Scientific Publications 2009
2009. "Protein-Based Nanomedicine Platforms for Drug Delivery." Small 5(15):1706-1721. doi:10.1002/smll.200801602 Abstract Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.
2009. "Improving FAIMS Sensitivity using a Planar Geometry with Slit Interfaces." Journal of the American Society for Mass Spectrometry 20(9):1768-1774. doi:10.1016/j.jasms.2009.05.019 Abstract Differential mobility spectrometry or field asymmetric waveform ion mobility spectrometry (FAIMS) is gaining broad acceptance for analyses of gas-phase ions, especially in conjunction with largely orthogonal separation methods such as mass spectrometry (MS) and/or conventional (drift tube) ion mobility spectrometry. In FAIMS, ions are filtered while passing through a gap between two electrodes that may have planar or curved (in particular, cylindrical) geometry. Despite substantial inherent advantages of the planar configuration and its universal acceptance in stand-alone FAIMS devices, commercial FAIMS/MS systems have employed curved FAIMS geometries that could be interfaced to MS more effectively. Here we report a new planar (p-) FAIMS design with slit-shaped entrance and exit apertures that substantially increase ion transmission in and out of the analyzer. The front slit interface effectively couples p-FAIMS to multi-emitter electrospray ionization (ESI) sources, improving greatly the ion current introduced to the device. The back slit interface increases the transmission of ribbon-shaped ion beams output by the p-FAIMS to downstream stages such as a MS. Overall, the ion signal in ESI/FAIMS/MS analyses is raised by over an order of magnitude without affecting the FAIMS resolution.
2009. "On the Determination of C0 (or A0), D0K, H0K, and Some Dark States for Symmetric-top Molecules from Infrared Spectra without the Need for Localized Perturbations." Journal of Molecular Spectroscopy 255(1):56-62. Abstract For symmetric top molecules, the normal k = 0, l = 0 and k = 1, l = 1 selection rules for parallel and perpendicular bands, respectively, do not allow the determination of the K-dependent rotational constants, C0 (or A0), D0K, and H0K. However, we show here that several different combinations of allowed and apparently unperturbed rovibrational infrared transitions can give access to those constants. A necessary ingredient for the application of this technique is a band with selection rules k = 1 (or k = 0), l = 2, such as an overtone or difference band, and appropriate other bands. Bands with selection rules k = 2, l = 1 are also useful but are seldom found. As a general rule, more than one vibrational transition is needed. Examples are given for boron trifluoride (BF3), sulfur trioxide (SO3), and cyclopropane (C3H6) for which there are microwave measurements that provide a check on the derived constants. The technique is also extended to a D2d molecule, allene, even though we have no measurements to use as an example. Examples are also given for the determination of dark states from difference bands, and/or hot bands, and also whole forbidden bands that arise from mixing with distant energy levels.
2009. "A Comparison of Simulated Cloud Radar Output from the Multiscale Modeling Framework Global Climate Model with CloudSat Cloud Radar Observations." Journal of Geophysical Research. D. (Atmospheres) 114:D00A20 (18 pp). doi:10.1029/2008JD009790 Abstract Over the last few years a new type of global climate model (GCM) has emerged in which a cloud-resolving model is embedded into each grid cell of a GCM. This new approach is frequently called a multiscale modeling framework (MMF) or superparameterization. In this article we present a comparison of MMF output with radar observations from the NASA CloudSat mission, which uses a near-nadir-pointing millimeter-wavelength radar to probe the vertical structure of clouds and precipitation. We account for radar detection limits by simulating the 94 GHz radar reflectivity that CloudSat would observe from the high-resolution cloud-resolving model output produced by the MMF. Overall, the MMF does a good job of reproducing the broad pattern of tropical convergence zones, subtropical belts, and midlatitude storm tracks, as well as their changes in position with the annual solar cycle. Nonetheless, the comparison also reveals a number of model shortfalls including (1) excessive hydrometeor coverage at all altitudes over many convectively active regions, (2) a lack of low-level hydrometeors over all subtropical oceanic basins, (3) excessive low-level hydrometeor coverage (principally precipitating hydrometeors) in the midlatitude storm tracks of both hemispheres during the summer season (in each hemisphere), and (4) a thin band of low-level hydrometeors in the Southern Hemisphere of the central (and at times eastern and western) Pacific in the MMF, which is not observed by CloudSat. This band resembles a second much weaker ITCZ but is restricted to low levels.
2009. "Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions." Journal of Physical Chemistry B 113(18):6378-6396. doi:10.1021/jp810292n Abstract We present a new continuum solvation model based on the quantum mechanical charge density of a solute molecule interacting with a continuum description of the solvent. The model is called SMD, where the “D” stands for “density” to denote that the full solute electron density is used without defining partial atomic charges. “Continuum” denotes that the solvent is not represented explicitly but rather as a dielectric medium with surface tension at the solute−solvent boundary. SMD is a universal solvation model, where “universal” denotes its applicability to any charged or uncharged solute in any solvent or liquid medium for which a few key descriptors are known (in particular, dielectric constant, refractive index, bulk surface tension, and acidity and basicity parameters). The model separates the observable solvation free energy into two main components. The first component is the bulk electrostatic contribution arising from a self-consistent reaction field treatment that involves the solution of the nonhomogeneous Poisson equation for electrostatics in terms of the integral-equation-formalism polarizable continuum model (IEF-PCM). The cavities for the bulk electrostatic calculation are defined by superpositions of nuclear-centered spheres. The second component is called the cavity-dispersion-solvent-structure term and is the contribution arising from short-range interactions between the solute and solvent molecules in the first solvation shell. This contribution is a sum of terms that are proportional (with geometry-dependent proportionality constants called atomic surface tensions) to the solvent-accessible surface areas of the individual atoms of the solute. The SMD model has been parametrized with a training set of 2821 solvation data including 112 aqueous ionic solvation free energies, 220 solvation free energies for 166 ions in acetonitrile, methanol, and dimethyl sulfoxide, 2346 solvation free energies for 318 neutral solutes in 91 solvents (90 nonaqueous organic solvents and water), and 143 transfer free energies for 93 neutral solutes between water and 15 organic solvents. The elements present in the solutes are H, C, N, O, F, Si, P, S, Cl, and Br. The SMD model employs a single set of parameters (intrinsic atomic Coulomb radii and atomic surface tension coefficients) optimized over six electronic structure methods: M05-2X/MIDI!6D, M05-2X/6-31G*, M05-2X/6-31+G**, M05-2X/cc-pVTZ, B3LYP/6-31G*, and HF/6-31G*. Although the SMD model has been parametrized using the IEF-PCM protocol for bulk electrostatics, it may also be employed with other algorithms for solving the nonhomogeneous Poisson equation for continuum solvation calculations in which the solute is represented by its electron density in real space. This includes, for example, the conductor-like screening algorithm. With the 6-31G* basis set, the SMD model achieves mean unsigned errors of 0.6−1.0 kcal/mol in the solvation free energies of tested neutrals and mean unsigned errors of 4 kcal/mol on average for ions with either Gaussian03 or GAMESS.
2009. "Effect of pressure on electrospray characteristics." Applied Physics Letters 95(18):Article Number: 184103 . Abstract An experimental study of sub-ambient pressure electrosprays is reported. The pressure domain that affords stable electrospray operation appears to be limited by the vapor pressure of the liquid. The voltage driving the electrospray is shown to have a logarithmic dependence on the pressure. This scaling amends the relationship currently in use to calculate the electric field at the tip of the meniscus of an electrified liquid
2009. "Selection of the Optimum Electrospray Voltage for Gradient Elution LC-MS Measurements." Journal of the American Society for Mass Spectrometry 20(4):682-688. Abstract Changes in liquid composition during gradient elution liquid chromatography (LC) and mass spectrometry (MS) analyses affect the electrospray operation. To establish methodologies for judicious selection of the electrospray voltage, we monitored in real-time the effect of the LC gradient on the spray current. The optimum range of the electrospray voltage shifted to lower values as the concentration of organic solvent in the eluent increased during reversed-phase LC analyses. These results provided the means to rationally select the voltage that ensured successful electrospray operation throughout gradient elution LC-MS experiments. A small run-to-run drift in the spray current was observed for electrosprays operated at constant voltage. This could be the result of fouling or degradation of the electrospray emitter, which affected the electric field driving the electrospray. Algorithms using feedback from spray current measurements to maintain the electrospray voltage within the optimum operating range throughout gradient elution LC-MS were evaluated. The electrospray operation with voltage regulation and at constant, judiciously selected voltage during gradient elution LC-MS measurements produced data with similar reproducibility.
2009. "Electron donor-dependent radionuclide reduction and nanoparticle formation by Anaeromyxobacter dehalogenans strain 2CP-C." Environmental Microbiology 11(2):534-543. Abstract Anaeromyxobacter dehalogenans strain 2CP-C can rapidly reduce U(VI) or Tc(VII) to U(IV)O2(s) or Tc(IV)O2(S) using either acetate or H2 as an electron donor source. Kinetic studies reveal that the H2-driven reduction of either U(VI) or Tc(VII) is faster than the acetate-driven reduction. The sub-cellular localization of reduced UO2 is extracellular while TcO2 nanoparticles are both periplasmic and extracellular. While electron donor-specific differences in UO2 nanoparticle aggregate size were observed, the association of UO2 nanoparticles with an exopolymeric substance (EPS) was observed and found to be independent of electron donor source. Electron donor-specific localization differences were not observed in cells incubated with Tc(VII). These finding have direct implications on immobilization strategies for highly soluble radionuclide contaminants in subsurface waters and the development of microbially assisted biostimulation efforts.
2009. "Analysis of the High-Resolution Infrared Spectrum of Cyclopropane." Journal of Molecular Spectroscopy 255(1):45-55. Abstract The high resolution infrared spectrum of cyclopropane (C3H6) has been measured from 100 cm-1 to 2200 cm-1. In that region we have identified 24 absorption bands attributed to 6 fundamental bands, 5 combination bands, 3 hot bands and 10 difference bands. Long pathlength spectra, up to 32 m, facilitated the identification and analysis of many previously unstudied infrared inactive, and Raman and infrared inactive vibrational states, including direct access to two forbidden fundamental states, 4 and 14. An improved set of constants for the ground vibrational state as well as for the fundamental vibrations 7, 9, 10, 11 are also reported. The spectral resolution of the measurements varied from 0.002 cm-1 to 0.004 cm-1.
2009. "Using Rare Gas Permeation to Probe Methanol Diffusion near the Glass Transition Temperature." Physical Review Letters 103(24):Article Number: 245902. Abstract The permeation of rare-gas atoms through deeply supercooled metastable liquid methanol films is used to probe the diffusivity. The technique allows for measurement of supercooled liquid self-diffusion at temperatures just above the glass transition. The diffusivity near the glass transition is characterized by an activation energy and prefactor that are seven and 1030 times greater, respectively, than those of the room temperature liquid. The temperature dependence of the diffusivity is well-described by a Vogel-Fulcher-Tamman (VFT) equation. These new measurements, their kinetic parameters, and temperature dependence provide clear evidence that methanol is a fragile liquid.
2009. "Low temperature sintering of lanthanum strontium manganite-based contact pastes for SOFCs." Journal of Power Sources 180(1):294-300. Abstract Electrical contact pastes of composition (La0.90Sr0.10)0.98MnO3+δ (LSM-10) formed strong bonds (~3 MPa) to (Co,Mn)3O4 spinel-coated Crofer 22 APU ferritic steel coupons when exposed to alternating flows of air and nitrogen (10 ppm O2) at 900oC for 2 hours or longer. When held at 900oC in air only, bond strengths were negligible. Substantial bonds could also be created between LSM-10 contact paste and (La0.80Sr0.20)0.98MnO3+δ (LSM-20) porous cathodes by processing in alternating air and nitrogen, without simultaneous densification of the cathode. Enhanced sintering of LSM-10 is attributed to transients in the defect structure induced by oxygen partial pressure changes.
2009. "Density Functional Studies of Methanol Decomposition on Subnanometer Pd Clusters." Journal of Physical Chemistry C 113(52):21789-21796. doi:10.1021/jp907772c Abstract A density functional theory study of the decomposition of methanol on subnanometer palladium clusters (primarily Pd4) is presented. Methanol dehydrogenation through C-H bond breaking to form hydroxymethyl (CH2OH) as the initial step, followed by steps involving formation of hydroxymethylene (CHOH), formyl (CHO), and carbon monoxide (CO), is found to be the most favorable reaction pathway. A competing dehydrogenation pathway with O-H bond breaking as the first step, followed by formation of methoxy (CH3O) and formaldehyde (CH2O), is slightly less favorable. In contrast, pathways involving C-O bond cleavage are much less energetically favorable, and no feasible pathways involving C-O bond formation to yield dimethyl ether (CH3OCH3) are found. Comparisons of the results are made with methanol decomposition products adsorbed on more extended Pd surfaces; all reaction intermediates are found to bind slightly more strongly to the clusters than to the surfaces.
2009. "Characterization of Surface and Bulk Nitrates of γ-Al2O3-Supported Alkaline Earth Oxides using Density Functional Theory." Physical Chemistry Chemical Physics. PCCP 11(18):3380-3389. doi:10.1039/b819347a Abstract “Surface" and "bulk" nitrates formed on a series of alkaline earth oxides (AEOs), AE(NO3)2, were investigated using first-principles density functional theory calculations. The formation of these surface and bulk nitrates was modeled by the adsorption of NO2+NO3 pairs on gamma-Al2O3-supported monomeric AEOs (MgO, CaO, SrO, and BaO) and on the extended AEO(001) surfaces, respectively. The calculated vibrational frequencies of the surface and bulk nitrates based on our proposed models are in good agreement with experimental measurements of AEO/gamma-Al2O3 materials after prolonged NO2 exposure. This indicates that experimentally observed "surface" nitrates are most likely formed with isolated two dimensional (including monomeric) AEO clusters on the gamma-Al2O3 substrate, while the "bulk" nitrates are formed on exposed (including (001)) surfaces (and likely in the bulk as well) of large three dimensional AEO particles supported on the gamma-Al2O3 substrate. Also in line with the experiments, our calculations show that the low and high frequency components of the vibrations for both surface and bulk nitrates are systematically red shifted with the increasing basicity and cationic size of the AEOs. The adsorption strengths of NO2+NO3 pairs are nearly the same for the series of alumina-supported monomeric AEOs, while the adsorption strengths of NO2+NO3 pairs on the AEO surfaces increase in the order of MgO < CaO < SrO ~ BaO. Compared to the NO2+NO3 pair that only interacts with monomeric AEOs, the stability of NO2+NO3 pairs that interact with both the monomeric AEO and the gamma-Al2O3 substrate is enhanced by about 0.5 eV. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.
2009. "First-principles Analysis of NOx Adsorption on Anhydrous γ-Al2O3 Surfaces." Journal of Physical Chemistry C 113(18):7779-7789. doi:10.1021/jp8103563 Abstract The interaction of nitrogen oxides NOx (x=1-3) with gamma Al2O3 has been investigated using first-principles density functional theory calculations. NO and NO2 weakly physisorb on the clean, dehydrated (100) and (110) surfaces of gamma Al2O3, whereas the adsorption of the NO3 radical is rather strong. Only the basic-like O-down adsorption configurations were found to be stable. The interaction between NOx and gamma Al2O3 can be described as a surface mediated electron transfer process. For single NOx adsorption, greater electron transfer from the surface to the adsorbate (negatively charged) yields stronger interactions between NOx and the surface. The adsorption of four combinations of NOx+NOy (x=1-3, y=2, 3) pairs on the (100) and the (110) facets of gamma Al2O3 were investigated. Except for the NO2+NO2 pair, a strong cooperative effect that substantially enhances the stability of NOx on both gamma Al2O3 surfaces was found. This cooperative effect consists of surface-mediated electron transfer processes resulting in a favorable electrostatic interaction between two adsorbed NOx species. The pair was found to be the thermodynamically most stable state among the co-adsorbed NOx+NOy pairs on both gamma Al2O3 surfaces. The results are used to analyze the experimentally observed NOx evolution during temperature programmed desorption from NO2-saturated gamma Al2O3 substrates. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.
2009. "Potential Energy Surface of Methanol Decomposition on Cu(110)." Journal of Physical Chemistry C 113(11):4522-4537. Abstract Combining the dimer saddle point searching method and periodic density functional theory calculations, the potential energy surface of methanol decomposition on Cu(110) has been mapped out. Each elementary step in the methanol decomposition reaction into CO and hydrogen occurs via one of three possible mechanisms: OH, CH or CO bond scission. Multiple reaction pathways for each bond scission have been identified in the present work. Reaction pathway calculations were started from an initial (reactant) state with methanol adsorbed in the most stable geometry on Cu(110). The saddle point and corresponding final state of each reaction or diffusion mechanism were determined without assuming the reaction mechanism. In this way, the reaction paths are determined without chemical intuition. The harmonic pre-exponential factor of each identified reaction is calculated from a normal mode analysis of the stationary points. Then, using harmonic transition state theory, the reaction rate of each identified reaction pathway in the entire reaction network is obtained. The most favorable decomposition route for methanol on Cu(110) is found as follows: . The rate-limiting step in this route is the dehydrogenation of methoxy to formaldehyde. Our calculation results are in agreement with previous experimental observations and results. This work was supported by a Laboratory Directed Research and Development (LDRD) project of the Pacific Northwest National Laboratory (PNNL). The computations were performed using the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), which is a U.S. Department of Energy national scientific user facility located at PNNL in Richland, Washington.
2009. "Structure and Function of Pseudomonas Aeruginosa Protein PA1324 (21-170)." Protein Science 18(3):606-618. Abstract Pseudomonas aeruginosa is the prototypical biofilm-forming Gram-negative opportunistic human pathogen. P. aeruginosa is causatively associated with nosocomial infections and with cystic fibrosis. Antibiotic resistance in some strains adds to the inherent difficulties that result from biofilm formation when treating P. aeruginosa infections. Transcriptional profiling studies suggest widespread changes in the proteome during quorum sensing and biofilm development. Many of the proteins found to be upregulated during these processes are poorly characterized from a functional standpoint. Here we report the solution NMR structure of PA1324, a protein of unknown function identified in these studies, and provide a putative biological functional assignment based on the observed prealbumin-like fold and FAST-NMR ligand screening studies. PA1324 is postulated to be involved in the binding and transport of sugars or polysaccharides associated with the peptidoglycan matrix during biofilm formation.
2009. "The Analysis of AGEs and ALEs by Mass Spectrometry: What does the Future Hold?" International Maillard Reaction Society Highlights 4(5):2-9. Abstract In 1912, Louis-Camille Maillard described a reaction between amino acids and reducing sugars that produced a discolored (brown) reaction mixture in the presence of heat . This complex network of reactions between reducing sugars and free amine groups on amino acids or proteins came to be known as the Maillard reaction and was the domain of food chemists for the next 50 years. Work in the 1960s began a very exciting era in the field. A few years earlier, several groups [2-5] reported on the heterogeneity of normal human adult hemoglobin (HbA) as determined chromatographically, and Allen et al were the first to use cation-exchange chromatography to separate a previously observed fast moving component (HbAI) into three fractions that they termed AIa, AIb, and AIc. An increase in the fast moving HbAI of four diabetic patients was subsequently reported by Huisman and Dozy in 1962 , and the link between diabetes and increased HbAI was later strengthened by Rahbar’s observation of increased HbAI – the majority of which is HbAIc – in 47 cases of diabetes . Bookchin and Gallop determined that HbAIc consisted of a hexose bound to both β-chains , and Bunn and colleagues subsequently proposed that glucose binds to the N-terminal amine groups of the β-chain valine residues in the form of a Schiff base, which then rearranges to form an Amadori compound . Thus, while Maillard chemistry was known to occur during the heating and processing of food, the identification of Amadori-modified hemoglobin proved that it also occurred in vivo (after all, as John Baynes likes to point out, humans are essentially low temperature ovens with long cooking cycles!).
2009. " Using Thin Films to Screen Possible Scintillator Materials ." IEEE Transactions on Nuclear Science 56(3, PT 3): 1650-1654. Abstract The discovery and optimization of new scintillators has traditionally been a rather slow process due to the difficulties of single crystal growth. This paper discusses the production of polycrystalline scintillator thin films (a few microns thick) which were tested in order to determine what characterizations could be made concerning a material’s ultimate potential as a scintillator prior to pursuing crystal growth. Thin films of CaF2(Eu), CeF3, and CeCl3, all known scintillators, were produced by vapor deposition. The hygroscopic CeCl3 was coated with multiple polymer-aluminum oxide bi-layers. Emission spectra peak wavelengths and decay times agreed with single crystal values. The films were too thin to measure gamma photopeaks, but using alpha energy deposition peaks, one could compare the relative photon yield/MeV between materials. The values obtained appear to give a relevant indication of a material’s light yield potential. The technique also appears useful for quickly determining the proper dopant amount for a given material.
2009. "The Electronic Structure of Oxygen Atom Vacancy and Hydroxyl Impurity Defects on Titanium Dioxide (110) Surface." Journal of Chemical Physics 130(12):124502-1 - 124502-11. Abstract Introducing a charge into a solid such as a metal oxide through chemical, electrical, or optical means can dramatically change its chemical or physical properties. To minimize its free energy, a lattice will distort in a material specific way to accommodate (screen) the Coulomb and exchange interactions presented by the excess charge. The carrier-lattice correlation in response to these interactions defines the spatial extent of the perturbing charge and can impart extraordinary physical and chemical properties such as superconductivity and catalytic activity. Here we investigate by experiment and theory the atomically resolved distribution of the excess charge created by a single oxygen atom vacancy and a hydroxyl (OH) impurity defects on rutile TiO₂ (110) surface. Contrary to the conventional model where the charge remains localized at the defect, scanning tunneling microscopy and density functional theory show it to be delocalized over multiple surrounding titanium atoms. The characteristic charge distribution controls the chemical, photocatalytic, and electronic properties of TiO₂ surfaces.
2009. "Molecular dynamics simulation of threshold displacement energies in zircon." Nuclear Instruments and Methods in Physics Research. Section B, Beam Interactions with Materials and Atoms 267(20):3431-3436. doi:10.1016/j.nimb.2009.07.023 Abstract Molecular-dynamics simulations were used to examine the displacement threshold energy (Ed) surface for Zr, Si and O in zircon using two different interatomic potentials. For each sublattice, the simulation was repeated from different initial conditions to estimate the uncertainty in the calculated value of Ed. The displacement threshold energies vary considerably with crystallographic direction and sublattice. The average displacement energy calculated with a recently developed transferable potential is about 120 and 60 eV for cations and anions, respectively. The oxygen displacement energy shows good agreement with experimental estimates in ceramics.
2009. "Balance of Attraction and Repulsion in Nucleic-Acid Base Stacking: CCSD(T)/Complete-Basis-Set-Limit Calculations on Uracil Dimer and a Comparison with the Force-Field Description." Journal of Chemical Theory and Computation 5(6):1524-1544. doi:10.1021/ct9000125 Abstract We have carried out reference quantum-chemical calculations for about 100 geometries of the uracil dimer in stacked conformations. The calculations have been specifically aimed at geometries with unoptimized distances between the monomers including geometries with mutually tilted monomers. Such geometries are characterized by a delicate balance between local steric clashes and local unstacking and had until now not been investigated using reference quantummechanics (QM) methods. Nonparallel stacking geometries often occur in nucleic acids and are of decisive importance, for example, for local conformational variations in B-DNA. Errors in the shortrange repulsion region would have a major impact on potential energy scans which were often used in the past to investigate local geometry variations in DNA. An incorrect description of such geometries may also partially affect molecular dynamics (MD) simulations in applications when quantitative accuracy is required. The reference QM calculations have been carried out using the MP2 method extrapolated to the complete basis-set limit and corrected for higher-order electron-correlation contributions using CCSD(T) calculations with a medium-sized basis set. These reference calculations have been used as benchmark data to test the performance of the DFT-D, SCS(MI)-MP2, and DFTSAPT QM methods and of the AMBER molecular-mechanics (MM) force field. The QM methods show close to quantitative agreement with the reference data, albeit the DFT-D method tends to modestly exaggerate the repulsion of steric clashes. The force field in general also provides a good description of base stacking for the systems studied here. However, for geometries with close interatomic contacts and clashes, the repulsion effects are rather severely exaggerated. The discrepancy reported here should not affect the overall stability of MD simulations and qualitative applications of the force field. However, it may affect the description of subtle quantitative effects such as the local conformational variations in B-DNA. Preliminary calculations for two H-bonded uracil base pairs, including one with a C-H· · ·O H-bond, indicate excellent performance of the tested QM methods for all intermonomer distances. The force field, on the other hand, is less satisfactory, especially in the repulsive regions.
2009. "c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry. ." Oncogene 28(27):2485-2491. doi:10.1038/onc.2009.112 Abstract Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA, and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell cycle entry is unknown. Here, we report the metabolic fates of [U-13C] glucose in serum-stimulated myc-/- and myc+/+ fibroblasts by 13C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased 13C-labeling of ribose sugars, purines, and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked GlcNAc protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing role for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its role in directing metabolic networks required for cell proliferation.
2009. "Intercomparison of model simulations of mixed-phase clouds observed during the ARM Mixed-Phase Arctic Cloud Experiment. II: Multi layered cloud." Quarterly Journal of the Royal Meteorological Society 135(641 Pt. B):1003-1019. doi:10.1002/qj.415 Abstract Results are presented from an intercomparison of single-column and cloud resolving model simulations of a deep, multi-layered, mixed-phase cloud system observed during the ARM Mixed-Phase Arctic Cloud Experiment. This cloud system was associated with strong surface turbulent sensible and latent heat fluxes as cold air flowed over the open Arctic Ocean, combined with a low pressure system that supplied moisture at mid-level. The simulations, performed by 13 single-column and 4 cloud-resolving models, generally overestimate the liquid water path and strongly underestimate the ice water path, although there is a large spread among the models. This finding is in contrast with results for the single-layer, low-level mixed-phase stratocumulus case in Part I of this study, as well as previous studies of shallow mixed-phase Arctic clouds, that showed an underprediction of liquid water path. The overestimate of liquid water path and underestimate of ice water path occur primarily when deeper mixed-phase clouds extending into the mid-troposphere were observed. These results suggest important differences in the ability of models to simulate Arctic mixed-phase clouds that are deep and multi-layered versus shallow and single-layered. In general, the cloud-resolving models and models with a more sophisticated, two-moment treatment of the cloud microphysics produce a somewhat smaller liquid water path that is closer to observations. The cloud-resolving models also tend to produce a larger cloud fraction than the single column models. The liquid water path and especially the cloud fraction have a large impact on the cloud radiative forcing at the surface, which is dominated by the longwave flux for this case.
2009. "Oxygen Coverage Dependence of NO Oxidation on Pt(111)." Journal of Physical Chemistry C 113(14):5766-5776. Abstract The interaction of NO with adsorbed atomic oxygen on Pt(111) was studied with temperature programmed desorption (TPD), infrared reflection absorption spectroscopy (IRAS) and low energy electron diffraction (LEED). Atomic oxygen adlayers with 0.25 and 0.75 ML coverages were prepared on a Pt(111) single crystal by dissociative chemisorption of O2 at 300 K and NO2 at 400 K, respectively. These two oxygen pre-covered surfaces were used to study the oxygen coverage dependence of NO oxidation at different sample temperatures. The well ordered p(2x2)-O layer, corresponding to ΘO = 0.25 ML, does not react with NO to form NO2 in the temperature range of 350 - 500 K, in contrast to CO oxidation which takes place readily at a sample temperature as low as 300 K. At ΘO = 0.75 ML, however, the NO oxidation reaction is facile, and the formation of NO2 is observed even at 150 K. However, the NO oxidation reaction completely stops as the atomic oxygen coverage drops below 0.28 ML, because all the weakly bound oxygen atoms available only at higher O coverages have been consumed. The remaining oxygen atoms are bound too strongly to the Pt(111) surface and, therefore, unable to participate in NO oxidation in the 150 – 500 K temperature range.
2009. "Reactivity of a Thick BaO Film Supported on Pt(111): Adsorption and Reaction of NO2, H2O and CO2." Langmuir 25(18):10820-10828. doi:10.1021/la901371g Abstract Reactions of NO2, H2O, and CO2 with a thick (> 20 MLE) BaO film supported on Pt(111) were studied with temperature programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS). NO2 reacts with a thick BaO to form surface nitrite-nitrate ion pairs at 300 K, while only nitrates form at 600 K. In the thermal decomposition process of nitrite–nitrate ion pairs, first nitrites decompose and desorb as NO. Then nitrates decompose in two steps : at lower temperature with the release of NO2 and at higher temperature, nitrates dissociate to NO + O2. The thick BaO layer converts completely to Ba(OH)2 following the adsorption of H2O at 300 K. Dehydration/dehydroxylation of this hydroxide layer can be fully achieved by annealing to 550 K. CO2 also reacts with BaO to form BaCO3 that completely decomposes to regenerate BaO upon annealing to 825 K. However, the thick BaO film cannot be converted completely to Ba(NOx)2 or BaCO3 under the experimental conditions employed in this study.
2009. "The Seattle Structure Genomics Center for Infectious Disease (SSGCID)." Infectious Disorders Drug Targets 9(5):493-506. Abstract The NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium established to apply structural genomics approaches to potential drug targets from NIAID priority organisms for biodefense and emerging and re-emerging diseases. The mission of the SSGCID is to determine ~400 protein structures over the next 5 years. In order to maximize biomedical impact ligand-based drug-lead discovery campaigns will be pursued for a small number of high-impact targets. Here we review the center’s target selection processes, which include pro-active engagement of the infectious disease research and drug therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. This is followed by a brief overview of the SSGCID structure determination pipeline and ligand screening methodology. Finally, specifics of our services to the scientific community are presented. Physical materials and data produced by SSGCID will be made available to the scientific community, with the aim that they will provide essential groundwork benefiting future research and drug discovery.