Physical Sciences and Mathematics Commons^™

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …

Mutation Of H63 And Its Catalytic Affect On The Methionine Aminopeptidase From Escherichia Coli, Sanghamitra Mitra, Brian Bennett, Richard C. Holz

Richard C. Holz

In order to gain insight into the mechanistic role of a flexible exterior loop near the active site, made up of Y62, H63, G64, and Y65, that has been proposed to play an important role in substrate binding and recognition in the methionyl aminopeptidase from Escherichia coli (EcMetAP-I), the H63A enzyme was prepared. Mutation of H63 to alanine does not affect the ability of the enzyme to bind divalent metal ions. The specific activity of H63A EcMetAP-I was determined using four different substrates of varying lengths, namely, l-Met-p-NA, MAS, MGMM and MSSHRWDW. For the smallest/shortest substrate (l-Met-p-NA) the specific activity …

Identification Of An Active Site-Bound Nitrile Hydratase Intermediate Through Single Turnover Stopped-Flow Spectroscopy, Natalie Gumataotao, Misty L. Kuhn, Natalia Hajnas, Richard C. Holz

Richard C. Holz

Stopped-flow kinetic data were obtained for the iron-type nitrile hydratase from Rhodococcus equi TG328-2 (ReNHase) using methacrylonitrile as the substrate. Multiple turnover experiments suggest a three-step kinetic model that allows for the reversible binding of substrate, the presence of an intermediate, and the formation of product. Microscopic rate constants determined from these data are in good agreement with steady state data confirming that the stopped-flow method used was appropriate for the reaction. Single turnover stopped-flow experiments were used to identify catalytic intermediates. These data were globally fit confirming a three-step kinetic model. Independent absorption spectra acquired between 0.005 …

Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta Gillner, Daniel P. Becker, Richard C. Holz

Richard C. Holz

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.

Conversion Of Red Fluorescent Protein Into A Bright Blue Probe, Oksana M. Subach, Illia S. Gundorov, Masami Yoshimura, Fedor V. Subach, Jinghang Zhang, David Grunwald, Ekaterina A. Souslova, Dmitriy M. Chudakov, Vladislav V. Verkhusha

David Grünwald

We used a red chromophore formation pathway, in which the anionic red chromophore is formed from the neutral blue intermediate, to suggest a rational design strategy to develop blue fluorescent proteins with a tyrosine-based chromophore. The strategy was applied to red fluorescent proteins of the different genetic backgrounds, such as TagRFP, mCherry, HcRed1, M355NA, and mKeima, which all were converted into blue probes. Further improvement of the blue variant of TagRFP by random mutagenesis resulted in an enhanced monomeric protein, mTagBFP, characterized by the substantially higher brightness, the faster chromophore maturation, and the higher pH stability than blue fluorescent proteins …

Composition And Optical Properties Of Secondary Organic Aerosol Particles, Felisha Imholt, Ryan Caylor, Matthew E. Wise, John Shilling

Matthew E. Wise

No abstract provided.

Optical Properties Of Secondary Organic Aerosols, Felisha Imholt, Ryan Caylor, Matthew E. Wise, John Shilling

Matthew E. Wise

Composition Of Secondary Organic Aerosols, Ryan Caylor, Felisha Imholt, Matthew E. Wise, John Shilling

Matthew E. Wise

A Generator-Produced Gallium-68 Radiopharmaceutical For Pet Imaging Of Myocardial Perfusion, Nigam Rath, Vijay Sharma, Jothilingam Sivapackiam, Scott E. Harpstrite, Julie L. Prior, Hannah Gu, David Piwnica-Worms

Nigam Rath

Magnetic Properties Of (Γ-Fe₂O₃)₈₀Ag₂₀ Nanocomposites Prepared In Reverse Micelles, Joan A. Wiemann, Jianbiao Dai, Jinke Tang, Gary J. Long, Leonard Spinu

Jinke Tang

The magnetic properties of nanoparticles of gamma-Fe2O3 prepared by reverse micelles have been studied by dc magnetization, transverse ac susceptibility, and Mössbauer spectroscopy. The nanoparticles of gamma-Fe2O3 in the nanocomposite (gamma-Fe2O3)80Ag20 exhibit superparamagnetic behavior. The blocking temperatures determined by the three methods indicate the superparamagnetic nature of (gamma-Fe2O3)80Ag20 above 70-80 K and show correlation with measuring time. The average particle diameter obtained by transmission electron microscopy of the gamma-Fe2O3 particles is ~10 nm and that of the Ag particles is ~20 nm. The average particle size determined from the magnetic analyses for the gamma-Fe2O3 particles is ~12 nm. Mössbauer spectra …

Receptor For Fluorescence Sensing Of Organic Acid And Method Of Preparation Thereof (유기산 형광 인지 수용체 및 이의 제조방법), Hong Seok Kim, Md Wasi Ahmad

Dr. Mohammad Wasi Ahmad (Md Wasi Ahmad)

The invention relates to the receptor it is the novel cholestane -based fluorescence which selectively reacts to the organic acid the pyrene group is bound as the fluorescence having the selectivity in the organic acid the receptor and a manufacturing method thereof in the imidazole -based cholestane introducing the imidazole to more detailed cholestane skeleton and manufacturing method thereof. By showing the organic acid, especially, the oxalic acid and high binding affinity the receptor has the effect that it selectively senses and the receptor can use in the sensing of the oxalic acid whether it is the imidazole -based cholestane …

Kink-Based Path Integral Calculations Of Atoms He-Ne, Randall W. Hall

Randall W. Hall

An adaptive, kink-based path integral formalism is used to calculate the ground state energies of the atoms He–Ne. The method uses an adaptive scheme to virtually eliminate the sign difficulties. This is done by using a Monte Carlo scheme to identify states that contribute significantly to the canonical partition function and then include them in the wavefunctions to calculate the canonical averages. The calculations use the 6-31G basis set and obtain both precision and accuracy.

Simulation Of Electronic And Geometric Degrees Of Freedom Using A Kink-Based Path Integral Formulation: Application To Molecular Systems, Randall W. Hall

Randall W. Hall

A kink-based path integral method, previously applied to atomic systems, is modified and used to study molecular systems. The method allows the simultaneous evolution of atomic and electronic degrees of freedom. Results for CH4, NH3, and H2O demonstrate this method to be accurate for both geometries and energies. Comparison with DFT and MP2 level calculations show the path integral approach to produce energies in close agreement with MP2 energies and geometries in close agreement with both DFT and MP2 results.

Constructing Explicit Magnetic Analogies For The Dynamics Of Glass Forming Liquids, Jacob D. Stevenson, Aleksandra M. Walczak, Randall W. Hall, Peter G. Wolynes

Randall W. Hall

By defining a spatially varying replica overlap parameter for a supercooled liquid referenced to an ensemble of fiducial liquid state configurations, we explicitly construct a constrained replica free energy functional that maps directly onto an Ising Hamiltonian with both random fields and random interactions whose statistics depend on the liquid structure. Renormalization group results for random magnets when combined with these statistics for the Lennard-Jones glass suggest that discontinuous replica symmetry breaking would occur if a liquid with short range interactions could be equilibrated at a sufficiently low temperature where its mean field configurational entropy would vanish, even though the …

Microscopic Theory Of Network Glasses, Randall W. Hall, Peter G. Wolynes

Randall W. Hall

A theory of the glass transition of network liquids is developed using self-consistent phonon and liquid state approaches. The dynamical transition and entropy crisis characteristic of random first-order transitions are mapped as a function of the degree of bonding and density. Using a scaling relation for a soft-core model to crudely translate the densities into temperatures, theory predicts that the ratio of the dynamical transition temperature to the laboratory transition temperature rises as the degree of bonding increases, while the Kauzmann temperature falls explaining why highly coordinated liquids are “strong” while van der Waals liquids without coordination are “fragile.”

An Adaptive, Kink-Based Approach To Path Integral Calculations, Randal W. Hall

Randall W. Hall

A kink-based expression for the canonical partition function is developed using Feynman’s path integral formulation of quantum mechanics and a discrete basis set. The approach is exact for a complete set of states. The method is tested on the 3×3 Hubbard model and overcomes the sign problem seen in traditional path integral studies of fermion systems. Kinks correspond to transitions between different N-electron states, much in the same manner as occurs in configuration interaction calculations in standard ab initio methods. The different N-electron states are updated, based on which states occur frequently during a Monte Carlo simulation, giving better estimates …

Divergence, Recombination And Retention Of Functionality During Protein Evolution, Yanong O. Xu, Randall W. Hall, Richard A. Goldstein, David D. Pollock

Randall W. Hall

We have only a vague idea of precisely how protein sequences evolve in the context of protein structure and function. This is primarily because structural and functional contexts are not easily predictable from the primary sequence, and evaluating patterns of evolution at individual residue positions is also difficult. As a result of increasing biodiversity in genomics studies, progress is being made in detecting context-dependent variation in substitution processes, but it remains unclear exactly what context-dependent patterns we should be looking for. To address this, we have been simulating protein evolution in the context of structure and function using lattice models …

Simulation Of Electronic And Geometric Degrees Of Freedom Using A Kink-Based Path Integral Formulation: Application To Molecular Systems, Randall W. Hall

Randall W. Hall

A kink-based path integral method, previously applied to atomic systems, is modified and used to study molecular systems. The method allows the simultaneous evolution of atomic and electronic degrees of freedom. Results for CH4, NH3, and H2O demonstrate this method to be accurate for both geometries and energies. Comparison with DFT and MP2 level calculations show the path integral approach to produce energies in close agreement with MP2 energies and geometries in close agreement with both DFT and MP2 results.

Constructing Explicit Magnetic Analogies For The Dynamics Of Glass Forming Liquids, Jacob D. Stevenson, Aleksandra M. Walczak, Randall W. Hall, Peter G. Wolynes

Randall W. Hall

By defining a spatially varying replica overlap parameter for a supercooled liquid referenced to an ensemble of fiducial liquid state configurations, we explicitly construct a constrained replica free energy functional that maps directly onto an Ising Hamiltonian with both random fields and random interactions whose statistics depend on the liquid structure. Renormalization group results for random magnets when combined with these statistics for the Lennard-Jones glass suggest that discontinuous replica symmetry breaking would occur if a liquid with short range interactions could be equilibrated at a sufficiently low temperature where its mean field configurational entropy would vanish, even though the …

An Adaptive, Kink-Based Approach To Path Integral Calculations, Randal W. Hall

Randall W. Hall

A kink-based expression for the canonical partition function is developed using Feynman’s path integral formulation of quantum mechanics and a discrete basis set. The approach is exact for a complete set of states. The method is tested on the 3×3 Hubbard model and overcomes the sign problem seen in traditional path integral studies of fermion systems. Kinks correspond to transitions between different N-electron states, much in the same manner as occurs in configuration interaction calculations in standard ab initio methods. The different N-electron states are updated, based on which states occur frequently during a Monte Carlo simulation, giving better estimates …

Divergence, Recombination And Retention Of Functionality During Protein Evolution, Yanong O. Xu, Randall W. Hall, Richard A. Goldstein, David D. Pollock

Randall W. Hall

We have only a vague idea of precisely how protein sequences evolve in the context of protein structure and function. This is primarily because structural and functional contexts are not easily predictable from the primary sequence, and evaluating patterns of evolution at individual residue positions is also difficult. As a result of increasing biodiversity in genomics studies, progress is being made in detecting context-dependent variation in substitution processes, but it remains unclear exactly what context-dependent patterns we should be looking for. To address this, we have been simulating protein evolution in the context of structure and function using lattice models …

Electrochemically Active Biofilm Assisted Synthesis Of Ag@Ceo2 Nanocomposites For Antimicrobial Activity, Photocatalysis And Photoelectrodes, Mohammad Mansoob Khan Dr, S. A. Ansari, J. H. Lee, M. O. Ansari, J Lee, M. H. Cho

Dr. Mohammad Mansoob Khan

Ag@CeO2 nanocomposites were synthesized by a biogenic and green approach using electrochemically active biofilms (EABs) as a reducing tool. The as-synthesized Ag@CeO2 nanocomposites were characterized and used in antimicrobial, visible light photocatalytic and photoelectrode studies. The Ag@CeO2 nanocomposites showed effective and efficient bactericidal activities and survival test against Escherichia coli O157:H7, and Pseudomonas aeruginosa. The as-synthesized Ag@CeO2 nanocomposites also exhibited enhanced visible light photocatalytic degradation of 4-nitrophenol and methylene blue than pure CeO2. A photocatalytic investigation showed that the Ag@CeO2 nanocomposites possessed excellent visible light photocatalytic activities compared to pure CeO2. Electrochemical impedance spectroscopy and photocurrent measurements showed that the …

Quantitative Mid-Infrared Spectra Of Allene And Propyne From Room To High Temperatures, Et. Es-Sebbar, A. Jolly, Y. Benilan, A. Farooq

Dr. Et-touhami Es-sebbar

Allene (a-C3H4; CH2CCH2) and propyne (p-C3H4; CH3C2H) have attracted much interest because of their relevance to the photochemistry in astrophysical environments as well as in combustion processes. Both allene and propyne have strong absorption in the infrared region. In the present work, infrared spectra of a-C3H4 and p-C3H4 are measured in the gas phase at temperatures ranging from 296 to 510 K. The spectra are measured over the 580–3400 cm−1 spectral region at resolutions of 0.08 and 0.25 cm−1 using Fourier Transform Infrared spectroscopy. Absolute integrated intensities of the main infrared bands are determined at room temperature and compared with …

Synthesis And Polymerization Of (E,E)-[6.2]-(2,5)Furanophane-1,5-Diene, Neil D. Doppler, Jeffrey H. Glans

Jeffrey H. Glans

The goal of this research is to polymerize (E,E)-[6.2]-(2,5)furanophane to give a linear polymer. It will be synthesized by a 1,8-Hofmann Elimination using trimethyl-[(E)-3-(5-methyl-2-furyl)allyl] ammonium iodide. This diene will then be polymerized. The resulting polymeric [3.2] furanophane will then be oxidized to form a polymeric macrocycle tetra ketone. This compound will be tested for cation complexation.

Synthesis And Polymerization Of (E,E)-[6.2]-(2,5)Furanophane-1,5-Diene, Neil D. Doppler, Jeffrey H. Glans

Jeffrey H. Glans

The goal of this research is to polymerize (E,E)-[6.2]-(2,5)furanophane to give a linear polymer. It will be synthesized by a 1,8-Hofmann Elimination using trimethyl-[(E)-3-(5-methyl-2-furyl)allyl] ammonium iodide. This diene will then be polymerized. The resulting polymeric [3.2] furanophane will then be oxidized to form a polymeric macrocycle tetra ketone. This compound will be tested for cation complexation.

The Mechanism Of Membrane Targeting Of Human Sphingosine Kinase 1, Robert V. Stahelin, Jeong H. Hwang, Jin-Hahn Kim, Zee-Yong Park, Korey R. Johnson, Lina M. Obeid, Wonhwa Cho

Jeong Choe

Sphingosine 1-phosphate is a bioactive sphingolipid that regu- lates cell growth and suppresses programmed cell death. The bio- synthesis of sphingosine 1-phosphate is catalyzed by sphingosine kinase (SK) but the mechanism by which the subcellular localization and activity of SK is regulated in response to various stimuli is not fully understood. To elucidate the origin and structural determi- nant of the specific subcellular localization of SK, we performed biophysical and cell studies of human SK1 (hSK1) and selected mutants. In vitro measurements showed that hSK1 selectively bound phosphatidylserine over other anionic phospholipids and strongly preferred the plasma membrane-mimicking membrane to …

Fabrication Conditions For Efficient Organic Photovoltaic Cells From Aqueous Dispersions Of Nanoparticles, Monojit Bag, Timothy S. Gehan, Lawrence A. Renna, Dana D. Algaier, Paulm M. Lahti, Dhandapani Venkataraman

Dhandapani Venkataraman

For environmentally friendly and cost-effective manufacturing of organic photovoltaic (OPV) cells, it is highly desirable to replace haloarenes with water as the active layer fabrication solvent. Replacing an organic solvent with water requires retooling the device fabrication steps. The optimization studies were conducted using poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) as active layer materials. These materials were dispersed in water as blend and separate nanoparticles using the miniemulsion method. Topologies of the active layers were investigated using atomic force microscopy and electron microscopy techniques. We have identified two essential steps to fabricate efficient OPVs from aqueous …

Physicochemical Modifications And Applications Of Carbon Nano-Onions For Electrochemical Energy Storage, Rituraj Borgohain

Rituraj Borgohain

Carbon nano-onions (CNOs), concentrically multilayered fullerenes, are prepared by several different methods. We are studying the properties of two specific CNOs: A-CNOs and N-CNOs. A-CNOs are synthesized by underwater arc discharge, and N-CNOs are synthesized by high-temperature graphitization of commercial nanodiamond. In this study the synthesis of A-CNOs are optimized by designing an arc discharge aparatus to control the arc plasma. Moreover other synthesis parameters such as arc power, duty cycles, temperature, graphitic and metal impurities are controlled for optimum production of A-CNOs. Also, a very efficient purification method is developed to screen out A-CNOs from carboneseous and metal impurities. …

Benchmark Structures And Binding Energies Of Small Water Clusters With Anharmonicity Corrections, Berhane Temelso, Kaye A. Archer, George C. Shields

Berhane Temelso

For (H2O)n where n = 1–10, we used a scheme combining molecular dynamics sampling with high level ab initio calculations to locate the global and many low lying local minima for each cluster. For each isomer, we extrapolated the RI-MP2 energies to their complete basis set limit, included a CCSD(T) correction using a smaller basis set and added finite temperature corrections within the rigid-rotor-harmonic-oscillator (RRHO) model using scaled and unscaled harmonic vibrational frequencies. The vibrational scaling factors were determined specifically for water clusters by comparing harmonic frequencies with VPT2 fundamental frequencies. We find the CCSD(T) correction to the RI-MP2 binding …