (Denmark)

    Beck Jørgensen, Torben; Sørensen, Ditte-Lene


    Good governance is a broad concept used by many international organizations to spell out how states or countries should be governed. Definitions vary, but there is a clear core of common public values, such as transparency, accountability, effectiveness, and the rule of law. It is quite likely......, however, that national views of good governance reflect different political cultures and institutional heritages. Fourteen national codes of conduct are analyzed. The findings suggest that public values converge and that they match model codes from the United Nations and the European Council as well...... as conceptions of good governance from other international organizations. While values converge, they are balanced and communicated differently, and seem to some extent to be translated into the national cultures. The set of global public values derived from this analysis include public interest, regime dignity...

  7. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank


    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  8. Government Risk-Bearing

    CERN Document Server


    The u.s. government bulks large in the nation's financial markets. The huge volume of government-issued and -sponsored debt affects the pricing and volume ofprivate debt and, consequently, resource allocation between competing alternatives. What is often not fully appreciated is the substantial influence the federal government wields overresource allocation through its provisionofcreditandrisk-bearing services to the private economy. Because peopleand firms generally seekto avoid risk, atsomeprice they are willing to pay another party to assume the risk they would otherwise face. Insurance companies are a class of private-sector firms one commonly thinks of as providing these services. As the federal government has expanded its presence in the U.S. economy during this century, it has increasingly developed programs aimed at bearing risks that the private sector either would not take on at any price, or would take on but atapricethoughtto besogreatthatmostpotentialbeneficiarieswouldnotpurchase the coverage. To...

  9. Governing the Conflicted Commons

    DEFF Research Database (Denmark)

    Sareen, Siddharth

    that presents a comprehensive overview and synthesis. Article 1 shows what nurtures democratisation using three dimensions of democratic practice: functional democratic institutions, people’s involvement with these institutions, and inclusive participation without co-option of decision-making and resources...... governance in Jharkhand, and (iii) what does local governance look like in practice in this state-building context? In the form of three research articles that prioritise the local impact of government action, it addresses specific versions of these research questions, namely: (i) What nurtures...... of government services is studied in three villages in West Singhbhum. One example is the regulation of trade in a non-wood forest product called the kendu leaf which is valuable for its use in rolling country cigarettes, while the other is a public scheme to provide minimum-wage labour work to every village...

  10. Enacting Governance through Strategy

    DEFF Research Database (Denmark)

    Brandtner, Christof; Höllerer, Markus A.; Meyer, Renate E.


    of strategy documents in city administration addresses these challenges. Our central claim is that strategy documents can be understood as a distinct discursive device through which local governments enact aspired governance configurations. We illustrate our argument empirically using two prominent examples...... that, while showing similar features and characteristics, are anchored in different administrative traditions and institutional frameworks: the city administrations of Sydney, Australia, and Vienna, Austria. The contribution of the paper is to show how strategy documents enact governance configurations...... along four core dimensions: the setting in space and time, the definition of the public, the framing of the res publica and legitimacy issues. Moreover, our comparative analysis of Sydney and Vienna gives evidence of differences in governance configurations enacted through strategy documents....

  11. Transgovernance: advancing sustainability governance

    National Research Council Canada - National Science Library

    Meuleman, Louis


    ... – together characterized as the emergence of a knowledge democracy – may imply for governance for sustainable development, on global and other levels of societal decision making, and the other way around...

  12. Tactics of the governed

    DEFF Research Database (Denmark)

    Rasmussen, Mattias Borg


    Abandonment has become a performative idiom in Andean Peru, where it retains its purchase despite the investments of the state. Local development is tied to the desire to be governed. In spite of prolonged state presence, the villages’ relationship to authorities is continuously and persistently ...... morally grounded claims to local authorities. The idiom of abandonment is therefore both effective and affective as a critique of governance and a claim to citizenship.......Abandonment has become a performative idiom in Andean Peru, where it retains its purchase despite the investments of the state. Local development is tied to the desire to be governed. In spite of prolonged state presence, the villages’ relationship to authorities is continuously and persistently...... figured as one of abandonment: villages are abandoned because someone is deliberately holding them in such unfortunate conditions. To figure abandonment in village politics is to draw on this idiom as an effective means of both communicating the historical experience of governance and putting forward...

  13. Oxygen Reduction Reaction on Pt Overlayers Deposited onto a Gold Film: Ligand, Strain, and Ensemble Effect

    DEFF Research Database (Denmark)

    Deng, Yu-Jia; Tripkovic, Vladimir; Rossmeisl, Jan


    on deposited Pt layers decreases with increasing Pt thickness. In the submonolayer region, however, the ORR activity is superior to that of bulk Pt. Using density functional theory (DFT) calculations, we correlate the observed activity trend to strain, ligand, and ensemble effects. At submonolayer coverage...... certain atom configurations weaken the binding energies of reaction intermediates due to a ligand and ensemble effect, thus effectively increasing the ORR activity. At higher Pt coverage the activity is governed by a strain effect, which lowers the activity by decreasing the oxidation potential of water...

  14. 77 FR 18258 - Government-to-Government Telephonic Consultation Meetings (United States)


    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR National Park Service Government-to-Government Telephonic Consultation Meetings AGENCY: National Park Service, Interior. SUMMARY: The National Park Service announces two telephonic government- to-government...

  15. Tension-filled Governance?

    DEFF Research Database (Denmark)

    Celik, Tim Holst

    on the statesituated tension-filled functional relationship between legitimation and accumulation, the study both historically and theoretically reworks this approach and reapplies it for the post-1970s/1990s governance period. It asks whether and to what extent governance has served as a distinctive post- 1970s/1990s...... state-facilitated way of bridging/altering the tension-filled relationship between legitimation and fiscal accumulation in Western European liberal-capitalist democratic polities....

  16. World Government: Utopia?


    Vahram Ayvazyan


    The aim of this paper is to analyze the possibility of having a world government, which world has been facing overarching changes since the end of Cold war, where bipolar world order has evolved into multipolar system through unipolarity. Analysis method in this paper have the sistematics: discussion of human nature and philosophical dimensions vis-à-vis individual, society and government, as well as society of societies; then briefly analyse globalization, the impact of individuals on inter...

  17. Corporate Governance Models


    Petre Brezeanu; Andrei Stănculescu


    In essence, the concept of corporate governance refers to the coordination of interests of the various stakeholders of the company: shareholders, managers, employees, creditors, customers, suppliers, state, etc. In every company’s environment there is a set of specific relationships between the physical or legal persons who have an interest (“stake”) in the business. In pursuit of entrepreneurial activity, the management or the governance of the company must take into account the inherent con...

  18. The first Government House


    Kelso, Jane


    The first Government House was not a simple singular structure but a complex with a yard, outbuildings, guardhouse, garden and great domain. It was a home, and office and a venue for public and private entertaining, but also a symbol of British authority, with all that that meant to different people, both then and now. A place of intimacy and officaldom, birth and death, celebration, confrontation and reconciliation, the first Government House was the scene of significant moments in the young...

  19. Competence, governance, and entrepreneurship

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahnke, Volker

    , what determines their boundaries and internal organization), but would also be helpful for informing strategy issues, such as understanding strategic flexibility, strategic options, and the sources of competitive advantage. This volume brings together prominent voices on competence, governance......This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives...

  20. Open Government and (Linked (Open (Government (Data

    Directory of Open Access Journals (Sweden)

    Christian Philipp Geiger


    Full Text Available This article explores the opening and the free usage of stored public sector data, supplied by state. In the age of Open Government and Open Data it’s not enough just to put data online. It should be rather weighed out whether, how and which supplied public sector data can be published. Open Data are defined as stored data which could be made accessible in a public interest without any restrictions for usage and distribution. These Open Data can possibly be statistics, geo data, maps, plans, environmental data and weather data in addition to materials of the parliaments, ministries and authorities. The preparation and the free access to existing data permit varied approaches to the reuse of data, discussed in the article. In addition, impulses can be given for Open Government – the opening of state and administration, to more transparency, participation and collaboration as well as to innovation and business development. The Open Data movement tries to get to the bottom of current publication processes in the public sector which could be formed even more friendly to citizens and enterprises.

  1. PatchSurfers: Two methods for local molecular property-based binding ligand prediction. (United States)

    Shin, Woong-Hee; Bures, Mark Gregory; Kihara, Daisuke


    Protein function prediction is an active area of research in computational biology. Function prediction can help biologists make hypotheses for characterization of genes and help interpret biological assays, and thus is a productive area for collaboration between experimental and computational biologists. Among various function prediction methods, predicting binding ligand molecules for a target protein is an important class because ligand binding events for a protein are usually closely intertwined with the proteins' biological function, and also because predicted binding ligands can often be directly tested by biochemical assays. Binding ligand prediction methods can be classified into two types: those which are based on protein-protein (or pocket-pocket) comparison, and those that compare a target pocket directly to ligands. Recently, our group proposed two computational binding ligand prediction methods, Patch-Surfer, which is a pocket-pocket comparison method, and PL-PatchSurfer, which compares a pocket to ligand molecules. The two programs apply surface patch-based descriptions to calculate similarity or complementarity between molecules. A surface patch is characterized by physicochemical properties such as shape, hydrophobicity, and electrostatic potentials. These properties on the surface are represented using three-dimensional Zernike descriptors (3DZD), which are based on a series expansion of a 3 dimensional function. Utilizing 3DZD for describing the physicochemical properties has two main advantages: (1) rotational invariance and (2) fast comparison. Here, we introduce Patch-Surfer and PL-PatchSurfer with an emphasis on PL-PatchSurfer, which is more recently developed. Illustrative examples of PL-PatchSurfer performance on binding ligand prediction as well as virtual drug screening are also provided. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The Role of Stress-Induced Ligands in Immune Response

    Directory of Open Access Journals (Sweden)

    G.Seyda Seydel


    Full Text Available Natural killer (NK cells which are a component of the immune system are capable of killing tumor cells and virally infected cells. The activation of NK cells is regulated by the balance of activating and inhibitory surface receptors. NKG2D is one of the these activating receptors. The ligands of NKG2D are the human class I like molecules MICA and MICB which are encoded within the human MHC. MICA and MICB are not expressed on normal cells but up-regulated under condition of stress such as heat schock and viral infection. Therefore, NKG2D ligands are defined as stress-induced antigens. [Archives Medical Review Journal 2011; 20(1.000: 1-19

  3. Single-molecule force spectroscopy on polyproteins and receptor-ligand complexes: The current toolbox. (United States)

    Ott, Wolfgang; Jobst, Markus A; Schoeler, Constantin; Gaub, Hermann E; Nash, Michael A


    Single-molecule force spectroscopy sheds light onto the free energy landscapes governing protein folding and molecular recognition. Since only a single molecule or single molecular complex is probed at any given point in time, the technique is capable of identifying low-probability conformations within a large ensemble of possibilities. It furthermore allows choosing certain unbinding pathways through careful selection of the points at which the force acts on the protein or molecular complex. This review focuses on recent innovations in construct design, site-specific bioconjugation, measurement techniques, instrumental advances, and data analysis methods for improving workflow, throughput, and data yield of AFM-based single-molecule force spectroscopy experiments. Current trends that we highlight include customized fingerprint domains, peptide tags for site-specific covalent surface attachment, and polyproteins that are formed through mechanostable receptor-ligand interactions. Recent methods to improve measurement stability, signal-to-noise ratio, and force precision are presented, and theoretical considerations, analysis methods, and algorithms for analyzing large numbers of force-extension curves are further discussed. The various innovations identified here will serve as a starting point to researchers in the field looking for opportunities to push the limits of the technique further. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Macrocyclic ligands for uranium complexation

    Energy Technology Data Exchange (ETDEWEB)

    Potts, K.T.


    A highly preorganized 24-macrocycle containing biuret, thiobiuret and pyridine subunits has been prepared by high dilution ring-closure procedures. Intermediate products to this macrocycle have been utilized to extend this synthetic route to include further representatives where solubility and stability will be influenced by substituent variation. A 1:1 complex has been formed from uranyl acetate and a quinquepyridine derivative, this representing a new type of ligand for the uranyl ion. A very convenient synthetic procedure that will allow the incorporation of these macrocycles into polymeric systems has been developed for the introduction of a vinyl substituent into the 4-position of the pyridine ring. Using triflate, vinyltributyltin and Pd{sup 0} chemistry, this procedure should make a variety of substituted 4-vinylpyridines available for the first time. 3 refs.

  5. Corporate Governance Country Assessment : Vietnam


    World Bank


    This report assesses Vietnam's corporate governance policy framework. It highlights recent improvements in corporate governance regulation, makes policy recommendations, and provides investors with a benchmark against which to measure corporate governance in Vietnam. It is an update of the 2006 Corporate Governance ROSC for Vietnam. Good corporate governance enhances investor trust, protec...

  6. Ligand-binding kinetics on histamine receptors

    NARCIS (Netherlands)

    Bosma, Reggie; Mocking, T.A.M.; Leurs, R.; Vischer, H.F.


    Equilibrium-binding affinities of ligands for a drug target do not always accurately reflect the success of drug candidates in the clinic. Affinity-based predictions concerning competitive antagonism on the target will only be accurate if equilibrium binding of both ligands is allowed. Unless

  7. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)



    Jun 21, 2010 ... deacetylases (HDAC) have emerged as an important class of anticancer agents. Various side effects like myocardium damage and ... calculated through the software Jmol. The proposed model has been .... The study was carried out using the software Ligand Scout (version. 2.03[i2_001]). Ligand Scout is a ...

  8. Simple tertiary phosphines to hexaphosphane ligands: Syntheses ...

    Indian Academy of Sciences (India)

    Abstract. Designing efficient phosphorus-based ligands to make catalysts for homogeneous catalysis has been a great challenge for chemists. Despite a plethora of phosphorus ligands ranging from simple tertiary phosphines to polyphosphines are known, the enthusiasm to generate new ones is mainly due to the demand.

  9. Organotellurium ligands – designing and complexation reactions

    Indian Academy of Sciences (India)


    Abstract. A variety of tellurium ligands has been designed and studied for their complexation reactions in the last decade. Of these hybrid telluroethers, halotellurium ligands and polytellurides are the most notable ones. RTe–and polytelluride ions have also been used to design clusters. Ligation of ditelluroethers and ...

  10. CXCR4 Ligands : The Next Big Hit?

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen


    The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

  11. Dangerous Liaisons? Governments, companies and Internet governance

    Directory of Open Access Journals (Sweden)

    Francesca Musiani


    Full Text Available Private actors in the information technology sector are currently playing an increasingly important role in content mediation, as well as in regulation of online forms of expression, with implications for both internet rights and economic freedom. The “privatisation of internet governance” (DeNardis, 2010, is not a new dynamic; however, in a scenario in which users are taking advantage of increasingly sophisticated technology, the centralisation and concentration characterising today’s most widespread internet services are contributing to the accentuation of this tendency. The 'inherently political' qualities of search engine algorithm development, video content removals, blocking of domain names – actions that originate and rest with the private sector’s handling of the internet’s infrastructure – should not be neglected in our assessment of the field of internet governance today.

  12. Flexible ligand docking using a genetic algorithm (United States)

    Oshiro, C. M.; Kuntz, I. D.; Dixon, J. Scott


    Two computational techniques have been developed to explore the orientational and conformational space of a flexible ligand within an enzyme. Both methods use the Genetic Algorithm (GA) to generate conformationally flexible ligands in conjunction with algorithms from the DOCK suite of programs to characterize the receptor site. The methods are applied to three enzyme-ligand complexes: dihydrofolate reductase-methotrexate, thymidylate synthase-phenolpthalein and HIV protease-thioketal haloperidol. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. The potential for the GA method to screen a database of compounds is also examined. A collection of ligands is evaluated simultaneously, rather than docking the ligands individually into the enzyme.

  13. Molecular Recognition and Immobilization of Ligand-Conjugated Redox-Responsive Polymer Nanocontainers. (United States)

    de Vries, Wilke C; Tesch, Matthias; Studer, Armido; Ravoo, Bart Jan


    We present the preparation of ligand-conjugated redox-responsive polymer nanocontainers by the supramolecular decoration of cyclodextrin vesicles with a thin redox-cleavable polymer shell that displays molecular recognition units on its surface. Two widely different recognition motifs (mannose-Concanavalin A and biotin-streptavidin) are compared and the impact of ligand density on the nanocontainer surface as well as an additional functionalization with nonadhesive poly(ethylene glycol) is studied. Aggregation assays, dynamic light scattering, and a fluorometric quantification reveal that the molecular recognition of ligand-conjugated polymer nanocontainers by receptor proteins is strongly affected by the multivalency of interactions and the association strength of the recognition motif. Finally, microcontact printing is used to prepare streptavidin-patterned surfaces, and the specific immobilization of biotin-conjugated nanocontainers is demonstrated. As a prototype of a nanosensor, these tethered nanocontainers can sense a reductive environment and react by releasing a payload.

  14. How nations govern growth. (United States)


    Officials in China admit that the killing or abondoning of baby girls stems from a government policy limiting couples to 1 child combined with an ancient preference for sons. At the same time leaders maintain that population growth is an national emergency and must be checked. And the 1-child policy remains. To enforce the policy, sterilization is compulsory for 1 parent in a 2-child family. Other reports claim that pregnant women face severe government and social pressure to have an abortion. Comunist governments are not alone in taking a forceful role in population control. In 1975 thousands of people in India were pressured to undergo "voluntary" sterilization. In many places, police and tax collectors, money in hand, "convinced" people to get sterilized. Critics recognize a horribla abuse of government powers in these population control efforts. Recognizing that the populations of the poorest nations will double in 20-30 years, 59 countries responded with some kind of population policy by 1980. These countries are spending an average of US$4.60 on population programs for each US$1 they received in UN aid. In many places, the effort is beginning to show results. A 1982 survey found that 35 countries -- with 88% of the 3rd world population -- had cut the growth of their birthrates by 5-34%. Generally, governments have chosen any of 3 ways to attack the problem: cash payments for sterilization or contraceptive use; penalties for big families; and "delayed incentives." At least 20 governments use money to convince people to have fewer babies. Some programs pay for sterilization,other for contraceptive use. All payments are low. Some governments personalize those who exceed a recommended family size. Other nations have adopted variations of the idea. Some governments, instead of paying up front cash, offer pension plans or bank accounts to limit family size. Almost all population experts believe that the mot successful programs are those which are not imposed from

  15. Romanian government bond market

    Directory of Open Access Journals (Sweden)

    Cornelia POP


    Full Text Available The present paper aims to present the level of development reached by Romanian government bond market segment, as part of the country financial market. The analysis will be descriptive (the data series available for Romania are short, based on the secondary data offered by the official bodies involved in the process of issuing and trading the Romanian government bonds (Romanian Ministry of Public Finance, Romanian National Bank and Bucharest Stock Exchange, and also on secondary data provided by the Federation of European Stock Exchanges.To enhance the market credibility as a benchmark, a various combination of measures is necessary; among these measures are mentioned: the extension of the yield curve; the issuance calendars in order to improve transparency; increasing the disclosure of information on public debt issuance and statistics; holding regular meetings with dealers, institutional investors and rating agencies; introducing a system of primary dealers; establishing a repurchase (repo market in the government bond market. These measures will be discussed based on the evolution presented inside the paper.The paper conclude with the fact that, until now, the Romanian government bond market did not provide a benchmark for the domestic financial market and that further efforts are needed in order to increase the government bond market transparency and liquidity.

  16. Climate change governance

    Energy Technology Data Exchange (ETDEWEB)

    Knieling, Joerg [HafenCity Univ. Hamburg (Germany). Urban Planning and Regional Development; Leal Filho, Walter (eds.) [HAW Hamburg (Germany). Research and Transfer Centre Applications of Life Science


    Climate change is a cause for concern both globally and locally. In order for it to be tackled holistically, its governance is an important topic needing scientific and practical consideration. Climate change governance is an emerging area, and one which is closely related to state and public administrative systems and the behaviour of private actors, including the business sector, as well as the civil society and non-governmental organisations. Questions of climate change governance deal both with mitigation and adaptation whilst at the same time trying to devise effective ways of managing the consequences of these measures across the different sectors. Many books have been produced on general matters related to climate change, such as climate modelling, temperature variations, sea level rise, but, to date, very few publications have addressed the political, economic and social elements of climate change and their links with governance. This book will address this gap. Furthermore, a particular feature of this book is that it not only presents different perspectives on climate change governance, but it also introduces theoretical approaches and brings these together with practical examples which show how main principles may be implemented in practice.

  17. Effects of anchor structure and glycosylation of Fcγ receptor III on ligand binding affinity (United States)

    Jiang, Ning; Chen, Wei; Jothikumar, Prithiviraj; Patel, Jaina M.; Shashidharamurthy, Rangaiah; Selvaraj, Periasamy; Zhu, Cheng


    Isoforms of the Fcγ receptor III (FcγRIII or CD16) are cell surface receptors for the Fc portion of IgG and important regulators of humoral immune responses. Different ligand binding kinetics of FcγRIII isoforms are obtained in three dimensions by surface plasmon resonance and in two dimensions by a micropipette adhesion frequency assay. We show that the anchor structure of CD16 isoforms isolated from the cell membrane affects their binding affinities in a ligand-specific manner. Changing the receptor anchor structure from full to partial to none decreases the ligand binding affinity for human IgG1 (hIgG1) but increases it for murine IgG2a (mIgG2a). Removing N-glycosylation from the CD16 protein core by tunicamycin also increases the ligand binding affinity. Molecular dynamics simulations indicate that deglycosylation at Asn-163 of CD16 removes the steric hindrance for the CD16-hIgG1 Fc binding and thus increases the binding affinity. These results highlight an unexpected sensitivity of ligand binding to the receptor anchor structure and glycosylation and suggest their respective roles in controlling allosterically the conformation of the ligand binding pocket of CD16. PMID:27582391

  18. Ideal CdSe/CdS core/shell nanocrystals enabled by entropic ligands and their core size-, shell thickness-, and ligand-dependent photoluminescence properties. (United States)

    Zhou, Jianhai; Zhu, Meiyi; Meng, Renyang; Qin, Haiyan; Peng, Xiaogang


    This work explored possibilities to obtain colloidal quantum dots (QDs) with ideal photoluminescence (PL) properties, i.e., mono-exponential PL decay dynamics, unity PL quantum yield, ensemble PL spectrum identical to that at single-dot level, single-dot PL non-blinking, and anti-bleaching. Using CdSe/CdS core/shell QDs as the model system, shell-epitaxy, ligand exchange, and shape conversion of the core/shell QDs were studied systematically to establish a strategy for reproducibly synthesizing QDs with the targeted properties. The key synthetic parameter during epitaxy was application of entropic ligands, i.e., mixed carboxylate ligands with different hydrocarbon-chain length and/or structure. While well-controlled epitaxial shells with certain thickness (~3-8 monolayers of the CdS shells) were found to be necessary to reach ideal photoluminescence properties, size of the core QDs was found to play a critical role in determining both photo-physical and photo-chemical properties of the core/shell QDs. Effects of shape of the core QDs were unnoticeable, and shape of the core/shell QDs only affected photo-physical properties quantitatively. Surface ligands-amines versus carboxylates-were important for photo-chemical properties (anti-blinking and anti-bleaching) but barely affected photo-physical properties as long as entropic ligands (mixed carboxylate ligands with distinguishable hydrocarbon chain lengths) were applied during epitaxy. Chemical environment (in polymer or in air), coupled with surface ligands, determined photo-chemical properties of the core/shell QDs with a given core size and shell thickness.

  19. Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Holm, Thomas L.; Krych, Lukasz


    Intestinal epithelial cells (IECs) are one of a few cell types in the body with constitutive surface expression of natural killer group 2 member D (NKG2D) ligands, although the magnitude of ligand expression by IECs varies. Here, we investigated whether the gut microbiota regulates the NKG2D ligand...... expression is kept in check by an intestinal regulatory immune milieu induced by members of the gut microbiota, for example A. muciniphila....... expression on small IECs. Germ-free and ampicillin-treated mice were shown to have a significant increase in NKG2D ligand expression. Interestingly, vancomycin treatment, which propagated the bacterium Akkermansia muciniphila and reduced the level of IFN-¿ and IL-15 in the intestine, decreased the NKG2D...

  20. Trialogue model for ecosystem governance.

    CSIR Research Space (South Africa)

    Hattingh, J


    Full Text Available The International Symposium on Ecosystem Governance held in South Africa during 2005 enabled scientists from several disciplines to debate issues relating to governance. The symposium provided an opportunity to explore the concept of governance...

  1. Managing e-government

    DEFF Research Database (Denmark)

    Rose, Jeremy; Persson, John Stouby; Heeager, Lise Tordrup


    Public sector managers take much of the responsibility for selecting, commissioning, implementing and realising benefits from information technology (IT) projects. However, e-Government initiatives often suffer from complexity, vision failure, lack of goal clarity and insufficient commitment....... These problems may stem from value traditions that are deeply ingrained in managers' cultural environments but not always in harmony with each other. A first step towards working with value complexity is to understand it; we synthesise a model of value positions for e-Government derived from major traditions...... in the public administration literature. Four value positions relevant to e-Government together with their IT assumptions are identified; they reflect the ideals of professionalism, efficiency, service and engagement. A qualitative investigation of Danish local authority managers displays both value congruence...

  2. Pension Fund Governing Board

    CERN Multimedia

    HR Department


    Note The CERN pension scheme is based on the principle of defined benefits, so beneficiaries continue to receive the benefits to which they are entitled in accordance with the Rules of the Pension Fund. This means that pension entitlements under the Rules are not directly affected by the financial crisis and the current economic situation. However, the adjustment of pensions to the cost of living is not automatic and, under the method applied since 2006, must take into account the Fund’s financial position. Meeting of the Pension Fund Governing Board The Pension Fund Governing Board held its eighth meeting at ESO in Garching, Germany (near Munich) on 24 October 2008. Before starting its work, the Governing Board had the privilege of hearing an opening address by Professor Tim de Zeeuw, the Director General of ESO. Professor de Zeeuw described the mission of ESO and the ambitious projects of his organisation, which performs astronomy observations using telescopes located in...

  3. Why Governments Intervene

    DEFF Research Database (Denmark)

    Brown, Dana; Knudsen, Jette Steen

    Why are national governments increasingly adopting policies on Corporate Social Responsibility (CSR)? What is the rationale and purpose of these policies? Scholars from various disciplines including Political Science, International Relations and Management Studies have offered explanations...... for this phenomenon. Research has tended either to rely on cross-country comparisons that generalize tendencies within given countries; or to over-generalize global trends. The current paper analyzes particular CSR policies in two countries – Denmark and the United Kingdom. We find that the rationales for government...... initiatives on CSR are neither consistent across countries or within them. Instead, CSR policies are utilized to address multiple issues crossing various areas of governance, including domestic social policy, global competitiveness policies and foreign policy....

  4. Corporate governance and liquidity

    DEFF Research Database (Denmark)

    Farooq, Omar; Derrabi, Mohamed; Naciri, Monir


    difference in liquidity between the two periods. Furthermore, our results indicate that more than 50% of this difference between the two periods can be explained by operational and informational complexity of a firm – proxy for transparency. We argue that poor corporate governance mechanisms increase......This paper examines the impact of corporate governance mechanisms on liquidity in the MENA region, i.e. Morocco, Egypt, Saudi Arabia, United Arab Emirates, Jordan, Kuwait, and Bahrain. Using turnover as a proxy for liquidity, we document significant difference in liquidity between the pre......- and the post-crisis periods in the MENA region. In addition, our results show that bulk of this reduction in turnover can be explained due to weaknesses of corporate governance mechanisms. For example, that dividend payout ratio and choice of auditors – proxies for agency problems – can explain the entire...

  5. Governance of the future

    DEFF Research Database (Denmark)

    Galløe, Lotte Rannveig

    a different future for both parents and children. Thus, the approach to PMTO as a technology of the future indicates its expected prevalence in the future and its attempt to reach in to the future becoming of the child. The technology’s involvement of the relatives and its orientation towards shaping...... governance seek to chance the possible future conditions and targets the marginalized child’s relatives? Parent Management Training (PMTO) is studied as a technology of the future that expands and transforms governance. PMTO targets parents with aggressive and asocial children and aims to “create the parent...... as the child’s best teacher”. The program involves parents as facilitators modifying the child’s behavior instead of working directly on the child, thereby widening the target of intervention. PMTO exemplifies an arrangement that engages the private sphere in the conduct of public governance aiming at creating...

  6. NMR and computational methods in the structural and dynamic characterization of ligand-receptor interactions. (United States)

    Ghitti, Michela; Musco, Giovanna; Spitaleri, Andrea


    The recurrent failures in drug discovery campaigns, the asymmetry between the enormous financial investments and the relatively scarce results have fostered the development of strategies based on complementary methods. In this context in recent years the rigid lock-and-key binding concept had to be revisited in favour of a dynamic model of molecular recognition accounting for conformational changes of both the ligand and the receptor. The high level of complexity required by a dynamic description of the processes underlying molecular recognition requires a multidisciplinary investigation approach. In this perspective, the combination of nuclear magnetic resonance spectroscopy with molecular docking, conformational searches along with molecular dynamics simulations has given new insights into the dynamic mechanisms governing ligand receptor interactions, thus giving an enormous contribution to the identification and design of new and effective drugs. Herein a succinct overview on the applications of both NMR and computational methods to the structural and dynamic characterization of ligand-receptor interactions will be presented.

  7. Transition Metal Complexes Coordinated by Water Soluble Phosphane Ligands: How Cyclodextrins Can Alter the Coordination Sphere?

    Directory of Open Access Journals (Sweden)

    Michel Ferreira


    Full Text Available The behaviour of platinum(II and palladium(0 complexes coordinated by various hydrosoluble monodentate phosphane ligands has been investigated by 31P{1H} NMR spectroscopy in the presence of randomly methylated β-cyclodextrin (RAME-β-CD. This molecular receptor can have no impact on the organometallic complexes, induce the formation of phosphane low-coordinated complexes or form coordination second sphere species. These three behaviours are under thermodynamic control and are governed not only by the affinity of RAME-β-CD for the phosphane but also by the phosphane stereoelectronic properties. When observed, the low-coordinated complexes may be formed either via a preliminary decoordination of the phosphane followed by a complexation of the free ligand by the CD or via the generation of organometallic species complexed by CD which then lead to expulsion of ligands to decrease their internal steric hindrance.

  8. Instruments of Transformative Governance

    DEFF Research Database (Denmark)

    Borrás, Susana

    production and distribution channels. PDPs aim at overcoming current market and government failures by pooling resources in the attempt to solve this global social challenge. Thus, PDPs are a case of instruments of transformative research and innovation, operating in a transnational governance context....... They exhibit three novelties: they address strategic long-term problems in a holistic manner, set substantive output-oriented goals, and are implemented through new organizational structures. After characterizing the different types of current PDPs and the context in which they emerged, the paper examines...

  9. Governance Vote Results (United States)

    Bamzai, Anjuli; Robinson, Robert; Shirey, Steven


    Voting by the membership for proposed changes to AGU bylaws and articles of incorporation was completed on 13 November 2009. The proposed changes would expand AGU's Council to focus it on science; shift the business and fiduciary responsibility for AGU to a newly created, smaller Board of Directors, freeing the Council to focus on science policy and other science-related matters; and modernize AGU's governing documents to reflect current practice in not-for-profit governance. All background information was provided in the 15 September 2009 issue of Eos and in subsequent issues.

  10. Making Migrants Governable

    DEFF Research Database (Denmark)

    Stenum, Helle


    This paper will investigate the production of knowledge regarding the number of illegalized migrants. Estimation of the number has been the common frame for production of this kind of knowledge, performed by social scientists, government officials, NGOs and others, but now biometric technology...... by biometric technology will produce increased objectivity and depolitization in numbers of irregular migrants which could not be obtained in the field of estimation. The level of truth reflects the level of control and surveillance fixed as a strategy of government of mobility in the biometric technology....

  11. Governing EU employment policy

    DEFF Research Database (Denmark)

    Sørensen, Eva; Triantafillou, Peter; Damgaard, Bodil


    In the European Union (EU), employment policy is a prerogative of the member states. Therefore the EU's ability to govern in this area depends on its capability to involve national governments and relevant stakeholders in a collaborative effort to formulate and implement shared policy objectives....... Drawing an analytical distinction between cooperation, coordination and collaboration, the article analyses the formulation and implementation of EU employment policies. It concludes that while the formulation of policy objectives and the discussion of national policy approaches do involve elements...

  12. Governing To‐day

    DEFF Research Database (Denmark)

    Turner, Kevin

    Governing To-day denotes a domain of research, and what the thesis undertakes is a theoretical discussion of some questions of method vis-à-vis researching this domain. There are two aspects to the title that enfold one another. Firstly, “governing to-day” signposts that it is to!day that is to b...... of departure in the research and writing of the French philosopher and historian, Michel Foucault. It is primarily within the writings of Foucault that the thesis seeks to find a workaround to the problem thrown forth by the aforementioned questions of method....

  13. Governing IT outsourcing relationships

    CERN Document Server

    Kuhlmann, Daniel


    Hauptbeschreibung The dynamics of the relationship between service recipient and service provider in IS outsourcing relationships recently gained increased attention as relationships are believed to have a considerable influence on IS outsourcing success. This study adds to this growing field of interest by developing an IS outsourcing relationship framework in the form of a process model. Three rather disjointed areas of research, namely contractual governance, relational norms, and control, have been set in a common context by interrelating them as the three main governance modes

  14. Competence, governance, and entrepreneurship

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahnke, Volker

    This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives on the f......This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives......, and entrepreneurship to advance and stimulate economic strategy research....

  15. Frontal affinity chromatography with MS detection of the ligand binding domain of PPARγ receptor: ligand affinity screening and stereoselective ligand-macromolecule interaction. (United States)

    Calleri, E; Fracchiolla, G; Montanari, R; Pochetti, G; Lavecchia, A; Loiodice, F; Laghezza, A; Piemontese, L; Massolini, G; Temporini, C


    In this study we report the development of new chromatographic tools for binding studies based on the gamma isoform ligand binding domain (LBD) of peroxisome proliferator-activated receptor (PPARγ) belonging to the nuclear receptor superfamily of ligand-activated transcription factors. PPARγ subtype plays important roles in the functions of adipocytes, muscles, and macrophages with a direct impact on type 2 diabetes, dyslipidemia, atherosclerosis, and cardiovascular disease. In order to set up a suitable immobilization chemistry, the LBD of PPARγ receptor was first covalently immobilized onto the surface of aminopropyl silica particles to create a PPARγ-Silica column for zonal elution experiments and then onto the surface of open tubular (OT) capillaries to create PPARγ-OT capillaries following different immobilization conditions. The capillaries were used in frontal affinity chromatography coupled to mass spectrometry (FAC-MS) experiments to determine the relative binding affinities of a series of chiral fibrates. The relative affinity orders obtained for these derivatives were consistent with the EC(50) values reported in literature. The optimized PPARγ-OT capillary was validated by determining the K(d) values of two selected compounds. Known the role of stereoselectivity in the binding of chiral fibrates, for the first time a detailed study was carried out by analysing two enantioselective couples on the LBD-PPARγ capillary by FAC and a characteristic two-stairs frontal profile was derived as the result of the two saturation events. All the obtained data indicate that the immobilized form of PPARγ-LBD retained the ability to specifically bind ligands. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Land Use and Land Cover, Impervious Surface - contains polygons that represent houses, buildings, roads, driveways, sidewalks, pools, patios, parking lots, pavements, Published in 2008, 1:2400 (1in=200ft) scale, Effingham County Government. (United States)

    NSGIC Local Govt | GIS Inventory — Land Use and Land Cover dataset current as of 2008. Impervious Surface - contains polygons that represent houses, buildings, roads, driveways, sidewalks, pools,...

  17. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert


    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  18. Crystal structure, Hirshfeld surface, physicochemical, thermal and DFT studies of (N1E, N2E)-N1,N2-bis((5-bromothiophen-2-yl)methylene)ethane-1,2-diamine N2S2 ligand and its [CuBr(N2S2)]Br complex (United States)

    Warad, Ismail; Al-Demeri, Yasmin; Al-Nuri, Mohammed; Shahwan, Said; Abdoh, Muneer; Naveen, Shivalingegowda; Lokanath, Neartur Krishnappagowda; Mubarak, Mohammad S.; Ben Hadda, Taibi; Mabkhot, Yahia N.


    A new tetradentate N2S2 Schiff base ligand derived from 5-bromothiophene-2-carbaldehyde and its [CuBr(N2S2)]Br complex were synthesized in good yield. FT-IR was investigated to monitor the condensation reaction during the ligand synthesis process. The ligand, N2S2, and its complex, [CuBr(N2S2)]Br, complex have been characterized with the aid of several spectroscopic techniques such as UV-vis., MS, FT-IR, EA, EDS, NMR (for N2S2), as well as by thermal (TG/DTG) analysis. In addition, cyclic voltammetry has been employed to examine the redox behavior of [CuBr(N2S2)]Br complex in N,N'-dimethylformamide (DMF) containing 0.10 M tetra-n-butylammonium perchlorate (TBAP). The anti-conformation EE isomer of the ligand (N2S2) was confirmed by means of X-ray crystallography; ligand crystallizes in to the monoclinic P21/c space group. N2S2 ligand was subjected to DFT-theoretical calculations and results are consistent with the experimental chemical analysis.

  19. Local government`s pollution prevention program

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, D. [Boulder Country Pollution Prevention Program, Boulder, CO (United States)


    The pollution prevention program operated by the Health Department of Boulder County is called Business Partners for a Clean Environment (Business Partners). It is a cooperative effort among local businesses, the City of Boulder, Boulder County, and the Boulder Chamber of Commerce. This nonregulatory, incentive-based program provides industry with pollution prevention information and technical assistance necessary to reduce and/or eliminate environmental waste. This paper provides an overview of the program development, creation of partnerships and trust, and some of the results from implementation of the program. Following the first 18 months of the program, 35 businesses were recognized as Business Partners. The Business Partners program has also received an achievement award from the National Association of Counties for promoting {open_quotes}responsible, responsive, and effective government{close_quotes} and two governor`s awards from the State of Colorado. Participating businesses have demonstrated that a pollution prevention program can reduce environmental waste, increase employee safety, and decrease costs. 4 refs., 4 figs., 5 tabs.

  20. Chemistry of marine ligands and siderophores. (United States)

    Vraspir, Julia M; Butler, Alison


    Marine microorganisms are presented with unique challenges to obtain essential metal ions required to survive and thrive in the ocean. The production of organic ligands to complex transition metal ions is one strategy to both facilitate uptake of specific metals, such as iron, and to mitigate the potential toxic effects of other metal ions, such as copper. A number of important trace metal ions are complexed by organic ligands in seawater, including iron, cobalt, nickel, copper, zinc, and cadmium, thus defining the speciation of these metal ions in the ocean. In the case of iron, siderophores have been identified and structurally characterized. Siderophores are low molecular weight iron-binding ligands produced by marine bacteria. Although progress has been made toward the identity of in situ iron-binding ligands, few compounds have been identified that coordinate the other trace metals. Deciphering the chemical structures and production stimuli of naturally produced organic ligands and the organisms they come from is fundamental to understanding metal speciation and bioavailability. The current evidence for marine ligands, with an emphasis on siderophores, and discussion of the importance and implications of metal-binding ligands in controlling metal speciation and cycling within the world's oceans are presented.

  1. On-surface magnetochemistry


    Wäckerlin, Christian


    This thesis reports on the on-surface magnetochemistry of square-planar transition-metal complexes adsorbed on ferromagnetic substrates. Specifically, the magnetochemistry of the transition-metal ions (Mn / Fe / Co / Ni) coordinated in square-planar porphyrin / phthalocyanine ligands arranged on native and oxygen-reconstructed ferromagnetic Ni(001) / Co(001) thin-films is studied. The metal-centers in the surface-adsorbed complexes are five-fold coordinated: four coordination-bonds with the s...

  2. The Russia Corporate Governance Manual : Part I. Corporate Governance Introduced


    International Finance Corporation; U.S. Department of Commerce


    The Russia corporate governance manual has been divided into and is published in six parts: (i) corporate governance introduced; (ii) good board practices; (iii) shareholder rights; (iv) information disclosure and transparency; (v) special focus section; and (vi) annexes model corporate governance documents. The first four parts contain chapters that focus on core corporate governance issu...

  3. E-Government for Good Governance in Developing Countries ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    E-Government for Good Governance in Developing Countries: Empirical Evidence from the eFez Project. Book cover E-Government for Good Governance in Developing Countries. Auteur(s) : Driss Kettani and Bernard Moulin. Maison(s) d'édition : Anthem Press, IDRC. 1 mai 2014. ISBN : 9781783082636. 298 pages.

  4. Molecular Basis of Ligand-Dependent Regulation of NadR, the Transcriptional Repressor of Meningococcal Virulence Factor NadA. (United States)

    Liguori, Alessia; Malito, Enrico; Lo Surdo, Paola; Fagnocchi, Luca; Cantini, Francesca; Haag, Andreas F; Brier, Sébastien; Pizza, Mariagrazia; Delany, Isabel; Bottomley, Matthew J


    Neisseria adhesin A (NadA) is present on the meningococcal surface and contributes to adhesion to and invasion of human cells. NadA is also one of three recombinant antigens in the recently-approved Bexsero vaccine, which protects against serogroup B meningococcus. The amount of NadA on the bacterial surface is of direct relevance in the constant battle of host-pathogen interactions: it influences the ability of the pathogen to engage human cell surface-exposed receptors and, conversely, the bacterial susceptibility to the antibody-mediated immune response. It is therefore important to understand the mechanisms which regulate nadA expression levels, which are predominantly controlled by the transcriptional regulator NadR (Neisseria adhesin A Regulator) both in vitro and in vivo. NadR binds the nadA promoter and represses gene transcription. In the presence of 4-hydroxyphenylacetate (4-HPA), a catabolite present in human saliva both under physiological conditions and during bacterial infection, the binding of NadR to the nadA promoter is attenuated and nadA expression is induced. NadR also mediates ligand-dependent regulation of many other meningococcal genes, for example the highly-conserved multiple adhesin family (maf) genes, which encode proteins emerging with important roles in host-pathogen interactions, immune evasion and niche adaptation. To gain insights into the regulation of NadR mediated by 4-HPA, we combined structural, biochemical, and mutagenesis studies. In particular, two new crystal structures of ligand-free and ligand-bound NadR revealed (i) the molecular basis of 'conformational selection' by which a single molecule of 4-HPA binds and stabilizes dimeric NadR in a conformation unsuitable for DNA-binding, (ii) molecular explanations for the binding specificities of different hydroxyphenylacetate ligands, including 3Cl,4-HPA which is produced during inflammation, (iii) the presence of a leucine residue essential for dimerization and conserved in

  5. Competence, governance, and entrepreneurship

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahnke, Volker

    This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives on the f......, and entrepreneurship to advance and stimulate economic strategy research....

  6. Contractual Corporate Governance

    NARCIS (Netherlands)

    Goergen, M.; Renneboog, L.D.R.


    Companies have the choice to deviate from their national corporate governance standards by opting into another system. They can do so via contractual devices – such as cross-border mergers and acquisitions, (re)incorporations, and cross-listings – which enable firms to choose their preferred level

  7. Getting Port Governance Right

    DEFF Research Database (Denmark)

    de Langen, Peter; Saragiotis, Periklis


    This chapter discusses the relevance of ports for economic development and next identifies port governance as a critical determinant of a well-functioning port industry. While in the past decades privately owned terminal operating companies have emerged and contributed to more efficient supply ch...

  8. Government by standards

    DEFF Research Database (Denmark)

    Triantafillou, Peter


    be contributing to accountability overload. This article seeks to provide an explanation for why hospital staff seems to accept, albeit grudgingly and partially, the imposition of a new, comprehensive accountability system with questionable clinical merits. Inspired by Michel Foucault’s analytics of government...

  9. Values and Governance Systems

    NARCIS (Netherlands)

    Ruys, P.H.M.; van den Brink, J.R.; Semenov, R.


    Cooperative behavior as well as other cultural rules and values are made explicit in organizational units that procure and provide a common service. The common service is procured by a club, which consists of a user-value function, a representation governance, and a budget-allocation function. The

  10. Corporate governance through codes

    NARCIS (Netherlands)

    Haxhi, I.; Aguilera, R.V.; Vodosek, M.; den Hartog, D.; McNett, J.M.


    The UK's 1992 Cadbury Report defines corporate governance (CG) as the system by which businesses are directed and controlled. CG codes are a set of best practices designed to address deficiencies in the formal contracts and institutions by suggesting prescriptions on the preferred role and

  11. Governability and Citizen Participation

    Directory of Open Access Journals (Sweden)

    Giancarla de Quiroga


    Full Text Available bjective conditions that allow for a harmonic relationship between the governors and the governed. We are speaking about a set of conditions for governing by consensus and in harmony. By “citizen participation” we refer to the fact that citizens share in the powerof decision over something that concerns them. In Bolivia, as well in other Latin American countries, citizenship participation in municipal management is a recent phenomena. This article describes the experience of citizenry participation in the municipality ofCochabamba (Bolivia in relation to quality of life and living conditions in a neighborhood. The municipality of Cochabamba has embarked upon a mission of rescue and evaluation of the neighborhood organizations, not only incorporating the population into the processes of participation, but also acting in favor of social integration because this stresses the commitment of the neighborhood citizens in the design of the plans. In conclusion, the unfolding experience in the municipality of Cochabamba makes the fact clear that beyond the concept of governability, the search for a co-government-type relation prevails, one that is more horizontal and equitable and where the population takes on a leading role for bringing about the social cohesion and the sense of belonging needed to face the serious problems that afflict Latin American cities.

  12. Governing Logistics Information Platforms

    NARCIS (Netherlands)

    Klievink, A.J.; Aldewereld, H.M.; Knol, A.; Tan, Y.H.


    The Extended Single Window (ESW) project aims to support goods flows by Information and Communication Technology (ICT). Specifically, the project takes the concept of Single Windows (often used in the sense that governments offer a single portal or interface to which businesses can submit

  13. Governing the water user

    NARCIS (Netherlands)

    Rap, Edwin; Wester, Flip


    This article traces a policy shift that makes the ‘water user’ the main subject of water governance. From a Foucauldian perspective on governmentality these new subjectivities accompany neo-liberal governmental technologies to devolve autonomy from state institutions to an active user base, whilst

  14. Government support of innovation

    CERN Multimedia

    Studt, T


    "One of the Federal government's few formal interagency enterprises, the Networking and Information Technology R&D (NITRD) program, is the collaborative framework of numerous federal agencies that conduct fundamental R&D in advanced networks, computing systems, software, and information management technologies" (1/2 page).

  15. Local government in Ethiopia

    African Journals Online (AJOL)


    farmers would find themselves being rounded up at gun point by the local defence squad, and forcibly dispatched...”69. The involvement of UDAs and PAs in the forceful conscription of young people into the government's army was another control oriented action. Derg was forcefully conscripting young Ethiopians for the ...

  16. 'developmental' local government to

    African Journals Online (AJOL)

    1. DEVELOPMENTAL CHALLENGES. FACING SOUTH AFRICAN. URBAN REGIONS AND. GOVERNMENTS. As an introduction to this article it would be appropriate to begin the discussion with some developmental acumen from the office of the Presidency. The new Green Paper: National Strategic. Planning, published by ...

  17. Corporate Media Governance

    NARCIS (Netherlands)

    Kempen, Petrus Cornelis


    The media can make or break a reputation. This being said, it seems to be essential for companies, governments and institutions to pay specific attention to corporate media management in their daily operations. However, this thesis shows that they often neglect to pay adequate attention to corporate

  18. Explaining governance outcomes

    DEFF Research Database (Denmark)

    Fawcett, Paul; Daugbjerg, Carsten


    between vertical coordination on the state–society axis and horizontal coordination on the interest integration axis. This produces a typology of governance arrangements, which are evaluated according to the level of input and output legitimacy that they are likely to generate, two criteria that are taken...

  19. The Governance of Services

    NARCIS (Netherlands)

    Ruys, P.H.M.


    The problem of assessing a system of governance for composite services in the social economy is approached by means of original methods.The main innovation is that the welfare structure of a society is separated from the legal transaction- or institutional structure.As both the various types of

  20. Coordinate unsaturation with fluorinated ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rack, J.L.; Hurlburt, P.K.; Anderson, O.P.; Strauss, S.H. [Colorado State Univ., Ft. Collins, CO (United States)


    The preparation and characterization of Zn(OTeF{sub 5}){sub 2} has resulted in a model compound with which to explore the concept of coordinative unsaturation. The coordination of solvents of varying donicity and dielectric constant to the Zn(II) ions in Zn(OTeF{sub 5}){sub 2} was studied by vapor phase monometry, NMR and IR spectroscopy, conductimetry, and X-Ray crystallography. The structures of [Zn(C{sub 6}H{sub 5}NO{sub 2}){sub 2}(OTeF{sub 5})2]2 and Zn(C{sub 6}H{sub 5}NO{sub 2}){sub 3}(OTEF{sub 5}){sub 2} demonstrate the electronic flexibility of some weakly coordinating solvents in that nitrobenzene can function as either an {eta}{sup 1}O or {eta}{sup 2}O,O`-ligand. The dependence of the number of bound solvent molecules and the degree of OTeF{sub 5}{minus} dissociation on solvent donor number and dielectric constant will be presented.

  1. Governability in Contemporary Mexico

    Directory of Open Access Journals (Sweden)

    Leonardo Curzio Gutiérrez


    Full Text Available Given the difficulties to establish a concept of governability and the frequent ideological usage of the term, it is much more operative to turn to the principle of governability, in the broad sense, which supports itself on five pillars: the political legitimacy of the government, the governmental efficiency to attend to the demands of society, the existence of shared social project, the agreement with the principle special interest groups, and international viability. The analysis of the structure and relevance of these five points during the long period of political transition that Mexico underwent between 1988 and 1997 shows how it was possible for this country to play off certain factors against each other in order to secure governability and safeguard against the consequences of any resultant imbalances. Between 1998-1993, the government of Salinas de Gotari based itself on the viability of a neoliberal project within an international context, and on this projectís attention to domestic demands as well as on the governmentís pact with elites. Institutional integration and legitimacy made up, then, for a process of discreet liberalization and the lack of democratic electoral commitment, which culminated in the PRI’s 1994 elections victory.The assassination of Colosia, though, and the appearance of the EZLN and the subsequent crisis surrounding the peso’s devaluation that accompanied Ernesto Zedilloís rise to power soon led to the collapse of those pillars of support. Crowning the process of the silenttransition were the elections of 1997, which makes it possible to say that in Mexico today there are now smooth elections, but that reform of the State is still unresolved —a subject that includes the reduction of the president’s competence. Seen in the short term, the most direct threats to Mexico’s governability will come as a result of the lack of attention to those demands of society’s underprivileged and the ill

  2. Exploring the composition of protein-ligand binding sites on a large scale.

    Directory of Open Access Journals (Sweden)

    Nickolay A Khazanov

    Full Text Available The residue composition of a ligand binding site determines the interactions available for diffusion-mediated ligand binding, and understanding general composition of these sites is of great importance if we are to gain insight into the functional diversity of the proteome. Many structure-based drug design methods utilize such heuristic information for improving prediction or characterization of ligand-binding sites in proteins of unknown function. The Binding MOAD database if one of the largest curated sets of protein-ligand complexes, and provides a source of diverse, high-quality data for establishing general trends of residue composition from currently available protein structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non-redundant binding sites to identify residues over-represented in binding regions versus the rest of the protein surface. The Binding MOAD database delineates biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound to the protein. Invalids are present in the crystallization medium and serve no known biological function. Contacts are found to differ between these classes of ligands, indicating that residue composition of biologically relevant binding sites is distinct not only from the rest of the protein surface, but also from surface regions capable of opportunistic binding of non-functional small molecules. To confirm these trends, we perform a rigorous analysis of the variation of residue propensity with respect to the size of the dataset and the content bias inherent in structure sets obtained from a large protein structure database. The optimal size of the dataset for establishing general trends of residue propensities, as well as strategies for assessing the significance of such trends, are suggested for future studies of binding-site composition.

  3. The Movable Type Method Applied to Protein-Ligand Binding. (United States)

    Zheng, Zheng; Ucisik, Melek N; Merz, Kenneth M


    energy surface eliminating the need to estimate the enthalpy and entropy components individually. Finally, low free energy structures can be obtained via a free energy minimization procedure yielding all low free energy poses on a given free energy surface. Besides revolutionizing the protein-ligand docking and scoring problem this approach can be utilized in a wide range of applications in computational biology which involve the computation of free energies for systems with extensive phase spaces including protein folding, protein-protein docking and protein design.

  4. Evaluating e-Government and Good Governance Correlation

    Directory of Open Access Journals (Sweden)

    Suhardi Suhardi


    Full Text Available Assessing the achievement of Indonesian government institutions in implementing e-government has been conducted since around a decade ago. Several national assessments are available with almost the same ranking results. There is an agreement that the ultimate goal of e-government implementation is to achieve good government governance (GGG, while success stories of e-government require good governance practices. This study explored the correlation between e-government achievement and GGG achievement in Indonesia. Spearman’s rank correlation was used to characterize the relationship strength between e-government assessment results and good governance assessment results. The data were collected from institutions that participated in e-government and good governance assessments. The results showed that the correlation between these two entities is not very strong. Most cases showed that e-government implementation and the achievement of good governance have only a moderate positive correlation and none of the studied cases indicated a significant connection. This result can be attributed to the lack of emphasis on goals achievement in the assessments. Thus, it is recommended that future Indonesian e-government assessments should involve impact indicators.

  5. Digital governance and institutional change

    DEFF Research Database (Denmark)

    Schlæger, Jesper


    Coal allocation in China is a seminal case of e-government in the political economy. The empirical phenomenon of market supporting e-government has not been systematically analysed. By developing and applying a digital governance model this article examines institutional change in a case of coal...... to the role of e-government in the political economy....

  6. Corporate Governance Country Assessment : Togo


    World Bank


    The purpose of this ROSC assessment of corporate governance in Togo is to help improve corporate governance in the country by assessing law and practice, suggesting reforms, and supporting the country in its effort to implement changes for better corporate governance. Corporate governance refers to the structures and processes for the direction and control of companies. Corporate governanc...

  7. Single molecule high-throughput footprinting of small and large DNA ligands. (United States)

    Manosas, Maria; Camunas-Soler, Joan; Croquette, Vincent; Ritort, Felix


    Most DNA processes are governed by molecular interactions that take place in a sequence-specific manner. Determining the sequence selectivity of DNA ligands is still a challenge, particularly for small drugs where labeling or sequencing methods do not perform well. Here, we present a fast and accurate method based on parallelized single molecule magnetic tweezers to detect the sequence selectivity and characterize the thermodynamics and kinetics of binding in a single assay. Mechanical manipulation of DNA hairpins with an engineered sequence is used to detect ligand binding as blocking events during DNA unzipping, allowing determination of ligand selectivity both for small drugs and large proteins with nearly base-pair resolution in an unbiased fashion. The assay allows investigation of subtle details such as the effect of flanking sequences or binding cooperativity. Unzipping assays on hairpin substrates with an optimized flat free energy landscape containing all binding motifs allows determination of the ligand mechanical footprint, recognition site, and binding orientation.Mapping the sequence specificity of DNA ligands remains a challenge, particularly for small drugs. Here the authors develop a parallelized single molecule magnetic tweezers approach using engineered DNA hairpins that can detect sequence selectivity, thermodynamics and kinetics of binding for small drugs and large proteins.

  8. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)



    Jun 21, 2010 ... for designing the pharmacophore onto the set of 70 compounds of three different classes and two subclasses. ... More effective anticancer drug production with novel modes of action .... with Ligand Scout using default settings.

  9. Organometallic chemistry of chiral diphosphazane ligands ...

    Indian Academy of Sciences (India)


    Organometallic chemistry of chiral diphosphazane ligands: Synthesis and structural characterisation. KANNAN RAGHURAMAN, SWADHIN K MANDAL,. T S VENKATAKRISHNAN, SETHARAMPATTU S. KRISHNAMURTHY* and MUNIRATHINAM NETHAJI. Department of Inorganic and Physical Chemistry, Indian Institute of ...

  10. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S


    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  11. Asymmetric hydrogenation using monodentate phosphoramidite ligands

    NARCIS (Netherlands)

    Minnaard, Adriaan J.; Feringa, Ben L.; Lefort, Laurent; De Vries, Johannes G.


    Monodentate phosphoramidites are excellent ligands for Rh-catalyzed asymmetric hydrogenations of substituted olefins. Enantioselectivities between 95 and 99% were obtained in the asymmetric hydrogenation of protected alpha- and beta-dehydroamino acids and esters, itaconic acid and esters, aromatic

  12. Hydrography, Surface water within Sedgwick County including rivers, streams, lakes, ponds and floodways. Some additional drainage ways and aqueducts are also included., Published in 2008, 1:1200 (1in=100ft) scale, Sedgwick County Government. (United States)

    NSGIC Local Govt | GIS Inventory — Hydrography dataset current as of 2008. Surface water within Sedgwick County including rivers, streams, lakes, ponds and floodways. Some additional drainage ways and...

  13. Chiral ligand-protected gold nanoclusters: Considering the optical activity from a viewpoint of ligand dissymmetric field

    Directory of Open Access Journals (Sweden)

    Hiroshi Yao


    Full Text Available Chirality is a geometric property of a physical, chemical, or biological object, which is not superimposable on its mirror image. Its significant presence has led to a strong demand in the development of chiral drugs, sensors, catalysts, and photofunctional materials. In recent years, chirality of nanoscale organic/inorganic hybrids has received tremendous attention owing to potential applications in chiral nanotechnology. In particular, with the recent progress in the syntheses and characterizations of atomically precise gold nanoclusters protected by achiral thiolates, atomic level origins of their chirality have been unveiled. On the other hand, chirality or optical activity in metal nanoclusters can also be introduced via the surface chiral ligands, which should be universal for the nanosystems. This tutorial review presents some optically-active metal (gold nanoclusters protected by chiral thiolates or phosphines, and their chiroptical (or circular dichroism; CD properties are discussed mostly from a viewpoint of the ligand dissymmetric field scheme. The examples are the gold nanoclusters protected by (R-/(S-2-phenylpropane-1-thiol, (R-/(S-mercaptosuccinic acid, phenylboronate-D/L-fructose complexes, phosphine sulfonate-ephedrinium ion pairs, or glutathione. Some methodologies for versatile asymmetric transformation and chiroptical controls of the nanocluster compounds are also described. In the dissymmetric field model as the origin of optical activity, the chiroptical responses of the gold nanoclusters are strongly associated with coupled oscillator and/or CD stealing mechanisms based on the concept of induced CD (ICD derived from a perturbation theory, so on this basis, some characteristic features of the observed CD responses of chiral ligand-protected gold nanoclusters are presented in detail. We believe that various kinds of origins of chirality found in ligand-protected gold nanoclusters may provide models for understanding those of

  14. Cadherin-dependent mechanotransduction depends on ligand identity but not affinity. (United States)

    Tabdili, Hamid; Langer, Matthew; Shi, Quanming; Poh, Yeh-Chuin; Wang, Ning; Leckband, Deborah


    This study investigates the relationship between classical cadherin binding affinities and mechanotransduction through cadherin-mediated adhesions. The mechanical properties of cadherin-dependent intercellular junctions are generally attributed to differences in the binding affinities of classical cadherin subtypes that contribute to cohesive energies between cells. However, cell mechanics and mechanotransduction may also regulate intercellular contacts. We used micropipette measurements to quantify the two-dimensional affinities of cadherins at the cell surface, and two complementary mechanical measurements to assess ligand-dependent mechanotransduction through cadherin adhesions. At the cell surface, the classical cadherins investigated in this study form both homophilic and heterophilic bonds with two-dimensional affinities that differ by less than threefold. In contrast, mechanotransduction through cadherin adhesions is strongly ligand dependent such that homophilic, but not heterophilic ligation mediates mechanotransduction, independent of the cadherin binding affinity. These findings suggest that ligand-selective mechanotransduction may supersede differences in cadherin binding affinities in regulating intercellular contacts.

  15. Competence, governance, and entrepreneurship

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul; Mahnke, Volker

    This title illustrates modern economics. Because it informs strategic choices, it is relevant to business administration in general, and for strategic management in particular. Two dominant streams may be identified in the literature, namely the "competence" and "governance" perspectives......, what determines their boundaries and internal organization), but would also be helpful for informing strategy issues, such as understanding strategic flexibility, strategic options, and the sources of competitive advantage. This volume brings together prominent voices on competence, governance...... on the firm. While there has been little direct discussion between the main proponents of these perspectives, both claim that they are reaching for a "strategic theory of the firm". Such a theory would not only shed light on the classical questions considered in the theory of the firm (e.g. why firms exist...

  16. Governance by algorithms

    Directory of Open Access Journals (Sweden)

    Francesca Musiani


    Full Text Available Algorithms are increasingly often cited as one of the fundamental shaping devices of our daily, immersed-in-information existence. Their importance is acknowledged, their performance scrutinised in numerous contexts. Yet, a lot of what constitutes 'algorithms' beyond their broad definition as “encoded procedures for transforming input data into a desired output, based on specified calculations” (Gillespie, 2013 is often taken for granted. This article seeks to contribute to the discussion about 'what algorithms do' and in which ways they are artefacts of governance, providing two examples drawing from the internet and ICT realm: search engine queries and e-commerce websites’ recommendations to customers. The question of the relationship between algorithms and rules is likely to occupy an increasingly central role in the study and the practice of internet governance, in terms of both institutions’ regulation of algorithms, and algorithms’ regulation of our society.

  17. Auditing IT Governance

    Directory of Open Access Journals (Sweden)

    Florin-Mihai ILIESCU


    Full Text Available Effective IT governance helps ensure that IT supports business goals, optimizes business investment in IT, and appropriately manages IT-related risks and opportunities. Organizations that realize the IT is no longer a support process and embeds value and risks need a structured approach for better managing Information Technology, enable its capability to deliver added value enterprise wide and for setting up a risk management program to address new risks arising for usage of IT in business processes. In order to assess if IT Governance is in line with industry practices, IT Auditors need a good understanding of processes and applicable standards, particular audit work programs and experience in assessing potential problem indicators.

  18. Website Quality in Government

    DEFF Research Database (Denmark)

    Sørum, Hanne; Andersen, Kim Normann; Clemmensen, Torkil


    . Social implications – The overall digital enabled transformation of government appears to be guided by a rather heterogeneous set of quality standards. While a variance of quality standards might stimulate innovation in websites, it can also lead to a substantial difference in digital services provided......Purpose – The objective of this paper is to investigate how webmasters within government bodies explain quality of websites. Despite the central position for advancing the communication, bridging usability tests and design, there are surprisingly few studies on how webmasters perceive, experience...... and explain website quality or design issues. Design/methodology/approach – The authors' unit of analysis is webmasters from Norwegian web-award-winning organizations. Eight webmasters from four types of websites were interviewed. The websites were purposefully sampled, using the strategy of maximal variation...

  19. Whole of Government Accounts

    DEFF Research Database (Denmark)

    Pontoppidan, Caroline Aggestam; Chow, Danny; Day, Ronald

    for influence. We highlight three arenas where such contests are being played out: 1. Statistical versus GAAP notions of accounting value, which features in all accounting debates over the merits and costs of ex-ante versus ex-post notions of value (i.e., the relevance versus reliability debate); 2. Private......In our comparative study, we surveyed an emerging literature on the use of consolidation in government accounting and develop a research agenda. We find heterogeneous approaches to the development of consolidation models across the five countries (Australia, New Zealand, UK, Canada and Sweden...... of financial reporting (GAAP)-based reforms when compared with budget-centric systems of accounting, which dominate government decision-making. At a trans-national level, there is a need to examine the embedded or implicit contests or ‘trials of strength’ between nations and/or institutions jockeying...

  20. Banking governance: New Approaches

    Directory of Open Access Journals (Sweden)

    Victor Mihăiţă Duţă


    Full Text Available Banks are companies like any other. However, banks are distinguished by certain intrinsic characteristics of companies that have a different impact on the motivation of stakeholders. Among these features, we mention:partnership and shareholders governance agreements; banks are heavily regulated companies; banking assets is the main source of haze banking and information asymmetry; between the bank and depositors there is a problem of moral hazard.

  1. Government and Health Policy, (United States)


    interests and pressures of others. Perhaps for these reasons, the eminent economist John Maynard Keynes once noted that, "The power of vested interests...subsidies, medical school subsidies and loans to students, and tax-exempt status of hospitals are but a few examples of government changing input or...planners. Loans to medical students tied to the promise of rural practice are one policy tool used. Subsidies to medical schools contingent on

  2. Shared Health Governance (United States)

    Ruger, Jennifer Prah


    Health and Social Justice (Ruger 2009a) developed the “health capability paradigm,” a conception of justice and health in domestic societies. This idea undergirds an alternative framework of social cooperation called “shared health governance” (SHG). SHG puts forth a set of moral responsibilities, motivational aspirations, and institutional arrangements, and apportions roles for implementation in striving for health justice. This article develops further the SHG framework and explains its importance and implications for governing health domestically. PMID:21745082

  3. Pension Fund Governing Board

    CERN Multimedia

    HR Department


    Note The CERN pension scheme is based on the principle of defined benefits, so beneficiaries continue to receive the benefits to which they are entitled in accordance with the Rules of the Pension Fund. This means that pension entitlements under the Rules are not directly affected by the financial crisis and the current economic situation. However, the adjustment of pensions to the cost of living is not automatic and, under the method applied since 2006, must take into account the Fund’s financial position. Meeting of the Pension Fund Governing Board The Pension Fund Governing Board held its eighth meeting at ESO in Garching (near Munich), Germany on 24 October 2008. Before starting its work, the Governing Board had the privilege of hearing an opening address by Professor Tim de Zeeuw, the Director General of ESO. Professor de Zeeuw described the mission of ESO and the ambitious projects of his organisation, which performs astronomy observations using telescopes located in Chile. The Director-General receiv...

  4. Educational Governance Today

    Directory of Open Access Journals (Sweden)

    Christoph Behrens


    Full Text Available In the communication and knowledge based global village, under the conditions of dynamic Change in an economy driven world, education has become a complex and challenging endeavor, both for individuals and organizations. Learning has changed dramatically: knowledge and skills are quickly outdated and devaluated, giving education a new meaning within an individual biography; schools, universities and other providers of education go through organizational revolutions, who are challenging their self-concept and management; governments are under pressure to reshape Educational Governance according to new paradigms with the overall goal to sustain national or regional competitiveness. Are key actors in the education system ready to face these challenges and to modernize their organizations? Starting from an overview on the Complexity of Learning in modern societies, generalizable consequences are reviewed in a case study on Germany. It leads to a framework for a necessary research project in countries such as Indonesia, which are still ahead of educational reform. The focus is on the organizational meso and macro level that is playing the key role in Educational Governance.

  5. Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology. (United States)

    Sakamoto, Kotaro; Kanematsu-Yamaki, Yoko; Kamada, Yusuke; Oka, Masahiro; Ohnishi, Toshiyuki; Miwa, Masanori; Asami, Taiji; Inooka, Hiroshi


    ActRIIB (activin receptor type-2B) is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN), growth differentiation factor 11 (GDF11), and bone morphogenetic protein 9 (BMP9). Notably, the protein-protein interaction (PPI) between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9), AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

  6. Designer TGFβ superfamily ligands with diversified functionality.

    Directory of Open Access Journals (Sweden)

    George P Allendorph

    Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

  7. Construction of dinuclear complexes using multidentate ligands

    Energy Technology Data Exchange (ETDEWEB)

    Sampson, C.L


    This work details the synthesis of novel copper(I), copper(II), nickel(II) and zinc(II) dinuclear complexes. Attempts have been made to control the co-ordination architectures of the metal centres by using bis-bidentate and tridentate chelating N,S- and N-donor ligands to generate dinuclear systems. The ligands were both symmetrically and asymmetrically disubstituted pyridazine-based and pyridine-based ligands consisting of a mixture of N-only and mixed N,S-donors. The study using the pyridazine-based ligands continues previous research in our group using 3,6-bis disubstituted pyridazine-based ligands to form complexes with copper(l) and copper(II). The pyridazine-based ligands have been seen to be bis-bidentate upon co-ordination of copper. The pyridazine-based ligands could be envisaged to generate dinuclear complexes by directly bridging between two metal ions. This study involved the formation of copper(l), nickel(II) and zinc(II) complexes with these ligands. The structural properties of two particular complexes have been explored using X-ray crystallography and spectroscopic techniques. Pyridine-based ligands have also been used previously in our group as tridentate chelating ligands. They have been seen to form dinuclear complexes with copper(I) and copper(II) when reacted with an additional bridging ligand e.g. 4,4'-bipyridine. This provides an alternative method for generating dinuclear complexes. Chapter 1 presents an introduction to the area of supramolecular chemistry from which we can learn the principles of polymer formation and them 'in reverse' to generate discrete dinuclear systems. Chapter 2 details the synthesis of the pyridazine and pyridine-based ligands including a detailed nmr study of the ligands. Since the ligands were synthesised using cyclic thioamides as terminal groups it has been found that thiol-thione tautomerisation occurred during synthesis giving rise to two possible ligand conformations. The nmr study has been used

  8. Semiconductor Quantum Dots with Photoresponsive Ligands. (United States)

    Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume


    Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

  9. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng


    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  10. Characterization of quinoxolinol salen ligands as selective ligands for chemosensors for uranium

    Energy Technology Data Exchange (ETDEWEB)

    DeVore, Michael A. II; Kerns, Spencer A.; Gorden, Anne E.V. [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL (United States)


    Quinoxalinol salen ligands have been characterized as selective ligands for the rapid identification of uranyl. The absorption maximum of ligand 1 presented a hypsochromic (blue) shift with the addition of UO{sub 2}{sup 2+} (as the acetate salt), and a bathochromic (red) shift in the presence of Cu{sup 2+} or Co{sup 2+} acetate salts, resulting in distinct, visible color changes for all three metal ions. The absorption maximum of ligand 2 was not observed to change with the addition of UO{sub 2}{sup 2+}; however, it does present a bathochromic shift with the addition of Cu{sup 2+}, and a hypsochromic shift with Co{sup 2+} added. Using TDDFT calculations, it was demonstrated that the hypsochromic shift for UO{sub 2}{sup 2+} ion complexation with ligand 1 is caused by a ligand-to-metal charge transfer, while the bathochromic shift observed with Cu{sup 2+} ion addition was caused by a metal-to-ligand charge transfer. Finally, it was found that the addition of Cu{sup 2+} (as metal salts) to either ligand resulted in rapid, complete quenching of the ligand fluorescence. (Copyright copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand.

    Directory of Open Access Journals (Sweden)

    Samuel DeLuca

    Full Text Available RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand making it unfeasible for use in virtual High Throughput Screening (vHTS. To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial 'low-resolution' docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10-15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the 'high-resolution' full atom refinement step.

  12. Design of a dual-ligand system using a specific ligand and cell penetrating peptide, resulting in a synergistic effect on selectivity and cellular uptake. (United States)

    Takara, Kazuhiro; Hatakeyama, Hiroto; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi


    In this study, a dual-ligand liposomal system comprised of a specific ligand and a cell penetrating peptide (CPP) is described to enhance selectivity and cellular uptake. Dual-ligand PEGylated liposomes were prepared by modifying the end of the PEG with an NGR motif peptide, followed by a surface coating of the liposomes with stearylated oligoarginine (STR-RX). The NGR motif recognizes CD13, a marker protein located on tumor endothelial cells. A suitable number of RX units was determined to be R4, since it can be masked by the PEG aqueous layer. Although no enhanced cellular uptake was observed when a single modification of PEGylated liposomes with either NGR- or STR-R4 was used, the dual-modification with NGR and STR-R4 stimulated uptake of PEGylated liposomes by CD13 positive cells, and this uptake was superior to that obtained by PEG-unmodified liposomes modified with STR-R4. The dual-ligand system shows a synergistic effect on cellular uptake. Collectively, the dual-ligand system promises to be useful in the development efficient and specific drug delivery systems. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Fringe-mediated extension of O-linked fucose in the ligand-binding region of Notch1 increases binding to mammalian Notch ligands. (United States)

    Taylor, Paul; Takeuchi, Hideyuki; Sheppard, Devon; Chillakuri, Chandramouli; Lea, Susan M; Haltiwanger, Robert S; Handford, Penny A


    The Notch signaling pathway is essential for many aspects of development, cell fate determination, and tissue homeostasis. Notch signaling can be modulated by posttranslational modifications to the Notch receptor, which are known to alter both ligand binding and receptor activation. We have modified the ligand-binding region (EGF domains 11-13) of human Notch1 (hN1) with O-fucose and O-glucose glycans and shown by flow cytometry and surface plasmon resonance that the Fringe-catalyzed addition of GlcNAc to the O-fucose at T466 in EGF12 substantially increases binding to Jagged1 and Delta-like 1 (DLL1) ligands. We have subsequently determined the crystal structures of EGF domains 11-13 of hN1 modified with either the O-fucose monosaccharide or the GlcNAc-fucose disaccharide at T466 of EGF12 and observed no change in backbone structure for each variant. Collectively, these data demonstrate a role for GlcNAc in modulating the ligand-binding site in hN1 EGF12, resulting in an increased affinity of this region for ligands Jagged1 and DLL1. We propose that this finding explains the Fringe-catalyzed enhancement of Notch-Delta signaling observed in flies and humans, but suggest that the inhibitory effect of Fringe on Jagged/Serrate mediated signaling involves other regions of Notch.

  14. RET Recognition of GDNF-GFRα1 Ligand by a Composite Binding Site Promotes Membrane-Proximal Self-Association

    Directory of Open Access Journals (Sweden)

    Kerry M. Goodman


    Full Text Available The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting in RET transmembrane signaling. We present a hybrid structural model, derived from electron microscopy (EM and low-angle X-ray scattering (SAXS data, of the RET extracellular domain (RETECD, GDNF, and GFRα1 ternary complex, defining the basis for ligand recognition. RETECD envelopes the dimeric ligand complex through a composite binding site comprising four discrete contact sites. The GFRα1-mediated contacts are crucial, particularly close to the invariant RET calcium-binding site, whereas few direct contacts are made by GDNF, explaining how distinct ligand/coreceptor pairs are accommodated. The RETECD cysteine-rich domain (CRD contacts both ligand components and makes homotypic membrane-proximal interactions occluding three different antibody epitopes. Coupling of these CRD-mediated interactions suggests models for ligand-induced RET activation and ligand-independent oncogenic deregulation.

  15. Crystal structure of the ligand-binding domain of the promiscuous EphA4 receptor reveals two distinct conformations

    Energy Technology Data Exchange (ETDEWEB)

    Singla, Nikhil; Goldgur, Yehuda; Xu, Kai; Paavilainen, Sari; Nikolov, Dimitar B.; Himanen, Juha P. (MSKCC); (Turku)


    Eph receptors and their ephrin ligands are important mediators of cell-cell communication. They are divided in two subclasses based on their affinities for each other and on sequence conservation. Receptor-ligand binding within each subclass is fairly promiscuous, while binding cross the subclasses happens rarely. EphA4 is an exception to this general rule, since it has long been known to bind both A- and B-class ephrin ligands but the reason for this exceptional behavior has not been worked out at molecular level. Recent structural and biochemical studies on EphA4 ligand-binding domain alone and in complex with its ligands have addressed this question. However, the published structures of EphA4/ephrin complexes differ considerably from each other and strikingly different explanations for the exceptional promiscuity of EphA4 were proposed. To address these contradictory findings, we have determined a crystal structure of the EphA4 ligand-binding domain at 2.3 {angstrom} resolution and show that the receptor has an unprecedented ability to exist in two very different, well-ordered conformations even in the unbound state. Our results suggest that the ligand promiscuity of the Ephs is directly correlated with the structural flexibility of the ligand-binding surface of the receptor.

  16. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.


    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  17. Distinct impacts of substrate elasticity and ligand affinity on traction force evolution. (United States)

    Müller, Christina; Pompe, Tilo


    Cell adhesion is regulated by the mechanical characteristics of the cell environment. The influences of different parameters of the adhesive substrates are convoluted in the cell response leading to questions on the underlying mechanisms, like biochemical signaling on the level of adhesion molecules, or viscoelastic properties of substrates and cell. By a time-resolved analysis of traction force generation during early cell adhesion, we wanted to elucidate the contributions of substrate mechanics to the adhesion process, in particular the impact of substrate elasticity and the molecular friction of adhesion ligands on the substrate surface. Both parameters were independently adjusted by (i) an elastic polyacrylamide hydrogel of variable crosslinking degree and (ii) a thin polymer coating of the hydrogel surface controlling the affinity (and the correlated substrate-ligand friction) of the adhesion ligand fibronectin. Our analysis showed two sequential regimes of considerable force generation, whose occurrence was found to be independent of substrate properties. The first regime is characterized by spreading of the cell and a succeeding force increase. After spreading cells enter the second regime with saturated forces. Substrate elasticity and viscosity, namely hydrogel elasticity and ligand affinity, were both found to affect the kinetics and absolute levels of traction force quantities. A faster increase and a higher saturation level of traction forces were observed for a higher substrate stiffness and a higher ligand affinity. The results complement recent modeling approaches on the evolution of forces in cell spreading and contribute to a better understanding of the dynamics of cell adhesion on viscoelastic substrates.

  18. Controlled adsorption of cytochrome c to nanostructured gold surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Ines [Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, REQUIMTE, Departamento de Quimica (Portugal); Feio, Maria J. [Faculdade de Ciencias da Universidade do Porto, REQUIMTE, Departamento de Quimica e Bioquimica (Portugal); Santos, Nuno C. [Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular (Portugal); Eaton, Peter [Faculdade de Ciencias da Universidade do Porto, REQUIMTE, Departamento de Quimica e Bioquimica (Portugal); Serro, Ana Paula; Saramago, Benilde [Centro de Quimica Estrutural, Instituto Superior Tecnico (Portugal); Pereira, Eulalia [Faculdade de Ciencias da Universidade do Porto, REQUIMTE, Departamento de Quimica e Bioquimica (Portugal); Franco, Ricardo, E-mail: [Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, REQUIMTE, Departamento de Quimica (Portugal)


    Controlled electrostatic physisorption of horse heart cytochrome c (Cyt c) onto nanostructured gold surfaces was investigated using Quartz-Crystal Microbalance measurements in planar gold surfaces with or without functionalization using a self-assembled monolayer (SAM) of the alkanethiol mercaptoundecanoic acid (MUA). MUA is a useful functionalization ligand for gold surfaces, shedding adsorbed biomolecules from the excessive electron density of the metal. A parallel analysis was conducted in the corresponding curved surfaces of 15 nm gold nanoparticles (AuNPs), using zeta-potential and UV- visible spectroscopy. Atomic Force Microscopy of both types of functionalized gold surfaces with a MUA SAM, allowed for visualization of Cyt c deposits on the nanostructured gold surface. The amount of Cyt c adsorbed onto the gold surface could be controlled by the solution pH. For the assays conducted at pH 4.5, when MUA SAM- functionalized planar gold surfaces are positive or neutral, and Cyt c has a positive net charge, only 13 % of the planar gold surface area was coated with protein. In contrast, at pH 7.4, when MUA SAM-functionalized planar gold surfaces and Cyt c have opposite charges, a protein coverage of 28 % could be observed implying an adsorption process strongly governed by electrostatic forces. Cyt c adsorption on planar and curved gold surfaces are found to be greatly favored by the presence of a MUA-capping layer. In particular, on the AuNPs, the binding constant is three times larger than the binding constant obtained for the original citrate-capped AuNPs.

  19. The utilization of BSA-modified chip on the investigation of ligand ...

    African Journals Online (AJOL)



    Dec 15, 2009 ... The utilization of BSA-modified chip on the investigation of ligand/protein interaction with surface plasma resonance. LiHua Chen, Qiang Wang and WanGuo Hou*. College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, Shandong,. People's Republic of ...

  20. A chemical biology approach for targeting of ligand-drug conjugates

    NARCIS (Netherlands)

    Hoogendoorn, Sascha


    Cells express a large array of membrane receptors on their surface that function as a communication channel between the extra- and intracellular environment of the cell. Ligands for these receptors span a wide range of biomolecules, from proteins to carbohydrates to small molecules. Some receptors

  1. Interpolation method for accurate affinity ranking of arrayed ligand analyte interactions

    NARCIS (Netherlands)

    Schasfoort, Richardus B.M.; Andree, Kiki Carlijn; van der Velde, N.; van der Kooi, A.; Stojanovic, Ivan; Terstappen, Leonardus Wendelinus Mathias Marie


    The values of the affinity constants (kd, ka, and KD) that are determined by label-free interaction analysis methods are affected by the ligand density. This article outlines a surface plasmon resonance (SPR) imaging method that yields high-throughput globally fitted affinity ranking values using a

  2. Intravesicular and intervesicular interaction by orthogonal multivalent host-guest and metal-ligand complexation

    NARCIS (Netherlands)

    Lim, Choon Woo; Crespo-Biel, Olga; Stuart, Marc C. A.; Reinhoudt, David N.; Huskens, Jurriaan; Ravoo, Bart Jan


    Host vesicles composed of amphiphilic beta-cyclodextrin CID1 recognize metal-coordination complexes of the adamantyl-functionalized ethylenediamine ligand L via hydrophobic inclusion in the beta-cyclodextrin cavities at the vesicle surface. In the case of Cu(II) and L, the resulting coordination

  3. Intravesicular and intervesicular interaction by orthogonal multivalent host-guest and metal-ligand complexation

    NARCIS (Netherlands)

    Lim, C.W.; Crespo biel, O.; Stuart, Marc C.A.; Reinhoudt, David; Huskens, Jurriaan; Ravoo, B.J.


    Host vesicles composed of amphiphilic beta-cyclodextrin CD1 recognize metal-coordination complexes of the adamantyl-functionalized ethylenediamine ligand L via hydrophobic inclusion in the beta-cyclodextrin cavities at the vesicle surface. In the case of Cu(II) and L, the resulting coordination

  4. The connection between metal ion affinity and ligand affinity in integrin I domains

    DEFF Research Database (Denmark)

    Vorup-Jensen, Thomas; Waldron, TT; Astrof, N


    Integrins are cell-surface heterodimeric proteins that mediate cell-cell, cell-matrix, and cell-pathogen interactions. Half of the known integrin alpha subunits contain inserted domains (I domains) that coordinate ligand through a metal ion. Although the importance of conformational changes withi...

  5. Palmitoylation of MICA, a ligand for NKG2D, mediates its recruitment to membrane microdomains and promotes its shedding


    Agüera-González, Sonia; Gross, Catharina C.; Fernández-Messina, Lola; Ashiru, Omodele; Esteso, Gloria; Hang, Howard C.; Reyburn, Hugh T.; Long, Eric O; Valés-Gómez, Mar


    MICA and MICB (MHC-class-I-related chain A/B) are transmembrane proteins expressed in pathological conditions that are ligands for NKG2D, an activating receptor found on cytotoxic lymphocytes. The recognition on target cells of NKG2D ligands leads to the activation of lysis and cytokine secretion by NK cells and T cells. Besides being expressed at the cell surface, MICA/B can be released as soluble proteins. Soluble NKG2D ligands downmodulate expression of the NKG2D receptor on lymphocytes, l...

  6. Tuning the topology and functionality of metal-organic frameworks by ligand design. (United States)

    Zhao, Dan; Timmons, Daren J; Yuan, Daqiang; Zhou, Hong-Cai


    collapsing, giving rise to the first case of mesoporous MOF that demonstrates the type IV isotherm. We use dendritic hexacarboxylate ligands to synthesize an isoreticular series of MOFs with (3,24)-connected network topology. The cuboctahedral cages serve as building blocks that narrow the opening of the mesocavities into microwindows and stabilize these MOFs. The resulting materials have exceptionally high surface areas and hydrogen uptake capacities. Despite the many achievements in MOF development, there is still ample opportunity for further exploration. We will be continuing our efforts and look forward to contributing to this blossoming field in the next decade.

  7. Alignment between business process governance and IT governance


    Rahimi, Fatemeh; Møller, Charles; Hvam, Lars


    The importance of business processes and the increasing centrality of IT to an organization's performance have called for a specific focus on business process governance and IT governance in contemporary enterprises. Despite the wide scope of business process management, which covers both business and IT domains, and the profound impact of IT on process innovations, the association between business process governance and IT governance remains under-explored. Analyzing the constituting element...

  8. Knowledge and Governance

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul

    Assumptions about the knowledge held by economic agents have been an integral part of the theory of economic organization since its inception. However, recent work—here called “knowledge governance”—has more explicitly highlighted knowledge as both an independent and dependent variable. Thus......, knowledge may also be seen as being caused by governance mechanisms and structures; specifically, incentives, allocations of decision rights, organizational structure and so on influence the search for knowledge, and the creation, sharing and integration of knowledge. More philosophically, the concern...

  9. 'Joined Up' Local Governments?

    DEFF Research Database (Denmark)

    Bjørnå, Hilde; Casale, Donatella; Hajnal, Gyorgy

    of such studies and comparative studies are lacking. With this, we ask how can local JUG initiatives be explained and what lessons can be drawn from a comparative perspective? Drawing on some components from the framework by Pollitt and Bouckaert (2011) for public management reforms, we analyse JUG reforms in six....... forthc. 2015, Lægreid et al. 2014, Pollitt 2003). A growing body of research analyses JUG initiatives in several countries, but often in the form of single-case studies with central government focus (see e.g. Talbot 2011 or Lægreid et al. 2014). On municipal level, however, there is only a scarce number...

  10. E-Government for Good Governance in Developing Countries ...

    International Development Research Centre (IDRC) Digital Library (Canada)


    May 1, 2014 ... E-Government for Good Governance in Developing Countries provides practical supporting material on information and communication technologies for development (ICT4D), specifically, e-government implementation. In this book, Kettani and Moulin develop their findings and methods from the eFez ...

  11. Immobilisation of ligands by radio-derivatized polymers; Immobilisering av ligander med radioderiverte polymerer

    Energy Technology Data Exchange (ETDEWEB)

    Varga, J.M.; Fritsch, P.


    The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs.

  12. Steuern und Governance

    Directory of Open Access Journals (Sweden)

    Eduard Müller


    Full Text Available ENGLISH: Taxation, in the modern state, has long been a mass phenomenon with an interdisciplinary outlook. On the macro level of the state, a new generation of administrative reforms has crystallized under the label “good public governance”. These reforms seek to resolve regulatory interdependence of state and non - state actors by way of cooperation and interaction. In parallel, on the micro level of businesses, “corporate governance” – voluntary compliance with legal and ethical standards – has become an increasingly important issue. With a view to tax law and tax collection, these developments open up new possibilities to raise tax compliance by means of consensual and cooperative instruments and, accordingly, address taxation as a mass phenomenon. DEUTSCH: Besteuerung ist im modernen Staat ein Massenphänomen und längst interdisziplinär ausgerichtet. Auf der Makro-Ebene des Staates hat sich unter dem Begriff Good Public Governance eine neue Generation von Staats- und Verwaltungsreformen herausgebildet, die Regelungsbeziehungen von staatlichen und nichtstaatlichen Akteuren durch Kooperationen und Interaktionen zu lösen versucht. Parallel dazu hat auf der Mikro-Ebene der Unternehmen mit dem Thema Corporate Governance die freiwillige Einhaltung von rechtlichen und ethischen Regeln an Bedeutung gewonnen. Für das Steuerrecht und den Steuervollzug resultieren aus diesen Entwicklungen neue Möglichkeiten, durch Nutzung konsens- und kooperationsorientierter Instrumente die Tax Compliance zu erhöhen und so dem Massenphänomen Besteuerung gerecht zu werden.

  13. Competitive adsorption of functionalized molecules on semiconductor nanocrystal surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Szwaykowska, K. [POM, TU Chemnitz (Germany); Engineering and Applied Sciences, California Inst. of Tech., Pasadena, CA (United States); Raja, C. [OSMP, TU Chemnitz (Germany); ABMC, Kansas State Univ., Manhattan, KS (United States); Blaudeck, T. [POM, TU Chemnitz (Germany); OSMP, TU Chemnitz (Germany); Cichos, F. [POM, TU Chemnitz (Germany); Molecular Nanophotonics, Leipzig Univ. (Germany); Borczyskowski, C. von [OSMP, TU Chemnitz (Germany)


    Inorganic/organic aggregates from semiconductor nanocrystals and functionalized molecules such as porphyrins are considered building blocks in future nanoelectronics as they may provide control on the charge and energy transfer processes. We report on the formation process and the stability of aggregates comprising CdSe and CdSe/ZnS nanocrystals and TOPO ligands in toluene at ambient conditions. Applying steady-state spectroscopy to binary and ternary mixtures we compare the results in presence and absence of additional molecules. The experiments show that the formation kinetics is related to by the absolute concentration of the compounds in parallel to their molar ratio. The importance of the local TOPO concentration at the NC surface indicates a dynamic equilibrium governing the number of adsorption sites available. The findings are discussed in the light of Monte-Carlo simulations. (orig.)

  14. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng


    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  15. Evaluation of immobilized metal-ion affinity chromatography and electrospray ionization tandem mass spectrometry for recovery and identification of copper(II-binding ligands in seawater using the model ligand 8-hydroxyquinoline

    Directory of Open Access Journals (Sweden)

    Richard L Nixon


    Full Text Available Complexation by organic ligands dominates the speciation of iron (Fe, copper (Cu, and other bioactive trace metals in seawater, controlling their bioavailability and distribution in the marine environment. Several classes of high-affinity Fe-binding ligands (siderophores have been identified in seawater but the chemical structures of marine Cu-complexing ligands remain unknown. Immobilized metal-ion affinity chromatography (IMAC allows Cu ligands to be isolated from bulk dissolved organic matter (DOM in seawater and separated into fractions which can be characterized independently using electrochemical and spectroscopic techniques. Attempts have been made to combine IMAC with electrospray ionization mass spectrometry (ESI-MS to characterize marine Cu ligands, but results have proven inconclusive due to the lack of tandem mass spectrometry (MS/MS data to confirm ligand recovery. We used 8-hydroxyquinoline (8-HQ, a well-characterized model ligand that forms strong 1:2 metal:ligand complexes with Cu2+ at pH 8 (log β2 = 18.3, to evaluate Cu(II-IMAC and ESI-MS/MS for recovery and identification of copper(II-complexing ligands in seawater. One-litre samples of 0.45µm-filtered surface seawater were spiked with 8-HQ at low concentrations (up to 100 nM and fractionated by IMAC. Fractions eluted with acidified artificial seawater were desalted and re-suspended in methanol via solid-phase extraction (SPE to obtain extracts suitable for ESI-MS analysis. Recovery of 8-HQ by Cu(II-IMAC was confirmed unambiguously by MS/MS and found to average 81% based upon accurate quantitation via multiple reaction monitoring (MRM. Cu(II-IMAC fractionation of unspiked seawater using multiple UV detection wavelengths suggests an optimal fraction size of 2 mL for isolating and analyzing Cu ligands with similar properties.

  16. PPARα Ligands as Antitumorigenic and Antiangiogenic Agents

    Directory of Open Access Journals (Sweden)

    Ambra Pozzi


    Full Text Available Peroxisome proliferator-activated receptors (PPARs belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members—PPARα, PPARδ, and PPARγ—that differ in their cell and tissue distribution as well as in their target genes. PPARα is abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPARα, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we focus on the contribution of PPARα to tumor and endothelial cell functions and provide compelling evidence that PPARα can be viewed as a new class of ligand activated tumor “suppressor” gene with antiangiogenic and antitumorigenic activities. Given that PPAR ligands are currently used in medicine as hypolipidemic drugs with excellent tolerance and limited toxicity, PPARα activation might offer a novel and potentially low-toxic approach for the treatment of tumor-associated angiogenesis and cancer.

  17. A screening cascade to identify ERβ ligands. (United States)

    Filgueira, Carly S; Benod, Cindy; Lou, Xiaohua; Gunamalai, Prem S; Villagomez, Rosa A; Strom, Anders; Gustafsson, Jan-Åke; Berkenstam, Anders L; Webb, Paul


    The establishment of effective high throughput screening cascades to identify nuclear receptor (NR) ligands that will trigger defined, therapeutically useful sets of NR activities is of considerable importance. Repositioning of existing approved drugs with known side effect profiles can provide advantages because de novo drug design suffers from high developmental failure rates and undesirable side effects which have dramatically increased costs. Ligands that target estrogen receptor β (ERβ) could be useful in a variety of diseases ranging from cancer to neurological to cardiovascular disorders. In this context, it is important to minimize cross-reactivity with ERα, which has been shown to trigger increased rates of several types of cancer. Because of high sequence similarities between the ligand binding domains of ERα and ERβ, preferentially targeting one subtype can prove challenging. Here, we describe a sequential ligand screening approach comprised of complementary in-house assays to identify small molecules that are selective for ERβ. Methods include differential scanning fluorimetry, fluorescence polarization and a GAL4 transactivation assay. We used this strategy to screen several commercially-available chemical libraries, identifying thirty ERβ binders that were examined for their selectivity for ERβ versus ERα, and tested the effects of selected ligands in a prostate cancer cell proliferation assay. We suggest that this approach could be used to rapidly identify candidates for drug repurposing.

  18. Open Government Data Publication Methodology

    National Research Council Canada - National Science Library

    Jan Kucera


    .... Open Government Data (OGD) initiatives aim at increasing availability of machine-readable data provided under an open license and therefore these initiatives might facilitate re-use of the government data which in turn might...

  19. Corporate Governance in Costa Rica


    Gilberto E. Arce; Edgar Robles C.


    This paper examines corporate governance practices in Costa Rica. First, it estimates corporate governance charter measures using firm-level data for 87 Costa Rican firms and studies their impact on the firms` performance; here, the mean of the corporate governance charters for the publicly traded firms is equal to 56. 14. Second, new evidence is presented on de jure and de facto corporate governance charter measures at the firm level and on their effect on the performance of the firm. The re...

  20. Business process management governance model


    Stenšak, Jožica


    Theoretical part of this Master’s thesis is based on business process management governance. The term business process governance refers to a high-level model defining structures, metrics, roles and responsibilities for measuring, improvement and management of company key processes. Governance is one of key activity areas for increased business process maturity provided by maturity models. Establishing Center of Excellence for business process management is a governance key concept, which ena...

  1. Surface-Layer (S-Layer) Proteins Sap and EA1 Govern the Binding of the S-Layer-Associated Protein BslO at the Cell Septa of Bacillus anthracis (United States)

    Kern, Valerie J.; Kern, Justin W.; Theriot, Julie A.; Schneewind, Olaf


    The Gram-positive pathogen Bacillus anthracis contains 24 genes whose products harbor the structurally conserved surface-layer (S-layer) homology (SLH) domain. Proteins endowed with the SLH domain associate with the secondary cell wall polysaccharide (SCWP) following secretion. Two such proteins, Sap and EA1, have the unique ability to self-assemble into a paracrystalline layer on the surface of bacilli and form S layers. Other SLH domain proteins can also be found within the S layer and have been designated Bacillus S-layer-associated protein (BSLs). While both S-layer proteins and BSLs bind the same SCWP, their deposition on the cell surface is not random. For example, BslO is targeted to septal peptidoglycan zones, where it catalyzes the separation of daughter cells. Here we show that an insertional lesion in the sap structural gene results in elongated chains of bacilli, as observed with a bslO mutant. The chain length of the sap mutant can be reduced by the addition of purified BslO in the culture medium. This complementation in trans can be explained by an increased deposition of BslO onto the surface of sap mutant bacilli that extends beyond chain septa. Using fluorescence microscopy, we observed that the Sap S layer does not overlap the EA1 S layer and slowly yields to the EA1 S layer in a growth-phase-dependent manner. Although present all over bacilli, Sap S-layer patches are not observed at septa. Thus, we propose that the dynamic Sap/EA1 S-layer coverage of the envelope restricts the deposition of BslO to the SCWP at septal rings. PMID:22609927

  2. Corporate Governance Country Assessment : Moldova


    World Bank


    This report provides an assessment of Moldova's corporate governance framework-its legal and policy framework, as well as enforcement and compliance practices. The report makes policy recommendations where appropriate, and provides investors with a benchmark to compare corporate governance with the 1999 OECD Principles of Corporate Governance. Moldova is beginning to upgrade its legal and ...

  3. Corporate Governance Country Assessment : Azerbaijan


    World Bank


    This report assesses Azerbaijan's corporate governance framework-its laws and regulations, enforcement and common business practices. The report notes recent improvements in corporate governance regulation, makes recommendations of policy and institutional strengthening, and provides a benchmark against which to measure corporate governance in Azerbaijan. Note that the report covers only p...

  4. The governance of hybrid organisations

    DEFF Research Database (Denmark)

    Spear, Roger; Cornforth, Chris


    The focus of this chapter is on the governance of third sector organizations (TSOs) and the challenges that are raised by hybridity. In particular it will focus on the question how does hybridity affect governance structures and processes and the challenges that governing bodies face?...

  5. Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens

    DEFF Research Database (Denmark)

    Andersen, P S; Geisler, C; Buus, S


    (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency...... of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands. Comparable studies using anti-TCR antibodies of known affinity confirmed these observations. By comparing the biological potency of the two sets of ligands, we found a significant...

  6. The Membrane-anchoring Domain of Epidermal Growth Factor Receptor Ligands Dictates Their Ability to Operate in Juxtacrine Mode

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Jianying; Opresko, Lee; Chrisler, William B.; Orr, Galya; Quesenberry, Ryan D.; Lauffenburger, Douglas A.; Wiley, H S.


    All ligands of the epidermal growth factor receptor (EGFR) are synthesized as membrane-anchored precursors. Previous work has suggested that some ligands, such as EGF, must be proteolytically released to be active, whereas others, such as heparin binding EGF-like growth factor (HB-EGF) can function while still anchored to the membrane (i.e., juxtacrine signaling). To explore the structural basis for these differences in ligand activity, we engineered a series of membrane-anchored ligands in which the core, receptor-binding domain of EGF was combined with different domains of both EGF and HB-EGF. We found that ligands having the N-terminal extension of EGF could not bind to the EGFR, even when released from the membrane. Ligands lacking an N-terminal extension, but possessing the membrane-anchoring domain of EGF still required proteolytic release for activity, whereas ligands with the membrane anchoring domain of HB-EGF could elicit full biological activity while still membrane anchored. Ligands containing the HB-EGF membrane anchor, but lacking an N-terminal extension, activated EGFR during their transit through the Golgi apparatus . However, cell-mixing experiments and fluorescence resonance energy transfer (FRET) studies showed that juxtacrine signaling typically occurred in trans at the cell surface, at points of cell-cell contact. Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode.

  7. Effects of PPARγ Ligands on Leukemia

    Directory of Open Access Journals (Sweden)

    Yoko Tabe


    Full Text Available Peroxisome proliferator-activated receptors (PPARs and retinoic acid receptors (RARs, members of the nuclear receptor superfamily, are transcription factors that regulate a variety of important cellular functions. PPARs form heterodimers retinoid X receptor (RXR, an obligate heterodimeric partner for other nuclear receptors. Several novel links between retinoid metabolism and PPAR responses have been identified, and activation of PPAR/RXR expression has been shown to increase response to retinoids. PPARγ has emerged as a key regulator of cell growth and survival, whose activity is modulated by a number of synthetic and natural ligands. While clinical trials in cancer patients with thiazolidinediones (TZD have been disappointing, novel structurally different PPARγ ligands, including triterpenoids, have entered clinical arena as therapeutic agents for epithelial and hematopoietic malignancies. Here we shall review the antitumor advances of PPARγ, alone and in combination with RARα ligands in control of cell proliferation, differentiation, and apoptosis and their potential therapeutic applications in hematological malignancies.

  8. Flexible Ligand Docking Using Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Thomsen, Rene


    The docking of ligands to proteins can be formulated as a computational problem where the task is to find the most favorable energetic conformation among the large space of possible protein–ligand complexes. Stochastic search methods such as evolutionary algorithms (EAs) can be used to sample large...... search spaces effectively and is one of the commonly used methods for flexible ligand docking. During the last decade, several EAs using different variation operators have been introduced, such as the ones provided with the AutoDock program. In this paper we evaluate the performance of different EA...... settings such as choice of variation operators, population size, and usage of local search. The comparison is performed on a suite of six docking problems previously used to evaluate the performance of search algorithms provided with the AutoDock program package. The results from our investigation confirm...

  9. Privatization Of Global Governance

    Directory of Open Access Journals (Sweden)

    T. J. Biersteker


    Full Text Available Thomas Biersteker graduated from Chicago University (BF in Political Science and MIT (MA in Political Science and got PhD in Political Science in MIT as well. Later professor Biersteker lectured in Yale University (1976-1985, South Carolina University (1985-1992 and Brown University (1992-2006. He could be described as a constructivist focusing his research on global governance, international organizations and transnational policy networks, construction of sovereignty and regimes of targeted sanctions. Professor Birsteker kindly agreed to give an interview to the “MGIMO Review of International Relations” during a seminar within the research project - Grant of RFBR No. 16-23-41004. The seminar was also attended by M.M. Lebedeva, Yu.A. Nikitin, A.I. Nikitin, I.A. Istomin.

  10. The government of life

    DEFF Research Database (Denmark)

    Villadsen, Kaspar; Wahlberg, Ayo


    . Subsequent research on biopolitics and governmentality has tended to separate the concepts, differentiating into distinct research traditions each with different intellectual pathways. We propose to bring these conceptual innovations together to understand contemporary problems of the government of life......The concepts of governmentality and biopolitics were contemporaneous and interlinked in Michel Foucault's initial analyses. These foregrounded how in the eighteenth century the population emerged as a ‘natural-cultural reality’ resulting from an integration of biological and economic knowledge......, that is, of managing, controlling and optimizing a living population. In this domain, the natural/biological continues to intersect with the social/cultural in novel and unexpected ways. Straddling the specter of biopolitics, we examine four dimensions of the concept: vital threats and the resurrection...

  11. Pension Fund governing board

    CERN Multimedia

    HR Department


    On 16 March and 7 May, the Pension Fund Governing Board (PFGB) held its fourth and fifth meetings The first of these meetings was primarily dedicated to the examination of the strategic asset allocation. The PFGB reaffirmed the main goal of the new strategic asset allocation: to improve the Pension Fund’s position with regard to risk by lowering overall portfolio volatility through suitable investments in less volatile asset classes such as real estate and absolute return strategies, where the return does not depend on market trends and negative growth is extremely unlikely. The finalised document will be presented to the Finance Committee and the Council at their June meetings for approval, in accordance with the provisions of the Levaux report. The PFGB also took note of the Internal Audit’s report on Pension Fund operations and decided to refer it to Working Group I as a working document for establishing a control and internal monitoring system for Pension Fund oper...

  12. Ab initio calculation of transport properties between PbSe quantum dots facets with iodide ligands (United States)

    Wang, B.; Patterson, R.; Chen, W.; Zhang, Z.; Yang, J.; Huang, S.; Shrestha, S.; Conibeer, G.


    The transport properties between Lead Selenide (PbSe) quantum dots decorated with iodide ligands has been studied using density functional theory (DFT). Quantum conductance at each selected energy levels has been calculated along with total density of states and projected density of states. The DFT calculation is carried on using a grid-based planar augmented wave (GPAW) code incorporated with the linear combination of atomic orbital (LCAO) mode and Perdew Burke Ernzerhof (PBE) exchange-correlation functional. Three iodide ligand attached low index facets including (001), (011), (111) are investigated in this work. P-orbital of iodide ligand majorly contributes to density of state (DOS) at near top valence band resulting a significant quantum conductance, whereas DOS of Pb p-orbital shows minor influence. Various values of quantum conductance observed along different planes are possibly reasoned from a combined effect electrical field over topmost surface and total distance between adjacent facets. Ligands attached to (001) and (011) planes possess similar bond length whereas it is significantly shortened in (111) plane, whereas transport between (011) has an overall low value due to newly formed electric field. On the other hand, (111) plane with a net surface dipole perpendicular to surface layers leading to stronger electron coupling suggests an apparent increase of transport probability. Apart from previously mentioned, the maximum transport energy levels located several eVs (1 2 eVs) from the edge of valence band top.

  13. Local Government System in Japan

    Directory of Open Access Journals (Sweden)

    Vladimir V. Redko


    Full Text Available The article is devoted to the issues of the activities of the local government of Japan. Particular attention is drawn to the legal framework and the material basis for the functioning of local self-government bodies. The system of local self-government is considered as a special form of self-government with a specific functional and meaning; system of municipal management and delegation of authority, as well as features of interaction between civil and imperious levels. The allocation of the city with a special status, as well as the financial structure of the local government of Japan, is considered in detail.

  14. Government-to-Government E-Government: A Case Study of a Federal Financial Program (United States)

    Faokunla, Olumide Adegboyega


    The problem with the study of the concept of electronic government (e-Gov) is that scholars in the field have not adequately explored various dimensions of the concept. Literature on e-Gov is replete with works on the form of government to consumer e-Gov. Much less work had been done on the government to government (G2G) e-Gov. This qualitative…

  15. Discovery of Aptamer Ligands for Hepatic Stellate Cells Using SELEX. (United States)

    Chen, Zhijin; Liu, Hao; Jain, Akshay; Zhang, Li; Liu, Chang; Cheng, Kun


    Insulin like growth factor II receptor (IGFIIR) is a transmembrane protein overexpressed in activated hepatic stellate cells (HSCs), which are the major target for the treatment of liver fibrosis. In this study, we aim to discover an IGFIIR-specific aptamer that can be potentially used as a targeting ligand for the treatment and diagnosis of liver fibrosis. Systematic evolution of ligands by exponential enrichment (SELEX) was conducted on recombinant human IGFIIR to identify IGFIIR-specific aptamers. The binding affinity and specificity of the discovered aptamers to IGFIIR and hepatic stellate cells were studied using flow cytometry and Surface Plasmon Resonance (SPR). Aptamer-20 showed the highest affinity to recombinant human IGFIIR protein with a K d of 35.5 nM, as determined by SPR. Aptamer-20 also has a high affinity (apparent K d 45.12 nM) to LX-2 human hepatic stellate cells. Binding of aptamer-20 to hepatic stellate cells could be inhibited by knockdown of IGFIIR using siRNA, indicating a high specificity of the aptamer. The aptamer formed a chimera with an anti-fibrotic PCBP2 siRNA and delivered the siRNA to HSC-T6 cells to trigger silencing activity. In Vivo biodistribution study of the siRNA-aptamer chimera also demonstrated a high and specific uptake in the liver of the rats with CCl 4 -induced liver fibrosis. These data suggest that aptamer-20 is a high-affinity ligand for antifibrotic and diagnostic agents for liver fibrosis.

  16. Tuning the Topology and Functionality of Metal–Organic Frameworks by Ligand Design

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Dan; Timmons, Daren J; Yuan, Daqiang; Zhou, Hong-Cai


    collapsing, giving rise to the first case of mesoporous MOF that demonstrates the type IV isotherm. We use dendritic hexacarboxylate ligands to synthesize an isoreticular series of MOFs with (3,24)-connected network topology. The cuboctahedral cages serve as building blocks that narrow the opening of the mesocavities into microwindows and stabilize these MOFs. The resulting materials have exceptionally high surface areas and hydrogen uptake capacities. Despite the many achievements in MOF development, there is still ample opportunity for further exploration. We will be continuing our efforts and look forward to contributing to this blossoming field in the next decade.

  17. Local Government Internal Audit Compliance

    Directory of Open Access Journals (Sweden)

    Greg Jones


    Full Text Available Local government councils (LGC rely on a number of funding sources including state and federal governments as well as their community constituents to enable them to provide a range of public services. Given the constraints on these funding sources councils need to have in place a range of strategies and policies capable of providing good governance and must appropriately discharge their financial accountabilities. To assist LGC with meeting their governance and accountability obligations they often seek guidance from their key stakeholders. For example, in the Australian State of New South Wales (NSW, the Office of Local Government has developed a set of guidelines, the Internal Audit Guidelines. In 2010 the NSW Office of Local Government issued revised guidelines emphasising that an internal audit committee is an essential component of good governance. In addition, the guidelines explained that to improve the governance and accountability of the councils, these committees should be composed of a majority of independent members. To maintain committee independence the guidelines indicated that the Mayor should not be a member of the committee. However these are only guidelines, not legislated requirements and as such compliance with the guidelines, before they were revised, has been demonstrated to be quite low (Jones & Bowrey 2013. This study, based on a review of NSW Local Government Councils’ 2012/2013 reports, including Annual Reportsrelation to internal audit committees, to determine if the guidelines are effective in improving local government council governance.

  18. Petra Governance Handbook - WP7 – Governance structures & business models : D7.3: Governance Handbook

    NARCIS (Netherlands)

    Veeneman, W.; Hirschhorn, F.; Klievink, A.J.; Steenhuisen, B.M.; van der Voort, H.G.


    This document represents the governance handbook on mobility data platforms for the PETRA project. The governance handbook provides metropolitan authorities contemplating the implementation of a mobility data platform in line with the PETRA project about governance issues and design.

  19. Managing stakeholders in transformational government

    DEFF Research Database (Denmark)

    Reinwald, Anja Kaldahl; Kræmmergaard, Pernille


    ). This paper contributes to this literature by reporting the findings from a case study in a Danish local government who has reached the stage of transformational government. Using a grounded theory approach, information about the local government was initially collected and further analyzed within...... a stakeholder perspective. The paper reports how they succeeded in involving the most important stakeholders in the process of reaching transformational government. Finally the paper offers six lessons learned, based on the case study, about how to manage the involved stakeholders to reach transformational......According to the e-government maturity literature public organizations will move through different stages of maturity implying that more mature e-government is better. For many public organizations the next stage to enter is the stage of transformational government (Dhillon et al., 2008...

  20. Governing the Nexus for Sustainability

    Directory of Open Access Journals (Sweden)

    Marx Sina


    Full Text Available This report summarizes the challenges of and requirements for effective governance of the water, energy and food nexus. With global dynamics such as climate change, urbanization and changing consumption patterns, governing resources in a coherent manner becomes both more complex and more relevant for sustainable development. Governance challenges include nexus economics (costs and benefits of different approaches to resource management, institutional design (like questions of how decision-making should be best distributed and good governance (how to make sure that nexus governance adheres to certain agreed upon principles and values. In terms of economics, a balance between sector specific actions and nexus governance is required. For effective decision-making it is important that power among different institutions is both distributed and coordinated. Good nexus governance requires targets that can be monitored to make sure that basic principles are followed and to examine whether progress toward sustainable development is being made.

  1. Characteristics of oncolytic vesicular stomatitis virus displaying tumor-targeting ligands. (United States)

    Ammayappan, Arun; Peng, Kah-Whye; Russell, Stephen J


    We sought proof of principle that tumor-targeting ligands can be displayed on the surface of vesicular stomatitis virus (VSV) by engineering its glycoprotein. Here, we successfully rescued VSVs displaying tumor vasculature-targeting ligands. By using a rational approach, we investigated various feasible insertion sites on the G protein of VSV (VSV-G) for display of tumor vasculature-targeting ligands, cyclic RGD (cRGD) and echistatin. We found seven sites on VSV-G that tolerated insertion of the 9-residue cRGD peptide, two of which could tolerate insertion of the 49-amino acid echistatin domain. All of the ligand-displaying viruses replicated as well as the parental virus. In vitro studies demonstrated that the VSV-echistatin viruses specifically bound to targeted integrins. Since the low-density lipoprotein receptor (LDLR) was recently identified as a major receptor for VSV, we investigated the entry of ligand-displaying viruses after masking LDLR. The experiment showed that the modified viruses can enter the cell independently of LDLR, whereas entry of unmodified virus is significantly blocked by a specific monoclonal antibody against LDLR. Both parental and ligand-displaying viruses displayed equal oncolytic efficacies in a syngeneic mouse myeloma model. We further demonstrated that single-chain antibody fragments against tumor-specific antigens can be inserted at the N terminus of the G protein and that corresponding replication-competent VSVs can be rescued efficiently. Overall, we demonstrated that functional tumor-targeting ligands can be displayed on replication-competent VSVs without perturbing viral growth and oncolytic efficacy. This study provides a rational foundation for the future development of fully retargeted oncolytic VSVs.

  2. Fabricating Water Dispersible Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications through Ligand Exchange and Direct Conjugation. (United States)

    Lam, Tina; Avti, Pramod K; Pouliot, Philippe; Maafi, Foued; Tardif, Jean-Claude; Rhéaume, Éric; Lesage, Frédéric; Kakkar, Ashok


    Stable superparamagnetic iron oxide nanoparticles (SPIONs), which can be easily dispersed in an aqueous medium and exhibit high magnetic relaxivities, are ideal candidates for biomedical applications including contrast agents for magnetic resonance imaging. We describe a versatile methodology to render water dispersibility to SPIONs using tetraethylene glycol (TEG)-based phosphonate ligands, which are easily introduced onto SPIONs by either a ligand exchange process of surface-anchored oleic-acid (OA) molecules or via direct conjugation. Both protocols confer good colloidal stability to SPIONs at different NaCl concentrations. A detailed characterization of functionalized SPIONs suggests that the ligand exchange method leads to nanoparticles with better magnetic properties but higher toxicity and cell death, than the direct conjugation methodology.

  3. Fabricating Water Dispersible Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications through Ligand Exchange and Direct Conjugation

    Directory of Open Access Journals (Sweden)

    Tina Lam


    Full Text Available Stable superparamagnetic iron oxide nanoparticles (SPIONs, which can be easily dispersed in an aqueous medium and exhibit high magnetic relaxivities, are ideal candidates for biomedical applications including contrast agents for magnetic resonance imaging. We describe a versatile methodology to render water dispersibility to SPIONs using tetraethylene glycol (TEG-based phosphonate ligands, which are easily introduced onto SPIONs by either a ligand exchange process of surface-anchored oleic-acid (OA molecules or via direct conjugation. Both protocols confer good colloidal stability to SPIONs at different NaCl concentrations. A detailed characterization of functionalized SPIONs suggests that the ligand exchange method leads to nanoparticles with better magnetic properties but higher toxicity and cell death, than the direct conjugation methodology.

  4. Isotherm of ligand adsorption on DNA at multiplicative noise. (United States)

    Arakelyan, Valeri; Harutyunyan, Sos; Andriasyan, Vardan; Arakelyan, Hakob


    Fluctuations of the number of ligands adsorbed on macromolecules are considered in the case when the number of ligands in the solution fluctuates under the action of fluctuations of the external medium (external noise). For the case of small filling, the multiplicative type of stochastic differential equation is obtained, describing the time variation of the number of ligands adsorbed on macromolecules. The isotherm of adsorption of ligands on DNA is obtained. It is shown that at small ligand concentrations, for some relations between adsorption parameters and the intensity of the external noise, no macromolecule adsorption of ligands takes place.

  5. Biological Redundancy of Endogenous GPCR Ligands in the Gut and the Potential for Endogenous Functional Selectivity

    Directory of Open Access Journals (Sweden)

    Georgina eThompson


    Full Text Available This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract (GIT. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals.

  6. Effects of low-molecular-weight organic ligands and phosphate on DNA adsorption by soil colloids and minerals. (United States)

    Cai, Peng; Huang, Qiaoyun; Zhu, Jun; Jiang, Daihua; Zhou, Xueyong; Rong, Xingmin; Liang, Wei


    Adsorption of DNA on montmorillonite, kaolinite, goethite and soil clays from an Alfisol in the presence of citrate, tartrate and phosphate was studied. A marked decrease in DNA adsorption was observed on montmorillonite and kaolinite with increasing anion concentrations from 0 to 5 mM. However, the amount of DNA adsorbed by montmorillonite and kaolinite was enhanced when ligand concentration was higher than 5 mM. In the system of soil colloids and goethite, with the increase of anion concentrations, a steady decrease was found and the ability of ligands in depressing DNA adsorption followed the sequence: phosphate > citrate > tartrate. Compared to H2O2-treated clays (inorganic clays), a sharp decrease in DNA adsorption was observed on goethite and organo-mineral complexes (organic clays) with increasing ligand concentrations. The results suggest that the influence of anions on DNA adsorption varies with the type and concentration of anion as well as the surface properties of soil components. Introduction of DNA into the system before the addition of ligands had the greatest amount of DNA adsorption on soil colloids and goethite. Organic and inorganic ligands promoted DNA adsorption on montmorillonite and kaolinite when ligands were introduced into the system before the addition of DNA. The results obtained in this study have important implications for the understanding of the persistence and fate of DNA in soil environments especially rhizosphere soil where various organic and inorganic ligands are active.

  7. Facet-Specific Ligand Interactions on Ternary AgSbS 2 Colloidal Quantum Dots

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyekyoung [Nano-Convergence Systems Research Division, Korea Institute of Machinery and Materials, Daejeon 34103 Republic of Korea; Kim, Sungwoo [Nano-Convergence Systems Research Division, Korea Institute of Machinery and Materials, Daejeon 34103 Republic of Korea; Luther, Joseph M. [Chemical and Materials Sciences Center, National Renewable Energy Laboratory, Golden CO 80401 USA; Kim, Sang-Wook [Department of Molecular Science and Technology, Ajou University, Suwon 16499 Republic of Korea; Shin, Dongwoon [Nano-Convergence Systems Research Division, Korea Institute of Machinery and Materials, Daejeon 34103 Republic of Korea; Department of Nanomechatronics, Korea University of Science and Technology (UST), Daejeon 34113 Republic of Korea; Beard, Matthew C. [Chemical and Materials Sciences Center, National Renewable Energy Laboratory, Golden CO 80401 USA; Jeong, Sohee [Nano-Convergence Systems Research Division, Korea Institute of Machinery and Materials, Daejeon 34103 Republic of Korea; Department of Nanomechatronics, Korea University of Science and Technology (UST), Daejeon 34113 Republic of Korea


    Silver dimetal chalcogenide (Ag-V-VI2) ternary quantum dots (QDs) are emerging lead-free materials for optoelectronic devices due to their NIR band gaps, large absorption coefficients, and superior electronic properties. However, thin film-based devices of the ternary QDs still lag behind due to the lack of understanding of the surface chemistry, compared to that of lead chalcogenide QDs even with the same crystal structure. Herein the surface ligand interactions of AgSbS2 QDs, synthesized with 1-dodecanethiol used as a stabilizer, are studied. For nonpolar (1 0 0) surfaces, it is suggested that the thiolate ligands are associated with the crystal lattices, thus preventing surface oxidation by protecting sulfur after air-exposure, as confirmed through optical and surface chemical analysis. Otherwise, silver rich (1 1 1) surfaces are passivated by thiolate ligands, allowing ligand exchange processes for the conductive films. This in-depth investigation of the surface chemistry of ternary QDs will prompt the performance enhancement of their optoelectronic devices.

  8. Government Governance, Legal Environment and Sustainable Economic Development

    Directory of Open Access Journals (Sweden)

    Feng Wei


    Full Text Available Based on China’s inter-provincial panel data from 1999–2009, this paper has tested the impact and extent of marketization, government governance, and legal environment of sustainable economic development by controlling physical capital, human capital and productivity, so as to find the institutional reality for the difference in China’s economic development and another explanation for it. It turns out that marketization, government governance, and legal environment play significant roles in promoting sustainable economic development. Further tests show that the results of Eastern China are consistent with China’s inter-provincial results; while in Western China, the promotion effect of marketization, government governance, and legal environment on sustainable economic development is not significant.

  9. Alignment between business process governance and IT governance

    DEFF Research Database (Denmark)

    Rahimi, Fatemeh; Møller, Charles; Hvam, Lars


    frameworks to enable business-IT strategic alignment, efficient process and IT requirements specification, and IT-enabled business value realization. We examine the actuality of this alignment in practice through a case study conducted in a relatively mature multinational corporation. The findings indicate......The importance of business processes and the increasing centrality of IT to an organization's performance have called for a specific focus on business process governance and IT governance in contemporary enterprises. Despite the wide scope of business process management, which covers both business...... and IT domains, and the profound impact of IT on process innovations, the association between business process governance and IT governance remains under-explored. Analyzing the constituting elements of the two governance concepts, we propose the necessity of alignment between business process and IT governance...

  10. Structural properties of MHC class II ligands, implications for the prediction of MHC class II epitopes.

    Directory of Open Access Journals (Sweden)

    Kasper Winther Jørgensen

    Full Text Available Major Histocompatibility class II (MHC-II molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100-200 peptides per allele to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined prediction method was shown to significantly outperform the state-of-the-art MHC class II peptide binding prediction method when used to identify MHC class II ligands. We also tried to integrate N- and O-glycosylation in our prediction methods but this additional information was found not to improve prediction performance. In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule.

  11. Ligand-assisted degradation of carbon tetrachloride by microscale zero-valent iron. (United States)

    Zhang, Xianlan; Deng, Baolin; Guo, Jing; Wang, Yang; Lan, Yeqing


    Degradation of carbon tetrachloride (CT) by microscale zero-valent iron (ZVI) was investigated in batch systems with or without organic ligands (ethylenediaminetetraacetic acid (EDTA), citric acid, tartaric acid, malic acid and oxalic acid) at pHs from 3.5 to 7.5. The results demonstrated that at 25°C, the dechlorination of CT by microscale ZVI is slow in the absence of organic ligands, with a pseudo-first-order rate constant of 0.0217 h(-1) at pH 3.5 and being further dropped to 0.0052 h(-1) at pH 7.5. However, addition of organic ligands significantly enhanced the rates and the extents of CT removal, as indicated by the rate constant increases of 39, 31, 32, 28 and 18 times in the presence of EDTA, citric acid, tartaric acid, malic acid and oxalic acid, respectively, at pH 3.5 and 25°C. The effect of EDTA was most significant; the dechlorination of CT at an initial concentration of 20 mg l(-1) increased from 16.3% (no ligands) to 89.1% (with EDTA) at the end of 8h reaction. The enhanced CT degradation in the presence of organic ligands was primarily attributed to the elimination of a surface passivation layer of Fe(III) (hydr)oxides on the microscale ZVI through chelating of organic ligands with Fe(III), which maintained the exposure of active sites on ZVI surface to CT. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Introduction of functionalized mesopores to metal-organic frameworks via metal-ligand-fragment coassembly. (United States)

    Park, Jinhee; Wang, Zhiyong U; Sun, Lin-Bing; Chen, Ying-Pin; Zhou, Hong-Cai


    Introduction of functionalized mesopores into microporous metal-organic frameworks (MOFs) can endow them with suitable properties for applications in gas storage, separation, catalysis, and drug delivery. However, common methods for functionalization (including pre- and post-synthetic modifications) of the internal surface of a MOF reduce the pore size of the MOF because the additional functional groups fill up the pores. We present a metal-ligand-fragment coassembly strategy for the introduction of (meso)pores functionalized with various substituent groups on the ligand fragments. Astonishingly, this new functionalization strategy increases the pore volume of a MOF instead of reducing it. Since the ligand fragments are often readily available or easily prepared, the new procedure for synthesis of the modified MOFs becomes much easier and more applicable than existing approaches. Remarkably, mesopores can be generated conveniently and controllably by the coassembly of a ligand and its fragment containing the desired functional groups. The fragment/ligand ratio has been optimized to preserve the parent structure and to promote maximum mesopore introduction, which has led to a systematic evaluation of the effectiveness of a series of functional groups for the adsorption of guest molecules.

  13. Structural linkage between ligand discrimination and receptor activation by type I interferons. (United States)

    Thomas, Christoph; Moraga, Ignacio; Levin, Doron; Krutzik, Peter O; Podoplelova, Yulia; Trejo, Angelica; Lee, Choongho; Yarden, Ganit; Vleck, Susan E; Glenn, Jeffrey S; Nolan, Garry P; Piehler, Jacob; Schreiber, Gideon; Garcia, K Christopher


    Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFNα2 and IFNω reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand "anchor points" interspersed among ligand-specific interactions that "tune" the relative IFN-binding affinities, in an apparent extracellular "ligand proofreading" mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Patent system governance. Theorizing about institucional, governance dimension rationale


    Ernesto Guevara Fernández


    This work deals with the patent governance as theoretical model for improving the functioning of the patent system. It provides an approach to the patent governance at the various levels, international, national and regional, that challenges the traditional, static patent system based on the central role of the examination and granted office by the new heterogeneous actors, relations between these actors and participatory mechanisms within the patent system. Patent governance impacts the inst...

  15. Promoted Iron Nanocrystals Obtained via Ligand Exchange as Active and Selective Catalysts for Synthesis Gas Conversion (United States)


    Colloidal synthesis routes have been recently used to fabricate heterogeneous catalysts with more controllable and homogeneous properties. Herein a method was developed to modify the surface composition of colloidal nanocrystal catalysts and to purposely introduce specific atoms via ligands and change the catalyst reactivity. Organic ligands adsorbed on the surface of iron oxide catalysts were exchanged with inorganic species such as Na2S, not only to provide an active surface but also to introduce controlled amounts of Na and S acting as promoters for the catalytic process. The catalyst composition was optimized for the Fischer–Tropsch direct conversion of synthesis gas into lower olefins. At industrially relevant conditions, these nanocrystal-based catalysts with controlled composition were more active, selective, and stable than catalysts with similar composition but synthesized using conventional methods, possibly due to their homogeneity of properties and synergic interaction of iron and promoters. PMID:28824820

  16. Supramolecular architectures constructed using angular bipyridyl ligands

    CERN Document Server

    Barnett, S A


    This work details the synthesis and characterization of a series of coordination frameworks that are formed using bidentate angular N-donor ligands. Pyrimidine was reacted with metal(ll) nitrate salts. Reactions using Cd(NO sub 3) sub 2 receive particular focus and the analogous reactions using the linear ligand, pyrazine, were studied for comparison. In all cases, two-dimensional coordination networks were prepared. Structural diversity is observed for the Cd(ll) centres including metal-nitrate bridging. In contrast, first row transition metal nitrates form isostructural one-dimensional chains with only the bridging N-donor ligands generating polymeric propagation. The angular ligand, 2,4-bis(4-pyridyl)-1,3,5-triazine (dpt), was reacted with Cd(NO sub 3) sub 2 and Zn(NO sub 3) sub 2. Whereas Zn(NO sub 3) sub 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO sub 3) sub 2 , including the first example of a doubly parallel interpenetrated 4.8 sup...

  17. Flexible Ligand Docking Using Differential Evolution

    DEFF Research Database (Denmark)

    Thomsen, René


    Molecular docking of biomolecules is becoming an increasingly important part in the process of developing new drugs, as well as searching compound databases for promising drug candidates. The docking of ligands to proteins can be formulated as an optimization problem where the task is to find...

  18. A versatile dinucleating ligand containing sulfonamide groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa


    Copper, iron, and gallium coordination chemistries of the new pentadentate bis-sulfonamide ligand 2,6-bis(N-2-pyridylmethylsulfonamido)-4-methylphenol (psmpH3) were investigated. PsmpH3 is capable of varying degrees of deprotonation, and notably, complexes containing the fully trideprotonated...

  19. Noncalcemic actions of vitamin D receptor ligands. (United States)

    Nagpal, Sunil; Na, Songqing; Rathnachalam, Radhakrishnan


    1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.


    African Journals Online (AJOL)

    Nwokem et al.

    ABSTRACT. The quality of biogas depends largely on the percentage of methane and hydrogen sulphide gas present. High concentration of hydrogen sulphide results in low quality biogas. This work employed the use of chelating ligands in scrubbing hydrogen sulphide gas while improving the yield of methane gas.

  1. Ligand sphere conversions in terminal carbide complexes

    DEFF Research Database (Denmark)

    Morsing, Thorbjørn Juul; Reinholdt, Anders; Sauer, Stephan P. A.


    Metathesis is introduced as a preparative route to terminal carbide complexes. The chloride ligands of the terminal carbide complex [RuC(Cl)2(PCy3)2] (RuC) can be exchanged, paving the way for a systematic variation of the ligand sphere. A series of substituted complexes, including the first...... demonstrates that details of the coordination geometry affect the carbide chemical shift equally as much as variations in the nature of the auxiliary ligands. Furthermore, the kinetics of formation of the sqaure pyramidal dicyano complex, trans-[RuC(CN)2(PCy3)2], from RuC has been examined and the reaction...... found to be quite sluggish and of first order in both RuC and cyanide with a rate constant of k = 0.0104(6) M–1 s–1. Further reaction with cyanide leads to loss of the carbide ligand and formation of trans-[Ru(CN)4(PCy3)2]2–, which was isolated and structurally characterized as its PPh4+ salt....

  2. Simple tertiary phosphines to hexaphosphane ligands: Syntheses ...

    Indian Academy of Sciences (India)

    In this context, we have developed new synthetic methodologies for making unusual inorganic ring systems containing trivalent phosphorus centres, novel phosphorus-based multidentate and hybrid ligands and explored their rich transition metal chemistry and catalytic applications. We have also fine tuned a few existing ...

  3. 01-ERD-111 - The Development of Synthetic High Affinity Ligands

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, J; Balhorn, R; Cosman, M; Lightstone, F; Zeller, L


    The aim of this project was to develop Synthetic High-Affinity Ligands (SHALs), which bind with high affinity and specificity to proteins of interest for national security and cancer therapy applications. The aim of producing synthetic ligands for sensory devices as an alternative to antibody-based detection assays and therapeutic agents is to overcome the drawbacks associated with antibody-based in next-generation sensors and systems. The focus area of the project was the chemical synthesis of the SHALs. The project concentrated on two different protein targets. (a) The C fragment of tetanus and botulinum toxin, potential biowarfare agents. A SHAL for tetanus or botulinum toxin would be incorporated into a sensory device for the toxins. (b) HLA-DR10, a protein found in high abundance on the surface of Non-Hodgkins Lymphoma. A SHAL specific to a tumor marker, labeled with a radionuclide, would enable the targeted delivery of radiation therapy to metastatic disease. The technical approach used to develop a SHAL for each protein target will be described in more detail below. However, in general, the development of a SHAL requires a combination of computational modeling techniques, modern nuclear magnetic resonance spectroscopy (NMR) and synthetic chemistry.

  4. Structure and function of the selectin ligand PSGL-1

    Directory of Open Access Journals (Sweden)

    R.D. Cummings


    Full Text Available P-selectin glycoprotein ligand-1 (PSGL-1 is a dimeric mucin-like 120-kDa glycoprotein on leukocyte surfaces that binds to P- and L-selectin and promotes cell adhesion in the inflammatory response. The extreme amino terminal extracellular domain of PSGL-1 is critical for these interactions, based on site-directed mutagenesis, blocking monoclonal antibodies, and biochemical analyses. The current hypothesis is that for high affinity interactions with P-selectin, PSGL-1 must contain O-glycans with a core-2 branched motif containing the sialyl Lewis x antigen (NeuAca2®3Galß1®4[Fuca1®3]GlcNAcß1®R. In addition, high affinity interactions require the co-expression of tyrosine sulfate on tyrosine residues near the critical O-glycan structure. This review addresses the biochemical evidence for this hypothesis and the evidence that PSGL-1 is an important in vivo ligand for cell adhesion.

  5. Portraying G Protein-Coupled Receptors with Fluorescent Ligands (United States)


    The thermodynamics of ligand–receptor interactions at the surface of living cells represents a fundamental aspect of G protein-coupled receptor (GPCR) biology; thus, its detailed elucidation constitutes a challenge for modern pharmacology. Interestingly, fluorescent ligands have been developed for a variety of GPCRs in order to monitor ligand–receptor binding in living cells. Accordingly, new methodological strategies derived from noninvasive fluorescence-based approaches, especially fluorescence resonance energy transfer (FRET), have been successfully developed to characterize ligand–receptor interactions. Importantly, these technologies are supplanting more hazardous and expensive radioactive binding assays. In addition, FRET-based tools have also become extremely powerful approaches for visualizing receptor–receptor interactions (i.e., GPCR oligomerization) in living cells. Thus, by means of the synthesis of compatible fluorescent ligands these novel techniques can be implemented to demonstrate the existence of GPCR oligomerization not only in heterologous systems but also in native tissues. Finally, there is no doubt that these methodologies would also be relevant in drug discovery in order to develop new high-throughput screening approaches or to identify new therapeutic targets. Overall, herein, we provide a thorough assessment of all technical and biological aspects, including strengths and weaknesses, of these fluorescence-based methodologies when applied to the study of GPCR biology at the plasma membrane of living cells. PMID:25010291

  6. Project governance: "Schools of thought"

    Directory of Open Access Journals (Sweden)

    Michiel Christiaan Bekker


    Full Text Available The terminology, definition and context of project governance have become a focal subject for research and discussions in project management literature. This article reviews literature on the subject of project governance and categorise the arguments into three schools of thought namely the single-firm school, multi-firm school and large capital school. The single-firm school is concerned with governance principles related to internal organisational projects and practice these principles at a technical level. The multi-firm school address the governance principles concerned with two of more organisations participating on a contractual basis on the same project and focus their governance efforts at the technical and strategic level. The large capital school consider projects as temporary organisations, forming their own entity and establishing governance principles at an institutional level. From these schools of thought it can be concluded that the definition of project governance is dependent on the type of project and hierarchical positioning in the organisation. It is also evident that further research is required to incorporate other governance variables and mechanisms such as transaction theory, social networks and agency theory. The development of project governance frameworks should also consider the complexity of projects spanning across international companies, across country borders and incorporating different value systems, legal systems, corporate governance guidelines, religions and business practices.

  7. Preventive self-governance

    Directory of Open Access Journals (Sweden)

    Sturloni Giancarlo


    Full Text Available No field of western society has remained untouched by the events of September 11. Lastly, science and science communication are also bearing the consequences. During the annual meeting of the American Association for the Advancement of Science in Denver, Colorado, on February 15, 2003, the major international scientific magazines, faced with the bioterrorism alarm and the fear of seeing important information fall in the wrong hands, announced their intention to resort to an unprecedented security measure: preventive self-governance.1 They consider the Statement on Scientific Publication and Security as a manifesto of the sense of responsibility that the scientific community feels about global terror. In part four, after recalling the 9/11tragedy, the 32 publishers, scientific associations and scientists who signed the Statement (among which also the directors of Nature and Science stated that “On occasion an editor may conclude that the potential harm of publication outweighs the potential societal benefits. Under such circumstances, the paper should be modified, or not be published ”

  8. Democracy over governance

    Directory of Open Access Journals (Sweden)

    Amelia Correa


    Full Text Available Varieties of institutional economics are available to evaluate varieties of capitalism. These methodologies dig behind preferences and technology to arrive at the ground on which agents make choices. The individual is at the foundation of these edifices, neoclassical and otherwise. Consequently, the denouement of all these models is that the market knows best in the absence of effective counterfactuals. A natural corollary is that the task of the government is to set effective mechanisms in place in order to approach the best outcomes. In contrast, we propose a framework which contends with the modern economy as an aggregate that evolves in historical time. Problems like effective demand failures are endemic to capitalist economies. Therefore, systematic State intervention is essential to their functioning. In particular, political economy teaches us that intervention must be in the interest of wage earners. In contrast to the earlier model, the fabric of norms and conventions that facilitate the growth and development of economies must emerge from the consciousness and practices of the working class.

  9. Ammonia formation by metal-ligand cooperative hydrogenolysis of a nitrido ligand (United States)

    Askevold, Bjorn; Nieto, Jorge Torres; Tussupbayev, Samat; Diefenbach, Martin; Herdtweck, Eberhardt; Holthausen, Max C.; Schneider, Sven


    Bioinspired hydrogenation of N2 to ammonia at ambient conditions by stepwise nitrogen protonation/reduction with metal complexes in solution has experienced remarkable progress. In contrast, the highly desirable direct hydrogenation with H2 remains difficult. In analogy to the heterogeneously catalysed Haber-Bosch process, such a reaction is conceivable via metal-centred N2 splitting and unprecedented hydrogenolysis of the nitrido ligands to ammonia. We report the synthesis of a ruthenium(IV) nitrido complex. The high nucleophilicity of the nitrido ligand is demonstrated by unusual N-C coupling with π-acidic CO. Furthermore, the terminal nitrido ligand undergoes facile hydrogenolysis with H2 at ambient conditions to produce ammonia in high yield. Kinetic and quantum chemical examinations of this reaction suggest cooperative behaviour of a phosphorus-nitrogen-phosphorus pincer ligand in rate-determining heterolytic hydrogen splitting.

  10. Government governance, executive networks and enterprise R&D

    Directory of Open Access Journals (Sweden)

    Xin Jin


    Full Text Available The increasingly competitive market environment makes independent innovation the core of the enterprise’s and evens the country’s competitiveness. In order to solve the problem of its own limited R&D resources, firms need to find access to outside resources. Since the government mainly provides policy and financial support, the information diffusion and learning effects of executive networks can effectively compensate for the shortage of formal institutional arrangements. In view of this, we manually collect data on R&D expenditures and executive networks having common management members in China A-share listed companies from 2007 to 2010. Combined with corporate governance and government governance data, this paper empirically tests the influence of government governance and executive networks on enterprise innovation. The empirical results reveal that the governance efficiency of the government where the enterprise is located determines the efficiency of resource allocation firms are faced with, which provides institutional constraints on corporate R&D intensity, and that the establishment and scale of executive networks do contribute to R&D decisions. Further testing shows that compared with non-state-owned enterprises, state-owned enterprises are faced with relatively weaker restraints and pressures in terms of policy, finance, technology and competition. Thus, they show no obvious reliance on government governance quality and the information diffusion of executive networks. The findings of this study help us to understand the role of informal systems in social economics, such as relationship networks and social capital, in the context of China’s economic development, and provide relevant evidence and enrich macro and micro studies of “government and market” and “market and enterprise” relationships.

  11. Jaarboek corporate governance 2011-2012

    NARCIS (Netherlands)

    Lückerath – Rovers, M.; Bier, B.; Kaptein, M.; Paape, L.


    In dit eerste Jaarboek Corporate Governance worden uiteenlopende aspecten van Corporate Governance nader besproken door toonaangevende schrijvers uit verschillende disciplines. Inclusief actuele corporate governance code.

  12. Quantum.Ligand.Dock: protein-ligand docking with quantum entanglement refinement on a GPU system. (United States)

    Kantardjiev, Alexander A


    Quantum.Ligand.Dock (protein-ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein-ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments-the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high-performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein-ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at

  13. Role of Lanthanide-Ligand bonding in the magnetization relaxation ...

    Indian Academy of Sciences (India)

    Ligand bonding. Our calculations transpire comparatively improved Single-Ion Magnet (SIM) behaviour for carbene analogues due to the more axially compressed trigonal prismatic ligand environment. Furthermore, our detailed Mulliken charge, ...

  14. Fluorescent GPCR ligands as new tools in pharmacology. (United States)

    Kuder, Kamil; Kieć-Kononowicz, Katarzyna


    The expansion of fluorescent techniques for studying the ligand-receptor interaction resulted in a burst of the novel fluorescent ligands development. The discovery of the ligand, that is of high affinity to the receptor and whose localization could be easily visualized, even on the single cell level, gave the researchers a strong impulse to investigate that field of GPCR ligands. Moreover, paying attention to the "non pharmacological" advantages of these ligands, as well as the techniques to be used, fluorescent ligands are becoming treated more seriously, as the ligands themselves, and as novel, useful tools for studying GPCRs. Herein, we review results described in the literature, starting from the year 2000, in the field of the fluorescent GPCR small, non-peptide ligands according to the affinity to the selected receptors (histamine, adenosine, adrenergic, cannabinoid, muscarinie, neuropeptide Y and serotonine) as well as the fluorophores that have been used to tag the molecules.


    Directory of Open Access Journals (Sweden)

    N. Versal


    Full Text Available It’s disclosed the features of the international government securities market during 1993 – 2012: main players are the developed countries (Western Europe, Canada, USA with the increasing role of developing countries; debt crises have the negative impact as on the development of the international government securities market, but also on the international capital market as a whole; debt crises are not a spontaneous phenomenon, and usually occur as a result of inadequate growth in GDP increasing government debt.

  16. Corporate governance of the environment.


    Purvis, B.


    The global pursuit of a more sustainable future cannot be achieved without the active engagement of the business community. The challenge for business has been to strategically engage with and embed environmental responsibility within their wider corporate governance to create effective corporate governance of the environment. The assumption would appear to be, that we have already witnessed the construction of such governance, delivered through the attainment of a paradigmatic shift in corpo...

  17. Governance and Australian Financial Institutions


    Kevin Davis


    This paper examines issues of corporate governance arising from the activities of financial institutions and markets. It is argued that governance problems are particularly severe in financial institutions vis-a-vis firms in other industries, and particularly important for society given the central role of financial institutions and markets in the financing and corporate governance activities of the economy. Processes of financial reform and financial system design have, it is argued, general...

  18. Translating diversity to Internet governance


    Napoli, Philip M.; Karppinen, Kari


    This paper examines the emergence of diversity as a guiding principle of Internet governance.  This paper compares how diversity is being interpreted and applied in Internet governance discourse and related research with its interpretation and application in traditional communications policy-making and policy research.  As this paper illustrates, a somewhat more narrow conceptualization of diversity has developed within the Internet governance context than has been the case in traditional com...

  19. Evolution of Russian Corporate Governance


    Mizobata, Satoshi


    The Russian corporate governance has evolved since the 1998 financial crisis. The author examines both normalization and preservation in the corporate structure, which can simultaneously be observed in the adaptation of Russian enterprises. The Russian corporate governance reflects the unique interests of its stakeholders and the embedded features of the society, for which the reforms are insufficient from the microeconomic aspects. Since the characteristics of corporate governance in Russia ...

  20. Transformative environmental governance | Science Inventory ... (United States)

    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to alternative, more desirable, or more functional regimes by altering the structures and processes that define the system. Transformative governance is rooted in ecological theories to explain cross-scale dynamics in complex systems, as well as social theories of change, innovation, and technological transformation. Similar to adaptive governance, transformative governance involves a broad set of governance components, but requires additional capacity to foster new social-ecological regimes including increased risk tolerance, significant systemic investment, and restructured economies and power relations. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds.

  1. Governance and Foreign Aid Allocation

    National Research Council Canada - National Science Library

    Akramov, Kamiljon T


    .... Specifically, the study explores how different categories of aid affect economic growth, whether the quality of governance is significant in explaining differences in economic growth, and whether...

  2. Dawn of e-government

    DEFF Research Database (Denmark)

    Henriksen, Helle Zinner; Damsgaard, Jan


    Most countries have defined strategies for e-government. The objectives for implementing e-government are often defined but the means for fuelling the adoption and diffusion of e-government are typically less well clear in the policy statements. The present study assesses the impact of latest...... internally and externally. The e-Day initiative represents a drastic change in the former policy statements concerning IT adoption and diffusion in Danish government. The policy statements had previously been based on voluntary adoption focusing on visions and pedagogical intervention in governmental...

  3. Government influence on patient organizations. (United States)

    Van de Bovenkamp, Hester M; Trappenburg, Margo J


    Patient organizations increasingly play an important role in health care decision-making in Western countries. The Netherlands is one of the countries where this trend has gone furthest. In the literature some problems are identified, such as instrumental use of patient organizations by care providers, health insurers and the pharmaceutical industry. To strengthen the position of patient organizations government funding is often recommended as a solution. In this paper we analyze the ties between Dutch government and Dutch patient organizations to learn more about the effects of such a relationship between government and this part of civil society. Our study is based on official government documents and existing empirical research on patient organizations. We found that government influence on patient organizations has become quite substantial with government influencing the organizational structure of patient organizations, the activities these organizations perform and even their ideology. Financing patient organizations offers the government an important means to hold them accountable. Although the ties between patient organizations and the government enable the former to play a role that can be valued as positive by both parties, we argue that they raise problems as well which warrant a discussion on how much government influence on civil society is acceptable.


    Directory of Open Access Journals (Sweden)

    Gavrea Corina


    Full Text Available Corporate governance is a key element of today’s economic reality being more and more present in many countries around the world. This paper has two main objectives. The first one is to offer more insight into the concept of corporate governance by a thorough literature review and by presenting and analyzing a framework of corporate governance. The second objective of this paper is to investigate the corporate governance situation in three developing economies (Romania, Bulgaria and Hungary. The World Bank and the European Bank for Reconstruction and Development published a series of reports on corporate governance. The present study uses data from these reports in order to illustrate how these developing economies are dealing with corporate governance. Based on ROSC Reports a corporate governance score was calculated. As this score shows, there is room for improvement for all three developing economies. This study is important because it shows the differences in corporate governance among developing economies and the need to study these nations at the individual country level. Corporate governance has many benefits for developing economies. It helps developing economies to register sustainable growth rates, to increases investors’ confidence in the national economy, and to increase the ability of capital markets to mobilize savings.

  5. Characterizing Government Social Media Research

    DEFF Research Database (Denmark)

    Medaglia, Rony; Zheng, Lei


    -government and Information Systems (IS) fields to identify research foci and gaps. We propose a research-grounded model that identifies the foci on context, user characteristics, user behaviour, design, management, and effects, and highlight the investigated relationships among them. Based on this analysis, we identify......As research on government social media continues to grow in quantity and scope, this area calls for mapping and systematization, in order to stimulate better-informed studies in the future. This paper draws on a comprehensive review of government social media literature in the e...... a four-point research agenda for future government social media research....

  6. GLIDA: GPCR-ligand database for chemical genomic drug discovery


    Okuno, Yasushi; Yang, Jiyoon; Taneishi, Kei; Yabuuchi, Hiroaki; Tsujimoto, Gozoh


    G-protein coupled receptors (GPCRs) represent one of the most important families of drug targets in pharmaceutical development. GPCR-LIgand DAtabase (GLIDA) is a novel public GPCR-related chemical genomic database that is primarily focused on the correlation of information between GPCRs and their ligands. It provides correlation data between GPCRs and their ligands, along with chemical information on the ligands, as well as access information to the various web databases regarding GPCRs. Thes...

  7. Good government and good governance: record keeping in a ...

    African Journals Online (AJOL)

    This article addresses the challenges that arise when record keeping systems are advocated as a necessary under-pinning for good government and good governance. The relationship between record keeping and accountability is analysed and contextualised in relation to transparency and Freedom of Information ...

  8. Governance of Higher Education--Implementation of Project Governance (United States)

    Macheridis, Nikos


    This article focuses on coordination between governance actors in higher education. The object of the study is a department at a public university, seen as a multi-project environment. The purpose of this article is to illustrate and analyze project governance as a tool that allows departmental management to coordinate with the authorities, the…

  9. E-Government for Good Governance in Developing Countries ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    E-government for good governance in developing countries : empirical evidence from the eFez project / Driss Kettani and Bernard Moulin. pages cm. Includes bibliographical references and index. ISBN 978-0-85728-125-8 (hardback : alk. paper). 1. Internet in public administration–Developing countries. I. Moulin, Bernard ...

  10. Danish Experiences with Coalition Governments and Coalition Governance

    DEFF Research Database (Denmark)

    Christiansen, Flemming Juul; Klemmensen, Robert


    In this chapter we outline the Danish and Scandinavian experiences with coalition governments and coalition governance. We do so by first briefly describing the historical path that has led to the political system we see working today in these countries. Then we tell about the political culture...

  11. Adopting service governance governing portfolio value for sound corporate citzenship

    CERN Document Server



    Adopting Service Governance provides a useful umbrella for a number of frameworks including ITIL®, TOGAF®, COBIT®, ITSM, BSM, Business Analysis, Programme Management, Management of Value, Management of Portfolios and Management of Risk by establishing the top-down governance of an organisation through services.

  12. Counterion-Mediated Ligand Exchange for PbS Colloidal Quantum Dot Superlattices. (United States)

    Balazs, Daniel M; Dirin, Dmitry N; Fang, Hong-Hua; Protesescu, Loredana; ten Brink, Gert H; Kooi, Bart J; Kovalenko, Maksym V; Loi, Maria Antonietta


    In the past years, halide capping became one of the most promising strategies to passivate the surface of colloidal quantum dots (CQDs) in thin films to be used for electronic and optoelectronic device fabrication. This is due to the convenient processing, strong n-type characteristics, and ambient stability of the devices. Here, we investigate the effect of three counterions (ammonium, methylammonium, and tetrabutylammonium) in iodide salts used for treating CQD thin films and shed light on the mechanism of the ligand exchange. We obtain two- and three-dimensional square-packed PbS CQD superlattices with epitaxial merging of nearest neighbor CQDs as a direct outcome of the ligand-exchange reaction and show that the order in the layer can be controlled by the nature of the counterion. Furthermore, we demonstrate that the acidity of the environment plays an important role in the substitution of the carboxylates by iodide ions at the surface of lead chalcogenide quantum dots. Tetrabutylammonium iodide shows lower reactivity compared to methylammonium and ammonium iodide due to the nonacidity of the cation, which eventually leads to higher order but also poorer carrier transport due to incomplete removal of the pristine ligands in the QD thin film. Finally, we show that single-step blade-coating and immersion in a ligand exchange solution such as the one containing methylammonium iodide can be used to fabricate well performing bottom-gate/bottom-contact PbS CQD field effect transistors with record subthreshold swing.

  13. CdSe Quantum Dots Functionalized with Chiral, Thiol-Free Carboxylic Acids: Unraveling Structural Requirements for Ligand-Induced Chirality. (United States)

    Varga, Krisztina; Tannir, Shambhavi; Haynie, Benjamin E; Leonard, Brian M; Dzyuba, Sergei V; Kubelka, Jan; Balaz, Milan


    Functionalization of colloidal quantum dots (QDs) with chiral cysteine derivatives by phase-transfer ligand exchange proved to be a simple yet powerful method for the synthesis of chiral, optically active QDs regardless of their size and chemical composition. Here, we present induction of chirality in CdSe by thiol-free chiral carboxylic acid capping ligands (l- and d-malic and tartaric acids). Our circular dichroism (CD) and infrared experimental data showed how the presence of a chiral carboxylic acid capping ligand on the surface of CdSe QDs was necessary but not sufficient for the induction of optical activity in QDs. A chiral bis-carboxylic acid capping ligand needed to have three oxygen-donor groups during the phase-transfer ligand exchange to successfully induce chirality in CdSe. Intrinsic chirality of CdSe nanocrystals was not observed as evidenced by transmission electron microscopy and reverse phase-transfer ligand exchange with achiral 1-dodecanethiol. Density functional theory geometry optimizations and CD spectra simulations suggest an explanation for these observations. The tridentate binding via three oxygen-donor groups had an energetic preference for one of the two possible binding orientations on the QD (111) surface, leading to the CD signal. By contrast, bidentate binding was nearly equienergetic, leading to cancellation of approximately oppositely signed corresponding CD signals. The resulting induced CD of CdSe functionalized with chiral carboxylic acid capping ligands was the result of hybridization of the (achiral) QD and (chiral) ligand electronic states controlled by the ligand's absolute configuration and the ligand's geometrical arrangement on the QD surface.

  14. Anchor side chains of short peptide fragments trigger ligand-exchange of class II MHC molecules.

    Directory of Open Access Journals (Sweden)

    Shashank Gupta

    Full Text Available Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a 'non-receptive' state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, the specific target site for the catalytic side chain of the dipeptide. The effect was evident also in CD4+ T cell assays, where the allele-selective influence of the dipeptides translated into increased sensitivities of the antigen-specific immune response. Molecular dynamic calculations support the hypothesis that occupation of P1 prevents the 'closure' of the empty peptide binding site into the non-receptive state. During antigen-processing and -presentation P1 may therefore function as important "sensor" for peptide-load. While it regulates maturation and trafficking of the complex, on the cell surface, short protein fragments present in blood or lymph could utilize this mechanism to alter the ligand composition on antigen presenting cells in a catalytic way.

  15. AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms (United States)

    Ravindranath, Pradeep Anand; Sanner, Michel F.


    Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: Contact: Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

  16. Integrating structural and mutagenesis data to elucidate GPCR ligand binding

    DEFF Research Database (Denmark)

    Munk, Christian; Harpsøe, Kasper; Hauser, Alexander S


    G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins, as well as drug targets. A recent boom in GPCR structural biology has provided detailed images of receptor ligand binding sites and interactions on the molecular level. An ever-increasing number of ligands...... elucidate new GPCR ligand binding sites, and ultimately design drugs with tailored pharmacological activity....

  17. New mixed ligand complexes of ruthenium (II) that incorporate a ...

    Indian Academy of Sciences (India)

    New mixed ligand complexes of ruthenium(II) that incorporate a modified phenanthroline ligand: Synthesis, spectral characterization and DNA binding. S Murali C V ... Fulltext. Click here to view fulltext PDF ... Ruthenium(II) complexes; modified phenanthroline ligand; spectroscopy; DNA binding; fluorescence enhancement.

  18. Novel peptide ligand with high binding capacity for antibody purification

    DEFF Research Database (Denmark)

    Lund, L. N.; Gustavsson, P. E.; Michael, R.


    ligands have an advantage over biological ligands; they are cheaper to produce, ligand leakage by enzymatic degradation is either eliminated or significantly reduced, and they can in general better withstand cleaning in place (CIP) conditions such as 0.1 M NaOH. Here, we present a novel synthetic peptide...


    African Journals Online (AJOL)

    The successive binding energies of up to six water ligands to ferric ion and the reduction in the gross binding energies by ligand-ligand repulsion are determined by electrostatic interaction. The gross binding energy is found to be both geometry and coordination nuitber dependent: whereas it increases with number of ...

  20. Metal halide solid-state surface treatment for nanocrystal materials

    Energy Technology Data Exchange (ETDEWEB)

    Luther, Joseph M.; Crisp, Ryan; Beard, Matthew C.


    Methods of treating nanocrystal and/or quantum dot devices are described. The methods include contacting the nanocrystals and/or quantum dots with a solution including metal ions and halogen ions, such that the solution displaces native ligands present on the surface of the nanocrystals and/or quantum dots via ligand exchange.