Search

Gungerite, TlAs5Sb4S13, is a new mineral from the Vorontsovskoye gold deposit in Northern Urals. It occurs in limestone breccias composed of calcite and dolomite and cemented by orpiment, pyrite, realgar, stibnite, and minor baryte and quartz. It belongs to the latest phases among sulfosalts (chiefly Tl-As-Sb ones) present in the ore. The empirical formula (based on the sum of all atoms = 23 pfu) is Tl0.99As5.29Sb3.77S12.95. The Raman spectrum exhibits bands corresponding to As-S and Sb-S stretching vibrations, and a band at 263 cm(-1) that is assigned to As-As stretching vibrations. Gungerite is bright orange with an orange streak, greasy luster, and perfect cleavage on {010}. It is translucent in thin fragments. The calculated density is 4.173 g/cm3. In reflected light, the mineral is yellowish-white with very weak bireflectance. In crossed polars, it is distinctly anisotropic but anisotropy efects are masked by strong internal reflections of bright orange color. Gungerite is orthorhombic, with the space group Pbcn. Unit-cell parameters determined from the single-crystal X-ray difraction data are as follows: a = 20.1958(3) angstrom, b = 11.5258(2) angstrom, c = 20.1430(2) angstrom, and V = 4688.74(12) Å3 (Z = 8). The crystal structure consists of doughnut-shaped (As,Sb)-S clusters, which have van der Waals contacts to most of the surroundings, and are connected to them only by sparse cation-sulfur bonds. These clusters are formed by a chelating mirror-symmetrical group, which is "stacked" on, around, and along rods of the TlS9 coordination polyhedra; these rods are oriented parallel to [010]. An individual doughnut-shaped cluster with a central TlS9 polyhedron half-inserted into it contains one As-As bond 2.449 Å long. The polar Tl rods form a chessboard arrangement with occasional stacking errors

Recent studies have shown that market construction is a dynamic process involving multiple actors in hegemonic and alternative positions. To understand the interconnection of these positions, the study aims to analyze how the dynamics of configuration and reconfiguration of a market frame the hegemonic and alternative positions in a multidimensional system. Using an interpretative approach, we examine the Southern Brazil (Rio Grande do Sul state) brewing market to describe the interconnection of craft (alternative) and mass (hegemonic) dimensions. We observe a constant process of overflowing and realignment of tensions and practices that enable the coexistence of different dimensions around a common market configuration. The results allow theorizing about a specific type of connection—covalent—between the multiple market dimensions, in which the practices of actors repel and attract both dimensions constantly, without definitive stabilization around a single dimension., Estudos recentes têm evidenciado que a construção de mercados é um processo dinâmico gerado por múltiplos atores em posições hegemônicas e alternativas. Buscando compreender a interligação dessas posições, o estudo tem como objetivo analisar como as dinâmicas de configuração e reconfiguração de um mercado resultam num enquadramento das posições hegemônicas e alternativas em um sistema multidimensional. Por meio de uma abordagem interpretativa, toma-se o mercado cervejeiro do Rio Grande do Sul como contexto para analisar a interligação das dimensões artesanal (alternativa) e massificada (hegemônica). Identifica-se um processo constante de transbordamento e realinhamento das tensões e práticas capaz de preservar a coexistência das diferentes dimensões. Os resultados permitem teorizar sobre uma forma distinta de ligação entre as dimensões de um mercado, denominada covalente, na qual as práticas desempenhadas por atores repelem e atraem ambas as dimensões constantemente, sem que ocorra a estabilização definitiva em torno de uma única dimensão.

Recent studies have shown that market construction is a dynamic process involving multiple actors in hegemonic and alternative positions. To understand the interconnection of these positions, the study aims to analyze how the dynamics of configuration and reconfiguration of a market frame the hegemonic and alternative positions in a multidimensional system. Using an interpretative approach, we examine the Southern Brazil (Rio Grande do Sul state) brewing market to describe the interconnection of craft (alternative) and mass (hegemonic) dimensions. We observe a constant process of overflowing and realignment of tensions and practices that enable the coexistence of different dimensions around a common market configuration. The results allow theorizing about a specific type of connection—covalent—between the multiple market dimensions, in which the practices of actors repel and attract both dimensions constantly, without definitive stabilization around a single dimension., Estudos recentes têm evidenciado que a construção de mercados é um processo dinâmico gerado por múltiplos atores em posições hegemônicas e alternativas. Buscando compreender a interligação dessas posições, o estudo tem como objetivo analisar como as dinâmicas de configuração e reconfiguração de um mercado resultam num enquadramento das posições hegemônicas e alternativas em um sistema multidimensional. Por meio de uma abordagem interpretativa, toma-se o mercado cervejeiro do Rio Grande do Sul como contexto para analisar a interligação das dimensões artesanal (alternativa) e massificada (hegemônica). Identifica-se um processo constante de transbordamento e realinhamento das tensões e práticas capaz de preservar a coexistência das diferentes dimensões. Os resultados permitem teorizar sobre uma forma distinta de ligação entre as dimensões de um mercado, denominada covalente, na qual as práticas desempenhadas por atores repelem e atraem ambas as dimensões constantemente, sem que ocorra a estabilização definitiva em torno de uma única dimensão.

Beer subjected to forced aging by five (Medium) or ten (High) heat/chill cycles (60 °C 48 h/0 °C 24 h) showed increased turbidity from 5.4 ± 0.4 EBC units without forced aging to 12.9 ± 0.7 and 48 ± 2 EBC units for Medium and High forced aged beers, respectively. The particle size diameter increased from 100–200 nm to 10–30 µm. The colloidal changes were associated with modifications of the low molecular weight fraction (∼1 kDa), which were found to increase in the soluble part of the beer as identified by size exclusion chromatography. Polyphenol analyses by liquid chromatography and mass spectrometry showed significant losses of gallic acid, hydroxyphenyllactic acid, salicylic acid, chlorogenic acid, vanillic acid, epicatechin, pyrocatechuic acid, ferulic acid, and luteolin during the forced aging, indicating that these phenolic compounds took part in the colloidal changes, proposedly upon polymerization into tannins. Gel electrophoresis coupled with staining by nitroblue tetrazolium indicated polyphenol modification of all proteins and especially LTP1 (lipid transfer protein 1). It is proposed that the di- and tri-hydroxyl phenolic compounds upon oxidation to quinones react with protein nucleophiles of especially LTP1 to generate the initial covalent bonds, which eventually leads to larger insoluble permanent haze particles.

Cyclotides are small cyclic polypeptides found in a variety of organisms, ranging from bacteria to plants. Their ring structure endows those polypeptides with specific properties, such as improved stability against enzymatic degradation. Optimal cyclotide activity is often observed only in the presence of intra-ring disulfide bonds. Synthesis of soft nano-objects mimicking the conformation of natural cyclotides remains challenging. Here, a new class of natural cyclotide mimics synthesized by a stepwise folding-activation-collapse process at high dilution starting from simple synthetic precursor polymers is established. The initial folding step is carried out by a photoactivated hetero Diels–Alder (HDA) ring-closing reaction, which is accompanied by chain compaction of the individual precursor polymer chains as determined by size exclusion chromatography (SEC). The subsequent activation step comprises a simple azidation procedure, whereas the final collapse step is driven by CuAAC in the presence of an external cross-linker, providing additional compaction to the final single-ring nanoparticles (SRNPs). The unique structure and compaction degree of the SRNPs is established via a detailed comparison with conventional single-chain nanoparticles (SCNPs) prepared exclusively by chain collapse from the exact same precursor polymer (without the prefolding step). The stepwise folding-activation-collapse approach opens new avenues for the preparation of artificial cyclotide mimetics.

An energy decomposition analysis (EDA) for single chemical bonds is presented within the framework of Kohn-Sham density functional theory based on spin projection equations that are exact within wave function theory. Chemical bond energies can then be understood in terms of stabilization caused by spin-coupling augmented by dispersion, polarization, and charge transfer in competition with destabilizing Pauli repulsions. The EDA reveals distinguishing features of chemical bonds ranging across nonpolar, polar, ionic, and charge-shift bonds. The effect of electron correlation is assessed by comparison with Hartree-Fock results. Substituent effects are illustrated by comparing the C-C bond in ethane against that in bis(diamantane), and dispersion stabilization in the latter is quantified. Finally, three metal-metal bonds in experimentally characterized compounds are examined: a [Formula: see text]-[Formula: see text] dimer, the [Formula: see text]-[Formula: see text] bond in dizincocene, and the Mn-Mn bond in dimanganese decacarbonyl.

An energy decomposition analysis (EDA) for single chemical bonds is presented within the framework of Kohn-Sham density functional theory based on spin projection equations that are exact within wave function theory. Chemical bond energies can then be understood in terms of stabilization caused by spin-coupling augmented by dispersion, polarization, and charge transfer in competition with destabilizing Pauli repulsions. The EDA reveals distinguishing features of chemical bonds ranging across nonpolar, polar, ionic, and charge-shift bonds. The effect of electron correlation is assessed by comparison with Hartree-Fock results. Substituent effects are illustrated by comparing the C-C bond in ethane against that in bis(diamantane), and dispersion stabilization in the latter is quantified. Finally, three metal-metal bonds in experimentally characterized compounds are examined: a [Formula: see text]-[Formula: see text] dimer, the [Formula: see text]-[Formula: see text] bond in dizincocene, and the Mn-Mn bond in dimanganese decacarbonyl.

This report is in extension of that presented in International Journal of Sciences: Basic and Applied Research (IJSBAR) by the current researcher (author) in respect of

Studies on the toughening mechanism of double network hydrogels (DN gels) show that the internal rupture of the brittle network, which effectively dissipates energy and prevents catastrophic crack propagation upon loading gives the extraordinarily high toughness of the material. Thus, the bonds of brittle network act as ‘sacrificial bonds’, in similar to the proposed model for toughening of bones. This sacrificial bond mechanism, accordingly, suggests a new strategy for designing high-strength materials: incorporating, on purpose, a mechanically fragile structure to toughen the material as a whole. As the internal rupture of DN gels is due to the irreversible breaking of the covalent bonds of the brittle network, a DN gel shows Mullins effect and degenerates gradually after repeated deformation. To address this problem, recent works have replaced the covalent bonds with non-covalent bonds to allow the sacrificial bonds to be reformed. The sacrificial bond concept has been successfully applied to develop tough double network and multiple network elastomer materials. Thus, sacrificial bond concept is proved to be a general approach for developing tough soft materials., Studies on the toughening mechanism of double network hydrogels (DN gels) show that the internal rupture of the brittle network, which effectively dissipates energy and prevents catastrophic crack propagation upon loading gives the extraordinarily high toughness of the material. Thus, the bonds of brittle network act as ‘sacrificial bonds’, in similar to the proposed model for toughening of bones. This sacrificial bond mechanism, accordingly, suggests a new strategy for designing high-strength materials: incorporating, on purpose, a mechanically fragile structure to toughen the material as a whole. As the internal rupture of DN gels is due to the irreversible breaking of the covalent bonds of the brittle network, a DN gel shows Mullins effect and degenerates gradually after repeated deformation. To address this problem, recent works have replaced the covalent bonds with non-covalent bonds to allow the sacrificial bonds to be reformed. The sacrificial bond concept has been successfully applied to develop tough double network and multiple network elastomer materials. Thus, sacrificial bond concept is proved to be a general approach for developing tough soft materials.

This report is in extension of that presented in International Journal of Sciences: Basic and Applied Research (IJSBAR) by the current researcher (author) in respect of

This report is in extension of that presented in International Journal of Sciences: Basic and Applied Research (IJSBAR) by the current researcher (author) in respect of

The minimum energy configuration for Molecular Dynamics (MD) simulations is found for a carbon nanotube (CNT)/polymer composite that is modeled using the Tersoff-Brenner and Reactive Empirical Bond Order(REBO)/Adaptive Intermolecular Reactive Empirical Bond Order (AIREBO) interatomic potentials. The Tersoff-Brenner potential is used to model C-C bonding and the REBO/AIREBO for non- bonding interactions. Using polyethylene (PE) monomers, the appropriate bonding coefficients are identified for a stable, low energy nanocomposite., The original document contains color images.

Silver is increasingly used in antimicrobial coatings of biomedical devices and implants to hinder infections. As proteins have been shown to largely influence the extent of released metals from various metal surfaces at biological conditions, silver may also be influenced in the same way. The aim of this study is to relate the structure of adsorbed lysozyme (LSZ) to the release of silver from metallic silver surfaces. Simultaneous adsorption measurements were performed in real time on the same surface using combined ellipsometry and quartz crystal microbalance with dissipation monitoring measurements to provide a more comprehensive understanding on the adsorption kinetics and the layer structures. The concentration of LSZ in 0.15 M NaNO3 solution (pH 7, 25 degrees C) influences the structure of the adsorbed layer. Monolayer coverage is obtained at concentrations =0.1 g/L, while a bilayer structure with a rigid inner layer and a relatively loosely adsorbed outer layer is formed at 1 g/L. The inner layer of LSZ is assumed to bind firmly to silver via disulfide bridges, which makes it irreversibly adsorbed with respect to dilution. The amount of released silver is further influenced by the structure of the LSZ layer. At low LSZ concentrations (=0.1 g/L) the amount of released silver is not significantly different compared with non-protein-containing NaNO3 solutions; however, noticeable reduction was observed at higher concentrations (1 g/L). This reduction in silver release has several possible explanations, including (i) surface complexation between LSZ and silver ions that may result in the incorporation of silver in the irreversible adsorbed layer and, hence, reduce the amount of released silver into solution, and (ii) net charge reversal at the protein/solution interface to slightly positive surface potentials. Any release of silver will therefore exhibit an electrostatic repulsion during transportation through the protein layer results in a reduced amount of silv, QC 20150109

Among US men, prostate cancer is the most common cancer (besides non-malignant skin cancer), afflicting over 200,000 each year, and is the second leading cause of cancer-related death, over 30,000 per year. Thus, our long term goal is to develop synthetic lectin (SL) arrays for the detection and diagnosis of prostate cancer. We are pursuing this goal because healthy and diseased cells produce different biomarkers, which provide unique signatures by which these cells can be distinguished. Taking advantage of the fact that aberrant protein glycosylation is a hallmark of cancer; we propose to develop a novel sensor platform that can be used to detect Cancer Associated Glycans/Glycoproteins for the diagnosis of prostate cancer. The basis of this diagnostic is the differential display of boronic acids on peptides and peptoids. Boronic acids are used because they form covalent yet reversible bonds with specific structural motifs (i.e., diols) present on all Cancer Associated Glycans/Glycoproteins. The covalent interaction increases the affinity of the SL for the target Cancer Associated Glycans/Glycoproteins, while the peptide/peptoid backbone and preorganization of the boronic acids define the selectivity of binding. Building on preliminary data, which demonstrated the ability to identify synthetic lectins, assemble them into an array, and discriminate between normal, cancerous and metastatic colon cancer cell lines, we will: (1) generate synthetic lectins that recognize specific Cancer Associated Glycans/Glycoproteins; (2) probe the biochemical and biophysical basis for the glycan-SL interactions to enhance binding affinities and selectivities; and (3) create multi-component sensor arrays to differentiate cell and tissue types to diagnose and monitor prostate cancer., The original document contains color images.

The width and energy of low-index interfacial boundaries (IFBs) in Ni?Ni3Al are calculated using first-principles methods for temperatures ranging from 0 to 1300 K. The low-temperature, coherent and chemically sharp (100), (110) and (111) IFBs are studied using conventional spin-polarized density functional methods. Cluster expansion methods, as implemented in the ATAT software suite, are used to estimate the interfacial excess free energies (IEFEs) and composition and long-range order profiles of these defects as a function of temperature. The simple face-centered cubic-based cluster expansion produces interfacial widths in the range of 1.5?3.0 nm at 1000 K. Interfacial widths double in size with an increase in temperature of 500 K. We also find that the IEFEs for the (100), (110) and (111) IFBs are strongly temperature dependent, decreasing by 90% as temperature increases from 0 to 1000 K. While vibrational and electronic entropic contributions were also considered, changes in free energy are dominated by the configurational entropy. The predicted high-temperature IEFE is approximately 10 mJ m-2 which is in excellent agreement with previous fits to experimentally measured coarsening rates.

Two-photon absorption (TPA) is a phenomenon of great interest for various optical limiting applications. The enhancement of molecular TPA cross-sections by placement of TPA chromophores within the plasmonic field of resonant and nonresonant plasmonic gold nanoparticles was explored. Polyelectrolyte layer-by-layer wrapping was employed to provide spacer layers between the chromophores and the gold surface. For on-resonant cases, TPA cross-sections could be enhanced by a factor of 40 for chromophores closest to the gold surface. The distance dependence of the TPA cross-section enhancement followed the calculated electric field. In contrast, for off-resonant gold nanoparticles, the calculated electric field dependence decreased then increased as a function of distance from the gold surface, in accord with experiment. Finally, TPA chromophores were covalently attached to the wrapping layers to put the chromophores even closer to the gold surface; but the observed distance dependence was flat, suggesting that chromophore orientation may have been compromised by covalent attachment., The original document contains color images.

Wheat gluten/glycerol (WGG) films were extruded with aqueous ammonia/salicylic acid or urea to investigate the reactions contributing to their hexagonal close-packed protein structures and material properties. The addition of aqueous ammonia and salicylic acid increased the pH, which, in turn, increased the level of intermolecular disulfide and lanthionine cross-links in the WGG films. Increased protein cross-linking reactions resulted in higher material strength and tensile modulus. These cross-linking reactions and the resulting material properties were similar for WGG films with 7.5% and 10% aqueous ammonia. Added urea into WGG film partially degraded into cyanate and ammonium. Cyanate subsequently reacted with lysine and cysteine to ε-carbamyllysine and S-carbamylcysteine, respectively. Even though these reactions resulted in a more alkaline reaction environment, hereby favoring disulfide bond formation and decreasing protein extractability, they also prevented the involvement of cysteine and lysine in protein cross-linking. The alkylation of these reactive amino acids, together with the plasticizing effect of urea, led to lower material strength and elastic modulus with increasing levels of urea., QC 20140120

High shear stresses are known to trigger destructive bond-scission reactions in polymers. Recent work has shown that the same shear forces can be used to accelerate non-destructive reactions in mechanophores along polymer backbones, and it is demonstrated here that such mechanochemical reactions can be used to strengthen a polymer subjected to otherwise destructive shear forces. Polybutadiene was functionalized with dibromocyclopropane mechanophores, whose mechanical activation generates allylic bromides that are crosslinked in situ by nucleophilic substitution reactions with carboxylates. The crosslinking is activated efficiently by shear forces both in solvated systems and in bulk materials, and the resulting covalent polymer networks possess moduli that are orders-ofmagnitude greater than those of the unactivated polymers. These molecular-level responses and their impact on polymer properties have implications for the design of materials that, like biological materials, actively remodel locally as a function of their physical environment., The original document contains color images. Pub. in Nature Chemistry v5 n9, p1-5, 2013. Sponsored in part by ARO grant no. W911NF-07-1-0409.

Here, we apply the harmonic Fourier beads (HFB) path optimization method to study chemical reactions involving covalent bond breaking and forming on quantum mechanical (QM) and hybrid QM/molecular mechanical (QM/MM) potential energy surfaces. To improve efficiency of the path optimization on such computationally demanding potentials, we combined HFB with conjugate gradient (CG) optimization. The combined CG-HFB method was used to study two biologically relevant reactions, namely, L- to D-alanine amino acid inversion and alcohol acylation by amides. The optimized paths revealed several unexpected reaction steps in the gas phase. For example, on the B3LYP/6-31G(d,p) potential, we found that alanine inversion proceeded via previously unknown intermediates, 2-iminopropane-1,1-diol and 3-amino-3-methyloxiran-2-ol. The CG-HFB method accurately located transition states, aiding in the interpretation of complex reaction mechanisms. Thus, on the B3LYP/6-31G(d,p) potential, the gas phase activation barriers for the inversion and acylation reactions were 50.5 and 39.9 kcal/mol, respectively. These barriers determine the spontaneous loss of amino acid chirality and cleavage of peptide bonds in proteins. We conclude that the combined CGHFB method further advances QM and QM/MM studies of reaction mechanisms., Published in The Journal of Chemical Physics, v139, 165104, 2013. Sponsored in part by DTRA.

This ER-2127 project is a Limited Scope SEED project with a fixed budget of $150K, starting in June 2011 and scheduled to complete in May 2014 after no cost extension. The project is proof of concept in nature, which was designed to investigate the feasibility of a novel scheme for the remediation of groundwater contaminated by perfluoroalkyl chemicals (PFCs). This approach is derived from our previous finding that PFCs can be effectively transformed during enzyme-catalyzed humification reactions in the presence of phenolic substrates as mediators (Colosi et al. 2009). The phenolic mediators generate highly reactive radical intermediates under the enzyme catalysis which in turn initiate fortuitous secondary reactions of PFCs, leading to their degradation. The primary objective of this study is to verify the feasibility of using a permeable reactive barrier system to induce effective enzyme-catalyzed humification reactions for in-situ remediation of groundwater PFC contamination. PFCs, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), have extremely high thermal and chemical stability, stemming from their unique structural features in which all hydrogens on carbon are replaced with fluorines. Carbon-fluorine bond is strong because fluorine has strong electronegativity that induces a partial positive charge on carbon and a negative charge on fluorine atoms, leading to electrostatic attraction that makes the bond shorter and stronger. Fluorine is the most electronegative element having a reduction potential of 3.6 V (Wardman 1989). It is thus thermodynamically unfavorable to oxidatively replace the fluorine atom with any other atom. In addition, the fluorine atoms, which are much larger than hydrogen in size, form a dense hydrophobic layer in PFOX (X=S or X=A) surrounding carbon-carbon bonds, which shields them from attack by oxidative reagents.

It has been suggested that PHSCN inhibits metastatic invasion by forming a covalent, disulfide bond with a cysteine residue on the beta1 ( 1) subunit of alpha5 beta1 ( 5 1) integrin1. However, these studies were performed with purified 5 1 integrin, which also produces evidence of covalent bond formation with the 5 subunit (tandem mass spectroscopy data not shown). Hence, the specificity of the reported interaction between PHSCN and the 1 subunit1 is suspect. Moreover, the cysteine rich 1 subunit can heterodimerize with 12 distinct alpha integrin subunits2, forming integrins that function in many pathways. In contrast, the 5 subunit interacts uniquely with the 1 subunit2 to induce invasion and support adhesion3-5; hence it is a much more desirable target., The original document contains color images.

Among US men, prostate cancer is the most common cancer (besides non-malignant skin cancer), afflicting over 200,000 each year, and is the second leading cause of cancer-related death, over 30,000 per year. Thus, our long term goal is to develop synthetic lectin(SL) arrays for the detection and diagnosis of prostate cancer. We are pursuing this goal because healthy and diseased cells produce different biomarkers, which provide unique signatures by which these cells can be distinguished. Taking advantage of the fact that aberrant protein glycosylation is a hallmark of cancer; we propose to develop a novel sensor platform that can be used to detect Cancer Associated Glycans/Glycoproteins for the diagnosis of prostate cancer. The basis of this diagnostic is the differential display of boronic acids on peptides and peptoids. Boronic acids are used because they form covalent yet reversible bonds with specific structural motifs (i.e., diols) present on all Cancer Associated Glycans/Glycoproteins. The covalent interaction increases the affinity of the SL for the target Cancer Associated Glycans/Glycoproteins, while the peptide/peptoid backbone and preorganization of the boronic acids define the selectivity of binding. Building on preliminary data, which demonstrated the ability to identify synthetic lectins, assemble them into an array, and discriminate between normal, cancerous and metastatic colon cancer cell lines, we will: (1) generate synthetic lectins that recognize specific Cancer Associated Glycans/Glycoproteins; (2) probe the biochemical and biophysical basis for the glycan-SL interactions to enhance binding affinities and selectivities; and (3) create multi-component sensor arrays to differentiate cell and tissue types to diagnose and monitor prostate cancer. The development of these synthetic lectins is highly significant because they can be used to generate an array based diagnostic that has the potential to revolutionize the early diagnosis of prostate cancer., The original document contains color images.

It has been suggested that PHSCN inhibits metastatic invasion by forming a covalent, disulfide bond with a cysteine residue on the beta1 ( 1) subunit of alpha5 beta1 ( 5 1) integrin1. However, these studies were performed with purified 5 1 integrin, which also produces evidence of covalent bond formation with the 5 subunit (tandem mass spectroscopy data not shown). Hence, the specificity of the reported interaction between PHSCN and the 1 subunit1 is suspect. Moreover, the cysteine rich 1 subunit can heterodimerize with 12 distinct alpha integrin subunits2, forming integrins that function in many pathways. In contrast, the 5 subunit interacts uniquely with the 1 subunit2 to induce invasion and support adhesion3-5; hence it is a much more desirable target., The original document contains color images.

Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α-amylase/subtilisin inhibitor (BASI), two loops in barley thioredoxin h2 (HvTrxh2), containing an invariant cis-proline (86EAMP89) and a conserved glycine (104VGA106), surround the active site cysteines ( 45WCGPC49) and contribute to binding of BASI through backbone-backbone hydrogen bonds [Maeda, K., Hägglund, P., Finnie, C., Svensson, B., and Henriksen, A. (2006) Structure 14, 1701-1710]. This study involves mutational analysis of key amino acid residues from these two loops in reactions with three protein disulfide substrates, BASI, barley glutathione peroxidase, and bovine insulin as well as with NADPH-dependent barley thioredoxin reductase. HvTrxh2 M88G and M88A adjacent to the invariant cis-proline lost efficiency in both BASI disulfide reduction and recycling by thioredoxin reductase. These effects were further pronounced in M88P lacking a backbone NH group. Remarkably, HvTrxh2 E86R in the same loop displayed overall retained catalytic properties, with the exception of a 3-fold increased activity toward BASI. From the 104VGA106 loop, a backbone hydrogen bond donated by A106 appears to be important for target disulfide recognition as A106P lost 90% activity toward BASI but was efficiently recycled by thioredoxin reductase. The findings support important roles in target recognition of backbone-backbone hydrogen bond and electrostatic interactions and are discussed in relation to earlier structural and functional studies of thioredoxins and related proteins. © 2012 American Chemical Society.

Aluminum aminoterephthalate MOF particulate materials (NH2-MIL-101(Al) and NH2-MIL-53(Al)), studied here as components of self-detoxifying surfaces, retained their reactivity following their covalent attachment to protective surfaces utilizing a newly developed strategy in which the MOF particles were deposited on a reactive adhesive composed of polyisobutylene/toluene diisocyanate (PIB/TDI) blends. Following MOF attachment and curing, the MOF primary amino groups were functionalized with highly nucleophilic 4-methylaminopyridine (4-MAP) by disuccinimidyl suberate-activated conjugation. The resulting MOF-4-MAP modified PIB/TDI elastomeric films were mechanically flexible and capable of degrading diisopropyl fluorophosphate (DFP), a chemical threat simulant., Pub. in ACS Applied Materials and Interfaces, v4, p4595-4602, 2012.

Many hydrophobic surfaces exist in nature, but there is no naturally occurring oleophobic surface. There is plenty of academic and commercial interest in the development of oleophobic surfaces. The focus is on commercially available textiles. This presentation shows that fluoroPOSS are superhydrophobic. FluoroPOSS polymer composite surfaces can be superhydrophobic and superoleophobic. Superhydrophilic and superoleophobic surfaces have been developed. Such sufaces are ideal for the separation of both free-oil and oil-water emulsions. These membranes, for the first time, allow continuous-flow oil-water emulsion separation. Functionality will allow the covalent attachment of these low energy materials to substrates of choice., The original document contains color images. Contains briefing charts only.

The goal of this project was to find novel routes to tune thermal conductivities and thermoelectric properties of materials mainly composed of relatively abundant light elements like boron, carbon, nitrogen, silicon, sulfur, oxygen, etc. Focus was on the control of the atomic network structure and symmetry in crystal structure of inorganic materials to lead to dramatic effects in the properties. One particularly studied system in the work was the recently discovered potential n-type counterpart (YB22C2N as a representative) to p-type boron carbide, which is one of the few thermoelectric materials with a history of commercialization. As a byproduct of attempting further control of the network structure by utilizing atomic bridging sites, we have discovered an anomalous vanadium doping effect in YB22C2N that increased the electrical conductivity by 50,000% while simultaneously increasing the Seebeck coefficient by 220%. Selective transition metal doping was also clearly demonstrated to modify the crystal structure of a borosilicide, leading to significant increase of the thermoelectric power factor and change of sign in the Seebeck coefficient. Such demonstration of the possibility to modify the crystal structures can expand the possibilities of borides as functional compounds. A series of indium-free novel TCO compounds with novel crystal structures, has revealed exceptionally low thermal conductivity through its homologous nature and mixing of the cation sites, and exhibited thermoelectric properties indicated to be better than the extensively studied IZO, as an n-type oxide. Furthermore, as an example of material design utilizing particular crystal structures, a unified description for crystal structures of another new homologous series in the gallium zinc Silicon or germanium based cage compounds with low thermal conductivity were also found to reveal enhanced properties through small substitution of the network atoms. A potential replacement material to boron car

The establishment of covalent junctions between carbon nanotubes (CNTs) and the modification of their straight tubular morphology are two strategies needed to successfully synthesize nanotube-based three-dimensional (3D) frameworks exhibiting superior material properties. Engineering such 3D structures in scalable synthetic processes still remains a challenge. This work pioneers the bulk synthesis of 3D macroscale nanotube elastic solids directly via a boron-doping strategy during chemical vapour deposition, which influences the formation of atomic-scale elbow junctions and nanotube covalent interconnections. Detailed elemental analysis revealed that the elbow junctions are preferred sites for excess boron atoms, indicating the role of boron and curvature in the junction formation mechanism, in agreement with our first principle theoretical calculations. Exploiting this material's ultra-light weight super-hydrophobicity, high porosity, thermal stability, and mechanical flexibility, the strongly oleophilic sponge-like solids are demonstrated as unique reusable sorbent scaffolds able to efficiently remove oil from contaminated seawater even after repeated use., Published in Scientific Reports, 13 April 2012, 1/20. The original document contains color images.

A newly developed method for the edge-selective functionalization of pristine graphite with 4-aminobenzoic acid was applied for the synthesis of 4-aminobenzoyl-functionalized graphite (AB-graphite) through a direct Friedel-Crafts acylation in a polyphosphoric acid (PPA)/phosphorous pentoxide medium (P2O5). The AB moiety at the edge of the AB-graphite played the role of a molecular wedge to exfoliate the AB-graphite into individual graphene and graphene-like platelets upon dispersion in polar solvents. These were used as a co-curing agent and a nanoscale additive to epoxy resin. The physical properties of the resulting epoxy/AB-graphite composites were improved because of the efficient load transfer between the additive and epoxy matrix through covalent links.

During the current project, we have identified classes of stable cluster motifs for implementation as building blocks of nanoenergetic materials and developed guiding principles for their synthesis. To begin, differing mechanisms that can stabilize clusters were identified. The first refers to crystal field like splitting of electronic shells via geometrical distortions that can lead to stable species at sub-shell fillings. Such a mechanism accounted for the stability of CuAl22- and more recently, CuMg8- and AuMg8- . It was shown that aromaticity, traditionally used to understand stability of organic systems, can also stabilize metallic clusters. Al3Bi was shown to be the first neutral all-metal aromatic species. Similar clusters containing As and Sn in place of Bi, are also stabilized by and delocalized orbitals. Nanoenergetic materials need to be air stable and hence studies on the reactivity of aluminum cluster anions with water were undertaken. Theoretical investigations showed that the reactivity proceeded through Lewis acid/Lewis base pair of complementary active sites that break OH bond and clusters with two pairs of such sites generated hydrogen. These findings also led to new class of nanocatalysts that can break polar covalent bonds and recent studies showed that such pairs can even break CO bonds. Finally, protocols that can enable synthesis of clusters assembled materials were formulated by focusing on cluster assemblies made from As11 and K that contain linear and helical chains., The original document contains color images.

Vascular disruption agents (VDAs) have been shown to selectively destroy established tumor vasculature, which results in the ischemic death of up to 99% of tumor cells. The weakness of VDA monotherapy is that it often leaves a rim of surviving tumor cells which can then regrow and spread. The overall goal of this study (addressed in Task 2) is to enhance VDA therapy by inducing hyperthermia, targeted to the neovascular endothelium, through the use of superparamagnetic iron oxide nanoparticles (SPIONs), in order to halt, or significantly slow down tumor growth. Therefore, the first aim of this study (Task 1) is to maximize the delivery of SPIONs to the tumor rim, through a combination of neovascular targeting and increased vascular permeability induced by the VDA. Covalent coupling of a primary amine on the antibody to a carboxyl on the SPIONs activated by EDC/Sulfo-NHS resulted in colloidally-stable particles that showed specific binding to VEGFR-2 expressing cells in vitro. Current in vivo results suggest a synergistic enhancement of SPION delivery to the tumor rim when VEGFR-2 targeting of PEG-coated particles and 15 min pre-administration of DMXAA (a VDA) are employed. The results suggest that the combination of targeting the neovasculature and increasing vascular permeability through the action of the VDA is an effective SPION delivery strategy. Quantitative chemical analysis of tumor samples are ongoing to obtain statistically-significant iron quantitation. In vitro testing of SPION heating in the presence of an alternating magnetic field has been successful and demonstrates that heating is optimized using 20 nm SPIONs. However, in vivo testing of hyperthermia therapy in mice receiving targeted SPIONs after DMXAA pre-treatment is currently on hold, pending a solution to the problem of poor long-term survival of the mice after DMXAA administration., The original document contains color images.

Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α-amylase/subtilisin inhibitor (BASI), two loops in barley thioredoxin h2 (HvTrxh2), containing an invariant cis-proline (86EAMP89) and a conserved glycine (104VGA106), surround the active site cysteines ( 45WCGPC49) and contribute to binding of BASI through backbone-backbone hydrogen bonds [Maeda, K., Hägglund, P., Finnie, C., Svensson, B., and Henriksen, A. (2006) Structure 14, 1701-1710]. This study involves mutational analysis of key amino acid residues from these two loops in reactions with three protein disulfide substrates, BASI, barley glutathione peroxidase, and bovine insulin as well as with NADPH-dependent barley thioredoxin reductase. HvTrxh2 M88G and M88A adjacent to the invariant cis-proline lost efficiency in both BASI disulfide reduction and recycling by thioredoxin reductase. These effects were further pronounced in M88P lacking a backbone NH group. Remarkably, HvTrxh2 E86R in the same loop displayed overall retained catalytic properties, with the exception of a 3-fold increased activity toward BASI. From the 104VGA106 loop, a backbone hydrogen bond donated by A106 appears to be important for target disulfide recognition as A106P lost 90% activity toward BASI but was efficiently recycled by thioredoxin reductase. The findings support important roles in target recognition of backbone-backbone hydrogen bond and electrostatic interactions and are discussed in relation to earlier structural and functional studies of thioredoxins and related proteins. © 2012 American Chemical Society.

We reported the functionalization of multiwalled carbon nanotube (MWCNT) with 4-aminobenzoic acid by a direct Friedel-Crafts acylation reaction in a mild polyphosphoric acid (PPA)/phosphorous pentoxide (P2O5) medium. The resulting 4- aminobenzoyl-functionalized MWCNT (AF-MWCNT) was used as a platform for the grafting of polypyrrole (PPy) in ammonium persulfate (APS)/aqueous hydrochloric acid solution to produce PPy-grafted MWCNT (PPy-g-MWCNT) composite. After dedoping with alkaline treatment, PPy-g-MWCNT displayed 20 times higher electrical conductivity than that of PPy. The current density and cycle stability of PPy-g-MWCNT composite were also remarkably improved compared with those of PPy homopolymer, suggesting that an efficient electron transfer between PPy and MWCNT was possible through covalent links. In addition, PPy-g-MWCNT displayed high electrocatalytic activity for oxygen reduction reaction (ORR)., Published in Journal of Polymer Science Part A: Polymer Chemistry, v49 p2529-2537, 2011.

There are many examples of improved oxidation-resistance in organic polymeric materials achieved through the incorporation of silicon-containing compounds. These compounds are often organically-modified particles, such as silicas, silicates, clays, or polyhedral oligomeric silsesquioxanes, which can be mechanically blended into a wide variety of polymer matrices. However, in order to achieve improved dispersion of the silicon phase, it is often desirable for the silicon-containing compound to be covalently bound to the polymer backbone. This can be accomplished by polymerization of silicon-containing monomers, copolymerization of silicon monomers with desired organic monomers, or chemical modification of organic polymers by reactive silicon-containing molecules. In thermoplastic polymers, examples of both blended and covalent incorporation are common. In thermosets, however, the covalent approach is typically desired due to the ease of monomer processing and the low potential for phase separation during cure. A variety of silicon-containing fillers monomers, polymers, and composites will be discussed, as well as the advantages of each.

The most common compounds formed from boron are boron carbide (B4C) and boron nitride (BN), which are generally not considered borides but which are included here since they are commercially available as high-quality powders. Borides are generally considered as compounds combining one, or more, metals with boron. Strong covalent bonding allows many of these borides to have high melting or decomposition temperatures, such that they can be used in reducing environments. LaB6, for example, is used as a replacement for W in thermoionic emitters, such as the filaments for electron microscopes, due to its high melting point and low work function. BN is used as a crucible material in its hexagonal form and as a cutting tool in its cubic state. B4C is used as an armor material due to its low specific gravity. A comprehensive survey of borides was performed by Cutler[1] based primarily on the earlier data of Samsonov and Vinitskii[2] and is still the best literature source for the properties of borides. Other excellent reviews include the work of Lundstrom[3] as well as information on ternary borides as discussed by Nowotny and Rogl[4]. Williams gives data on selected borides[5]. Borides are processed like other non-oxide ceramics, using methods well known in the literature[6-11]., The original document contains color images.

A recent crystallographic study has shown that, in the solid state, P(C6H5)4N3 and As(C6H5)4N3 have ionic [M(C6H5)4]+N3- type structures, whereas Sb(C6H5)4N3 exists as a pentacoordinated covalent solid. Using the results from density functional theory, lattice energy (VBT) calculations, sublimation energy estimates, and Born-Fajans-Haber cycles, it is shown that the maximum coordination numbers of the central atom M, the lattice energies of the ionic solids, and the sublimation energies of the covalent solids have no or little influence on the nature of the solids. Unexpectedly, the main factor determining whether the covalent or the ionic structures are energetically favored, is the first ionization potential of [M(C6H5)4]. The calculations show that at ambient temperature the ionic structure is favored for P(C6H5)4N3 and covalent structures are favored for Sb(C6H5)4N3 and Bi(C6H5)4N3, while As(C6H5)4N3 presents a borderline case., For publication in Inorganic Chemistry in April 2011. Sponsored in part by ONR and DTRA.

The surface, interfacial and dispersion properties of carbon nanotubes (CNTs), and the mechanical properties of the CNT/epoxy composites affected by CNT functionalization are investigated. It is demonstrated that there exists strong correlations between amino-functionalization, dispersion, wettability, interfacial interaction and re-agglomeration behaviour of CNTs and the corresponding mechanical and thermo-mechanical properties of CNT/epoxy composites. The amino-functionalized CNTs exhibit higher surface energy and much better wettability with epoxy resin than the pristine CNTs, and the attached amine molecules arising from the functionalization effectively inhibit the re-agglomeration of CNTs during the curing of resin. These ameliorating effects along with improved interfacial adhesion between the matrix and functionalized CNTs through covalent bonds result in improved flexural and thermo-mechanical properties compared with those without functionalization. (C) 2010 Elsevier Ltd. All rights reserved.

The surface, interfacial and dispersion properties of carbon nanotubes (CNTs), and the mechanical properties of the CNT/epoxy composites affected by CNT functionalization are investigated. It is demonstrated that there exists strong correlations between amino-functionalization, dispersion, wettability, interfacial interaction and re-agglomeration behaviour of CNTs and the corresponding mechanical and thermo-mechanical properties of CNT/epoxy composites. The amino-functionalized CNTs exhibit higher surface energy and much better wettability with epoxy resin than the pristine CNTs, and the attached amine molecules arising from the functionalization effectively inhibit the re-agglomeration of CNTs during the curing of resin. These ameliorating effects along with improved interfacial adhesion between the matrix and functionalized CNTs through covalent bonds result in improved flexural and thermo-mechanical properties compared with those without functionalization. (C) 2010 Elsevier Ltd. All rights reserved.

The surface, interfacial and dispersion properties of carbon nanotubes (CNTs), and the mechanical properties of the CNT/epoxy composites affected by CNT functionalization are investigated. It is demonstrated that there exists strong correlations between amino-functionalization, dispersion, wettability, interfacial interaction and re-agglomeration behaviour of CNTs and the corresponding mechanical and thermo-mechanical properties of CNT/epoxy composites. The amino-functionalized CNTs exhibit higher surface energy and much better wettability with epoxy resin than the pristine CNTs, and the attached amine molecules arising from the functionalization effectively inhibit the re-agglomeration of CNTs during the curing of resin. These ameliorating effects along with improved interfacial adhesion between the matrix and functionalized CNTs through covalent bonds result in improved flexural and thermo-mechanical properties compared with those without functionalization. (C) 2010 Elsevier Ltd. All rights reserved.

CH2OH-terminated regioregular poly(3-hexylthiophene) (P3HT) was chemically grafted onto carboxylic groups of graphene oxide (GO) via esterification reaction. The resultant P3HT-grafted GO sheets (GP3HT) are soluble in common organic solvents, facilitating the structure/property characterization and the device fabrication by solution processing. The covalent linkage and the strong electronic interaction between the P3HT and graphene moieties in G-P3HT were confirmed by spectroscopic analyses and electrochemical measurements. A bilayer photovoltaic device based on the solution-cast G-P3HT/C60 heterostructures showed a 200% increase of the power conversion efficiency ( 0.61%) with respect to the P3HT/C60 counterpart under AM 1.5 illumination (100 mW/cm2)., Published in ACSNano, v4 n10 p5633-5640, 2010.

The accepted target for oganophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence GlyXSerXGly of acetylcholinesterase. By using mass spectrometry to fragment OP-labeled peptides, we have found that OP can make covalent bonds not only with serine, but also with tyrosine and lysine in proteins that have no active site serine. The OP-tyrosine bond is stable, and does not undergo the decay seen with OP-serine. Human blood treated with nerve agents in vitro has adducts on tyrosine 411 of albumin. To test whether adducts on tyrosine are formed when people are exposed to OP, we analyzed blood from humans poisoned by pesticides, a surrogate for nerve agents. Humans exposed to dichlorvos had OP-labeled tyrosine 411 in plasma albumin. We conclude that albumin is a new biomarker of OP exposure. Mice treated with chlorpyrifos at doses too low to inhibit acetylcholinesterase had OP-labeled tubulin in brain. It is expected that the new OP binding motif will aid in the search for a mechanism of low dose OP toxicity., The original document contains color images.

Biomaterial bridges constructed from electrospun fibers offer a promising alternative to traditional nerve tissue regeneration substrates. Aligned and unaligned polycaprolactone PCL electrospun fibers were prepared and functionalized with the extracellular matrix proteins collagen and laminin using covalent and physical adsorption attachment chemistries. The effect of the protein modified and native PCL nanofiber scaffolds on cell proliferation, neurite outgrowth rate, and orientation was examined with neuronlike PC12 cells. All protein modified scaffolds showed enhanced cellular adhesion and neurite outgrowth compared to unmodified PCL scaffolds. Neurite orientation was found to be in near perfect alignment with the fiber axis for cells grown on aligned fibers, with difference angles of less than 7? from the fiber axis, regardless of the surface chemistry. The bioavailability of PCL fibers with covalently attached laminin was found to be identical to that of PCL fibers with physically adsorbed laminin, indicating that the covalent chemistry did not change the protein conformation into a less active form and the covalent attachment of protein is a suitable method for enhancing the biocompatibility of tissue engineering scaffolds., Performed in collaboration with the University of Delaware, Newark, DE. Published in Biointerphases, v5 n4 p149-158, December 2010.

Recent studies have been increasingly utilizing fluoroalkyl-substituted Polyhedral Oligomeric SilSesquioxanes (POSS) molecules, known as fluoroPOSS, for producing non-wetting surfaces. Most commonly, (1H,1H,2H,2H-perfluorodecyl)8Si9O12 (fluorodecyl POSS, has been utilized for its extraordinarily low surface energy (=10 mN/m) and phase behavior in polymer blends. However, fluoroPOSS surfaces can seldom experience abrasion, or extended exposure to certain liquids, and still retain their non-wetting properties. A route to synthesize a functional fluoroPOSS molecule or monomer, with the ability to be covalently attached to a textured surface or polymer, is desired for the potential ability to develop a mechanically robust omniphobic surface. In the current study, mono-, di-, and tri-chlorosilanes tethered to a fluorodecyl POSS cage are synthesized via hydrosilylation of (vinyl, methyl) (1H,1H,2H,2H-perfluorodecyl)8Si9O13 POSS. Products are identified by NMR spectrometry. The synthesized monochlorosilyl-functional fluoroPOSS compound is subsequently used to treat silicon dioxide surfaces. Covalent attachment is confirmed by atomic force microscopy and dynamic contact angle analysis.

Gallium nitride has attracted significant interest as a material for biosensors; however, techniques for biofunctionalizing GaN surfaces have received limited attention. Here, we present a method for producing amine groups directly on GaN surfaces through exposure to a glow discharge plasma fed with humidified air, thereby eliminating the need for complex organic functionalization chemistry. Amine formation is tracked via X-ray photoelectron spectroscopy (XPS) by labeling the plasma-formed surface groups with a fluorinated probe that binds specifically to primary amines. These amine groups can subsequently couple covalently to a wide range of biomolecules. The covalent immobilization of a NeutrAvidin layer is demonstrated using Fourier transform infrared spectroscopy (FT-IR) and fluorescent biotin-binding assays. Finally, we show that plasma exposure times sufficient for the formation of amine groups do not significantly alter the conductivity of the GaN substrate., Sponsored in part by the Defense Threat Reduction Agency (DTRA). Performed in collaboration with Nova Research, Inc., Alexandria, VA. Published in Applied Surface Science, v256 p4171-4175, 2010.

Chemical structure determines the inherent properties displayed by a given compound, and these properties, in turn, produce a specific performance behavior. Rationally designing chemical structure to predictably modify compound properties, such that performance behavior can be tailored in a controlled manner, defines the objective of a pertinent synthesis effort. Achieving this objective by introducing structural alterations in a neutral covalent compound offers only one approach for resultant properties modification. Heterocyclic salts significantly enhance the flexibility for achieving properties modification via three strategic approaches: (1) compositionally pairing various cation structural classes with a number of anion structural classes, (2) systematically altering the structure of the cation; and, (3) systematically altering the structure of the anion. To illustrate this premise, four general synthesis methods to synthesize heterocyclic salts, including several new binary heterocyclium icosahedral closo-borane and closo-carborane salts, first are outlined. Secondly, properties modification approaches of neutral covalent compounds are then compared with those approaches available for various heterocyclic salts. Lastly, a key example, using three unsaturated bridged heterocyclium di-cation salts, demonstrates how rational structure design, and its effect on resultant predictable properties modification, produces tailored performance behavior to reach the thermochemical initiation threshold needed for combustion. This is achieved with predictable properties modifications that increase salt energy content, or that accelerate the reaction kinetics of the thermochemical initiation process., Performed in collaboration with ERC, Inc., Edwards Airforce Base, California. Presented at the International New Trends in Research of Energetic Materials Seminar held Pardubice, Czech Republic on 1-3 April 2009. Submitted for publication in the Central European Journal of Energetic Materials.

In this funded research, we have described "zfration" - a naturally occurring small-size peptide Zfra undergoes selfcovalent binding and aggregation, and may covalently interact with tumor suppressors for functional inactivation. Zfra is a 31-amino-acid peptide, whose composition is similar to that of zinc finger family proteins. In the original Specific Aims, we proposed to 1) determine how Zfra undergoes covalent self-aggregation and binding with tumor suppressor proteins for regulating their functions; 2) determine the overall protein targets with which Zfra interact; 3) investigate the effect of Zfra deficiency in breast cancer cells. As research ongoing as planned, we have achieved excellent progress and determined that Zfra can 1) induce degradation of intracellular zfrated proteins, 2) undergo enzyme-independent self-polymerization for more than 200 fold of its original size, and 3) significantly increase the growth of breast and skin basal cell carcinoma in nude mice by 3-4 fold in 3 months, suggestive of its inactivation of tumor suppressors in vivo., The original document contains color images.

Organophosphorus esters (OP) are known to make a covalent bond with the active site serine in the consensus sequence GXSXG of esterases and proteases. However, the site of attachment to proteins that have no active site serine has only recently been recognized as tyrosine. In last year's report we provided mass spectrometry evidence that soman, sarin, DFP, chlorpyrifos oxon, dichlorvos, and FP-biotin bound to tyrosine in 3 proteins. We now report binding of organophosphorus agents to tyrosinein 12 proteins. This suggests that diagnosis of exposure to OP may become possible by monitoring adducts on tyrosine, for example in albumin. The advantages of using organophosphorus-labeled albumin as a biomarker of exposure are that the albumin adduct is stable, and the OPalbumin adduct does not age. The soman adduct on plasma butyrylcholinesterase was used to determine the limit of detection of soman exposure ex vivo. A concentration of soman that inhibited butyrylcholinesterase in human plasma 2% was detectable in the multiple reaction monitoring mode of the mass spectrometer.

Platinum(II) acetylides were incorporated into poly(methyl methacrylate) (PMMA) glasses to obtain solid-state nonlinear optical devices. We report on device fabrication, structural, chemical, and mechanical properties, as well as the optical limiting capabilities of the final solids. Two different guest-host systems are presented: 1) Dye molecules functionalized to be readily dispersed in methyl methacrylate (MMA) and subsequent in situ polymerization of the MMA yielding solid PMMA host matrices. 2) Dye molecules functionalized to copolymerize with MMA forming covalent bonds between the guest and the PMMA host matrix. A range of doped organic solids were prepared, reaching concentrations up to 13 wt% of the guest molecule. Raman spectra of the doped solid devices indicate that the chemical structure of the nonlinear dyes remains intact upon the polymerization of the solid matrix. Luminescence spectra confirm that the basic photophysical properties observed for the same solute molecules in THF are maintained also in the solid state. Optical power limiting (OPL) characterization reveal clamping levels for the dyes nonbonded to the solid host being less than 4 μJ at pulse energies up to 110 μJ at 532 nm (f/5 arrangement and 5 ns pulses), which is comparable to the performance of similar dyes in THF solutions. In contrast, the highly crosslinked solid possesses a higher clamping level (8 μj) at the same nominal concentration., QC 20100910

Dichloroacetic acid (DCA) is a common disinfection byproduct in surface waters and a probable minor metabolite of trichloroethylene. DCA liver carcinogenicity has been demonstrated in rodents but epidemiological evidence in humans is not available. High doses of DCA (10-50 mg/kg) are used to treat metabolic acidosis. Biotransformation of DCA by glutathione transferase zeta (GSTzeta) in the liver is the major elimination pathway in humans. GSTzeta is inactivated by DCA, leading to slower systemic clearance and nonlinear pharmacokinetics after multiple doses. A physiologically-based pharmacokinetic (PBPK) model was developed to quantitatively describe DCA biotransformation and kinetics in humans administered DCA by intravenous infusion and oral ingestion. GSTzeta metabolism was described using a Michaelis-Menten equation coupled with rate constants to account for normal GSTzeta synthesis, degradation, and irreversible covalent binding and inhibition by the glutathione-bound-DCA intermediate. The human DCA PBPK model adequately predicted the DCA plasma kinetics over a 20,000 fold range in administered doses. Apparent inhibition of GSTzeta mediated metabolism of DCA was minimal for low doses of DCA (microgram/kg/day), but was significant for therapeutic doses of DCA. Plasma protein binding of DCA was assumed to be an important factor influencing the kinetics of low doses of DCA (microgram/kg/day). Human equivalent doses (HEDs) were calculated for a 10% increase in mice hepatic liver cancer (2.1 mg/kg/day). The HEDs for the dosimetrics (area under the curve (AUC) for total and free DCA in plasma, AUC of DCA in liver, and amount of DCA metabolized) per day were 0.02, 0.1, 0.1, and 1.0 mg/kg/day, respectively., Prepared in collaboration with the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA; Battelle Pacific NW Division, Sequim, WA; Statistics and Modeling Supporting Informed Decisions, Athens, GA; and the Henry M. Jackson Foundation, Wright-Patterson AFB OH. Sponsored in part by the Department of Energy.