Extended polarization in 3rd order SCC-DFTB from chemical potential equilization

PubMed Central

Kaminski, Steve; Giese, Timothy J.; Gaus, Michael; York, Darrin M.; Elstner, Marcus

2012-01-01

In this work we augment the approximate density functional method SCC-DFTB (DFTB3) with the chemical potential equilization (CPE) approach in order to improve the performance for molecular electronic polarizabilities. The CPE method, originally implemented for NDDO type methods by Giese and York, has been shown to emend minimal basis methods wrt response properties significantly, and has been applied to SCC-DFTB recently. CPE allows to overcome this inherent limitation of minimal basis methods by supplying an additional response density. The systematic underestimation is thereby corrected quantitatively without the need to extend the atomic orbital basis, i.e. without increasing the overall computational cost significantly. Especially the dependency of polarizability as a function of molecular charge state was significantly improved from the CPE extension of DFTB3. The empirical parameters introduced by the CPE approach were optimized for 172 organic molecules in order to match the results from density functional methods (DFT) methods using large basis sets. However, the first order derivatives of molecular polarizabilities, as e.g. required to compute Raman activities, are not improved by the current CPE implementation, i.e. Raman spectra are not improved. PMID:22894819

DFTB+ and lanthanides

NASA Astrophysics Data System (ADS)

Hourahine, B.; Aradi, B.; Frauenheim, T.

2010-07-01

DFTB+ is a recent general purpose implementation of density-functional based tight binding. One of the early motivators to develop this code was to investigate lanthanide impurities in nitride semiconductors, leading to a series of successful studies into structure and electrical properties of these systems. Here we describe our general framework to treat the physical effects needed for these problematic impurities within a tight-binding formalism, additionally discussing forces and stresses in DFTB. We also present an approach to evaluate the general case of Slater-Koster transforms and all of their derivatives in Cartesian coordinates. These developments are illustrated by simulating isolated Gd impurities in GaN.

Dynamic Responses and Initial Decomposition under Shock Loading: A DFTB Calculation Combined with MSST Method for β-HMX with Molecular Vacancy.

PubMed

He, Zheng-Hua; Chen, Jun; Ji, Guang-Fu; Liu, Li-Min; Zhu, Wen-Jun; Wu, Qiang

2015-08-20

Despite extensive efforts on studying the decomposition mechanism of HMX under extreme condition, an intrinsic understanding of mechanical and chemical response processes, inducing the initial chemical reaction, is not yet achieved. In this work, the microscopic dynamic response and initial decomposition of β-HMX with (1 0 0) surface and molecular vacancy under shock condition, were explored by means of the self-consistent-charge density-functional tight-binding method (SCC-DFTB) in conjunction with multiscale shock technique (MSST). The evolutions of various bond lengths and charge transfers were analyzed to explore and understand the initial reaction mechanism of HMX. Our results discovered that the C-N bond close to major axes had less compression sensitivity and higher stretch activity. The charge was transferred mainly from the N-NO2 group along the minor axes and H atom to C atom during the early compression process. The first reaction of HMX primarily initiated with the fission of the molecular ring at the site of the C-N bond close to major axes. Further breaking of the molecular ring enhanced intermolecular interactions and promoted the cleavage of C-H and N-NO2 bonds. More significantly, the dynamic response behavior clearly depended on the angle between chemical bond and shock direction.

Ultrafast Coulomb explosion of a diiodomethane molecule induced by an X-ray free-electron laser pulse.

PubMed

Takanashi, Tsukasa; Nakamura, Kosuke; Kukk, Edwin; Motomura, Koji; Fukuzawa, Hironobu; Nagaya, Kiyonobu; Wada, Shin-Ichi; Kumagai, Yoshiaki; Iablonskyi, Denys; Ito, Yuta; Sakakibara, Yuta; You, Daehyun; Nishiyama, Toshiyuki; Asa, Kazuki; Sato, Yuhiro; Umemoto, Takayuki; Kariyazono, Kango; Ochiai, Kohei; Kanno, Manabu; Yamazaki, Kaoru; Kooser, Kuno; Nicolas, Christophe; Miron, Catalin; Asavei, Theodor; Neagu, Liviu; Schöffler, Markus; Kastirke, Gregor; Liu, Xiao-Jing; Rudenko, Artem; Owada, Shigeki; Katayama, Tetsuo; Togashi, Tadashi; Tono, Kensuke; Yabashi, Makina; Kono, Hirohiko; Ueda, Kiyoshi

2017-08-02

Coulomb explosion of diiodomethane CH 2 I 2 molecules irradiated by ultrashort and intense X-ray pulses from SACLA, the Japanese X-ray free electron laser facility, was investigated by multi-ion coincidence measurements and self-consistent charge density-functional-based tight-binding (SCC-DFTB) simulations. The diiodomethane molecule, containing two heavy-atom X-ray absorbing sites, exhibits a rather different charge generation and nuclear motion dynamics compared to iodomethane CH 3 I with only a single heavy atom, as studied earlier. We focus on charge creation and distribution in CH 2 I 2 in comparison to CH 3 I. The release of kinetic energy into atomic ion fragments is also studied by comparing SCC-DFTB simulations with the experiment. Compared to earlier simulations, several key enhancements are made, such as the introduction of a bond axis recoil model, where vibrational energy generated during charge creation processes induces only bond stretching or shrinking. We also propose an analytical Coulomb energy partition model to extract the essential mechanism of Coulomb explosion of molecules from the computed and the experimentally measured kinetic energies of fragment atomic ions by partitioning each pair Coulomb interaction energy into two ions of the pair under the constraint of momentum conservation. Effective internuclear distances assigned to individual fragment ions at the critical moment of the Coulomb explosion are then estimated from the average kinetic energies of the ions. We demonstrate, with good agreement between the experiment and the SCC-DFTB simulation, how the more heavily charged iodine fragments and their interplay define the characteristic features of the Coulomb explosion of CH 2 I 2 . The present study also confirms earlier findings concerning the magnitude of bond elongation in the ultrashort X-ray pulse duration, showing that structural damage to all but C-H bonds does not develop to a noticeable degree in the pulse length of ∼10 fs.

Long-range correction for tight-binding TD-DFT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humeniuk, Alexander; Mitrić, Roland, E-mail: roland.mitric@uni-wuerzburg.de

2015-10-07

We present two improvements to the tight-binding approximation of time-dependent density functional theory (TD-DFTB): First, we add an exact Hartree-Fock exchange term, which is switched on at large distances, to the ground state Hamiltonian and similarly to the coupling matrix that enters the linear response equations for the calculation of excited electronic states. We show that the excitation energies of charge transfer states are improved relative to the standard approach without the long-range correction by testing the method on a set of molecules from the database in Peach et al. [J. Chem. Phys. 128, 044118 (2008)] which are known tomore » exhibit problematic charge transfer states. The degree of spatial overlap between occupied and virtual orbitals indicates where TD-DFTB and long-range corrected TD-DFTB (lc-TD-DFTB) can be expected to produce large errors. Second, we improve the calculation of oscillator strengths. The transition dipoles are obtained from Slater Koster files for the dipole matrix elements between valence orbitals. In particular, excitations localized on a single atom, which appear dark when using Mulliken transition charges, acquire a more realistic oscillator strength in this way. These extensions pave the way for using lc-TD-DFTB to describe the electronic structure of large chromophoric polymers, where uncorrected TD-DFTB fails to describe the high degree of conjugation and produces spurious low-lying charge transfer states.« less

Improving Density Functional Tight Binding Predictions of Free Energy Surfaces for Slow Chemical Reactions in Solution

NASA Astrophysics Data System (ADS)

Kroonblawd, Matthew; Goldman, Nir

2017-06-01

First principles molecular dynamics using highly accurate density functional theory (DFT) is a common tool for predicting chemistry, but the accessible time and space scales are often orders of magnitude beyond the resolution of experiments. Semi-empirical methods such as density functional tight binding (DFTB) offer up to a thousand-fold reduction in required CPU hours and can approach experimental scales. However, standard DFTB parameter sets lack good transferability and calibration for a particular system is usually necessary. Force matching the pairwise repulsive energy term in DFTB to short DFT trajectories can improve the former's accuracy for reactions that are fast relative to DFT simulation times (<10 ps), but the effects on slow reactions and the free energy surface are not well-known. We present a force matching approach to improve the chemical accuracy of DFTB. Accelerated sampling techniques are combined with path collective variables to generate the reference DFT data set and validate fitted DFTB potentials. Accuracy of force-matched DFTB free energy surfaces is assessed for slow peptide-forming reactions by direct comparison to DFT for particular paths. Extensions to model prebiotic chemistry under shock conditions are discussed. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Improving density functional tight binding predictions of free energy surfaces for peptide condensation reactions in solution

NASA Astrophysics Data System (ADS)

Kroonblawd, Matthew; Goldman, Nir

First principles molecular dynamics using highly accurate density functional theory (DFT) is a common tool for predicting chemistry, but the accessible time and space scales are often orders of magnitude beyond the resolution of experiments. Semi-empirical methods such as density functional tight binding (DFTB) offer up to a thousand-fold reduction in required CPU hours and can approach experimental scales. However, standard DFTB parameter sets lack good transferability and calibration for a particular system is usually necessary. Force matching the pairwise repulsive energy term in DFTB to short DFT trajectories can improve the former's accuracy for chemistry that is fast relative to DFT simulation times (<10 ps), but the effects on slow chemistry and the free energy surface are not well-known. We present a force matching approach to increase the accuracy of DFTB predictions for free energy surfaces. Accelerated sampling techniques are combined with path collective variables to generate the reference DFT data set and validate fitted DFTB potentials without a priori knowledge of transition states. Accuracy of force-matched DFTB free energy surfaces is assessed for slow peptide-forming reactions by direct comparison to DFT results for particular paths. Extensions to model prebiotic chemistry under shock conditions are discussed. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Vibrational spectroscopy and molecular dynamics of water monomers and dimers adsorbed on polycyclic aromatic hydrocarbons.

PubMed

Simon, Aude; Rapacioli, Mathias; Mascetti, Joëlle; Spiegelman, Fernand

2012-05-21

This paper reports structures, energetics, dynamics and spectroscopy of H2O and (H2O)2 systems adsorbed on coronene (C24H12), a compact polycyclic aromatic hydrocarbon (PAH). On-the-fly Born-Oppenheimer molecular dynamics simulations are performed for temperatures T varying from 10 to 300 K, on a potential energy surface obtained within the self-consistent-charge density-functional based tight-binding (SCC-DFTB) approach. Anharmonic infrared (IR) spectra are extracted from these simulations. We first benchmark the SCC-DFTB semi-empirical hamiltonian vs. DFT (Density Functional Theory) calculations that include dispersion, on (C6H6)(H2O)1,2 small complexes. We find that charge corrections and inclusion of dispersion contributions in DFTB are necessary to obtain consistent structures, energetics and IR spectra. Using this Hamiltonian, the structures, energetics and IR features of the low-energy isomers of (C24H12)(H2O)1,2 are found to be similar to the DFT ones, with evidence for a stabilizing edge-coordination. The temperature dependence of the motions of H2O and (H2O)2 on the surface of C24H12 is analysed, revealing ultra-fast periodic motion. The water dimer starts diffusing at a higher temperature than the water monomer (150 K vs. 10 K respectively), which appears to be consistent with the binding energies. Qualitative and quantitative analyses of the effects of T on the IR spectra are performed. Anharmonic factors in particular are derived and it is shown that they can be used as signatures for the presence of PAH-water complexes. Finally, this paper lays the foundations for the studies of larger (PAH)m(H2O)n clusters, that can be treated with the efficient computational approach benchmarked in this paper.

Density functional tight-binding and infrequent metadynamics can capture entropic effects in intramolecular hydrogen transfer reactions

NASA Astrophysics Data System (ADS)

Oliveira, Luiz F. L.; Fu, Christopher D.; Pfaendtner, Jim

2018-04-01

Infrequent metadynamics uses biased simulations to estimate the unbiased kinetics of a system, facilitating the calculation of rates and barriers. Here the method is applied to study intramolecular hydrogen transfer reactions involving peroxy radicals, a class of reactions that is challenging to model due to the entropic contributions of the formation of ring structures in the transition state. Using the self-consistent charge density-functional based tight-binding (DFTB) method, we applied infrequent metadynamics to the study of four intramolecular H-transfer reactions, demonstrating that the method can qualitatively reproduce these high entropic contributions, as observed in experiments and those predicted by transition state theory modeled by higher levels of theory. We also show that infrequent metadynamics and DFTB are successful in describing the relationship between transition state ring size and kinetic coefficients (e.g., activation energies and the pre-exponential factors).

Proton transfer along water bridges in biological systems with density-functional tight-binding

NASA Astrophysics Data System (ADS)

Reiss, Krystle; Wise, Abigail; Mazzuca, James

2015-03-01

When examining the dynamics of charge transfer in high dimensional enzymatic systems, the cost of quantum mechanical treatment of electrons increases exponentially with the size of the system. As a semi-empirical method, density-functional tight-binding aids in shortening these calculation times, but can be inaccurate in the regime where bonds are being formed and broken. To address these inaccuracies with respect to proton transfer in an enzymatic system, DFTB is being used to calculate small model systems containing only a single amino acid residue donor, represented by an imidazole molecule, and a water acceptor. When DFTB calculations are compared to B3LYP geometry calculations of the donor molecule, we observe a bond angle error on the order of 1.2 degrees and a bond length error on the order of 0.011 Å. As we move forward with small donor-acceptor systems, comparisons between DFTB and B3LYP energy profiles will provide a better clue as to what extent improvements need to be made. To improve the accuracy of the DFTB calculations, the internuclear repulsion term may be altered. This would result in energy profiles that closely resemble those produced by higher-level theory. Alma College Provost's Office.

DFTB Parameters for the Periodic Table: Part 1, Electronic Structure.

PubMed

Wahiduzzaman, Mohammad; Oliveira, Augusto F; Philipsen, Pier; Zhechkov, Lyuben; van Lenthe, Erik; Witek, Henryk A; Heine, Thomas

2013-09-10

A parametrization scheme for the electronic part of the density-functional based tight-binding (DFTB) method that covers the periodic table is presented. A semiautomatic parametrization scheme has been developed that uses Kohn-Sham energies and band structure curvatures of real and fictitious homoatomic crystal structures as reference data. A confinement potential is used to tighten the Kohn-Sham orbitals, which includes two free parameters that are used to optimize the performance of the method. The method is tested on more than 100 systems and shows excellent overall performance.

Tight binding simulation study on zigzag single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Sharma, Deepa; Jaggi, Neena; Gupta, Vishu

2018-01-01

Tight binding simulation studies using the density functional tight binding (DFTB) model have been performed on various zigzag single-walled carbon-nanotubes (SWCNTs) to investigate their electronic properties using DFTB module of the Material Studio Software version 7.0. Various combinations of different eigen-solvers and charge mixing schemes available in the DFTB Module have been tried to chalk out the electronic structure. The analytically deduced values of the bandgap of (9, 0) SWCNT were compared with the experimentally determined value reported in the literature. On comparison, it was found that the tight binding approximations tend to drastically underestimate the bandgap values. However, the combination of Anderson charge mixing method with standard eigensolver when implemented using the smart algorithm was found to produce fairly close results. These optimized model parameters were then used to determine the band structures of various zigzag SWCNTs. (9, 0) Single-walled Nanotube which is extensively being used for sensing NH3, CH4 and NO2 has been picked up as a reference material since its experimental bandgap value has been reported in the literature. It has been found to exhibit a finite energy bandgap in contrast to its expected metallic nature. The study is of utmost significance as it not only probes and validates the simulation route for predicting suitable properties of nanomaterials but also throws light on the comparative efficacy of the different approximation and rationalization quantum mechanical techniques used in simulation studies. Such simulation studies if used intelligently prove to be immensely useful to the material scientists as they not only save time and effort but also pave the way to new experiments by making valuable predictions.

Proton transfer pathways, energy landscape, and kinetics in creatine-water systems.

PubMed

Ivchenko, Olga; Whittleston, Chris S; Carr, Joanne M; Imhof, Petra; Goerke, Steffen; Bachert, Peter; Wales, David J

2014-02-27

We study the exchange processes of the metabolite creatine, which is present in both tumorous and normal tissues and has NH2 and NH groups that can transfer protons to water. Creatine produces chemical exchange saturation transfer (CEST) contrast in magnetic resonance imaging (MRI). The proton transfer pathway from zwitterionic creatine to water is examined using a kinetic transition network constructed from the discrete path sampling approach and an approximate quantum-chemical energy function, employing the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. The resulting potential energy surface is visualized by constructing disconnectivity graphs. The energy landscape consists of two distinct regions corresponding to the zwitterionic creatine structures and deprotonated creatine. The activation energy that characterizes the proton transfer from the creatine NH2 group to water was determined from an Arrhenius fit of rate constants as a function of temperature, obtained from harmonic transition state theory. The result is in reasonable agreement with values obtained in water exchange spectroscopy (WEX) experiments.

Structural modification of P-glycoprotein induced by OH radicals: Insights from atomistic simulations

NASA Astrophysics Data System (ADS)

Khosravian, N.; Kamaraj, B.; Neyts, E. C.; Bogaerts, A.

2016-02-01

This study reports on the possible effects of OH radical impact on the transmembrane domain 6 of P-glycoprotein, TM6, which plays a crucial role in drug binding in human cells. For the first time, we employ molecular dynamics (MD) simulations based on the self-consistent charge density functional tight binding (SCC-DFTB) method to elucidate the potential sites of fragmentation and mutation in this domain upon impact of OH radicals, and to obtain fundamental information about the underlying reaction mechanisms. Furthermore, we apply non-reactive MD simulations to investigate the long-term effect of this mutation, with possible implications for drug binding. Our simulations indicate that the interaction of OH radicals with TM6 might lead to the breaking of C-C and C-N peptide bonds, which eventually cause fragmentation of TM6. Moreover, according to our simulations, the OH radicals can yield mutation in the aromatic ring of phenylalanine in TM6, which in turn affects its structure. As TM6 plays an important role in the binding of a range of cytotoxic drugs with P-glycoprotein, any changes in its structure are likely to affect the response of the tumor cell in chemotherapy. This is crucial for cancer therapies based on reactive oxygen species, such as plasma treatment.

Numerical Optimization of Density Functional Tight Binding Models: Application to Molecules Containing Carbon, Hydrogen, Nitrogen, and Oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnapriyan, A.; Yang, P.; Niklasson, A. M. N.

New parametrizations for semiempirical density functional tight binding (DFTB) theory have been developed by the numerical optimization of adjustable parameters to minimize errors in the atomization energy and interatomic forces with respect to ab initio calculated data. Initial guesses for the radial dependences of the Slater- Koster bond integrals and overlap integrals were obtained from minimum basis density functional theory calculations. The radial dependences of the pair potentials and the bond and overlap integrals were represented by simple analytic functions. The adjustable parameters in these functions were optimized by simulated annealing and steepest descent algorithms to minimize the value ofmore » an objective function that quantifies the error between the DFTB model and ab initio calculated data. The accuracy and transferability of the resulting DFTB models for the C, H, N, and O system were assessed by comparing the predicted atomization energies and equilibrium molecular geometries of small molecules that were not included in the training data from DFTB to ab initio data. The DFTB models provide accurate predictions of the properties of hydrocarbons and more complex molecules containing C, H, N, and O.« less

Numerical Optimization of Density Functional Tight Binding Models: Application to Molecules Containing Carbon, Hydrogen, Nitrogen, and Oxygen

DOE PAGES

Krishnapriyan, A.; Yang, P.; Niklasson, A. M. N.; ...

2017-10-17

New parametrizations for semiempirical density functional tight binding (DFTB) theory have been developed by the numerical optimization of adjustable parameters to minimize errors in the atomization energy and interatomic forces with respect to ab initio calculated data. Initial guesses for the radial dependences of the Slater- Koster bond integrals and overlap integrals were obtained from minimum basis density functional theory calculations. The radial dependences of the pair potentials and the bond and overlap integrals were represented by simple analytic functions. The adjustable parameters in these functions were optimized by simulated annealing and steepest descent algorithms to minimize the value ofmore » an objective function that quantifies the error between the DFTB model and ab initio calculated data. The accuracy and transferability of the resulting DFTB models for the C, H, N, and O system were assessed by comparing the predicted atomization energies and equilibrium molecular geometries of small molecules that were not included in the training data from DFTB to ab initio data. The DFTB models provide accurate predictions of the properties of hydrocarbons and more complex molecules containing C, H, N, and O.« less

Molecular dynamics simulations of the amino acid-ZnO (10-10) interface: a comparison between density functional theory and density functional tight binding results.

PubMed

grosse Holthaus, Svea; Köppen, Susan; Frauenheim, Thomas; Ciacchi, Lucio Colombi

2014-06-21

We investigate the adsorption behavior of four different amino acids (glutamine, glutamate, serine, cysteine) on the zinc oxide (101̄0) surface, comparing the geometry and energy associated with a number of different adsorption configurations. In doing this, we highlight the benefits and limits of using density-functional tight-binding (DFTB) with respect to standard density functional theory (DFT). The DFTB method is found to reliably reproduce the DFT adsorption geometries. Analysis of the adsorption configurations emphasizes the fundamental role of the first hydration layer in mediating the interactions between the amino acids and the surface. Direct surface-molecule bonds are found to form predominantly via the carboxylate groups of the studied amino acids. No surface-mediated chemical reactions are observed, with the notable exception of a proton transfer from the thiol group of cysteine to a hydroxyl group of the surface hydration layer. The adsorption energies are found to be dominated both by the formation of direct or indirect surface-molecule hydrogen bonds, but also by the rearrangement of the hydrogen-bond network in surface proximity in a non-intuitive way. Energetic comparisons between DFTB and DFT are made difficult on one side by the long time necessary to achieve convergence of potential energy values in MD simulations and on the other side by the necessity of including higher-order corrections to DFTB to obtain a good description of the hydrogen bond energetics. Overall, our results suggest that DFTB is a good reference method to set the correct chemical states and the initial geometries of hybrid biomolecule/ZnO systems to be simulated with non-reactive force fields.

Molecular dynamics simulations of the amino acid-ZnO (10-10) interface: A comparison between density functional theory and density functional tight binding results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holthaus, Svea große; Köppen, Susan, E-mail: koeppen@hmi.uni-bremen.de; Frauenheim, Thomas

2014-06-21

We investigate the adsorption behavior of four different amino acids (glutamine, glutamate, serine, cysteine) on the zinc oxide (101{sup ¯}0) surface, comparing the geometry and energy associated with a number of different adsorption configurations. In doing this, we highlight the benefits and limits of using density-functional tight-binding (DFTB) with respect to standard density functional theory (DFT). The DFTB method is found to reliably reproduce the DFT adsorption geometries. Analysis of the adsorption configurations emphasizes the fundamental role of the first hydration layer in mediating the interactions between the amino acids and the surface. Direct surface-molecule bonds are found to formmore » predominantly via the carboxylate groups of the studied amino acids. No surface-mediated chemical reactions are observed, with the notable exception of a proton transfer from the thiol group of cysteine to a hydroxyl group of the surface hydration layer. The adsorption energies are found to be dominated both by the formation of direct or indirect surface-molecule hydrogen bonds, but also by the rearrangement of the hydrogen-bond network in surface proximity in a non-intuitive way. Energetic comparisons between DFTB and DFT are made difficult on one side by the long time necessary to achieve convergence of potential energy values in MD simulations and on the other side by the necessity of including higher-order corrections to DFTB to obtain a good description of the hydrogen bond energetics. Overall, our results suggest that DFTB is a good reference method to set the correct chemical states and the initial geometries of hybrid biomolecule/ZnO systems to be simulated with non-reactive force fields.« less

Initial decomposition of the condensed-phase β-HMX under shock waves: molecular dynamics simulations.

PubMed

Ge, Ni-Na; Wei, Yong-Kai; Ji, Guang-Fu; Chen, Xiang-Rong; Zhao, Feng; Wei, Dong-Qing

2012-11-26

We have performed quantum-based multiscale simulations to study the initial chemical processes of condensed-phase octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) under shock wave loading. A self-consistent charge density-functional tight-binding (SCC-DFTB) method was employed. The results show that the initial decomposition of shocked HMX is triggered by the N-NO(2) bond breaking under the low velocity impact (8 km/s). As the shock velocity increases (11 km/s), the homolytic cleavage of the N-NO(2) bond is suppressed under high pressure, the C-H bond dissociation becomes the primary pathway for HMX decomposition in its early stages. It is accompanied by a five-membered ring formation and hydrogen transfer from the CH(2) group to the -NO(2) group. Our simulations suggest that the initial chemical processes of shocked HMX are dependent on the impact velocity, which gain new insights into the initial decomposition mechanism of HMX upon shock loading at the atomistic level, and have important implications for understanding and development of energetic materials.

Parametrization and Benchmark of Long-Range Corrected DFTB2 for Organic Molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vuong, Van Quan; Akkarapattiakal Kuriappan, Jissy; Kubillus, Maximilian

In this paper, we present the parametrization and benchmark of long-range corrected second-order density functional tight binding (DFTB), LC-DFTB2, for organic and biological molecules. The LC-DFTB2 model not only improves fundamental orbital energy gaps but also ameliorates the DFT self-interaction error and overpolarization problem, and further improves charge-transfer excited states significantly. Electronic parameters for the construction of the DFTB2 Hamiltonian as well as repulsive potentials were optimized for molecules containing C, H, N, and O chemical elements. We use a semiautomatic parametrization scheme based on a genetic algorithm. With the new parameters, LC-DFTB2 describes geometries and vibrational frequencies of organicmore » molecules similarly well as third-order DFTB3/3OB, the de facto standard parametrization based on a GGA functional. Finally, LC-DFTB2 performs well also for atomization and reaction energies, however, slightly less satisfactorily than DFTB3/3OB.« less

Parametrization and Benchmark of Long-Range Corrected DFTB2 for Organic Molecules

DOE PAGES

Vuong, Van Quan; Akkarapattiakal Kuriappan, Jissy; Kubillus, Maximilian; ...

2017-12-12

In this paper, we present the parametrization and benchmark of long-range corrected second-order density functional tight binding (DFTB), LC-DFTB2, for organic and biological molecules. The LC-DFTB2 model not only improves fundamental orbital energy gaps but also ameliorates the DFT self-interaction error and overpolarization problem, and further improves charge-transfer excited states significantly. Electronic parameters for the construction of the DFTB2 Hamiltonian as well as repulsive potentials were optimized for molecules containing C, H, N, and O chemical elements. We use a semiautomatic parametrization scheme based on a genetic algorithm. With the new parameters, LC-DFTB2 describes geometries and vibrational frequencies of organicmore » molecules similarly well as third-order DFTB3/3OB, the de facto standard parametrization based on a GGA functional. Finally, LC-DFTB2 performs well also for atomization and reaction energies, however, slightly less satisfactorily than DFTB3/3OB.« less

Studying the varied shapes of gold clusters by an elegant optimization algorithm that hybridizes the density functional tight-binding theory and the density functional theory

NASA Astrophysics Data System (ADS)

Yen, Tsung-Wen; Lim, Thong-Leng; Yoon, Tiem-Leong; Lai, S. K.

2017-11-01

We combined a new parametrized density functional tight-binding (DFTB) theory (Fihey et al. 2015) with an unbiased modified basin hopping (MBH) optimization algorithm (Yen and Lai 2015) and applied it to calculate the lowest energy structures of Au clusters. From the calculated topologies and their conformational changes, we find that this DFTB/MBH method is a necessary procedure for a systematic study of the structural development of Au clusters but is somewhat insufficient for a quantitative study. As a result, we propose an extended hybridized algorithm. This improved algorithm proceeds in two steps. In the first step, the DFTB theory is employed to calculate the total energy of the cluster and this step (through running DFTB/MBH optimization for given Monte-Carlo steps) is meant to efficiently bring the Au cluster near to the region of the lowest energy minimum since the cluster as a whole has explicitly considered the interactions of valence electrons with ions, albeit semi-quantitatively. Then, in the second succeeding step, the energy-minimum searching process will continue with a skilledly replacement of the energy function calculated by the DFTB theory in the first step by one calculated in the full density functional theory (DFT). In these subsequent calculations, we couple the DFT energy also with the MBH strategy and proceed with the DFT/MBH optimization until the lowest energy value is found. We checked that this extended hybridized algorithm successfully predicts the twisted pyramidal structure for the Au40 cluster and correctly confirms also the linear shape of C8 which our previous DFTB/MBH method failed to do so. Perhaps more remarkable is the topological growth of Aun: it changes from a planar (n =3-11) → an oblate-like cage (n =12-15) → a hollow-shape cage (n =16-18) and finally a pyramidal-like cage (n =19, 20). These varied forms of the cluster's shapes are consistent with those reported in the literature.

DFTB Parameters for the Periodic Table, Part 2: Energies and Energy Gradients from Hydrogen to Calcium.

PubMed

Oliveira, Augusto F; Philipsen, Pier; Heine, Thomas

2015-11-10

In the first part of this series, we presented a parametrization strategy to obtain high-quality electronic band structures on the basis of density-functional-based tight-binding (DFTB) calculations and published a parameter set called QUASINANO2013.1. Here, we extend our parametrization effort to include the remaining terms that are needed to compute the total energy and its gradient, commonly referred to as repulsive potential. Instead of parametrizing these terms as a two-body potential, we calculate them explicitly from the DFTB analogues of the Kohn-Sham total energy expression. This strategy requires only two further numerical parameters per element. Thus, the atomic configuration and four real numbers per element are sufficient to define the DFTB model at this level of parametrization. The QUASINANO2015 parameter set allows the calculation of energy, structure, and electronic structure of all systems composed of elements ranging from H to Ca. Extensive benchmarks show that the overall accuracy of QUASINANO2015 is comparable to that of well-established methods, including PM7 and hand-tuned DFTB parameter sets, while coverage of a much larger range of chemical systems is available.

Pressure-induced metallization of condensed phase β-HMX under shock loadings via molecular dynamics simulations in conjunction with multi-scale shock technique.

PubMed

Ge, Ni-Na; Wei, Yong-Kai; Zhao, Feng; Chen, Xiang-Rong; Ji, Guang-Fu

2014-07-01

The electronic structure and initial decomposition in high explosive HMX under conditions of shock loading are examined. The simulation is performed using quantum molecular dynamics in conjunction with multi-scale shock technique (MSST). A self-consistent charge density-functional tight-binding (SCC-DFTB) method is adapted. The results show that the N-N-C angle has a drastic change under shock wave compression along lattice vector b at shock velocity 11 km/s, which is the main reason that leads to an insulator-to-metal transition for the HMX system. The metallization pressure (about 130 GPa) of condensed-phase HMX is predicted firstly. We also detect the formation of several key products of condensed-phase HMX decomposition, such as NO2, NO, N2, N2O, H2O, CO, and CO2, and all of them have been observed in previous experimental studies. Moreover, the initial decomposition products include H2 due to the C-H bond breaking as a primary reaction pathway at extreme condition, which presents a new insight into the initial decomposition mechanism of HMX under shock loading at the atomistic level.

Generating Converged Accurate Free Energy Surfaces for Chemical Reactions with a Force-Matched Semiempirical Model.

PubMed

Kroonblawd, Matthew P; Pietrucci, Fabio; Saitta, Antonino Marco; Goldman, Nir

2018-04-10

We demonstrate the capability of creating robust density functional tight binding (DFTB) models for chemical reactivity in prebiotic mixtures through force matching to short time scale quantum free energy estimates. Molecular dynamics using density functional theory (DFT) is a highly accurate approach to generate free energy surfaces for chemical reactions, but the extreme computational cost often limits the time scales and range of thermodynamic states that can feasibly be studied. In contrast, DFTB is a semiempirical quantum method that affords up to a thousandfold reduction in cost and can recover DFT-level accuracy. Here, we show that a force-matched DFTB model for aqueous glycine condensation reactions yields free energy surfaces that are consistent with experimental observations of reaction energetics. Convergence analysis reveals that multiple nanoseconds of combined trajectory are needed to reach a steady-fluctuating free energy estimate for glycine condensation. Predictive accuracy of force-matched DFTB is demonstrated by direct comparison to DFT, with the two approaches yielding surfaces with large regions that differ by only a few kcal mol -1 .

Communication: Photoinduced carbon dioxide binding with surface-functionalized silicon quantum dots.

PubMed

Douglas-Gallardo, Oscar A; Sánchez, Cristián Gabriel; Vöhringer-Martinez, Esteban

2018-04-14

Nowadays, the search for efficient methods able to reduce the high atmospheric carbon dioxide concentration has turned into a very dynamic research area. Several environmental problems have been closely associated with the high atmospheric level of this greenhouse gas. Here, a novel system based on the use of surface-functionalized silicon quantum dots (sf-SiQDs) is theoretically proposed as a versatile device to bind carbon dioxide. Within this approach, carbon dioxide trapping is modulated by a photoinduced charge redistribution between the capping molecule and the silicon quantum dots (SiQDs). The chemical and electronic properties of the proposed SiQDs have been studied with a Density Functional Theory and Density Functional Tight-Binding (DFTB) approach along with a time-dependent model based on the DFTB framework. To the best of our knowledge, this is the first report that proposes and explores the potential application of a versatile and friendly device based on the use of sf-SiQDs for photochemically activated carbon dioxide fixation.

Communication: Photoinduced carbon dioxide binding with surface-functionalized silicon quantum dots

NASA Astrophysics Data System (ADS)

Douglas-Gallardo, Oscar A.; Sánchez, Cristián Gabriel; Vöhringer-Martinez, Esteban

2018-04-01

Nowadays, the search for efficient methods able to reduce the high atmospheric carbon dioxide concentration has turned into a very dynamic research area. Several environmental problems have been closely associated with the high atmospheric level of this greenhouse gas. Here, a novel system based on the use of surface-functionalized silicon quantum dots (sf-SiQDs) is theoretically proposed as a versatile device to bind carbon dioxide. Within this approach, carbon dioxide trapping is modulated by a photoinduced charge redistribution between the capping molecule and the silicon quantum dots (SiQDs). The chemical and electronic properties of the proposed SiQDs have been studied with a Density Functional Theory and Density Functional Tight-Binding (DFTB) approach along with a time-dependent model based on the DFTB framework. To the best of our knowledge, this is the first report that proposes and explores the potential application of a versatile and friendly device based on the use of sf-SiQDs for photochemically activated carbon dioxide fixation.

Nucleic acid reactivity : challenges for next-generation semiempirical quantum models

PubMed Central

Huang, Ming; Giese, Timothy J.; York, Darrin M.

2016-01-01

Semiempirical quantum models are routinely used to study mechanisms of RNA catalysis and phosphoryl transfer reactions using combined quantum mechanical/molecular mechanical methods. Herein, we provide a broad assessment of the performance of existing semiempirical quantum models to describe nucleic acid structure and reactivity in order to quantify their limitations and guide the development of next-generation quantum models with improved accuracy. Neglect of diatomic diffierential overlap (NDDO) and self-consistent density-functional tight-binding (SCC-DFTB) semiempirical models are evaluated against high-level quantum mechanical benchmark calculations for seven biologically important data sets. The data sets include: proton affinities, polarizabilities, nucleobase dimer interactions, dimethyl phosphate anion, nucleoside sugar and glycosidic torsion conformations, and RNA phosphoryl transfer model reactions. As an additional baseline, comparisons are made with several commonly used density-functional models, including M062X and B3LYP (in some cases with dispersion corrections). The results show that, among the semiempirical models examined, the AM1/d-PhoT model is the most robust at predicting proton affinities. AM1/d-PhoT and DFTB3-3ob/OPhyd reproduce the MP2 potential energy surfaces of 6 associative RNA phosphoryl transfer model reactions reasonably well. Further, a recently developed linear-scaling “modified divide-and-conquer” model exhibits the most accurate results for binding energies of both hydrogen bonded and stacked nucleobase dimers. The semiempirical models considered here are shown to underestimate the isotropic polarizabilities of neutral molecules by approximately 30%. The semiempirical models also fail to adequately describe torsion profiles within the dimethyl phosphate anion, the nucleoside sugar ring puckers, and the rotations about the nucleoside glycosidic bond. The modeling of pentavalent phosphorus, particularly with thio substitutions often used experimentally as mechanistic probes, was problematic for all of the models considered. Analysis of the strengths and weakness of the models suggest that the creation of robust next-generation models should emphasize the improvement of relative conformational energies and barriers, and nonbond interactions. PMID:25943338

Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids.

PubMed

Aradi, Bálint; Niklasson, Anders M N; Frauenheim, Thomas

2015-07-14

A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born-Oppenheimer molecular dynamics. For systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can be applied to a broad range of problems in materials science, chemistry, and biology.

Dissociation of polycyclic aromatic hydrocarbons: molecular dynamics studies

NASA Astrophysics Data System (ADS)

Simon, A.; Rapacioli, M.; Rouaut, G.; Trinquier, G.; Gadéa, F. X.

2017-03-01

We present dynamical studies of the dissociation of polycyclic aromatic hydrocarbon (PAH) radical cations in their ground electronic states with significant internal energy. Molecular dynamics simulations are performed, the electronic structure being described on-the-fly at the self-consistent-charge density functional-based tight binding (SCC-DFTB) level of theory. The SCC-DFTB approach is first benchmarked against DFT results. Extensive simulations are achieved for naphthalene , pyrene and coronene at several energies. Such studies enable one to derive significant trends on branching ratios, kinetics, structures and hints on the formation mechanism of the ejected neutral fragments. In particular, dependence of branching ratios on PAH size and energy were retrieved. The losses of H and C2H2 (recognized as the ethyne molecule) were identified as major dissociation channels. The H/C2H2 ratio was found to increase with PAH size and to decrease with energy. For , which is the most interesting PAH from the astrophysical point of view, the loss of H was found as the quasi-only channel for an internal energy of 30 eV. Overall, in line with experimental trends, decreasing the internal energy or increasing the PAH size will favour the hydrogen loss channels with respect to carbonaceous fragments. This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.

Spectral densities for Frenkel exciton dynamics in molecular crystals: A TD-DFTB approach

NASA Astrophysics Data System (ADS)

Plötz, Per-Arno; Megow, Jörg; Niehaus, Thomas; Kühn, Oliver

2017-02-01

Effects of thermal fluctuations on the electronic excitation energies and intermonomeric Coulomb couplings are investigated for a perylene-tetracarboxylic-diimide crystal. To this end, time dependent density functional theory based tight binding (TD-DFTB) in the linear response formulation is used in combination with electronic ground state classical molecular dynamics. As a result, a parametrized Frenkel exciton Hamiltonian is obtained, with the effect of exciton-vibrational coupling being described by spectral densities. Employing dynamically defined normal modes, these spectral densities are analyzed in great detail, thus providing insight into the effect of specific intramolecular motions on excitation energies and Coulomb couplings. This distinguishes the present method from approaches using fixed transition densities. The efficiency by which intramolecular contributions to the spectral density can be calculated is a clear advantage of this method as compared with standard TD-DFT.

An efficient method for quantum transport simulations in the time domain

NASA Astrophysics Data System (ADS)

Wang, Y.; Yam, C.-Y.; Frauenheim, Th.; Chen, G. H.; Niehaus, T. A.

2011-11-01

An approximate method based on adiabatic time dependent density functional theory (TDDFT) is presented, that allows for the description of the electron dynamics in nanoscale junctions under arbitrary time dependent external potentials. The density matrix of the device region is propagated according to the Liouville-von Neumann equation. The semi-infinite leads give rise to dissipative terms in the equation of motion which are calculated from first principles in the wide band limit. In contrast to earlier ab initio implementations of this formalism, the Hamiltonian is here approximated in the spirit of the density functional based tight-binding (DFTB) method. Results are presented for two prototypical molecular devices and compared to full TDDFT calculations. The temporal profile of the current traces is qualitatively well captured by the DFTB scheme. Steady state currents show considerable variations, both in comparison of approximate and full TDDFT, but also among TDDFT calculations with different basis sets.

Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmore » science, chemistry, and biology.« less

Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

DOE PAGES

Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

2015-06-26

A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmore » science, chemistry, and biology.« less

Parameterization of DFTB3/3OB for Sulfur and Phosphorus for Chemical and Biological Applications

PubMed Central

2015-01-01

We report the parametrization of the approximate density functional tight binding method, DFTB3, for sulfur and phosphorus. The parametrization is done in a framework consistent with our previous 3OB set established for O, N, C, and H, thus the resulting parameters can be used to describe a broad set of organic and biologically relevant molecules. The 3d orbitals are included in the parametrization, and the electronic parameters are chosen to minimize errors in the atomization energies. The parameters are tested using a fairly diverse set of molecules of biological relevance, focusing on the geometries, reaction energies, proton affinities, and hydrogen bonding interactions of these molecules; vibrational frequencies are also examined, although less systematically. The results of DFTB3/3OB are compared to those from DFT (B3LYP and PBE), ab initio (MP2, G3B3), and several popular semiempirical methods (PM6 and PDDG), as well as predictions of DFTB3 with the older parametrization (the MIO set). In general, DFTB3/3OB is a major improvement over the previous parametrization (DFTB3/MIO), and for the majority cases tested here, it also outperforms PM6 and PDDG, especially for structural properties, vibrational frequencies, hydrogen bonding interactions, and proton affinities. For reaction energies, DFTB3/3OB exhibits major improvement over DFTB3/MIO, due mainly to significant reduction of errors in atomization energies; compared to PM6 and PDDG, DFTB3/3OB also generally performs better, although the magnitude of improvement is more modest. Compared to high-level calculations, DFTB3/3OB is most successful at predicting geometries; larger errors are found in the energies, although the results can be greatly improved by computing single point energies at a high level with DFTB3 geometries. There are several remaining issues with the DFTB3/3OB approach, most notably its difficulty in describing phosphate hydrolysis reactions involving a change in the coordination number of the phosphorus, for which a specific parametrization (3OB/OPhyd) is developed as a temporary solution; this suggests that the current DFTB3 methodology has limited transferability for complex phosphorus chemistry at the level of accuracy required for detailed mechanistic investigations. Therefore, fundamental improvements in the DFTB3 methodology are needed for a reliable method that describes phosphorus chemistry without ad hoc parameters. Nevertheless, DFTB3/3OB is expected to be a competitive QM method in QM/MM calculations for studying phosphorus/sulfur chemistry in condensed phase systems, especially as a low-level method that drives the sampling in a dual-level QM/MM framework. PMID:24803865

Low-energy hydrogen uptake by small-cage C n and C n-1B fullerenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dominguez-Gutierrez, F. Javier; Krstic, Predrag S.; Irle, Stephan

We present a theoretical study of the hydrogen uptake capability of carbon fullerene cages Cn and their boron-doped heterofullerene equivalents C n-1B, with n = 20, 40, and 60, irradiated by hydrogen atoms in an impact energy range of 0.1–100 eV. In order to predict exohedral and endohedral hydrogen captures as well as the scattering probability of hydrogen for various cage types and sizes, we perform quantum-classical molecular dynamics (QCMD) calculations using the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. Maximum endohedral hydrogen capture probabilities of 20% for n = 60 and 14% for n = 40 are found at impact energiesmore » close to 15 eV for both C n and C n-1B systems. For n = 20, however, endohedral capture is observed at a maximum of 2%, while the exohedral capture reaches a maximum of 5% both at 15 eV. Similar results for the hydrogen capture are obtained by classical molecular dynamics based on the ReaxFF potential. Lastly, the stopping cross section per carbon atom from the QCMD simulations for all cage sizes displays a linear dependence on the projectile velocity with a threshold at 0.8 eV, and extrapolates well to the available theoretical data.« less

Low-energy hydrogen uptake by small-cage C n and C n-1B fullerenes

DOE PAGES

Dominguez-Gutierrez, F. Javier; Krstic, Predrag S.; Irle, Stephan; ...

2018-08-29

We present a theoretical study of the hydrogen uptake capability of carbon fullerene cages Cn and their boron-doped heterofullerene equivalents C n-1B, with n = 20, 40, and 60, irradiated by hydrogen atoms in an impact energy range of 0.1–100 eV. In order to predict exohedral and endohedral hydrogen captures as well as the scattering probability of hydrogen for various cage types and sizes, we perform quantum-classical molecular dynamics (QCMD) calculations using the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. Maximum endohedral hydrogen capture probabilities of 20% for n = 60 and 14% for n = 40 are found at impact energiesmore » close to 15 eV for both C n and C n-1B systems. For n = 20, however, endohedral capture is observed at a maximum of 2%, while the exohedral capture reaches a maximum of 5% both at 15 eV. Similar results for the hydrogen capture are obtained by classical molecular dynamics based on the ReaxFF potential. Lastly, the stopping cross section per carbon atom from the QCMD simulations for all cage sizes displays a linear dependence on the projectile velocity with a threshold at 0.8 eV, and extrapolates well to the available theoretical data.« less

Error estimates for (semi-)empirical dispersion terms and large biomacromolecules.

PubMed

Korth, Martin

2013-10-14

The first-principles modeling of biomaterials has made tremendous advances over the last few years with the ongoing growth of computing power and impressive developments in the application of density functional theory (DFT) codes to large systems. One important step forward was the development of dispersion corrections for DFT methods, which account for the otherwise neglected dispersive van der Waals (vdW) interactions. Approaches at different levels of theory exist, with the most often used (semi-)empirical ones based on pair-wise interatomic C6R(-6) terms. Similar terms are now also used in connection with semiempirical QM (SQM) methods and density functional tight binding methods (SCC-DFTB). Their basic structure equals the attractive term in Lennard-Jones potentials, common to most force field approaches, but they usually use some type of cutoff function to make the mixing of the (long-range) dispersion term with the already existing (short-range) dispersion and exchange-repulsion effects from the electronic structure theory methods possible. All these dispersion approximations were found to perform accurately for smaller systems, but error estimates for larger systems are very rare and completely missing for really large biomolecules. We derive such estimates for the dispersion terms of DFT, SQM and MM methods using error statistics for smaller systems and dispersion contribution estimates for the PDBbind database of protein-ligand interactions. We find that dispersion terms will usually not be a limiting factor for reaching chemical accuracy, though some force fields and large ligand sizes are problematic.

III-Nitride, SiC and Diamond Materials for Electronic Devices. Symposium Held April 8-12 1996, San Francisco, California, U.S.A. Volume 423.

DTIC Science & Technology

1996-12-01

gallium, nitrogen and gallium nitride structures. Thus it can be shown to be transferable and efficient for predictive molecular -dynamic simulations on...potentials and forces for the molecular dynamics simulations are derived by means of a density-functional based nonorthogonal tight-binding (DF-TB) scheme...LDA). Molecular -dynamics simulations for determining the different reconstructions of the SiC surface use the slab method (two-dimensional periodic

Improving intermolecular interactions in DFTB3 using extended polarization from chemical-potential equalization

PubMed Central

Christensen, Anders S.; Elstner, Marcus; Cui, Qiang

2015-01-01

Semi-empirical quantum mechanical methods traditionally expand the electron density in a minimal, valence-only electron basis set. The minimal-basis approximation causes molecular polarization to be underestimated, and hence intermolecular interaction energies are also underestimated, especially for intermolecular interactions involving charged species. In this work, the third-order self-consistent charge density functional tight-binding method (DFTB3) is augmented with an auxiliary response density using the chemical-potential equalization (CPE) method and an empirical dispersion correction (D3). The parameters in the CPE and D3 models are fitted to high-level CCSD(T) reference interaction energies for a broad range of chemical species, as well as dipole moments calculated at the DFT level; the impact of including polarizabilities of molecules in the parameterization is also considered. Parameters for the elements H, C, N, O, and S are presented. The Root Mean Square Deviation (RMSD) interaction energy is improved from 6.07 kcal/mol to 1.49 kcal/mol for interactions with one charged species, whereas the RMSD is improved from 5.60 kcal/mol to 1.73 for a set of 9 salt bridges, compared to uncorrected DFTB3. For large water clusters and complexes that are dominated by dispersion interactions, the already satisfactory performance of the DFTB3-D3 model is retained; polarizabilities of neutral molecules are also notably improved. Overall, the CPE extension of DFTB3-D3 provides a more balanced description of different types of non-covalent interactions than Neglect of Diatomic Differential Overlap type of semi-empirical methods (e.g., PM6-D3H4) and PBE-D3 with modest basis sets. PMID:26328834

Improving intermolecular interactions in DFTB3 using extended polarization from chemical-potential equalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christensen, Anders S., E-mail: andersx@chem.wisc.edu, E-mail: cui@chem.wisc.edu; Cui, Qiang, E-mail: andersx@chem.wisc.edu, E-mail: cui@chem.wisc.edu; Elstner, Marcus

Semi-empirical quantum mechanical methods traditionally expand the electron density in a minimal, valence-only electron basis set. The minimal-basis approximation causes molecular polarization to be underestimated, and hence intermolecular interaction energies are also underestimated, especially for intermolecular interactions involving charged species. In this work, the third-order self-consistent charge density functional tight-binding method (DFTB3) is augmented with an auxiliary response density using the chemical-potential equalization (CPE) method and an empirical dispersion correction (D3). The parameters in the CPE and D3 models are fitted to high-level CCSD(T) reference interaction energies for a broad range of chemical species, as well as dipole moments calculatedmore » at the DFT level; the impact of including polarizabilities of molecules in the parameterization is also considered. Parameters for the elements H, C, N, O, and S are presented. The Root Mean Square Deviation (RMSD) interaction energy is improved from 6.07 kcal/mol to 1.49 kcal/mol for interactions with one charged species, whereas the RMSD is improved from 5.60 kcal/mol to 1.73 for a set of 9 salt bridges, compared to uncorrected DFTB3. For large water clusters and complexes that are dominated by dispersion interactions, the already satisfactory performance of the DFTB3-D3 model is retained; polarizabilities of neutral molecules are also notably improved. Overall, the CPE extension of DFTB3-D3 provides a more balanced description of different types of non-covalent interactions than Neglect of Diatomic Differential Overlap type of semi-empirical methods (e.g., PM6-D3H4) and PBE-D3 with modest basis sets.« less

Generating Converged Accurate Free Energy Surfaces for Chemical Reactions with a Force-Matched Semiempirical Model

DOE PAGES

Kroonblawd, Matthew P.; Pietrucci, Fabio; Saitta, Antonino Marco; ...

2018-03-15

Here, we demonstrate the capability of creating robust density functional tight binding (DFTB) models for chemical reactivity in prebiotic mixtures through force matching to short time scale quantum free energy estimates. Molecular dynamics using density functional theory (DFT) is a highly accurate approach to generate free energy surfaces for chemical reactions, but the extreme computational cost often limits the time scales and range of thermodynamic states that can feasibly be studied. In contrast, DFTB is a semiempirical quantum method that affords up to a thousandfold reduction in cost and can recover DFT-level accuracy. Here, we show that a force-matched DFTBmore » model for aqueous glycine condensation reactions yields free energy surfaces that are consistent with experimental observations of reaction energetics. Convergence analysis reveals that multiple nanoseconds of combined trajectory are needed to reach a steady-fluctuating free energy estimate for glycine condensation. Predictive accuracy of force-matched DFTB is demonstrated by direct comparison to DFT, with the two approaches yielding surfaces with large regions that differ by only a few kcal mol –1.« less

Generating Converged Accurate Free Energy Surfaces for Chemical Reactions with a Force-Matched Semiempirical Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroonblawd, Matthew P.; Pietrucci, Fabio; Saitta, Antonino Marco

Here, we demonstrate the capability of creating robust density functional tight binding (DFTB) models for chemical reactivity in prebiotic mixtures through force matching to short time scale quantum free energy estimates. Molecular dynamics using density functional theory (DFT) is a highly accurate approach to generate free energy surfaces for chemical reactions, but the extreme computational cost often limits the time scales and range of thermodynamic states that can feasibly be studied. In contrast, DFTB is a semiempirical quantum method that affords up to a thousandfold reduction in cost and can recover DFT-level accuracy. Here, we show that a force-matched DFTBmore » model for aqueous glycine condensation reactions yields free energy surfaces that are consistent with experimental observations of reaction energetics. Convergence analysis reveals that multiple nanoseconds of combined trajectory are needed to reach a steady-fluctuating free energy estimate for glycine condensation. Predictive accuracy of force-matched DFTB is demonstrated by direct comparison to DFT, with the two approaches yielding surfaces with large regions that differ by only a few kcal mol –1.« less

Development of a Multicenter Density Functional Tight Binding Model for Plutonium Surface Hydriding.

PubMed

Goldman, Nir; Aradi, Bálint; Lindsey, Rebecca K; Fried, Laurence E

2018-05-08

We detail the creation of a multicenter density functional tight binding (DFTB) model for hydrogen on δ-plutonium, using a framework of new Slater-Koster interaction parameters and a repulsive energy based on the Chebyshev Interaction Model for Efficient Simulation (ChIMES), where two- and three-center atomic interactions are represented by linear combinations of Chebyshev polynomials. We find that our DFTB/ChIMES model yields a total electron density of states for bulk δ-Pu that compares well to that from Density Functional Theory, as well as to a grid of energy calculations representing approximate H 2 dissociation paths on the δ-Pu (100) surface. We then perform molecular dynamics simulations and minimum energy pathway calculations to determine the energetics of surface dissociation and subsurface diffusion on the (100) and (111) surfaces. Our approach allows for the efficient creation of multicenter repulsive energies with a relatively small investment in initial DFT calculations. Our efforts are particularly pertinent to studies that rely on quantum calculations for interpretation and validation, such as experimental determination of chemical reactivity both on surfaces and in condensed phases.

Shift-and-invert parallel spectral transformation eigensolver: Massively parallel performance for density-functional based tight-binding

DOE PAGES

Zhang, Hong; Zapol, Peter; Dixon, David A.; ...

2015-11-17

The Shift-and-invert parallel spectral transformations (SIPs), a computational approach to solve sparse eigenvalue problems, is developed for massively parallel architectures with exceptional parallel scalability and robustness. The capabilities of SIPs are demonstrated by diagonalization of density-functional based tight-binding (DFTB) Hamiltonian and overlap matrices for single-wall metallic carbon nanotubes, diamond nanowires, and bulk diamond crystals. The largest (smallest) example studied is a 128,000 (2000) atom nanotube for which ~330,000 (~5600) eigenvalues and eigenfunctions are obtained in ~190 (~5) seconds when parallelized over 266,144 (16,384) Blue Gene/Q cores. Weak scaling and strong scaling of SIPs are analyzed and the performance of SIPsmore » is compared with other novel methods. Different matrix ordering methods are investigated to reduce the cost of the factorization step, which dominates the time-to-solution at the strong scaling limit. As a result, a parallel implementation of assembling the density matrix from the distributed eigenvectors is demonstrated.« less

Shift-and-invert parallel spectral transformation eigensolver: Massively parallel performance for density-functional based tight-binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hong; Zapol, Peter; Dixon, David A.

The Shift-and-invert parallel spectral transformations (SIPs), a computational approach to solve sparse eigenvalue problems, is developed for massively parallel architectures with exceptional parallel scalability and robustness. The capabilities of SIPs are demonstrated by diagonalization of density-functional based tight-binding (DFTB) Hamiltonian and overlap matrices for single-wall metallic carbon nanotubes, diamond nanowires, and bulk diamond crystals. The largest (smallest) example studied is a 128,000 (2000) atom nanotube for which ~330,000 (~5600) eigenvalues and eigenfunctions are obtained in ~190 (~5) seconds when parallelized over 266,144 (16,384) Blue Gene/Q cores. Weak scaling and strong scaling of SIPs are analyzed and the performance of SIPsmore » is compared with other novel methods. Different matrix ordering methods are investigated to reduce the cost of the factorization step, which dominates the time-to-solution at the strong scaling limit. As a result, a parallel implementation of assembling the density matrix from the distributed eigenvectors is demonstrated.« less

Stability and electronic properties of oxygen-doped ZnS polytypes: DFTB study

NASA Astrophysics Data System (ADS)

Popov, Ilya S.; Vorokh, Andrey S.; Enyashin, Andrey N.

2018-06-01

Synthesis from aqueous solutions is an affordable method for fabrication of II-VI semiconductors. However, application of this method often imposes a disorder of crystal lattice, manifesting as a rich variety of polytypes arising from wurtzite and zinc blende phases. The origin of this disordering still remains debatable. Here, the influence of the most likely impurity at water environment - substitutional oxygen - on the polytypic equilibrium of zinc sulphide is studied by means of density-functional tight-binding method. According to calculations, the inclusion of such oxygen does not affect the polytypic equilibrium. Apart of thermodynamic stability, the electronic and elastic properties of ZnS polytypes are studied as the function of oxygen distribution.

Absorption of CO2 on Carbon-based Sensors: First-Principle Analysis

NASA Astrophysics Data System (ADS)

Tit, Nacir; Elezzi, Mohammed; Abdullah, Hasan; Bahlouli, Hocine; Yamani, Zain

We present first-principle investigation of the adsorption properties of CO and CO2 molecules on both graphene and carbon nano-tubes (CNTs) in presence of metal catalysis, mainly iron (Fe). The relaxations were carried out using the self-consistent-charge density-functional tight-binding (SCC-DFTB) code in neglect of heat effects. The results show the following: (1) Defected graphene is found to have high sensitivity and high selectivity towards chemisorption of CO molecules and weak physisorption with CO2 molecules. (2) In case of CNTs, the iron ``Fe'' catalyst plays an essential role in capturing CO2 molecules. The Fe ad-atoms on the surface of CNT introduce huge density of states at Fermi level, but the capture of CO2 molecules would reduce that density and consequently reduce conductivity and increase sensitivity. Concerning the selectivity, we have studied the sensitivity versus various gas molecules (such as: O2, N2, H2, H2O, and CO). Furthermore, to assess the effect of catalysis on sensitivity, we have studied the sensitivity of other metal catalysts (such as: Ni, Co, Ti, and Sc). We found that CNT-Fe is highly sensitive and selective towards detection of CO and CO2 molecules. CNT being conductive or semiconducting does not matter much on the adsorption properties.

The structure and stability of Si60 and Ge60 cages: a computational study.

PubMed

Chen, Zhongfang; Jiao, Haijun; Seifert, Gotthard; Horn, Anselm H C; Yu, Dengke; Clark, Tim; Thiel, Walter; von Ragué Schleyer, Paul

2003-06-01

Structural studies of fullerene-like Si(60) and Ge(60) cages using ab initio methods were augmented by density functional tight-binding molecular dynamics (DFTB-MD) simulations of finite temperature effects. Neither the perfect I(h) symmetry nor the distorted T(h) structures are true minima. The energies of both are high relative to distorted, lower symmetry minima, C(i) and T, respectively, which still preserve C(60)-type connectivity. Both Si(60) and Ge(60) favor C(i) symmetry cages in which Si and Ge vertexes exhibit either near-trigonal or pyramidal geometries. These structural variations imply significant reactivity differences between different positions. The small magnetic shielding effects (NICS) indicate that aromaticity is not important in these systems. The inorganic fullerene cages have lower stabilities compared with their carbon analogs. Si(60) is stable towards spontaneous disintegration up to 700 K according to DFTB-MD simulations, and thus has potential for experimental observation. In contrast, Ge(60) preserves its cage structure only up to 200 K. Copyright 2003 Wiley Periodicals, Inc. J Comput Chem 24: 948-953, 2003

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuechler, Erich R.; Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455-0431; Giese, Timothy J.

To better represent the solvation effects observed along reaction pathways, and of ionic species in general, a charge-dependent variable-radii smooth conductor-like screening model (VR-SCOSMO) is developed. This model is implemented and parameterized with a third order density-functional tight binding quantum model, DFTB3/3OB-OPhyd, a quantum method which was developed for organic and biological compounds, utilizing a specific parameterization for phosphate hydrolysis reactions. Unlike most other applications with the DFTB3/3OB model, an auxiliary set of atomic multipoles is constructed from the underlying DFTB3 density matrix which is used to interact the solute with the solvent response surface. The resulting method is variational,more » produces smooth energies, and has analytic gradients. As a baseline, a conventional SCOSMO model with fixed radii is also parameterized. The SCOSMO and VR-SCOSMO models shown have comparable accuracy in reproducing neutral-molecule absolute solvation free energies; however, the VR-SCOSMO model is shown to reduce the mean unsigned errors (MUEs) of ionic compounds by half (about 2-3 kcal/mol). The VR-SCOSMO model presents similar accuracy as a charge-dependent Poisson-Boltzmann model introduced by Hou et al. [J. Chem. Theory Comput. 6, 2303 (2010)]. VR-SCOSMO is then used to examine the hydrolysis of trimethylphosphate and seven other phosphoryl transesterification reactions with different leaving groups. Two-dimensional energy landscapes are constructed for these reactions and calculated barriers are compared to those obtained from ab initio polarizable continuum calculations and experiment. Results of the VR-SCOSMO model are in good agreement in both cases, capturing the rate-limiting reaction barrier and the nature of the transition state.« less

Quantum Effects in Cation Interactions with First and Second Coordination Shell Ligands in Metalloproteins

PubMed Central

2015-01-01

Despite decades of investigations, the principal mechanisms responsible for the high affinity and specificity of proteins for key physiological cations K+, Na+, and Ca2+ remain a hotly debated topic. At the core of the debate is an apparent need (or lack thereof) for an accurate description of the electrostatic response of the charge distribution in a protein to the binding of an ion. These effects range from partial electronic polarization of the directly ligating atoms to long-range effects related to partial charge transfer and electronic delocalization effects. While accurate modeling of cation recognition by metalloproteins warrants the use of quantum-mechanics (QM) calculations, the most popular approximations used in major biomolecular simulation packages rely on the implicit modeling of electronic polarization effects. That is, high-level QM computations for ion binding to proteins are desirable, but they are often unfeasible, because of the large size of the reactive-site models and the need to sample conformational space exhaustively at finite temperature. Several solutions to this challenge have been proposed in the field, ranging from the recently developed Drude polarizable force-field for simulations of metalloproteins to approximate tight-binding density functional theory (DFTB). To delineate the usefulness of different approximations, we examined the accuracy of three recent and commonly used theoretical models and numerical algorithms, namely, CHARMM C36, the latest developed Drude polarizable force fields, and DFTB3 with the latest 3OB parameters. We performed MD simulations for 30 cation-selective proteins with high-resolution X-ray structures to create ensembles of structures for analysis with different levels of theory, e.g., additive and polarizable force fields, DFTB3, and DFT. The results from DFT computations were used to benchmark CHARMM C36, Drude, and DFTB3 performance. The explicit modeling of quantum effects unveils the key electrostatic properties of the protein sites and the importance of specific ion-protein interactions. One of the most interesting findings is that secondary coordination shells of proteins are noticeably perturbed in a cation-dependent manner, showing significant delocalization and long-range effects of charge transfer and polarization upon binding Ca2+. PMID:26574284

QM/MM free-energy simulations of reaction in Serratia marcescens Chitinase B reveal the protonation state of Asp142 and the critical role of Tyr214.

PubMed

Jitonnom, Jitrayut; Limb, Michael A L; Mulholland, Adrian J

2014-05-08

Serratia marcescens Chitinase B (ChiB), belonging to the glycosidase family 18 (GH18), catalyzes the hydrolysis of β-1,4-glycosidic bond, with retention of configuration, via an unusual substrate-assisted mechanism, in which the substrate itself acts as an intramolecular nucleophile. Here, both elementary steps (glycosylation and deglycosylation) of the ChiB-catalyzed reaction are investigated by means of combined quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics (MD) simulations at the SCC-DFTB/CHARMM22 level of theory. We examine the influence of the Asp142 protonation state on the reaction and the role that this residue performs in the reaction. Our simulations show that reaction with a neutral Asp142 is preferred and demonstrate that this residue provides electrostatic stabilization of the oxazolinium ion intermediate formed in the reaction. Insight into the conformational itinerary ((1,4)B↔(4)H5↔(4)C1) adopted by the substrate (bound in subsite -1) along the preferred reaction pathway is also provided by the simulations. The relative energies of the stationary points found along the reaction pathway calculated with SCC-DFTB and B3LYP were compared. The results suggest that SCC-DFTB is an accurate method for estimating the relative barriers for both steps of the reaction; however, it was found to overestimate the relative energy of an intermediate formed in the reaction when compared with the higher level of theory. Glycosylation is suggested to be a rate-determining step in the reaction with calculated overall reaction free-energy barrier of 20.5 kcal/mol, in a reasonable agreement with the 16.1 kcal/mol barrier derived from the experiment. The role of Tyr214 in catalysis was also investigated with the results, indicating that the residue plays a critical role in the deglycosylation step of the reaction. Simulations of the enzyme-product complex were also performed with an unbinding event suggested to have been observed, affording potential new mechanistic insight into the release of the product of ChiB.

Dynamical discrete/continuum linear response shells theory of solvation: convergence test for NH4+ and OH- ions in water solution using DFT and DFTB methods.

PubMed

de Lima, Guilherme Ferreira; Duarte, Hélio Anderson; Pliego, Josefredo R

2010-12-09

A new dynamical discrete/continuum solvation model was tested for NH(4)(+) and OH(-) ions in water solvent. The method is similar to continuum solvation models in a sense that the linear response approximation is used. However, different from pure continuum models, explicit solvent molecules are included in the inner shell, which allows adequate treatment of specific solute-solvent interactions present in the first solvation shell, the main drawback of continuum models. Molecular dynamics calculations coupled with SCC-DFTB method are used to generate the configurations of the solute in a box with 64 water molecules, while the interaction energies are calculated at the DFT level. We have tested the convergence of the method using a variable number of explicit water molecules and it was found that even a small number of waters (as low as 14) are able to produce converged values. Our results also point out that the Born model, often used for long-range correction, is not reliable and our method should be applied for more accurate calculations.

Phase transition, thermodynamics properties and IR spectrum of α- and γ-RDX: First principles and MD studies

NASA Astrophysics Data System (ADS)

Yuan, Jiaonan; Ji, Guangfu; Chen, Xiangrong; Wei, Dongqing; Zhao, Feng; Wu, Qiang

2016-01-01

In present letter, based on density functional theory plus dispersion (DFT-D) and a self-consistent charge density-functional tight-binding (SCC-DFTB) method, the structural and electronic properties are reported, and the phase transition are investigated by analyzing its thermodynamics properties and IR spectrum of RDX. The anisotropy of α- and γ-RDX were discussed at 0⿿10 GPa. By fitting the third-order Birch⿿Murnaghan equation of states, the bulk modulus and its pressure derivative of RDX were determined. The α-RDX phase is found stable at ambient condition, however, under pressures, both the values of lattice constants a, b, c and the οEvdw at around 4 GPa show abrupt changes which indicate a structural transition occurred. By analyzing the linear compressibility of a, b, c axes at 0⿿8 GPa, one clearly see that the molecules in α-RDX phase underwent rotations and translational motion to their position in the γ-RDX phase at about 4 GPa, which validates the α⿿γ phase transition. The IR spectra of α-form and γ-form RDX was calculated by analyzing the trajectory of molecules motion, which also show the phase transition from the spectra changes. Employing the quasi-harmonic Debye model, the enthalpy and specific heat were investigated at various pressures of both phases. The condition of equal enthalpies in both phases also indicates the phase transition of α-form to γ-form at around 4 GPa. The variation of specific heat with temperature approaches to the classical Dulong⿿Petit's law at high temperature, while at low-temperature it obeys the Debye's T3 law.

Anisotropic responses and initial decomposition of condensed-phase β-HMX under shock loadings via molecular dynamics simulations in conjunction with multiscale shock technique.

PubMed

Ge, Ni-Na; Wei, Yong-Kai; Song, Zhen-Fei; Chen, Xiang-Rong; Ji, Guang-Fu; Zhao, Feng; Wei, Dong-Qing

2014-07-24

Molecular dynamics simulations in conjunction with multiscale shock technique (MSST) are performed to study the initial chemical processes and the anisotropy of shock sensitivity of the condensed-phase HMX under shock loadings applied along the a, b, and c lattice vectors. A self-consistent charge density-functional tight-binding (SCC-DFTB) method was employed. Our results show that there is a difference between lattice vector a (or c) and lattice vector b in the response to a shock wave velocity of 11 km/s, which is investigated through reaction temperature and relative sliding rate between adjacent slipping planes. The response along lattice vectors a and c are similar to each other, whose reaction temperature is up to 7000 K, but quite different along lattice vector b, whose reaction temperature is only up to 4000 K. When compared with shock wave propagation along the lattice vectors a (18 Å/ps) and c (21 Å/ps), the relative sliding rate between adjacent slipping planes along lattice vector b is only 0.2 Å/ps. Thus, the small relative sliding rate between adjacent slipping planes results in the temperature and energy under shock loading increasing at a slower rate, which is the main reason leading to less sensitivity under shock wave compression along lattice vector b. In addition, the C-H bond dissociation is the primary pathway for HMX decomposition in early stages under high shock loading from various directions. Compared with the observation for shock velocities V(imp) = 10 and 11 km/s, the homolytic cleavage of N-NO2 bond was obviously suppressed with increasing pressure.

VR-SCOSMO: A smooth conductor-like screening model with charge-dependent radii for modeling chemical reactions.

PubMed

Kuechler, Erich R; Giese, Timothy J; York, Darrin M

2016-04-28

To better represent the solvation effects observed along reaction pathways, and of ionic species in general, a charge-dependent variable-radii smooth conductor-like screening model (VR-SCOSMO) is developed. This model is implemented and parameterized with a third order density-functional tight binding quantum model, DFTB3/3OB-OPhyd, a quantum method which was developed for organic and biological compounds, utilizing a specific parameterization for phosphate hydrolysis reactions. Unlike most other applications with the DFTB3/3OB model, an auxiliary set of atomic multipoles is constructed from the underlying DFTB3 density matrix which is used to interact the solute with the solvent response surface. The resulting method is variational, produces smooth energies, and has analytic gradients. As a baseline, a conventional SCOSMO model with fixed radii is also parameterized. The SCOSMO and VR-SCOSMO models shown have comparable accuracy in reproducing neutral-molecule absolute solvation free energies; however, the VR-SCOSMO model is shown to reduce the mean unsigned errors (MUEs) of ionic compounds by half (about 2-3 kcal/mol). The VR-SCOSMO model presents similar accuracy as a charge-dependent Poisson-Boltzmann model introduced by Hou et al. [J. Chem. Theory Comput. 6, 2303 (2010)]. VR-SCOSMO is then used to examine the hydrolysis of trimethylphosphate and seven other phosphoryl transesterification reactions with different leaving groups. Two-dimensional energy landscapes are constructed for these reactions and calculated barriers are compared to those obtained from ab initio polarizable continuum calculations and experiment. Results of the VR-SCOSMO model are in good agreement in both cases, capturing the rate-limiting reaction barrier and the nature of the transition state.

Bandgap engineering of GaN nanowires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ming, Bang-Ming; Yan, Hui; Wang, Ru-Zhi, E-mail: wrz@bjut.edu.cn, E-mail: yamcy@csrc.ac.cn

2016-05-15

Bandgap engineering has been a powerful technique for manipulating the electronic and optical properties of semiconductors. In this work, a systematic investigation of the electronic properties of [0001] GaN nanowires was carried out using the density functional based tight-binding method (DFTB). We studied the effects of geometric structure and uniaxial strain on the electronic properties of GaN nanowires with diameters ranging from 0.8 to 10 nm. Our results show that the band gap of GaN nanowires depends linearly on both the surface to volume ratio (S/V) and tensile strain. The band gap of GaN nanowires increases linearly with S/V, whilemore » it decreases linearly with increasing tensile strain. These linear relationships provide an effect way in designing GaN nanowires for their applications in novel nano-devices.« less

Intermolecular interactions in the condensed phase: Evaluation of semi-empirical quantum mechanical methods

NASA Astrophysics Data System (ADS)

Christensen, Anders S.; Kromann, Jimmy C.; Jensen, Jan H.; Cui, Qiang

2017-10-01

To facilitate further development of approximate quantum mechanical methods for condensed phase applications, we present a new benchmark dataset of intermolecular interaction energies in the solution phase for a set of 15 dimers, each containing one charged monomer. The reference interaction energy in solution is computed via a thermodynamic cycle that integrates dimer binding energy in the gas phase at the coupled cluster level and solute-solvent interaction with density functional theory; the estimated uncertainty of such calculated interaction energy is ±1.5 kcal/mol. The dataset is used to benchmark the performance of a set of semi-empirical quantum mechanical (SQM) methods that include DFTB3-D3, DFTB3/CPE-D3, OM2-D3, PM6-D3, PM6-D3H+, and PM7 as well as the HF-3c method. We find that while all tested SQM methods tend to underestimate binding energies in the gas phase with a root-mean-squared error (RMSE) of 2-5 kcal/mol, they overestimate binding energies in the solution phase with an RMSE of 3-4 kcal/mol, with the exception of DFTB3/CPE-D3 and OM2-D3, for which the systematic deviation is less pronounced. In addition, we find that HF-3c systematically overestimates binding energies in both gas and solution phases. As most approximate QM methods are parametrized and evaluated using data measured or calculated in the gas phase, the dataset represents an important first step toward calibrating QM based methods for application in the condensed phase where polarization and exchange repulsion need to be treated in a balanced fashion.

Ultrafast semi-metallic layer formation in detonating nitromethane

NASA Astrophysics Data System (ADS)

Reed, Evan; Manaa, M. Riad; Fried, Laurence; Glaesemann, Kurt; Joannopoulos, John

2008-03-01

We present the first quantum molecular dynamics simulations behind a detonation front (up to 0.2 ns) of the explosive nitromethane (CH3NO2) represented by the density-functional-based tight-binding method (DFTB). This simulation is enabled by our recently developed multi-scale shock wave molecular dynamics technique (MSST) that opens the door to longer duration simulations by several orders of magnitude. The electronic density of states around the Fermi energy initially increases as metastable material states are produced but then later decreases, perhaps unexpectedly. These changes indicate that the shock front is characterized by an increase in optical thickness and conductivity followed by a reduction around 100 picoseconds behind the front. We find that a significant population of intermediate metastable molecules are charged and charged species play an important role in the density of states evolution. The transient transformation to a semi-metallic state can be understood within the Anderson picture of metallization.

A semi-metallic layer in detonating nitromethane

NASA Astrophysics Data System (ADS)

Reed, Evan; Manaa, Riad; Fried, Laurence; Glaesemann, Kurt; Joannopoulos, John

2007-06-01

We present the first ever glimpse behind a detonation front in a chemically reactive quantum molecular dynamics simulation (up to 0.2 ns) of the explosive nitromethane (CH3NO2) represented by the density-functional-based tight-binding method (DFTB). This simulation is enabled by our recently developed multi-scale shock wave molecular dynamics technique (MSST) that opens the door to longer duration simulations by several orders of magnitude. The electronic DOS around the Fermi energy initially increases as metastable material states are produced but then later decreases, perhaps unexpectedly. These changes indicate that the shock front is characterized by an increase in optical thickness followed by a reduction in optical thickness hundreds of picoseconds behind the front, explaining recent experimental observations. We find that a significant population of intermediate metastable molecules are charged and charged species play an important role in the density of states evolution and a possible Mott metal-insulator transition.

A new efficient method for calculation of Frenkel exciton parameters in molecular aggregates

NASA Astrophysics Data System (ADS)

Plötz, Per-Arno; Niehaus, Thomas; Kühn, Oliver

2014-05-01

The Frenkel exciton Hamiltonian is at the heart of many simulations of excitation energy transfer in molecular aggregates. It separates the aggregate into Coulomb-coupled monomers. Here it is shown that the respective parameters, i.e., monomeric excitation energies and Coulomb couplings between transition densities can be efficiently calculated using time-dependent tight-binding-based density functional theory (TD-DFTB). Specifically, Coulomb couplings are expressed in terms of self-consistently determined Mulliken transition charges. The approach is applied to two dimer systems. First, formaldehyde oxime for which a detailed comparison with standard DFT using the B3LYP and the PBE functionals as well as with SCS-CC2 is provided. Second, the Coulomb coupling is explored in dependence on the intermolecular coordinates for a perylene bisimide dimer. This provides structural evidence for the previously observed biphasic aggregation behavior of this dye.

Computational predictions of the new Gallium nitride nanoporous structures

NASA Astrophysics Data System (ADS)

Lien, Le Thi Hong; Tuoc, Vu Ngoc; Duong, Do Thi; Thu Huyen, Nguyen

2018-05-01

Nanoporous structural prediction is emerging area of research because of their advantages for a wide range of materials science and technology applications in opto-electronics, environment, sensors, shape-selective and bio-catalysis, to name just a few. We propose a computationally and technically feasible approach for predicting Gallium nitride nanoporous structures with hollows at the nano scale. The designed porous structures are studied with computations using the density functional tight binding (DFTB) and conventional density functional theory methods, revealing a variety of promising mechanical and electronic properties, which can potentially find future realistic applications. Their stability is discussed by means of the free energy computed within the lattice-dynamics approach. Our calculations also indicate that all the reported hollow structures are wide band gap semiconductors in the same fashion with their parent’s bulk stable phase. The electronic band structures of these nanoporous structures are finally examined in detail.

Use of density functional theory method to calculate structures of neutral carbon clusters C{sub n} (3 ≤ n ≤ 24) and study their variability of structural forms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yen, T. W.; Lai, S. K., E-mail: sklai@coll.phy.ncu.edu.tw

2015-02-28

In this work, we present modifications to the well-known basin hopping (BH) optimization algorithm [D. J. Wales and J. P. Doye, J. Phys. Chem. A 101, 5111 (1997)] by incorporating in it the unique and specific nature of interactions among valence electrons and ions in carbon atoms through calculating the cluster’s total energy by the density functional tight-binding (DFTB) theory, using it to find the lowest energy structures of carbon clusters and, from these optimized atomic and electronic structures, studying their varied forms of topological transitions, which include a linear chain, a monocyclic to a polycyclic ring, and a fullerene/cage-likemore » geometry. In this modified BH (MBH) algorithm, we define a spatial volume within which the cluster’s lowest energy structure is to be searched, and introduce in addition a cut-and-splice genetic operator to increase the searching performance of the energy minimum than the original BH technique. The present MBH/DFTB algorithm is, therefore, characteristically distinguishable from the original BH technique commonly applied to nonmetallic and metallic clusters, technically more thorough and natural in describing the intricate couplings between valence electrons and ions in a carbon cluster, and thus theoretically sound in putting these two charged components on an equal footing. The proposed modified minimization algorithm should be more appropriate, accurate, and precise in the description of a carbon cluster. We evaluate the present algorithm, its energy-minimum searching in particular, by its optimization robustness. Specifically, we first check the MBH/DFTB technique for two representative carbon clusters of larger size, i.e., C{sub 60} and C{sub 72} against the popular cut-and-splice approach [D. M. Deaven and K. M. Ho, Phys. Rev. Lett. 75, 288 (1995)] that normally is combined with the genetic algorithm method for finding the cluster’s energy minimum, before employing it to investigate carbon clusters in the size range C{sub 3}-C{sub 24} studying their topological transitions. An effort was also made to compare our MBH/DFTB and its re-optimized results carried out by full density functional theory (DFT) calculations with some early DFT-based studies.« less

Assessing the Accuracy of Density Functional and Semiempirical Wave Function Methods for Water Nanoparticles: Comparing Binding and Relative Energies of (H2O)16 and (H2O)17 to CCSD(T) Results.

PubMed

Leverentz, Hannah R; Qi, Helena W; Truhlar, Donald G

2013-02-12

The binding energies and relative conformational energies of five configurations of the water 16-mer are computed using 61 levels of density functional (DF) theory, 12 methods combining DF theory with molecular mechanics damped dispersion (DF-MM), seven semiempirical-wave function (SWF) methods, and five methods combining SWF theory with molecular mechanics damped dispersion (SWF-MM). The accuracies of the computed energies are assessed by comparing them to recent high-level ab initio results; this assessment is more relevant to bulk water than previous tests on small clusters because a 16-mer is large enough to have water molecules that participate in more than three hydrogen bonds. We find that for water 16-mer binding energies the best DF, DF-MM, SWF, and SWF-MM methods (and their mean unsigned errors in kcal/mol) are respectively M06-2X (1.6), ωB97X-D (2.3), SCC-DFTB-γ(h) (35.2), and PM3-D (3.2). We also mention the good performance of CAM-B3LYP (1.8), M05-2X (1.9), and TPSSLYP (3.0). In contrast, for relative energies of various water nanoparticle 16-mer structures, the best methods (and mean unsigned errors in kcal/mol), in the same order of classes of methods, are SOGGA11-X (0.3), ωB97X-D (0.2), PM6 (0.4), and PMOv1 (0.6). We also mention the good performance of LC-ωPBE-D3 (0.3) and ωB97X (0.4). When both relative and binding energies are taken into consideration, the best methods overall (out of the 85 tested) are M05-2X without molecular mechanics and ωB97X-D when molecular mechanics corrections are included; with considerably higher average errors and considerably lower cost, the best SWF or SWF-MM method is PMOv1. We use six of the best methods for binding energies of the water 16-mers to calculate the binding energies of water hexamers and water 17-mers to test whether these methods are also reliable for binding energy calculations on other types of water clusters.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xingchen; Salahub, Dennis R.

There is no doubt that a huge gap exists in understanding heterogeneous catalysis between a cluster model of a few atoms and a bulk model of periodic slabs. Nanoparticles, which are crucial in heterogeneous catalysis in industry, lie in the middle of the gap. We present here our work on the computational modelling of molybdenum carbide nanoparticles (MCNPs) as the catalysts for the upgrading of oil sands in the in-situ environment, using benzene hydrogenation as a model reaction. With a cluster model, efforts were first made to understand the mechanism of the reaction with a density functional theory (DFT) studymore » on the adsorption of benzene and its hydrogenation product – cyclohexane, as well as the cyclic hydrogenation reaction intermediates on the Mo{sub 2}C(0001) surface. From the thermodynamic data, along with literature information, it was found that the benzene hydrogenation reaction on molybdenum carbide happens most likely through a Langmuir-Hinshelwood mechanism with the gradual lifting up of the benzene molecule. The electron localization function (ELF) was then used to help understand the nature of the interactions between the MCNPs, identifying strong multi-center interactions between the adsorbates and the MCNPs. To enable the treatment of larger nanoparticles, a fast semi-empirical density functional tight-binding (DFTB) method was parameterized. With this method, the potential energy profiles of benzene hydrogenation reactions on different sizes of MCNPs are calculated. The study was then extended to consider a MCNP embedded in solvent (benzene), using a quantum mechanical (DFTB) / molecular mechanical approach. Calculations on the free energies profiles with the umbrella sampling method show that the entropy of the MCNPs and the solvent are essential in understanding the catalytic activity of the transition metal related nanoparticles for solid/liquid heterogeneous catalysis.« less

Interaction energies for the purine inhibitor roscovitine with cyclin-dependent kinase 2: correlated ab initio quantum-chemical, DFT and empirical calculations.

PubMed

Dobes, Petr; Otyepka, Michal; Strnad, Miroslav; Hobza, Pavel

2006-05-24

The interaction between roscovitine and cyclin-dependent kinase 2 (cdk2) was investigated by performing correlated ab initio quantum-chemical calculations. The whole protein was fragmented into smaller systems consisting of one or a few amino acids, and the interaction energies of these fragments with roscovitine were determined by using the MP2 method with the extended aug-cc-pVDZ basis set. For selected complexes, the complete basis set limit MP2 interaction energies, as well as the coupled-cluster corrections with inclusion of single, double and noninteractive triples contributions [CCSD(T)], were also evaluated. The energies of interaction between roscovitine and small fragments and between roscovitine and substantial sections of protein (722 atoms) were also computed by using density-functional tight-binding methods covering dispersion energy (DFTB-D) and the Cornell empirical potential. Total stabilisation energy originates predominantly from dispersion energy and methods that do not account for the dispersion energy cannot, therefore, be recommended for the study of protein-inhibitor interactions. The Cornell empirical potential describes reasonably well the interaction between roscovitine and protein; therefore, this method can be applied in future thermodynamic calculations. A limited number of amino acid residues contribute significantly to the binding of roscovitine and cdk2, whereas a rather large number of amino acids make a negligible contribution.

Structural, electronic properties and stability of metatitanic acid (H 2TiO 3) nanotubes

NASA Astrophysics Data System (ADS)

Enyashin, A. N.; Denisova, T. A.; Ivanovskii, A. L.

2009-12-01

Quite recently, metatitanic acid (H 2TiO 3) has been successfully prepared, which extended the family of known titanic acids H 2Ti nO 2n+1 ( n = 2, 3 and 4). Here the atomic models for nanotubes (NTs) of metatitanic acid are designed and their cohesive and electronic properties are considered depending on their chirality and radii by means of density-functional theory-tight-binding (DFTB) method. Our main findings are that the proposed H 2TiO 3 tubes are stable and that all these NTs will be the insulators (independently from their chirality and the diameters) with forbidden gaps at about ˜4.6 eV. We have found also that aforementioned properties of predicted H 2TiO 3 NTs are very similar with those of recently prepared fabricated nanotubes of polytitanic acids; thus, it is possible to expect that the proposed H 2TiO 3 tubular materials may be fabricated.

Multi-level molecular modelling for plasma medicine

NASA Astrophysics Data System (ADS)

Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

2016-02-01

Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

Effects of oxidation on the plasmonic properties of aluminum nanoclusters.

PubMed

Douglas-Gallardo, Oscar A; Soldano, Germán J; Mariscal, Marcelo M; Sánchez, Cristián Gabriel

2017-11-16

The scouting of alternative plasmonic materials able to enhance and extend the optical properties of noble metal nanostructures is on the rise. Aluminum is endowed with a set of interesting properties which turn it into an attractive plasmonic material. Here we present the optical and electronic features of different aluminum nanostructures stemming from a multilevel computational study. Molecular Dynamics (MD) simulations using a reactive force field (ReaxFF), carefully validated with Density Functional Theory (DFT), were employed to mimic the oxidation of icosahedral aluminum nanoclusters. Resulting structures with different oxidation degrees were then studied through the Time-Dependent Density Functional Tight Binding (TD-DFTB) method. A similar approach was used in aluminum nanoclusters with a disordered structure to study how the loss of crystallinity affects the optical properties. To the best of our knowledge, this is the first report that addresses this issue from the fully atomistic time-dependent approach by means of two different and powerful simulation tools able to describe quantum and physicochemical properties associated with nanostructured particles.

Role of substrate dynamics in protein prenylation reactions.

PubMed

Chakravorty, Dhruva K; Merz, Kenneth M

2015-02-17

CONSPECTUS: The role dynamics plays in proteins is of intense contemporary interest. Fundamental insights into how dynamics affects reactivity and product distributions will facilitate the design of novel catalysts that can produce high quality compounds that can be employed, for example, as fuels and life saving drugs. We have used molecular dynamics (MD) methods and combined quantum mechanical/molecular mechanical (QM/MM) methods to study a series of proteins either whose substrates are too far away from the catalytic center or whose experimentally resolved substrate binding modes cannot explain the observed product distribution. In particular, we describe studies of farnesyl transferase (FTase) where the farnesyl pyrophosphate (FPP) substrate is ∼8 Å from the zinc-bound peptide in the active site of FTase. Using MD and QM/MM studies, we explain how the FPP substrate spans the gulf between it and the active site, and we have elucidated the nature of the transition state (TS) and offered an alternate explanation of experimentally observed kinetic isotope effects (KIEs). Our second story focuses on the nature of substrate dynamics in the aromatic prenyltransferase (APTase) protein NphB and how substrate dynamics affects the observed product distribution. Through the examples chosen we show the power of MD and QM/MM methods to provide unique insights into how protein substrate dynamics affects catalytic efficiency. We also illustrate how complex these reactions are and highlight the challenges faced when attempting to design de novo catalysts. While the methods used in our previous studies provided useful insights, several clear challenges still remain. In particular, we have utilized a semiempirical QM model (self-consistent charge density functional tight binding, SCC-DFTB) in our QM/MM studies since the problems we were addressing required extensive sampling. For the problems illustrated, this approach performed admirably (we estimate for these systems an uncertainty of ∼2 kcal/mol), but it is still a semiempirical model, and studies of this type would benefit greatly from more accurate ab initio or DFT models. However, the challenge with these methods is to reach the level of sampling needed to study systems where large conformational changes happen in the many nanoseconds to microsecond time regimes. Hence, how to couple expensive and accurate QM methods with sophisticated sampling algorithms is an important future challenge especially when large-scale studies of catalyst design become of interest. The use of MD and QM/MM models to elucidate enzyme catalytic pathways and to design novel catalytic agents is in its infancy but shows tremendous promise. While this Account summarizes where we have been, we also discuss briefly future directions that improve our fundamental ability to understand enzyme catalysis.

BH-DFTB/DFT calculations for iron clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aktürk, Abdurrahman; Sebetci, Ali, E-mail: asebetci@mevlana.edu.tr

2016-05-15

We present a study on the structural, electronic, and magnetic properties of Fe{sub n}(n  =  2  −  20) clusters by performing density functional tight binding (DFTB) calculations within a basin hopping (BH) global optimization search followed by density functional theory (DFT) investigations. The structures, total energies and total spin magnetic moments are calculated and compared with previously reported theoretical and experimental results. Two basis sets SDD with ECP and 6-31G** are employed in the DFT calculations together with BLYP GGA exchange-correlation functional. The results indicate that the offered BH-DFTB/DFT strategy collects all the global minima of which different minima havemore » been reported in the previous studies by different groups. Small Fe clusters have three kinds of packing; icosahedral (Fe{sub 9−13}), centered hexagonal antiprism (Fe{sub 14−17}, Fe{sub 20}), and truncated decahedral (Fe{sub 17(2)}, Fe{sub 18−19}). It is obtained in a qualitative agreement with the time of flight mass spectra that the magic numbers for the small Fe clusters are 7, 13, 15, and 19 and with the collision induced dissociation experiments that the sizes 6, 7, 13, 15, and 19 are thermodynamically more stable than their neighboring sizes. The spin magnetic moment per atom of Fe{sub n}(n = 2 − 20) clusters is between 2.4 and 3.6 μ{sub B} for the most of the sizes. The antiferromagnetic coupling between the central and the surface atoms of the Fe{sub 13} icosahedron, which have already been reported by experimental and theoretical studies, is verified by our calculations as well. The quantitative disagreements between the calculations and measurements of the magnetic moments of the individual sizes are still to be resolved.« less

Atomic scale behavior of oxygen-based radicals in water

NASA Astrophysics Data System (ADS)

Verlackt, C. C. W.; Neyts, E. C.; Bogaerts, A.

2017-03-01

Cold atmospheric pressure plasmas in and in contact with liquids represent a growing field of research for various applications. Understanding the interactions between the plasma generated species and the liquid is crucial. In this work we perform molecular dynamics (MD) simulations based on a quantum mechanical method, i.e. density-functional based tight-binding (DFTB), to examine the interactions of OH radicals and O atoms in bulk water. Our calculations reveal that the transport of OH radicals through water is not only governed by diffusion, but also by an equilibrium reaction of H-abstraction with water molecules. Furthermore, when two OH radicals encounter each other, they either form a stable cluster, or react, resulting in the formation of a new water molecule and an O atom. In addition, the O atoms form either oxywater (when in singlet configuration) or they remain stable in solution (when in triplet configuration), stressing the important role that O atoms can play in aqueous solution, and in contact with biomolecules. Our observations are in line with both experimental and ab initio results from the literature.

Influence of the aggregate state on band structure and optical properties of C60 computed with different methods

NASA Astrophysics Data System (ADS)

Pal, Amrita; Arabnejad, Saeid; Yamashita, Koichi; Manzhos, Sergei

2018-05-01

C60 and C60 based molecules are efficient acceptors and electron transport layers for planar perovskite solar cells. While properties of these molecules are well studied by ab initio methods, those of solid C60, specifically its optical absorption properties, are not. We present a combined density functional theory-Density Functional Tight Binding (DFTB) study of the effect of solid state packing on the band structure and optical absorption of C60. The valence and conduction band edge energies of solid C60 differ on the order of 0.1 eV from single molecule frontier orbital energies. We show that calculations of optical properties using linear response time dependent-DFT(B) or the imaginary part of the dielectric constant (dipole approximation) can result in unrealistically large redshifts in the presence of intermolecular interactions compared to available experimental data. We show that optical spectra computed from the frequency-dependent real polarizability can better reproduce the effect of C60 aggregation on optical absorption, specifically with a generalized gradient approximation functional, and may be more suited to study effects of molecular aggregation.

Fullerene-like Mo(W)(1-x)Re(x)S2 nanoparticles.

PubMed

Deepak, Francis Leonard; Popovitz-Biro, Ronit; Feldman, Yishay; Cohen, Hagai; Enyashin, Andrey; Seifert, Gotthard; Tenne, Reshef

2008-09-01

Inorganic fullerene-like (IF) Mo(1-x)Re(x)S(2) and W(1-x)Re(x)S(2) nanoparticles have been synthesized by a gas-phase reaction involving the respective metal halides with H(2)S. The IF-Mo(W)(1-x)Re(x)S(2) nanoparticles, containing up to 5 % Re, were characterized by a variety of experimental techniques. Analyses of the X-ray powder diffraction and different electron microscopy techniques show that the Re is doped in the MoS(2) host lattice. Interestingly, Re-doped MoS(2) nanotubes are present as well, although in small quantities ( approximately 5 %). XPS results confirm the nanoparticles to be more n-type arising from the effect of Re doping. Additionally, density-functional tight-binding (DFTB) calculations support the observed n-type behavior.

Simulations of the synthesis of boron-nitride nanostructures in a hot, high pressure gas volume† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc00667a

PubMed Central

Han, Longtao; Irle, Stephan; Nakai, Hiromi

2018-01-01

We performed nanosecond timescale computer simulations of clusterization and agglomeration processes of boron nitride (BN) nanostructures in hot, high pressure gas, starting from eleven different atomic and molecular precursor systems containing boron, nitrogen and hydrogen at various temperatures from 1500 to 6000 K. The synthesized BN nanostructures self-assemble in the form of cages, flakes, and tubes as well as amorphous structures. The simulations facilitate the analysis of chemical dynamics and we are able to predict the optimal conditions concerning temperature and chemical precursor composition for controlling the synthesis process in a high temperature gas volume, at high pressure. We identify the optimal precursor/temperature choices that lead to the nanostructures of highest quality with the highest rate of synthesis, using a novel parameter of the quality of the synthesis (PQS). Two distinct mechanisms of BN nanotube growth were found, neither of them based on the root-growth process. The simulations were performed using quantum-classical molecular dynamics (QCMD) based on the density-functional tight-binding (DFTB) quantum mechanics in conjunction with a divide-and-conquer (DC) linear scaling algorithm, as implemented in the DC-DFTB-K code, enabling the study of systems as large as 1300 atoms in canonical NVT ensembles for 1 ns time. PMID:29780513

Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1.

PubMed

Lee, Byung-Gil; Roig, Maurici B; Jansma, Marijke; Petela, Naomi; Metson, Jean; Nasmyth, Kim; Löwe, Jan

2016-03-08

Sister chromatid cohesion is mediated by cohesin, whose Smc1, Smc3, and kleisin (Scc1) subunits form a ring structure that entraps sister DNAs. The ring is opened either by separase, which cleaves Scc1 during anaphase, or by a releasing activity involving Wapl, Scc3, and Pds5, which bind to Scc1 and open its interface with Smc3. We present crystal structures of Pds5 from the yeast L. thermotolerans in the presence and absence of the conserved Scc1 region that interacts with Pds5. Scc1 binds along the spine of the Pds5 HEAT repeat fold and is wedged between the spine and C-terminal hook of Pds5. We have isolated mutants that confirm the observed binding mode of Scc1 and verified their effect on cohesin by immunoprecipitation and calibrated ChIP-seq. The Pds5 structure also reveals architectural similarities to Scc3, the other large HEAT repeat protein of cohesin and, most likely, Scc2. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Semi-empirical quantum evaluation of peptide - MHC class II binding

NASA Astrophysics Data System (ADS)

González, Ronald; Suárez, Carlos F.; Bohórquez, Hugo J.; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2017-01-01

Peptide presentation by the major histocompatibility complex (MHC) is a key process for triggering a specific immune response. Studying peptide-MHC (pMHC) binding from a structural-based approach has potential for reducing the costs of investigation into vaccine development. This study involved using two semi-empirical quantum chemistry methods (PM7 and FMO-DFTB) for computing the binding energies of peptides bonded to HLA-DR1 and HLA-DR2. We found that key stabilising water molecules involved in the peptide binding mechanism were required for finding high correlation with IC50 experimental values. Our proposal is computationally non-intensive, and is a reliable alternative for studying pMHC binding interactions.

Amino acid analogues bind to carbon nanotube via π-π interactions: Comparison of molecular mechanical and quantum mechanical calculations

NASA Astrophysics Data System (ADS)

Yang, Zaixing; Wang, Zhigang; Tian, Xingling; Xiu, Peng; Zhou, Ruhong

2012-01-01

Understanding the interaction between carbon nanotubes (CNTs) and biomolecules is essential to the CNT-based nanotechnology and biotechnology. Some recent experiments have suggested that the π-π stacking interactions between protein's aromatic residues and CNTs might play a key role in their binding, which raises interest in large scale modeling of protein-CNT complexes and associated π-π interactions at atomic detail. However, there is concern on the accuracy of classical fixed-charge molecular force fields due to their classical treatments and lack of polarizability. Here, we study the binding of three aromatic residue analogues (mimicking phenylalanine, tyrosine, and tryptophan) and benzene to a single-walled CNT, and compare the molecular mechanical (MM) calculations using three popular fixed-charge force fields (OPLSAA, AMBER, and CHARMM), with quantum mechanical (QM) calculations using the density-functional tight-binding method with the inclusion of dispersion correction (DFTB-D). Two typical configurations commonly found in π-π interactions are used, one with the aromatic rings parallel to the CNT surface (flat), and the other perpendicular (edge). Our calculations reveal that compared to the QM results the MM approaches can appropriately reproduce the strength of π-π interactions for both configurations, and more importantly, the energy difference between them, indicating that the various contributions to π-π interactions have been implicitly included in the van der Waals parameters of the standard MM force fields. Meanwhile, these MM models are less accurate in predicting the exact structural binding patterns (matching surface), meaning there are still rooms to be improved. In addition, we have provided a comprehensive and reliable QM picture for the π-π interactions of aromatic molecules with CNTs in gas phase, which might be used as a benchmark for future force field developments.

Amino acid analogues bind to carbon nanotube via π-π interactions: comparison of molecular mechanical and quantum mechanical calculations.

PubMed

Yang, Zaixing; Wang, Zhigang; Tian, Xingling; Xiu, Peng; Zhou, Ruhong

2012-01-14

Understanding the interaction between carbon nanotubes (CNTs) and biomolecules is essential to the CNT-based nanotechnology and biotechnology. Some recent experiments have suggested that the π-π stacking interactions between protein's aromatic residues and CNTs might play a key role in their binding, which raises interest in large scale modeling of protein-CNT complexes and associated π-π interactions at atomic detail. However, there is concern on the accuracy of classical fixed-charge molecular force fields due to their classical treatments and lack of polarizability. Here, we study the binding of three aromatic residue analogues (mimicking phenylalanine, tyrosine, and tryptophan) and benzene to a single-walled CNT, and compare the molecular mechanical (MM) calculations using three popular fixed-charge force fields (OPLSAA, AMBER, and CHARMM), with quantum mechanical (QM) calculations using the density-functional tight-binding method with the inclusion of dispersion correction (DFTB-D). Two typical configurations commonly found in π-π interactions are used, one with the aromatic rings parallel to the CNT surface (flat), and the other perpendicular (edge). Our calculations reveal that compared to the QM results the MM approaches can appropriately reproduce the strength of π-π interactions for both configurations, and more importantly, the energy difference between them, indicating that the various contributions to π-π interactions have been implicitly included in the van der Waals parameters of the standard MM force fields. Meanwhile, these MM models are less accurate in predicting the exact structural binding patterns (matching surface), meaning there are still rooms to be improved. In addition, we have provided a comprehensive and reliable QM picture for the π-π interactions of aromatic molecules with CNTs in gas phase, which might be used as a benchmark for future force field developments.

Signatures in vibrational and UV-visible absorption spectra for identifying cyclic hydrocarbons by graphene fragments.

PubMed

Meng, Yan; Wu, Qi; Chen, Lei; Wangmo, Sonam; Gao, Yang; Wang, Zhigang; Zhang, Rui-Qin; Ding, Dajun; Niehaus, Thomas A; Frauenheim, Thomas

2013-12-21

To promote possible applications of graphene in molecular identification based on stacking effects, in particular in recognizing aromatic amino acids and even sequencing nucleobases in life sciences, we comprehensively study the interaction between graphene segments and different cyclic organic hydrocarbons including benzene (C6H6), cyclohexane (C6H12), benzyne (C6H4), cyclohexene (C6H10), 1,3-cyclohexadiene (C6H8(1)) and 1,4-cyclohexadiene (C6H8(2)), using the density-functional tight-binding (DFTB) method. Interestingly, we find obviously different characteristics in Raman vibrational and ultraviolet visible absorption spectra of the small molecules adsorbed on the graphene sheet. Specifically, we find that both spectra involve clearly different characteristic peaks, belonging to the different small molecules upon adsorption, with the ones of ionized molecules being more substantial. Further analysis shows that the adsorptions are almost all due to the presence of dispersion energy in neutral cases and involve charge transfer from the graphene to the small molecules. In contrast, the main binding force in the ionic adsorption systems is the electronic interaction. The results present clear signatures that can be used to recognize different kinds of aromatic hydrocarbon rings on graphene sheets. We expect that our findings will be helpful for designing molecular recognition devices using graphene.

Structure and vibrational spectra of low-energy silicon clusters

NASA Astrophysics Data System (ADS)

Sieck, A.; Porezag, D.; Frauenheim, Th.; Pederson, M. R.; Jackson, K.

1997-12-01

We have identified low-energy structures of silicon clusters with 9 to 14 atoms using a nonorthogonal tight-binding method (TB) based on density-functional theory (DF). We have further investigated the resulting structures with an accurate all-electron first-principles technique. The results for cohesive energies, cluster geometries, and highest occupied to lowest unoccupied molecular orbital (HOMO-LUMO) gaps show an overall good agreement between DF-TB and self-consistent-field (SCF) DF theory. For Si9 and Si14, we have found equilibrium structures, whereas for Si11, Si12, and Si13, we present clusters with energies close to that of the corresponding ground-state structure recently proposed in the literature. The bonding scheme of clusters in this size range is different from the bulk tetrahedral symmetry. The most stable structures, characterized by low energies and large HOMO-LUMO gaps, have similar common subunits. To aid in their experimental identification, we have computed the full vibrational spectra of the structures, along with the Raman activities, IR intensities, and static polarizabilities, using SCF-DF theory within the local-density approximation (LDA). This method has already been successfully applied to the determination of Raman and IR spectra of silicon clusters with 3-8, 10, 13, 20, and 21 atoms.

Fluorescence photon migration techniques for the on-farm measurement of somatic cell count in fresh cow's milk

NASA Astrophysics Data System (ADS)

Khoo, Geoffrey; Kuennemeyer, Rainer; Claycomb, Rod W.

2005-04-01

Currently, the state of the art of mastitis detection in dairy cows is the laboratory-based measurement of somatic cell count (SCC), which is time consuming and expensive. Alternative, rapid, and reliable on-farm measurement methods are required for effective farm management. We have investigated whether fluorescence lifetime measurements can determine SCC in fresh, unprocessed milk. The method is based on the change in fluorescence lifetime of ethidium bromide when it binds to DNA from the somatic cells. Milk samples were obtained from a Fullwood Merlin Automated Milking System and analysed within a twenty-four hour period, over which the SCC does not change appreciably. For reference, the milk samples were also sent to a testing laboratory where the SCC was determined by traditional methods. The results show that we can quantify SCC using the fluorescence photon migration method from a lower bound of 4x105 cells mL-1 to an upper bound of 1 x 107 cells mL-1. The upper bound is due to the reference method used while the cause of the lower boundary is unknown, yet.

Dielectric response of molecules in empirical tight-binding theory

NASA Astrophysics Data System (ADS)

Boykin, Timothy B.; Vogl, P.

2002-01-01

In this paper we generalize our previous approach to electromagnetic interactions within empirical tight-binding theory to encompass molecular solids and isolated molecules. In order to guarantee physically meaningful results, we rederive the expressions for relevant observables using commutation relations appropriate to the finite tight-binding Hilbert space. In carrying out this generalization, we examine in detail the consequences of various prescriptions for the position and momentum operators in tight binding. We show that attempting to fit parameters of the momentum matrix directly generally results in a momentum operator which is incompatible with the underlying tight-binding model, while adding extra position parameters results in numerous difficulties, including the loss of gauge invariance. We have applied our scheme, which we term the Peierls-coupling tight-binding method, to the optical dielectric function of the molecular solid PPP, showing that this approach successfully predicts its known optical properties even in the limit of isolated molecules.

Multipolar Ewald Methods, 2: Applications Using a Quantum Mechanical Force Field

PubMed Central

2015-01-01

A fully quantum mechanical force field (QMFF) based on a modified “divide-and-conquer” (mDC) framework is applied to a series of molecular simulation applications, using a generalized Particle Mesh Ewald method extended to multipolar charge densities. Simulation results are presented for three example applications: liquid water, p-nitrophenylphosphate reactivity in solution, and crystalline N,N-dimethylglycine. Simulations of liquid water using a parametrized mDC model are compared to TIP3P and TIP4P/Ew water models and experiment. The mDC model is shown to be superior for cluster binding energies and generally comparable for bulk properties. Examination of the dissociative pathway for dephosphorylation of p-nitrophenylphosphate shows that the mDC method evaluated with the DFTB3/3OB and DFTB3/OPhyd semiempirical models bracket the experimental barrier, whereas DFTB2 and AM1/d-PhoT QM/MM simulations exhibit deficiencies in the barriers, the latter for which is related, in part, to the anomalous underestimation of the p-nitrophenylate leaving group pKa. Simulations of crystalline N,N-dimethylglycine are performed and the overall structure and atomic fluctuations are compared with the experiment and the general AMBER force field (GAFF). The QMFF, which was not parametrized for this application, was shown to be in better agreement with crystallographic data than GAFF. Our simulations highlight some of the application areas that may benefit from using new QMFFs, and they demonstrate progress toward the development of accurate QMFFs using the recently developed mDC framework. PMID:25691830

Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma.

PubMed

Babkair, Hamzah; Yamazaki, Manabu; Uddin, Md Shihab; Maruyama, Satoshi; Abé, Tatsuya; Essa, Ahmed; Sumita, Yoshimasa; Ahsan, Md Shahidul; Swelam, Wael; Cheng, Jun; Saku, Takashi

2016-11-01

We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Formulation and validation of a reduced order model of 2D materials exhibiting a two-phase microstructure as applied to graphene oxide

NASA Astrophysics Data System (ADS)

Benedetti, Ivano; Nguyen, Hoang; Soler-Crespo, Rafael A.; Gao, Wei; Mao, Lily; Ghasemi, Arman; Wen, Jianguo; Nguyen, SonBinh; Espinosa, Horacio D.

2018-03-01

Novel 2D materials, e.g., graphene oxide (GO), are attractive building blocks in the design of advanced materials due to their reactive chemistry, which can enhance interfacial interactions while providing good in-plane mechanical properties. Recent studies have hypothesized that the randomly distributed two-phase microstructure of GO, which arises due to its oxidized chemistry, leads to differences in nano- vs meso-scale mechanical responses. However, this effect has not been carefully studied using molecular dynamics due to computational limitations. Herein, a continuum mechanics model, formulated based on density functional based tight binding (DFTB) constitutive results for GO nano-flakes, is establish for capturing the effect of oxidation patterns on the material mechanical properties. GO is idealized as a continuum heterogeneous two-phase material, where the mechanical response of each phase, graphitic and oxidized, is informed from DFTB simulations. A finite element implementation of the model is validated via MD simulations and then used to investigate the existence of GO representative volume elements (RVE). We find that for the studied GO, an RVE behavior arises for monolayer sizes in excess to 40 nm. Moreover, we reveal that the response of monolayers with two main different functional chemistries, epoxide-rich and hydroxyl-rich, present distinct differences in mechanical behavior. In addition, we explored the role of defect density in GO, and validate the applicability of the model to larger length scales by predicting membrane deflection behavior, in close agreement with previous experimental and theoretical observations. As such the work presents a reduced order modeling framework applicable in the study of mechanical properties and deformation mechanisms in 2D multiphase materials.

Tight-Binding study of Boron structures

NASA Astrophysics Data System (ADS)

McGrady, Joseph W.; Papaconstantopoulos, Dimitrios A.; Mehl, Michael J.

2014-10-01

We have performed Linearized Augmented Plane Wave (LAPW) calculations for five crystal structures (alpha, dhcp, sc, fcc, bcc) of Boron which we then fitted to a non-orthogonal tight-binding model following the Naval Research Laboratory Tight-Binding (NRL-TB) method. The predictions of the NRL-TB approach for complicated Boron structures such as R105 (or β-rhombohedral) and T190 are in agreement with recent first-principles calculations. Fully utilizing the computational speed of the NRL-TB method we calculated the energy differences of various structures, including those containing vacancies using supercells with up to 5000 atoms.

Hybrid molecular dynamics simulation for plasma induced damage analysis

NASA Astrophysics Data System (ADS)

Matsukuma, Masaaki

2016-09-01

In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam experiments. This observed damage profile dependence on species and substrate cannot be reproduced using classical MD simulations. While the Moliere potential is convenient to describe the interactions between halogens and other atoms, more accurate interatomic modeling such as DFTB method which takes the molecular orbitals into account should be utilized to make the simulations more realistic. Based on the simulations results, the damage formation scenario will be discussed.

SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas

PubMed Central

Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Adelmant, Guillaume; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M.; Pedamallu, Chandra Sekhar; DeLuca, David S.; Brooks, Angela N.; Wang, Su; Que, Jianwen; Rustgi, Anil K.; Wong, Kwok-kin; Ligon, Keith L.; Liu, X. Shirley; Marto, Jarrod A.; Meyerson, Matthew; Bass, Adam J.

2014-01-01

The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology. PMID:24590290

SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.

PubMed

Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Adelmant, Guillaume; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M; Pedamallu, Chandra Sekhar; DeLuca, David S; Brooks, Angela N; Wang, Su; Que, Jianwen; Rustgi, Anil K; Wong, Kwok-kin; Ligon, Keith L; Liu, X Shirley; Marto, Jarrod A; Meyerson, Matthew; Bass, Adam J

2014-04-01

The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.

Modeling electronic trap state distributions in nanocrystalline anatase

NASA Astrophysics Data System (ADS)

Le, Nam; Schweigert, Igor

The charge transport properties of nanocrystalline TiO2 films, and thus the catalytic performance of devices that incorporate them, are affected strongly by the spatial and energetic distribution of localized electronic trap states. Such traps may arise from a variety of defects: Ti interstitials, O vacancies, step edges at surfaces, and grain boundaries. We have developed a procedure for applying density functional theory (DFT) and density functional tight binding (DFTB) calculations to characterize distributions of localized states arising from multiple types of defects. We have applied the procedure to investigate how the morphologies of interfaces between pairs of attached anatase nanoparticles determine the energies of trap states therein. Our results complement recent experimental findings that subtle changes in the morphology of highly porous TiO2 aerogel networks can have a dramatic effect on catalytic performance, which was attributed to changes in the distribution of trap states. This work was supported by the U.S. Naval Research Laboratory via the National Research Council and by the Office of Naval Research through the U.S. Naval Research Laboratory.

Coaxial nanocable composed by imogolite and carbon nanotubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramírez, M.; González, R. I.; Munoz, F.

2015-12-31

The discovery and development of Carbon Nanotubes (CNTs) at the beginning of the 1990s has driven a major part of solid state research. The electronic properties of the CNTs have generated a large number of ideas, as building coaxial nanocables. In this work we propose a possible type of such nanocables, which is formed by three nanostructures: two conducting CNTs, where one of them is covered by an insulator (an inorganic oxide nanotube: the imogolite aluminosilicate). The theoretical calculations were carried out using the density functional tight-binding formalism, by means of the DFTB+ code. This formalism allows to calculate themore » band structure, which compares favorably with DFT calculations, but with a significantly lower computational cost. As a first step, we reproduce the calculations of already published results, where the formation of a nanocable composed by one CNT and the imogolite as an insulator. Afterwards, we simulate the band structure for the proposed structure to study the feasibility of the coaxial nanocable. Finally, using classical MD simulations, we study the possible mechanisms of formation of these nanocables.« less

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

PubMed Central

2012-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. Methods Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. Results Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. Conclusions These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver. PMID:22569330

Total-energy Assisted Tight-binding Method Based on Local Density Approximation of Density Functional Theory

NASA Astrophysics Data System (ADS)

Fujiwara, Takeo; Nishino, Shinya; Yamamoto, Susumu; Suzuki, Takashi; Ikeda, Minoru; Ohtani, Yasuaki

2018-06-01

A novel tight-binding method is developed, based on the extended Hückel approximation and charge self-consistency, with referring the band structure and the total energy of the local density approximation of the density functional theory. The parameters are so adjusted by computer that the result reproduces the band structure and the total energy, and the algorithm for determining parameters is established. The set of determined parameters is applicable to a variety of crystalline compounds and change of lattice constants, and, in other words, it is transferable. Examples are demonstrated for Si crystals of several crystalline structures varying lattice constants. Since the set of parameters is transferable, the present tight-binding method may be applicable also to molecular dynamics simulations of large-scale systems and long-time dynamical processes.

An ab initio study of the molecular properties of the propyne water hydrogen-bonded complex

NASA Astrophysics Data System (ADS)

Lopes, Kelson C.; Araújo, Regiane C. M. U.; Rusu, Victor H.; Ramos, Mozart N.

2007-05-01

We have employed ab initio MP2 and DFT/B3LYP calculations with the 6-31++G(d,p) basis set to obtain structural, electronic and vibrational properties of the H-bonded complex between propyne and water. This study has revealed that H 2O can doubly complex with propyne forming a quasi five-membered ring. The first complexation occurs through the hydrogen bond between the acid hydrogen of H 2O and the C tbnd C triple bond, whereas the second complexation involves the oxygen atom of H 2O and the in-plane hydrogen atom of the methyl group in propyne. Our calculations have shown that the H-bond lengths between H⋯π and O⋯HC) are 2.419 and 2.707 Å, respectively, employing the DFT/B3LYP calculation whereas the corresponding MP2 values are 2.373 and 2.651 Å. The binding energies including both BSSE and ZPE corrections are -6.16 and -6.72 kJ mol -1, respectively, using the DFT/B3LYP and MP2 calculations. For example, the O-H stretching frequencies of water are decreased by -60 and -29 cm -1 using the DFT/B3LYP calculation, whereas the bending frequency is increased by +15 cm -1. As expected, the infrared intensities for the stretching modes are increased after complexation, especially involving the O-H b bond forming the hydrogen bond with the C tbnd C triple bond.

New insights into cohesin loading.

PubMed

Litwin, Ireneusz; Wysocki, Robert

2018-02-01

Cohesin is a conserved, ring-shaped protein complex that encircles sister chromatids and ensures correct chromosome segregation during mitosis and meiosis. It also plays a crucial role in the regulation of gene expression, DNA condensation, and DNA repair through both non-homologous end joining and homologous recombination. Cohesins are spatiotemporally regulated by the Scc2-Scc4 complex which facilitates cohesin loading onto chromatin at specific chromosomal sites. Over the last few years, much attention has been paid to cohesin and cohesin loader as it became clear that even minor disruptions of these complexes may lead to developmental disorders and cancers. Here we summarize recent developments in the structure of Scc2-Scc4 complex, cohesin loading process, and mediators that determine the Scc2-Scc4 binding patterns to chromatin.

Microwave emulations and tight-binding calculations of transport in polyacetylene

NASA Astrophysics Data System (ADS)

Stegmann, Thomas; Franco-Villafañe, John A.; Ortiz, Yenni P.; Kuhl, Ulrich; Mortessagne, Fabrice; Seligman, Thomas H.

2017-01-01

A novel approach to investigate the electron transport of cis- and trans-polyacetylene chains in the single-electron approximation is presented by using microwave emulation measurements and tight-binding calculations. In the emulation we take into account the different electronic couplings due to the double bonds leading to coupled dimer chains. The relative coupling constants are adjusted by DFT calculations. For sufficiently long chains a transport band gap is observed if the double bonds are present, whereas for identical couplings no band gap opens. The band gap can be observed also in relatively short chains, if additional edge atoms are absent, which cause strong resonance peaks within the band gap. The experimental results are in agreement with our tight-binding calculations using the nonequilibrium Green's function method. The tight-binding calculations show that it is crucial to include third nearest neighbor couplings to obtain the gap in the cis-polyacetylene.

Cleavage of cohesin rings coordinates the separation of centrioles and chromatids.

PubMed

Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf

2011-07-10

Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.

The mannose 6-phosphate-binding sites of M6P/IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells

PubMed Central

Probst, Olivia C.; Karayel, Evren; Schida, Nicole; Nimmerfall, Elisabeth; Hehenberger, Elisabeth; Puxbaum, Verena; Mach, Lukas

2013-01-01

The M6P (mannose 6-phosphate)/IGF2R (insulin-like growth factor II receptor) interacts with a variety of factors that impinge on tumour invasion and metastasis. It has been shown that expression of wild-type M6P/IGF2R reduces the tumorigenic and invasive properties of receptor-deficient SCC-VII squamous cell carcinoma cells. We have now used mutant forms of M6P/IGF2R to assess the relevance of the different ligand-binding sites of the receptor for its biological activities in this cellular system. The results of the present study demonstrate that M6P/IGF2R does not require a functional binding site for insulin-like growth factor II for inhibition of anchorage-independent growth and matrix invasion by SCC-VII cells. In contrast, the simultaneous mutation of both M6P-binding sites is sufficient to impair all cellular functions of the receptor tested. These findings highlight that the interaction between M6P/IGF2R and M6P-modified ligands is not only important for intracellular accumulation of lysosomal enzymes and formation of dense lysosomes, but is also crucial for the ability of the receptor to suppress SCC-VII growth and invasion. The present study also shows that some of the biological activities of M6P/IGF2R in SCC-VII cells strongly depend on a functional M6P-binding site within domain 3, thus providing further evidence for the non-redundant cellular functions of the individual carbohydrate-binding domains of the receptor. PMID:23347038

Parametrization of DFTB3/3OB for Magnesium and Zinc for Chemical and Biological Applications

PubMed Central

2015-01-01

We report the parametrization of the approximate density functional theory, DFTB3, for magnesium and zinc for chemical and biological applications. The parametrization strategy follows that established in previous work that parametrized several key main group elements (O, N, C, H, P, and S). This 3OB set of parameters can thus be used to study many chemical and biochemical systems. The parameters are benchmarked using both gas-phase and condensed-phase systems. The gas-phase results are compared to DFT (mostly B3LYP), ab initio (MP2 and G3B3), and PM6, as well as to a previous DFTB parametrization (MIO). The results indicate that DFTB3/3OB is particularly successful at predicting structures, including rather complex dinuclear metalloenzyme active sites, while being semiquantitative (with a typical mean absolute deviation (MAD) of ∼3–5 kcal/mol) for energetics. Single-point calculations with high-level quantum mechanics (QM) methods generally lead to very satisfying (a typical MAD of ∼1 kcal/mol) energetic properties. DFTB3/MM simulations for solution and two enzyme systems also lead to encouraging structural and energetic properties in comparison to available experimental data. The remaining limitations of DFTB3, such as the treatment of interaction between metal ions and highly charged/polarizable ligands, are also discussed. PMID:25178644

Tight-binding calculation of single-band and generalized Wannier functions of graphene

NASA Astrophysics Data System (ADS)

Ribeiro, Allan Victor; Bruno-Alfonso, Alexys

Recent work has shown that a tight-binding approach associated with Wannier functions (WFs) provides an intuitive physical image of the electronic structure of graphene. Regarding the case of graphene, Marzari et al. displayed the calculated WFs and presented a comparison between the Wannier-interpolated bands and the bands generated by using the density-functional code. Jung and MacDonald provided a tight-binding model for the π-bands of graphene that involves maximally localized Wannier functions (MLWFs). The mixing of the bands yields better localized WFs. In the present work, the MLWFs of graphene are calculated by combining the Quantum-ESPRESSO code and tight-binding approach. The MLWFs of graphene are calculated from the Bloch functions obtained through a tight binding approach that includes interactions and overlapping obtained by partially fitting the DFT bands. The phase of the Bloch functions of each band is appropriately chosen to produce MLWFs. The same thing applies to the coefficients of their linear combination in the generalized case. The method allows for an intuitive understanding of the maximally localized WFs of graphene and shows excellent agreement with the literature. Moreover, it provides accurate results at reduced computational cost.

Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

PubMed

Annunziata, Clorinda; Pezzuto, Francesca; Greggi, Stefano; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

2018-03-31

Two recurrent mutations (-124 G > A and -146 G > A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position -124 or -146. TERT promoter was mutated at nucleotide -146 (G > A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (-124G > A or -146G > A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression. © 2018 UICC.

Molecular simulation of water and hydration effects in different environments: challenges and developments for DFTB based models.

PubMed

Goyal, Puja; Qian, Hu-Jun; Irle, Stephan; Lu, Xiya; Roston, Daniel; Mori, Toshifumi; Elstner, Marcus; Cui, Qiang

2014-09-25

We discuss the description of water and hydration effects that employs an approximate density functional theory, DFTB3, in either a full QM or QM/MM framework. The goal is to explore, with the current formulation of DFTB3, the performance of this method for treating water in different chemical environments, the magnitude and nature of changes required to improve its performance, and factors that dictate its applicability to reactions in the condensed phase in a QM/MM framework. A relatively minor change (on the scale of kBT) in the O-H repulsive potential is observed to substantially improve the structural properties of bulk water under ambient conditions; modest improvements are also seen in dynamic properties of bulk water. This simple change also improves the description of protonated water clusters, a solvated proton, and to a more limited degree, a solvated hydroxide. By comparing results from DFTB3 models that differ in the description of water, we confirm that proton transfer energetics are adequately described by the standard DFTB3/3OB model for meaningful mechanistic analyses. For QM/MM applications, a robust parametrization of QM-MM interactions requires an explicit consideration of condensed phase properties, for which an efficient sampling technique was developed recently and is reviewed here. The discussions help make clear the value and limitations of DFTB3 based simulations, as well as the developments needed to further improve the accuracy and transferability of the methodology.

Tight-binding calculation studies of vacancy and adatom defects in graphene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Wei; Lu, Wen-Cai; Zhang, Hong-Xing

2016-02-19

Computational studies of complex defects in graphene usually need to deal with a larger number of atoms than the current first-principles methods can handle. We show a recently developed three-center tight-binding potential for carbon is very efficient for large scale atomistic simulations and can accurately describe the structures and energies of various defects in graphene. Using the three-center tight-binding potential, we have systematically studied the stable structures and formation energies of vacancy and embedded-atom defects of various sizes up to 4 vacancies and 4 embedded atoms in graphene. In conclusion, our calculations reveal low-energy defect structures and provide a moremore » comprehensive understanding of the structures and stability of defects in graphene.« less

Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography

PubMed Central

Chen, Haojun; Tong, Xiao; Lang, Lixin; Jacobson, Orit; Yung, Bryant C.; Yang, Xiangyu; Bai, Ruiliang; Kiesewetter, Dale O.; Ma, Ying; Wu, Hua; Niu, Gang; Chen, Xiaoyuan

2017-01-01

Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Pswere overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis. PMID:28744320

Transferable tight-binding model for strained group IV and III-V materials and heterostructures

NASA Astrophysics Data System (ADS)

Tan, Yaohua; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

2016-07-01

It is critical to capture the effect due to strain and material interface for device level transistor modeling. We introduce a transferable s p3d5s* tight-binding model with nearest-neighbor interactions for arbitrarily strained group IV and III-V materials. The tight-binding model is parametrized with respect to hybrid functional (HSE06) calculations for varieties of strained systems. The tight-binding calculations of ultrasmall superlattices formed by group IV and group III-V materials show good agreement with the corresponding HSE06 calculations. The application of the tight-binding model to superlattices demonstrates that the transferable tight-binding model with nearest-neighbor interactions can be obtained for group IV and III-V materials.

Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition.

PubMed

Shen, Donglai; Skibbens, Robert V

2017-01-01

Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex.

Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition

PubMed Central

Shen, Donglai

2017-01-01

Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex. PMID:29186203

Regulation of transepithelial ion transport by intracellular calcium ions.

PubMed

Cuthbert, A W

1985-01-01

A photodynamic effect of erythrosine B on the basolateral surface of rat colon epithelium under short circuit conditions is described. The resulting irreversible increase in short circuit current was the result of electrogenic chloride secretion. The effect was dependent upon oxygen and calcium ions, and is probably due to the generation of singlet oxygen which then permeabilises the membranes to calcium. Half maximal activation of secretion in permeabilised preparations occurred at an external calcium concentration of 1 microM. In tight sodium transporting epithelia increased Cai reduces SCC, possibly by a direct effect on apical sodium permeability. In toad urinary bladder SCC fell in response to conditions outlined above for rat colon.

Nucleic acid reactivity: challenges for next-generation semiempirical quantum models.

PubMed

Huang, Ming; Giese, Timothy J; York, Darrin M

2015-07-05

Semiempirical quantum models are routinely used to study mechanisms of RNA catalysis and phosphoryl transfer reactions using combined quantum mechanical (QM)/molecular mechanical methods. Herein, we provide a broad assessment of the performance of existing semiempirical quantum models to describe nucleic acid structure and reactivity to quantify their limitations and guide the development of next-generation quantum models with improved accuracy. Neglect of diatomic differential overlap and self-consistent density-functional tight-binding semiempirical models are evaluated against high-level QM benchmark calculations for seven biologically important datasets. The datasets include: proton affinities, polarizabilities, nucleobase dimer interactions, dimethyl phosphate anion, nucleoside sugar and glycosidic torsion conformations, and RNA phosphoryl transfer model reactions. As an additional baseline, comparisons are made with several commonly used density-functional models, including M062X and B3LYP (in some cases with dispersion corrections). The results show that, among the semiempirical models examined, the AM1/d-PhoT model is the most robust at predicting proton affinities. AM1/d-PhoT and DFTB3-3ob/OPhyd reproduce the MP2 potential energy surfaces of 6 associative RNA phosphoryl transfer model reactions reasonably well. Further, a recently developed linear-scaling "modified divide-and-conquer" model exhibits the most accurate results for binding energies of both hydrogen bonded and stacked nucleobase dimers. The semiempirical models considered here are shown to underestimate the isotropic polarizabilities of neutral molecules by approximately 30%. The semiempirical models also fail to adequately describe torsion profiles for the dimethyl phosphate anion, the nucleoside sugar ring puckers, and the rotations about the nucleoside glycosidic bond. The modeling of pentavalent phosphorus, particularly with thio substitutions often used experimentally as mechanistic probes, was problematic for all of the models considered. Analysis of the strengths and weakness of the models suggests that the creation of robust next-generation models should emphasize the improvement of relative conformational energies and barriers, and nonbonded interactions. © 2015 Wiley Periodicals, Inc.

Structure of the Pds5-Scc1 Complex and Implications for Cohesin Function.

PubMed

Muir, Kyle W; Kschonsak, Marc; Li, Yan; Metz, Jutta; Haering, Christian H; Panne, Daniel

2016-03-08

Sister chromatid cohesion is a fundamental prerequisite to faithful genome segregation. Cohesion is precisely regulated by accessory factors that modulate the stability with which the cohesin complex embraces chromosomes. One of these factors, Pds5, engages cohesin through Scc1 and is both a facilitator of cohesion, and, conversely also mediates the release of cohesin from chromatin. We present here the crystal structure of a complex between budding yeast Pds5 and Scc1, thus elucidating the molecular basis of Pds5 function. Pds5 forms an elongated HEAT repeat that binds to Scc1 via a conserved surface patch. We demonstrate that the integrity of the Pds5-Scc1 interface is indispensable for the recruitment of Pds5 to cohesin, and that its abrogation results in loss of sister chromatid cohesion and cell viability. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Scattering matrix of arbitrary tight-binding Hamiltonians

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramírez, C., E-mail: carlos@ciencias.unam.mx; Medina-Amayo, L.A.

2017-03-15

A novel efficient method to calculate the scattering matrix (SM) of arbitrary tight-binding Hamiltonians is proposed, including cases with multiterminal structures. In particular, the SM of two kinds of fundamental structures is given, which can be used to obtain the SM of bigger systems iteratively. Also, a procedure to obtain the SM of layer-composed periodic leads is described. This method allows renormalization approaches, which permits computations over macroscopic length systems without introducing additional approximations. Finally, the transmission coefficient of a ring-shaped multiterminal system and the transmission function of a square-lattice nanoribbon with a reduced width region are calculated.

Spectroscopic (FT-IR, FT-Raman) and quantum mechanical studies of 3t-pentyl-2r,6c-diphenylpiperidin-4-one thiosemicarbazone

NASA Astrophysics Data System (ADS)

Savithiri, S.; Arockia doss, M.; Rajarajan, G.; Thanikachalam, V.; Bharanidharan, S.; Saleem, H.

2015-02-01

In this study, the molecular structure and vibrational spectra of 3t-pentyl2r,6c-diphenylpiperidin-4-one thiosemicarbazone (PDPOTSC) were studied. The ground-state molecular geometry was ascertained by using the density functional theory (DFT)/B3LYP method using 6-31++G(d,p) as a basis set. The vibrational (FT-IR and FT-Raman) spectra of PDPOTSC were computed using DFT/B3LYP and HF methods with 6-31++G(d,p) basis set. The fundamental vibrations were assigned on the basis of the total energy distribution (TED ⩾ 10%) of the vibrational modes, calculated with scaled quantum mechanics (SQM) methods PQS program. The electrical dipole moment (μ) and first hyperpolarizability (βo) values have been computed using DFT/B3LYP and HF methods. The calculated result (βo) shows that the title molecule might have nonlinear optical (NLO) behavior. Atomic charges of C, N, S and molecular electrostatic potential (MEP) were calculated using B3LYP/6-31G++(d,p). The HOMO-LUMO energies were calculated and natural bonding orbital (NBO) analysis has also been carried out.

Surface Passivation in Empirical Tight Binding

NASA Astrophysics Data System (ADS)

He, Yu; Tan, Yaohua; Jiang, Zhengping; Povolotskyi, Michael; Klimeck, Gerhard; Kubis, Tillmann

2016-03-01

Empirical Tight Binding (TB) methods are widely used in atomistic device simulations. Existing TB methods to passivate dangling bonds fall into two categories: 1) Method that explicitly includes passivation atoms is limited to passivation with atoms and small molecules only. 2) Method that implicitly incorporates passivation does not distinguish passivation atom types. This work introduces an implicit passivation method that is applicable to any passivation scenario with appropriate parameters. This method is applied to a Si quantum well and a Si ultra-thin body transistor oxidized with SiO2 in several oxidation configurations. Comparison with ab-initio results and experiments verifies the presented method. Oxidation configurations that severely hamper the transistor performance are identified. It is also shown that the commonly used implicit H atom passivation overestimates the transistor performance.

Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.

PubMed

Hasegawa, Mayumi; Cheng, Jun; Maruyama, Satoshi; Yamazaki, Manabu; Abé, Tatsuya; Babkair, Hamzah; Saito, Chikara; Saku, Takashi

2016-05-01

The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

The accuracy of quantum chemical methods for large noncovalent complexes

PubMed Central

Pitoňák, Michal; Řezáč, Jan; Pulay, Peter

2013-01-01

We evaluate the performance of the most widely used wavefunction, density functional theory, and semiempirical methods for the description of noncovalent interactions in a set of larger, mostly dispersion-stabilized noncovalent complexes (the L7 data set). The methods tested include MP2, MP3, SCS-MP2, SCS(MI)-MP2, MP2.5, MP2.X, MP2C, DFT-D, DFT-D3 (B3-LYP-D3, B-LYP-D3, TPSS-D3, PW6B95-D3, M06-2X-D3) and M06-2X, and semiempirical methods augmented with dispersion and hydrogen bonding corrections: SCC-DFTB-D, PM6-D, PM6-DH2 and PM6-D3H4. The test complexes are the octadecane dimer, the guanine trimer, the circumcoronene…adenine dimer, the coronene dimer, the guanine-cytosine dimer, the circumcoronene…guanine-cytosine dimer, and an amyloid fragment trimer containing phenylalanine residues. The best performing method is MP2.5 with relative root mean square deviation (rRMSD) of 4 %. It can thus be recommended as an alternative to the CCSD(T)/CBS (alternatively QCISD(T)/CBS) benchmark for molecular systems which exceed current computational capacity. The second best non-DFT method is MP2C with rRMSD of 8 %. A method with the most favorable “accuracy/cost” ratio belongs to the DFT family: BLYP-D3, with an rRMSD of 8 %. Semiempirical methods deliver less accurate results (the rRMSD exceeds 25 %). Nevertheless, their absolute errors are close to some much more expensive methods such as M06-2X, MP2 or SCS(MI)-MP2, and thus their price/performance ratio is excellent. PMID:24098094

Perfect transmission at oblique incidence by trigonal warping in graphene P-N junctions

NASA Astrophysics Data System (ADS)

Zhang, Shu-Hui; Yang, Wen

2018-01-01

We develop an analytical mode-matching technique for the tight-binding model to describe electron transport across graphene P-N junctions. This method shares the simplicity of the conventional mode-matching technique for the low-energy continuum model and the accuracy of the tight-binding model over a wide range of energies. It further reveals an interesting phenomenon on a sharp P-N junction: the disappearance of the well-known Klein tunneling (i.e., perfect transmission) at normal incidence and the appearance of perfect transmission at oblique incidence due to trigonal warping at energies beyond the linear Dirac regime. We show that this phenomenon arises from the conservation of a generalized pseudospin in the tight-binding model. We expect this effect to be experimentally observable in graphene and other Dirac fermions systems, such as the surface of three-dimensional topological insulators.

Design of graphene nanoparticle undergoing axial compression: quantum study

NASA Astrophysics Data System (ADS)

Glukhova, O. E.; Kirillova, I. V.; Saliy, I. N.; Kolesnikova, A. S.; Slepchenkov, M. M.

2011-03-01

We report the results of quantum mechanical investigations of the atomic structure and deformations of graphene nanoparticle undergoing axial compression. We applied the tight-binding (TB) method. Our transferable tightbinding potential correctly reproduced tight-binding changes in the electronic configuration as a function of the local bonding geometry around each carbon atom. The tight-binding method applied provided the consideration and calculation of the rehybridization between σ- and π-orbitals. To research nanoribbons using tight-binding potential our own program was used. We adapted TB method to be able to run the algorithm on a parallel computing machine (computer cluster). To simulate axial compression of graphene nanoparticles the atoms on the ends were fixed on the plates. The plates were moved towards each other to decrease the length at some percent. Plane atomic network undergoing axial compression became wave-like. The amplitude of wave and its period were not constant and changed along axis. This is a phase transition. The strain energy collapse occurs at the value of axial compression 0.03-0.04. The strain energy increased up to the quantity compression 0.03, then collapsed sharply and decreased. So according to our theoretical investigation, the elasticity of graphene nanoparticles is more than the elasticity of nanotubes the same width and length. The curvature of the atomic network because of compression will decrease the reactivity of graphene nanoparticles. We have calculated the atomic structure and electronic structure of the compression graphene nanopaticle at each step of strain of axial compression. We have come to the conclusion that the wave-like graphenes adsorbing protein and nucleic acid are the effective nanosensors and bionanosensors.

Scc2 regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis

PubMed Central

Lin, Weiqiang; Jin, Hui; Liu, Xiuwen; Hampton, Kristin; Yu, Hong-Guo

2011-01-01

To tether sister chromatids, a protein-loading complex, including Scc2, recruits cohesin to the chromosome at discrete loci. Cohesin facilitates the formation of a higher-order chromosome structure that could also influence gene expression. How cohesin directly regulates transcription remains to be further elucidated. We report that in budding yeast Scc2 is required for sister-chromatid cohesion during meiosis for two reasons. First, Scc2 is required for activating the expression of REC8, which encodes a meiosis-specific cohesin subunit; second, Scc2 is necessary for recruiting meiotic cohesin to the chromosome to generate sister-chromatid cohesion. Using a heterologous reporter assay, we have found that Scc2 increases the activity of its target promoters by recruiting cohesin to establish an upstream cohesin-associated region in a position-dependent manner. Rec8-associated meiotic cohesin is required for the full activation of the REC8 promoter, revealing that cohesin has a positive feedback on transcriptional regulation. Finally, we provide evidence that chromosomal binding of cohesin is sufficient for target-gene activation during meiosis. Our data support a noncanonical role for cohesin as a transcriptional activator during cell differentiation. PMID:21508318

Releasing the cohesin ring: A rigid scaffold model for opening the DNA exit gate by Pds5 and Wapl.

PubMed

Ouyang, Zhuqing; Yu, Hongtao

2017-04-01

The ring-shaped ATPase machine, cohesin, regulates sister chromatid cohesion, transcription, and DNA repair by topologically entrapping DNA. Here, we propose a rigid scaffold model to explain how the cohesin regulators Pds5 and Wapl release cohesin from chromosomes. Recent studies have established the Smc3-Scc1 interface as the DNA exit gate of cohesin, revealed a requirement for ATP hydrolysis in ring opening, suggested regulation of the cohesin ATPase activity by DNA and Smc3 acetylation, and provided insights into how Pds5 and Wapl open this exit gate. We hypothesize that Pds5, Wapl, and SA1/2 form a rigid scaffold that docks on Scc1 and anchors the N-terminal domain of Scc1 (Scc1N) to the Smc1 ATPase head. Relative movements between the Smc1-3 ATPase heads driven by ATP and Wapl disrupt the Smc3-Scc1 interface. Pds5 binds the dissociated Scc1N and prolongs this open state of cohesin, releasing DNA. We review the evidence supporting this model and suggest experiments that can further test its key principles. © 2017 WILEY Periodicals, Inc.

Tight-binding calculation of radiation loss in photonic crystal CROW.

PubMed

Ma, Jing; Martínez, Luis Javier; Fan, Shanhui; Povinelli, Michelle L

2013-01-28

The tight binding approximation (TBA) is used to relate the intrinsic, radiation loss of a coupled resonator optical waveguide (CROW) to that of a single constituent resonator within a light cone picture. We verify the validity of the TBA via direct, full-field simulation of CROWs based on the L2 photonic crystal cavity. The TBA predicts that the quality factor of the CROW increases with that of the isolated cavity. Moreover, our results provide a method to design CROWs with low intrinsic loss across the entire waveguide band.

Rapid calculation method for Frenkel-type two-exciton states in one to three dimensions

NASA Astrophysics Data System (ADS)

Ajiki, Hiroshi

2014-07-01

Biexciton and two-exciton dissociated states of Frenkel-type excitons are well described by a tight-binding model with a nearest-neighbor approximation. Such two-exciton states in a finite-size lattice are usually calculated by numerical diagonalization of the Hamiltonian, which requires an increasing amount of computational time and memory as the lattice size increases. I develop here a rapid, memory-saving method to calculate the energies and wave functions of two-exciton states by employing a bisection method. In addition, an attractive interaction between two excitons in the tight-binding model can be obtained directly so that the biexciton energy agrees with the observed energy, without the need for the trial-and-error procedure implemented in the numerical diagonalization method.

Eddy Current for Sizing Cracks in Canisters for Dry Storage of Used Nuclear Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Ryan M.; Jones, Anthony M.; Pardini, Allan F.

2014-01-01

The storage of used nuclear fuel (UNF) in dry canister storage systems (DCSSs) at Independent Spent Fuel Storage Installations (ISFSI) sites is a temporary measure to accommodate UNF inventory until it can be reprocessed or transferred to a repository for permanent disposal. Policy uncertainty surrounding the long-term management of UNF indicates that DCSSs will need to store UNF for much longer periods than originally envisioned. Meanwhile, the structural and leak-tight integrity of DCSSs must not be compromised. The eddy current technique is presented as a potential tool for inspecting the outer surfaces of DCSS canisters for degradation, particularly atmospheric stressmore » corrosion cracking (SCC). Results are presented that demonstrate that eddy current can detect flaws that cannot be detected reliably using standard visual techniques. In addition, simulations are performed to explore the best parameters of a pancake coil probe for sizing of SCC flaws in DCSS canisters and to identify features in frequency sweep curves that may potentially be useful for facilitating accurate depth sizing of atmospheric SCC flaws from eddy current measurements.« less

Estimation of radiative forcing and chore length of shallow convective clouds (SCC) based on broadband pyranometer measurement network

NASA Astrophysics Data System (ADS)

Shi, H.

2017-12-01

We presented a method to identify and calculate cloud radiative forcing (CRF) and horizontal chore length (L) of shallow convective clouds (SCC) using a network of 9 broadband pyranometers. The analyzing data was collected from the SCC campaign during two years summers (2015 2016) at Baiqi site over Inner Mongolia grassland. The network of pyranometers was operated across a spatial domain covering 42.16-42.30° N and 114.83-114.98° E. The SCC detection method was verified by observer reports and cameras, which showed that the detection method and human observations were in agreement about 75 %. The differences between the SCC detection method and human observations can be responsible for following factors: 1) small or dissipating clouds can be neglected for the value of 1 min of temporal resolution of pyranometer; 2) human observation recorded weather conditions four times every day; 3) SCC was indistinguishable from coexistence of SCC and Cirrus (Ci); 4) the SCC detection method is weighted toward clouds crossing the sun's path, while the human observer can view clouds over the entire sky. The deviation of L can be attributed to two factors: 1) the accuracy of wind speed at height of SCC and the ratio of horizontal and vertical length play a key role in determine values of L; 2) the effect of variance of solar zenith angle can be negligible. The downwelling shortwave CRF of SCC was -134.1 Wm-2. The average value of L of SCC was 1129 m. Besides, the distribution of normalized cloud chore length agreed well with power-law fit.

Tight-binding study of stacking fault energies and the Rice criterion of ductility in the fcc metals

NASA Astrophysics Data System (ADS)

Mehl, Michael J.; Papaconstantopoulos, Dimitrios A.; Kioussis, Nicholas; Herbranson, M.

2000-02-01

We have used the Naval Research Laboratory (NRL) tight-binding (TB) method to calculate the generalized stacking fault energy and the Rice ductility criterion in the fcc metals Al, Cu, Rh, Pd, Ag, Ir, Pt, Au, and Pb. The method works well for all classes of metals, i.e., simple metals, noble metals, and transition metals. We compared our results with full potential linear-muffin-tin orbital and embedded atom method (EAM) calculations, as well as experiment, and found good agreement. This is impressive, since the NRL-TB approach only fits to first-principles full-potential linearized augmented plane-wave equations of state and band structures for cubic systems. Comparable accuracy with EAM potentials can be achieved only by fitting to the stacking fault energy.

Tight-binding model for borophene and borophane

NASA Astrophysics Data System (ADS)

Nakhaee, M.; Ketabi, S. A.; Peeters, F. M.

2018-03-01

Starting from the simplified linear combination of atomic orbitals method in combination with first-principles calculations, we construct a tight-binding (TB) model in the two-centre approximation for borophene and hydrogenated borophene (borophane). The Slater and Koster approach is applied to calculate the TB Hamiltonian of these systems. We obtain expressions for the Hamiltonian and overlap matrix elements between different orbitals for the different atoms and present the SK coefficients in a nonorthogonal basis set. An anisotropic Dirac cone is found in the band structure of borophane. We derive a Dirac low-energy Hamiltonian and compare the Fermi velocities with that of graphene.

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break

PubMed Central

Lindgren, Emma; Hägg, Sara; Giordano, Fosco; Björkegren, Johan; Ström, Lena

2014-01-01

Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding. PMID:25483075

Communication: Charge-population based dispersion interactions for molecules and materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stöhr, Martin; Department Chemie, Technische Universität München, Lichtenbergstr. 4, D-85748 Garching; Michelitsch, Georg S.

2016-04-21

We introduce a system-independent method to derive effective atomic C{sub 6} coefficients and polarizabilities in molecules and materials purely from charge population analysis. This enables the use of dispersion-correction schemes in electronic structure calculations without recourse to electron-density partitioning schemes and expands their applicability to semi-empirical methods and tight-binding Hamiltonians. We show that the accuracy of our method is en par with established electron-density partitioning based approaches in describing intermolecular C{sub 6} coefficients as well as dispersion energies of weakly bound molecular dimers, organic crystals, and supramolecular complexes. We showcase the utility of our approach by incorporation of the recentlymore » developed many-body dispersion method [Tkatchenko et al., Phys. Rev. Lett. 108, 236402 (2012)] into the semi-empirical density functional tight-binding method and propose the latter as a viable technique to study hybrid organic-inorganic interfaces.« less

Universal Sign Control of Coupling in Tight-Binding Lattices

NASA Astrophysics Data System (ADS)

Keil, Robert; Poli, Charles; Heinrich, Matthias; Arkinstall, Jake; Weihs, Gregor; Schomerus, Henning; Szameit, Alexander

2016-05-01

We present a method of locally inverting the sign of the coupling term in tight-binding systems, by means of inserting a judiciously designed ancillary site and eigenmode matching of the resulting vertex triplet. Our technique can be universally applied to all lattice configurations, as long as the individual sites can be detuned. We experimentally verify this method in laser-written photonic lattices and confirm both the magnitude and the sign of the coupling by interferometric measurements. Based on these findings, we demonstrate how such universal sign-flipped coupling links can be embedded into extended lattice structures to impose a Z2-gauge transformation. This opens a new avenue for investigations on topological effects arising from magnetic fields with aperiodic flux patterns or in disordered systems.

Grain-Boundary Resistance in Copper Interconnects: From an Atomistic Model to a Neural Network

NASA Astrophysics Data System (ADS)

Valencia, Daniel; Wilson, Evan; Jiang, Zhengping; Valencia-Zapata, Gustavo A.; Wang, Kuang-Chung; Klimeck, Gerhard; Povolotskyi, Michael

2018-04-01

Orientation effects on the specific resistance of copper grain boundaries are studied systematically with two different atomistic tight-binding methods. A methodology is developed to model the specific resistance of grain boundaries in the ballistic limit using the embedded atom model, tight- binding methods, and nonequilibrium Green's functions. The methodology is validated against first-principles calculations for thin films with a single coincident grain boundary, with 6.4% deviation in the specific resistance. A statistical ensemble of 600 large, random structures with grains is studied. For structures with three grains, it is found that the distribution of specific resistances is close to normal. Finally, a compact model for grain-boundary-specific resistance is constructed based on a neural network.

Acceleration of Semiempirical QM/MM Methods through Message Passage Interface (MPI), Hybrid MPI/Open Multiprocessing, and Self-Consistent Field Accelerator Implementations.

PubMed

Ojeda-May, Pedro; Nam, Kwangho

2017-08-08

The strategy and implementation of scalable and efficient semiempirical (SE) QM/MM methods in CHARMM are described. The serial version of the code was first profiled to identify routines that required parallelization. Afterward, the code was parallelized and accelerated with three approaches. The first approach was the parallelization of the entire QM/MM routines, including the Fock matrix diagonalization routines, using the CHARMM message passage interface (MPI) machinery. In the second approach, two different self-consistent field (SCF) energy convergence accelerators were implemented using density and Fock matrices as targets for their extrapolations in the SCF procedure. In the third approach, the entire QM/MM and MM energy routines were accelerated by implementing the hybrid MPI/open multiprocessing (OpenMP) model in which both the task- and loop-level parallelization strategies were adopted to balance loads between different OpenMP threads. The present implementation was tested on two solvated enzyme systems (including <100 QM atoms) and an S N 2 symmetric reaction in water. The MPI version exceeded existing SE QM methods in CHARMM, which include the SCC-DFTB and SQUANTUM methods, by at least 4-fold. The use of SCF convergence accelerators further accelerated the code by ∼12-35% depending on the size of the QM region and the number of CPU cores used. Although the MPI version displayed good scalability, the performance was diminished for large numbers of MPI processes due to the overhead associated with MPI communications between nodes. This issue was partially overcome by the hybrid MPI/OpenMP approach which displayed a better scalability for a larger number of CPU cores (up to 64 CPUs in the tested systems).

Development of tight-binding based GW algorithm and its computational implementation for graphene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Majidi, Muhammad Aziz; NUSNNI-NanoCore, Department of Physics, National University of Singapore; Singapore Synchrotron Light Source

Graphene has been a hot subject of research in the last decade as it holds a promise for various applications. One interesting issue is whether or not graphene should be classified into a strongly or weakly correlated system, as the optical properties may change upon several factors, such as the substrate, voltage bias, adatoms, etc. As the Coulomb repulsive interactions among electrons can generate the correlation effects that may modify the single-particle spectra (density of states) and the two-particle spectra (optical conductivity) of graphene, we aim to explore such interactions in this study. The understanding of such correlation effects ismore » important because eventually they play an important role in inducing the effective attractive interactions between electrons and holes that bind them into excitons. We do this study theoretically by developing a GW method implemented on the basis of the tight-binding (TB) model Hamiltonian. Unlike the well-known GW method developed within density functional theory (DFT) framework, our TB-based GW implementation may serve as an alternative technique suitable for systems which Hamiltonian is to be constructed through a tight-binding based or similar models. This study includes theoretical formulation of the Green’s function G, the renormalized interaction function W from random phase approximation (RPA), and the corresponding self energy derived from Feynman diagrams, as well as the development of the algorithm to compute those quantities. As an evaluation of the method, we perform calculations of the density of states and the optical conductivity of graphene, and analyze the results.« less

Gaussian polarizable-ion tight binding.

PubMed

Boleininger, Max; Guilbert, Anne Ay; Horsfield, Andrew P

2016-10-14

To interpret ultrafast dynamics experiments on large molecules, computer simulation is required due to the complex response to the laser field. We present a method capable of efficiently computing the static electronic response of large systems to external electric fields. This is achieved by extending the density-functional tight binding method to include larger basis sets and by multipole expansion of the charge density into electrostatically interacting Gaussian distributions. Polarizabilities for a range of hydrocarbon molecules are computed for a multipole expansion up to quadrupole order, giving excellent agreement with experimental values, with average errors similar to those from density functional theory, but at a small fraction of the cost. We apply the model in conjunction with the polarizable-point-dipoles model to estimate the internal fields in amorphous poly(3-hexylthiophene-2,5-diyl).

Gaussian polarizable-ion tight binding

NASA Astrophysics Data System (ADS)

Boleininger, Max; Guilbert, Anne AY; Horsfield, Andrew P.

2016-10-01

To interpret ultrafast dynamics experiments on large molecules, computer simulation is required due to the complex response to the laser field. We present a method capable of efficiently computing the static electronic response of large systems to external electric fields. This is achieved by extending the density-functional tight binding method to include larger basis sets and by multipole expansion of the charge density into electrostatically interacting Gaussian distributions. Polarizabilities for a range of hydrocarbon molecules are computed for a multipole expansion up to quadrupole order, giving excellent agreement with experimental values, with average errors similar to those from density functional theory, but at a small fraction of the cost. We apply the model in conjunction with the polarizable-point-dipoles model to estimate the internal fields in amorphous poly(3-hexylthiophene-2,5-diyl).

Tight-binding tunneling amplitude of an optical lattice

NASA Astrophysics Data System (ADS)

Arzamasovs, Maksims; Liu, Bo

2017-11-01

The particle in a periodic potential is an important topic in an undergraduate quantum mechanics curriculum and a stepping stone on the way to more advanced topics, such as courses on interacting electrons in crystalline solids, and graduate-level research in solid-state and condensed matter physics. The interacting many-body phenomena are usually described in terms of the second quantized lattice Hamiltonians which treat single-particle physics on the level of tight-binding approximation and add interactions on top of it. The aim of this paper is to show how the tight-binding tunneling amplitude can be related to the strength of the periodic potential for the case of a cosine potential used in the burgeoning field of ultracold atoms. We show how to approach the problem of computing the tunneling amplitude of a deep lattice using the JWKB (Jeffreys-Wentzel-Kramers-Brillouin, also known as semiclassical) approximation. We also point out that care should be taken when applying the method of the linear combination of atomic orbitals (LCAO) in an optical lattice context. A summary of the exact solution in terms of Mathieu functions is also given.

Students Explaining Science--Assessment of Science Communication Competence

ERIC Educational Resources Information Center

Kulgemeyer, Christoph; Schecker, Horst

2013-01-01

Science communication competence (SCC) is an important educational goal in the school science curricula of several countries. However, there is a lack of research about the structure and the assessment of SCC. This paper specifies the theoretical framework of SCC by a competence model. We developed a qualitative assessment method for SCC that is…

Atomistic Simulations of Chemical Reactivity of TATB Under Thermal and Shock Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manaa, M R; Reed, E J; Fried, L E

2009-09-23

The study of chemical transformations that occur at the reactive shock front of energetic materials provides important information for the development of predictive models at the grain-and continuum scales. A major shortcoming of current high explosives models is the lack of chemical kinetics data of the reacting explosive in the high pressure and temperature regimes. In the absence of experimental data, long-time scale atomistic molecular dynamics simulations with reactive chemistry become a viable recourse to provide an insight into the decomposition mechanism of explosives, and to obtain effective reaction rate laws. These rates can then be incorporated into thermo-chemical-hydro codesmore » (such as Cheetah linked to ALE3D) for accurate description of the grain and macro scales dynamics of reacting explosives. In this talk, I will present quantum simulations of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) crystals under thermal decomposition (high density and temperature) and shock compression conditions. This is the first time that condensed phase quantum methods have been used to study the chemistry of insensitive high explosives. We used the quantum-based, self-consistent charge density functional tight binding method (SCC{_}DFTB) to calculate the interatomic forces for reliable predictions of chemical reactions, and to examine electronic properties at detonation conditions for a relatively long time-scale on the order of several hundreds of picoseconds. For thermal decomposition of TATB, we conducted constant volume-temperature simulations, ranging from 0.35 to 2 nanoseconds, at {rho} = 2.87 g/cm{sup 3} at T = 3500, 3000, 2500, and 1500 K, and {rho} = 2.9 g/cm{sup 3} and 2.72 g/cm{sup 3}, at T = 3000 K. We also simulated crystal TATB's reactivity under steady overdriven shock compression using the multi-scale shock technique. We conducted shock simulations with specified shock speeds of 8, 9, and 10 km/s for up to 0.43 ns duration, enabling us to track the reactivity of TATB well into the formation of several stable gas products, such as H{sub 2}O, N{sub 2}, and CO{sub 2}. Although complex chemical transformations are occurring continuously in the dynamical, high temperature, reactive environment of our simulations, a simple overall scheme for the decomposition of TATB emerges: Water is the earliest decomposition products to form, followed by a polymerization (or condensation) process in which several TATB remaining fragments are joined together, initiating the early step in the formation of high-nitrogen clusters, along with stable products such as N{sub 2} and CO{sub 2}. Remarkably, these clusters with high concentration of carbon and nitrogen (and little oxygen) remain dynamically stable for the remaining period of the simulations. Our simulations, thus, reveal a hitherto unidentified region of high concentrations of nitrogen-rich heterocyclic clusters in reacting TATB, whose persistence impede further reactivity towards final products of fluid N{sub 2} and solid carbon. These simulations also predict significant populations of charged species such as NCO{sup -}, H{sup +}, OH{sup -}, H{sub 3}O{sup +}, and O{sup -2}, the first such observation in a reacting explosive. Finally, A reduced four steps, global reaction mechanism with Arrhenius kinetic rates for the decomposition of TATB, along with comparative Cheetah decomposition kinetics at various temperatures has been constructed and will be discussed.« less

Mechanisms of single-walled carbon nanotube nucleation, growth, and healing determined using QM/MD methods.

PubMed

Page, Alister J; Ohta, Yasuhito; Irle, Stephan; Morokuma, Keiji

2010-10-19

Since their discovery in the early 1990s, single-walled carbon nanotubes (SWNTs) have spawned previously unimaginable commercial and industrial technologies. Their versatility stems from their unique electronic, physical/chemical, and mechanical properties, which set them apart from traditional materials. Many researchers have investigated SWNT growth mechanisms in the years since their discovery. The most prevalent of these is the vapor-liquid-solid (VLS) mechanism, which is based on experimental observations. Within the VLS mechanism, researchers assume that the formation of a SWNT starts with co-condensation of carbon and metal atoms from vapor to form liquid metal carbide. Once the liquid reaches supersaturation, the solid phase nanotubes begin to grow. The growth process is partitioned into three distinct stages: nucleation of a carbon "cap-precursor," "cap-to-tube" transformation, and continued SWNT growth. In recent years, molecular dynamics (MD) simulations have come to the fore with respect to SWNT growth. MD simulations lead to spatial and temporal resolutions of these processes that are superior to those possible using current experimental techniques, and so provide valuable information regarding the growth process that researchers cannot obtain experimentally. In this Account, we review our own recent efforts to simulate SWNT nucleation, growth, and healing phenomena on transition-metal catalysts using quantum mechanical molecular dynamics (QM/MD) methods. In particular, we have validated each stage of the SWNT condensation mechanism using a self-consistent-charge density-functional tight-binding (SCC-DFTB) methodology. With respect to the nucleation of a SWNT cap-precursor (stage 1), we have shown that the presence of a transition-metal carbide particle is not a necessary prerequisite for SWNT nucleation, contrary to conventional experimental presumptions. The formation and coalescence of polyyne chains on the metal surface occur first, followed by the formation of the SWNT cap-precursor, "ring condensation", and the creation of an sp(2)-hybridized carbon structure. In our simulations, the nucleation process takes approximately 400 ps. This first step occurs over a much longer time scale than the second stage of SWNT condensation (approximately 50 ps). We therefore observe SWNT nucleation to be akin to the rate-limiting step of the SWNT formation process. In addition to the QM/MD simulation of various stages of SWNT nucleation, growth, and healing processes, we have determined the effects of temperature, catalyst composition, and catalyst size on the kinetics and mechanism of SWNT growth. With respect to temperature dependence, we observe a "sweet-spot" with respect to the efficiency of SWNT growth. In addition, Ni-catalyzed SWNT growth is observed to be 70-100% faster compared to Fe-catalyzed SWNT growth, depending on the catalyst particle size. We also observe a noticeable increase in SWNT growth rates using smaller catalyst particles. Finally, we review our recent QM/MD investigation of SWNT healing. In particular, we recount mechanisms by which adatom defects, monovacancy defects, and a "5-7 defect" are removed from a nascent SWNT. The effectiveness of these healing mechanisms depends on the rate at which carbon moieties are incorporated into the growing SWNT. Explicitly, we observe that healing is promoted using a slower carbon supply rate. From this rudimentary control of SWNT healing, we propose a route towards chirality-controlled SWNT growth.

Compositional segmentation and complexity measurement in stock indices

NASA Astrophysics Data System (ADS)

Wang, Haifeng; Shang, Pengjian; Xia, Jianan

2016-01-01

In this paper, we introduce a complexity measure based on the entropic segmentation called sequence compositional complexity (SCC) into the analysis of financial time series. SCC was first used to deal directly with the complex heterogeneity in nonstationary DNA sequences. We already know that SCC was found to be higher in sequences with long-range correlation than those with low long-range correlation, especially in the DNA sequences. Now, we introduce this method into financial index data, subsequently, we find that the values of SCC of some mature stock indices, such as S & P 500 (simplified with S & P in the following) and HSI, are likely to be lower than the SCC value of Chinese index data (such as SSE). What is more, we find that, if we classify the indices with the method of SCC, the financial market of Hong Kong has more similarities with mature foreign markets than Chinese ones. So we believe that a good correspondence is found between the SCC of the index sequence and the complexity of the market involved.

Experimental study of optimal self compacting concrete with spent foundry sand as partial replacement for M-sand using Taguchi approach

NASA Astrophysics Data System (ADS)

Nirmala, D. B.; Raviraj, S.

2016-06-01

This paper presents the application of Taguchi approach to obtain optimal mix proportion for Self Compacting Concrete (SCC) containing spent foundry sand and M-sand. Spent foundry sand is used as a partial replacement for M-sand. The SCC mix has seven control factors namely, Coarse aggregate, M-sand with Spent Foundry sand, Cement, Fly ash, Water, Super plasticizer and Viscosity modifying agent. Modified Nan Su method is used to proportion the initial SCC mix. L18 (21×37) Orthogonal Arrays (OA) with the seven control factors having 3 levels is used in Taguchi approach which resulted in 18 SCC mix proportions. All mixtures are extensively tested both in fresh and hardened states to verify whether they meet the practical and technical requirements of SCC. The quality characteristics considering "Nominal the better" situation is applied to the test results to arrive at the optimal SCC mix proportion. Test results indicate that the optimal mix satisfies the requirements of fresh and hardened properties of SCC. The study reveals the feasibility of using spent foundry sand as a partial replacement of M-sand in SCC and also that Taguchi method is a reliable tool to arrive at optimal mix proportion of SCC.

TU-H-BRC-01: A New Fabrication Method for Secondary Skin Collimation Using 3D Scanner and 3D Printer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, J; Potter, N; Suh, T

Purpose: Using secondary skin collimation (SSC) to protect the critical organ surrounding the tumors is always desirable for electron and/or ortho-voltage treatments. However, the time-consuming and labor-intensive fabrication processes of current method (manually fabricate the lead mask) restrict the general use of SSC. The aim of this study is to develop a new SSC fabrication method using 3D scanning and 3D printing technologies in order to largely decrease the human labor involvement and fabrication time, also improve the fabrication accuracy. Methods: First, the patient surface was scanned with a 3D scanner (Structure Sensor, Occipital, CO). The raw scan data wasmore » subsequently transferred to a 3D modeling software (Rhinoceros, Ver. 5.0, McNeel North America, Seattle, WA). The tumor contour was then digitized and shielding region was determined by clinicians in the same software. The corresponding SCC conformed to the skin surface was then automatically generated by the software with the proper shielding thickness. The shell of the SCC (with hollow inside) was consequently printed by a 3D printer (Lulzbot TAZ, Aleph Objects, CO) using plastic material. Finally, the hollow mold of SCC was filled up with a melted cerrobend alloy. Once the cerrobend alloy cooled down, the fabrication of SCC was accomplished. Results: The results indicated the proposed method can achieve a much shorter time on making a SCC compared with tradition fabrication method. The processes of making a skin contour model for patients have been eliminated with the new method. SCC created by the new method possessed better accuracy and better conformality to patient’s skin contours. Conclusion: In this study, we have demonstrated a new method for the SCC fabrication. It is anticipated that our method can be an alternative way to replace conventional manual-based methods for electron and/or ortho-voltage SCC fabrication. This research was supported by the Global Ph.D. Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. 2015H1A2A1034071), Republic of Korea.« less

Comparison of conventional and self-consolidating concrete for drilled shaft construction.

DOT National Transportation Integrated Search

2015-04-01

Many entities currently use self-consolidating concrete (SCC), especially for drilled shaft construction. This project investigated the use of SCC : and various test methods to assess the suitability of SCC in underwater placement conditions. Eight m...

The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression

PubMed Central

Balda, Maria S.; Matter, Karl

2000-01-01

Epithelial tight junctions regulate paracellular diffusion and restrict the intermixing of apical and basolateral plasma membrane components. We now identify a Y-box transcription factor, ZONAB (ZO-1-associated nucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a submembrane protein of tight junctions. ZONAB localizes to the nucleus and at tight junctions, and binds to sequences of specific promoters containing an inverted CCAAT box. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manner. In stably transfected overexpressing cells, ZO-1 and ZONAB control expression of endogenous ErbB-2 and function in the regulation of paracellular permeability. These data indicate that tight junctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation. PMID:10790369

Electronic Coupling Calculations for Bridge-Mediated Charge Transfer Using Constrained Density Functional Theory (CDFT) and Effective Hamiltonian Approaches at the Density Functional Theory (DFT) and Fragment-Orbital Density Functional Tight Binding (FODFTB) Level

DOE PAGES

Gillet, Natacha; Berstis, Laura; Wu, Xiaojing; ...

2016-09-09

In this paper, four methods to calculate charge transfer integrals in the context of bridge-mediated electron transfer are tested. These methods are based on density functional theory (DFT). We consider two perturbative Green's function effective Hamiltonian methods (first, at the DFT level of theory, using localized molecular orbitals; second, applying a tight-binding DFT approach, using fragment orbitals) and two constrained DFT implementations with either plane-wave or local basis sets. To assess the performance of the methods for through-bond (TB)-dominated or through-space (TS)-dominated transfer, different sets of molecules are considered. For through-bond electron transfer (ET), several molecules that were originally synthesizedmore » by Paddon-Row and co-workers for the deduction of electronic coupling values from photoemission and electron transmission spectroscopies, are analyzed. The tested methodologies prove to be successful in reproducing experimental data, the exponential distance decay constant and the superbridge effects arising from interference among ET pathways. For through-space ET, dedicated p-stacked systems with heterocyclopentadiene molecules were created and analyzed on the basis of electronic coupling dependence on donor-acceptor distance, structure of the bridge, and ET barrier height. The inexpensive fragment-orbital density functional tight binding (FODFTB) method gives similar results to constrained density functional theory (CDFT) and both reproduce the expected exponential decay of the coupling with donor-acceptor distances and the number of bridging units. Finally, these four approaches appear to give reliable results for both TB and TS ET and present a good alternative to expensive ab initio methodologies for large systems involving long-range charge transfers.« less

Electronic Coupling Calculations for Bridge-Mediated Charge Transfer Using Constrained Density Functional Theory (CDFT) and Effective Hamiltonian Approaches at the Density Functional Theory (DFT) and Fragment-Orbital Density Functional Tight Binding (FODFTB) Level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillet, Natacha; Berstis, Laura; Wu, Xiaojing

In this paper, four methods to calculate charge transfer integrals in the context of bridge-mediated electron transfer are tested. These methods are based on density functional theory (DFT). We consider two perturbative Green's function effective Hamiltonian methods (first, at the DFT level of theory, using localized molecular orbitals; second, applying a tight-binding DFT approach, using fragment orbitals) and two constrained DFT implementations with either plane-wave or local basis sets. To assess the performance of the methods for through-bond (TB)-dominated or through-space (TS)-dominated transfer, different sets of molecules are considered. For through-bond electron transfer (ET), several molecules that were originally synthesizedmore » by Paddon-Row and co-workers for the deduction of electronic coupling values from photoemission and electron transmission spectroscopies, are analyzed. The tested methodologies prove to be successful in reproducing experimental data, the exponential distance decay constant and the superbridge effects arising from interference among ET pathways. For through-space ET, dedicated p-stacked systems with heterocyclopentadiene molecules were created and analyzed on the basis of electronic coupling dependence on donor-acceptor distance, structure of the bridge, and ET barrier height. The inexpensive fragment-orbital density functional tight binding (FODFTB) method gives similar results to constrained density functional theory (CDFT) and both reproduce the expected exponential decay of the coupling with donor-acceptor distances and the number of bridging units. Finally, these four approaches appear to give reliable results for both TB and TS ET and present a good alternative to expensive ab initio methodologies for large systems involving long-range charge transfers.« less

Electronic Coupling Calculations for Bridge-Mediated Charge Transfer Using Constrained Density Functional Theory (CDFT) and Effective Hamiltonian Approaches at the Density Functional Theory (DFT) and Fragment-Orbital Density Functional Tight Binding (FODFTB) Level.

PubMed

Gillet, Natacha; Berstis, Laura; Wu, Xiaojing; Gajdos, Fruzsina; Heck, Alexander; de la Lande, Aurélien; Blumberger, Jochen; Elstner, Marcus

2016-10-11

In this article, four methods to calculate charge transfer integrals in the context of bridge-mediated electron transfer are tested. These methods are based on density functional theory (DFT). We consider two perturbative Green's function effective Hamiltonian methods (first, at the DFT level of theory, using localized molecular orbitals; second, applying a tight-binding DFT approach, using fragment orbitals) and two constrained DFT implementations with either plane-wave or local basis sets. To assess the performance of the methods for through-bond (TB)-dominated or through-space (TS)-dominated transfer, different sets of molecules are considered. For through-bond electron transfer (ET), several molecules that were originally synthesized by Paddon-Row and co-workers for the deduction of electronic coupling values from photoemission and electron transmission spectroscopies, are analyzed. The tested methodologies prove to be successful in reproducing experimental data, the exponential distance decay constant and the superbridge effects arising from interference among ET pathways. For through-space ET, dedicated π-stacked systems with heterocyclopentadiene molecules were created and analyzed on the basis of electronic coupling dependence on donor-acceptor distance, structure of the bridge, and ET barrier height. The inexpensive fragment-orbital density functional tight binding (FODFTB) method gives similar results to constrained density functional theory (CDFT) and both reproduce the expected exponential decay of the coupling with donor-acceptor distances and the number of bridging units. These four approaches appear to give reliable results for both TB and TS ET and present a good alternative to expensive ab initio methodologies for large systems involving long-range charge transfers.

Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altamura, Gennaro, E-mail: gennaro.altamura@unina.it; Corteggio, Annunziata, E-mail: ancorteg@unina.it; Pacini, Laura, E-mail: PaciniL@students.iarc.fr

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting inmore » upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. - Highlights: • FcaPV2 E6 binds to and deregulates feline p53 protein. • FcaPV2 E7 binds to and deregulates feline pRb protein. • FcaPV2 oncogenes inhibit UVB-induced apoptosis. • FcaPV2 E6E7 and E7 increase the lifespan of primary cells. • FcaPV2 E2, E6 and E7 are expressed at the mRNA level in feline SCC in vivo.« less

The tightly bound nuclei in the liquid drop model

NASA Astrophysics Data System (ADS)

Sree Harsha, N. R.

2018-05-01

In this paper, we shall maximise the binding energy per nucleon function in the semi-empirical mass formula of the liquid drop model of the atomic nuclei to analytically prove that the mean binding energy per nucleon curve has local extrema at A ≈ 58.6960, Z ≈ 26.3908 and at A ≈ 62.0178, Z ≈ 27.7506. The Lagrange method of multipliers is used to arrive at these results, while we have let the values of A and Z take continuous fractional values. The shell model that shows why 62Ni is the most tightly bound nucleus is outlined. A brief account on stellar nucleosynthesis is presented to show why 56Fe is more abundant than 62Ni and 58Fe. We believe that the analytical proof presented in this paper can be a useful tool to the instructors to introduce the nucleus with the highest mean binding energy per nucleon.

Students Explaining Science—Assessment of Science Communication Competence

NASA Astrophysics Data System (ADS)

Kulgemeyer, Christoph; Schecker, Horst

2013-12-01

Science communication competence (SCC) is an important educational goal in the school science curricula of several countries. However, there is a lack of research about the structure and the assessment of SCC. This paper specifies the theoretical framework of SCC by a competence model. We developed a qualitative assessment method for SCC that is based on an expert-novice dialog: an older student (explainer, expert) explains a physics phenomenon to a younger peer (addressee, novice) in a controlled test setting. The explanations are video-recorded and analysed by qualitative content analysis. The method was applied in a study with 46 secondary school students as explainers. Our aims were (a) to evaluate whether our model covers the relevant features of SCC, (b) to validate the assessment method and (c) to find characteristics of addressee-adequate explanations. A performance index was calculated to quantify the explainers' levels of competence on an ordinal scale. We present qualitative and quantitative evidence that the index is adequate for assessment purposes. It correlates with results from a written SCC test and a perspective taking test (convergent validity). Addressee-adequate explanations can be characterized by use of graphical representations and deliberate switches between scientific and everyday language.

Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer?

PubMed Central

COGHILL, Anna E.; SHIELS, Meredith S.; RYCROFT, Randi K.; COPELAND, Glenn; FINCH, Jack L.; HAKENEWERTH, Anne M.; PAWLISH, Karen S.; ENGELS, Eric A.

2015-01-01

Objective Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people. Design Population-based registry Methods We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991–2010), to ascertain cases of anal SCC, rectal SCC, rectal non-SCC, and colon non-SCC. We compared risk in HIV-infected persons to the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases. Results HIV-infected persons had an excess risk of rectal SCC compared to the general population (SIR=28.9; 95%CI 23.2–35.6), similar to the increase for anal SCC (SIR=37.3). Excess rectal SCC risk was most pronounced among HIV-infected men who have sex with men (MSM, SIR=61.2). Risk was not elevated for rectal non-SCC (SIR=0.88) or colon non-SCC (SIR=0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio=1.86; 95%CI 1.04–3.31). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer. Conclusions HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumor location is needed to prove that rectal SCC is a distinct entity. PMID:26372482

Quantum chemical studies on structural, vibrational, nonlinear optical properties and chemical reactivity of indigo carmine dye

NASA Astrophysics Data System (ADS)

El-Mansy, M. A. M.

2017-08-01

Structural and vibrational spectroscopic studies were performed on indigo carmine (IC) isomers using FT-IR spectral analysis along with DFT/B3LYP method utilizing Gaussian 09 software. GaussView 5 program has been employed to perform a detailed interpretation of vibrational spectra. Simulation of infrared spectra has led to an excellent overall agreement with the observed spectral patterns. Mulliken population analyses on atomic charges, MEP, HOMO-LUMO, NLO, first order hyperpolarizability and thermodynamic properties have been examined by (DFT/B3LYP) method with the SDD basis set level. Density of state spectra (DOS) were calculated using GaussSum 3 at the same level of theory. Molecular modeling approved that DOS Spectra are the most significant tools for differentiating between two IC isomers so far. Moreover, The IC isomers (cis-isomer) have shown an extended applicability for manufacturing both NLO and photovoltaic devices such as solar cells.

SCCmecFinder, a Web-Based Tool for Typing of Staphylococcal Cassette Chromosome mec in Staphylococcus aureus Using Whole-Genome Sequence Data.

PubMed

Kaya, Hülya; Hasman, Henrik; Larsen, Jesper; Stegger, Marc; Johannesen, Thor Bech; Allesøe, Rosa Lundbye; Lemvigh, Camilla Koldbæk; Aarestrup, Frank Møller; Lund, Ole; Larsen, Anders Rhod

2018-01-01

Typing of methicillin-resistant Staphylococcus aureus (MRSA) is important in infection control and surveillance. The current nomenclature of MRSA includes the genetic background of the S. aureus strain determined by multilocus sequence typing (MLST) or equivalent methods like spa typing and typing of the mobile genetic element staphylococcal cassette chromosome mec (SCC mec ), which carries the mecA or mecC gene. Whereas MLST and spa typing are relatively simple, typing of SCC mec is less trivial because of its heterogeneity. Whole-genome sequencing (WGS) provides the essential data for typing of the genetic background and SCC mec , but so far, no bioinformatic tools for SCC mec typing have been available. Here, we report the development and evaluation of SCC mec Finder for characterization of the SCC mec element from S. aureus WGS data. SCC mec Finder is able to identify all SCC mec element types, designated I to XIII, with subtyping of SCC mec types IV (2B) and V (5C2). SCC mec elements are characterized by two different gene prediction approaches to achieve correct annotation, a Basic Local Alignment Search Tool (BLAST)-based approach and a k -mer-based approach. Evaluation of SCC mec Finder by using a diverse collection of clinical isolates ( n = 93) showed a high typeability level of 96.7%, which increased to 98.9% upon modification of the default settings. In conclusion, SCC mec Finder can be an alternative to more laborious SCC mec typing methods and is freely available at https://cge.cbs.dtu.dk/services/SCCmecFinder. IMPORTANCE SCC mec in MRSA is acknowledged to be of importance not only because it contains the mecA or mecC gene but also for staphylococcal adaptation to different environments, e.g., in hospitals, the community, and livestock. Typing of SCC mec by PCR techniques has, because of its heterogeneity, been challenging, and whole-genome sequencing has only partially solved this since no good bioinformatic tools have been available. In this article, we describe the development of a new bioinformatic tool, SCC mec Finder, that includes most of the needs for infection control professionals and researchers regarding the interpretation of SCC mec elements. The software detects all of the SCC mec elements accepted by the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements, and users will be prompted if diverging and potential new elements are uploaded. Furthermore, SCC mec Finder will be curated and updated as new elements are found and it is easy to use and freely accessible.

Molecular structure, FT IR, NMR, UV, NBO and HOMO-LUMO of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile by DFT/B3LYP and PBEPBE methods with LanL2DZ and 6-311 ++G(d,2p) basis sets

NASA Astrophysics Data System (ADS)

Khajehzadeh, Mostafa; Moghadam, Majid

2017-06-01

Structural and molecular properties of antidepressants 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile were examined using quantum mechanics of Density Functional Theory (DFT)/B3LYP and PBEPBE methods with 6-311 ++ G(d,2p) and LanL2DZ basis sets to study the therapeutic properties of the drug. For this, the structure of desired material was optimized by the computer calculation method and with the use of powerful Gaussian 09 software. Then the lowest energy value and the bond length, bond angle and dihedral angle between its constituent atoms in the crystal structure of the desired material were measured from the optimized values. Then the amount of positive and negative charges, polarizability and dipole moment of its atoms using Mulliken charge and Natural atomic charges, DFT/B3LYP and PBEPBE methods with 6-311 ++ G(d,2p) and LanL2DZ basis sets were determined and the results were compared with each other for individual atoms and by mentioned methods. Also the type of stretching vibrations and bending vibrations between the constituent atoms of the molecule were specified using mentioned computational methods and FT IR vibrational spectra. The experimental spectrum of this material was taken to determine the functional groups and the computational and experimental values were compared to each other and Nuclear Magnetic Resonance (NMR) was used to specify the isomer shift between the carbons and protons in the presence of polar and nonpolar solvents. Also Natural Bond Orbital (NBO) was used to determine the type of electron transfers in σ → σ ∗ and π → π ∗ and LP(1) → σ ∗ and LP(2) → σ ∗ and the amount of hardness and softness in molecule was determined using the difference between ionization energy and electron affinity energy in constituent atoms of that molecule in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and in the presence of solvents H2O, CH3CN and C6H12. UV-Vis spectrum of the drug was taken using DFT/B3LYP and PBEPBE methods with 6-311 ++ G(d,2p) and LanL2DZ basis sets as well as solvents H2O, CH3CN and C6H12 and the associated transmissions were examined.

Molecular recognition of pyr mRNA by the Bacillus subtilis attenuation regulatory protein PyrR

PubMed Central

Bonner, Eric R.; D’Elia, John N.; Billips, Benjamin K.; Switzer, Robert L.

2001-01-01

The pyrimidine nucleotide biosynthesis (pyr) operon in Bacillus subtilis is regulated by transcriptional attenuation. The PyrR protein binds in a uridine nucleotide-dependent manner to three attenuation sites at the 5′-end of pyr mRNA. PyrR binds an RNA-binding loop, allowing a terminator hairpin to form and repressing the downstream genes. The binding of PyrR to defined RNA molecules was characterized by a gel mobility shift assay. Titration indicated that PyrR binds RNA in an equimolar ratio. PyrR bound more tightly to the binding loops from the second (BL2 RNA) and third (BL3 RNA) attenuation sites than to the binding loop from the first (BL1 RNA) attenuation site. PyrR bound BL2 RNA 4–5-fold tighter in the presence of saturating UMP or UDP and 150- fold tighter with saturating UTP, suggesting that UTP is the more important co-regulator. The minimal RNA that bound tightly to PyrR was 28 nt long. Thirty-one structural variants of BL2 RNA were tested for PyrR binding affinity. Two highly conserved regions of the RNA, the terminal loop and top of the upper stem and a purine-rich internal bulge and the base pairs below it, were crucial for tight binding. Conserved elements of RNA secondary structure were also required for tight binding. PyrR protected conserved areas of the binding loop in hydroxyl radical footprinting experiments. PyrR likely recognizes conserved RNA sequences, but only if they are properly positioned in the correct secondary structure. PMID:11726695

The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast

PubMed Central

Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert

2017-01-01

Abstract Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. PMID:28383696

Extended Lagrangian formulation of charge-constrained tight-binding molecular dynamics.

PubMed

Cawkwell, M J; Coe, J D; Yadav, S K; Liu, X-Y; Niklasson, A M N

2015-06-09

The extended Lagrangian Born-Oppenheimer molecular dynamics formalism [Niklasson, Phys. Rev. Lett., 2008, 100, 123004] has been applied to a tight-binding model under the constraint of local charge neutrality to yield microcanonical trajectories with both precise, long-term energy conservation and a reduced number of self-consistent field optimizations at each time step. The extended Lagrangian molecular dynamics formalism restores time reversal symmetry in the propagation of the electronic degrees of freedom, and it enables the efficient and accurate self-consistent optimization of the chemical potential and atomwise potential energy shifts in the on-site elements of the tight-binding Hamiltonian that are required when enforcing local charge neutrality. These capabilities are illustrated with microcanonical molecular dynamics simulations of a small metallic cluster using an sd-valent tight-binding model for titanium. The effects of weak dissipation on the propagation of the auxiliary degrees of freedom for the chemical potential and on-site Hamiltonian matrix elements that is used to counteract the accumulation of numerical noise during trajectories was also investigated.

Molecular structure, natural bond analysis, vibrational and electronic spectra, surface enhanced Raman scattering and Mulliken atomic charges of the normal modes of [Mn(DDTC)2] complex.

PubMed

Téllez S, Claudio A; Costa, Anilton C; Mondragón, M A; Ferreira, Glaucio B; Versiane, O; Rangel, J L; Lima, G Müller; Martin, A A

2016-12-05

Theoretical and experimental bands have been assigned for the Fourier Transform Infrared and Raman spectra of the bis(diethyldithiocarbamate)Mn(II) complex, [Mn(DDTC)2]. The calculations have been based on the DFT/B3LYP method, second derivative spectra and band deconvolution analysis. The UV-vis experimental spectra were measured in acetonitrile solution, and the calculated electronic spectrum was obtained using the TD/B3LYP method with 6-311G(d, p) basis set for all atoms. Charge transfer bands and those d-d spin forbidden were assigned in the UV-vis spectrum. The natural bond orbital analysis was carried out using the DFT/B3LYP method and the Mn(II) hybridization leading to the planar geometry of the framework was discussed. Surface enhanced Raman scattering (SERS) was also performed. Mulliken charges of the normal modes were obtained and related to the SERS enhanced bands. Copyright © 2016 Elsevier B.V. All rights reserved.

Acene-modified triphenylamine dyes for dye-sensitized solar cells: a computational study.

PubMed

Fan, Wenjie; Tan, Dazhi; Deng, Wei-Qiao

2012-06-04

A series of metal-free acene-modified triphenylamine dyes (benzene to pentacene, denoted as TPA-AC1 to TPA-AC5) are investigated as organic sensitizers for application in dye-sensitized solar cells (DSSCs). A combination of density functional theory (DFT), density functional tight-binding (DFTB), and time-dependent DFT (TDDFT) approaches is employed. The effects of acene units on the spectra and electrochemical properties of the acene-modified TPA organic dyes are demonstrated. The dye/(TiO(2))(46) anatase nanoparticle systems are also simulated to show the electronic structures at the interface. The results show that from TPA-AC1 to TPA-AC5 with increasing sizes of the acenes, the absorption and fluorescence spectra are systematically broadened and red-shifted, but the oscillator strength and electron injection properties are reduced. The molecular orbital contributions show increasing localization on the bridging acene units from TPA-AC1 to TPA-AC5. From the theoretical examination of some key parameters including free enthalpy related to the electron injection, light-harvesting efficiency, and the shift of semiconductor conduction band, TPA-AC3 with an anthracene moiety demonstrates a balance of the above crucial factors. TPA-AC3 is expected to be a promising dye with desirable energetic and spectroscopic parameters in the DSSC field, which is consistent with recent experimental work. This study is expected to deepen our understanding of TPA-based organic dyes and assist the molecular design of new metal-free dyes for the further optimization of DSSCs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Proportioning and performance evaluation of self-consolidating concrete

NASA Astrophysics Data System (ADS)

Wang, Xuhao

A well-proportioned self-consolidating concrete (SCC) mixture can be achieved by controlling the aggregate system, paste quality, and paste quantity. The work presented in this dissertation involves an effort to study and improve particle packing of the concrete system and reduce the paste quantity while maintaining concrete quality and performance. This dissertation is composed of four papers resulting from the study: (1) Assessing Particle Packing Based Self-Consolidating Concrete Mix Design; (2) Using Paste-To-Voids Volume Ratio to Evaluate the Performance of Self-Consolidating Concrete Mixtures; (3) Image Analysis Applications on Assessing Static Stability and Flowability of Self-Consolidating Concrete, and (4) Using Ultrasonic Wave Propagation to Monitor Stiffening Process of Self-Consolidating Concrete. Tests were conducted on a large matrix of SCC mixtures that were designed for cast-in-place bridge construction. The mixtures were made with different aggregate types, sizes, and different cementitious materials. In Paper 1, a modified particle-packing based mix design method, originally proposed by Brouwers (2005), was applied to the design of self-consolidating concrete (SCC) mixs. Using this method, a large matrix of SCC mixes was designed to have a particle distribution modulus (q) ranging from 0.23 to 0.29. Fresh properties (such as flowability, passing ability, segregation resistance, yield stress, viscosity, set time and formwork pressure) and hardened properties (such as compressive strength, surface resistance, shrinkage, and air structure) of these concrete mixes were experimentally evaluated. In Paper 2, a concept that is based on paste-to-voids volume ratio (Vpaste/Vvoids) was employed to assess the performance of SCC mixtures. The relationship between excess paste theory and Vpaste/Vvoids was investigated. The workability, flow properties, compressive strength, shrinkage, and surface resistivity of SCC mixtures were determined at various ages. Statistical analyses, response surface models and Tukey Honestly Significant Difference (HSD) tests, were conducted to relate the mix design parameters to the concrete performance. The work discussed in Paper 3 was to apply a digital image processing (DIP) method associated with a MATLAB algorithm to evaluate cross sectional images of self-consolidating concrete (SCC). Parameters, such as inter-particle spacing between coarse aggregate particles and average mortar to aggregate ratio defined as average mortar thickness index (MTI), were derived from DIP method and applied to evaluate the static stability and develop statistical models to predict flowability of SCC mixtures. The last paper investigated technologies available to monitor changing properties of a fresh mixture, particularly for use with self-consolidating concrete (SCC). A number of techniques were used to monitor setting time, stiffening and formwork pressure of SCC mixtures. These included longitudinal (P-wave) ultrasonic wave propagation, penetrometer based setting time, semi-adiabatic calorimetry, and formwork pressure. The first study demonstrated that the concrete mixes designed using the modified Brouwers mix design algorithm and particle packing concept had a potential to reduce up to 20% SCMs content compared to existing SCC mix proportioning methods and still maintain good performance. The second paper concluded that slump flow of the SCC mixtures increased with Vpaste/Vvoids at a given viscosity of mortar. Compressive trength increases with increasing Vpaste/Vvoids up to a point (~150%), after which the strength becomes independent of Vpaste/Vvoids, even slightly decreases. Vpaste/Vvoids has little effect on the shrinkage mixtures, while SCC mixtures tend to have a higher shrinkage than CC for a given Vpaste/Vvoids. Vpaste/Vvoids has little effects on surface resistivity of SCC mixtures. The paste quality tends to have a dominant effect. Statistical analysis is an efficient tool to identify the significance of influence factors on concrete performance. In third paper, proposed DIP method and MATLAB algorithm can be successfully used to derive inter-particle spacing and MTI, and quantitatively evaluate the static stability in hardened SCC samples. These parameters can be applied to overcome the limitations and challenges of existing theoretical frames and construct statistical models associated with rheological parameters to predict flowability of SCC mixtures. The outcome of this study can be of practical value for providing an efficient and useful tool in designing mixture proportions of SCC. Last paper compared several concrete performance measurement techniques, the P-wave test and calorimetric measurements can be efficiently used to monitor the stiffening and setting of SCC mixtures.

Potential mesogens based on pyridine derivatives: The geometric structure, conformational properties and characteristics of intermolecular hydrogen bonds

NASA Astrophysics Data System (ADS)

Fedorov, Mikhail S.; Giricheva, Nina I.; Shpilevaya, Kseniya E.; Lapykina, Elena A.; Syrbu, Svetlana A.

2017-03-01

Conformational properties of the main part (excluding sbnd OC3H7 radicals) of the p-n-propyloxybenzoic (A1) and p-n-propyloxycinnamic (A2) acids molecules (relating to mesomorphic compounds) as well as p-n-propyloxybenzoic acid pyridine ester (B1) and p-n-propyloxyphenylazopyridine (B2) molecules (relating to non-mesomorphic compounds) were studied by DFT(B3LYP)/cc-pVTZ method. It was shown that the main parts of A1 and A2 acids are rigid. The barrier to internal rotation of pyridine fragment in the B1 and B2 molecules depends on the nature of the bridging group. It was determined that all studied A1⋯B1, A2⋯B1 and A2⋯B2 complexes are characterized by a strong hydrogen bond. The binding energy of complexes (≈14 kcal/mol, with BSSE corrections, DFT(B97D)/6-311++G**) exceeds the energy per hydrogen bond in the corresponding acid dimers (≈10 kcal/mol). The structural non-rigidity of A⋯B complexes is mainly caused by possibility of sbnd OC3H7 radicals internal rotation and A and B molecules rotation about the (H)O⋯N line. The characteristics of intermolecular hydrogen bonds were determined by NBO-analysis. The obtained results indicate that examined complexes correspond to the basic requirements to mesogen molecular forms. The thermodynamic functions of the gas-phase complexation reactions (idealized model of the complexes formation in the condensed state) were calculated. Preliminary studies of mesogen-non-mesogen A1⋯B2 system by differential scanning calorimetry and polarizing optical microscopy, showed that it has mesomorphic properties.

Preparation of Shrinkage Compensating Concrete with HCSA Expansive Agent

NASA Astrophysics Data System (ADS)

Li, Changcheng; Jia, Fujia

2017-10-01

Shrinkage compensating concrete (SCC) has become one of the best effective methods of preventing and reducing concrete cracking. SCC is prepared by HCSA high performance expansive agent for concrete which restrained expansion rate is optimized by 0.057%. Slump, compressive strength, restrained expansion rate and cracking resistance test were carried out on SCC. The results show that the initial slump of fresh SCC was about 220mm-230mm, while slump after 2 hours was 180mm-200mm. The restrained expansion rate of SCC increased with the mixing amount of expansive agent. After cured in water for 14 days, the restrained expansion rate of C35 and C40 SCC were 0.020%-0.032%. With the dosage of expansive agent increasing, restrained expansion rate of SCC increased, maximum compressive stress and cracking stress improved, cracking temperature fell, thus cracking resistance got effectively improvement.

Facile synthesis of fluoro, methoxy, and methyl substituted ferrocene-based urea complexes as potential therapeutic agents.

PubMed

Asghar, Faiza; Badshah, Amin; Lal, Bhajan; Zubair, Shumaila; Fatima, Saira; Butler, Ian S

2017-06-01

In the present work, the synthesis, characterization (FT-IR, multinuclear ( 1 H and 13 C) NMR, AAS, Raman, and elemental analysis), DNA binding (cyclic voltammetry, UV-Vis spectroscopy and viscometry), and in vitro biological assessment of nine new ferrocene-based ureas are reported. The desulphurization of ferrocenyl thioureas to the corresponding oxo analogues using aqueous sodium hydroxide and mercuric chloride led to the ferrocenyl ureas (F1-F9) in high yields. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The nature and the extent of interaction with DNA was further investigated by viscometry. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl derivatives exhibited good scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned for their in vitro cytotoxicity against human carcinoma cell line THP-1 (leukemia cells). The results showed a moderate level of cytotoxicity against the subjected cancer cell line as compared with the standard chemotherapeutic drug (cisplatin). Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-orbit tight binding calculations for spin transfer torque in magnetic tunneling junctions

NASA Astrophysics Data System (ADS)

You, Chun-Yeol; Han, Jae-Ho; Lee, Hyun-Woo

2012-04-01

We investigate the spin transfer torque (STT) with multi-orbit tight binding model in the magnetic tunneling junctions (MTJs). So far, most of the theoretical works based on the non-equilibrium Keldysh Green's function method employ a single band model for the simplicity, except a few first principle studies. Even though the single band model captures main physics of STT in MTJ, multi-band calculation reveals new features of the STT that depend on band parameters, such as insulator bandgap, inter-band hopping energy of the ferromagnetic layer. We find that the sign change of perpendicular torkance with bandgap of the insulator layer, and when we allow the inter-band hopping, the bias dependences of perpendicular STT are dramatically changed, while no noticeable changes in parallel STT are found.

Non-collinear magnetism with analytic Bond-Order Potentials

NASA Astrophysics Data System (ADS)

Ford, Michael E.; Pettifor, D. G.; Drautz, Ralf

2015-03-01

The theory of analytic Bond-Order Potentials as applied to non-collinear magnetic structures of transition metals is extended to take into account explicit rotations of Hamiltonian and local moment matrix elements between locally and globally defined spin-coordinate systems. Expressions for the gradients of the energy with respect to the Hamiltonian matrix elements, the interatomic forces and the magnetic torques are derived. The method is applied to simulations of the rotation of magnetic moments in α iron, as well as α and β manganese, based on d-valent orthogonal tight-binding parametrizations of the electronic structure. A new weighted-average terminator is introduced to improve the convergence of the Bond-Order Potential energies and torques with respect to tight-binding reference values, although the general behavior is qualitatively correct for low-moment expansions.

Study of the IGA/SCC behavior of Alloy 600 and 690 in high temperature solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsujikawa, S.; Yashima, S.; Ohnishi, K.

1995-09-01

IGA/SCC of Alloy 600 steam generator (SG) tubes in the secondary side has been recognized as a matter of great concern for PWRs. IGA/SCC behavior of Alloy 600 and 690 in high temperature solutions were studied using CERT method under potentiostatic conditions. The IGA/SCC susceptible regions were investigated as the function of pH and electrode potential. To understand the cause of IGA/SCC, the electrochemical measurements and surface film analysis were also performed in acidic and alkaline solutions. To verify the results of CERT test, the long term model boiler tests were also carried out. Thermally treated Alloy 690 showed highermore » IGA/SCC resistance than Alloy 600 under both acid and alkaline conditions.« less

Bulk tank somatic cell counts analyzed by statistical process control tools to identify and monitor subclinical mastitis incidence.

PubMed

Lukas, J M; Hawkins, D M; Kinsel, M L; Reneau, J K

2005-11-01

The objective of this study was to examine the relationship between monthly Dairy Herd Improvement (DHI) subclinical mastitis and new infection rate estimates and daily bulk tank somatic cell count (SCC) summarized by statistical process control tools. Dairy Herd Improvement Association test-day subclinical mastitis and new infection rate estimates along with daily or every other day bulk tank SCC data were collected for 12 mo of 2003 from 275 Upper Midwest dairy herds. Herds were divided into 5 herd production categories. A linear score [LNS = ln(BTSCC/100,000)/0.693147 + 3] was calculated for each individual bulk tank SCC. For both the raw SCC and the transformed data, the mean and sigma were calculated using the statistical quality control individual measurement and moving range chart procedure of Statistical Analysis System. One hundred eighty-three herds of the 275 herds from the study data set were then randomly selected and the raw (method 1) and transformed (method 2) bulk tank SCC mean and sigma were used to develop models for predicting subclinical mastitis and new infection rate estimates. Herd production category was also included in all models as 5 dummy variables. Models were validated by calculating estimates of subclinical mastitis and new infection rates for the remaining 92 herds and plotting them against observed values of each of the dependents. Only herd production category and bulk tank SCC mean were significant and remained in the final models. High R2 values (0.83 and 0.81 for methods 1 and 2, respectively) indicated a strong correlation between the bulk tank SCC and herd's subclinical mastitis prevalence. The standard errors of the estimate were 4.02 and 4.28% for methods 1 and 2, respectively, and decreased with increasing herd production. As a case study, Shewhart Individual Measurement Charts were plotted from the bulk tank SCC to identify shifts in mastitis incidence. Four of 5 charts examined signaled a change in bulk tank SCC before the DHI test day identified the change in subclinical mastitis prevalence. It can be concluded that applying statistical process control tools to daily bulk tank SCC can be used to estimate subclinical mastitis prevalence in the herd and observe for change in the subclinical mastitis status. Single DHI test day estimates of new infection rate were insufficient to accurately describe its dynamics.

Assessment of salivary total antioxidant capacity in patients with primary untreated head and neck squamous cell carcinoma with ORAC.

PubMed

Wesołowski, Piotr; Zawada, Katarzyna; Wojtowicz, Andrzej; Strużycka, Izabela; Kamiński, Tomasz

2016-11-01

Oxidative DNA damage leads to abnormalities in endogenous cellular processes and constitutes a direct link between free radicals, antioxidants and squamous cell carcinoma (SCC). Oxygen radical absorbance capacity (ORAC) method is used to measure antioxidant capacity versus oxygen free radicals. There is no report on the application of ORAC to evaluate salivary antioxidant capacity in patients with head and neck SCC. This study investigated the relation between total antioxidant capacity of saliva, measured with ORAC method, and the incidence, location, size and histopathological grading of SCC. Salivary antioxidant capacity was assessed in 30 male and female patients with histopathologically confirmed oral and laryngeal SCC. Histopathological grading of SCC was based on WHO classification. Mean ORAC in patients with SCC was higher than the mean value in the control group. Statistically significant difference was observed in the study group versus the control group. No significant differences were observed for ORAC values in relation to histopathological grading, tumour size and spread to lymph nodes. The obtained results can advocate local compensatory mechanism in saliva in response to increased oxidative stress associated with primary tumour. ORAC can become an additional factor in head and neck SCC prognosis, but further investigation is required. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Everyday Functioning and Cognitive Correlates in Healthy Older Adults with Subjective Cognitive Concerns

PubMed Central

McAlister, Courtney; Schmitter-Edgecombe, Maureen

2016-01-01

Objective Few studies have examined functional abilities and complaints in healthy older adults with subjective cognitive concerns (SCC). The aims of this study were to assess everyday functioning in healthy older adults reporting high and low amounts of SCC, and examine cognitive correlates of functional abilities. Method Twenty-six healthy older adults with high SCC, and 25 healthy older adults with low SCC, as well as their knowledgeable informants completed the Instrumental Activities of Daily Living-Compensation (IADL-C), a questionnaire measure of everyday functioning. Results After controlling for depression, the high SCC group self-reported significantly more everyday difficulties on the IADL-C, including all subdomains. Compared to the low SCC group, informants for the high SCC group endorsed more difficulties on the IADL-C and specifically the social skills subdomain. For the high SCC group, poorer self-report of everyday functioning was related to poorer executive functioning and temporal order memory. Conclusions These findings indicate that there may be subtle functional changes that occur early in the spectrum of cognitive decline in individuals with high SCC, and these functional changes are evident to informants. Further work is needed to investigate whether individuals with both SCC and functional difficulties are at an even higher risk for progression to mild cognitive impairment. PMID:27240886

Conductance of AFM Deformed Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Svizhenko, Alexei; Maiti, Amitesh; Anatram, M. P.; Biegel, Bryan (Technical Monitor)

2002-01-01

This viewgraph presentation provides information on the electrical conductivity of carbon nanotubes upon deformation by atomic force microscopy (AFM). The density of states and conductance were computed using four orbital tight-binding method with various parameterizations. Different chiralities develop bandgap that varies with chirality.

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

PubMed Central

Zhan, Ping; Xi, Guang-Min; Liu, Hong-Bing; Liu, Ya-Fang; Xu, Wu-Jian; Zhu, Qingqing; Zhou, Ze-Jun; Miao, Ying-Ying; Wang, Xiao-Xia; Jin, Jia-Jia

2017-01-01

Background Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC. Methods PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. Results In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. Conclusions Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC. PMID:28840006

MicroRNA-588 suppresses tumor cell migration and invasion by targeting GRN in lung squamous cell carcinoma

PubMed Central

Qian, Li; Lin, Longlong; Du, Yufeng; Hao, Xiaoyan; Zhao, Yuze; Liu, Xuejun

2016-01-01

MicroRNAs (miRNAs) have been demonstrated to be critical in regulating tumor development and progression. The present study investigated the expression of miR-588 using reverse transcription-quantitative polymerase chain reaction analysis in 85 cases of lung squamous cell carcinoma (SCC), and observed the correlation between the expression of miR-588 with clinical pathologic features. The results indicated that the expression of miR-588 was predominantly lower in the tumor samples, compared with non-tumorous samples, and was negatively associated with tumor stages and lymph node invasion. The present study also examined the significance of the expression of miR-588 in SCC using gain- and loss-of-function analyses. It was found that miR-588 inhibited tumor cell migration and invasion. In addition, it was revealed that the overexpression of miR-588 in SCC cells reduced the mRNA and protein levels of progranulin (GRN), whereas miR-588 silencing increased the expression of GRN. A luciferase activity assay showed that miR-588 was able to directly bind to the 3′untranslated region of GRN and regulate its expression. Furthermore, it was found that the expression of GRN was inversely correlated with the expression of miR-588 in 85 paired SCC samples. These results indicated that GRN was involved in the miR-588-mediated suppressive functions in the progression of SCC. PMID:27571908

Molecular Histopathology Using Gold Nanorods and Optical Coherence Tomography

PubMed Central

Prabhulkar, Shradha; Matthews, Jared; Rawal, Siddarth; Awdeh, Richard M.

2013-01-01

Purpose. To examine the novel application of a commercially available optical coherence tomography (OCT) system toward molecular histopathology using gold nanorod (GNR) linked antibodies as a functionalized contrast agent to evaluate ocular surface squamous neoplasia (OSSN). Methods. GNRs were synthesized and covalently attached to anti–glucose transporter-1 (GLUT-1) antibodies via carbodiimide chemistry. Three specimens from each of three distinct categories of human conjunctival tissue were selected for analysis, including conjunctiva without epithelial atypia (controls); conjunctival intraepithelial neoplasia, carcinoma in situ (CIS); and conjunctival squamous cell carcinoma (SCC). Tissue sections were incubated initially with GNR tagged anti–GLUT-1 antibodies and then with a fluorescent-tagged secondary antibody. Immunofluorescence and OCT imaging of the tissue was performed and the results were correlated to the light microscopic findings on traditional hemotoxyin and eosin stained sections. Results. No binding of the functionalized GNRs was observed within the epithelium of three normal conjunctiva controls. While immunofluorescence disclosed variable binding of the functionalized GNRs to atypical epithelial cells in all six cases of OSSN, the enhancement of the OCT signal in three cases of CIS was insufficient to distinguish these specimens from normal controls. In two of three cases of SCC, binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to atypical epithelial cells which stained intensely on immunofluorescence imaging. Binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to regions of erythrocytes and hemorrhage which stained intensely on immunofluorescence imaging within all nine tested samples. Conclusions. We have demonstrated the use of OCT for molecular histopathology using functionalized gold nanorods in the setting of OSSN. Our results suggest a threshold concentration of functionalized GNRs within tissue is required to achieve a detectable enhancement in scattering of the OCT signal. PMID:23307958

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mir-Sanchis, Ignacio; Roman, Christina A.; Misiura, Agnieszka

2016-08-29

Methicillin-resistant Staphylococcus aureus (MRSA) is a public-health threat worldwide. Although the mobile genomic island responsible for this phenotype, staphylococcal cassette chromosome (SCC), has been thought to be nonreplicative, we predicted DNA-replication-related functions for some of the conserved proteins encoded by SCC. We show that one of these, Cch, is homologous to the self-loading initiator helicases of an unrelated family of genomic islands, that it is an active 3'-to-5' helicase and that the adjacent ORF encodes a single-stranded DNA–binding protein. Our 2.9-Å crystal structure of intact Cch shows that it forms a hexameric ring. Cch, like the archaeal and eukaryotic MCM-familymore » replicative helicases, belongs to the pre–sensor II insert clade of AAA+ ATPases. Additionally, we found that SCC elements are part of a broader family of mobile elements, all of which encode a replication initiator upstream of their recombinases. Replication after excision would enhance the efficiency of horizontal gene transfer.« less

Epidermal growth factor receptor (EGFR) density may not be the only determinant for the efficacy of EGFR-targeted photoimmunotherapy in human head and neck cancer cell lines.

PubMed

Peng, Wei; de Bruijn, Henriette S; Farrell, Eric; Sioud, Mouldy; Mashayekhi, Vida; Oliveira, Sabrina; van Dam, Go M; Roodenburg, Jan L N; Witjes, Max J H; Robinson, Dominic J

2018-05-19

The aim of this study was to investigate the effects of targeted photoimmunotherapy (PIT) in vitro on cell lines with various expression levels of epidermal growth factor receptor (EGFR) using an anti-EGFR targeted conjugate composed of Cetuximab and IR700DX, phthalocyanine dye. Relative EGFR density and cell binding assay was conducted in three human head & neck cancer cell lines (scc-U2, scc-U8, and OSC19) and one reference cell line A431. After incubation with the conjugate for 1 or 24 hours, cellular uptake and localization were investigated by confocal laser scanning microscopy and quantified by image analysis. Cell survival was determined using the MTS assay and alamarBlue assay after PIT with a 690 nm laser to a dose of 7 J.cm -2 (at 5 mW.cm -2 ). The mode of cell death was examined with flow cytometry using apoptosis/necrosis staining by Annexin V/propidium iodide, together with immunoblots of anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL. A431 cells had the highest EGFR density followed by OSC19, and then scc-U2 and scc-U8. The conjugates were localized both on the surface and in the cytosol of the cells after 1- and 24-hour incubation. After 24-hour incubation the granular pattern was more pronounced and in a similar pattern of a lysosomal probe, suggesting that the uptake of conjugates by cells was via receptor-mediated endocytosis. The results obtained from the quantitative imaging analysis correlate with the level of EGFR expression. Targeted PIT killed scc-U8 and A431 cells efficiently; while scc-U2 and OSC19 were less sensitive to this treatment, despite having similar EGFR density, uptake and localization pattern. Scc-U2 cells showed less apoptotic cell dealth than in A431 after 24-hour targeted PIT. Immunoblots showed significantly higher expression of anti-apoptotic Bcl-2 and Bcl-xL proteins in scc-U2 cell lines compared to scc-U8. Our study suggests that the effectiveness of EGFR targeted PIT is not only dependent upon EGFR density. Intrinsic biological properties of tumor cell lines also play a role in determining the efficacy of targeted PIT. We have shown that in scc-U2 cells this difference may be caused by differences in the apoptopic pathway. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

2014-09-01

Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

Actinide electronic structure and atomic forces

NASA Astrophysics Data System (ADS)

Albers, R. C.; Rudin, Sven P.; Trinkle, Dallas R.; Jones, M. D.

2000-07-01

We have developed a new method[1] of fitting tight-binding parameterizations based on functional forms developed at the Naval Research Laboratory.[2] We have applied these methods to actinide metals and report our success using them (see below). The fitting procedure uses first-principles local-density-approximation (LDA) linear augmented plane-wave (LAPW) band structure techniques[3] to first calculate an electronic-structure band structure and total energy for fcc, bcc, and simple cubic crystal structures for the actinide of interest. The tight-binding parameterization is then chosen to fit the detailed energy eigenvalues of the bands along symmetry directions, and the symmetry of the parameterization is constrained to agree with the correct symmetry of the LDA band structure at each eigenvalue and k-vector that is fit to. By fitting to a range of different volumes and the three different crystal structures, we find that the resulting parameterization is robust and appears to accurately calculate other crystal structures and properties of interest.

The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast.

PubMed

Litwin, Ireneusz; Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert

2017-06-20

Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Tight-binding analysis of Si and GaAs ultrathin bodies with subatomic wave-function resolution

NASA Astrophysics Data System (ADS)

Tan, Yaohua P.; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

2015-08-01

Empirical tight-binding (ETB) methods are widely used in atomistic device simulations. Traditional ways of generating the ETB parameters rely on direct fitting to bulk experiments or theoretical electronic bands. However, ETB calculations based on existing parameters lead to unphysical results in ultrasmall structures like the As-terminated GaAs ultrathin bodies (UTBs). In this work, it is shown that more transferable ETB parameters with a short interaction range can be obtained by a process of mapping ab initio bands and wave functions to ETB models. This process enables the calibration of not only the ETB energy bands but also the ETB wave functions with corresponding ab initio calculations. Based on the mapping process, ETB models of Si and GaAs are parameterized with respect to hybrid functional calculations. Highly localized ETB basis functions are obtained. Both the ETB energy bands and wave functions with subatomic resolution of UTBs show good agreement with the corresponding hybrid functional calculations. The ETB methods can then be used to explain realistically extended devices in nonequilibrium that cannot be tackled with ab initio methods.

Case–Control Study of Cutaneous Human Papillomaviruses in Squamous Cell Carcinoma of the Skin

PubMed Central

Iannacone, Michelle R.; Gheit, Tarik; Waterboer, Tim; Giuliano, Anna R.; Messina, Jane L.; Fenske, Neil A.; Cherpelis, Basil S.; Sondak, Vernon K.; Roetzheim, Richard G.; Michael, Kristina M.; Tommasino, Massimo; Pawlita, Michael; Rollison, Dana E.

2015-01-01

Background Cutaneous human papillomavirus (HPV) infection may be a risk factor for squamous cell carcinoma (SCC) of the skin. Methods To investigate the association between cutaneous HPV and SCC, a case–control study was conducted, including 173 SCC cases from a university dermatology clinic and 300 controls that screened negative for skin cancer. Serum antibodies against cutaneous HPV types in genera alpha, beta, gamma, mu, and nu were measured. Tumor tissue from 159 SCC cases was tested for the presence of DNA for genus-beta HPV types. Using logistic regression ORs and 95% confidence intervals (CI) were estimated for the associations between SCC and cutaneous HPV infection, adjusting for age and sex. The Bonferroni method was used to account for multiple comparisons. Results SCC was positively associated with seropositivity to any genus-beta HPV type (OR, 1.93; 95% CI, 1.23–3.02), particularly with types in species-1 (OR, 1.86; 95% CI, 1.22–2.85). Type-specific associations with SCC were observed for HPV 8 (OR, 1.80; 95% CI, 1.14–2.84), 17 (OR, 1.59; 95% CI, 1.02–2.49) and HPV 10 from genus-alpha (OR, 2.24; 95% CI, 1.04–4.85). None of the type-specific associations remained statistically significant after correction for multiple comparisons. When DNA-positive SCC cases were compared with controls, strong serologic associations were observed for HPVs 5 (OR, 3.48; 95% CI, 1.27–9.59), 17 (OR, 3.36; 95% CI, 1.29–8.72), and 24 (OR, 3.79; 95% CI, 1.24–11.5). Conclusion Genus-beta HPV infections were associated with SCC in our study population. Impact Identifying the role of cutaneous HPV infection in SCC may lead to improved characterization of high-risk individuals and the development of novel prevention strategies. PMID:22707711

Blocking Mechanism Study of Self-Compacting Concrete Based on Discrete Element Method

NASA Astrophysics Data System (ADS)

Zhang, Xuan; Li, Zhida; Zhang, Zhihua

2017-11-01

In order to study the influence factors of blocking mechanism of Self-Compaction Concrete (SCC), Roussel’s granular blocking model was verified and extended by establishing the discrete element model of SCC. The influence of different parameters on the filling capacity and blocking mechanism of SCC were also investigated. The results showed that: it was feasible to simulate the blocking mechanism of SCC by using Discrete Element Method (DEM). The passing ability of pebble aggregate was superior to the gravel aggregate and the passing ability of hexahedron particles was bigger than tetrahedron particles, while the tetrahedron particle simulation results were closer to the actual situation. The flow of SCC as another significant factor affected the passing ability that with the flow increased, the passing ability increased. The correction coefficient λ of the steel arrangement (channel section shape) and flow rate γ in the block model were introduced that the value of λ was 0.90-0.95 and the maximum casting rate was 7.8 L/min.

2D Quantum Simulation of MOSFET Using the Non Equilibrium Green's Function Method

NASA Technical Reports Server (NTRS)

Svizhenko, Alexel; Anantram, M. P.; Govindan, T. R.; Yan, Jerry (Technical Monitor)

2000-01-01

The objectives this viewgraph presentation summarizes include: (1) the development of a quantum mechanical simulator for ultra short channel MOSFET simulation, including theory, physical approximations, and computer code; (2) explore physics that is not accessible by semiclassical methods; (3) benchmarking of semiclassical and classical methods; and (4) study other two-dimensional devices and molecular structure, from discretized Hamiltonian to tight-binding Hamiltonian.

Transport gap engineering by contact geometry in graphene nanoribbons: Experimental and theoretical studies on artificial materials

NASA Astrophysics Data System (ADS)

Stegmann, Thomas; Franco-Villafañe, John A.; Kuhl, Ulrich; Mortessagne, Fabrice; Seligman, Thomas H.

2017-01-01

Electron transport in small graphene nanoribbons is studied by microwave emulation experiments and tight-binding calculations. In particular, it is investigated under which conditions a transport gap can be observed. Our experiments provide evidence that armchair ribbons of width 3 m +2 with integer m are metallic and otherwise semiconducting, whereas zigzag ribbons are metallic independent of their width. The contact geometry, defining to which atoms at the ribbon edges the source and drain leads are attached, has strong effects on the transport. If leads are attached only to the inner atoms of zigzag edges, broad transport gaps can be observed in all armchair ribbons as well as in rhomboid-shaped zigzag ribbons. All experimental results agree qualitatively with tight-binding calculations using the nonequilibrium Green's function method.

Electronic Properties of SiNTs Under External Electric and Magnetic Fields Using the Tight-Binding Method

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh

2014-02-01

We investigated the electronic properties of silicon nanotubes (SiNTs) under external transverse electric fields and axial magnetic fields using the tight-binding approximation. It was found that, after switching on the electric and magnetic fields, band modifications such as distortion of degeneracy, change in energy dispersion and subband spacing, and bandgap size reduction occur. The bandgap of silicon gear-like nanotubes (Si g-NTs) decreases linearly with increasing electric field strength, but the bandgap for silicon hexagonal nanotubes (Si h-NTs) first increases and then decreases (metallic) or first remains constant and then decreases (semiconducting). Our results show that the bandgap of Si h-NTs is very sensitive to both electric and magnetic fields, unlike Si g-NTs, which are more sensitive to electric than magnetic fields.

Conductance of three-terminal molecular bridge based on tight-binding theory

NASA Astrophysics Data System (ADS)

Wang, Li-Guang; Li, Yong; Yu, Ding-Wen; Katsunori, Tagami; Masaru, Tsukada

2005-05-01

The quantum transmission characteristic of three-benzene ring nano-molecular bridge is investigated theoretically by using Green's function approach based on tight-binding theory with only a π orbital per carbon atom at the site. The transmission probabilities that electrons transport through the molecular bridge from one terminal to the other two terminals are obtained. The electronic current distributions inside the molecular bridge are calculated and shown in graphical analogy by the current density method based on Fisher-Lee formula at the energy points E = ±0.42, ±1.06 and ±1.5, respectively, where the transmission spectra appear peaks. We find that the transmission spectra are related to the incident electronic energy and the molecular levels strongly and the current distributions agree well with Kirchhoff quantum current momentum conservation law.

Unraveling the differences of the hydrolytic activity of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase: a quantum mechanics-molecular mechanics modeling study.

PubMed

Bueren-Calabuig, Juan A; Pierdominici-Sottile, Gustavo; Roitberg, Adrian E

2014-06-05

Chagas' disease, also known as American trypanosomiasis, is a lethal, chronic disease that currently affects more than 10 million people in Central and South America. The trans-sialidase from Trypanosoma cruzi (T. cruzi, TcTS) is a crucial enzyme for the survival of this parasite: sialic acids from the host are transferred to the cell surface glycoproteins of the trypanosome, thereby evading the host's immune system. On the other hand, the sialidase of T. rangeli (TrSA), which shares 70% sequence identity with TcTS, is a strict hydrolase and shows no trans-sialidase activity. Therefore, TcTS and TrSA represent an excellent framework to understand how different catalytic activities can be achieved with extremely similar structures. By means of combined quantum mechanics-molecular mechanics (QM/MM, SCC-DFTB/Amberff99SB) calculations and umbrella sampling simulations, we investigated the hydrolysis mechanisms of TcTS and TrSA and computed the free energy profiles of these reactions. The results, together with our previous computational investigations, are able to explain the catalytic mechanism of sialidases and describe how subtle differences in the active site make TrSA a strict hydrolase and TcTS a more efficient trans-sialidase.

Molecular structure, FT IR, NMR, UV, NBO and HOMO-LUMO of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile by DFT/B3LYP and PBEPBE methods with LanL2DZ and 6-311++G(d,2p) basis sets.

PubMed

Khajehzadeh, Mostafa; Moghadam, Majid

2017-06-05

Structural and molecular properties of antidepressants 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile were examined using quantum mechanics of Density Functional Theory (DFT)/B3LYP and PBEPBE methods with 6-311++G(d,2p) and LanL2DZ basis sets to study the therapeutic properties of the drug. For this, the structure of desired material was optimized by the computer calculation method and with the use of powerful Gaussian 09 software. Then the lowest energy value and the bond length, bond angle and dihedral angle between its constituent atoms in the crystal structure of the desired material were measured from the optimized values. Then the amount of positive and negative charges, polarizability and dipole moment of its atoms using Mulliken charge and Natural atomic charges, DFT/B3LYP and PBEPBE methods with 6-311++G(d,2p) and LanL2DZ basis sets were determined and the results were compared with each other for individual atoms and by mentioned methods. Also the type of stretching vibrations and bending vibrations between the constituent atoms of the molecule were specified using mentioned computational methods and FT IR vibrational spectra. The experimental spectrum of this material was taken to determine the functional groups and the computational and experimental values were compared to each other and Nuclear Magnetic Resonance (NMR) was used to specify the isomer shift between the carbons and protons in the presence of polar and nonpolar solvents. Also Natural Bond Orbital (NBO) was used to determine the type of electron transfers in σ→σ∗ and π→π∗ and LP(1)→σ∗ and LP(2)→σ∗ and the amount of hardness and softness in molecule was determined using the difference between ionization energy and electron affinity energy in constituent atoms of that molecule in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and in the presence of solvents H 2 O, CH 3 CN and C 6 H 12 . UV-Vis spectrum of the drug was taken using DFT/B3LYP and PBEPBE methods with 6-311++G(d,2p) and LanL2DZ basis sets as well as solvents H 2 O, CH 3 CN and C 6 H 12 and the associated transmissions were examined. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural, vibrational spectroscopic and quantum chemical studies on indole-3-carboxaldehyde

NASA Astrophysics Data System (ADS)

Premkumar, R.; Asath, R. Mohamed; Mathavan, T.; Benial, A. Milton Franklin

2017-05-01

The potential energy surface (PES) scan was performed for indole-3-carboxaldehyde (ICA) and the most stable optimized conformer was predicted using DFT/B3LYP method with 6-31G basis set. The vibrational frequencies of ICA were theoretically calculated by the DFT/B3LYP method with cc-pVTZ basis set using Gaussian 09 program. The vibrational spectra were experimentally recorded by Fourier transform-infrared (FT-IR) and Fourier transform-Raman spectrometer (FT-Raman). The computed vibrational frequencies were scaled by scaling factors to yield a good agreement with observed vibrational frequencies. The theoretically calculated and experimentally observed vibrational frequencies were assigned on the basis of potential energy distribution (PED) calculation using VEDA 4.0 program. The molecular interaction, stability and intramolecular charge transfer of ICA were studied using frontier molecular orbitals (FMOs) analysis and Mulliken atomic charge distribution shows the distribution of the atomic charges. The presence of intramolecular charge transfer was studied using natural bond orbital (NBO) analysis.

NDE to Manage Atmospheric SCC in Canisters for Dry Storage of Spent Fuel: An Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Ryan M.; Pardini, Allan F.; Cuta, Judith M.

2013-09-01

This report documents efforts to assess representative horizontal (Transuclear NUHOMS®) and vertical (Holtec HI-STORM) storage systems for the implementation of non-destructive examination (NDE) methods or techniques to manage atmospheric stress corrosion cracking (SCC) in canisters for dry storage of used nuclear fuel. The assessment is conducted by assessing accessibility and deployment, environmental compatibility, and applicability of NDE methods. A recommendation of this assessment is to focus on bulk ultrasonic and eddy current techniques for direct canister monitoring of atmospheric SCC. This assessment also highlights canister regions that may be most vulnerable to atmospheric SCC to guide the use of bulkmore » ultrasonic and eddy current examinations. An assessment of accessibility also identifies canister regions that are easiest and more difficult to access through the ventilation paths of the concrete shielding modules. A conceivable sampling strategy for canister inspections is to sample only the easiest to access portions of vulnerable regions. There are aspects to performing an NDE inspection of dry canister storage system (DCSS) canisters for atmospheric SCC that have not been addressed in previous performance studies. These aspects provide the basis for recommendations of future efforts to determine the capability and performance of eddy current and bulk ultrasonic examinations for atmospheric SCC in DCSS canisters. Finally, other important areas of investigation are identified including the development of instrumented surveillance specimens to identify when conditions are conducive for atmospheric SCC, characterization of atmospheric SCC morphology, and an assessment of air flow patterns over canister surfaces and their influence on chloride deposition.« less

Efficient self-consistency for magnetic tight binding

NASA Astrophysics Data System (ADS)

Soin, Preetma; Horsfield, A. P.; Nguyen-Manh, D.

2011-06-01

Tight binding can be extended to magnetic systems by including an exchange interaction on an atomic site that favours net spin polarisation. We have used a published model, extended to include long-ranged Coulomb interactions, to study defects in iron. We have found that achieving self-consistency using conventional techniques was either unstable or very slow. By formulating the problem of achieving charge and spin self-consistency as a search for stationary points of a Harris-Foulkes functional, extended to include spin, we have derived a much more efficient scheme based on a Newton-Raphson procedure. We demonstrate the capabilities of our method by looking at vacancies and self-interstitials in iron. Self-consistency can indeed be achieved in a more efficient and stable manner, but care needs to be taken to manage this. The algorithm is implemented in the code PLATO. Program summaryProgram title:PLATO Catalogue identifier: AEFC_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEFC_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 228 747 No. of bytes in distributed program, including test data, etc.: 1 880 369 Distribution format: tar.gz Programming language: C and PERL Computer: Apple Macintosh, PC, Unix machines Operating system: Unix, Linux, Mac OS X, Windows XP Has the code been vectorised or parallelised?: Yes. Up to 256 processors tested RAM: Up to 2 Gbytes per processor Classification: 7.3 External routines: LAPACK, BLAS and optionally ScaLAPACK, BLACS, PBLAS, FFTW Catalogue identifier of previous version: AEFC_v1_0 Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 2616 Does the new version supersede the previous version?: Yes Nature of problem: Achieving charge and spin self-consistency in magnetic tight binding can be very difficult. Our existing schemes failed altogether, or were very slow. Solution method: A new scheme for achieving self-consistency in orthogonal tight binding has been introduced that explicitly evaluates the first and second derivatives of the energy with respect to input charge and spin, and then uses these to search for stationary values of the energy. Reasons for new version: Bug fixes and new functionality. Summary of revisions: New charge and spin mixing scheme for orthogonal tight binding. Numerous small bug fixes. Restrictions: The new mixing scheme scales poorly with system size. In particular the memory usage scales as number of atoms to the power 4. It is restricted to systems with about 200 atoms or less. Running time: Test cases will run in a few minutes, large calculations may run for several days.

A Point Mutation in Suppressor of Cytokine Signalling 2 (Socs2) Increases the Susceptibility to Inflammation of the Mammary Gland while Associated with Higher Body Weight and Size and Higher Milk Production in a Sheep Model

PubMed Central

Rupp, Rachel; Senin, Pavel; Sarry, Julien; Allain, Charlotte; Tasca, Christian; Ligat, Laeticia; Portes, David; Woloszyn, Florent; Bouchez, Olivier; Tabouret, Guillaume; Lebastard, Mathieu; Caubet, Cécile

2015-01-01

Mastitis is an infectious disease mainly caused by bacteria invading the mammary gland. Genetic control of susceptibility to mastitis has been widely evidenced in dairy ruminants, but the genetic basis and underlying mechanisms are still largely unknown. We describe the discovery, fine mapping and functional characterization of a genetic variant associated with elevated milk leukocytes count, or SCC, as a proxy for mastitis. After implementing genome-wide association studies, we identified a major QTL associated with SCC on ovine chromosome 3. Fine mapping of the region, using full sequencing with 12X coverage in three animals, provided one strong candidate SNP that mapped to the coding sequence of a highly conserved gene, suppressor of cytokine signalling 2 (Socs2). The frequency of the SNP associated with increased SCC was 21.7% and the Socs2 genotype explained 12% of the variance of the trait. The point mutation induces the p.R96C substitution in the SH2 functional domain of SOCS2 i.e. the binding site of the protein to various ligands, as well-established for the growth hormone receptor GHR. Using surface plasmon resonance we showed that the p.R96C point mutation completely abrogates SOCS2 binding affinity for the phosphopeptide of GHR. Additionally, the size, weight and milk production in p.R96C homozygote sheep, were significantly increased by 24%, 18%, and 4.4%, respectively, when compared to wild type sheep, supporting the view that the point mutation causes a loss of SOCS2 functional activity. Altogether these results provide strong evidence for a causal mutation controlling SCC in sheep and highlight the major role of SOCS2 as a tradeoff between the host’s inflammatory response to mammary infections, and body growth and milk production, which are all mediated by the JAK/STAT signaling pathway. PMID:26658352

A Point Mutation in Suppressor of Cytokine Signalling 2 (Socs2) Increases the Susceptibility to Inflammation of the Mammary Gland while Associated with Higher Body Weight and Size and Higher Milk Production in a Sheep Model.

PubMed

Rupp, Rachel; Senin, Pavel; Sarry, Julien; Allain, Charlotte; Tasca, Christian; Ligat, Laeticia; Portes, David; Woloszyn, Florent; Bouchez, Olivier; Tabouret, Guillaume; Lebastard, Mathieu; Caubet, Cécile; Foucras, Gilles; Tosser-Klopp, Gwenola

2015-12-01

Mastitis is an infectious disease mainly caused by bacteria invading the mammary gland. Genetic control of susceptibility to mastitis has been widely evidenced in dairy ruminants, but the genetic basis and underlying mechanisms are still largely unknown. We describe the discovery, fine mapping and functional characterization of a genetic variant associated with elevated milk leukocytes count, or SCC, as a proxy for mastitis. After implementing genome-wide association studies, we identified a major QTL associated with SCC on ovine chromosome 3. Fine mapping of the region, using full sequencing with 12X coverage in three animals, provided one strong candidate SNP that mapped to the coding sequence of a highly conserved gene, suppressor of cytokine signalling 2 (Socs2). The frequency of the SNP associated with increased SCC was 21.7% and the Socs2 genotype explained 12% of the variance of the trait. The point mutation induces the p.R96C substitution in the SH2 functional domain of SOCS2 i.e. the binding site of the protein to various ligands, as well-established for the growth hormone receptor GHR. Using surface plasmon resonance we showed that the p.R96C point mutation completely abrogates SOCS2 binding affinity for the phosphopeptide of GHR. Additionally, the size, weight and milk production in p.R96C homozygote sheep, were significantly increased by 24%, 18%, and 4.4%, respectively, when compared to wild type sheep, supporting the view that the point mutation causes a loss of SOCS2 functional activity. Altogether these results provide strong evidence for a causal mutation controlling SCC in sheep and highlight the major role of SOCS2 as a tradeoff between the host's inflammatory response to mammary infections, and body growth and milk production, which are all mediated by the JAK/STAT signaling pathway.

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not “high risk”: Diagnosis, management, and clinical outcomes in a series of 115 cases

PubMed Central

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H.; Fung, Maxwell A.

2017-01-01

Background Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. Objective We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Methods Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Results Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. Limitations This was a single-institution retrospective study from the United States. Conclusions The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. PMID:27889291

Dpb11 may function with RPA and DNA to initiate DNA replication.

PubMed

Bruck, Irina; Dhingra, Nalini; Martinez, Matthew P; Kaplan, Daniel L

2017-01-01

Dpb11 is required for the initiation of DNA replication in budding yeast. We found that Dpb11 binds tightly to single-stranded DNA (ssDNA) or branched DNA structures, while its human homolog, TopBP1, binds tightly to branched-DNA structures. We also found that Dpb11 binds stably to CDK-phosphorylated RPA, the eukaryotic ssDNA binding protein, in the presence of branched DNA. A Dpb11 mutant specifically defective for DNA binding did not exhibit tight binding to RPA in the presence of DNA, suggesting that Dpb11-interaction with DNA may promote the recruitment of RPA to melted DNA. We then characterized a mutant of Dpb11 that is specifically defective in DNA binding in budding yeast cells. Expression of dpb11-m1,2,3,5,ΔC results in a substantial decrease in RPA recruitment to origins, suggesting that Dpb11 interaction with DNA may be required for RPA recruitment to origins. Expression of dpb11-m1,2,3,5,ΔC also results in diminished GINS interaction with Mcm2-7 during S phase, while Cdc45 interaction with Mcm2-7 is like wild-type. The reduced GINS interaction with Mcm2-7 may be an indirect consequence of diminished origin melting. We propose that the tight interaction between Dpb11, CDK-phosphorylated RPA, and branched-DNA may be required for the essential function of stabilizing melted origin DNA in vivo. We also propose an alternative model, wherein Dpb11-DNA interaction is required for some other function in DNA replication initiation, such as helicase activation.

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation

PubMed Central

Shin, Jung-Min; Chang, In-Kyu; Lee, Young-Ho; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon

2016-01-01

Background S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. Objective This study aims to investigate the relationship between S100A8 and cutaneous SCC development. Methods We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. Results S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. Conclusion S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin. PMID:27081264

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

PubMed

Zhang, Wei; Liu, Yuan; Li, Yu Feng; Yue, Yun; Yang, Xinghua; Peng, Lin

2016-01-01

Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-x03BA;B. YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-x03BA;B and downregulation of NF-x03BA;B downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC. © 2016 The Author(s) Published by S. Karger AG, Basel.

Safer Conception Methods and Counseling: Psychometric Evaluation of New Measures of Attitudes and Beliefs Among HIV Clients and Providers.

PubMed

Woldetsadik, Mahlet Atakilt; Goggin, Kathy; Staggs, Vincent S; Wanyenze, Rhoda K; Beyeza-Kashesya, Jolly; Mindry, Deborah; Finocchario-Kessler, Sarah; Khanakwa, Sarah; Wagner, Glenn J

2016-06-01

With data from 400 HIV clients with fertility intentions and 57 HIV providers in Uganda, we evaluated the psychometrics of new client and provider scales measuring constructs related to safer conception methods (SCM) and safer conception counselling (SCC). Several forms of validity (i.e., content, face, and construct validity) were examined using standard methods including exploratory and confirmatory factor analysis. Internal consistency was established using Cronbach's alpha correlation coefficient. The final scales consisted of measures of attitudes towards use of SCM and delivery of SCC, including measures of self-efficacy and motivation to use SCM, and perceived community stigma towards childbearing. Most client and all provider measures had moderate to high internal consistency (alphas 0.60-0.94), most had convergent validity (associations with other SCM or SCC-related measures), and client measures had divergent validity (poor associations with depression). These findings establish preliminary psychometric properties of these scales and should facilitate future studies of SCM and SCC.

Extraction channel design based on an equivalent lumped parameter method for a SCC-250 MeV superconducting cyclotron

NASA Astrophysics Data System (ADS)

Zhang, Lige; Fan, Kuanjun; Hu, Shengwei; Li, Xiaofei; Mei, Zhiyuan; Zeng, Zhijie; Chen, Wei; Qin, Bin; Rao, Yinong

2018-07-01

A SCC-250 MeV cyclotron, producing a 250 MeV proton beam, is under development in Huazhong University of Science and Technology (HUST) for proton therapy. The magnetic flux density, as a function of radius, decreases rapidly in the beam extraction region, which increases the radial beam size continuously along the extraction orbit. In this paper, an extraction channel inside the SCC-250 MeV is designed to control the beam size using passive magnetic channels. An equivalent lumped parameter method is used to establish the model of the extraction channel in the complex fringe magnetic field of the main magnet. Then, the extraction channel is designed using the lattice design software MADX. The beam envelopes are verified using particle tracing method. The maximum radial size of 6.8 mm and axial size of 4.3 mm meet the requirements of the extraction from the SCC-250 MeV.

Tight-binding calculation of the magnetic moment of CrAs under pressure

NASA Astrophysics Data System (ADS)

Autieri, Carmine; Cuono, Giuseppe; Forte, Filomena; Noce, Canio

2018-03-01

We analyze the evolution of the local magnetic moment of the newly discovered pressure-induced superconductor CrAs, as a function of the applied pressure. Our theoretical method is based on a combination of the tight-binding approximation and the Löwdin down-folding procedure, which enables us to derive a low-energy effective Hamiltonian projected onto the Cr-subsector. We set up our calculations by considering several sets of ab initio derived hopping parameters, corresponding to different volumes of the unit cell, and use them to obtain the simulated pressure-dependence of the Cr magnetic moment, which is evaluated within a mean-field treatment of the Coulomb repulsion between the electrons at the Cr sites. Our calculations show good agreement with available experimental data, both for the normal phase measured 1.7 µB for Cr magnetic moment, and concerning the observed reduction of its amplitude for values that exceed the characteristic critical pressure.

ProbeZT: Simulation of transport coefficients of molecular electronic junctions under environmental effects using Büttiker's probes

NASA Astrophysics Data System (ADS)

Korol, Roman; Kilgour, Michael; Segal, Dvira

2018-03-01

We present our in-house quantum transport package, ProbeZT. This program provides linear response coefficients: electrical and electronic thermal conductances, as well as the thermopower of molecular junctions in which electrons interact with the surrounding thermal environment. Calculations are performed based on the Büttiker probe method, which introduces decoherence, energy exchange and dissipation effects phenomenologically using virtual electrode terminals called probes. The program can realize different types of probes, each introducing various environmental effects, including elastic and inelastic scattering of electrons. The molecular system is described by an arbitrary tight-binding Hamiltonian, allowing the study of different geometries beyond simple one-dimensional wires. Applications of the program to study the thermoelectric performance of molecular junctions are illustrated. The program also has a built-in functionality to simulate electron transport in double-stranded DNA molecules based on a tight-binding (ladder) description of the junction.

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

PubMed Central

Walko, Gernot; Woodhouse, Samuel; Pisco, Angela Oliveira; Rognoni, Emanuel; Liakath-Ali, Kifayathullah; Lichtenberger, Beate M.; Mishra, Ajay; Telerman, Stephanie B.; Viswanathan, Priyalakshmi; Logtenberg, Meike; Renz, Lisa M.; Donati, Giacomo; Quist, Sven R.; Watt, Fiona M.

2017-01-01

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2. PMID:28332498

Mechanistic Basis Of Calmodulin Mediated Estrogen Receptor Alpha Activation and Antiestrogen Resistance

DTIC Science & Technology

2010-06-01

for solubility (Figure 5). We call this protein Trx -ERA241-320. We also produced a similar protein construct, but with only residues 241-273 of...ERa, as a “control” (Figure 5). We call this protein Trx -ERA241-273. Because CaM binds tightly to the N-terminal extended ligand binding domain of...ERa (residues 286- 552, see above), we hypothesized that Trx - ERA241-320 would bind tightly to CaM, but that Trx -ERA241-273 would not. The genetic

Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

NASA Astrophysics Data System (ADS)

Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

2015-03-01

Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

Substrate-Triggered Exosite Binding: Synergistic Dendrimer/Folic Acid Action for Achieving Specific, Tight-Binding to Folate Binding Protein.

PubMed

Chen, Junjie; van Dongen, Mallory A; Merzel, Rachel L; Dougherty, Casey A; Orr, Bradford G; Kanduluru, Ananda Kumar; Low, Philip S; Marsh, E Neil G; Banaszak Holl, Mark M

2016-03-14

Polymer-ligand conjugates are designed to bind proteins for applications as drugs, imaging agents, and transport scaffolds. In this work, we demonstrate a folic acid (FA)-triggered exosite binding of a generation five poly(amidoamine) (G5 PAMAM) dendrimer scaffold to bovine folate binding protein (bFBP). The protein exosite is a secondary binding site on the protein surface, separate from the FA binding pocket, to which the dendrimer binds. Exosite binding is required to achieve the greatly enhanced binding constants and protein structural change observed in this study. The G5Ac-COG-FA1.0 conjugate bound tightly to bFBP, was not displaced by a 28-fold excess of FA, and quenched roughly 80% of the initial fluorescence. Two-step binding kinetics were measured using the intrinsic fluorescence of the FBP tryptophan residues to give a KD in the low nanomolar range for formation of the initial G5Ac-COG-FA1.0/FBP* complex, and a slow conversion to the tight complex formed between the dendrimer and the FBP exosite. The extent of quenching was sensitive to the choice of FA-dendrimer linker chemistry. Direct amide conjugation of FA to G5-PAMAM resulted in roughly 50% fluorescence quenching of the FBP. The G5Ac-COG-FA, which has a longer linker containing a 1,2,3-triazole ring, exhibited an ∼80% fluorescence quenching. The binding of the G5Ac-COG-FA1.0 conjugate was compared to poly(ethylene glycol) (PEG) conjugates of FA (PEGn-FA). PEG2k-FA had a binding strength similar to that of FA, whereas other PEG conjugates with higher molecular weight showed weaker binding. However, no PEG conjugates gave an increased degree of total fluorescence quenching.

Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

DTIC Science & Technology

2016-06-01

simulations of the oxidation of Al4Cp * 4 show reasonable comparison with a DFT-based Car -Parrinello method, including correct prediction of hydride transfers...comparison with a DFT-based Car -Parrinello method, including correct prediction of hydride transfers from Cp* to the metal centers during the...initio molecular dynamics of the oxidation of Al4Cp * 4 using a DFT-based Car -Parrinello method. This simulation, which 43 several months on the

Accurate modeling of defects in graphene transport calculations

NASA Astrophysics Data System (ADS)

Linhart, Lukas; Burgdörfer, Joachim; Libisch, Florian

2018-01-01

We present an approach for embedding defect structures modeled by density functional theory into large-scale tight-binding simulations. We extract local tight-binding parameters for the vicinity of the defect site using Wannier functions. In the transition region between the bulk lattice and the defect the tight-binding parameters are continuously adjusted to approach the bulk limit far away from the defect. This embedding approach allows for an accurate high-level treatment of the defect orbitals using as many as ten nearest neighbors while keeping a small number of nearest neighbors in the bulk to render the overall computational cost reasonable. As an example of our approach, we consider an extended graphene lattice decorated with Stone-Wales defects, flower defects, double vacancies, or silicon substitutes. We predict distinct scattering patterns mirroring the defect symmetries and magnitude that should be experimentally accessible.

DFTBaby: A software package for non-adiabatic molecular dynamics simulations based on long-range corrected tight-binding TD-DFT(B)

NASA Astrophysics Data System (ADS)

Humeniuk, Alexander; Mitrić, Roland

2017-12-01

A software package, called DFTBaby, is published, which provides the electronic structure needed for running non-adiabatic molecular dynamics simulations at the level of tight-binding DFT. A long-range correction is incorporated to avoid spurious charge transfer states. Excited state energies, their analytic gradients and scalar non-adiabatic couplings are computed using tight-binding TD-DFT. These quantities are fed into a molecular dynamics code, which integrates Newton's equations of motion for the nuclei together with the electronic Schrödinger equation. Non-adiabatic effects are included by surface hopping. As an example, the program is applied to the optimization of excited states and non-adiabatic dynamics of polyfluorene. The python and Fortran source code is available at http://www.dftbaby.chemie.uni-wuerzburg.de.

A general intermolecular force field based on tight-binding quantum chemical calculations

NASA Astrophysics Data System (ADS)

Grimme, Stefan; Bannwarth, Christoph; Caldeweyher, Eike; Pisarek, Jana; Hansen, Andreas

2017-10-01

A black-box type procedure is presented for the generation of a molecule-specific, intermolecular potential energy function. The method uses quantum chemical (QC) information from our recently published extended tight-binding semi-empirical scheme (GFN-xTB) and can treat non-covalently bound complexes and aggregates with almost arbitrary chemical structure. The necessary QC information consists of the equilibrium structure, Mulliken atomic charges, charge centers of localized molecular orbitals, and also of frontier orbitals and orbital energies. The molecular pair potential includes model density dependent Pauli repulsion, penetration, as well as point charge electrostatics, the newly developed D4 dispersion energy model, Drude oscillators for polarization, and a charge-transfer term. Only one element-specific and about 20 global empirical parameters are needed to cover systems with nuclear charges up to radon (Z = 86). The method is tested for standard small molecule interaction energy benchmark sets where it provides accurate intermolecular energies and equilibrium distances. Examples for structures with a few hundred atoms including charged systems demonstrate the versatility of the approach. The method is implemented in a stand-alone computer code which enables rigid-body, global minimum energy searches for molecular aggregation or alignment.

Preparation and stability of milk somatic cell reference materials.

PubMed

Di Marzo, Larissa; Wojciechowski, Karen L; Barbano, David M

2016-09-01

Our objectives were to develop a method to produce milk somatic cell count (SCC) reference materials for calibration of electronic somatic cell count (ESCC) using gravity separation and to determine the effect of refrigerated storage (4°C) and freeze-thaw stability of the skim and whole milk SCC reference materials. Whole raw milk was high-temperature short-time pasteurized and split into 2 portions. One portion was gravity separated at 4°C for 22 h and the second portion was centrifugally separated to produce skim milk that was also gravity separated with somatic cells rising to the surface. After 22 h, stock solutions (low SCC skim milk, high SCC skim milk, high SCC whole milk) were prepared and preserved (bronopol). Two experiments were conducted, one to compare the shelf-life of skim and whole milk SCC standards at 4°C and one to determine the effect of freezing and thawing on SCC standards. Both experiments were replicated 3 times. Gravity separation was an effective approach to isolate and concentrate somatic cells from bovine milk and redistribute them in a skim or whole milk matrix to create a set of reference materials with a wider and more uniformly distributed range of SCC than current calibration sets. The liquid SCC reference materials stored using the common industry practice at 4°C were stable (i.e., fit for purpose, no large decrease in SCC) for a 2-wk period, whereas frozen and thawed reference materials may have a much longer useful life. A gradual decrease occurred in residual difference in ESCC (SCC × 1,000/mL) versus original assigned reference SCC over duration of refrigerated storage for both skim and whole milk SCC samples, indicating that milk ESCC of the preserved milks was gradually decreasing during 28 d of storage at 4°C by about 15,000 SCC/mL. No difference in the ESCC for skim milk was detected between refrigerated and frozen storage, whereas for whole milk the ESCC for frozen was lower than refrigerated samples. Future work is needed to determine the time and temperature of longer term frozen storage over which the SCC results are stable. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dpb11 may function with RPA and DNA to initiate DNA replication

PubMed Central

Bruck, Irina; Dhingra, Nalini; Martinez, Matthew P.

2017-01-01

Dpb11 is required for the initiation of DNA replication in budding yeast. We found that Dpb11 binds tightly to single-stranded DNA (ssDNA) or branched DNA structures, while its human homolog, TopBP1, binds tightly to branched-DNA structures. We also found that Dpb11 binds stably to CDK-phosphorylated RPA, the eukaryotic ssDNA binding protein, in the presence of branched DNA. A Dpb11 mutant specifically defective for DNA binding did not exhibit tight binding to RPA in the presence of DNA, suggesting that Dpb11-interaction with DNA may promote the recruitment of RPA to melted DNA. We then characterized a mutant of Dpb11 that is specifically defective in DNA binding in budding yeast cells. Expression of dpb11-m1,2,3,5,ΔC results in a substantial decrease in RPA recruitment to origins, suggesting that Dpb11 interaction with DNA may be required for RPA recruitment to origins. Expression of dpb11-m1,2,3,5,ΔC also results in diminished GINS interaction with Mcm2-7 during S phase, while Cdc45 interaction with Mcm2-7 is like wild-type. The reduced GINS interaction with Mcm2-7 may be an indirect consequence of diminished origin melting. We propose that the tight interaction between Dpb11, CDK-phosphorylated RPA, and branched-DNA may be required for the essential function of stabilizing melted origin DNA in vivo. We also propose an alternative model, wherein Dpb11-DNA interaction is required for some other function in DNA replication initiation, such as helicase activation. PMID:28467467

Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination.

PubMed

Fonseca, Nuno A; Rodrigues, Ana S; Rodrigues-Santos, Paulo; Alves, Vera; Gregório, Ana C; Valério-Fernandes, Ângela; Gomes-da-Silva, Lígia C; Rosa, Manuel Santos; Moura, Vera; Ramalho-Santos, João; Simões, Sérgio; Moreira, João Nuno

2015-11-01

Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization and active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem cancer cells (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance for successful therapeutic intervention is the identification of surface receptors overexpressed in both CSC and non-SCC. Cell surface nucleolin has been described as overexpressed in cancer cells as well as a tumor angiogenic marker. Herein we have addressed the questions on whether nucleolin was a common receptor among breast CSC and non-SCC and whether it could be exploited for targeting purposes. Liposomes functionalized with the nucleolin-binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative breast CSC and non-SCC, which was paralleled by OCT4 and NANOG mRNA levels in cells from triple negative breast cancer (TNBC) origin. In murine embryonic stem cells, both nucleolin mRNA levels and F3 peptide-targeted liposomes cellular association were dependent on the stemness status. An in vivo tumorigenic assay suggested that surface nucleolin overexpression per se, could be associated with the identification of highly tumorigenic TNBC cells. This proposed link between nucleolin expression and the stem-like phenotype in TNBC, enabled 100% cell death mediated by F3 peptide-targeted synergistic drug combination, suggesting the potential to abrogate the plasticity and adaptability associated with CSC and non-SCC. Ultimately, nucleolin-specific therapeutic tools capable of simultaneous debulk multiple cellular compartments of the tumor microenvironment may pave the way towards a specific treatment for TNBC patient care. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential protein-coding gene and long noncoding RNA expression in smoking-related lung squamous cell carcinoma.

PubMed

Li, Shicheng; Sun, Xiao; Miao, Shuncheng; Liu, Jia; Jiao, Wenjie

2017-11-01

Cigarette smoking is one of the greatest preventable risk factors for developing cancer, and most cases of lung squamous cell carcinoma (lung SCC) are associated with smoking. The pathogenesis mechanism of tumor progress is unclear. This study aimed to identify biomarkers in smoking-related lung cancer, including protein-coding gene, long noncoding RNA, and transcription factors. We selected and obtained messenger RNA microarray datasets and clinical data from the Gene Expression Omnibus database to identify gene expression altered by cigarette smoking. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the construction of a protein-protein interaction network, transcription factor, and statistical analyses. Subsequent quantitative real-time PCR was utilized to verify these bioinformatic analyses. Five hundred and ninety-eight differentially expressed genes and 21 long noncoding RNA were identified in smoking-related lung SCC. GO and KEGG pathway analysis showed that identified genes were enriched in the cancer-related functions and pathways. The protein-protein interaction network revealed seven hub genes identified in lung SCC. Several transcription factors and their binding sites were predicted. The results of real-time quantitative PCR revealed that AURKA and BIRC5 were significantly upregulated and LINC00094 was downregulated in the tumor tissues of smoking patients. Further statistical analysis indicated that dysregulation of AURKA, BIRC5, and LINC00094 indicated poor prognosis in lung SCC. Protein-coding genes AURKA, BIRC5, and LINC00094 could be biomarkers or therapeutic targets for smoking-related lung SCC. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Estimating milk yield and value losses from increased somatic cell count on US dairy farms.

PubMed

Hadrich, J C; Wolf, C A; Lombard, J; Dolak, T M

2018-04-01

Milk loss due to increased somatic cell counts (SCC) results in economic losses for dairy producers. This research uses 10 mo of consecutive dairy herd improvement data from 2013 and 2014 to estimate milk yield loss using SCC as a proxy for clinical and subclinical mastitis. A fixed effects regression was used to examine factors that affected milk yield while controlling for herd-level management. Breed, milking frequency, days in milk, seasonality, SCC, cumulative months with SCC greater than 100,000 cells/mL, lactation, and herd size were variables included in the regression analysis. The cumulative months with SCC above a threshold was included as a proxy for chronic mastitis. Milk yield loss increased as the number of test days with SCC ≥100,000 cells/mL increased. Results from the regression were used to estimate a monetary value of milk loss related to SCC as a function of cow and operation related explanatory variables for a representative dairy cow. The largest losses occurred from increased cumulative test days with a SCC ≥100,000 cells/mL, with daily losses of $1.20/cow per day in the first month to $2.06/cow per day in mo 10. Results demonstrate the importance of including the duration of months above a threshold SCC when estimating milk yield losses. Cows with chronic mastitis, measured by increased consecutive test days with SCC ≥100,000 cells/mL, resulted in higher milk losses than cows with a new infection. This provides farm managers with a method to evaluate the trade-off between treatment and culling decisions as it relates to mastitis control and early detection. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Most of the tight positional conservation of transcription factor binding sites near the transcription start site reflects their co-localization within regulatory modules.

PubMed

Acevedo-Luna, Natalia; Mariño-Ramírez, Leonardo; Halbert, Armand; Hansen, Ulla; Landsman, David; Spouge, John L

2016-11-21

Transcription factors (TFs) form complexes that bind regulatory modules (RMs) within DNA, to control specific sets of genes. Some transcription factor binding sites (TFBSs) near the transcription start site (TSS) display tight positional preferences relative to the TSS. Furthermore, near the TSS, RMs can co-localize TFBSs with each other and the TSS. The proportion of TFBS positional preferences due to TFBS co-localization within RMs is unknown, however. ChIP experiments confirm co-localization of some TFBSs genome-wide, including near the TSS, but they typically examine only a few TFs at a time, using non-physiological conditions that can vary from lab to lab. In contrast, sequence analysis can examine many TFs uniformly and methodically, broadly surveying the co-localization of TFBSs with tight positional preferences relative to the TSS. Our statistics found 43 significant sets of human motifs in the JASPAR TF Database with positional preferences relative to the TSS, with 38 preferences tight (±5 bp). Each set of motifs corresponded to a gene group of 135 to 3304 genes, with 42/43 (98%) gene groups independently validated by DAVID, a gene ontology database, with FDR < 0.05. Motifs corresponding to two TFBSs in a RM should co-occur more than by chance alone, enriching the intersection of the gene groups corresponding to the two TFs. Thus, a gene-group intersection systematically enriched beyond chance alone provides evidence that the two TFs participate in an RM. Of the 903 = 43*42/2 intersections of the 43 significant gene groups, we found 768/903 (85%) pairs of gene groups with significantly enriched intersections, with 564/768 (73%) intersections independently validated by DAVID with FDR < 0.05. A user-friendly web site at http://go.usa.gov/3kjsH permits biologists to explore the interaction network of our TFBSs to identify candidate subunit RMs. Gene duplication and convergent evolution within a genome provide obvious biological mechanisms for replicating an RM near the TSS that binds a particular TF subunit. Of all intersections of our 43 significant gene groups, 85% were significantly enriched, with 73% of the significant enrichments independently validated by gene ontology. The co-localization of TFBSs within RMs therefore likely explains much of the tight TFBS positional preferences near the TSS.

Universal tight binding model for chemical reactions in solution and at surfaces. II. Water.

PubMed

Lozovoi, A Y; Sheppard, T J; Pashov, D L; Kohanoff, J J; Paxton, A T

2014-07-28

A revised water model intended for use in condensed phase simulations in the framework of the self consistent polarizable ion tight binding theory is constructed. The model is applied to water monomer, dimer, hexamers, ice, and liquid, where it demonstrates good agreement with theoretical results obtained by more accurate methods, such as DFT and CCSD(T), and with experiment. In particular, the temperature dependence of the self diffusion coefficient in liquid water predicted by the model, closely reproduces experimental curves in the temperature interval between 230 K and 350 K. In addition, and in contrast to standard DFT, the model properly orders the relative densities of liquid water and ice. A notable, but inevitable, shortcoming of the model is underestimation of the static dielectric constant by a factor of two. We demonstrate that the description of inter and intramolecular forces embodied in the tight binding approximation in quantum mechanics leads to a number of valuable insights which can be missing from ab initio quantum chemistry and classical force fields. These include a discussion of the origin of the enhanced molecular electric dipole moment in the condensed phases, and a detailed explanation for the increase of coordination number in liquid water as a function of temperature and compared with ice--leading to insights into the anomalous expansion on freezing. The theory holds out the prospect of an understanding of the currently unexplained density maximum of water near the freezing point.

Separating Spike Count Correlation from Firing Rate Correlation

PubMed Central

Vinci, Giuseppe; Ventura, Valérie; Smith, Matthew A.; Kass, Robert E.

2016-01-01

Populations of cortical neurons exhibit shared fluctuations in spiking activity over time. When measured for a pair of neurons over multiple repetitions of an identical stimulus, this phenomenon emerges as correlated trial-to-trial response variability via spike count correlation (SCC). However, spike counts can be viewed as noisy versions of firing rates, which can vary from trial to trial. From this perspective, the SCC for a pair of neurons becomes a noisy version of the corresponding firing-rate correlation (FRC). Furthermore, the magnitude of the SCC is generally smaller than that of the FRC, and is likely to be less sensitive to experimental manipulation. We provide statistical methods for disambiguating time-averaged drive from within-trial noise, thereby separating FRC from SCC. We study these methods to document their reliability, and we apply them to neurons recorded in vivo from area V4, in an alert animal. We show how the various effects we describe are reflected in the data: within-trial effects are largely negligible, while attenuation due to trial-to-trial variation dominates, and frequently produces comparisons in SCC that, because of noise, do not accurately reflect those based on the underlying FRC. PMID:26942746

Microbiological quality and somatic cell count in bulk milk of dromedary camels (Camelus dromedarius): descriptive statistics, correlations, and factors of variation.

PubMed

Nagy, P; Faye, B; Marko, O; Thomas, S; Wernery, U; Juhasz, J

2013-09-01

The objectives of the present study were to monitor the microbiological quality and somatic cell count (SCC) of bulk tank milk at the world's first large-scale camel dairy farm for a 2-yr period, to compare the results of 2 methods for the enumeration of SCC, to evaluate correlation among milk quality indicators, and to determine the effect of specific factors (year, season, stage of lactation, and level of production) on milk quality indicators. The study was conducted from January 2008 to January 2010. Total viable count (TVC), coliform count (CC), California Mastitis Test (CMT) score, and SCC were determined from daily bulk milk samples. Somatic cell count was measured by using a direct microscopic method and with an automatic cell counter. In addition, production parameters [total daily milk production (TDM, kg), number of milking camels (NMC), average milk per camel (AMC, kg)] and stage of lactation (average postpartum days, PPD) were recorded for each test day. A strong correlation (r=0.33) was found between the 2 methods for SCC enumeration; however, values derived using the microscopic method were higher. The geometric means of SCC and TVC were 394×10(3) cells/mL and 5,157 cfu/mL during the observation period, respectively. Somatic cell count was >500×10(3) cells/mL on 14.6% (106/725) and TVC was >10×10(3) cfu/mL on 4.0% (30/742) of the test days. Both milk quality indicators had a distinct seasonal pattern. For log SCC, the mean was lowest in summer and highest in autumn. The seasonal pattern of log TVC was slightly different, with the lowest values being recorded during the spring. The monthly mean TVC pattern showed a clear difference between years. Coliform count was <10 cfu/mL in most of the samples (709/742, 95.6%). A positive correlation was found between log SCC and log TVC (r=0.32), between log SCC and CMT score (r=0.26), and between log TVC and CC in yr 1 (r=0.30). All production parameters and stage of lactation showed strong seasonal variation. Log SCC was negatively correlated with TDM (r=-0.35), AMC (r=-0.37), and NMC (r=-0.15) and positively correlated with PPD (r=0.40). Log TVC had a negative correlation with AMC (r=-0.40) but a positive correlation with NMC (r=0.32), TDM (r=0.16), and PPD (r=0.45). The linear mixed model with stepwise variable selection showed that the main sources of log SCC variation were PPD, TDM, PPD × season, and season. For log TVC, the same factors and year contributed to the variation. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Transmission eigenchannels from nonequilibrium Green's functions

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Brandbyge, Mads

2007-09-01

The concept of transmission eigenchannels is described in a tight-binding nonequilibrium Green’s function (NEGF) framework. A simple procedure for calculating the eigenchannels is derived using only the properties of the device subspace and quantities normally available in a NEGF calculation. The method is exemplified by visualization in real space of the eigenchannels for three different molecular and atomic wires.

Improved Stress Corrosion Cracking Resistance and Strength of a Two-Step Aged Al-Zn-Mg-Cu Alloy Using Taguchi Method

NASA Astrophysics Data System (ADS)

Lin, Lianghua; Liu, Zhiyi; Ying, Puyou; Liu, Meng

2015-12-01

Multi-step heat treatment effectively enhances the stress corrosion cracking (SCC) resistance but usually degrades the mechanical properties of Al-Zn-Mg-Cu alloys. With the aim to enhance SCC resistance as well as strength of Al-Zn-Mg-Cu alloys, we have optimized the process parameters during two-step aging of Al-6.1Zn-2.8Mg-1.9Cu alloy by Taguchi's L9 orthogonal array. In this work, analysis of variance (ANOVA) was performed to find out the significant heat treatment parameters. The slow strain rate testing combined with scanning electron microscope and transmission electron microscope was employed to study the SCC behaviors of Al-Zn-Mg-Cu alloy. Results showed that the contour map produced by ANOVA offered a reliable reference for selection of optimum heat treatment parameters. By using this method, a desired combination of mechanical performances and SCC resistance was obtained.

Physical and metabolic requirements for early interaction of poliovirus and human rhinovirus with HeLa cells.

PubMed Central

Lonberg-Holm, K; Whiteley, N M

1976-01-01

Attachment, ""tight binding'' and eclipse of radioactive poliovirus 2 (P2) and human rhinovirus 2 (HRV 2) were investigated. The activation energy for attachment of both HRV2 and P2 was about 13 kcal/mol. HRV2 differed from P2 in two respects: the Arrhenius plot for attachment of HRV2 showed a break at 15 to 19 degrees C when the cells were first treated several hours at 0 degrees C, and attachment of HRV2 was inhibited by treatment of cells with metabolic poisons able to reduce cellular ATP by more than 90%. Tight binding was determined by isolation of a specific P2-membrane complex or by loss of EDTA dissociability of HRV2. Tight binding of both viruses was slowed by 0.01 M iodoacetamide but not by 0.02 M F-; F- plus 0.002 M CN- slowed tight binding of HRV2 but not of P2. Eclipse, the irreversible alteration of parental virions, was detected by isolation of cell-associated subviral particles or by loss of cell-associated infectious virus. Eclipse of both viruses is slowed by iodoacetamide or F-. It seems likely that the early steps of infection with picornaviruses may be sensitive to alterations in the cell membrane produced by metabolic inhibitors or by treatment at low temperature. PMID:184301

Edge currents in frustrated Josephson junction ladders

NASA Astrophysics Data System (ADS)

Marques, A. M.; Santos, F. D. R.; Dias, R. G.

2016-09-01

We present a numerical study of quasi-1D frustrated Josephson junction ladders with diagonal couplings and open boundary conditions, in the large capacitance limit. We derive a correspondence between the energy of this Josephson junction ladder and the expectation value of the Hamiltonian of an analogous tight-binding model, and show how the overall superconducting state of the chain is equivalent to the minimum energy state of the tight-binding model in the subspace of one-particle states with uniform density. To satisfy the constraint of uniform density, the superconducting state of the ladder is written as a linear combination of the allowed k-states of the tight-binding model with open boundaries. Above a critical value of the parameter t (ratio between the intra-rung and inter-rung Josephson couplings) the ladder spontaneously develops currents at the edges, which spread to the bulk as t is increased until complete coverage is reached. Above a certain value of t, which varies with ladder size (t = 1 for an infinite-sized ladder), the edge currents are destroyed. The value t = 1 corresponds, in the tight-binding model, to the opening of a gap between two bands. We argue that the disappearance of the edge currents with this gap opening is not coincidental, and that this points to a topological origin for these edge current states.

Bak Conformational Changes Induced by Ligand Binding: Insight into BH3 Domain Binding and Bak Homo-Oligomerization

PubMed Central

Pang, Yuan-Ping; Dai, Haiming; Smith, Alyson; Meng, X. Wei; Schneider, Paula A.; Kaufmann, Scott H.

2012-01-01

Recently we reported that the BH3-only proteins Bim and Noxa bind tightly but transiently to the BH3-binding groove of Bak to initiate Bak homo-oligomerization. However, it is unclear how such tight binding can induce Bak homo-oligomerization. Here we report the ligand-induced Bak conformational changes observed in 3D models of Noxa·Bak and Bim·Bak refined by molecular dynamics simulations. In particular, upon binding to the BH3-binding groove, Bim and Noxa induce a large conformational change of the loop between helices 1 and 2 and in turn partially expose a remote groove between helices 1 and 6 in Bak. These observations, coupled with the reported experimental data, suggest formation of a pore-forming Bak octamer, in which the BH3-binding groove is at the interface on one side of each monomer and the groove between helices 1 and 6 is at the interface on the opposite side, initiated by ligand binding to the BH3-binding groove. PMID:22355769

Two different protein expression profiles of oral squamous cell carcinoma analyzed by immunoprecipitation high-performance liquid chromatography.

PubMed

Kim, Soung Min; Jeong, Dasul; Kim, Min Keun; Lee, Sang Shin; Lee, Suk Keun

2017-08-08

Oral squamous cell carcinoma (OSCC) is one of the most dangerous cancers in the body, producing serious complications with individual behaviors. Many different pathogenetic factors are involved in the carcinogenesis of OSCC. Cancer cells derived from oral keratinocytes can produce different carcinogenic signaling pathways through differences in protein expression, but their protein expression profiles cannot be easily explored with ordinary detection methods. The present study compared the protein expression profiles between two different types of OSCCs, which were analyzed through immunoprecipitation high-performance liquid chromatography (IP-HPLC). Two types of squamous cell carcinoma (SCC) occurred in a mandibular (SCC-1) and maxillary gingiva (SCC-2), but their clinical features and progression were quite different from each other. SCC-1 showed a large gingival ulceration with severe halitosis and extensive bony destruction, while SCC-2 showed a relatively small papillary gingival swelling but rapidly grew to form a large submucosal mass, followed by early cervical lymph node metastasis. In the histological observation, SCC-1 was relatively well differentiated with a severe inflammatory reaction, while SCC-2 showed severely infiltrative growth of each cancer islets accompanied with a mild inflammatory reaction. IP-HPLC analysis revealed contrary protein expression profiles analyzed by 72 different oncogenic proteins. SCC-1 showed more cellular apoptosis and invasive growth than SCC-2 through increased expression of caspases, MMPs, p53 signaling, FAS signaling, TGF-β1 signaling, and angiogenesis factors, while SCC-2 showed more cellular growth and survival than SCC-1 through the increased expression of proliferating factors, RAS signaling, eIF5A signaling, WNT signaling, and survivin. The increased trends of cellular apoptosis and invasiveness in the protein expression profiles of SCC-1 were implicative of its extensive gingival ulceration and bony destruction, while the increased trends of cellular proliferation and survival in the protein profile of SCC-2 were implicative of its rapid growing tumor mass and early lymph node metastasis. These analyses of the essential oncogenic protein expression profiles in OSCC provide important information for genetic counseling or customized gene therapy in cancer treatment. Therefore, protein expression profile analysis through IP-HPLC is helpful not only for the molecular genetic diagnosis of cancer but also in identifying target molecules for customized gene therapy in near future.

Convergence of Molecular Dynamics Simulation of Protein Native States: Feasibility vs Self-Consistency Dilemma.

PubMed

Sawle, Lucas; Ghosh, Kingshuk

2016-02-09

All-atom molecular dynamics simulations need convergence tests to evaluate the quality of data. The notion of "true" convergence is elusive, and one can only hope to satisfy self-consistency checks (SCC). There are multiple SCC criteria, and their assessment of all-atom simulations of the native state for real globular proteins is sparse. Here, we present a systematic study of different SCC algorithms, both in terms of their ability to detect the lack of self-consistency and their computational demand, for the all-atom native state simulations of four globular proteins (CSP, CheA, CheW, and BPTI). Somewhat surprisingly, we notice some of the most stringent SCC criteria, e.g., the criteria demanding similarity of the cluster probability distribution between the first and the second halves of the trajectory or the comparison of fluctuations between different blocks using covariance overlap measure, can require tens of microseconds of simulation even for proteins with less than 100 amino acids. We notice such long simulation times can sometimes be associated with traps, but these traps cannot be detected by some of the common SCC methods. We suggest an additional, and simple, SCC algorithm to quickly detect such traps by monitoring the constancy of the cluster entropy (CCE). CCE is a necessary but not sufficient criteria, and additional SCC algorithms must be combined with it. Furthermore, as seen in the explicit solvent simulation of 1 ms long trajectory of BPTI,1 passing self-consistency checks at an earlier stage may be misleading due to conformational changes taking place later in the simulation, resulting in different, but segregated regions of SCC. Although there is a hierarchy of complex SCC algorithms, caution must be exercised in their application with the knowledge of their limitations and computational expense.

Band gap engineering for poly(p-phenylene) and poly(p-phenylene vinylene) copolymers using the tight-binding approach

NASA Astrophysics Data System (ADS)

Giro, R.; Caldas, M. J.; Galvão, D. S.

The interest in poly(p-phenylene) (PPP) and poly(p-phenylene vinylene) (PPV) copolymers stems from the fact that these homopolymers present interesting optical and electronic properties that allow a great variety of technological applications. Combining different numbers of PPP and PPV units it is possible, in principle, to obtain new structures presenting intermediate gap values (2.8 eV and 2.4 eV for PPP and PPV, respectively). For this study we used a Hückel Hamiltonian tight-binding coupled to the negative factor counting (NFC) technique. We carried out a systematic search to determine optimum relative concentrations for disordered binary polymeric alloys with predefined gap values. Once these structures were obtained, we used the semiempirical methods AM1/PM3 and ZINDO/S-CI for geometrical and optical studies, respectively. Our theoretical results show that it is possible to obtain copolymers of PPP and PPV with intermediate gap values of their parent structures.

Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin

PubMed Central

Lee, Yang; Willers, Chrissie; Kunji, Edmund R. S.; Crichton, Paul G.

2015-01-01

Uncoupling protein 1 (UCP1) catalyzes fatty acid-activated, purine nucleotide-sensitive proton leak across the mitochondrial inner membrane of brown adipose tissue to produce heat, and could help combat obesity and metabolic disease in humans. Studies over the last 30 years conclude that the protein is a dimer, binding one nucleotide molecule per two proteins, and unlike the related mitochondrial ADP/ATP carrier, does not bind cardiolipin. Here, we have developed novel methods to purify milligram amounts of UCP1 from native sources by using covalent chromatography that, unlike past methods, allows the protein to be prepared in defined conditions, free of excess detergent and lipid. Assessment of purified preparations by TLC reveal that UCP1 retains tightly bound cardiolipin, with a lipid phosphorus content equating to three molecules per protein, like the ADP/ATP carrier. Cardiolipin stabilizes UCP1, as demonstrated by reconstitution experiments and thermostability assays, indicating that the lipid has an integral role in the functioning of the protein, similar to other mitochondrial carriers. Furthermore, we find that UCP1 is not dimeric but monomeric, as indicated by size exclusion analysis, and has a ligand titration profile in isothermal calorimetric measurements that clearly shows that one nucleotide binds per monomer. These findings reveal the fundamental composition of UCP1, which is essential for understanding the mechanism of the protein. Our assessment of the properties of UCP1 indicate that it is not unique among mitochondrial carriers and so is likely to use a common exchange mechanism in its primary function in brown adipose tissue mitochondria. PMID:26038550

Limitations of on-site dairy farm regulatory debits as milk quality predictors.

PubMed

Borneman, Darand L; Stiegert, Kyle; Ingham, Steve

2015-03-01

In the United States, compliance with grade A raw fluid milk regulatory standards is assessed via laboratory milk quality testing and by on-site inspection of producers (farms). This study evaluated the correlation between on-site survey debits being marked and somatic cell count (SCC) or standard plate count (SPC) laboratory results for 1,301 Wisconsin grade A dairy farms in 2012. Debits recorded on the survey form were tested as predictors of laboratory results utilizing ordinary least squares regression to determine if results of the current method for on-site evaluation of grade A dairy farms accurately predict SCC and SPC test results. Such a correlation may indicate that current methods of on-site inspection serve the primary intended purpose of assuring availability of high-quality milk. A model for predicting SCC was estimated using ordinary least squares regression methods. Step-wise selected regressors of grouped debit items were able to predict SCC levels with some degree of accuracy (adjusted R2=0.1432). Specific debit items, seasonality, and farm size were the best predictors of SCC levels. The SPC data presented an analytical challenge because over 75% of the SPC observations were at or below a 25,000 cfu/mL threshold but were recorded by testing laboratories as at the threshold value. This classic censoring problem necessitated the use of a Tobit regression approach. Even with this approach, prediction of SPC values based on on-site survey criteria was much less successful (adjusted R2=0.034) and provided little support for the on-site survey system as a way to inform farmers about making improvements that would improve SPC. The lower level of correlation with SPC may indicate that factors affecting SPC are more varied and differ from those affecting SCC. Further, unobserved deficiencies in postmilking handling and storage sanitation could enhance bacterial growth and increase SPC, whereas postmilking sanitation will have no effect on SCC because somatic cells do not reproduce in stored milk. Results suggest that close examination, and perhaps redefinition, of survey debits, along with making the survey coincident with SCC and SPC sampling, could make the on-site survey a better tool for ensuring availability of high-quality milk. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores

NASA Astrophysics Data System (ADS)

Miller, Jessica P.; Habimana-Griffin, LeMoyne; Edwards, Tracy S.; Achilefu, Samuel

2017-06-01

Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57±0.026 ns and 0.61±0.021 ns, respectively (p=0.004). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

Performance-Based Specifications of Workability Characteristics of Prestressed, Precast Self-Consolidating Concrete-A North American Prospective.

PubMed

Long, Wu-Jian; Khayat, Kamal Henri; Lemieux, Guillaume; Hwang, Soo-Duck; Han, Ning-Xu

2014-03-27

Adequate selection of material constituents and test methods are necessary for workability specifications and performance of hardened concrete. An experimental program was performed to evaluate the suitability of various test methods for workability assessment and to propose performance specifications of prestressed concrete. In total, 33 self-consolidating concrete (SCC) mixtures made with various mixture proportioning parameters, including maximum size and type of aggregate, type and content of binder, and w/cm were evaluated. Correlations among various test results used in evaluating the workability responses are established. It is recommended that SCC should have slump flow values of 635-760 mm. To ensure proper filling capacity greater than 80%, such concrete should have a passing ability that corresponds to L-box blocking ratio (h₂/h₁) ≥ 0.5, J-Ring flow of 570-685 mm, slump flow minus J-Ring flow diameter ≤75 mm. Moreover, Stable SCC should develop a column segregation index lower than 5%, and rate of settlement at 30 min of 0.27%/h for SCC proportioned with 12.5 or 9.5 mm MSA. It is recommended that SCC should have a plastic viscosity of 100-225 Pa·s and 100-400 Pa·s for concrete made with crushed aggregate and gravel, respectively, to ensure proper workability.

Kindler syndrome in mice and men.

PubMed

Duperret, Elizabeth K; Ridky, Todd W

2014-09-01

Kindler syndrome (KS) in humans is a severe skin blistering disease associated with inflammation and increased risk of epidermal squamous cell carcinoma (SCC). This disease is known to be caused by loss-of-function mutations in Kindlin-1, a focal adhesion β-integrin binding protein. Thus far, it has been unclear what specific signaling events occur in KS keratinocytes to promote tumorigenesis, especially since loss of β-integrins and focal adhesion complexes has been previously shown to prevent or delay tumor formation. In the April issue of Nature Medicine, Rognoni and colleagues generate a transgenic mouse lacking Kindlin-1 in the epidermis to model the key features of KS, and show that Kindlin-1 regulates Wnt and TGFβ signaling independent of β-integrins. These β1-integrin-independent functions of Kindlin-1 may contribute to the increased SCC risk in KS patients.

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Hidalgo, Alejandro A.; Luo, Wei; Delansorne, Remi; Johnson, Candace S.; Trump, Donald L.

2013-01-01

Epidemiological data suggest an important role of vitamin D signaling in cancer development and progression, and experimental studies demonstrate that the active vitamin D metabolite 1α, 25-dihydroxyvitamin D₃ (1,25D₃) has broad spectrum antitumor activity. Hypercalcemia has often been suggested to limit the clinical application of these data. The 14-epi-analog of 1,25D₃, inecalcitol [19-nor-14-epi-23-yne-1,25-(OH)₂D₃; TX522], was developed to have superagonistic antitumor activities but low hypercalcemia potential. We examined the antitumor activity of inecalcitol and the underlying mechanisms in a murine squamous cell carcinoma (SCC) model system. In vitro, compared with 1,25D₃, inecalcitol showed enhanced vitamin D receptor (VDR)-mediated transcriptional activity. Inecalcitol suppressed SCC cell proliferation in a dose-dependent manner with an IC₅₀ value 30 times lower than that of 1,25D₃. Both inecalcitol and 1,25D₃ induced a comparable level of G₀/G₁ cell cycle arrest in SCC cells. The level of apoptosis induced by inecalcitol was markedly higher than that of 1,25D₃. Apoptosis was mediated through the activation of the caspase 8/10- caspase 3 pathway. Further, inecalcitol markedly inhibited the mRNA and protein expression of c-IAP1 and XIAP compared with 1,25D₃. In vivo, inecalcitol inhibits SCC tumor growth in a dose-dependent fashion. Notably, inecalcitol induced a significantly higher level of apoptosis in the SCC xenograft model. While in vitro inecalcitol demonstrates apparent enhanced VDR binding and antiproliferative effects compared to 1,25D₃, in vivo these advantages disappear; at doses of inecalcitol that have equivalent antitumor effects, similar hypercalcemia is seen. This may be explained by the pharmacokinetics of 1,25D₃ vs. inecalcitol and attributed to the much shorter serum half-life of inecalcitol.We show that inecalcitol has potent antitumor activity in the SCC model system, and this is associated with a strong induction of apoptosis. These findings support the further development of inecalcitol in cancer treatment. PMID:23388458

Prediction of Mean and Design Fatigue Lives of Self Compacting Concrete Beams in Flexure

NASA Astrophysics Data System (ADS)

Goel, S.; Singh, S. P.; Singh, P.; Kaushik, S. K.

2012-02-01

In this paper, result of an investigation conducted to study the flexural fatigue characteristics of self compacting concrete (SCC) beams in flexure are presented. An experimental programme was planned in which approximately 60 SCC beam specimens of size 100 × 100 × 500 mm were tested under flexural fatigue loading. Approximately 45 static flexural tests were also conducted to facilitate fatigue testing. The flexural fatigue and static flexural strength tests were conducted on a 100 kN servo-controlled actuator. The fatigue life data thus obtained have been used to establish the probability distributions of fatigue life of SCC using two-parameter Weibull distribution. The parameters of the Weibull distribution have been obtained by different methods of analysis. Using the distribution parameters, the mean and design fatigue lives of SCC have been estimated and compared with Normally vibrated concrete (NVC), the data for which have been taken from literature. It has been observed that SCC exhibits higher mean and design fatigue lives compared to NVC.

Environmental effects on aluminum fracture

NASA Technical Reports Server (NTRS)

Schwartzberg, F. R.; Shepic, J. A.

1976-01-01

The sustained load stress corrosion cracking (SCC) threshold for aluminum alloy 214 was determined using smooth (sigma sub TH) and precracked (K sub ISCC) specimens, and cyclic load growth behavior in 3.5% NaCl salt solution was studied. The relationship between K sub ISCC and sigma sub TH was also studied. The work showed that 2124-T851 aluminum alloy in plate gage has a moderately high resistance to stress corrosion attack. Experimental results showed that no SCC occurred in the longitudinal and long transverse directions in any of the tests. Some SCC was found by smooth tests in the short transverse direction, and the data were confirmed by two test methods-sigma sub TH = 275 MN/sq m (40 ksi). No SCC was found from compact specimen tests in any direction: surface flaw and center notch specimens evaluated in the short transverse direction exhibited SCC. The data indicate that stress corrosion behavior is defect, size, and stress dependent, but not entirely in accordance with a stress intensity controlled mechanism.

Regulation of Motility, Invasion and Metastatic Potential of Squamous Cell Carcinoma by 1,25D3

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Su, Bing; Seshadri, Mukund; Luo, Wei; Trump, Donald L.; Johnson, Candace S.

2012-01-01

BACKGROUND 1,25D3, the active metabolite of vitamin D, has been shown to exhibit broad spectrum anti-tumor activity in xenograft animal models. However, its activity against metastatic disease has not been extensively investigated. METHODS Squamous cell carcinoma (SCC) or 1,25D3-resistant variant SCC-DR cells were treated with 1,25D3. Actin organization was examined by immunofluorescence assay. Cell migration was assessed by “wound” healing and chemotactic migration assay. Cell invasion was assessed by Matrigel-based invasion assay and in situ zymography. MMP-2 and MMP-9 expression and secretion was examined by immunoblot analysis and ELISA, respectively. E-cadherin expression was assessed by flow cytometry, immunoblot analysis and immunohistochemistry. Knockdown of E-cadherin was achieved by siRNA. Experimental metastasis mouse model was done by intravenous injection of tumor cells. Lung tumor development was assessed by magnetic resonance imaging, gross observation and histology. RESULTS SCC cellular morphology and actin organization were altered by 10 nM of 1,25D3. 1,25D3 inhibited SCC cell motility and invasion, which was associated with reduced expression and secretion of MMP-2 and MMP-9. 1,25D3 promoted the expression of E-cadherin. These findings were not observed in SCC-DR cells. Knock down of E-cadherin rescued 1,25D3-inhibited cell migration. Intravenous injection of SCC or SCC-DR cells resulted in the establishment of extensive pulmonary lesions in saline-treated C3H mice. Treatment with 1,25D3 resulted in a marked reduction in the formation of lung tumor colonies in animals injected with SCC but not SCC-DR cells. CONCLUSIONS 1,25D3 suppresses SCC cell motility, invasion and metastasis, partially through the promotion of E-cadherin-mediated cell-cell adhesion. PMID:22833444

Anal Cancer Incidence in the United States, 1977–2011: Distinct Patterns by Histology and Behavior

PubMed Central

Shiels, Meredith S.; Kreimer, Aimée R.; Coghill, Anna E.; Darragh, Teresa M.; Devesa, Susan S.

2015-01-01

Background Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are generally combined in cancer surveillance, their etiologies likely differ. Here, we describe demographic characteristics and trends in incidence rates (IRs) of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the United States. Methods With data from the Surveillance, Epidemiology and End Results (SEER) Program, we estimated age-adjusted anal cancer IRs across behavior/histology by demographic and tumor characteristics for 2000–2011. Trends in IRs and annual percent changes during 1977–2011 were also estimated and compared to rectal cancer. Results Women had higher rates of SCC (rate ratio [RR]=1.45; 95%CI 1.40–1.50) and lower rates of ADC (RR=0.68; 95%CI 0.62–0.74) and squamous carcinoma in situ (CIS) (RR=0.36; 95%CI 0.34–0.38) than men. Blacks had lower rates of SCC (RR=0.82; 95%CI 0.77–0.87) and CIS (RR=0.90; 95%CI 0.83–0.98) than non-Hispanic whites, but higher rates of ADC (RR=1.48; 95%CI 1.29–1.70). Anal cancer IRs were higher in men and blacks aged <40 years. During 1992–2011, SCC IRs increased 2.9%/year, ADC IRs declined non-significantly, and CIS IRs rose 14.2%/year. SCC and ADC IR patterns and trends were similar across anal and rectal cancers. Conclusions Rates of anal SCC and CIS have increased strongly over time, in contrast to rates of anal ADC, similar to trends observed for rectal SCC and ADC. Impact Anal SCC and ADC likely have different etiologies, but may have similar etiologies to rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may reflect anal cancer screening patterns. PMID:26224796

Schematic baryon models, their tight binding description and their microwave realization

NASA Astrophysics Data System (ADS)

Sadurní, E.; Franco-Villafañe, J. A.; Kuhl, U.; Mortessagne, F.; Seligman, T. H.

2013-12-01

A schematic model for baryon excitations is presented in terms of a symmetric Dirac gyroscope, a relativistic model solvable in closed form, that reduces to a rotor in the non-relativistic limit. The model is then mapped on a nearest neighbour tight binding model. In its simplest one-dimensional form this model yields a finite equidistant spectrum. This is experimentally implemented as a chain of dielectric resonators under conditions where their coupling is evanescent and a good agreement with the prediction is achieved.

Magnetic susceptibilities of actinide 3d-metal intermetallic compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muniz, R.B.; d'Albuquerque e Castro, J.; Troper, A.

1988-04-15

We have numerically calculated the magnetic susceptibilities which appear in the Hartree--Fock instability criterion for actinide 3d transition-metal intermetallic compounds. This calculation is based on a previous tight-binding description of these actinide-based compounds (A. Troper and A. A. Gomes, Phys. Rev. B 34, 6487 (1986)). The parameters of the calculation, which starts from simple tight-binding d and f bands are (i) occupation numbers, (ii) ratio of d-f hybridization to d bandwidth, and (iii) electron-electron Coulomb-type interactions.

Atomistic analysis of valley-orbit hybrid states and inter-dot tunnel rates in a Si double quantum dot

NASA Astrophysics Data System (ADS)

Ferdous, Rifat; Rahman, Rajib; Klimeck, Gerhard

2014-03-01

Silicon quantum dots are promising candidates for solid-state quantum computing due to the long spin coherence times in silicon, arising from small spin-orbit interaction and a nearly spin free host lattice. However, the conduction band valley degeneracy adds an additional degree of freedom to the electronic structure, complicating the encoding and operation of qubits. Although the valley and the orbital indices can be uniquely identified in an ideal silicon quantum dot, atomic-scale disorder mixes valley and orbital states in realistic dots. Such valley-orbit hybridization, strongly influences the inter-dot tunnel rates.Using a full-band atomistic tight-binding method, we analyze the effect of atomic-scale interface disorder in a silicon double quantum dot. Fourier transform of the tight-binding wavefunctions helps to analyze the effect of disorder on valley-orbit hybridization. We also calculate and compare inter-dot inter-valley and intra-valley tunneling, in the presence of realistic disorder, such as interface tilt, surface roughness, alloy disorder, and interface charges. The method provides a useful way to compute electronic states in realistically disordered systems without any posteriori fitting parameters.

Crumbs3 Is Essential for Proper Epithelial Development and Viability

PubMed Central

Whiteman, Eileen L.; Fan, Shuling; Harder, Jennifer L.; Walton, Katherine D.; Liu, Chia-Jen; Soofi, Abdul; Fogg, Vanessa C.; Hershenson, Marc B.; Dressler, Gregory R.; Deutsch, Gail H.; Gumucio, Deborah L.

2014-01-01

First identified in Drosophila, the Crumbs (Crb) proteins are important in epithelial polarity, apical membrane formation, and tight junction (TJ) assembly. The conserved Crb intracellular region includes a FERM (band 4.1/ezrin/radixin/moesin) binding domain (FBD) whose mammalian binding partners are not well understood and a PDZ binding motif that interacts with mammalian Pals1 (protein associated with lin seven) (also known as MPP5). Pals1 binds Patj (Pals1-associated tight-junction protein), a multi-PDZ-domain protein that associates with many tight junction proteins. The Crb complex also binds the conserved Par3/Par6/atypical protein kinase C (aPKC) polarity cassette that restricts migration of basolateral proteins through phosphorylation. Here, we describe a Crb3 knockout mouse that demonstrates extensive defects in epithelial morphogenesis. The mice die shortly after birth, with cystic kidneys and proteinaceous debris throughout the lungs. The intestines display villus fusion, apical membrane blebs, and disrupted microvilli. These intestinal defects phenocopy those of Ezrin knockout mice, and we demonstrate an interaction between Crumbs3 and ezrin. Taken together, our data indicate that Crumbs3 is crucial for epithelial morphogenesis and plays a role in linking the apical membrane to the underlying ezrin-containing cytoskeleton. PMID:24164893

Reductive half-reaction of aldehyde oxidoreductase toward acetaldehyde: Ab initio and free energy quantum mechanical/molecular mechanical calculations.

PubMed

Dieterich, Johannes M; Werner, Hans-Joachim; Mata, Ricardo A; Metz, Sebastian; Thiel, Walter

2010-01-21

Energy and free energy barriers for acetaldehyde conversion in aldehyde oxidoreductase are determined for three reaction pathways using quantum mechanical/molecular mechanical (QM/MM) calculations on the solvated enzyme. Ab initio single-point QM/MM energies are obtained at the stationary points optimized at the DFT(B3LYP)/MM level. These ab initio calculations employ local correlation treatments [LMP2 and LCCSD(T0)] in combination with augmented triple- and quadruple-zeta basis sets, and the final coupled cluster results include MP2-based corrections for basis set incompleteness and for the domain approximation. Free energy perturbation (FEP) theory is used to generate free energy profiles at the DFT(B3LYP)/MM level for the most important reaction steps by sampling along the corresponding reaction paths using molecular dynamics. The ab initio and FEP QM/MM results are combined to derive improved estimates of the free energy barriers, which differ from the corresponding DFT(B3LYP)/MM energy barriers by about 3 kcal mol(-1). The present results confirm the qualitative mechanistic conclusions from a previous DFT(B3LYP)/MM study. Most favorable is a three-step Lewis base catalyzed mechanism with an initial proton transfer from the cofactor to the Glu869 residue, a subsequent nucleophilic attack that yields a tetrahedral intermediate (IM2), and a final rate-limiting hydride transfer. The competing metal center activated pathway has the same final step but needs to overcome a higher barrier in the initial step on the route to IM2. The concerted mechanism has the highest free energy barrier and can be ruled out. While confirming the qualitative mechanistic scenario proposed previously on the basis of DFT(B3LYP)/MM energy profiles, the present ab initio and FEP QM/MM calculations provide corrections to the barriers that are important when aiming at high accuracy.

Occludin Is Involved in Adhesion, Apoptosis, Differentiation and Ca2+-Homeostasis of Human Keratinocytes: Implications for Tumorigenesis

PubMed Central

Ohnemus, Ulrich; Kirschner, Nina; Vidal-y-Sy, Sabine; von den Driesch, Peter; Börnchen, Christian; Eberle, Jürgen; Mildner, Michael; Vettorazzi, Eik; Rosenthal, Rita; Moll, Ingrid; Brandner, Johanna M.

2013-01-01

Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca2+-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention. PMID:23390516

Measurement of free glucocorticoids: quantifying corticosteroid-binding globulin binding affinity and its variation within and among mammalian species.

PubMed

Delehanty, Brendan; Hossain, Sabrina; Jen, Chao Ching; Crawshaw, Graham J; Boonstra, Rudy

2015-01-01

Plasma glucocorticoids (GCs) are commonly used as measures of stress in wildlife. A great deal of evidence indicates that only free GC (GC not bound by the specific binding protein, corticosteroid-binding globulin, CBG) leaves the circulation and exerts biological effects on GC-sensitive tissues. Free hormone concentrations are difficult to measure directly, so researchers estimate free GC using two measures: the binding affinity and the binding capacity in plasma. We provide an inexpensive saturation binding method for calculating the binding affinity (equilibrium dissociation constant, K d) of CBG that can be run without specialized laboratory equipment. Given that other plasma proteins, such as albumin, also bind GCs, the method compensates for this non-specific binding. Separation of bound GC from free GC was achieved with dextran-coated charcoal. The method provides repeatable estimates (12% coefficient of variation in the red squirrel, Tamiasciurus hudsonicus), and there is little evidence of inter-individual variation in K d (range 2.0-7.3 nM for 16 Richardson's ground squirrels, Urocitellus richardsonii). The K d values of 28 mammalian species we assessed were mostly clustered around a median of 4 nM, but five species had values between 13 and 61 nM. This pattern may be distinct from birds, for which published values are more tightly distributed (1.5-5.1 nM). The charcoal separation method provides a reliable and robust method for measuring the K d in a wide range of species. It uses basic laboratory equipment to provide rapid results at very low cost. Given the importance of CBG in regulating the biological activity of GCs, this method is a useful tool for physiological ecologists.

Experimental study of self-compacted concrete in hardened state

NASA Astrophysics Data System (ADS)

Parra Costa, Carlos Jose

The main aim of this work is to investigate the hardened behaviour of Self-Compacting Concrete (SCC). Self compacting Concrete is a special concrete that can flow in its gravity and fill in the formwork alone to its self-weight, passing through the bars and congested sections without the need of any internal or external vibration, while maintaining adequate homogeneity. SCC avoids most of the materials defects due to bleeding or segregation. With regard to its composition, SCC consists of the same components as traditional vibrated concrete (TC), but in different proportions. Thus, the high amount of superplasticizer and high powder content have to taken into account. The high workability of SCC does not allow to use traditional methods for measuring the fresh state properties, so new tests has developed (slump-flow, V-funnel, L-box, and others). The properties of the hardened SCC, which depend on the mix design, should be different from traditional concrete. In order to study the possible modifications of SCC hardened state properties, a review of the bibliography was done. The state of art was focused on the mechanical behaviour (compressive strength, tension strength and elastic modulus), on bond strength of reinforcement steel, and on material durability. The experimental program consisted in the production of two types of concretes: Self-Compacting Concrete and Traditional Concrete. Four different dosages was made with three different water/cement ratio and two strength types of Portland cement, in order to cover the ordinary strength used in construction. Based on this study it can be concluded that compressive strength of SCC and TC are similar (the differences are lesser than 10%), whereas the tensile strength of TC are up to 18% higher. The values of elastic modulus of both concrete are similar. On the other hand, in the ultimate state the bond strength of SCC and TC is similar, although SCC shows higher bond stiffness in the serviceability state (initial displacement). Thus SCC reaches higher average bond strength. Although the variation in bond strength at different elevations, due to top-bar effect, is also observed in SCC the extent is less significant than that of TC. Finally, tests show that water depth penetration under pressure is much lower for SCC than for TC.

Investigation of electronic transport through a ladder-like graphene nanoribbon including random distributed impurities

NASA Astrophysics Data System (ADS)

Esmaili, Esmat; Mardaani, Mohammad; Rabani, Hassan

2018-01-01

The electronic transport of a ladder-like graphene nanoribbon which the on-site or hopping energies of a small part of it can be random is modeled by using the Green's function technique within the nearest neighbor tight-binding approach. We employ a unitary transformation in order to convert the Hamiltonian of the nanoribbon to the Hamiltonian of a tight-binding ladder-like network. In this case, the disturbed part of the system includes the second neighbor hopping interactions. While, the converted Hamiltonian of each ideal part is equivalent to the Hamiltonian of two periodic on-site chains. Therefore, we can insert the self-energies of the alternative on-site tight-binding chains to the inverse of the Green's function matrix of the ladder-like part. In this viewpoint, the conductance is constructed from two trans and cis contributions. The results show that increasing the disorder strength causes the increase and decrease of the conductance of the trans and cis contributions, respectively.

Use of procainamide gels in the purification of human and horse serum cholinesterases.

PubMed Central

Ralston, J S; Main, A R; Kilpatrick, B F; Chasson, A L

1983-01-01

Two large-scale methods based primarily on the use of procainamide-Sepharose gels were developed for the purification of horse and human serum non-specific cholinesterases. With method I, the procainamide-Sepharose 4B gel was used in the first step to handle large volumes of serum. With method II, the procainamide-Sepharose 4B gel was used in the final step to obtain pure enzyme. Although both methods gave electrophoretically pure cholinesterase preparations in good yields, they were significantly more efficient at purifying the horse enzyme than the human enzyme. To study this problem, the relative binding of human and horse cholinesterases to procainamide-, methylacridinium (MAC)-, m-trimethylammoniophenyl (m-PTA)- and p-trimethylammoniophenyl (p-PTA)-Sepharose 4B gels were measured, by using two approaches. In one, binding was measured by a procedure involving equilibration of pure cholinesterase in a small volume of diluted gel slurry (4%, v/v). A partially purified preparation of Electrophorus acetylcholinesterase was included. Pure human cholinesterase bound consistently more tightly to each of the gels than did horse cholinesterase, and the acetylcholinesterase appeared to bind the gels 10-100 times more tightly than did the non-specific cholinesterases. The order of binding for the cholinesterases, beginning with the tightest, was: procainamide-Sepharose 4B, MAC-Sepharose 4B, p-PTA-Sepharose 4B and m-PTA-Sepharose 4B. For the acetylcholinesterase the order was: MAC-Sepharose 4B, procainamide-Sepharose 4B, p-PTA-Sepharose 4B and m-PTA-Sepharose 4B. The second approach involved passing native sera or partially purified sera fractions through 1 ml test columns of each of the four affinity gels to determine their retention capacity for the cholinesterases. With these impure samples, the MAC-Sepharose 4B gels proved superior to the procainamide-Sepharose 4B gels at retaining human cholinesterase, but the opposite was true for the horse cholinesterase. PMID:6870822

Evaluation of the grand-canonical partition function using expanded Wang-Landau simulations. IV. Performance of many-body force fields and tight-binding schemes for the fluid phases of silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desgranges, Caroline; Delhommelle, Jerome

We extend Expanded Wang-Landau (EWL) simulations beyond classical systems and develop the EWL method for systems modeled with a tight-binding Hamiltonian. We then apply the method to determine the partition function and thus all thermodynamic properties, including the Gibbs free energy and entropy, of the fluid phases of Si. We compare the results from quantum many-body (QMB) tight binding models, which explicitly calculate the overlap between the atomic orbitals of neighboring atoms, to those obtained with classical many-body (CMB) force fields, which allow to recover the tetrahedral organization in condensed phases of Si through, e.g., a repulsive 3-body term thatmore » favors the ideal tetrahedral angle. Along the vapor-liquid coexistence, between 3000 K and 6000 K, the densities for the two coexisting phases are found to vary significantly (by 5 orders of magnitude for the vapor and by up to 25% for the liquid) and to provide a stringent test of the models. Transitions from vapor to liquid are predicted to occur for chemical potentials that are 10%–15% higher for CMB models than for QMB models, and a ranking of the force fields is provided by comparing the predictions for the vapor pressure to the experimental data. QMB models also reveal the formation of a gap in the electronic density of states of the coexisting liquid at high temperatures. Subjecting Si to a nanoscopic confinement has a dramatic effect on the phase diagram with, e.g. at 6000 K, a decrease in liquid densities by about 50% for both CMB and QMB models and an increase in vapor densities between 90% (CMB) and 170% (QMB). The results presented here provide a full picture of the impact of the strategy (CMB or QMB) chosen to model many-body effects on the thermodynamic properties of the fluid phases of Si.« less

Urinary Copper Elevation in a Mouse Model of Wilson's Disease Is a Regulated Process to Specifically Decrease the Hepatic Copper Load

PubMed Central

Gray, Lawrence W.; Peng, Fangyu; Molloy, Shannon A.; Pendyala, Venkata S.; Muchenditsi, Abigael; Muzik, Otto; Lee, Jaekwon; Kaplan, Jack H.; Lutsenko, Svetlana

2012-01-01

Body copper homeostasis is regulated by the liver, which removes excess copper via bile. In Wilson's disease (WD), this function is disrupted due to inactivation of the copper transporter ATP7B resulting in hepatic copper overload. High urinary copper is a diagnostic feature of WD linked to liver malfunction; the mechanism behind urinary copper elevation is not fully understood. Using Positron Emission Tomography-Computed Tomography (PET-CT) imaging of live Atp7b−/− mice at different stages of disease, a longitudinal metal analysis, and characterization of copper-binding molecules, we show that urinary copper elevation is a specific regulatory process mediated by distinct molecules. PET-CT and atomic absorption spectroscopy directly demonstrate an age-dependent decrease in the capacity of Atp7b−/− livers to accumulate copper, concomitant with an increase in urinary copper. This reciprocal relationship is specific for copper, indicating that cell necrosis is not the primary cause for the initial phase of metal elevation in the urine. Instead, the urinary copper increase is associated with the down-regulation of the copper-transporter Ctr1 in the liver and appearance of a 2 kDa Small Copper Carrier, SCC, in the urine. SCC is also elevated in the urine of the liver-specific Ctr1 −/− knockouts, which have normal ATP7B function, suggesting that SCC is a normal metabolite carrying copper in the serum. In agreement with this hypothesis, partially purified SCC-Cu competes with free copper for uptake by Ctr1. Thus, hepatic down-regulation of Ctr1 allows switching to an SCC-mediated removal of copper via kidney when liver function is impaired. These results demonstrate that the body regulates copper export through more than one mechanism; better understanding of urinary copper excretion may contribute to an improved diagnosis and monitoring of WD. PMID:22802922

Pathogen-group specific association between CXCR1 polymorphisms and subclinical mastitis in dairy heifers.

PubMed

Verbeke, Joren; Piepers, Sofie; Peelman, Luc; Van Poucke, Mario; De Vliegher, Sarne

2012-08-01

The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes (PMNL). Binding causes migration from blood to milk, activation and prolonged survival of PMNL, a crucial process in the innate immune defence of the bovine mammary gland against invading mastitis-causing pathogens. The main objective of this study was to screen the entire coding region of the CXCR1 gene for polymorphisms and to analyse their association with udder health of dairy heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20 commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data on udder health was available including quarter bacteriological culture results and somatic cell count (SCC) in early lactation and composite milk SCC during first lactation. In total, 16 polymorphisms (including 8 missense mutations) were detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI: heifers with genotype AG were less likely to have an IMI due to major mastitis pathogens compared with heifers with genotype GG but did not have less IMI by coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was neither associated with quarter SCC in early lactation nor with composite SCC during lactation. Although mastitis susceptibility is influenced by many factors, some genetic polymorphisms potentially have major effects on udder health of heifers, as was shown here. These results trigger us to further study the relationship between CXCR1 polymorphisms and mastitis susceptibility in both observational and experimental trials.

Stress Corrosion Cracking of Pipeline Steels in Fuel Grade Ethanol and Blends - Study to Evaluate Alternate Standard Tests and Phenomenological Understanding of SCC

DOT National Transportation Integrated Search

2011-10-30

Main aim of this project was to evaluate alternate standard test methods for stress corrosion cracking (SCC) and compare them with the results from slow strain rate test (SSRT) results under equivalent environmental conditions. Other important aim of...

Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes.

PubMed

Morgan, Sarah V; Garwood, Claire J; Jennings, Luke; Simpson, Julie E; Castelli, Lydia M; Heath, Paul R; Mihaylov, Simeon R; Vaquéz-Villaseñor, Irina; Minshull, Thomas C; Ince, Paul G; Dickman, Mark J; Hautbergue, Guillaume M; Wharton, Stephen B

2018-05-08

Occludin is a component of tight junctions, which are essential structural components of the blood-brain barrier. However, occludin is expressed in cells without tight junctions, implying additional functions. We determined the expression and localisation of occludin in astrocytes in cell culture and in human brain tissue, and sought novel binding partners using a proteomic approach. Expression was investigated by immunocytochemistry and immunoblotting in the 1321N1 astrocytoma cell line and ScienCell human primary astrocytes, and by immunohistochemistry in human autopsy brain tissue. Recombinant N- and C-terminal occludin was used to pull-down proteins from 1321N1 cell lysates and protein-binding partners identified by mass spectrometry analysis. Occludin was expressed in both the cytoplasm and nucleus of astrocytes in vitro and in vivo. Mass spectrometry identified binding to nuclear and cytoplasmic proteins, particularly those related to RNA metabolism and nuclear function. Occludin is expressed in several subcellular compartments of brain cell-types that do not form tight junctions and the expression patterns in cell culture reflect those in human brain tissue, indicating they are suitable model systems. Proteomic analysis suggests that occludin has novel functions in neuroepithelial cells that are unrelated to tight junction formation. Further research will establish the roles of these functions in both cellular physiology and in disease states. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Squamous cell carcinoma of the scrotum in a radiation technologist and the use of sentinel lymph node biopsy in recurrent disease.

PubMed

Shifrin, David A; Lange, Marianne K; Kahnoski, Richard J; Avallone, Anthony N

2007-03-01

Squamous cell carcinoma (SCC) of the scrotum is an uncommon neoplasm. It has been described in many different occupations and is associated with a myriad of carcinogens, yet the etiology still remains a mystery. This is the first report of its occurrence in a radiation technologist. Additionally, the use of sentinel lymph node biopsy in SCC has been advocated as a safe method of limiting the morbidity associated with bilateral ilioinguinal dissections. This is the first report of its use in recurrent metastatic SCC of the scrotum.

Synthesis, X-ray diffraction method, spectroscopic characterization (FT-IR, 1H and 13C NMR), antimicrobial activity, Hirshfeld surface analysis and DFT computations of novel sulfonamide derivatives

NASA Astrophysics Data System (ADS)

Demircioğlu, Zeynep; Özdemir, Fethi Ahmet; Dayan, Osman; Şerbetçi, Zafer; Özdemir, Namık

2018-06-01

Synthesized compounds of N-(2-aminophenyl)benzenesulfonamide 1 and (Z)-N-(2-((2-nitrobenzylidene)amino)phenyl)benzenesulfonamide 2 were characterized by antimicrobial activity, FT-IR, 1H and 13C NMR. Two new Schiff base ligands containing aromatic sulfonamide fragment of (Z)-N-(2-((3-nitrobenzylidene)amino)phenyl)benzenesulfonamide 3 and (Z)-N-(2-((4-nitrobenzylidene)amino)phenyl)benzenesulfonamide 4 were synthesized and investigated by spectroscopic techniques including 1H and 13C NMR, FT-IR, single crystal X-ray diffraction, Hirshfeld surface, theoretical method analyses and by antimicrobial activity. The molecular geometry obtained from the X-ray structure determination was optimized Density Functional Theory (DFT/B3LYP) method with the 6-311++G(d,p) basis set in ground state. From the optimized geometry of the molecules of 3 and 4, the geometric parameters, vibrational wavenumbers and chemical shifts were computed. The optimized geometry results, which were well represented the X-ray data, were shown that the chosen of DFT/B3LYP 6-311G++(d,p) was a successful choice. After a successful optimization, frontier molecular orbitals, chemical activity, non-linear optical properties (NLO), molecular electrostatic mep (MEP), Mulliken population method, natural population analysis (NPA) and natural bond orbital analysis (NBO), which cannot be obtained experimentally, were calculated and investigated.

The relationship between solar keratoses and squamous cell carcinomas among Japanese.

PubMed

Takemiya, M; Ohtsuka, H; Miki, Y

1990-06-01

Between 1976 and 1988, 135 patients with solar keratosis (SK) and 53 patients with squamous cell carcinoma (SCC) on the sun-exposed skin, but without apparent preceding diseases such as burn scars, chronic radiodermatitis, chronic arsenic poisoning, or xeroderma pigmentosum, were encountered. Sixteen of the SCC patients also had SK on other areas of sun-exposed skin. There were 31 SCC patients also showing SK (SK-SCC) and 22 SCC not showing SK (DN-SCC) within the same histologic sections. The mean ages of the patients with SK-SCC and with DN-SCC were similar. Metastases to regional lymph nodes were observed in 5 SK-SCC patients, of whom 3 died of the disease, and in 5 DN-SCC patients, of whom 4 died of the disease. The five-year post-operative survival rates were 70% in SK-SCC and 74% in DN-SCC; the ten-year post-operative survival rates were 70% in SK-SCC and 44% in DN-SCC.

Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population

PubMed Central

Li, Dan; Wang, Siying; Ye, Hongfei; Tang, Yating; Qiu, Xiaodi; Fan, Qi; Rong, Xianfang; Liu, Xin; Chen, Yuhong; Yang, Jin

2016-01-01

Purpose This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC). Methods We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination. Results By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes. Conclusions From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC. PMID:27307692

Fibroblast Senescence and Squamous Cell Carcinoma: How wounding therapies could be protective

PubMed Central

Travers, Jeffrey B.; Spandau, Dan F; Lewis, Davina A.; Machado, Christiane; Kingsley, Melanie; Mousdicas, Nico; Somani, Ally-Khan

2014-01-01

Background Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age-dependent disease as the majority of these cancers are diagnosed in people over 70 years of age. Recent findings have led to a new hypothesis on the pathogenesis of SCC. Objectives To evaluate the potential of preventive therapies to reduce the incidence of SCC in at-risk geriatric patients. Materials and Methods Survey of current literature on wounding therapies to prevent SCCs. Results This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in geriatric dermis resulting in a reduction in dermal insulin-like growth factor-1 (IGF-1) expression. This lack of IGF-1 expression sensitizes epidermal keratinocytes to fail to suppress UVB-induced mutations leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF-1 expression, and correct the inappropriate UVB response found in geriatric skin, thus protecting geriatric keratinocytes from UVB-induced SCC initiation. Conclusions In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC. PMID:23437969

Vertical electronic transport in van de waals heterostructures

NASA Astrophysics Data System (ADS)

Qiao, Zhenhua; Zhenhua Qiao's Group Team

In this work, we will introduce the theoretical investigation of the vertical electronic transport in various heterostructrues by using both tight-binding method and first-principles calculations. Counterintuitively, we find that the maximum electronic transport is achieved at very limited scattering regions but not at large overlapped catering regions. Based on this finding, we design a special setup to measure the tunneling effect in rotated bilayer systems.

Meat and heme iron intake and risk of squamous cell carcinoma of the upper aero-digestive tract in the European Prospective Investigation into Cancer and Nutrition (EPIC)

PubMed Central

Steffen, Annika; Bergmann, Manuela M.; Sánchez, María-José; Chirlaque, Maria-Dolores; Jakszyn, Paula; Amiano, Pilar; Quirós, J. Ramón; Gurrea, Aurelio Barricarte; Ferrari, Pietro; Romieu, Isabelle; Fedirko, Veronika; Bueno-de-Mesquita, H. B(as).; Siersema, Peter D.; Peeters, Petra HM; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E.; Crowe, Francesca L.; Skeie, Guri; Hallmanns, Göran; Johansson, Ingegerd; Borgquist, Signe; Ericson, Ulrika; Egeberg, Rikke; Tjønneland, Anne; Overvad, Kim; Grote, Verena; Li, Kuanrong; Trichopoulou, Antonia; Oikonomidou, Despoina; Pantzalis, Menelaos; Tumino, Rosario; Panico, Salvatore; Palli, Domenico; Krogh, Vittorio; Naccarati, Alessio; Mouw, Traci; Vergnaud, Anne-Claire; Norat, Teresa; Boeing, Heiner

2012-01-01

Background Evidence from prospective studies on intake of meat and fish and risk of squamous cell carcinoma (SCC) of the upper aero-digestive tract (UADT) is scarce. We prospectively investigated the association of meat and fish intake with risk of SCC of the UADT and the possible mechanism via heme iron in the large multi-center European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods Multivariable proportional hazards models were used to estimate relative risks of SCC of the UADT in relation to intake of total meat, as well as subtypes of meat, fish and heme iron among 348,738 individuals from 7 European countries. Results During an average follow-up of 11.8 years, a total of 682 incident cases of UADT SCC were accrued. Intake of processed meat was positively associated with risk of SCC of the UADT in the total cohort (highest versus lowest quintile: RR=1.41; 95% CI=1.03-1.94), however, in stratified analyses, this association was confined to the group of current smokers (highest versus lowest quintile: RR=1.89; 95% CI=1.22-2.93). Red meat, poultry, fish and heme iron were not consistently related to UADT SCC. Conclusion Higher intake of processed meat was positively associated with SCC of the UADT among smokers. Although this finding was stable in various sensitivity analyses, we cannot rule out residual confounding by smoking. Confirmation in future studies and identification of biological mechanisms is warranted. Impact Smokers may further increase their risk for SCC of the UADT if they additionally consume large amounts of processed meat. PMID:23033453

History of Allergy and Atopic Dermatitis in Relation to Squamous Cell and Basal Cell Carcinoma of the Skin

PubMed Central

Cheng, Judy; Zens, M. Scot; Duell, Eric; Perry, Ann E.; Chapman, M. Shane; Karagas, Margaret R.

2015-01-01

Background Little is known about whether history of allergies and atopy are related to the occurrence of keratinocyte cancers. Thus, we evaluated the association between history of allergies and atopy and the incidence of squamous cell carcinoma (SCC) and early onset basal cell carcinoma (BCC). Methods As part of a population-based case-control study, interviews were conducted with 1,050 residents of New Hampshire (375 early onset BCC cases and 251 controls, 254 SCC cases and 432 controls). Odds ratios (ORs) of SCC and early onset BCC and history of allergy and atopic dermatitis were computed using logistic regression, while controlling for potential confounding factors. Results An overall inverse association was observed between a history of allergy and early onset BCC (OR 0.61, 95% CI 0.38-0.97) but not SCC (OR 1.18, 95% CI 0.78-1.79). Among women, we found reduced ORs of both early onset BCC and for SCC in relation to allergy history (early onset BCC OR 0.53, 95% CI 0.31-0.92 and SCC OR 0.59, 95% CI 0.29-1.19). Among men, we observed no clear association with early onset BCC (OR 0.87, 95% CI 0.39-1.99) and an increased risk of SCC (OR 1.58, 95% CI 0.93-2.69). Conclusion Our findings suggest that allergies and atopy may influence risk of early onset BCC and SCC, and that effects may be gender specific. Impact A deeper understanding of the immune mechanisms underlying allergies and atopy may provide new routes of preventing keratinocyte cancer. PMID:25670807

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin – a case–control study

PubMed Central

2012-01-01

Background Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. Methods A case–control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. Results A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. Conclusions Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC. PMID:22994655

Dual binding in cohesin-dockerin complexes: the energy landscape and the role of short, terminal segments of the dockerin module.

PubMed

Wojciechowski, Michał; Różycki, Bartosz; Huy, Pham Dinh Quoc; Li, Mai Suan; Bayer, Edward A; Cieplak, Marek

2018-03-22

The assembly of the polysaccharide degradating cellulosome machinery is mediated by tight binding between cohesin and dockerin domains. We have used an empirical model known as FoldX as well as molecular mechanics methods to determine the free energy of binding between a cohesin and a dockerin from Clostridium thermocellum in two possible modes that differ by an approximately 180° rotation. Our studies suggest that the full-length wild-type complex exhibits dual binding at room temperature, i.e., the two modes of binding have comparable probabilities at equilibrium. The ability to bind in the two modes persists at elevated temperatures. However, single-point mutations or truncations of terminal segments in the dockerin result in shifting the equilibrium towards one of the binding modes. Our molecular dynamics simulations of mechanical stretching of the full-length wild-type cohesin-dockerin complex indicate that each mode of binding leads to two kinds of stretching pathways, which may be mistakenly taken as evidence of dual binding.

Histogram analysis of apparent diffusion coefficient maps for the differentiation between lymphoma and metastatic lymph nodes of squamous cell carcinoma in head and neck region.

PubMed

Wang, Yan-Jun; Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Shen, Jie; Shi, Hai-Bin; Wu, Fei-Yun

2018-06-01

Background To clarify the nature of cervical malignant lymphadenopathy is highly important for the diagnosis and differential diagnosis of head and neck tumors. Purpose To investigate the role of first-order apparent diffusion coefficient (ADC) histogram analysis for differentiating lymphoma from metastatic lymph nodes of squamous cell carcinoma (SCC) in the head and neck region. Material and Methods Diffusion-weighted imaging (DWI) data of 67 patients (lymphoma, n = 20; SCC, n = 47) with malignant lymphadenopathy were retrospectively analyzed. The SCC group was divided into nasopharyngeal SCC and non-nasopharyngeal SCC groups. The ADC histogram features (ADC 10 , ADC 25 , ADC mean , ADC median , ADC 75 , ADC 90 , skewness, and kurtosis) were derived and then compared by independent-samples t-test and one-way analysis of variance test, respectively. Receiver operating characteristic curve analyses were employed to investigate diagnostic performance of the significant parameters. Results Lymphoma showed significantly lower ADC mean , ADC median , ADC 75 , and ADC 90 than SCC (all P < 0.05). Setting ADC 90  = 0.719 × 10 -3  mm 2 /s as the threshold value, optimal diagnostic performance was achieved (area under the curve [AUC] = 0.719, sensitivity = 95.7%, specificity = 50.0%). Subgroup analyses showed no significant difference between lymphoma and NPC (all P > 0.05). Lymphoma showed significantly lower ADC 25 , ADC mean , ADC median , ADC 75 , and ADC 90 than non-nasopharyngeal SCC (all P < 0.05). Optimal diagnostic performance (AUC = 0.847, sensitivity = 86.7%, specificity = 80.0%) could be achieved when setting ADC 90  = 0.943 × 10 -3  mm 2 /s as the threshold value. Conclusion Given its limitations, our study has shown that first-order ADC histogram analysis is capable of differentiating lymphoma from metastatic lymph nodes of SCC, especially those of non-nasopharyngeal SCC.

Results from Alloy 600 And Alloy 690 Caustic SCC Model Boiler Tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Frederick D.; Thomas, Larry E.

2009-08-03

A versatile model boiler test methodology was developed and used to compare caustic stress corrosion cracking (SCC) of mill annealed Alloy 600 and thermally treated Alloy 690. The model boiler included simulated crevice devices that efficiently and consistently concentrated Na2CO3, resulting in volatilization of CO2 with the steam and concentration of NaOH at the tube surfaces. The test methodology also included variation in tube stress, either produced by the primary to secondary side pressure differential, or by a novel method that reproducibly yields a higher stress condition on the tube. The significant effect of residual stress on tube SCC wasmore » also considered. SCC of both Alloy 600 and Alloy 690 were evaluated as a function of temperature and stress. Analytical transmission electron microscopy (ATEM) evaluations of the cracks and the grain boundaries ahead of the cracks were performed, providing insight into the SCC mechanism. This model boiler test methodology may be applicable to a range of bulkwater secondary chemistries that concentrate to produce aggressive crevice environments.« less

Finite temperature magnon spectra in yttrium iron garnet from a mean field approach in a tight-binding model

NASA Astrophysics Data System (ADS)

Shen, Ka

2018-04-01

We study magnon spectra at finite temperature in yttrium iron garnet using a tight-binding model with nearest-neighbor exchange interaction. The spin reduction due to thermal magnon excitation is taken into account via the mean field approximation to the local spin and is found to be different at two sets of iron atoms. The resulting temperature dependence of the spin wave gap shows good agreement with experiment. We find that only two magnon modes are relevant to the ferromagnetic resonance.

OLIFE: Tight Binding Code for Transmission Coefficient Calculation

NASA Astrophysics Data System (ADS)

Mijbil, Zainelabideen Yousif

2018-05-01

A new and human friendly transport calculation code has been developed. It requires a simple tight binding Hamiltonian as the only input file and uses a convenient graphical user interface to control calculations. The effect of magnetic field on junction has also been included. Furthermore the transmission coefficient can be calculated between any two points on the scatterer which ensures high flexibility to check the system. Therefore Olife can highly be recommended as an essential tool for pretesting studying and teaching electron transport in molecular devices that saves a lot of time and effort.

Electronic Structure of Alpha-Quartz and the Influence of Some Local Disorder: A Tight Binding Study,

DTIC Science & Technology

1977-01-01

An s extended summary of the theoretical and ex- perimental work on Si02 is to be found in that paper. The tight-binding basis con- sists of the four... theoretical and experimental works contained therein. 4. B. Fischer, R. A. Pollak, T. H. Distefano and W. D. Grobman, "Electronic Structure of SiO 2, SixGe 1 x...and GeO 2 from Photoemission Spectroscopy," Phys. Rev. BI5, 3193 (1977), and references to earlier works therein. 5. J. H. Scofield , "Hartree-Slater

Porosity of Self-Compacting Concrete (SCC) incorporating high volume fly ash

NASA Astrophysics Data System (ADS)

Kristiawan, S. A.; Sunarmasto; Murti, G. Y.

2017-02-01

Degradation of concrete could be triggered by the presence of aggressive agents from the environment into the body of concrete. The penetration of these agents is influenced by the pore characteristics of the concrete. Incorporating a pozzolanic material such as fly ash could modify the pore characteristic of the concrete. This research aims to investigate the influence of incorporating fly ash at high volume level on the porosity of Self-Compacting Concrete (SCC). Laboratory investigations were carried out following the ASTM C642 for measuring density and volume of permeable pores (voids) of the SCC with varying fly ash contents (50-70% by weight of total binder). In addition, a measurement of permeable voids by saturation method was carried out to obtain an additional volume of voids that could not be measured by the immersion and boiling method of ASTM C642. The results show that the influence of fly ash content on the porosity appears to be dependent on age of SCC. At age less than 56 d, fly ash tends to cause an increase of voids but at 90 d of age it reduces the pores. The additional pores that can be penetrated by vacuum saturation method counts about 50% of the total voids.

Genetic evaluation of mastitis liability and recovery through longitudinal analysis of transition probabilities

PubMed Central

2012-01-01

Background Many methods for the genetic analysis of mastitis use a cross-sectional approach, which omits information on, e.g., repeated mastitis cases during lactation, somatic cell count fluctuations, and recovery process. Acknowledging the dynamic behavior of mastitis during lactation and taking into account that there is more than one binary response variable to consider, can enhance the genetic evaluation of mastitis. Methods Genetic evaluation of mastitis was carried out by modeling the dynamic nature of somatic cell count (SCC) within the lactation. The SCC patterns were captured by modeling transition probabilities between assumed states of mastitis and non-mastitis. A widely dispersed SCC pattern generates high transition probabilities between states and vice versa. This method can model transitions to and from states of infection simultaneously, i.e. both the mastitis liability and the recovery process are considered. A multilevel discrete time survival model was applied to estimate breeding values on simulated data with different dataset sizes, mastitis frequencies, and genetic correlations. Results Correlations between estimated and simulated breeding values showed that the estimated accuracies for mastitis liability were similar to those from previously tested methods that used data of confirmed mastitis cases, while our results were based on SCC as an indicator of mastitis. In addition, unlike the other methods, our method also generates breeding values for the recovery process. Conclusions The developed method provides an effective tool for the genetic evaluation of mastitis when considering the whole disease course and will contribute to improving the genetic evaluation of udder health. PMID:22475575

Identification of Logic Relationships between Genes and Subtypes of Non-Small Cell Lung Cancer

PubMed Central

Su, Yansen; Pan, Linqiang

2014-01-01

Non-small cell lung cancer (NSCLC) has two major subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). The diagnosis and treatment of NSCLC are hindered by the limited knowledge about the pathogenesis mechanisms of subtypes of NSCLC. It is necessary to research the molecular mechanisms related with AC and SCC. In this work, we improved the logic analysis algorithm to mine the sufficient and necessary conditions for the presence states (presence or absence) of phenotypes. We applied our method to AC and SCC specimens, and identified lower and higher logic relationships between genes and two subtypes of NSCLC. The discovered relationships were independent of specimens selected, and their significance was validated by statistic test. Compared with the two earlier methods (the non-negative matrix factorization method and the relevance analysis method), the current method outperformed these methods in the recall rate and classification accuracy on NSCLC and normal specimens. We obtained biomarkers. Among biomarkers, genes have been used to distinguish AC from SCC in practice, and other six genes were newly discovered biomarkers for distinguishing subtypes. Furthermore, NKX2-1 has been considered as a molecular target for the targeted therapy of AC, and other genes may be novel molecular targets. By gene ontology analysis, we found that two biological processes (‘epidermis development’ and ‘cell adhesion’) were closely related with the tumorigenesis of subtypes of NSCLC. More generally, the current method could be extended to other complex diseases for distinguishing subtypes and detecting the molecular targets for targeted therapy. PMID:24743794

Complex absorbing potential based Lorentzian fitting scheme and time dependent quantum transport.

PubMed

Xie, Hang; Kwok, Yanho; Jiang, Feng; Zheng, Xiao; Chen, GuanHua

2014-10-28

Based on the complex absorbing potential (CAP) method, a Lorentzian expansion scheme is developed to express the self-energy. The CAP-based Lorentzian expansion of self-energy is employed to solve efficiently the Liouville-von Neumann equation of one-electron density matrix. The resulting method is applicable for both tight-binding and first-principles models and is used to simulate the transient currents through graphene nanoribbons and a benzene molecule sandwiched between two carbon-atom chains.

SOX2 as a New Regulator of HPV16 Transcription.

PubMed

Martínez-Ramírez, Imelda; Del-Castillo-Falconi, Víctor; Mitre-Aguilar, Irma B; Amador-Molina, Alfredo; Carrillo-García, Adela; Langley, Elizabeth; Zentella-Dehesa, Alejandro; Soto-Reyes, Ernesto; García-Carrancá, Alejandro; Herrera, Luis A; Lizano, Marcela

2017-07-05

Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context.

Glucocorticoid Regulation of the Vitamin D Receptor

PubMed Central

Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.

2010-01-01

Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

Electrostatic Interactions in the Binding Pathway of a Transient Protein Complex Studied by NMR and Isothermal Titration Calorimetry*

PubMed Central

Meneses, Erick; Mittermaier, Anthony

2014-01-01

Much of our knowledge of protein binding pathways is derived from extremely stable complexes that interact very tightly, with lifetimes of hours to days. Much less is known about weaker interactions and transient complexes because these are challenging to characterize experimentally. Nevertheless, these types of interactions are ubiquitous in living systems. The combination of NMR relaxation dispersion Carr–Purcell–Meiboom–Gill (CPMG) experiments and isothermal titration calorimetry allows the quantification of rapid binding kinetics for complexes with submillisecond lifetimes that are difficult to study using conventional techniques. We have used this approach to investigate the binding pathway of the Src homology 3 (SH3) domain from the Fyn tyrosine kinase, which forms complexes with peptide targets whose lifetimes are on the order of about a millisecond. Long range electrostatic interactions have been shown to play a critical role in the binding pathways of tightly binding complexes. The role of electrostatics in the binding pathways of transient complexes is less well understood. Similarly to previously studied tight complexes, we find that SH3 domain association rates are enhanced by long range electrostatics, whereas short range interactions are formed late in the docking process. However, the extent of electrostatic association rate enhancement is several orders of magnitudes less, whereas the electrostatic-free basal association rate is significantly greater. Thus, the SH3 domain is far less reliant on electrostatic enhancement to achieve rapid association kinetics than are previously studied systems. This suggests that there may be overall differences in the role played by electrostatics in the binding pathways of extremely stable versus transient complexes. PMID:25122758

Vibrational dynamics (IR, Raman, NRVS) and DFT study of new antitumor tetranuclearstannoxanecluster, Sn(IV)$-$oxo$-$${di$$-$o$-$vanillin} dimethyl dichloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arjmand, F.; Sharma, S.; Usman, M.

2016-06-21

The vibrational dynamics of a newly synthesized tetrastannoxane was characterized with a combination of experimental (Raman, IR and tin-based nuclear resonance vibrational spectroscopy) and computational (DFT/B3LYP) methods, with an emphasis on the vibrations of the tin sites. The cytotoxic activity revealed a significant regression selectively against the human pancreatic cell lines.

A Computational Analysis of ATP Binding of SV40 Large Tumor Antigen Helicase Motor

PubMed Central

Shi, Yemin; Liu, Hanbin; Gai, Dahai; Ma, Jianpeng; Chen, Xiaojiang S.

2009-01-01

Simian Virus 40 Large Tumor Antigen (LTag) is an efficient helicase motor that unwinds and translocates DNA. The DNA unwinding and translocation of LTag is powered by ATP binding and hydrolysis at the nucleotide pocket between two adjacent subunits of an LTag hexamer. Based on the set of high-resolution hexameric structures of LTag helicase in different nucleotide binding states, we simulated a conformational transition pathway of the ATP binding process using the targeted molecular dynamics method and calculated the corresponding energy profile using the linear response approximation (LRA) version of the semi-macroscopic Protein Dipoles Langevin Dipoles method (PDLD/S). The simulation results suggest a three-step process for the ATP binding from the initial interaction to the final tight binding at the nucleotide pocket, in which ATP is eventually “locked” by three pairs of charge-charge interactions across the pocket. Such a “cross-locking” ATP binding process is similar to the binding zipper model reported for the F1-ATPase hexameric motor. The simulation also shows a transition mechanism of Mg2+ coordination to form the Mg-ATP complex during ATP binding, which is accompanied by the large conformational changes of LTag. This simulation study of the ATP binding process to an LTag and the accompanying conformational changes in the context of a hexamer leads to a refined cooperative iris model that has been proposed previously. PMID:19779548

Tight-binding study of Si2Cn (n = 3 to 42) fullerene-like or nanodiamonds microclusters: are Si atoms isolated or adjacent?

NASA Astrophysics Data System (ADS)

Leleyter, M.; Olivi-Tran, N.

2008-12-01

We studied in tight-binding approximation involving spν hybridization (ν=2,3), some Si2Cn (n=3 to 42) microclusters. We then investigated, on one hand, fragments of fullerene-like structures (sp2), and on the other hand, nanodiamonds (sp3) of adamantane-type or a 44-atom nanodiamond (with 2 inner atoms which are assumed to play the role of bulk atoms). We compared the stabilities, i.e. the electronic energies of these clusters, according to the various positions of the 2 Si atoms. Results are very different in the two kinds of hybridization. Besides, they can be analysed according to two different points of view: either the clusters are considered as small particles with limited sizes, or they are assumed to be used as models in order to simulate the Si-atom behaviour in very larger systems. In sp2 hybridization (fullerene-like geometries), the most stable isomer is always encountered when the 2 Si atoms build a Si2 group, and this result holds for both viewpoints quoted above. Conversely, in sp3 hybridization (nanodiamonds), since Si atoms “prefer” sites having the minimum connectivity, they are never found in adjacent sites. We see that with a simple and fast computational method we can explain an experimental fact which is very interesting such as the relative position of two heteroatoms in the cluster. This enhances the generality and the fecondity in the tight binding approximation due essentially to the link between this model and the graph theory, link based on the topology of the clusters.

Study of gas-phase O-H bond dissociation enthalpies and ionization potentials of substituted phenols - Applicability of ab initio and DFT/B3LYP methods

NASA Astrophysics Data System (ADS)

Klein, Erik; Lukeš, Vladimír

2006-11-01

In this paper, the study of phenol and 37 compounds representing various ortho-, para-, and meta-substituted phenols is presented. Molecules and their radical structures were studied using ab initio methods with inclusion of correlation energy and DFT in order to calculate the O-H bond dissociation enthalpies (BDEs) and vertical ionization potentials (IPs). Calculated BDEs and IPs were compared with available experimental values to ascertain the suitability of used methods, especially for the description of the substituent induced changes in BDE and IP. MP2, MP3, and MP4 methods do not give reliable results, since they significantly underestimate substituent induced changes in BDE and do not reflect distinct effect of substituents related to para and meta position correctly. DFT/B3LYP method reflects the effect of substituents on BDE satisfactorily, though ΔBDEs are in narrower range than experimental values. BDE of phenol was calculated also using CCSD(T) method in various basis sets. Both, DFT and HF methods describe the effect of substituents on IP identically. However, DFT considerably underestimates individual values. HF method gives IPs in very good agreement with experimental data. Obtained results show that dependences of BDEs and IPs on Hammett constants of the substituents are linear. Linearity of DFT BDE vs. IP dependence is even better than the dependences on Hammett constants and obtained equations allow estimating of O-H BDEs of meta- and para-substituted phenols from calculated IPs.

The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Starska, Katarzyna, E-mail: katarzyna.starska@umed.lodz.pl; Krześlak, Anna; Forma, Ewa

2014-10-15

Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determinedmore » by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. - Highlights: • MT2A gene expression and metal content in laryngeal cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn and Cu levels • Negative correlation between MT2A gene expression and Cd, Zn and Cu levels.« less

Limitations and opportunities for the social cost of carbon (Invited)

NASA Astrophysics Data System (ADS)

Rose, S. K.

2010-12-01

Estimates of the marginal value of carbon dioxide-the social cost of carbon (SCC)-were recently adopted by the U.S. Government in order to satisfy requirements to value estimated GHG changes of new federal regulations. However, the development and use of SCC estimates of avoided climate change impacts comes with significant challenges and controversial decisions. Fortunately, economics can provide some guidance for conceptually appropriate estimates. At the same time, economics defaults to a benefit-cost decision framework to identify socially optimal policies. However, not all current policy decisions are benefit-cost based, nor depend on monetized information, or even have the same threshold for information. While a conceptually appropriate SCC is a useful metric, how far can we take it? This talk discusses potential applications of the SCC, limitations based on the state of research and methods, as well as opportunities for among other things consistency with climate risk management and research and decision-making tools.

Priority for the worse-off and the social cost of carbon

NASA Astrophysics Data System (ADS)

Adler, Matthew; Anthoff, David; Bosetti, Valentina; Garner, Greg; Keller, Klaus; Treich, Nicolas

2017-06-01

The social cost of carbon (SCC) is a key tool in climate policy. The SCC expresses in monetary terms the social impact of the emission of a ton of CO2 in a given year. The SCC is calculated using a `social welfare function’ (SWF): a method for assessing social welfare. The dominant SWF in climate policy is the discounted-utilitarian SWF. Individuals’ well-being numbers (utilities) are summed, and the values for later generations are reduced (`discounted’). This SWF has been criticized for ignoring the distribution of well-being and including an arbitrary time preference. Here, we use a `prioritarian’ SWF, with no time discount, to calculate the SCC. This SWF gives extra weight (`priority’) to worse-off individuals. Prioritarianism is a well-developed concept in ethics and welfare economics, but has been rarely used in climate scholarship. We find substantial differences between the discounted-utilitarian and non-discounted prioritarian SCCs.

Predicting permanent and transient protein-protein interfaces.

PubMed

La, David; Kong, Misun; Hoffman, William; Choi, Youn Im; Kihara, Daisuke

2013-05-01

Protein-protein interactions (PPIs) are involved in diverse functions in a cell. To optimize functional roles of interactions, proteins interact with a spectrum of binding affinities. Interactions are conventionally classified into permanent and transient, where the former denotes tight binding between proteins that result in strong complexes, whereas the latter compose of relatively weak interactions that can dissociate after binding to regulate functional activity at specific time point. Knowing the type of interactions has significant implications for understanding the nature and function of PPIs. In this study, we constructed amino acid substitution models that capture mutation patterns at permanent and transient type of protein interfaces, which were found to be different with statistical significance. Using the substitution models, we developed a novel computational method that predicts permanent and transient protein binding interfaces (PBIs) in protein surfaces. Without knowledge of the interacting partner, the method uses a single query protein structure and a multiple sequence alignment of the sequence family. Using a large dataset of permanent and transient proteins, we show that our method, BindML+, performs very well in protein interface classification. A very high area under the curve (AUC) value of 0.957 was observed when predicted protein binding sites were classified. Remarkably, near prefect accuracy was achieved with an AUC of 0.991 when actual binding sites were classified. The developed method will be also useful for protein design of permanent and transient PBIs. Copyright © 2013 Wiley Periodicals, Inc.

Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping

NASA Astrophysics Data System (ADS)

Henke, Paul S.; Mak, Chi H.

2014-08-01

The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg2+ that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

Current's Fluctuations through Molecular Wires Composed of Thiophene Rings.

PubMed

Ojeda Silva, Judith Helena; Cortés Peñaranda, Juan Camilo; Gómez Castaño, Jovanny A; Duque, Carlos Alberto

2018-04-11

We study theoretically the electronic transport and quantum fluctuations in single-molecule systems using thiophene rings as integrated elementary functions, as well as the dependence of these properties with the increase of the coupled rings, i.e., as a quantum wire. In order to analyze the current flow through these molecular systems, the thiophene rings are considered to be connected to metal contacts, which, in general terms, will be related to the application of voltages (bias voltages or gate voltages) to generate non-equilibrium behavior between the contacts. Due to the nonlinear behavior that is generated when said voltages are applied, it is possible to observe quantum fluctuations in the transport properties of these molecular wires. For the calculation of the transport properties, we applied a tight-binding approach using the Landauer-Büttiker formalism and the Fischer-Lee relationship, by means of a semi-analytic Green's function method within a real-space renormalization (decimation procedure). Our results showed an excellent agreement with results using a tight-binding model with a minimal number of parameters reported so far for these molecular systems.

Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping.

PubMed

Henke, Paul S; Mak, Chi H

2014-08-14

The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg(2+) that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

Nonlocal torque operators in ab initio theory of the Gilbert damping in random ferromagnetic alloys

NASA Astrophysics Data System (ADS)

Turek, I.; Kudrnovský, J.; Drchal, V.

2015-12-01

We present an ab initio theory of the Gilbert damping in substitutionally disordered ferromagnetic alloys. The theory rests on introduced nonlocal torques which replace traditional local torque operators in the well-known torque-correlation formula and which can be formulated within the atomic-sphere approximation. The formalism is sketched in a simple tight-binding model and worked out in detail in the relativistic tight-binding linear muffin-tin orbital method and the coherent potential approximation (CPA). The resulting nonlocal torques are represented by nonrandom, non-site-diagonal, and spin-independent matrices, which simplifies the configuration averaging. The CPA-vertex corrections play a crucial role for the internal consistency of the theory and for its exact equivalence to other first-principles approaches based on the random local torques. This equivalence is also illustrated by the calculated Gilbert damping parameters for binary NiFe and FeCo random alloys, for pure iron with a model atomic-level disorder, and for stoichiometric FePt alloys with a varying degree of L 10 atomic long-range order.

A Sparse Self-Consistent Field Algorithm and Its Parallel Implementation: Application to Density-Functional-Based Tight Binding.

PubMed

Scemama, Anthony; Renon, Nicolas; Rapacioli, Mathias

2014-06-10

We present an algorithm and its parallel implementation for solving a self-consistent problem as encountered in Hartree-Fock or density functional theory. The algorithm takes advantage of the sparsity of matrices through the use of local molecular orbitals. The implementation allows one to exploit efficiently modern symmetric multiprocessing (SMP) computer architectures. As a first application, the algorithm is used within the density-functional-based tight binding method, for which most of the computational time is spent in the linear algebra routines (diagonalization of the Fock/Kohn-Sham matrix). We show that with this algorithm (i) single point calculations on very large systems (millions of atoms) can be performed on large SMP machines, (ii) calculations involving intermediate size systems (1000-100 000 atoms) are also strongly accelerated and can run efficiently on standard servers, and (iii) the error on the total energy due to the use of a cutoff in the molecular orbital coefficients can be controlled such that it remains smaller than the SCF convergence criterion.

Shape of the self-concept clarity change during group psychotherapy predicts the outcome: an empirical validation of the theoretical model of the self-concept change

PubMed Central

Styła, Rafał

2015-01-01

Background: Self-Concept Clarity (SCC) describes the extent to which the schemas of the self are internally integrated, well defined, and temporally stable. This article presents a theoretical model that describes how different shapes of SCC change (especially stable increase and “V” shape) observed in the course of psychotherapy are related to the therapy outcome. Linking the concept of Jean Piaget and the dynamic systems theory, the study postulates that a stable SCC increase is needed for the participants with a rather healthy personality structure, while SCC change characterized by a “V” shape or fluctuations is optimal for more disturbed patients. Method: Correlational study in a naturalistic setting with repeated measurements (M = 5.8) was conducted on the sample of 85 patients diagnosed with neurosis and personality disorders receiving intensive eclectic group psychotherapy under routine inpatient conditions. Participants filled in the Self-Concept Clarity Scale (SCCS), Symptoms' Questionnaire KS-II, and Neurotic Personality Questionnaire KON-2006 at the beginning and at the end of the course of psychotherapy. The SCCS was also administered every 2 weeks during psychotherapy. Results: As hypothesized, among the relatively healthiest group of patients the stable SCC increase was related to positive treatment outcome, while more disturbed patients benefited from the fluctuations and “V” shape of SCC change. Conclusions: The findings support the idea that for different personality dispositions either a monotonic increase or transient destabilization of SCC is a sign of a good treatment prognosis. PMID:26579001

Comparison of ANN and RKS approaches to model SCC strength

NASA Astrophysics Data System (ADS)

Prakash, Aravind J.; Sathyan, Dhanya; Anand, K. B.; Aravind, N. R.

2018-02-01

Self compacting concrete (SCC) is a high performance concrete that has high flowability and can be used in heavily reinforced concrete members with minimal compaction segregation and bleeding. The mix proportioning of SCC is highly complex and large number of trials are required to get the mix with the desired properties resulting in the wastage of materials and time. The research on SCC has been highly empirical and no theoretical relationships have been developed between the mixture proportioning and engineering properties of SCC. In this work effectiveness of artificial neural network (ANN) and random kitchen sink algorithm(RKS) with regularized least square algorithm(RLS) in predicting the split tensile strength of the SCC is analysed. Random kitchen sink algorithm is used for mapping data to higher dimension and classification of this data is done using Regularized least square algorithm. The training and testing data for the algorithm was obtained experimentally using standard test procedures and materials available. Total of 40 trials were done which were used as the training and testing data. Trials were performed by varying the amount of fine aggregate, coarse aggregate, dosage and type of super plasticizer and water. Prediction accuracy of the ANN and RKS model is checked by comparing the RMSE value of both ANN and RKS. Analysis shows that eventhough the RKS model is good for large data set, its prediction accuracy is as good as conventional prediction method like ANN so the split tensile strength model developed by RKS can be used in industries for the proportioning of SCC with tailor made property.

Generation and characterization of a human oral squamous carcinoma cell line SCC-9 with CRISPR/Cas9-mediated deletion of the p75 neurotrophin receptor.

PubMed

Huang, Ping; Tong, Dongdong; Sun, Jing; Li, Qing; Zhang, Fenghe

2017-10-01

To investigate the importance of the p75 neurotrophin receptor (p75 NTR ) in human tongue squamous carcinoma cells, we exploited the CRISPR/Cas9 technology to establish a p75 NTR -knockout SCC-9 cell line and to explore the effect on biological functions. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas9) system was used to generate genomic deletion mutants of p75 NTR in the tongue squamous carcinoma cell lines SCC-9. Single-guide RNA (sgRNA) sequences were designed to target the p75 NTR genomic sequence and were cloned into plasmid pGK1.1. The linearized vector was electroporated into SCC-9 cells and p75 NTR deletion was confirmed using Cruiser™ enzyme digestion and PCR amplification. SCC-9 clones with successful deletion of p75 NTR were identified and verified by sequencing and selected for functional testing in cell proliferation, invasion, migration, and colony-forming assays. Compared with control cells, p75 NTR -knockout SCC-9 cells showed significantly diminished abilities to proliferate, invade, migrate, and form colonies, indicating a reduction in pro-tumorigenic behavior. These data demonstrate, first, that the CRISPR/Cas9 system is a simplified method for generating p75 NTR knockouts with relatively high efficiency, and second, that deletion of p75 NTR suppresses several tumor-promoting properties of SCC-9 cells, suggesting that p75 NTR is a potential target for the development of novel therapies for tongue cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and Interaction-Based Assays

PubMed Central

Salas-Sarduy, Emir; Guerra, Yasel; Covaleda Cortés, Giovanni; Avilés, Francesc Xavier; Chávez Planes, María A.

2017-01-01

Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. In the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model enzymes. To this end, we first developed a screening strategy that combined enzymatic with interaction-based assays and then validated screening conditions using five reference extracts. Interferences were evaluated and minimized. The results from the massive screening of such extracts, the validation of several hits by a variety of interaction-based assays and the purification and functional characterization of PhPI, a multifunctional and reversible tight-binding inhibitor for Plasmepsin II and Falcipain 2 from the gorgonian Plexaura homomalla, are presented. PMID:28430158

Various Stone-Wales defects in phagraphene

NASA Astrophysics Data System (ADS)

Openov, L. A.; Podlivaev, A. I.

2016-08-01

Various Stone-Wales defects in phagraphene, which is a graphene allotrope, predicted recently are studied in terms of the nonorthogonal tight-binding model. The energies of the defect formation and the heights of energy barriers preventing the formation and annealing of the defects are found. Corresponding frequency factors in the Arrhenius formula are calculated. The evolution of the defect structure is studied in the real-time mode using the molecular dynamics method.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinshaw, Stephen M.; Makrantoni, Vasso; Kerr, Alastair

The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2NIPBL/Scc4Mau2 (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surfacemore » of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres.« less

Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

PubMed

Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

2014-01-01

Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

Advanced cutaneous squamous cell carcinoma: A retrospective analysis of patient profiles and treatment patterns-Results of a non-interventional study of the DeCOG.

PubMed

Hillen, Uwe; Leiter, Ulrike; Haase, Sylvie; Kaufmann, Roland; Becker, Jürgen; Gutzmer, Ralf; Terheyden, Patrick; Krause-Bergmann, Albrecht; Schulze, Hans-Joachim; Hassel, Jessica; Lahner, Nina; Wollina, Uwe; Ziller, Fabian; Utikal, Jochen; Hafner, Christine; Ulrich, Jens; Machens, Hans-Günther; Weishaupt, Carsten; Hauschild, Axel; Mohr, Peter; Pföhler, Claudia; Maurer, Jan; Wolff, Patrick; Windemuth-Kieselbach, Christine; Schadendorf, Dirk; Livingstone, Elisabeth

2018-04-14

Advanced cutaneous squamous cell carcinoma (aSCC) is an area of unmet medical need and no treatment standards are established. Recently, an anti-PD-1 inhibitor received FDA breakthrough therapy designation. The aim of the study was to describe the clinical course, therapeutic management and prognosis of aSCC under real-life conditions. In a retrospective study performed in 24 German and Austrian hospitals and doctor's offices, patient and tumour characteristics of patients diagnosed with aSCC between January 1, 2010 and December 31, 2011 and their disease course was documented. Advanced SCC comprised either locally advanced SCCs (laSCC) or metastatic SCCs (mSCC) with any kind of metastatic spread. Data of 190 patients with aSCC were analysed. Median age at time of diagnosis of aSCC was 78 years. LaSCC was diagnosed in 76 patients (40%), 114 patients (60%) had mSCC. Once diagnosed with laSCC, most patients (59%) did not receive any therapy, whereas in 92% of mSCC patients at least one type of therapy was performed. Only 32 patients (29 mSCC, 3 laSCC) received systemic antitumour therapies, mostly EGFR inhibitor-based regimens. Mean duration of response was short (17-months laSCC patients, 3-months mSCC patients). Only 2 patients achieved a complete response, 27% had a partial response, 43% disease stabilisation. At diagnosis of aSCC, ECOG status was 0-1 in most patients. Non-malignant comorbidities influenced the decision on SCC-specific therapy in 39 patients (21%). Our data show the high medical need for efficient and tolerable antitumour therapies and demonstrate that despite older age and comorbidities, most patients can be expected to be fit for treatment. This study provides a historical context for emerging aSCC treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Systematical analysis of cutaneous squamous cell carcinoma network of microRNAs, transcription factors, and target and host genes.

PubMed

Wang, Ning; Xu, Zhi-Wen; Wang, Kun-Hao

2014-01-01

MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

Height, height-related SNPs, and risk of non-melanoma skin cancer

PubMed Central

Li, Xin; Liang, Liming; Feng, Yen-Chen Anne; De Vivo, Immaculata; Giovannucci, Edward; Tang, Jean Y; Han, Jiali

2017-01-01

Background: Adult height has been associated with risk of several site-specific cancers, including melanoma. However, less attention has been given to non-melanoma skin cancer (NMSC). Methods: We prospectively examined the risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in relation to adult height in the Nurses' Health Study (NHS, n=117 863) and the Health Professionals Follow-up Study (HPFS, n=51 111). We also investigated the relationships between height-related genetic markers and risk of BCC and SCC in the genetic data sets of the NHS and HPFS (3898 BCC cases, and 8530 BCC controls; 527 SCC cases, and 8962 SCC controls). Results: After controlling for potential confounding factors, the hazard ratios were 1.09 (95% CI: 1.02, 1.15) and 1.10 (95% CI: 1.07, 1.13) for the associations between every 10 cm increase in height and risk of SCC and BCC respectively. None of the 687 height-related single-nucleotide polymorphisms (SNPs) was significantly associated with the risk of SCC or BCC, nor were the genetic scores combining independent height-related loci. Conclusions: Our data from two large cohorts provide further evidence that height is associated with an increased risk of NMSC. More studies on height-related genetic loci and early-life exposures may help clarify the underlying mechanisms. PMID:27846199

Formwork pressure exerted by self-consolidating concrete

NASA Astrophysics Data System (ADS)

Omran, Ahmed Fathy

Self-consolidating concrete (SCC) is an emerging technology that utilizes flowable concrete that eliminates the need for consolidation. The advantages of SCC lie in a remarkable reduction of the casting time, facilitating the casting of congested and complex structural elements, possibility to reduce labor demand, elimination of mechanical vibrations and noise, improvement of surface appearance, producing a better and premium concrete product. The research focussed on capturing existing knowledge and making recommendations for current practice. An experimental program was undertaken at the Universite de Sherbrooke to evaluate the lateral pressure developed by SCC mixtures. A portable devise (UofS2 pressure column) for measuring and predicting lateral pressure and its rate of decay of SCC was developed and validated. The UofS2 pressure column is cast with 0.5 m high fresh concrete and air pressure is introduced from the top to simulate casting depth up to 13 m. Then, develop and implement test method for field evaluation of relevant plastic and thixotropic properties of SCC that affect formwork pressure were done. Portable vane (PV) test based on the hand-held vane test method used to determine the undrained shear strength property of clay soil was the first setup as well as the inclined plane (IP) test. The IP device involves slumping a small concrete cylinder on a horizontal plate and then lifting up the plate at different durations of rest until the slumped sample starts to move. Identifying role of material constituents, mix design, concrete placement characteristics (casting rate, waiting periods between lifts, and casting depth), temperature, and formwork characteristics that have major influence on formwork pressure exerted by SCC were evaluated in laboratory and validated by actual field measurements. Relating the maximum lateral pressure and its rate of decay to the plastic properties of SCC were established. In the analytical part of the research, effective ways to reduce lateral pressure by developing formulation expertise and practical guidelines to lower lateral pressure of SCC were proposed. Various design equations as well as chart diagrams to predict formwork pressure that can be exerted by SCC on column and wall elements were derived and reported. In general, the results obtained show that measured lateral pressure is lower than corresponding hydrostatic pressure. The study has shown that lateral pressure exerted by SCC is closely related to the structural build-up at rest (or thixotropy) of SCC. The latter can be controlled using different mixture proportionings, material constituents, and chemical admixtures. SCC mixture with a high rate of structural build-up at rest can develop low lateral pressure on formwork. Increased rate of structural build-up at rest can be ensured by incorporating a greater volume of coarse aggregate, lower paste volume, and/or lower sand-to-total aggregate ratio. Incorporating coarse aggregate of larger maximum size could also increase the thixotropy and hence reduce the lateral pressure. This can also be achieved by reducing the workability of SCC using less HRWRA concentration. Indeed, all mixture factors have been replaced by measuring the rate of structural build-up at rest (or thixotropy) using the developed portable vane and inclined plane field-oriented test as well as the modified Tattersall MK-III concrete rheometer. On the other hand, increasing or maintaining the concrete temperature at a certain level plays an important role to reduce the lateral pressure. The higher concrete temperature can accelerate the heat of hydration of cement with water and increase the internal friction leading to higher thixotropy. Controlling the placement rate has a great impact on the resultant lateral pressure of SCC. The lateral pressure can be reduced by slowing down the casting rate, as concrete has more time to build-up. However, this can slow down the rate of construction. The casting rate should be optimized to yield a cost effective formwork system. Pausing the continuous casting by a waiting period can reduce the exerted lateral pressure. The research investigation could accelerate the acceptance and implementation of SCC technology in cast-in-place applications, which is the preponderate business of the ready mixed concrete suppliers. The research findings could also contribute to the removal of some of the major barriers hindering the acceptance of SCC in cast-in-place applications and provide the industry with much needed guidelines on formwork pressure. (Abstract shortened by UMI.)

Mechanism of calmodulin recognition of the binding domain of isoform 1b of the plasma membrane Ca2+-ATPase: kinetic pathway and effects of methionine oxidation

PubMed Central

Slaughter, Brian D.; Bieber Urbauer, Ramona J.; Urbauer, Jeffrey L.; Johnson, Carey K.

2008-01-01

Calmodulin (CaM) binds to a domain near the C-terminus of the plasma-membrane Ca2+-ATPase (PMCA), causing the release of this domain and relief of its autoinhibitory function. We investigated the kinetics of dissociation and binding of Ca2+-CaM with a 28-residue peptide (C28W(1b)) corresponding to the CaM binding domain of isoform 1b of PMCA. CaM was labeled with a fluorescent probe on either the N-terminal domain at residue 34 or on the C-terminal domain at residue 110. Formation of complexes of CaM with C28W(1b) results in a decrease in the fluorescence yield of the fluorophore, allowing the kinetics of dissociation or binding to be detected. Using a maximum entropy method, we determined the minimum number and magnitudes of rate constants required to fit the data. Comparison of the fluorescence changes for CaM labeled on the C-terminal or N-terminal domain suggests sequential and ordered binding of the C-terminal and N-terminal domains of CaM with C28W(1b). For dissociation of C28W(1b) from CaM labeled on the N-terminal domain, we observed three time constants, indicating the presence of two intermediate states in the dissociation pathway. However, for CaM labeled on the C-terminal domain, we observed only two time constants, suggesting that the fluorescence label on the C-terminal domain was not sensitive to one of the kinetic steps. The results were modeled by a kinetic mechanism where an initial complex forms upon binding of the C-terminal domain of CaM to C28W(1b), followed by binding of the N-terminal domain, and then formation of a tight binding complex. Oxidation of methionine residues in CaM resulted in significant perturbations to the binding kinetics. The rate of formation of a tight binding complex was reduced, consistent with the lower effectiveness of oxidized CaM in activating the Ca2+ pump. PMID:17343368

Surface passivation for tight-binding calculations of covalent solids.

PubMed

Bernstein, N

2007-07-04

Simulation of a cluster representing a finite portion of a larger covalently bonded system requires the passivation of the cluster surface. We compute the effects of an explicit hybrid orbital passivation (EHOP) on the atomic structure in a model bulk, three-dimensional, narrow gap semiconductor, which is very different from the wide gap, quasi-one-dimensional organic molecules where most passivation schemes have been studied in detail. The EHOP approach is directly applicable to minimal atomic orbital basis methods such as tight-binding. Each broken bond is passivated by a hybrid created from an explicitly expressed linear combination of basis orbitals, chosen to represent the contribution of the missing neighbour, e.g. a sp(3) hybrid for a single bond. The method is tested by computing the forces on atoms near a point defect as a function of cluster geometry. We show that, compared to alternatives such as pseudo-hydrogen passivation, the force on an atom converges to the correct bulk limit more quickly as a function of cluster radius, and that the force is more stable with respect to perturbations in the position of the cluster centre. The EHOP method also obviates the need for parameterizing the interactions between the system atoms and the passivating atoms. The method is useful for cluster calculations of non-periodic defects in large systems and for hybrid schemes that simulate large systems by treating finite regions with a quantum-mechanical model, coupled to an interatomic potential description of the rest of the system.

Surface passivation for tight-binding calculations of covalent solids

NASA Astrophysics Data System (ADS)

Bernstein, N.

2007-07-01

Simulation of a cluster representing a finite portion of a larger covalently bonded system requires the passivation of the cluster surface. We compute the effects of an explicit hybrid orbital passivation (EHOP) on the atomic structure in a model bulk, three-dimensional, narrow gap semiconductor, which is very different from the wide gap, quasi-one-dimensional organic molecules where most passivation schemes have been studied in detail. The EHOP approach is directly applicable to minimal atomic orbital basis methods such as tight-binding. Each broken bond is passivated by a hybrid created from an explicitly expressed linear combination of basis orbitals, chosen to represent the contribution of the missing neighbour, e.g. a sp3 hybrid for a single bond. The method is tested by computing the forces on atoms near a point defect as a function of cluster geometry. We show that, compared to alternatives such as pseudo-hydrogen passivation, the force on an atom converges to the correct bulk limit more quickly as a function of cluster radius, and that the force is more stable with respect to perturbations in the position of the cluster centre. The EHOP method also obviates the need for parameterizing the interactions between the system atoms and the passivating atoms. The method is useful for cluster calculations of non-periodic defects in large systems and for hybrid schemes that simulate large systems by treating finite regions with a quantum-mechanical model, coupled to an interatomic potential description of the rest of the system.

Practical issues relating to soil column chromatography for sorption parameter determination.

PubMed

Bi, Erping; Schmidt, Torsten C; Haderlein, Stefan B

2010-08-01

Determination of sorption distribution coefficients (K(d)) of organic compounds by a dynamic soil column chromatography (SCC) method was developed and validated. Eurosoil 4, quartz, and alumina were chosen as exemplary packing materials. Heterocyclic aromatic compounds were selected in the validation of SCC. The prerequisites of SCC with regard to column dimension, packing procedure, and sample injection volume are discussed. Reproducible soil column packing was achieved by addition of a pre-column and an HPLC pump for subsequent compression of the packed material. Various methods to determine retention times from breakthrough curves are discussed and the use of the half mass method is recommended. To dilute soil with inert material can prevent column-clogging and help to complete experiments in a reasonable period of time. For the chosen probe compounds, quartz rather than alumina proved a suitable dilution material. Non-equilibrium issue can be overcome by conducting the experiments under different flowrates and/or performing numerical simulation. Copyright 2010 Elsevier Ltd. All rights reserved.

A small cellulose binding domain protein (CBD1) is highly variable in the nonbinding amino terminus

USDA-ARS?s Scientific Manuscript database

The small cellulose binding domain protein CBD1 is tightly bound to the cellulosic cell wall of the plant pathogenic stramenophile Phytophthora infestans. Transgene expression of the protein in plants has also demonstrated binding to plant cell walls. A study was undertaken using 47 isolates of P. ...

Rationalizing Tight Ligand Binding through Cooperative Interaction Networks

PubMed Central

2011-01-01

Small modifications of the molecular structure of a ligand sometimes cause strong gains in binding affinity to a protein target, rendering a weakly active chemical series suddenly attractive for further optimization. Our goal in this study is to better rationalize and predict the occurrence of such interaction hot-spots in receptor binding sites. To this end, we introduce two new concepts into the computational description of molecular recognition. First, we take a broader view of noncovalent interactions and describe protein–ligand binding with a comprehensive set of favorable and unfavorable contact types, including for example halogen bonding and orthogonal multipolar interactions. Second, we go beyond the commonly used pairwise additive treatment of atomic interactions and use a small world network approach to describe how interactions are modulated by their environment. This approach allows us to capture local cooperativity effects and considerably improves the performance of a newly derived empirical scoring function, ScorpionScore. More importantly, however, we demonstrate how an intuitive visualization of key intermolecular interactions, interaction networks, and binding hot-spots supports the identification and rationalization of tight ligand binding. PMID:22087588

Interrelationships of somatic cell count, mastitis, and milk yield in a low somatic cell count herd.

PubMed

Deluyker, H A; Gay, J M; Weaver, L D

1993-11-01

In a high yielding low SCC herd, changes in milk yield associated with SCC and occurrence of clinical mastitis and differences in SCC with parity, clinical mastitis, and DIM were investigated. Milk yield data were obtained at every milking, and SCC was measured once every 48 h in 117 cows during the first 119 d postpartum. Effects of SCC and clinical mastitis on cumulative milk yield in the first 119 d postpartum were evaluated with least squares linear regression. Repeated measures ANOVA was used to detect changes in SCC. The SCC was highest at lactation onset, and cows with clinical mastitis had significantly higher SCC. During the 10 d prior to onset of clinical mastitis, SCC was higher in affected cows than in matched unaffected controls and surged just prior to diagnosis. During the 10-d period following a mastitis treatment, SCC differences between treated and control cows remained significant but became smaller with time and returned to the premastitis differences. Occurrence of clinical mastitis was associated with 5% milk yield loss. Cows with mean SCC > 245,000 cells/ml over the 119 d showed 6.2% yield loss compared with cows with SCC < or = 90,000 cells/ml. Cows with clinical mastitis had higher SCC prior to and following the end of treatment for mastitis than did controls. Clinical mastitis and SCC were associated with significant yield loss. Milk yield loss attributed to clinical mastitis was greater than that associated with elevated SCC (> 245,000 cells/ml) because a greater percentage of cows (26%) had clinical mastitis than elevated SCC (12.5%).

Differentiating oral lesions in different carcinogenesis stages with optical coherence tomography

NASA Astrophysics Data System (ADS)

Tsai, Meng-Tsan; Lee, Cheng-Kuang; Lee, Hsiang-Chieh; Chen, Hsin-Ming; Chiang, Chun-Pin; Wang, Yih-Ming; Yang, Chih-Chung

2009-07-01

A swept-source optical coherence tomography (SS-OCT) system is used to clinically scan oral lesions in different oral carcinogenesis stages, including normal oral mucosa control, mild dysplasia (MiD), moderate dysplasia (MoD), early-stage squamous cell carcinoma (ES-SCC), and well-developed SCC (WD-SCC), for diagnosis purpose. On the basis of the analyses of the SS-OCT images, the stages of dysplasia (MiD and MoD), and SCC (ES-SCC and WD-SCC) can be differentiated from normal control by evaluating the depth-dependent standard deviation (SD) values of lateral variations. In the dysplasia stage, the boundary between the epithelium (EP) and lamina propria (LP) layers can still be identified and the EP layer becomes significantly thicker than that of normal control. Also, in a certain range of the EP layer above the EP/LP boundary, the SD value becomes larger than a certain percentage of the maximum level, which is observed around the EP/LP boundary. On the other hand, in the ES-SCC and WD-SCC stages, the EP/LP boundary disappears. Because of the higher density of connective tissue papillae in the ES-SCC stage, the SD values of the slowly varying lateral scan profiles in the ES-SCC samples are significantly larger than those in the WD-SCC sample. Also, ES-SCC can be differentiated from WD-SCC by comparing the exponential decay constants of averaged A-mode scan profiles. Because of the higher tissue absorption in the WD-SCC lesion, the decay constants in the WD-SCC samples are significantly higher than those in the ES-SCC samples.

First Experimental Realization of the Dirac Oscillator

NASA Astrophysics Data System (ADS)

Franco-Villafañe, J. A.; Sadurní, E.; Barkhofen, S.; Kuhl, U.; Mortessagne, F.; Seligman, T. H.

2013-10-01

We present the first experimental microwave realization of the one-dimensional Dirac oscillator, a paradigm in exactly solvable relativistic systems. The experiment relies on a relation of the Dirac oscillator to a corresponding tight-binding system. This tight-binding system is implemented as a microwave system by a chain of coupled dielectric disks, where the coupling is evanescent and can be adjusted appropriately. The resonances of the finite microwave system yield the spectrum of the one-dimensional Dirac oscillator with and without a mass term. The flexibility of the experimental setup allows the implementation of other one-dimensional Dirac-type equations.

A tight binding model study of tunneling conductance spectra of spin and orbitally ordered CMR manganites

NASA Astrophysics Data System (ADS)

Panda, Saswati; Sahoo, D. D.; Rout, G. C.

2018-04-01

We report here a tight binding model for colossal magnetoresistive (CMR) manganites to study the pseudo gap (PG) behavior near Fermi level. In the Kubo-Ohata type DE model, we consider first and second nearest neighbor interactions for transverse spin fluctuations in core band and hopping integrals in conduction band, in the presence of static band Jahn-Teller distortion. The model Hamiltonian is solved using Zubarev's Green's function technique. The electron density of states (DOS) is found out from the Green's functions. We observe clear PG near Fermi level in the electron DOS.

The tight binding model study of the role of band filling on the charge gap in graphene-on-substrate in paramagnetic state

NASA Astrophysics Data System (ADS)

Panda, Rudrashish; Sahu, Sivabrata; Rout, G. C.

2017-05-01

We communicate here a tight binding theoretical model study of the band filling effect on the charge gap in graphene-on-substrate. The Hamiltonian consists of nearest neighbor electron hopping and substrate induced gap. Besides this the Coulomb interaction is considered here within mean-field approximation in the paramagnetic limit. The electron occupancies at two sublattices are calculated by Green's function technique and are solved self consistently. Finally the charge gap i.e. Δ ¯=U [ < na > -< nb > ] is calculated and computed numerically. The results are reported.

DFT calculation and vibrational spectroscopic studies of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine

NASA Astrophysics Data System (ADS)

Premkumar, S.; Jawahar, A.; Mathavan, T.; Kumara Dhas, M.; Sathe, V. G.; Milton Franklin Benial, A.

2014-08-01

The molecular structure of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine (BABP) was optimized by the DFT/B3LYP method with 6-311G (d,p), 6-311++G (d,p) and cc-pVTZ basis sets using the Gaussian 09 program. The most stable optimized structure of the molecule was predicted by the DFT/B3LYP method with cc-pVTZ basis set. The vibrational frequencies, Mulliken atomic charge distribution, frontier molecular orbitals and thermodynamical parameters were calculated. These calculations were done at the ground state energy level of BABP without applying any constraint on the potential energy surface. The vibrational spectra were experimentally recorded using Fourier Transform-Infrared (FT-IR) and micro-Raman spectrometer. The computed vibrational frequencies were scaled by scale factors to yield a good agreement with observed experimental vibrational frequencies. The complete theoretically calculated and experimentally observed vibrational frequencies were assigned on the basis of Potential Energy Distribution (PED) calculation using the VEDA 4.0 program. The vibrational modes assignments were performed by using the animation option of GaussView 05 graphical interface for Gaussian program. The Mulliken atomic charge distribution was calculated for BABP molecule. The molecular reactivity and stability of BABP were also studied by frontier molecular orbitals (FMOs) analysis.

Study of IGA/SCC behavior of alloy 600 and 690 SG tubing materials in high temperature solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsujikawa, S.; Yashima, S.; Hattori, T.

1996-09-01

Intergranular attack/stress corrosion cracking (IGA/SCC) of Alloy 600 Steam Generator (SG) tubes in the secondary side has been recognized as a matter of great concern for PWRs. Here, IGA/SCC behavior of Alloy 600 and 690 in high temperature solutions was studied using constant extension rate testing (CERT) method under potentiostatic conditions. The IGA/SCC susceptible regions were investigated as a function of pH and electrode potential. The IGA/SCC resistance of SG tubing materials were ranked as, MA600 = TT600 {much_lt} TT690 in acidic solutions, and MA600 < TT600 < TT690 in alkaline solutions. TT690 showed higher corrosion resistance than MA600 andmore » TT600 in both acidic and alkaline conditions. To verify the results of CERT test, long term model boiler tests were also carried out. The model boiler which consists of combinations of several SG tubing materials and tube support plate configurations, operated for more than 15,000 hrs under the simulated operating plant conditions. The results of destructive examination showed good correspondence with the results of a fundamental study, CERT test. The improved performance of alternate SG tubing material was confirmed.« less

Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer.

PubMed

Lopes, Maria Luiza Diniz de Sousa; de Oliveira, Denise Hélen Imaculada Pereira; Sarmento, Dmitry José de Santana; Queiroz, Lélia Maria Guedes; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-04-01

This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p > 0.05). Immunoexpression of p53 was higher in SCC than in AC (p < 0.001), while p21 expression was more observed in AC when compared to SCC group (p = 0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r = -0.30, p = 0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process.

Convectively coupled Kelvin waves in aquachannel simulations: 2. Life cycle and dynamical-convective coupling

NASA Astrophysics Data System (ADS)

Blanco, Joaquín. E.; Nolan, David S.; Mapes, Brian E.

2016-10-01

This second part of a two-part study uses Weather Research and Forecasting simulations with aquachannel and aquapatch domains to investigate the time evolution of convectively coupled Kelvin waves (CCKWs). Power spectra, filtering, and compositing are combined with object-tracking methods to assess the structure and phase speed propagation of CCKWs during their strengthening, mature, and decaying phases. In this regard, we introduce an innovative approach to more closely investigate the wave (Kelvin) versus entity (super cloud cluster or "SCC") dualism. In general, the composite CCKW structures represent a dynamical response to the organized convective activity. However, pressure and thermodynamic fields in the boundary layer behave differently. Further analysis of the time evolution of pressure and low-level moist static energy finds that these fields propagate eastward as a "moist" Kelvin wave (MKW), faster than the envelope of organized convection or SCC. When the separation is sufficiently large the SCC dissipates, and a new SCC generates to the east, in the region of strongest negative pressure perturbations. We revisit the concept itself of the "coupling" between convection and dynamics, and we also propose a conceptual model for CCKWs, with a clear distinction between the SCC and the MKW components.

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helbig, Linda; Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden; Koi, Lydia

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluatedmore » 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of radiation response. Whether this mechanism contributes to the improved outcome of fractionated chemoradiation therapy warrants further investigation.« less

Invited review: effect of udder health management practices on herd somatic cell count.

PubMed

Dufour, S; Fréchette, A; Barkema, H W; Mussell, A; Scholl, D T

2011-02-01

A systematic review of the scientific literature on relationships between management practices used on dairy farms and herd somatic cell count (SCC) was undertaken to distinguish those management practices that have been consistently shown to be associated with herd SCC from those lacking evidence of association. Relevant literature was identified using a combination of database searches (PubMed, Medline, CAB, Agricola, and Web of Science) and iterative screening of references. To be included in the review, a manuscript had to be published after 1979 in French, English, or Dutch; study design had to be other than case report or case series; herds studied had to be composed of ≥ 40 milking cows producing on average ≥ 7,000kg of milk in 305 d; interventions studied had to be management practices applied at the herd level and used as udder health control strategies; and SCC had to be measured using electronic cell counting methods. The 36 manuscripts selected were mainly observational cross-sectional studies; 8 manuscripts dealt exclusively with automatic milking systems and 4 with management of calves and heifers and its effect on SCC in early lactation heifers. Most practices having consistent associations with SCC were related to milking procedures: wearing gloves during milking, using automatic take-offs, using postmilking teat dipping, milking problem cows last, yearly inspection of the milking system, and use of a technique to keep cows standing following milking; all were consistently associated with lower herd SCC. Other practices associated with lower SCC were the use of a freestall system, sand bedding, cleaning the calving pen after each calving, surveillance of dry-cow udders for mastitis, use of blanket dry-cow therapy, parenteral selenium supplementation, udder hair management, and frequent use of the California Mastitis Test. Regarding SCC of heifers, most of the consistent associations reported were related to interventions made during the peripartum period. Studies on automatic milking systems have frequently reported elevation of the herd SCC following transition to the new system. These elevations seemed to be mediated both by the lack of monitoring of chronically infected cows and by an elevated incidence of intramammary infections. By assembling the results reported in many different studies, this review generates a more comprehensive understanding of the management practices influencing SCC and highlights areas of SCC control knowledge that lack evidence of effectiveness. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF/MEK inhibitors in cancer patients: a meta-analysis

PubMed Central

Peng, Ling; Wang, Yina; Hong, Yun; Ye, Xianghua; Shi, Peng; Zhang, Junyan; Zhao, Qiong

2017-01-01

Background BRAF inhibitor and dual BRAF/MEK inhibitors have been approved for the treatment of BRAF-mutated melanoma. Cutaneous squamous cell carcinoma (cuSCC) is an adverse event associated with these drugs. The contribution of BRAF inhibitor and dual BRAF/MEK inhibitors to cuSCC are still unknown. We performed this meta-analysis to determine the overall incidence and relative risk of cuSCC in cancer patients treated with these drugs. Results A total of 7,442 patients from 24 primary studies were included. The incidences of all-grade and high-grade cuSCC in cancer patients treated with BRAF inhibitor were 12.5% (95% CI: 10.8–14.6%) and 11.6% (95% CI: 9.8–13.8%), and dual BRAF/MEK inhibitors were 3.0% (95% CI: 2.0–4.5%) and 2.8% (95% CI: 1.9–4.0%), respectively. On subgroup analysis and meta-regression, the incidence of cuSCC did not vary with tumor type, study design and specific drug used. The use of single agent BRAF inhibitor significantly increased the risk of developing cuSCC comparing with dual BRAF/MEK inhibitors for all-grade (RR 4.72, 95% CI: 2.42–9.20) and high-grade (RR 4.92, 95% CI: 2.64–9.16) in cancer patients. Materials and Methods The databases of PubMed, Embase and abstracts published in ASCO proceedings were searched for relevant studies from January 2000 to June 2017. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies. Conclusions BRAF inhibitor significantly increases the risk of developing cuSCC compared with dual BRAF/MEK inhibitors in cancer patients. Clinicians should be aware of the risks of cuSCC with the administration of these drugs in cancer patients. PMID:29137342

Using dairy herd improvement records and clinical mastitis history to identify subclinical mastitis infections at dry-off.

PubMed

Torres, Audrey H; Rajala-Schultz, Päivi J; Degraves, Fred J; Hoblet, Kent H

2008-05-01

Interest in selective dry cow therapy (SDCT) has been increasing owing to concerns over development of antimicrobial resistance. Implementation of SDCT, however, requires a quick and cost-effective on-farm method for identifying cows for treatment and cows that can be left without treatment. The objective of the present study was to evaluate the use of clinical mastitis (CM) history and somatic cell counts (SCC) from monthly Dairy Herd Improvement (DHI) records in identification of infected and uninfected cows at dry-off. A total of 647 Holstein cows were classified as uninfected or infected at dry-off based on CM history and varying number of monthly SCC records (with three different SCC cut-offs). Cows were considered uninfected based on the following criteria: (1) SCC <100,000 cells/ml and no CM during the lactation; (2) SCC <200,000 cells/ml and no CM during the lactation; (3) as criterion two, but additionally a cow was also considered uninfected if it experienced a case of CM during the first 3 months of the lactation and the SCC was <100,000 cells/ml for the rest of the lactation; (4) SCC <300,000 cells/ml and no CM during the lactation; otherwise they were considered infected. Infected and uninfected cows at dry-off were most efficiently identified using three months' SCC records with a threshold of 200,000 cells/ml for cows without CM during the lactation and a threshold of 100,000 cells/ml during the rest of lactation for cows with CM during the first 90 days in milk. Moreover, this criterion also most efficiently identified cows infected with major pathogens only at dry-off. The success of the criteria used for identifying infected and uninfected cows will, however, depend on herd characteristics, such as prevalence of infection and type of pathogens present in the herd.

Prognostischer Wert der Fläche und Dichte von Lymphgefäßen bei kutanem Plattenepithelkarzinom.

PubMed

Krediet, Jorien Tannette; Kanitakis, Jean; Bob, Adrienne; Schmitter, Julia; Carine Krediet, Annelot; Röwert, Joachim; Stockfleth, Eggert; Painsi, Clemens; Hügel, Rainer; Terhorst, Dorothea; Lange-Asschenfeldt, Bernhard

2016-11-01

Kutane Plattenepithelkarzinome (SCC) sind bekannt für ihre Fähigkeit, über Lymphgefäße zu metastasieren. In neueren Studien wird das Ausmaß der Lymphangiogenese als möglicher prognostischer Faktor bei einigen Hauttumoren genannt. Ziel dieser Studie war die Quantifizierung der Lymphangiogenese bei SCC entweder durch computergestützte Bildanalyse oder mithilfe der Zählmethode nach Chalkley. Gefäßparameter wurden im Hinblick auf ihre Vorhersagekraft für die Bildung von Tumormetastasen beurteilt und verglichen. In dieser Fallkontrollstudie wurden die klinischen und histologischen Daten von jeweils 15 SCC-Patienten mit bzw. ohne Metastasen retrospektiv analysiert. In den SCC-Proben wurde der für das Lymphendothel spezifische Marker D2-40 und der pan-vaskuläre Marker CD31 immunhistochemisch angefärbt und durch computergestützte morphometrische Bildanalyse in Hotspots sowie mithilfe der digitalisierten Zählmethode nach Chalkley analysiert. Die Dichte von Lymphgefäßen, die relative Lymphgefäßfläche und die mit der Chalkley-Methode ermittelte Zahl an Lymphgefäßen (Chalkley-Count) waren bei metastasierten SCC signifikant erhöht. Die Tumordicke war bei metastasierten SCC signifikant höher und besaß die höchste Vorhersagekraft für eine Metastasierung. Die Tumordicke war ein signifikanter Prädiktor für Lymphangiogeneseparameter. Die Lymphangiogenese ist bei metastasierten SCC erhöht, doch ihr Ausmaß wird von der Tumordicke beeinflusst. Die Tumordicke bildet weiterhin den zuverlässigsten prädiktiven Faktor für die Metastasierung. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology

PubMed Central

van Seters, M; Kate, F J W ten; van Beurden, M; Verheijen, R H M; Meijer, C J L M; Burger, M P M; Helmerhorst, T J M

2007-01-01

Background Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. Aim To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. Methods Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. Results Twenty‐seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n = 10), VIN 2 (n = 11) and VIN 3 (n = 6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow‐up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. Conclusions VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high‐grade VIN. PMID:16714399

Excitons in boron nitride single layer

NASA Astrophysics Data System (ADS)

Galvani, Thomas; Paleari, Fulvio; Miranda, Henrique P. C.; Molina-Sánchez, Alejandro; Wirtz, Ludger; Latil, Sylvain; Amara, Hakim; Ducastelle, François

2016-09-01

Boron nitride single layer belongs to the family of two-dimensional materials whose optical properties are currently receiving considerable attention. Strong excitonic effects have already been observed in the bulk and still stronger effects are predicted for single layers. We present here a detailed study of these properties by combining ab initio calculations and a tight-binding Wannier analysis in both real and reciprocal space. Due to the simplicity of the band structure with single valence (π ) and conduction (π*) bands the tight-binding analysis becomes quasiquantitative with only two adjustable parameters and provides tools for a detailed analysis of the exciton properties. Strong deviations from the usual hydrogenic model are evidenced. The ground-state exciton is not a genuine Frenkel exciton, but a very localized tightly bound one. The other ones are similar to those found in transition-metal dichalcogenides and, although more localized, can be described within a Wannier-Mott scheme.

Electronic properties of Bilayer Fullerene onions

NASA Astrophysics Data System (ADS)

Pincak, R.; Shunaev, V. V.; Smotlacha, J.; Slepchenkov, M. M.; Glukhova, O. E.

2017-10-01

The HOMO-LUMO gaps of the bilayer fullerene onions were investigated. For this purpose, the HOMO and LUMO energies were calculated for the isolated fullerenes using the parametrization of the tight binding method with the Harrison-Goodwin modification. Next, the difference of the Fermi levels of the outer and inner shell was calculated by considering the hybridization of the orbitals on the base of the geometric parameters. The results were obtained by the combination of these calculations.

Structures of Aln (n= 27, 28, 29, and 30) clusters with double-tetrahedron structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, W.; Lu, W. C.; Sun, J.

2008-01-31

Global search for lowest-energy structures of neutral aluminum clusters Al{sub n} (n = 27, 28, 29 and 30) was performed using a genetic algorithm (GA) coupled with a tight-binding (TB) method. Structural candidates obtained from our GA search were further optimized with first-principles calculations. It is found that the medium-sized aluminum clusters Al{sub 27} to Al{sub 30} favor double-tetrahedron structures.

Green's function calculations for semi-infinite carbon nanotubes

NASA Astrophysics Data System (ADS)

John, D. L.; Pulfrey, D. L.

2006-02-01

In the modeling of nanoscale electronic devices, the non-equilibrium Green's function technique is gaining increasing popularity. One complication in this method is the need for computation of the self-energy functions that account for the interactions between the active portion of a device and its leads. In the one-dimensional case, these functions may be computed analytically. In higher dimensions, a numerical approach is required. In this work, we generalize earlier methods that were developed for tight-binding Hamiltonians, and present results for the case of a carbon nanotube.

Ti(IV) and the Siderophore Desferrioxamine B: A Tight Complex Has Biological and Environmental Implications.

PubMed

Jones, Kayleigh E; Batchler, Kathleen L; Zalouk, Célia; Valentine, Ann M

2017-02-06

The siderophore desferrioxamine B (DFOB) binds Ti(IV) tightly and precludes its hydrolytic precipitation under biologically and environmentally relevant conditions. This interaction of DFOB with Ti(IV) is investigated by using spectro-potentiometric and spectro-photometric titrations, mass spectrometry, isothermal titration calorimetry (ITC), and computational modeling. The data from pH 2-10 suggest two one-proton equilibria among three species, with one species predominating below pH 3.5, a second from pH 3.5 to 8, and a third above pH 8. The latter species is prone to slow hydrolytic precipitation. Electrospray mass spectrometry allowed the detection of [Ti(IV) (HDFOB)] 2+ and [Ti(DFOB)] + ; these species were assigned as the pH < 3.5 and the 3.5 < pH < 8 species, respectively. The stability constant for Ti(IV)-DFOB was determined by using UV/vis-monitored competition with ethylenediaminetetraacetic acid (EDTA). Taking into consideration the available binding constant of Ti(IV) and EDTA, the data reveal values of log β 111 = 41.7, log β 110 = 38.1, and log β 11-1 = 30.1. The former value was supported by ITC, with the transfer of Ti(IV) from EDTA to DFOB determined to be both enthalpically and entropically favorable. Computational methods yielded a model of Ti-DFOB. The physiological and environmental implications of this tight interaction and the potential role of DFOB in solubilizing Ti(IV) are discussed.

Nitric oxide metabolite levels in acute vaso-occlusive sickle-cell crisis.

PubMed

Lopez, B L; Barnett, J; Ballas, S K; Christopher, T A; Davis-Moon, L; Ma, X

1996-12-01

1) To measure nitric oxide (NO) metabolite levels in patients presenting to the ED in acute vaso-occlusive sickle-cell crisis (SCC), and 2) to determine whether a relationship exists between NO metabolite levels and pain. A prospective, observational study of patients with documented sickle-cell anemia (SCA), aged > or = 18 years, presenting in typical, acute SCC was conducted in an urban, university teaching hospital. Excluded were those with atypical pain or acute, coexistent disease (as evidenced by fever, tachycardia, tachypnea, or hypotension). Pain scores were measured by a 10-cm visual analog scale (VAS). Blood NO metabolite levels for SCC patients and control subjects (healthy volunteers, n = 9; SCA control subjects not in SCC, n = 10) were determined using an NO-specific chemiluminescence technique that measured plasma nitrite and nitrate, the stable end-products of NO. The acute SCC patients were divided into 3 groups, with the range for the SCC-normal (n = 5) group defined as within 2 SD of the healthy volunteer control patients. The SCC-low patients (n = 21) had NO metabolite levels below this range and the SCC-high (n = 21) patients had levels above this range. The SCA and healthy volunteer control groups had similar NO metabolite levels (25.3 vs 22.6 mumol; p = 0.10). The 3 acute SCC groups had the following mean NO levels: 1) SCC-normal = 21.3 +/- 1.6 mumol; 2) SCC-low = 7.2 +/- 1.1 mumol; and 3) SCC-high = 43.7 +/- 3.5 mumol. The SCC-high NO-level group had significantly lower VAS pain scores when compared with the SCC-low and SCC-normal NO-level groups (6.52 +/- 1.85 cm vs 8.76 +/- 0.83 cm, and 8.62 +/- 1.29 cm, p = 0.02). NO metabolite levels vary in SCC patients. Elevated levels are associated with lower pain scores, while lower levels are associated with higher pain scores, indicating that NO metabolites may potentially represent a marker for compensatory mechanisms in SCC tissue ischemia. Further work is needed to delineate the usefulness of NO metabolites in assessing the severity of SCC.

Polymerase/DNA interactions and enzymatic activity: multi-parameter analysis with electro-switchable biosurfaces

NASA Astrophysics Data System (ADS)

Langer, Andreas; Schräml, Michael; Strasser, Ralf; Daub, Herwin; Myers, Thomas; Heindl, Dieter; Rant, Ulrich

2015-07-01

The engineering of high-performance enzymes for future sequencing and PCR technologies as well as the development of many anticancer drugs requires a detailed analysis of DNA/RNA synthesis processes. However, due to the complex molecular interplay involved, real-time methodologies have not been available to obtain comprehensive information on both binding parameters and enzymatic activities. Here we introduce a chip-based method to investigate polymerases and their interactions with nucleic acids, which employs an electrical actuation of DNA templates on microelectrodes. Two measurement modes track both the dynamics of the induced switching process and the DNA extension simultaneously to quantitate binding kinetics, dissociation constants and thermodynamic energies. The high sensitivity of the method reveals previously unidentified tight binding states for Taq and Pol I (KF) DNA polymerases. Furthermore, the incorporation of label-free nucleotides can be followed in real-time and changes in the DNA polymerase conformation (finger closing) during enzymatic activity are observable.

Properties of complexes formed by Na(+), Mg(2+), and Fe(2+) binding with benzene molecules.

PubMed

Kolakkandy, Sujitha; Pratihar, Subha; Aquino, Adelia J A; Wang, Hai; Hase, William L

2014-10-09

A theoretical investigation was performed to study cation-π interactions in complexes of benzene (Bz) with cations, that is, M(z+)(Bz)n for M(z+) = Na(+), Mg(2+), Fe(2+) and n = 1-3, using MP2 theory with the 6-31+G* and 6-311++G** basis sets and the DFT/(B3LYP and B3LYP-D)/6-311++G** methods. Binding energies and structures of the complexes are reported. The splitting between the quintet and single states of the Fe(2+) complexes was found to depend on the number of benzene molecules in the complex and the complex's structure. All of the M(z+)(Bz) complexes prefer a half-sandwich geometry. A geometry with the cation sandwiched between the two benzene rings was found for the M(z+)(Bz)2 complexes, with the benzene rings either in an eclipsed or staggered conformation. An approximate cyclic structure, with the cation at its center, was found for three benzene molecules interacting with the cation. The cation-benzene binding energy is substantial and equal to 22, 108, and 151 kcal/mol for the Na(+)(Bz), Mg(2+)(Bz), and Fe(2+)(Bz) complexes, respectively. The strength of the interaction of the cation with an individual benzene molecule decreases as the number of benzene molecules bound to the cation increases; for example, it is 108 kcal/mol for Mg(2+)(Bz), but only 71 kcal/mol for Mg(2+)(Bz)3. There is a range of values for the M(z+)(Bz)n intermolecular vibrational frequencies; for example, they are ∼230-360 and ∼10-330 cm(-1) for the Mg(2+)(Bz) and Mg(2+)(Bz)3 complexes, respectively. Binding of the cation to benzene both red and blue shifts the benzene vibrational frequencies. This shifting is larger for the Mg(2+) and Fe(2+) complexes, as compared to those for Na(+), as a result of the former's stronger cation-benzene binding. The present study is an initial step to understand the possible importance of cation-π interactions for polycyclic aromatic hydrocarbon aggregation processes during soot formation.

Family matters: sibling rivalry and bonding between p53 and p63 in cancer.

PubMed

Romano, Rose-Anne; Sinha, Satrajit

2014-04-01

The p53 family (p53, p63 and p73) is intimately linked with an overwhelming number of cellular processes during normal physiological as well as pathological conditions including cancer. The fact that these proteins are expressed in myriad isoforms, each with unique biochemical properties and distinct effects on tumorigenesis, complicates their study. A case in point is Squamous Cell Carcinoma (SCC) where p53 is often mutated and the ΔNp63 isoform is overexpressed. Given that p53 and p63 can hetero-dimerize, bind to quite similar DNA elements and share common co-factors, any alterations in their individual expression levels, activity and/or mutation can severely disrupt the family equilibrium. The burgeoning genomics data sets and new additions to the experimental toolbox are offering crucial insights into the complex role of the p53 family in SCC, but more mechanistic studies are needed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of Guidelines for Identification of SCC Sites and Estimation of Re-Inspection Intervals for SCC Direct Assessment

DOT National Transportation Integrated Search

2010-05-31

This report describes the development of a series of guidelines for the identification of SCC sites and the estimation of re-inspection intervals. These SCC Guidelines are designed to complement and supplement existing SCC Direct Assessment protocols...

Tight-binding modeling and low-energy behavior of the semi-Dirac point.

PubMed

Banerjee, S; Singh, R R P; Pardo, V; Pickett, W E

2009-07-03

We develop a tight-binding model description of semi-Dirac electronic spectra, with highly anisotropic dispersion around point Fermi surfaces, recently discovered in electronic structure calculations of VO2-TiO2 nanoheterostructures. We contrast their spectral properties with the well-known Dirac points on the honeycomb lattice relevant to graphene layers and the spectra of bands touching each other in zero-gap semiconductors. We also consider the lowest order dispersion around one of the semi-Dirac points and calculate the resulting electronic energy levels in an external magnetic field. In spite of apparently similar electronic structures, Dirac and semi-Dirac systems support diverse low-energy physics.

Hybrid k .p tight-binding model for intersubband optics in atomically thin InSe films

NASA Astrophysics Data System (ADS)

Magorrian, S. J.; Ceferino, A.; Zólyomi, V.; Fal'ko, V. I.

2018-04-01

We propose atomic films of n -doped γ -InSe as a platform for intersubband optics in the infrared and far-infrared range, coupled to out-of-plane polarized light. Depending on the film thickness (number of layers) and the amount of n -doping of the InSe film, these transitions span from ˜0.7 eV for bilayer to ˜0.05 eV for 15-layer InSe. We use a hybrid k .p theory and tight-binding model, fully parametrized using density-functional theory, to predict their oscillator strengths and thermal linewidths at room temperature.

The tight binding model study of the role of anisotropic AFM spin ordering in the charge ordered CMR manganites

NASA Astrophysics Data System (ADS)

Kar, J. K.; Panda, Saswati; Rout, G. C.

2017-05-01

We propose here a tight binding model study of the interplay between charge and spin orderings in the CMR manganites taking anisotropic effect due to electron hoppings and spin exchanges. The Hamiltonian consists of the kinetic energies of eg and t2g electrons of manganese ion. It further includes double exchange and Heisenberg interactions. The charge density wave interaction (CDW) describes an extra mechanism for the insulating character of the system. The CDW gap and spin parameters are calculated using Zubarev's Green's function technique and computed self-consistently. The results are reported in this communication.

Identification of protein-ligand binding sites by the level-set variational implicit-solvent approach.

PubMed

Guo, Zuojun; Li, Bo; Cheng, Li-Tien; Zhou, Shenggao; McCammon, J Andrew; Che, Jianwei

2015-02-10

Protein–ligand binding is a key biological process at the molecular level. The identification and characterization of small-molecule binding sites on therapeutically relevant proteins have tremendous implications for target evaluation and rational drug design. In this work, we used the recently developed level-set variational implicit-solvent model (VISM) with the Coulomb field approximation (CFA) to locate and characterize potential protein–small-molecule binding sites. We applied our method to a data set of 515 protein–ligand complexes and found that 96.9% of the cocrystallized ligands bind to the VISM-CFA-identified pockets and that 71.8% of the identified pockets are occupied by cocrystallized ligands. For 228 tight-binding protein–ligand complexes (i.e, complexes with experimental pKd values larger than 6), 99.1% of the cocrystallized ligands are in the VISM-CFA-identified pockets. In addition, it was found that the ligand binding orientations are consistent with the hydrophilic and hydrophobic descriptions provided by VISM. Quantitative characterization of binding pockets with topological and physicochemical parameters was used to assess the “ligandability” of the pockets. The results illustrate the key interactions between ligands and receptors and can be very informative for rational drug design.

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability.

PubMed

Qian, Yi-Wen; Li, Chuan; Jiang, Ai-Ping; Ge, Shengfang; Gu, Ping; Fan, Xianqun; Li, Tai-Sheng; Jin, Xia; Wang, Jian-Hua; Wang, Zhi-Liang

2016-10-28

Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-κB signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Report C : self-consolidating concrete (SCC) for infrastructure elements - bond behavior of mild reinforcing steel in SCC.

DOT National Transportation Integrated Search

2012-08-01

The main objective of this study was to determine the effect on bond performance : of mild reinforcing steel in self-consolidating concrete (SCC). The SCC test program : consisted of comparing the bond performance of normal and high strength SCC with...

Effects of milk somatic cell counts on some physicochemical and functional characteristics of skim and whole milk powders.

PubMed

Sert, Durmuş; Mercan, Emin; Aydemir, Serdar; Civelek, Mustafa

2016-07-01

The aim of this work was to study the influence of milk somatic cell count (SCC) levels on spray-dried milk powders. For this reason, 3 cow milks with different SCC (<300,000, 300,000-700,000, >700,000 SCC/mL) were processed into skim (SMP) and whole milk powder (WMP). The effect of SCC on the physicochemical and functional characteristics of the milk powders and textural properties of set-type yogurts produced from reconstituted milk powders with different SCC was evaluated. A crucial difference was noted between milk powders depending on different SCC. Protein values and ash content of powder samples decreased correlatively with increasing SCC. The hydroxymethylfurfural content of SMP was higher than WMP. We noted an increase in hydroxymethylfurfural content of both SMP and WMP depending on elevated SCC. Solubility index of SMP and WMP was 1.280 to 1.632 and 0.940 to 1.208mL, respectively; with increasing SCC, solubility index was affected adversely. The highest foam stability was determined in SMP containing >700,000 SCC. Bulk density of SMP and WMP was between 0.682 and 0.708 and 0.660 to 0.685g/cm(3), respectively. An increase was observed in scorched particle of both SMP and WMP depending on increasing SCC. We found significant differences in particle size distribution of milk powders produced from milk with SCC at different levels. Although WMP had more uniform and big particle structure, SMP had more specific area. A negative correlation was noted between yogurt texture and SCC. Results indicate that milk SCC has negative influences on milk powder quality. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Spin structure of electron subbands in (110)-grown quantum wells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nestoklon, M. O.; Tarasenko, S. A.; Jancu, J.-M.

We present the theory of fine structure of electron states in symmetric and asymmetric zinc-blende-type quantum wells with the (110) crystallographic orientation. By combining the symmetry analysis, sp{sup 3}d{sup 5}s* tight-binding method, and envelope-function approach we obtain quantitative description of in-plane wave vector, well width and applied electric field dependencies of the zero-magnetic-field spin splitting of electron subbands and extract spin-orbit-coupling parameters.

Differences in survival outcome between oropharyngeal and oral cavity squamous cell carcinoma in relation to HPV status.

PubMed

Lai, Kenneth; Killingsworth, Murray; Matthews, Slade; Caixeiro, Nicole; Evangelista, Carlyn; Wu, Xiao; Wykes, James; Samakeh, Alan; Forstner, Dion; Niles, Navin; Hong, Angela; Lee, Cheok Soon

2017-09-01

This study examined the prognostic significance of human papillomavirus (HPV) in patients with oropharyngeal and oral cavity squamous cell carcinoma (SCC). Tissue microarrays were constructed from oropharyngeal and oral cavity SCC (n = 143). The presence of functional HPV in tumour was determined by combined assessments of p16 immunohistochemistry and HPV in situ hybridisation. Oropharyngeal SCC patients presented with more advanced disease in comparison with oral cavity SCC patients (P = 0.001). HPV is present in 60% and 61% of oropharyngeal and oral cavity SCC patients, respectively. HPV-positive oropharyngeal SCC patients with advanced TNM stages displayed better overall and disease-free survival outcomes than HPV-negative patients (P = 0.022 and 0.046, respectively). Such survival differences were not observed in oral cavity SCC. HPV is common in both oropharyngeal and oral cavity SCC and is associated with better survival outcome in oropharyngeal SCC but not in oral cavity SCC patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sodium copper chlorophyllin: in vitro digestive stability and accumulation by Caco-2 human intestinal cells.

PubMed

Ferruzzi, Mario G; Failla, Mark L; Schwartz, Steven J

2002-03-27

Sodium copper chlorophyllin (SCC), a mixture of water-soluble chlorophyll derivatives, is used as both a food colorant and a common dietary supplement. Although the potential antimutagenic and antioxidant properties of this commercial preparation have been demonstrated, limited information is available on its digestion and absorption by humans. Stability of SCC was examined during simulated gastric and small intestinal digestion. Three preparations were subjected to in vitro digestion: SCC in water, SCC in water + 10% corn oil, and SCC in applesauce. SCC components from raw material preparations and in digested samples were analyzed by C(18) HPLC with photodiode array detection. Cu(II)chlorin e(4), the major chlorin component of SCC, was relatively stable during simulated digestion. In contrast, greater than 90% of Cu(II)chlorin e(6) was degraded to undetermined products during digestion. Recovery of Cu(II)chlorin e(6) after digestion was increased by incorporation of SCC into applesauce, suggesting a protective role of the inclusion matrix for stabilization of labile SCC components. Accumulation of SCC derivatives was investigated by using differentiated cultures of the TC7 clone of the Caco-2 human intestinal cell line. Cellular accumulation from media containing 0.5 to 60 ppm SCC was linear with intracellular content ranging between 0.2 and 29.6 microg of total SCC per mg of cellular protein. Uptake of SCC by Caco-2 cells was significantly (p < 0.01) lower in cultures incubated at 4 degrees C than in those incubated at 37 degrees C. Although intracellular SCC was transported into both apical and basolateral compartments when Caco-2 cells were grown on inserts, apical efflux was significantly greater (p < 0.01) than basolateral efflux. Stability of Cu(II)chlorin e(4) during in vitro digestion and effective uptake by Caco-2 enterocyte-like cells support the likelihood that a portion of this SCC component or its metabolites is absorbed from the human intestine.

Comparing Immunohistologic and Demographic Variables of Head and Neck Squamous Cell Carcinoma

DTIC Science & Technology

2015-06-01

HPV 16 and 18 which have a well-established association with cervical cancers . However, HPV 16 accounts for the majority ofHPV...These cancers are now subdivided into HPV associated ( HPV - SCC) and non- HPV associated squamous cell (SCC) carcinomas. HPV -SCG is a distinct entity... cell carcinomas. Laryngoscope 2009; 119(8): 1542-1549. 13. Venuti A, Paolini F. HPV detection methods in head and neck cancer . Head Neck

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

PubMed Central

Head, Christian S; Luu, Quang; Sercarz, Joel; Saxton, Romaine

2006-01-01

Background Conventional cancer therapy including surgery, radiation, and chemotherapy often are physically debilitating and largely ineffective in previously treated patients with recurrent head and neck squamous cell carcinoma (SCC). A natural photochemical, hypericin, could be a less invasive method for laser photodynamic therapy (PDT) of these recurrent head and neck malignancies. Hypericin has powerful photo-oxidizing ability, tumor localization properties, and fluorescent imaging capabilities as well as minimal dark toxicity. The current study defined hypericin PDT in vitro with human SCC cells before the cells were grown as tumor transplants in nude mice and tested as a model for hypericin induced tumor fluorescence and PDT via laser fiberoptics. Methods SNU squamous carcinoma cells were grown in tissue culture, detached from monolayers with trypsin, and incubated with 0.1 μg to 10 μg/ml of hypericin before exposure to laser light at 514, 550, or 593 nm to define optimal dose, time, and wavelength for PDT of tumor cells. The SCC cells also were injected subcutaneously in nude mice and grown for 6–8 weeks to form tumors before hypericin injection and insertion of fiberoptics from a KTP532 surgical laser to assess the feasibility of this operating room instrument in stimulating fluorescence and PDT of tumors. Results In vitro testing revealed a hypericin dose of 0.2–0.5 μg/ml was needed for PDT of the SCC cells with an optimal tumoricidal response seen at the 593 nm light absorption maximum. In vivo tumor retention of injected hypericin was seen for 7 to10 days using KTP532 laser induced fluorescence and biweekly PDT via laser fiberoptics led to regression of SCC tumor transplants under 0.4 cm2 diameter, but resulted in progression of larger size tumors in the nude mice. Conclusion In this preclinical study, hypericin was tested for 514–593 nm dye laser PDT of human SCC cells in vitro and for KTP532 surgical laser targeting of SCC tumors in mice. The results suggest hypericin is a potent tumor imaging agent using this surgical laser that may prove useful in defining tumor margins and possibly in sterilizing post-resection margins. Deeply penetrating pulsed infrared laser emissions will be needed for PDT of larger and more inaccessible tumors. PMID:17147827

On the Electronic Structure of Cu Chlorophyllin and Its Breakdown Products: A Carbon K-Edge X-ray Absorption Spectroscopy Study.

PubMed

Witte, Katharina; Mantouvalou, Ioanna; Sánchez-de-Armas, Rocío; Lokstein, Heiko; Lebendig-Kuhla, Janina; Jonas, Adrian; Roth, Friedrich; Kanngießer, Birgit; Stiel, Holger

2018-02-15

Using near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, the carbon backbone of sodium copper chlorophyllin (SCC), a widely used chlorophyll derivative, and its breakdown products are analyzed to elucidate their electronic structure and physicochemical properties. Using various sample preparation methods and complementary spectroscopic methods (including UV/Vis, X-ray photoelectron spectroscopy), a comprehensive insight into the SCC breakdown process is presented. The experimental results are supported by density functional theory calculations, allowing a detailed assignment of characteristic NEXAFS features to specific C bonds. SCC can be seen as a model system for the large group of porphyrins; thus, this work provides a novel and detailed description of the electronic structure of the carbon backbone of those molecules and their breakdown products. The achieved results also promise prospective optical pump/X-ray probe investigations of dynamic processes in chlorophyll-containing photosynthetic complexes to be analyzed more precisely.

Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

PubMed Central

Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

2017-01-01

Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

Attitudes, Knowledge, and Correlates of Self-Efficacy for the Provision of Safer Conception Counseling Among Ugandan HIV Providers.

PubMed

Goggin, Kathy; Finocchario-Kessler, Sarah; Staggs, Vincent; Woldetsadik, Mahlet Atakilt; Wanyenze, Rhoda K; Beyeza-Kashesya, Jolly; Mindry, Deborah; Khanakwa, Sarah; Wagner, Glenn J

2015-12-01

High rates of childbearing desires (59%) and serodiscordant partnerships (50%) among people living with HIV (PHLA) in Uganda highlight the need for safer conception counseling (SCC). Provider attitudes about counseling PLHA on the use of safer conception methods (SCM) have been explored in qualitative studies, but published quantitative investigations are scarce. Data from 57 Ugandan providers were collected to examine providers' attitudes about childbearing among PLHA and engagement in discussions about childbearing, as well as their knowledge, interest, self-efficacy, and intentions to provide SCC. Correlates of self-efficacy for the provision of SCC were explored to inform the development of training programs. Providers reported a general awareness of most SCM, especially timed unprotected intercourse (TUI); but just over half felt they knew enough to counsel clients in the future and all wanted more training. Childbearing was discussed with less than a third of reproductive aged patients and was mostly initiated by patients. Most providers saw value in providing SCC and believed that most aspects of SCM would be acceptable to their clients, but numerous barriers were endorsed. Self-efficacy was greatest among providers who had had more childbearing conversations, greater SCM awareness, perceived fewer barriers and greater intentions to counsel on TUI. Providers evidence fewer stigmatizing attitudes than in the past. However, those who endorsed more stigmatizing attitudes evidenced a trend for reporting lower self-efficacy for providing SCC. Training will need to simultaneously focus on increasing providers' SCC knowledge and skills while instilling a more realistic appraisal of the risks of assisting couples to employ SCM versus doing nothing.

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

PubMed Central

Fan, Huijie; Yuan, Yuan; Wang, Junsheng; Zhou, Fuyou; Zhang, Mingzhi; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

2013-01-01

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. PMID:23570416

C-Jun expression in lichen planus, psoriasis, and cutaneous squamous cell carcinoma, an immunohistochemical study.

PubMed

Abdou, Asmaa Gaber; Marae, Alaa Hassan; Shoeib, Mohammed; Dawood, Ghada; Abouelfath, Enas

2018-01-01

The AP-1 transcription factor complex is a key player in regulating inflammatory processes, cell proliferation, differentiation, and cell transformation. The aim of the present study is to investigate C-Jun (one of AP-1complex) expression and its proliferative role in skin samples of lichen planus, psoriasis as common inflammatory skin diseases and squamous cell carcinoma using immunohistochemical method. The present study was carried out on skin biopsies of 15 psoriatic patients, 15 lichen planus patients, 15 SCC, and 15 normal skin biopsies. Nuclear expression of C-Jun was detected in basal and few suprabasal layers of epidermis of normal skin. C-Jun was expressed in the whole epidermal layers of both psoriasis (14/15) and lichen planus (15/15) in addition to its expression in lymphocytic infiltrate in the latter in about half of cases (8/15). C-Jun was also expressed in 93.3% (14/15) of SCC in a percentage lower than that of psoriasis, lichen planus, and normal skin. The percentage of C-Jun expression in SCC was significantly associated with an early stage (p = 0.000), free surgical margins (p = 0.022), and small tumour size (p = 0.003). The marked reduction of C-Jun in SCC in comparison to normal skin and inflammatory skin dermatoses may refer to its tumour suppressor activity. C-Jun expression in SCC carries favourable prognosis. Absence of significant association between C-Jun and Ki-67 either in SCC or inflammatory skin diseases indicates that it does not affect proliferative capacity of cells.

Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mai, Binh Khanh; Li, Mai Suan, E-mail: masli@ifpan.edu.pl

2011-07-08

Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenzamore » virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.« less

Role of dermatoglyphics as an indicator of precancerous and cancerous lesions of the oral cavity

PubMed Central

Gupta, Ambika; Karjodkar, Freny R

2013-01-01

Background: Oral squamous cell carcinoma (SCC) is one name that causes panic and holds an undeserved high ranking as a killer. Another important condition which has become a major public health issue in South East Asia is oral submucous fibrosis (OSF). Not all the people using tobacco suffer from these diseases. Genetic predisposition might explain such an individual variability that can be predicted by using various cytogenetic markers. However, these studies are far more costly and complicated. So, dermatoglyphics may be of immense clinical significance to segregate those individuals who are at an increased risk for developing these diseases. Aim: The present study was conducted to analyze the palmar dermatoglyphics in SCC and OSF and find a dermatoglyphic marker, if any. Study Design: Cross sectional study. Materials and Methods: 120 individuals were divided into four groups based upon their habits of tobacco/areca nut usage and presence of OSF/SCC. Dermatoglyphic patterns were recorded using standard ink method. Various patterns were analysed statistically in the four groups. Results and Conclusion: In SCC, there was an increase in frequency of arch and ulnar loop patterns on fingertips, decrease in frequency of simple whorl patterns on fingertips, decrease in frequency of palmar accessory triradii on right and left hands. Significant findings in OSF included an increase in frequency of arch and ulnar loop pattern, decrease in frequency of simple whorl patterns on fingertips, decrease in atd angle on right hand, decrease in frequency of palmar accessory triradii on right hand. The results revealed that the field of dermatoglyphics holds promising results for determining the genetic susceptibility of individuals to develop SCC and OSF. PMID:24403787

DFT calculation and vibrational spectroscopic studies of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine.

PubMed

Premkumar, S; Jawahar, A; Mathavan, T; Kumara Dhas, M; Sathe, V G; Milton Franklin Benial, A

2014-08-14

The molecular structure of 2-(tert-butoxycarbonyl (Boc) -amino)-5-bromopyridine (BABP) was optimized by the DFT/B3LYP method with 6-311G (d,p), 6-311++G (d,p) and cc-pVTZ basis sets using the Gaussian 09 program. The most stable optimized structure of the molecule was predicted by the DFT/B3LYP method with cc-pVTZ basis set. The vibrational frequencies, Mulliken atomic charge distribution, frontier molecular orbitals and thermodynamical parameters were calculated. These calculations were done at the ground state energy level of BABP without applying any constraint on the potential energy surface. The vibrational spectra were experimentally recorded using Fourier Transform-Infrared (FT-IR) and micro-Raman spectrometer. The computed vibrational frequencies were scaled by scale factors to yield a good agreement with observed experimental vibrational frequencies. The complete theoretically calculated and experimentally observed vibrational frequencies were assigned on the basis of Potential Energy Distribution (PED) calculation using the VEDA 4.0 program. The vibrational modes assignments were performed by using the animation option of GaussView 05 graphical interface for Gaussian program. The Mulliken atomic charge distribution was calculated for BABP molecule. The molecular reactivity and stability of BABP were also studied by frontier molecular orbitals (FMOs) analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Systematic spatial and stoichiometric screening towards understanding the surface of ultrasmall oxygenated silicon nanocrystal

NASA Astrophysics Data System (ADS)

Niaz, Shanawer; Zdetsis, Aristides D.; Koukaras, Emmanuel N.; Gülseren, Oǧuz; Sadiq, Imran

2016-11-01

In most of the realistic ab initio and model calculations which have appeared on the emission of light from silicon nanocrystals, the role of surface oxygen has been usually ignored, underestimated or completely ruled out. We investigate theoretically, by density functional theory (DFT/B3LYP) possible modes of oxygen bonding in hydrogen terminated silicon quantum dots using as a representative case of the Si29 nanocrystal. We have considered Bridge-bonded oxygen (BBO), Doubly-bonded oxygen (DBO), hydroxyl (OH) and Mix of these oxidizing agents. Due to stoichiometry, all comparisons performed are unbiased with respect to composition whereas spatial distribution of oxygen species pointed out drastic change in electronic and cohesive characteristics of nanocrytals. From an overall perspective of this study, it is shown that bridge bonded oxygenated Si nanocrystals accompanied by Mix have higher binding energies and large electronic gap compared to nanocrystals with doubly bonded oxygen atoms. In addition, it is observed that the presence of OH along with BBO, DBO and mixed configurations further lowers electronic gaps and binding energies but trends in same fashion. It is also demonstrated that within same composition, oxidizing constituent, along with their spatial distribution substantially alters binding energy, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) gap (up to 1.48 eV) and localization of frontier orbitals.

Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression.

PubMed

da Silva-Diz, Victoria; Simón-Extremera, Pilar; Bernat-Peguera, Adrià; de Sostoa, Jana; Urpí, Maria; Penín, Rosa M; Sidelnikova, Diana Pérez; Bermejo, Oriol; Viñals, Joan Maria; Rodolosse, Annie; González-Suárez, Eva; Moruno, Antonio Gómez; Pujana, Miguel Ángel; Esteller, Manel; Villanueva, Alberto; Viñals, Francesc; Muñoz, Purificación

2016-03-01

Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. β-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC. ©2015 American Association for Cancer Research.

Characteristics of Aerococcus viridans isolated from bovine subclinical mastitis and its effect on milk SCC, yield, and composition.

PubMed

Sun, Meng; Gao, Jian; Ali, Tariq; Yu, Dan; Zhang, Shiyao; Khan, Saeed U; Fanning, Séamus; Han, Bo

2017-04-01

Aerococcus viridians (A. viridans), an environmental Gram-positive bacterium, has been documented to be associated with bovine mastitis. However, its exact role in bovine mastitis and the changes it brings about in milk characteristics are not yet known. The objectives of the current study were to describe the antibiotic resistance of A. viridans from bovine mastitis as well as the correlation between existence of this pathogen in udders and the somatic cell counts (SCC), daily milk yield, and composition of individual cow. One-year sampling for subclinical mastitis composite milk was conducted based on monthly DHI data from September 2013 to August 2014, in a commercial herd located in Beijing, China. All samples were cultured and pathogens were identified using microbiology method. A. viridians isolates were further identified by API identification system and 16S ribosomal RNA (rRNA) sequencing method. Kirby-Bauer disk diffusion method was used to test the antibiotic resistance of A. viridians against kinds of antimicrobial substance. SCC, milk yield, and milk composition data were from monthly Dairy Herd Improvement (DHI) results. Results showed that a total of 279 (16.67%) A. viridans isolates were identified from among 1674 bacterial isolates cultured from milk samples with high SCC. The incidence of mastitis caused by A. viridans was the highest (48-53%) during the summer season. Majority of the isolates were susceptible to most of antimicrobial compounds tested, especially to β-lactams, but were found to be resistant (50-90%) to aminoglycosides, sulfonamides, and tetracycline. The average SCC of the A. viridans infected cows was significantly higher (1000.0 × 10 3  cells/mL) (P < 0.01) as compared to healthy cows (72.4 × 10 3  cells/mL) and daily milk yield decreased (P > 0.05) by 1.86 kg/day. Reductions were also observed in fat content (P > 0.05), lactose (P < 0.01), and total solids (P > 0.05), whereas protein content increased significantly (P < 0.01) in milk samples of cows infected with A. viridans. The results of this study suggest that A. viridans could be considered as an emerging aetiological agent of bovine subclinical mastitis wherein it exerts an effect on SCC, milk yield, and composition.

Comparison of Conjugate Gradient Density Matrix Search and Chebyshev Expansion Methods for Avoiding Diagonalization in Large-Scale Electronic Structure Calculations

NASA Technical Reports Server (NTRS)

Bates, Kevin R.; Daniels, Andrew D.; Scuseria, Gustavo E.

1998-01-01

We report a comparison of two linear-scaling methods which avoid the diagonalization bottleneck of traditional electronic structure algorithms. The Chebyshev expansion method (CEM) is implemented for carbon tight-binding calculations of large systems and its memory and timing requirements compared to those of our previously implemented conjugate gradient density matrix search (CG-DMS). Benchmark calculations are carried out on icosahedral fullerenes from C60 to C8640 and the linear scaling memory and CPU requirements of the CEM demonstrated. We show that the CPU requisites of the CEM and CG-DMS are similar for calculations with comparable accuracy.

The relationship between water binding and desiccation tolerance in tissues

NASA Technical Reports Server (NTRS)

Vertucci, C. W.; Leopold, A. C.

1987-01-01

In an effort to define the nature of desiccation tolerance, a comparison of the water sorption characteristics was made between tissues that were resistant and tissues that were sensitive to desiccation. Water sorption isotherms were constructed for germinated and ungerminated soybean axes and also for fronds of several species of Polypodium with varying tolerance to dehydration. The strength of water binding was determined by van't Hoff as well as D'Arcy/Watt analyses of the isotherms at 5, 15, and/or 25 degrees C. Tissues which were sensitive to desiccation had a poor capacity to bind water tightly. Tightly bound water can be removed from soybean and pea seeds by equilibration at 35 degrees C over very low relative humidities; this results in a reduction in the viability of the seed. We suggest that region 1 water (i.e. water bound with very negative enthalpy values) is an important component of desiccation tolerance.

Study on Flexural Behaviour of Ternary Blended Reinforced Self Compacting Concrete Beam with Conventional RCC Beam

NASA Astrophysics Data System (ADS)

Marshaline Seles, M.; Suryanarayanan, R.; Vivek, S. S.; Dhinakaran, G.

2017-07-01

The conventional concrete when used for structures having dense congested reinforcement, the problems such as external compaction and vibration needs special attention. In such case, the self compacting concrete (SCC) which has the properties like flow ability, passing and filling ability would be an obvious answer. All those SCC flow behavior was governed by EFNARC specifications. In present study, the combination type of SCC was prepared by replacing cement with silica fume (SF) and metakaolin (MK) along with optimum dosages of chemical admixtures. From the fresh property test, cube compressive strength and cylinder split tensile strength, optimum ternary mix was obtained. In order to study the flexural behavior, the optimum ternary mix was taken in which beam specimens of size 1200 mm x 100 mm x 200 mm was designed as singly reinforced section according to IS: 456-2000, Limit state method. Finally the comparative experimental analysis was made between conventional RCC and SCC beams of same grade in terms of flexural strength namely yield load & ultimate load, load- deflection curve, crack size and pattern respectively.

Bond behavior of self compacting concrete

NASA Astrophysics Data System (ADS)

Ponmalar, S.

2018-03-01

The success of an optimum design lies in the effective load transfer done by the bond forces at the steel-concrete interface. Self Compacting Concrete, is a new innovative concrete capable of filling intrinsic reinforcement and gets compacted by itself, without the need of external mechanical vibration. For this reason, it is replacing the conventional vibrated concrete in the construction industry. The present paper outlays the materials and methods adopted for attaining the self compacting concrete and describes about the bond behavior of this concrete. The bond stress-slip curve is similar in the bottom bars for both SCC and normal concrete whereas a higher bond stress and stiffness is experienced in the top and middle bars, for SCC compared to normal concrete. Also the interfacial properties revealed that the elastic modulus and micro-strength of interfacial transition zone [ITZ] were better on the both top and bottom side of horizontal steel bar in the SCC mixes than in normal vibrated concrete. The local bond strength of top bars for SCC is about 20% less than that for NC. For the bottom bars, however, the results were almost the same.

Discussing a diagnosis of human papillomavirus oropharyngeal cancer with patients: An exploratory qualitative study of health professionals

PubMed Central

Dodd, Rachael H.; Marlow, Laura A. V.

2015-01-01

Abstract Background The role of human papillomavirus (HPV) in oropharyngeal squamous cell cancer (SCC) has now been well established. Clinicians' experiences and challenges of talking to patients about HPV have yet to be explored. Methods Fifteen health professionals caring for patients with oropharyngeal SCC were interviewed. Interviews were analyzed thematically. Results Participants expressed mixed views about explaining the causal role of HPV to their patients. Normalizing HPV and emphasizing the positive prognosis associated with it were regarded as key messages to be communicated. Challenging experiences included managing couples in a consultation and patients' concerns about transmitting HPV to their partners. Some participants described limitations to their HPV knowledge and identified the need for further information and training. Conclusion This study identified challenges experienced by health professionals working with patients with oropharyngeal SCC and highlights some key messages to convey to patients. Clinical guidance for health professionals and further information for patients about HPV‐positive oropharyngeal SCC are needed. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: 394–401, 2016 PMID:25351993

Tight-binding model of the photosystem II reaction center: application to two-dimensional electronic spectroscopy

NASA Astrophysics Data System (ADS)

Gelzinis, Andrius; Valkunas, Leonas; Fuller, Franklin D.; Ogilvie, Jennifer P.; Mukamel, Shaul; Abramavicius, Darius

2013-07-01

We propose an optimized tight-binding electron-hole model of the photosystem II (PSII) reaction center (RC). Our model incorporates two charge separation pathways and spatial correlations of both static disorder and fast fluctuations of energy levels. It captures the main experimental features observed in time-resolved two-dimensional (2D) optical spectra at 77 K: peak pattern, lineshapes and time traces. Analysis of 2D spectra kinetics reveals that specific regions of the 2D spectra of the PSII RC are sensitive to the charge transfer states. We find that the energy disorder of two peripheral chlorophylls is four times larger than the other RC pigments.

FAST TRACK COMMUNICATION: Finite-temperature magnetism in bcc Fe under compression

NASA Astrophysics Data System (ADS)

Sha, Xianwei; Cohen, R. E.

2010-09-01

We investigate the contributions of finite-temperature magnetic fluctuations to the thermodynamic properties of bcc Fe as functions of pressure. First, we apply a tight-binding total-energy model parameterized to first-principles linearized augmented plane-wave computations to examine various ferromagnetic, anti-ferromagnetic, and noncollinear spin spiral states at zero temperature. The tight-binding data are fit to a generalized Heisenberg Hamiltonian to describe the magnetic energy functional based on local moments. We then use Monte Carlo simulations to compute the magnetic susceptibility, the Curie temperature, heat capacity, and magnetic free energy. Including the finite-temperature magnetism improves the agreement with experiment for the calculated thermal expansion coefficients.

[Research on hyperspectral remote sensing in monitoring snow contamination concentration].

PubMed

Tang, Xu-guang; Liu, Dian-wei; Zhang, Bai; Du, Jia; Lei, Xiao-chun; Zeng, Li-hong; Wang, Yuan-dong; Song, Kai-shan

2011-05-01

Contaminants in the snow can be used to reflect regional and global environmental pollution caused by human activities. However, so far, the research on space-time monitoring of snow contamination concentration for a wide range or areas difficult for human to reach is very scarce. In the present paper, based on the simulated atmospheric deposition experiments, the spectroscopy technique method was applied to analyze the effect of different contamination concentration on the snow reflectance spectra. Then an evaluation of snow contamination concentration (SCC) retrieval methods was conducted using characteristic index method (SDI), principal component analysis (PCA), BP neural network and RBF neural network method, and the estimate effects of four methods were compared. The results showed that the neural network model combined with hyperspectral remote sensing data could estimate the SCC well.

A Population-based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA

PubMed Central

Li, Zhigang; Perry, Ann E.; Spencer, Steven K.; Gandolfi, A. Jay; Karagas, Margaret R.

2013-01-01

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association. Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178 PMID:23872349

Mitochondrial 3 beta-hydroxysteroid dehydrogenase (HSD) is essential for the synthesis of progesterone by corpora lutea: An hypothesis

PubMed Central

Chapman, John C; Polanco, Jose R; Min, Soohong; Michael, Sandra D

2005-01-01

In mouse ovaries, the enzyme 3 beta-hydroxysteroid dehydrogenase (HSD) is distributed between microsomes and mitochondria. Throughout the follicular phase of the estrous cycle, the HSD activity in microsomes is predominant; whereas, after LH stimulation, HSD activity during the luteal phase is highest in the mitochondria. The current study examined whether or not LH stimulation always results in an increase in mitochondrial HSD activity. This was accomplished by measuring the HSD activity in microsomal and mitochondrial fractions from ovaries of pregnant mice. These animals have two peaks of LH during gestation, and one peak of LH after parturition. It was found that mitochondrial HSD activity was highest after each peak of LH. It is proposed that mitochondrial HSD is essential for the synthesis of high levels of progesterone. The increase in HSD activity in mitochondria after LH stimulation occurs because: 1) LH initiates the simultaneous synthesis of HSD and the cholesterol side-chain cleavage enzyme (P450scc); and, 2) HSD and P450scc bind together to form a complex, which becomes inserted into the inner membrane of the mitochondria. High levels of progesterone are synthesized by mitochondrial HSD because: 1) the requisite NAD+ cofactor for progesterone synthesis is provided directly by the mitochondria, rather than indirectly via the rate limiting malate-aspartate shuttle; and, 2) the end-product inhibition of P450scc by pregnenolone is eliminated because pregnenolone is converted to progesterone. PMID:15804366

Dynamics and molecular determinants of cytoplasmic lipid droplet clustering and dispersion.

PubMed

Orlicky, David J; Monks, Jenifer; Stefanski, Adrianne L; McManaman, James L

2013-01-01

Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps.

Synthesis, DNA binding, topoisomerase inhibition and cytotoxic properties of 2-chloroethylnitrosourea derivatives of hoechst 33258.

PubMed

Bielawski, Krzysztof; Bielawska, Anna; Anchim, Tomasz; Wołczyński, Sławomir

2005-06-01

A number of novel 2-chloroethylnitrosourea derivatives of Hoechst 33258 were synthesized and examined for cytotoxicity in breast cancer cell cultures and for inhibition of topoisomerases I and II. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than Hoechst 33258. The DNA-binding ability of these compounds was evaluated by an ultrafiltration method using calf thymus DNA, poly(dA-dT)2 and poly(dG-dC)2, indicated that these compounds as well as Hoechst 33258 well interact with AT base pair compared with GC pair. Binding studies indicate that these compounds bind more tightly to double-stranded DNA than the parent compound Hoechst 33258. The degree to which these compounds inhibited cell growth breast cancer cells was generally consistent with their relative DNA binding affinity. Mechanistic studies revealed that these compounds act as topoisomerase I (topo I) or topoisomerase II (topo II) inhibitors in plasmid relaxation assays.

Weak partitioning chromatography for anion exchange purification of monoclonal antibodies.

PubMed

Kelley, Brian D; Tobler, Scott A; Brown, Paul; Coffman, Jonathan L; Godavarti, Ranga; Iskra, Timothy; Switzer, Mary; Vunnum, Suresh

2008-10-15

Weak partitioning chromatography (WPC) is an isocratic chromatographic protein separation method performed under mobile phase conditions where a significant amount of the product protein binds to the resin, well in excess of typical flowthrough operations. The more stringent load and wash conditions lead to improved removal of more tightly binding impurities, although at the cost of a reduction in step yield. The step yield can be restored by extending the column load and incorporating a short wash at the end of the load stage. The use of WPC with anion exchange resins enables a two-column cGMP purification platform to be used for many different mAbs. The operating window for WPC can be easily established using high throughput batch-binding screens. Under conditions that favor very strong product binding, competitive effects from product binding can give rise to a reduction in column loading capacity. Robust performance of WPC anion exchange chromatography has been demonstrated in multiple cGMP mAb purification processes. Excellent clearance of host cell proteins, leached Protein A, DNA, high molecular weight species, and model virus has been achieved. (c) 2008 Wiley Periodicals, Inc.

Computational Nanotechnology Program

NASA Technical Reports Server (NTRS)

Scuseria, Gustavo E.

1997-01-01

The objectives are: (1) development of methodological and computational tool for the quantum chemistry study of carbon nanostructures and (2) development of the fundamental understanding of the bonding, reactivity, and electronic structure of carbon nanostructures. Our calculations have continued to play a central role in understanding the outcome of the carbon nanotube macroscopic production experiment. The calculations on buckyonions offer the resolution of a long controversy between experiment and theory. Our new tight binding method offers increased speed for realistic simulations of large carbon nanostructures.

Model Modules to Assist Assessing and Controlling SCC

DOT National Transportation Integrated Search

2008-04-04

This project developed and validated tools to assist in integrity assessment and management both forms of SCC. Because the understanding that underlies integrity management tools was most comprehensive for high-pH SCC, development targeted NN-pH SCC,...

Spectroscopic (FT-IR and UV-Vis) and theoretical (HF and DFT) investigation of 2-Ethyl-N-[(5-nitrothiophene-2-yl)methylidene]aniline

NASA Astrophysics Data System (ADS)

Ceylan, Ümit; Tarı, Gonca Özdemir; Gökce, Halil; Ağar, Erbil

2016-04-01

Crystal structure of the title compound, 2-Ethyl-N-[(5-nitrothiophene-2-yl)methylidene]aniline, C13H12N2O2S, has been synthesized and characterized by FT-IR and UV-Vis spectrum. The compound crystallized in the monoclinic space group P 21/c with a = 11.3578 (4) Å, b = 7.4923 (2) Å, c = 14.9676 (6) Å and β = 99.589 (3)° and Z = 4 in the unit cell. The molecular geometry was also calculated using the Gaussian 03 software and structure was optimized using the HF and DFT/B3LYP methods with the 6-311++G(d,p) basis set in ground state. Using the TD-DFT method, the electronic absorption spectra of the title compound was computed in both the gas phase and ethanol solvent. The harmonic vibrational frequencies of the title compound were calculated using the same methods with the 6-311++G(d,p) basis set. The calculated results were compared with the experimental determination results of the compound. It was seen that the optimized structure was in excellent agreement with the X-ray crystal structure. The energetic behaviors of the title compound in solvent media were examined using the HF and DFT/B3LYP methods with the 6-311++G(d,p) basis set applying the polarizable continuum model (PCM). In addition, the molecular orbitals (FMOs) analysis, molecular electrostatic potential (MEP), nonlinear optical and thermodynamic properties of the title compound were performed using the same methods with the 6-311++G(d,p) basis set.

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

PubMed Central

Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

2017-01-01

Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

The Boundary of Tectonic Units of the South China Continent in the Meso-Neoproterozoic - Early Paleozoic: Insights from Integrated Geophysical Study

NASA Astrophysics Data System (ADS)

Guo, L.; Gao, R.; Meng, X.; Zhang, J.; Wang, H.; Liu, Y.

2013-12-01

The South China continent (SCC), located in the transition zone of the Eurasia, India and Pacific plates, formed in the Meso-Neoproterozoic by collision of the Yangtze block and the Cathaysia block. However, the boundaries of the two blocks before the late Paleozoic (from Meso-Neoproterozoic to early Paleozoic) remain debated in the literature due to strong and complex tectonic and magmatic activities since then. The south of Jiangnan archicontinent is covered mostly by the thick strata since the late Paleozoic, the surface of which is widely covered by the vegetation. And the regional tectonic deformation is extremely complicated with few basal outcrops. For decades, a variety of geophysical detections have been performed in the SCC for understanding the deep structure and tectonic evolution, including deep seismic sounding (DSS) profiles, magnetotelluric sounding (MT) profiles, gravity and magnetic surveys and a small amount of deep seismic reflection profiles. However, due to the limitations of resolution and accuracy of the observed geophysical data in the past, especially short of the deep seismic reflection profiles to reveal fine lithosphere structure, different scientists presented various views on the division of tectonic units in the SCC. In quite recent years, the SinoProbe-02 project launched a long profile of geophysical detections across the two blocks in the SCC, including deep seismic reflection, DSS, MT, and broadband seismic observation, the resolution and accuracy of which had been improved greatly. These newly data will benefit better understanding the deep structure and tectonic evolution of the SCC. Here, we assembled high-resolution Bouguer gravity anomalies and aeromagnetic anomalies data in the SCC. The magnetic data were reduced to the pole by used a varying magnetic inclinations algorithm. We then performed anomaly separation and multi-scales lineation structure analysis on the gravity and RTP magnetic data, and then did 3D fusion analysis on them. Seismic reflection profiles focus on fine lithosphere structure vertically along the profile, while gravity and magnetic methods are beneficial to reveal regional tectonic features laterally. The integrate study of seismic, gravity and magnetic data will play the advantages of various methods and constraint and confirm each other. Hence, we did the interpretation of gravity and magnetic data with constraints of the newly seismic reflection profile. Based on the above studies, we traced the boundaries of tectonic units in the SCC from Meso-Neoproterozoic to early Paleozoic, and formed a certain understanding of the tectonic evolution in the SCC before the late Paleozoic. Acknowledgment: We acknowledge the financial support of the SinoProbe-02-01 and SinoProbe-01-05 projects, and the Fundamental Research Funds for the Central Universities.

Intermediate band formation in a δ-doped like QW superlattices of GaAs/AlxGa1-xAs for solar cell design

NASA Astrophysics Data System (ADS)

Del Río-De Santiago, A.; Martínez-Orozco, J. C.; Rodríguez-Magdaleno, K. A.; Contreras-Solorio, D. A.; Rodríguez-Vargas, I.; Ungan, F.

2018-03-01

It is reported a numerical computation of the local density of states for a δ-doped like QW superlattices of AlxGa1-xAs, as a possible heterostructure that, being integrated into a solar cell device design, can provide an intermediate band of allowed states to assist the absorption of photons with lower energies than that of the energy gap of the solar-cell constituent materials. This work was performed using the nearest neighbors sp3s* tight-binding model including spin. The confining potential caused by the ionized donor impurities in δ-doped impurities seeding that was obtained analytically within the lines of the Thomas-Fermi approximation was reproduced here by the Al concentration x variation. This potential is considered as an external perturbation in the tight-binding methodology and it is included in the diagonal terms of the tight-binding Hamiltonian. Special attention is paid to the width of the intermediate band caused by the change in the considered aluminium concentration x, the inter-well distance between δ-doped like QW wells and the number of them in the superlattice. In general we can conclude that this kind of superlattices can be suitable for intermediate band formation for possible intermediate-band solar cell design.

A complex mechanism determines polarity of DNA replication fork arrest by the replication terminator complex of Bacillus subtilis.

PubMed

Duggin, Iain G; Matthews, Jacqueline M; Dixon, Nicholas E; Wake, R Gerry; Mackay, Joel P

2005-04-01

Two dimers of the replication terminator protein (RTP) of Bacillus subtilis bind to a chromosomal DNA terminator site to effect polar replication fork arrest. Cooperative binding of the dimers to overlapping half-sites within the terminator is essential for arrest. It was suggested previously that polarity of fork arrest is the result of the RTP dimer at the blocking (proximal) side within the complex binding very tightly and the permissive-side RTP dimer binding relatively weakly. In order to investigate this "differential binding affinity" model, we have constructed a series of mutant terminators that contain half-sites of widely different RTP binding affinities in various combinations. Although there appeared to be a correlation between binding affinity at the proximal half-site and fork arrest efficiency in vivo for some terminators, several deviated significantly from this correlation. Some terminators exhibited greatly reduced binding cooperativity (and therefore have reduced affinity at each half-site) but were highly efficient in fork arrest, whereas one terminator had normal affinity over the proximal half-site, yet had low fork arrest efficiency. The results show clearly that there is no direct correlation between the RTP binding affinity (either within the full complex or at the proximal half-site within the full complex) and the efficiency of replication fork arrest in vivo. Thus, the differential binding affinity over the proximal and distal half-sites cannot be solely responsible for functional polarity of fork arrest. Furthermore, efficient fork arrest relies on features in addition to the tight binding of RTP to terminator DNA.

Magnesium alloys as body implants: fracture mechanism under dynamic and static loadings in a physiological environment.

PubMed

Choudhary, Lokesh; Raman, R K Singh

2012-02-01

It is essential that a metallic implant material possesses adequate resistance to cracking/fracture under the synergistic action of a corrosive physiological environment and mechanical loading (i.e. stress corrosion cracking (SCC)), before the implant can be put to actual use. This paper presents a critique of the fundamental issues with an assessment of SCC of a rapidly corroding material such as magnesium alloys, and describes an investigation into the mechanism of SCC of a magnesium alloy in a physiological environment. The SCC susceptibility of the alloy in a simulated human body fluid was established by slow strain rate tensile (SSRT) testing using smooth specimens under different electrochemical conditions for understanding the mechanism of SCC. However, to assess the life of the implant devices that often possess fine micro-cracks, SCC susceptibility of notched specimens was investigated by circumferential notch tensile (CNT) testing. CNT tests also produced important design data, i.e. threshold stress intensity for SCC (KISCC) and SCC crack growth rate. Fractographic features of SCC were examined using scanning electron microscopy. The SSRT and CNT results, together with fractographic evidence, confirmed the SCC susceptibility of both smooth and notched specimens of a magnesium alloy in the physiological environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Subjective cognitive complaints after stroke: a systematic review.

PubMed

van Rijsbergen, Marielle W A; Mark, Ruth E; de Kort, Paul L M; Sitskoorn, Margriet M

2014-03-01

Most studies to date have assessed poststroke cognitive impairment objectively, whereas less attention is paid to subjective cognitive complaints (SCC). We, therefore, systematically searched the literature to summarize and evaluate the current knowledge about poststroke SCC. Articles were included in this review if the study evaluated SCC in adult stroke survivors, and the publication was an original empirical article from which the full text was available. There were no year or language restrictions. Twenty-six studies were found on poststroke SCC. There is a huge heterogeneity among these studies with respect to stroke sample, SCC definitions, and instruments used, but they all showed that SCC are very common after stroke. Other main findings are that SCC tend to increase over time and that there is moderate agreement between patients and their proxies on prevalence and severity of patients' SCC. Furthermore, SCC are inconsistently associated with current depressive symptoms and objective cognitive performances, whereas they may predict future emotional and cognitive functioning. This review highlights that poststroke SCC are highly prevalent and that clinicians should take such complaints seriously. More research is, however, needed to gain further insight into poststroke SCC, to be able to accurately inform patients and relatives, and to develop adequate treatment programs. Based on the limitations of the studies to date, suggestions are made on how both future research and ultimately patient-centered care may be improved in stroke survivors. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The economic burden of occupational non-melanoma skin cancer due to solar radiation.

PubMed

Mofidi, Amirabbas; Tompa, Emile; Spencer, James; Kalcevich, Christina; Peters, Cheryl E; Kim, Joanne; Song, Chaojie; Mortazavi, Seyed Bagher; Demers, Paul A

2018-06-01

Solar ultraviolet (UV) radiation is the second most prevalent carcinogenic exposure in Canada and is similarly important in other countries with large Caucasian populations. The objective of this article was to estimate the economic burden associated with newly diagnosed non-melanoma skin cancers (NMSCs) attributable to occupational solar radiation exposure. Key cost categories considered were direct costs (healthcare costs, out-of-pocket costs (OOPCs), and informal caregiver costs); indirect costs (productivity/output costs and home production costs); and intangible costs (monetary value of the loss of health-related quality of life (HRQoL)). To generate the burden estimates, we used secondary data from multiple sources applied to computational methods developed from an extensive review of the literature. An estimated 2,846 (5.3%) of the 53,696 newly diagnosed cases of basal cell carcinoma (BCC) and 1,710 (9.2%) of the 18,549 newly diagnosed cases of squamous cell carcinoma (SCC) in 2011 in Canada were attributable to occupational solar radiation exposure. The combined total for direct and indirect costs of occupational NMSC cases is $28.9 million ($15.9 million for BCC and $13.0 million for SCC), and for intangible costs is $5.7 million ($0.6 million for BCC and $5.1 million for SCC). On a per-case basis, the total costs are $5,670 for BCC and $10,555 for SCC. The higher per-case cost for SCC is largely a result of a lower survival rate, and hence higher indirect and intangible costs. Our estimates can be used to raise awareness of occupational solar UV exposure as an important causal factor in NMSCs and can highlight the importance of occupational BCC and SCC among other occupational cancers.

Mediation analysis to estimate direct and indirect milk losses due to clinical mastitis in dairy cattle.

PubMed

Detilleux, J; Kastelic, J P; Barkema, H W

2015-03-01

Milk losses associated with mastitis can be attributed to either effects of pathogens per se (i.e., direct losses) or effects of the immune response triggered by intramammary infection (indirect losses). The distinction is important in terms of mastitis prevention and treatment. Regardless, the number of pathogens is often unknown (particularly in field studies), making it difficult to estimate direct losses, whereas indirect losses can be approximated by measuring the association between increased somatic cell count (SCC) and milk production. An alternative is to perform a mediation analysis in which changes in milk yield are allocated into their direct and indirect components. We applied this method on data for clinical mastitis, milk and SCC test-day recordings, results of bacteriological cultures (Escherichia coli, Staphylococcus aureus, Streptococcus uberis, coagulase-negative staphylococci, Streptococcus dysgalactiae, and streptococci other than Strep. dysgalactiae and Strep. uberis), and cow characteristics. Following a diagnosis of clinical mastitis, the cow was treated and changes (increase or decrease) in milk production before and after a diagnosis were interpreted counterfactually. On a daily basis, indirect changes, mediated by SCC increase, were significantly different from zero for all bacterial species, with a milk yield decrease (ranging among species from 4 to 33g and mediated by an increase of 1000 SCC/mL/day) before and a daily milk increase (ranging among species from 2 to 12g and mediated by a decrease of 1000 SCC/mL/day) after detection. Direct changes, not mediated by SCC, were only different from zero for coagulase-negative staphylococci before diagnosis (72g per day). We concluded that mixed structural equation models were useful to estimate direct and indirect effects of the presence of clinical mastitis on milk yield. Copyright © 2015 Elsevier B.V. All rights reserved.

Attitudes, Knowledge, and Correlates of Self-Efficacy for the Provision of Safer Conception Counseling Among Ugandan HIV Providers

PubMed Central

Finocchario-Kessler, Sarah; Staggs, Vincent; Woldetsadik, Mahlet Atakilt; Wanyenze, Rhoda K.; Beyeza-Kashesya, Jolly; Mindry, Deborah; Khanakwa, Sarah; Wagner, Glenn J.

2015-01-01

Abstract High rates of childbearing desires (59%) and serodiscordant partnerships (50%) among people living with HIV (PHLA) in Uganda highlight the need for safer conception counseling (SCC). Provider attitudes about counseling PLHA on the use of safer conception methods (SCM) have been explored in qualitative studies, but published quantitative investigations are scarce. Data from 57 Ugandan providers were collected to examine providers' attitudes about childbearing among PLHA and engagement in discussions about childbearing, as well as their knowledge, interest, self-efficacy, and intentions to provide SCC. Correlates of self-efficacy for the provision of SCC were explored to inform the development of training programs. Providers reported a general awareness of most SCM, especially timed unprotected intercourse (TUI); but just over half felt they knew enough to counsel clients in the future and all wanted more training. Childbearing was discussed with less than a third of reproductive aged patients and was mostly initiated by patients. Most providers saw value in providing SCC and believed that most aspects of SCM would be acceptable to their clients, but numerous barriers were endorsed. Self-efficacy was greatest among providers who had had more childbearing conversations, greater SCM awareness, perceived fewer barriers and greater intentions to counsel on TUI. Providers evidence fewer stigmatizing attitudes than in the past. However, those who endorsed more stigmatizing attitudes evidenced a trend for reporting lower self-efficacy for providing SCC. Training will need to simultaneously focus on increasing providers' SCC knowledge and skills while instilling a more realistic appraisal of the risks of assisting couples to employ SCM versus doing nothing. PMID:26588429

Investigating the Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of the Larynx and Its Correlation with Disease Prognosis

PubMed Central

Atighechi, Saeid; Meybodian, Mojtaba; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Behniafard, Nasim

2016-01-01

Introduction: The human papilloma virus (HPV) can play a role in the development of head and neck squamous cell carcinoma (SCC). Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated. Materials and Methods: This case-control study was performed in 44 patients with SCC of the larynx (case group), while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples) to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR) was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS). Results: PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25%) samples, while only two (5.6%) HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031). No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235). Conclusion: Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients. PMID:27429948

How actin binds and assembles onto plasma membranes from Dictyostelium discoideum

PubMed Central

1988-01-01

We have shown previously (Schwartz, M. A., and E. J. Luna. 1986. J. Cell Biol. 102: 2067-2075) that actin binds with positive cooperativity to plasma membranes from Dictyostelium discoideum. Actin is polymerized at the membrane surface even at concentrations well below the critical concentration for polymerization in solution. Low salt buffer that blocks actin polymerization in solution also prevents actin binding to membranes. To further explore the relationship between actin polymerization and binding to membranes, we prepared four chemically modified actins that appear to be incapable of polymerizing in solution. Three of these derivatives also lost their ability to bind to membranes. The fourth derivative (EF actin), in which histidine-40 is labeled with ethoxyformic anhydride, binds to membranes with reduced affinity. Binding curves exhibit positive cooperativity, and cross- linking experiments show that membrane-bound actin is multimeric. Thus, binding and polymerization are tightly coupled, and the ability of these membranes to polymerize actin is dramatically demonstrated. EF actin coassembles weakly with untreated actin in solution, but coassembles well on membranes. Binding by untreated actin and EF actin are mutually competitive, indicating that they bind to the same membrane sites. Hill plots indicate that an actin trimer is the minimum assembly state required for tight binding to membranes. The best explanation for our data is a model in which actin oligomers assemble by binding to clustered membrane sites with successive monomers on one side of the actin filament bound to the membrane. Individual binding affinities are expected to be low, but the overall actin-membrane avidity is high, due to multivalency. Our results imply that extracellular factors that cluster membrane proteins may create sites for the formation of actin nuclei and thus trigger actin polymerization in the cell. PMID:3392099

Effects of irradiation on human leukocyte antigen class I expression in human papillomavirus positive and negative base of tongue and mobile tongue squamous cell carcinoma cell lines.

PubMed

Haeggblom, Linnea; Nordfors, Cecilia; Tertipis, Nikolaos; Bersani, Cinzia; Ramqvist, Torbjörn; Näsman, Anders; Dalianis, Tina

2017-03-16

Human papillomavirus (HPV) infection is a risk factor for oropharyngeal cancer, besides smoking and alcohol. Patients with HPV-positive tumors have a better prognosis than those with HPV-negative tumors. Furthermore, patients with HPV-positive tumors, with high CD8+ tumor infiltrating lymphocyte counts or absent/low human leukocyte antigen (HLA) class I expression have the best outcome. The latter is paradoxical, since HLA class I expression is important for tumor recognition. Below, the hypothesis that radiation therapy increases HLA class I expression was tested. HPV16 positive head and neck cancer cell lines UPCI-SCC-154, UPCI-SCC-090 and UM-SCC-47, and the HPV-negative cancer cell line UT-SCC-14, were treated with 2-10 Gray (Gy) and tested for HLA class I expression, cell cycle changes and apoptosis by flow cytometry. HPV16 E5, E7 and HLA-A mRNA expression was tested by quantitative PCR. A dose of 10 Gy resulted in a tendency of increased HLA class I cell surface expression for all cell lines and reached statistical significance for UPCI-SCC-154 and UPCI-SCC-090. There were, however, no significant changes in HLA-A mRNA expression in any of the cell lines, or HPV16 E5, or E7 mRNA expression for UPCI-SCC-47 and UPCI-SCC-154, while for UPCI-SCC-090 HPV16 E5 mRNA decreased. In all cell lines there was a shift towards G2/M phase and increased apoptosis after irradiation with 10 Gy. To conclude, irradiation with 10 Gy increased HLA class I expression in the HPV-positive cell lines UPCI-SCC-154 and UPCI-SCC-090. A similar tendency was observed for HPV-positive UM-SCC-47 and HPV-negative UT-SCC-14.

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

PubMed Central

Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A.; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H.; Ching, Grace; Nguyen, Tran N.; Nicholas, Courtney; Thomas, Valencia D.; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A.; Abbas, Hussein A.; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R.; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N.; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P.; Wheeler, David A.; Hawk, Ernest T.; Flores, Elsa R.; Tsai, Kenneth Y.

2016-01-01

Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction.

PubMed

Prudnick, Colton; Morley, Chad; Shapiro, Robert; Zaslau, Stanley

2013-01-01

Squamous cell carcinoma (SCC) of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC) but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

PubMed Central

Lotti, Roberta; Palazzo, Elisabetta; Petrachi, Tiziana; Dallaglio, Katiuscia; Saltari, Annalisa; Truzzi, Francesca; Quadri, Marika; Puviani, Mario; Maiorana, Antonino; Marconi, Alessandra; Pincelli, Carlo

2016-01-01

Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development. PMID:26771605

Squamous Cell Carcinoma Arising in Hypertrophic Lichen Planus: A Review and Analysis of 38 Cases.

PubMed

Knackstedt, Thomas J; Collins, Lindsey K; Li, Zhongze; Yan, Shaofeng; Samie, Faramarz H

2015-12-01

Hypertrophic lichen planus is a chronic variant of lichen planus with controversial malignant association. To describe and analyze the relationship of squamous cell carcinoma (SCC) and hypertrophic lichen planus. A retrospective chart review of patients with hypertrophic lichen planus and SCC was performed at the authors' institution. Thereafter, scientific databases were searched for articles reporting cases of SCC arising in hypertrophic lichen planus. Patient demographics, immune status, lichen planus features, and SCC data points were extracted for each patient and evaluated. Thirty-eight cases of SCC in hypertrophic lichen planus occurred in 16 women, average age: 61.4, and 22 men, average age: 51.3, after a lag time of 88 days to 40 years. Squamous cell carcinoma was uniformly located on the lower extremity. Men had larger SCC than women (p = .027) and a significantly longer lag time to SCC development (p = .002). Long lag time was associated with a smaller SCC size (p = .032). In the past, hypertrophic lichen planus and SCC have been considered isolated diseases. Based on an increasing number of cases, the association between hypertrophic lichen planus and keratinocyte malignancies warrants surveillance.

The effect of somatic cell count data adjustment and interpretation, as outlined in European Union legislation, on herd eligibility to supply raw milk for processing of dairy products.

PubMed

More, S J; Clegg, T A; Lynch, P J; O'Grady, L

2013-06-01

Somatic cell count (SCC) limits are a key component of national and international regulation for milk quality. As yet, very limited work has been published on SCC regulatory standards, including on the effect of different approaches to SCC data adjustment and interpretation. This study examines the effect of SCC data adjustment and interpretation, as outlined in current European Union (EU) legislation, on herd eligibility to supply raw milk for processing of dairy products for human consumption, using Irish data for illustration. The study used Irish milk-recording data as a proxy for bulk tank SCC (BTSCC) data, to calculate an unadjusted monthly SCC value for each herd during each month of participation. Subsequently, 4 data adjustments were applied, as outlined in EU and national legislation: seasonal adjustment; 3-mo rolling geometric average, without accounting for a break in the supply; 3-mo rolling geometric average, after accounting for a break in the supply; and seasonal adjustment and 3-mo rolling geometric average combined, after accounting for a break in the supply. Analyses were conducted to examine the effect, during the period from 2004 to 2010, of data adjustment on the percentage of herds with herd SCC >400,000 cells/mL. In all, 4 interpretation scenarios, incorporating different data adjustment combinations, were used to estimate herd eligibility (compliant, under warning, or suspended, as defined by legislation) to supply raw milk for processing. The 4 methods of data adjustment each led to a sizable reduction (6.7, 5.0, 5.3, and 11.1 percentage points, respectively, compared with the unadjusted data) in the percentage of herds exceeding a herd SCC of 400,000 cells/mL. Herd eligibility varied by interpretation scenarios, in particular those incorporating seasonal adjustment. The study provides new perspectives on the effect of data adjustment on herd SCC and of interpretation scenarios on herd eligibility. The results provide an illustrative, rather than definitive, picture of this effect, as national authorities use BTSCC data when determining herd eligibility, whereas this study was conducted using milk-recording data as a proxy. Some aspects of the primary EU legislation are unclear, which may lead to differences in interpretation and application. The potential impact of data adjustment and milk purchaser pricing on farm-level mastitis control in Ireland is considered. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[The succinyl-choline drip as a muscle relaxant for ether-air anesthesia (author's transl)].

PubMed

Lunt, R L; Kamm, G

1976-11-19

We made a test series with ether-air anesthesia in combination with the succinyl-choline (SCC) drip-method. The 53 patients (40 Africans, 10 Indians, 3 Europeans) were 1 to 85 years old. The results we obtained were good: There were no fundamental changes with regard to the circulatory system; the risk of an overdose as well as of a dual block can be reduced by careful observation of the muscular action after the first SCC dose; post-operative complications, too, can be reduced. The ether-air anesthesia is an uncomplicated and cheap method. It is, in combination with succinyl-choline infusion as a muscle relaxant, a most useful anesthetic method for short operations in developing countries.

Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

PubMed

Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

2012-12-01

Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones

PubMed Central

Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

2013-01-01

RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous ‘polyamide amino acids’ (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy–entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets. PMID:23605042

Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones.

PubMed

Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

2013-06-01

RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous 'polyamide amino acids' (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy-entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets.

Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

PubMed

Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

2015-07-01

Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of 2 oral ultrasonography contrast agents: simethicone-coated cellulose and simethicone-water rotation in improving pancreatic visualization.

PubMed

Ishigami, Kousei; Abu-Yousef, Dina M; Kao, Simon C S; Abu-Yousef, Monzer M

2014-06-01

The purpose of this study was to prospectively compare the efficacy of 2 oral ultrasonography (US) contrast agents (simethicone-water rotation [SWR] and simethicone-coated cellulose [SCC]) in improving visualization of the pancreas. Two sessions (SWR and SCC) of transabdominal US studies were performed on 38 healthy volunteers. In each session, US images were obtained in precontrast supine and upright positions and postcontrast supine and upright positions. The visualization of the pancreas was graded on a scale of 1 to 5 (1 = nonvisualization, 5 = excellent visualization), grading the head, body, and tail separately. In the supine position, SWR significantly improved the visualization of the pancreatic head, body, and tail, whereas there were no significant differences between SCC and precontrast images. Simethicone-water rotation showed significantly better visualization than SCC. The average scores of the head, body, and tail of the pancreas that graded 4 or more were 15.8% of precontrast, 21.1% of SCC, and 50% of SWR. In the upright position, both SWR and SCC significantly improved the visualization of the pancreas, except for the pancreatic body on SCC. There were no significant differences between SWR and SCC. The average scores that graded 4 or more were 26.3% of precontrast, 57.9% of SCC, and 65.8% of SWR. Simethicone-water rotation was more effective than SCC in improving the visualization of the pancreas.

Tight Junction–Associated Signaling Pathways Modulate Cell Proliferation in Uveal Melanoma

PubMed Central

Jayagopal, Ashwath; Yang, Jin-Long; Haselton, Frederick R.; Chang, Min S.

2011-01-01

Purpose. To investigate the role of tight junction (TJ)–associated signaling pathways in the proliferation of uveal melanoma. Methods. Human uveal melanoma cell lines overexpressing the TJ molecule blood vessel epicardial substance (Bves) were generated. The effects of Bves overexpression on TJ protein expression, cell proliferation, and cell cycle distribution were quantified. In addition, localization and transcription activity of the TJ-associated protein ZO-1–associated nucleic acid binding protein (ZONAB) were evaluated using immunofluorescence and bioluminescence reporter assays to study the involvement of Bves signaling in cell proliferation-associated pathways. Results. Bves overexpression in uveal melanoma cell lines resulted in increased expression of the TJ proteins occludin and ZO-1, reduced cell proliferation, and increased sequestration of ZONAB at TJs and reduced ZONAB transcriptional activity. Conclusions. TJ proteins are present in uveal melanoma, and TJ-associated signaling pathways modulate cell signaling pathways relevant to proliferation in uveal melanoma. PMID:20861479

Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients.

PubMed

Hock, B D; McIntosh, N D; McKenzie, J L; Pearson, J F; Simcock, J W; MacPherson, S A

2016-12-01

Chronic lymphocytic leukaemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, particularly cutaneous squamous cell carcinoma (cSCC), but little is known about cSCC incidence in Australasian CLL patients. In this retrospective study, we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ). We retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who presented to the Haematology Department, Christchurch Hospital, NZ during the period 1996-2015. Baseline characteristics, incidence of second cancers, treatment details and overall survival were analysed. During follow-up (median = 11.8 years), 221 second cancers were recorded in 88 patients. Of these cancers, 185 were cSCC, removed from 61 patients. In 56% of these patients, >1 cSCC was removed, and the majority of cSCC occurred following the treatment for CLL. The cumulative incidence of a first cSCC was 11% at 5 years, whereas the cumulative incidence of a subsequent cSCC was 88% at 5 years. The incidence of cSCC in male patients was threefold higher than that reported for the general NZ population. NZ CLL patients have a high incidence of cSCC relative to the levels observed in the general population, which are themselves among the highest in the world. The careful monitoring of CLL patients is warranted, particularly those who have a progressive disease or have had a first cSCC removed. © 2016 Royal Australasian College of Physicians.

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not "high risk": Diagnosis, management, and clinical outcomes in a series of 115 cases.

PubMed

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H; Fung, Maxwell A

2017-02-01

Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. This was a single-institution retrospective study from the United States. The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, J.R.; Lu, Z.; Ring, D.M.

We have examined a variety of structures for the {l_brace}510{r_brace} symmetric tilt boundary in Si and Ge, using tight-binding and first-principles calculations. These calculations show that the observed structure in Si is the lowest-energy structure, despite the fact that it is more complicated than what is necessary to preserve fourfold coordination. Contrary to calculations using a Tersoff potential, first-principles calculations show that the energy depends strongly upon the structure. A recently developed tight-binding model for Si produces results in very good agreement with the first-principles calculations. Electronic density of states calculations based upon this model show no evidence of midgapmore » states and little evidence of electronic states localized to the grain boundary. {copyright} {ital 1998} {ital The American Physical Society}« less

Multiscale real-space quantum-mechanical tight-binding calculations of electronic structure in crystals with defects using perfectly matched layers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pourmatin, Hossein, E-mail: mpourmat@andrew.cmu.edu; Dayal, Kaushik, E-mail: kaushik@cmu.edu

2016-10-15

Graphical abstract: - Abstract: We consider the scattering of incident plane-wave electrons from a defect in a crystal modeled by the time-harmonic Schrödinger equation. While the defect potential is localized, the far-field potential is periodic, unlike standard free-space scattering problems. Previous work on the Schrödinger equation has been almost entirely in free-space conditions; a few works on crystals have been in one-dimension. We construct absorbing boundary conditions for this problem using perfectly matched layers in a tight-binding formulation. Using the example of a point defect in graphene, we examine the efficiency and convergence of the proposed absorbing boundary condition.

Report B : self-consolidating concrete (SCC) for infrastructure elements - bond, transfer length, and development length of prestressing strand in SCC.

DOT National Transportation Integrated Search

2012-08-01

Due to its economic advantages, the use of self-consolidating concrete (SCC) has : increased rapidly in recent years. However, because SCC mixes typically have decreased : amounts of coarse aggregate and high amounts of admixtures, industry members h...

Direct vascular control results in less physiologic derangement than proximal aortic clamping in a porcine model of noncompressible extrathoracic torso hemorrhage.

PubMed

White, Joseph M; Cannon, Jeremy W; Stannard, Adam; Burkhardt, Gabriel E; Spencer, Jerry R; Williams, Ken; Oh, John S; Rasmussen, Todd E

2011-11-01

The optimal method of vascular control and resuscitation in patients with life-threatening, extrathoracic torso hemorrhage remains debated. Guidelines recommend emergency department thoracotomy (EDT) with aortic clamping, although transabdominal aortic clamping followed by vascular control and direct vascular control (DVC) without aortic clamping are alternatives. The objective of this study is to compare the effectiveness of three approaches to extrathoracic torso hemorrhage in a large animal model. Adolescent swine (Sus Scrofa) (mean weight = 80.9 kg) were randomized into three groups all of which had class IV shock established by hemorrhage from an iliac artery injury. Group 1: EDT with thoracic aortic clamping (N = 6); group 2: transabdominal supraceliac aortic clamping (SCC; N = 6); and group 3: DVC of bleeding site without aortic clamping (N = 6). After hemorrhage, EDT or SCC was performed in groups 1 and 2, respectively, with subsequent exploration of the bleeding site and placement of a temporary vascular shunt (TVS). Group 3 (DVC) underwent direct exploration of the injury and placement of a TVS. All groups were resuscitated to predefined physiologic endpoints over 6 hours with repeated measures of central and cerebral perfusion and end-organ function at standardized time points. Postmortem tissue analysis was performed to quantify injury to critical tissue beds. There was no difference in mortality among the groups and no TVS failures. Central aortic pressure, carotid flow, and partial pressure brain tissue oximetry, all demonstrated increases in EDT and SCC after application of the aortic clamp relative to DVC (p < 0.05). During resuscitation, serum lactate levels were higher in EDT compared with SCC and DVC (6.85 vs. 3.08 and 2.15, respectively; p < 0.05) and serum pH in EDT reflected greater acidosis than SCC and DVC (7.24 vs. 7.36 and 7.39, respectively; p < 0.05). EDT and SCC required more intravenous fluid than DVC (2,166 mL and 2,166 mL vs. 667 mL, respectively; p < 0.05) and more vasopressors were used in EDT and SCC compared with DVC (52.1 μg and 43.5 μg vs. 12.4 μg, respectively; p < 0.05). Brain and myocardial tissue stains demonstrated the same degree of acute ischemic changes in all groups. Although aortic clamping increases central and cerebral perfusion, DVC results in less physiologic derangement. The optimal method of aortic control would incorporate the benefits of maintained central pressure with less associated morbidity. Clinical studies evaluating DVC are warranted.

Optimization of binding electrostatics: Charge complementarity in the barnase-barstar protein complex

PubMed Central

lee, Lee-Peng; Tidor, Bruce

2001-01-01

Theoretical and experimental studies have shown that the large desolvation penalty required for polar and charged groups frequently precludes their involvement in electrostatic interactions that contribute strongly to net stability in the folding or binding of proteins in aqueous solution near room temperature. We have previously developed a theoretical framework for computing optimized electrostatic interactions and illustrated use of the algorithm with simplified geometries. Given a receptor and model assumptions, the method computes the ligand-charge distribution that provides the most favorable balance of desolvation and interaction effects on binding. In this paper the method has been extended to treat complexes using actual molecular shapes. The barnase-barstar protein complex was investigated with barnase treated as a target receptor. The atomic point charges of barstar were varied to optimize the electrostatic binding free energy. Barnase and natural barstar form a tight complex (Kd ∼ 10−14 M) with many charged and polar groups near the interface that make this a particularly relevant system for investigating the role of electrostatic effects on binding. The results show that sets of barstar charges (resulting from optimization with different constraints) can be found that give rise to relatively large predicted improvements in electrostatic binding free energy. Principles for enhancing the effect of electrostatic interactions in molecular binding in aqueous environments are discussed in light of the optima. Our findings suggest that, in general, the enhancements in electrostatic binding free energy resulting from modification of polar and charged groups can be substantial. Moreover, a recently proposed definition of electrostatic complementarity is shown to be a useful tool for examining binding interfaces. Finally, calculational results suggest that wild-type barstar is closer to being affinity optimized than is barnase for their mutual binding, consistent with the known roles of these proteins. PMID:11266622

Stress corrosion study of PH13-8Mo stainless steel using the Slow Strain Rate Technique

NASA Technical Reports Server (NTRS)

Torres, Pablo D.

1989-01-01

The need for a fast and reliable method to study stress corrosion in metals has caused increased interest in the Slow Strain Rate Technique (SSRT) during the last few decades. PH13-8MoH950 and H1000 round tensile specimens were studied by this method. Percent reduction-in-area, time-to-failure, elongation at fracture, and fracture energy were used to express the loss in ductility, which has been used to indicate susceptibility to stress corrosion cracking (SCC). Results from a 3.5 percent salt solution (corrosive medium) were compared to those in air (inert medium). A tendency to early failure was found when testing in the vicinity of 1.0 x 10(-6) mm/mm/sec in the 3.5 percent salt solution. PH13-8Mo H1000 was found to be less likely to suffer SCC than PH13-8Mo H950. This program showed that the SSRT is promising for the SCC characterization of metals and results can be obtained in much shorter times (18 hr for PH steels) than those required using conventional techniques.

Mutation-Linked Defective Inter-Domain Interactions within Ryanodine Receptor Cause Aberrant Ca2+ Release Leading to Catecholaminergic Polymorphic Ventricular Tachycardia

PubMed Central

Suetomi, Takeshi; Yano, Masafumi; Uchinoumi, Hitoshi; Fukuda, Masakazu; Hino, Akihiro; Ono, Makoto; Xu, Xiaojuan; Tateishi, Hiroki; Okuda, Shinichi; Doi, Masahiro; Kobayashi, Shigeki; Ikeda, Yasuhiho; Yamamoto, Takeshi; Ikemoto, Noriaki; Matsuzaki, Masunori

2011-01-01

Background The molecular mechanism by which catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by single amino acid mutations within the cardiac ryanodine receptor (RyR2) remains elusive. Here, we investigated mutation-induced conformational defects of RyR2 using a knock-in (KI) mouse model expressing the human CPVT-associated RyR2 mutant (S2246L; Serine to Leucine mutation at the residue 2246). Methods and Results All KI mice we examined produced VT after exercise on a treadmill. cAMP-dependent increase in the frequency of Ca2+ sparks was more pronounced in saponin-permeabilized KI cardiomyocytes than in WT cardiomyocytes. Site-directed fluorescent labeling and quartz microbalance assays of the specific binding of DP2246 (a peptide corresponding to the 2232–2266 region: the 2246 domain) showed that DP2246 binds with the K201-binding sequence of RyR2 (1741– 2270). Introduction of S2246L mutation into the DP2246 increased the affinity of peptide binding. Fluorescence quench assays of inter-domain interactions within RyR2 showed that tight interaction of the 2246 domain/K201-binding domain is coupled with domain unzipping of the N-terminal (1-600)/central (2000–2500) domain pair in an allosteric manner. Dantrolene corrected the mutation-caused domain unzipping of the domain switch, and stopped the exercise-induced ventricular tachycardia. Conclusions The CPVT-linked mutation of RyR2, S2246L, causes an abnormally tight local sub-domain/sub-domain interaction within the central domain involving the mutation site, which induces defective interaction between the N-terminal and central domains. This results in an erroneous activation of Ca2+ channel in a diastolic state reflecting on the increased Ca2+ spark frequency, which then leads to lethal arrhythmia. PMID:21768539

Physics and performances of III-V nanowire broken-gap heterojunction TFETs using an efficient tight-binding mode-space NEGF model enabling million-atom nanowire simulations.

PubMed

Afzalian, A; Vasen, T; Ramvall, P; Shen, T-M; Wu, J; Passlack, M

2018-06-27

We report the capability to simulate in a quantum-mechanical atomistic fashion record-large nanowire devices, featuring several hundred to millions of atoms and a diameter up to 18.2 nm. We have employed a tight-binding mode-space NEGF technique demonstrating by far the fastest (up to 10 000  ×  faster) but accurate (error  <  1%) atomistic simulations to date. Such technique and capability opens new avenues to explore and understand the physics of nanoscale and mesoscopic devices dominated by quantum effects. In particular, our method addresses in an unprecedented way the technologically-relevant case of band-to-band tunneling (BTBT) in III-V nanowire broken-gap heterojunction tunnel-FETs (HTFETs). We demonstrate an accurate match of simulated BTBT currents to experimental measurements in a 12 nm diameter InAs NW and in an InAs/GaSb Esaki tunneling diode. We apply our TB MS simulations and report the first in-depth atomistic study of the scaling potential of III-V GAA nanowire HTFETs including the effect of electron-phonon scattering and discrete dopant impurity band tails, quantifying the benefits of this technology for low-power low-voltage CMOS applications.

Maximally localized Wannier functions in LaMnO3 within PBE + U, hybrid functionals and partially self-consistent GW: an efficient route to construct ab initio tight-binding parameters for eg perovskites.

PubMed

Franchini, C; Kováčik, R; Marsman, M; Murthy, S Sathyanarayana; He, J; Ederer, C; Kresse, G

2012-06-13

Using the newly developed VASP2WANNIER90 interface we have constructed maximally localized Wannier functions (MLWFs) for the e(g) states of the prototypical Jahn-Teller magnetic perovskite LaMnO(3) at different levels of approximation for the exchange-correlation kernel. These include conventional density functional theory (DFT) with and without the additional on-site Hubbard U term, hybrid DFT and partially self-consistent GW. By suitably mapping the MLWFs onto an effective e(g) tight-binding (TB) Hamiltonian we have computed a complete set of TB parameters which should serve as guidance for more elaborate treatments of correlation effects in effective Hamiltonian-based approaches. The method-dependent changes of the calculated TB parameters and their interplay with the electron-electron (el-el) interaction term are discussed and interpreted. We discuss two alternative model parameterizations: one in which the effects of the el-el interaction are implicitly incorporated in the otherwise 'noninteracting' TB parameters and a second where we include an explicit mean-field el-el interaction term in the TB Hamiltonian. Both models yield a set of tabulated TB parameters which provide the band dispersion in excellent agreement with the underlying ab initio and MLWF bands.

Physics and performances of III–V nanowire broken-gap heterojunction TFETs using an efficient tight-binding mode-space NEGF model enabling million-atom nanowire simulations

NASA Astrophysics Data System (ADS)

Afzalian, A.; Vasen, T.; Ramvall, P.; Shen, T.-M.; Wu, J.; Passlack, M.

2018-06-01

We report the capability to simulate in a quantum-mechanical atomistic fashion record-large nanowire devices, featuring several hundred to millions of atoms and a diameter up to 18.2 nm. We have employed a tight-binding mode-space NEGF technique demonstrating by far the fastest (up to 10 000  ×  faster) but accurate (error  <  1%) atomistic simulations to date. Such technique and capability opens new avenues to explore and understand the physics of nanoscale and mesoscopic devices dominated by quantum effects. In particular, our method addresses in an unprecedented way the technologically-relevant case of band-to-band tunneling (BTBT) in III–V nanowire broken-gap heterojunction tunnel-FETs (HTFETs). We demonstrate an accurate match of simulated BTBT currents to experimental measurements in a 12 nm diameter InAs NW and in an InAs/GaSb Esaki tunneling diode. We apply our TB MS simulations and report the first in-depth atomistic study of the scaling potential of III–V GAA nanowire HTFETs including the effect of electron–phonon scattering and discrete dopant impurity band tails, quantifying the benefits of this technology for low-power low-voltage CMOS applications.

Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis.

PubMed

Darido, Charbel; Georgy, Smitha R; Wilanowski, Tomasz; Dworkin, Sebastian; Auden, Alana; Zhao, Quan; Rank, Gerhard; Srivastava, Seema; Finlay, Moira J; Papenfuss, Anthony T; Pandolfi, Pier Paolo; Pearson, Richard B; Jane, Stephen M

2011-11-15

Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC. 2011 Elsevier Inc. All rights reserved.

Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Charles, E-mail: Charles_Lin@health.qld.gov.au; Tripcony, Lee; Keller, Jacqui

2012-01-01

Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis.more » Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.« less

Analysis of Dermatologic Events in Vemurafenib-Treated Patients With Melanoma

PubMed Central

Duvic, Madeleine; Hauschild, Axel; Prieto, Victor G.; Robert, Caroline; Schadendorf, Dirk; Kim, Caroline C.; McCormack, Christopher J.; Myskowski, Patricia L.; Spleiss, Olivia; Trunzer, Kerstin; Su, Fei; Nelson, Betty; Nolop, Keith B.; Grippo, Joseph F.; Lee, Richard J.; Klimek, Matthew J.; Troy, James L.; Joe, Andrew K.

2013-01-01

Background. Vemurafenib has been approved for the treatment of patients with advanced BRAFV600E-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC). Methods. Dermatologic AEs were assessed from three ongoing trials of BRAFV600E mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions. Results. A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%–95% of patients. Rash was the most common AE (64%–75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%–63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%–10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%–26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy without dose reduction after resection. Genetic analysis of 29 cuSCC/KA samples demonstrated HRAS mutations in 41%. Conclusions. Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in <10% of patients. PMID:23457002

Use of dairy herd improvement somatic cell information by Ohio dairy producers and their perceptions of mastitis.

PubMed

Miller, G Y; Eastridge, M L; Hueston, W D; Hoblet, K H

1988-08-01

A telephone survey was conducted of 149 current recipients of the Ohio DHIA SCC option, 30 past recipients of the SCC option, and 30 producers who had never received the SCC option. Producers were questioned to ascertain their knowledge of mastitis, how they used SCC information, their treatment and prevention of mastitis, and their use of veterinary services. Producers' perceptions of mastitis indicated a high awareness of the consequences of mastitis. However, 10% of producers on DHI still did not practice postmilking teat dipping, and 16% did not handle mastitic cows any differently during milking. Current recipients of SCC data used the data more frequently than did past recipients of the SCC data to evaluate mastitis treatment or control, choose cows to cull, identify cows to dry off early, indicate herd infection, and evaluate mastitis control. The major reason given by nonrecipients for never having enrolled in the SCC program was that they did not perceive a need for it. Further educational programs explaining SCC and its use to producers seems warranted.

Dynamics and Molecular Determinants of Cytoplasmic Lipid Droplet Clustering and Dispersion

PubMed Central

Stefanski, Adrianne L.; McManaman, James L.

2013-01-01

Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps. PMID:23825572

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation.

PubMed

Shin, Jung-Min; Chang, In-Kyu; Lee, Young-Ho; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Lee, Young

2016-04-01

S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. This study aims to investigate the relationship between S100A8 and cutaneous SCC development. We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin.

Nonlinear ultrasonic assessment of stress corrosion cracking damage in sensitized 304 stainless steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morlock, Florian, E-mail: fmorlock3@gatech.edu; Jacobs, Laurence J., E-mail: fmorlock3@gatech.edu; Kim, Jin-Yeon, E-mail: fmorlock3@gatech.edu

2015-03-31

This research uses nonlinear Rayleigh surface waves to characterize stress corrosion cracking (SCC) damage in welded 304 Stainless Steel (304 SS). 304 SS is widely used in reactor pressure vessels, where a corrosive environment in combination with applied stress due to high internal pressures can cause SCC. Welds and the nearby heat affected zones (HAZ) in the vessel material are especially sensitive to SCC damage. SCC damage results in microstructural changes such as dislocation formation and microcrack initiation that in the long term lead to reduced structural integrity and material failure. Therefore, the early detection of SCC is crucial tomore » ensure safe operation. It has been shown that the microstructural changes caused by SCC can generate higher harmonic waves when excited harmonically. This research considers different levels of SCC damage induced in samples of welded 304 SS by applying stress to a specimen held in a corrosive medium (Sodium Thiosulfate). A nonlinear Rayleigh surface wave is introduced in the material and the fundamental and the second harmonic waves are measured using wedge detection. The nonlinearity parameter that relates the fundamental and the second harmonic amplitudes, is computed to quantify the SCC damage in each sample. These results are used to demonstrate the feasibility of using nonlinear Rayleigh waves to characterize SCC damage.« less

CD10-bearing fibroblast inhibits matrigel invasive potency of interleukin-1α-producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment.

PubMed

Xie, Lining; Moroi, Yoichi; Tsuji, Gaku; Liu, Min; Hayashida, Sayaka; Takahara, Masakazu; Fukagawa, Shuji; Takeuchi, Satoshi; Shan, Baoen; Nakahara, Takeshi; Uchi, Hiroshi; Yokomizo, Takehiko; Furue, Masutaka

2010-12-01

CD10 is a neutral endopeptidase, which cleaves various peptide substrates including substance P. CD10 expression has been detected in peritumoral fibroblasts (Fb) within the invasive area of various cancers such as squamous cell carcinoma (SCC). However, the biological significance of CD10-bearing Fb remains largely unknown. We examined dynamic interactions of Fb with tumorigenic A431 SCC cells or non-tumorigenic HaCaT squamous cells. The SCC and HaCaT cells did not synthesize CD10, while Fb constitutively expressed CD10. When co-cultured, SCC markedly upregulated fibroblastic CD10 expression compared with HaCaT, which was mainly attributable to SCC-derived interleukin-1α (IL-1α). Both SCC and Fb autonomously secreted substance P, which eventually enhanced the invasive capacity of SCC in a matrigel invasion assay by upregulating matrix metalloproteinase (MMP)-1 and MMP-2, but not MMP-9. Transfection of siRNA for CD10 successfully knocked down the CD10 expression in Fb (CD10ND-Fb). In the presence of CD10ND-Fb, substance P levels in supernatants as well as MMP production and the invasive potency of SCC were significantly augmented compared with control scramble RNA-transfected Fb. We also transfected CD10 vector to Fb and found that the matrigel invasive ability of SCC cells was downregulated co-cultured with CD10 vector-transfected Fb rather than empty vector-transfected Fb. In conclusion, the CD10-bearing Fb generated by SCC-derived IL-1 inhibited the invasive capacity of SCC by diminishing the microenvironmental concentration of substance P. © 2010 Japanese Cancer Association.

Contribution of Beta-HPV Infection and UV-Damage to Rapid-onset Cutaneous Squamous Cell Carcinoma during BRAF-inhibition Therapy

PubMed Central

Cohen, Daniel N.; Lawson, Steven K.; Shaver, Aaron C.; Du, Liping; Nguyen, Harrison P.; He, Qin; Johnson, Douglas B.; Lumbang, Wilfred A.; Moody, Brent R.; Prescott, James L.; Chandra, Pranil K.; Boyd, Alan S.; Zwerner, Jeffrey P.; Robbins, Jason B.; Tyring, Stephen K.; Rady, Peter L.; Chappell, James D.; Shyr, Yu; Infante, Jeffrey R.; Sosman, Jeffrey A.

2015-01-01

Purpose BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. Ultraviolet (UV) radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib (Vem) or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During Vem therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional-cSCC when controlled for gender and UV-exposure (p-value=0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK and EGFR mutations also detected. Conclusions We examined clinical, histopathologic, viral and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. PMID:25724524

Varied clinical presentations of seven patients with mutations in CYP11A1 encoding the cholesterol side-chain cleavage enzyme, P450scc.

PubMed

Tee, Meng Kian; Abramsohn, Michal; Loewenthal, Neta; Harris, Mark; Siwach, Sudeep; Kaplinsky, Ana; Markus, Barak; Birk, Ohad; Sheffield, Val C; Parvari, Ruti; Pavari, Ruti; Hershkovitz, Eli; Miller, Walter L

2013-02-01

The cholesterol side-chain cleavage enzyme P450scc, encoded by CYP11A1, converts cholesterol to pregnenolone to initiate steroidogenesis. P450scc deficiency can disrupt adrenal and gonadal steroidogenesis, resembling congenital lipoid adrenal hyperplasia clinically and hormonally; only 12 such patients have been reported previously. We sought to expand clinical and genetic experience with P450scc deficiency. We sequenced candidate genes in 7 children with adrenal insufficiency who lacked disordered sexual development. P450scc missense mutations were recreated in the F2 vector, which expresses the fusion protein P450scc-Ferredoxin Reductase-Ferredoxin. COS-1 cells were transfected, production of pregnenolone was assayed, and apparent kinetic parameters were calculated. Previously described P450scc mutants were assayed in parallel. Four of five Bedouin children in one kindred were compound heterozygotes for mutations c.694C>T (Arg232Stop) and c.644T>C (Phe215Ser). Single-nucleotide polymorphism analysis confirmed segregation of these mutations. The fifth kindred member and another Bedouin patient presented in infancy and were homozygous for Arg232Stop. A patient from Fiji presenting in infancy was homozygous for c.358T>C (Arg120Stop). All mutations are novel. As assayed in the F2 fusion protein, P450scc Phe215Ser retained 2.5% of wild-type activity; previously described mutants Leu141Trp and Ala269Val had 2.6% and 12% of wild-type activity, respectively, and Val415Glu and c.835delA lacked detectable activity. Although P450scc is required to produce placental progesterone required to maintain pregnancy, severe mutations in P450scc are compatible with term gestation; milder P450scc mutations may present later without disordered sexual development. Enlarged adrenals usually distinguish steroidogenic acute regulatory protein deficiency from P450scc deficiency, but only DNA sequencing is definitive.

Distribution of non-aureus staphylococci species in udder quarters with low and high somatic cell count, and clinical mastitis.

PubMed

Condas, Larissa A Z; De Buck, Jeroen; Nobrega, Diego B; Carson, Domonique A; Roy, Jean-Philippe; Keefe, Greg P; DeVries, Trevor J; Middleton, John R; Dufour, Simon; Barkema, Herman W

2017-07-01

The effect of non-aureus staphylococci (NAS) in bovine mammary health is controversial. Overall, NAS intramammary infections (IMI) increase somatic cell count (SCC), with an effect categorized as mild, mostly causing subclinical or mild to moderate clinical mastitis. However, based on recent studies, specific NAS may affect the udder more severely. Some of these apparent discrepancies could be attributed to the large number of species that compose the NAS group. The objectives of this study were to determine (1) the SCC of quarters infected by individual NAS species compared with NAS as a group, culture-negative, and major pathogen-infected quarters; (2) the distribution of NAS species isolated from quarters with low SCC (<200,000 cells/mL) and high SCC (≥200,000 cells/mL), and clinical mastitis; and (3) the prevalence of NAS species across quarters with low and high SCC. A total of 5,507 NAS isolates, 3,561 from low SCC quarters, 1,873 from high SCC quarters, and 73 from clinical mastitis cases, were obtained from the National Cohort of Dairy Farms of the Canadian Bovine Mastitis Research Network. Of quarters with low SCC, high SCC, or clinical mastitis, 7.6, 18.5, and 4.3% were NAS positive, respectively. The effect of NAS IMI on SCC was estimated using mixed-effect linear regression; prevalence of NAS IMI was estimated using Bayesian analyses. Mean SCC of NAS-positive quarters was 70,000 cells/mL, which was higher than culture-negative quarters (32,000 cells/mL) and lower than major pathogen-positive quarters (129,000 to 183,000 cells/mL). Compared with other NAS species, SCC was highest in quarters positive for Staphylococcus capitis, Staphylococcus gallinarum, Staphylococcus hyicus, Staphylococcus agnetis, or Staphylococcus simulans. In NAS-positive quarters, Staphylococcus xylosus (12.6%), Staphylococcus cohnii (3.1%), and Staphylococcus equorum (0.6%) were more frequently isolated from quarters with low SCC than other NAS species, whereas Staphylococcus sciuri (14%) was most frequently isolated from clinical mastitis cases. Finally, in NAS-positive quarters, Staphylococcus chromogenes, S. simulans, Staphylococcus epidermidis, and Staphylococcus haemolyticus were isolated with similar frequency from among low SCC and high SCC quarters and clinical mastitis cases. Staphylococcus chromogenes, S. simulans, S. xylosus, S. haemolyticus, S. epidermidis, S. agnetis, Staphylococcus arlettae, S. capitis, S. gallinarum, S. sciuri, and Staphylococcus warneri were more prevalent in high than in low SCC quarters. Because the NAS are a large, heterogeneous group, considering them as a single group rather than at the species, or even subspecies level, has undoubtedly contributed to apparent discrepancies among studies as to their distribution and importance in IMI and mastitis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of retinoids on differentiation, lipid metabolism, epidermal growth factor, and low-density lipoprotein binding in squamous carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ponec, M.; Weerheim, A.; Havekes, L.

The relationship among keratinocyte differentiation capacity, lipid synthesis, low-density lipoprotein (LDL) metabolism, plasma membrane composition, and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells. The differentiation capacity of the cells, i.e., ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e., retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethylsulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis resulting in changes in the plasma membrane composition. Hydrocortisonemore » stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect. These results clearly demonstrate that the plasma membrane composition is not related to keratinocyte differentiation capacity, but most likely does determine EGF binding. Furthermore, EGF binding does not determine keratinocyte differentiation capacity.« less

Coupling the Torpedo microplate-receptor binding assay with mass spectrometry to detect cyclic imine neurotoxins.

PubMed

Aráoz, Rómulo; Ramos, Suzanne; Pelissier, Franck; Guérineau, Vincent; Benoit, Evelyne; Vilariño, Natalia; Botana, Luis M; Zakarian, Armen; Molgó, Jordi

2012-12-04

Cyclic imine neurotoxins constitute an emergent family of neurotoxins of dinoflagellate origin that are potent antagonists of nicotinic acetylcholine receptors. We developed a target-directed functional method based on the mechanism of action of competitive agonists/antagonists of nicotinic acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The key step for method development was the immobilization of Torpedo electrocyte membranes rich in nicotinic acetylcholine receptors on the surface of microplate wells and the use of biotinylated-α-bungarotoxin as tracer. Cyclic imine neurotoxins competitively inhibit biotinylated-α-bungarotoxin binding to Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner. The microplate-receptor binding assay allowed rapid detection of nanomolar concentrations of cyclic imine neurotoxins directly in shellfish samples. Although highly sensitive and specific for the detection of neurotoxins targeting nicotinic acetylcholine receptors as a class, the receptor binding assay cannot identify a given analyte. To address the low selectivity of the microplate-receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of the eluted ligands was identified by mass spectrometry. The immobilization of Torpedo electrocyte membranes on the surface of microplate wells proved to be a high-throughput format for the survey of neurotoxins targeting nicotinic acetylcholine receptors directly in shellfish matrixes with high sensitivity and reproducibility.

Coupling the Torpedo Microplate-Receptor Binding Assay with Mass Spectrometry to Detect Cyclic Imine Neurotoxins

PubMed Central

Aráoz, Rómulo; Ramos, Suzanne; Pelissier, Franck; Guérineau, Vincent; Benoit, Evelyne; Vilariño, Natalia; Botana, Luis M.; Zakarian, Armen; Molgó, Jordi

2014-01-01

Cyclic imine neurotoxins constitute an emergent family of neurotoxins of dinoflagellate origin that are potent antagonists of nicotinic acetylcholine receptors. We developed a target-directed functional method based on the mechanism of action of competitive agonists/antagonists of nicotinic acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The key step for method development was the immobilization of Torpedo electrocyte membranes rich in nicotinic acetylcholine receptors on the surface of microplate wells and the use of biotinylated-α-bungarotoxin as tracer. Cyclic imine neurotoxins competitively inhibit biotinylated-α-bungarotoxin binding to Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner. The microplate-receptor binding assay allowed rapid detection of nanomolar concentrations of cyclic imine neurotoxins directly in shellfish samples. Although highly sensitive and specific for the detection of neurotoxins targeting nicotinic acetylcholine receptors as a class, the receptor binding assay cannot identify a given analyte. To address the low selectivity of the microplate-receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of the eluted ligands was identified by mass spectrometry. The immobilization of Torpedo electrocyte membranes on the surface of microplate wells proved to be a high-throughput format for the survey of neurotoxins targeting nicotinic acetylcholine receptors directly in shellfish matrixes with high sensitivity and reproducibility. PMID:23131021

Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

PubMed

He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

2012-07-01

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

Genome-scale cluster analysis of replicated microarrays using shrinkage correlation coefficient.

PubMed

Yao, Jianchao; Chang, Chunqi; Salmi, Mari L; Hung, Yeung Sam; Loraine, Ann; Roux, Stanley J

2008-06-18

Currently, clustering with some form of correlation coefficient as the gene similarity metric has become a popular method for profiling genomic data. The Pearson correlation coefficient and the standard deviation (SD)-weighted correlation coefficient are the two most widely-used correlations as the similarity metrics in clustering microarray data. However, these two correlations are not optimal for analyzing replicated microarray data generated by most laboratories. An effective correlation coefficient is needed to provide statistically sufficient analysis of replicated microarray data. In this study, we describe a novel correlation coefficient, shrinkage correlation coefficient (SCC), that fully exploits the similarity between the replicated microarray experimental samples. The methodology considers both the number of replicates and the variance within each experimental group in clustering expression data, and provides a robust statistical estimation of the error of replicated microarray data. The value of SCC is revealed by its comparison with two other correlation coefficients that are currently the most widely-used (Pearson correlation coefficient and SD-weighted correlation coefficient) using statistical measures on both synthetic expression data as well as real gene expression data from Saccharomyces cerevisiae. Two leading clustering methods, hierarchical and k-means clustering were applied for the comparison. The comparison indicated that using SCC achieves better clustering performance. Applying SCC-based hierarchical clustering to the replicated microarray data obtained from germinating spores of the fern Ceratopteris richardii, we discovered two clusters of genes with shared expression patterns during spore germination. Functional analysis suggested that some of the genetic mechanisms that control germination in such diverse plant lineages as mosses and angiosperms are also conserved among ferns. This study shows that SCC is an alternative to the Pearson correlation coefficient and the SD-weighted correlation coefficient, and is particularly useful for clustering replicated microarray data. This computational approach should be generally useful for proteomic data or other high-throughput analysis methodology.

A combined representation method for use in band structure calculations. 1: Method

NASA Technical Reports Server (NTRS)

Friedli, C.; Ashcroft, N. W.

1975-01-01

A representation was described whose basis levels combine the important physical aspects of a finite set of plane waves with those of a set of Bloch tight-binding levels. The chosen combination has a particularly simple dependence on the wave vector within the Brillouin Zone, and its use in reducing the standard one-electron band structure problem to the usual secular equation has the advantage that the lattice sums involved in the calculation of the matrix elements are actually independent of the wave vector. For systems with complicated crystal structures, for which the Korringa-Kohn-Rostoker (KKR), Augmented-Plane Wave (APW) and Orthogonalized-Plane Wave (OPW) methods are difficult to apply, the present method leads to results with satisfactory accuracy and convergence.

Prothymosin-α and parathymosin expression predicts poor prognosis in squamous and adenosquamous carcinomas of the gallbladder

PubMed Central

Chen, Kang; Xiong, Li; Yang, Zhuling; Huang, Shengfu; Zeng, Rong; Miao, Xiongying

2018-01-01

The present study aimed to investigate the expression patterns of prothymosin-α (PTMA) and parathymosin (PTMS) in patients with squamous cell carcinoma (SCC), adenosquamous cell carcinoma (ASC) and adenocarcinoma (AC) of the gallbladder, and to assess their association with the clinicopathological characteristics and prognosis of the patients. A retrospective analysis of data pertaining to patients with SCC/ASC (n=46) and AC (n=80) of the gallbladder, who were treated with surgical resection, was conducted. Kaplan-Meier survival analysis was also performed to assess the correlation of the expression pattern with survival. The results revealed a higher percentage of patients with a large tumor diameter (>3 cm) in the SCC/ASC group as compared with those in the AC group (P<0.05). No significant differences were observed between patients with SCC/ASC and those with AC with respect to the patient sex, presence of gallstones, TNM stage, lymph node metastasis, invasive growth into anatomically contiguous structures, surgical methods used, survival rate, and the expression levels of PTMA and PTMA (P>0.05). However, positive expression of PTMA and PTMA was associated with tumor size, TNM stage, lymph node metastasis, locally invasive growth, and treatment with radical resection in patients with SCC/ASC and AC (P<0.05). In addition, positive expression of PTMA and PTMA was observed in a significantly lower number of patients with advanced AC as compared with those in early AC (P<0.05), while these expression levels were also associated with shorter survival in the SCC/ASC group and AC group (P<0.05). Cox multivariate analysis also demonstrated a negative correlation between PTMA and PTMA levels, and the postoperative survival rate in the two groups. In conclusion, the present study indicated that the expression levels of PTMA and PTMA were closely associated with the tumorigenesis and progression of SCC, ASC and AC of the gallbladder. Positive expression of PTMA and PTMA may serve as a valuable prognostic factor in these patients. PMID:29541218

Burden of Invasive Squamous Cell Carcinoma of the Penis in the United States, 1998–2003

PubMed Central

Hernandez, Brenda Y.; Barnholtz-Sloan, Jill; German, Robert R.; Giuliano, Anna; Goodman, Marc T.; King, Jessica B.; Negoita, Serban; Villalon-Gomez, Jose M.

2009-01-01

BACKGROUND Invasive squamous cell carcinoma (SCC) of the penis is rare in the United States. Although human papillomavirus (HPV) infection is an established etiologic agent in at least 40% of penile SCCs, relatively little is known about the epidemiology of this malignancy. METHODS Population-based data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, the Centers for Disease Control and Prevention's National Program for Cancer Registries, and the National Center for Health Statistics were used to examine invasive penile SCC incidence and mortality in the United States. SEER data were used to examine treatment of penile SCC. RESULTS From 1998 to 2003, 4967 men were diagnosed with histologically confirmed invasive penile SCC in the United States, representing less than 1% of new cancers in men. The annual, average age-adjusted incidence rate was 0.81 cases per 100,000 men, and rates increased steadily with age. Overall, penile SCC incidence was comparable in whites and blacks, but approximately 2-fold lower in Asians/Pacific Islanders. Rates among Hispanics were 72% higher compared with non-Hispanics. Blacks compared with whites and Asians/Pacific Islanders and Hispanics compared with non-Hispanics were diagnosed at significantly younger ages. Higher rates of mortality were also observed among blacks compared with whites and Hispanics compared with non-Hispanics. Penile SCC incidence and mortality were elevated in Southern states and in regions of low socioeconomic status (SES). Some histologic and anatomic site differences were observed by race and ethnicity. Treatment of penile SCC varied with age, stage, and other tumor characteristics. CONCLUSIONS There are considerable disparities in invasive penile cancer incidence and mortality in the United States. Key risk factors for excess incidence include Hispanic ethnicity and residence in the South and in low SES regions. Risks for excess mortality include these factors in addition to black race. Decreases in penile cancer incidence and mortality in the United States may be realized in the future as the indirect result of prophylactic HPV vaccination of females. Further research is needed to better understand the epidemiology of penile cancer including the role of HPV. PMID:18980292

Milk amyloid A as a biomarker for diagnosis of subclinical mastitis in cattle

PubMed Central

Hussein, Hany Ahmed; El-Razik, Khaled Abd El-Hamid Abd; Gomaa, Alaa Mohamed; Elbayoumy, Mohamed Karam; Abdelrahman, Khaled A.; Hosein, H. I.

2018-01-01

Background and Aim: Mastitis is one of the most vital noteworthy monetary risks to dairy ranchers and affects reproductive performance in dairy cattle. However, subclinical mastitis (SCM) negatively affects milk quality and quantity and associated with economic losses as clinical mastitis. It is recognizable only by additional testing. Somatic cell count (SCC) is currently used worldwide for the screening of intramammary infection (IMI) infections. However, somatic cells (SC) are affected by numerous factors and not always correlate with infection of the udder. Therefore, the aim of the present study was to evaluate the milk amyloid A (MAA) in the milk of normal and SCM cows and compare the sensitivity of both MAA secretion and SCC in response to mammary gland bacterial infection. Materials and Methods: A total of 272 quarter milk samples collected from 68 Friesian cows after clinical examination for detection of clinical mastitis were employed in this study. All quarter milk samples (272) were subjected to bacteriological examination, while SCs were assessed in samples (220). Following SCC estimation and bacteriological examination, the apparently normal quarter milk samples were categorized into 7 groups and MAA concentration was estimated in normal and subclinical mastitic milk samples. Results: Prevalence of clinical mastitis was 19.12 % (52 quarters), while 80.88 % (220 quarters) were clinically healthy with normal milk secretion. Of those 220 clinically healthy quarter milk samples, 72 (32.73%) showed SCM as detected by SCC (SCC ≥500,000 cells/ml). The most prevalent bacteria detected in this study were streptococci (48.53%), Staphylococcus aureus (29.41%), Escherichia coli (36.76%), and coagulase-negative staphylococci (11.76%). Results of MAA estimation revealed a strong correlation between MAA secretion level and SCC in agreement with the bacteriological examination. Interestingly, there was a prompt increase in MAA concentration in Group III (G III) (group of milk samples had SCC ≤200,000 cells/ml and bacteriologically positive) than Group I (G I) (group of milk samples with SCC ≤500,000 cells/ml and bacteriologically negative), as MAA concentration in G III was about 4 times its concentration in G I. Conclusion: Our study provides a strong evidence for the significance of MAA measurement in milk during SCM, and MAA is more sensitive to IMI than SCC. This can be attributed to rapid and sensitive marker of inflammation. The advantage of MAA over other diagnostic markers of SCM is attributed the minute or even undetectable level of MAA in the milk of healthy animals, it is not influenced by factors other than mastitis, and could be estimated in preserved samples. Therefore, we recommend that estimation of MAA concentration in milk is a more useful diagnostic tool than SCC to detect SCM and to monitor the udder health in dairy cattle. PMID:29479155

Interface Schottky barrier engineering via strain in metal-semiconductor composites

NASA Astrophysics Data System (ADS)

Ma, Xiangchao; Dai, Ying; Yu, Lin; Huang, Baibiao

2016-01-01

The interfacial carrier transfer property, which is dominated by the interface Schottky barrier height (SBH), plays a crucial role in determining the performance of metal-semiconductor heterostructures in a variety of applications. Therefore, artificially controlling the interface SBH is of great importance for their industrial applications. As a model system, the Au/TiO2 (001) heterostructure is studied using first-principles calculations and the tight-binding method in the present study. Our investigation demonstrates that strain can be an effective way to decrease the interface SBH and that the n-type SBH can be more effectively decreased than the p-type SBH. Astonishingly, strain affects the interface SBH mainly by changing the intrinsic properties of Au and TiO2, whereas the interfacial potential alignment is almost independent of strain due to two opposite effects, which are induced by strain at the interfacial region. These observed trends can be understood on the basis of the general free-electron gas model of typical metals, the tight-binding theory and the crystal-field theory, which suggest that similar trends may be generalized for many other metal-semiconductor heterostructures. Given the commonness and tunability of strain in typical heterostructures, we anticipate that the tunability of the interface SBH with strain described here can provide an alternative effective way for realizing more efficient applications of relevant heterostructures.The interfacial carrier transfer property, which is dominated by the interface Schottky barrier height (SBH), plays a crucial role in determining the performance of metal-semiconductor heterostructures in a variety of applications. Therefore, artificially controlling the interface SBH is of great importance for their industrial applications. As a model system, the Au/TiO2 (001) heterostructure is studied using first-principles calculations and the tight-binding method in the present study. Our investigation demonstrates that strain can be an effective way to decrease the interface SBH and that the n-type SBH can be more effectively decreased than the p-type SBH. Astonishingly, strain affects the interface SBH mainly by changing the intrinsic properties of Au and TiO2, whereas the interfacial potential alignment is almost independent of strain due to two opposite effects, which are induced by strain at the interfacial region. These observed trends can be understood on the basis of the general free-electron gas model of typical metals, the tight-binding theory and the crystal-field theory, which suggest that similar trends may be generalized for many other metal-semiconductor heterostructures. Given the commonness and tunability of strain in typical heterostructures, we anticipate that the tunability of the interface SBH with strain described here can provide an alternative effective way for realizing more efficient applications of relevant heterostructures. Electronic supplementary information (ESI) available: The changes of Au 5d DOS, valence bands of TiO2, the interfacial bond length and interfacial energy with strain, and the local DOS results for the change of SBH with strain. See DOI: 10.1039/c5nr05583k

Oxidation of Са2+-Binding Domain of NADPH Oxidase 5 (NOX5): Toward Understanding the Mechanism of Inactivation of NOX5 by ROS.

PubMed

Petrushanko, Irina Yu; Lobachev, Vladimir M; Kononikhin, Alexey S; Makarov, Alexander A; Devred, Francois; Kovacic, Hervé; Kubatiev, Aslan A; Tsvetkov, Philipp O

2016-01-01

NOX5 protein, one of the most active generators of reactive oxygen species (ROS), plays an important role in many processes, including regulation of cell growth, death and differentiation. Because of its central role in ROS generation, it needs to be tightly regulated to guarantee cellular homeostasis. Contrary to other members of NADPH-oxidases family, NOX5 has its own regulatory calcium-binding domain and thus could be activated directly by calcium ions. While several mechanisms of activation have been described, very little is known about the mechanisms that could prevent the overproduction of ROS by NOX5. In the present study using calorimetric methods and circular dichroism we found that oxidation of cysteine and methionine residues of NOX5 decreases binding of Ca2+ ions and perturbs both secondary and tertiary structure of protein. Our data strongly suggest that oxidation of calcium-binding domain of NOX5 could be implicated in its inactivation, serving as a possible defense mechanism against oxidative stress.

Vacancy Mediated Mechanism of Nitrogen Substitution in Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Menon, Madhu; Sadanadan, Bindu; Rao, Apparao M.

2003-01-01

Nitrogen substitution reaction in a graphene sheet and carbon nanotubes of different diameter are investigated using the generalized tight-binding molecular dynamics method. The formation of a vacancy in curved graphene sheet or a carbon nanotube is found to cause a curvature dependent local reconstruction of the surface. Our simulations and analysis show that vacancy mediated N substitution (rather than N chemisorption) is favored on the surface of nanotubes with diameter larger than 8 nm. This predicted value of the critical minimum diameter for N incorporation is confirmed by experimental results presented.

Atomic Structure and Properties of Extended Defects in Silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buczko, R.; Chisholm, M.F.; Kaplan, T.

1998-10-15

The Z-contrast technique represents a new approach to high-resolution electron microscopy allowing for the first time incoherent imaging of materials on the atomic scale. The key advantages of the technique, an intrinsically higher resolution limit and directly interpretable, compositionally sensitive imaging, allow a new level of insight into the atomic configurations of extended defects in silicon. This experimental technique has been combined with theoretical calculations (a combination of first principles, tight binding, and classical methods) to extend this level of insight by obtaining the energetic and electronic structure of the defects.

Polarizable atomistic calculation of site energy disorder in amorphous Alq3.

PubMed

Nagata, Yuki

2010-02-01

A polarizable molecular dynamics simulation and calculation scheme for site energy disorder is presented in amorphous tris(8-hydroxyquinolinato)aluminum (Alq(3)) by means of the charge response kernel (CRK) method. The CRK fit to the electrostatic potential and the tight-binding approximation are introduced, which enables modeling of the polarizable electrostatic interaction for a large molecule systematically from an ab initio calculation. The site energy disorder for electron and hole transfers is calculated in amorphous Alq(3) and the effect of the polarization on the site energy disorder is discussed.

Investigation of the effect of scattering centers on low dimensional nanowire channel

NASA Astrophysics Data System (ADS)

Cariappa, K. S.; Shukla, Raja; Sarkar, Niladri

2018-05-01

In this work, we studied the effect of scattering centers on the electron density profiles of a one dimensional Nanowire channel. Density Matrix Formalism is used for calculating the local electron densities at room temperature. Various scattering centers have been simulated in the channel. The nearest neighbor tight binding method is applied to construct the Hamiltonian of nanoscale devices. We invoke scattering centers by adding local scattering potentials to the Hamiltonian. This analysis could give an insight into the understanding and utilization of defects for device engineering.

Structure and Ligand Binding Properties of the Epoxidase Component of Styrene Monooxygenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ukaegbu, Uchechi E.; Kantz, Auric; Beaton, Michelle

2010-07-23

Styrene monooxygenase (SMO) is a two-component flavoprotein monooxygenase that transforms styrene to styrene oxide in the first step of the styrene catabolic and detoxification pathway of Pseudomonas putida S12. The crystal structure of the N-terminally histidine-tagged epoxidase component of this system, NSMOA, determined to 2.3 {angstrom} resolution, indicates the enzyme exists as a homodimer in which each monomer forms two distinct domains. The overall architecture is most similar to that of p-hydroxybenzoate hydroxylase (PHBH), although there are some significant differences in secondary structure. Structural comparisons suggest that a large cavity open to the surface forms the FAD binding site. Atmore » the base of this pocket is another cavity that likely represents the styrene binding site. Flavin binding and redox equilibria are tightly coupled such that reduced FAD binds apo NSMOA {approx}8000 times more tightly than the oxidized coenzyme. Equilibrium fluorescence and isothermal titration calorimetry data using benzene as a substrate analogue indicate that the oxidized flavin and substrate analogue binding equilibria of NSMOA are linked such that the binding affinity of each is increased by 60-fold when the enzyme is saturated with the other. A much weaker {approx}2-fold positive cooperative interaction is observed for the linked binding equilibria of benzene and reduced FAD. The low affinity of the substrate analogue for the reduced FAD complex of NSMOA is consistent with a preferred reaction order in which flavin reduction and reaction with oxygen precede the binding of styrene, identifying the apoenzyme structure as the key catalytic resting state of NSMOA poised to bind reduced FAD and initiate the oxygen reaction.« less

Human polyomaviruses and incidence of cutaneous squamous cell carcinoma in the New Hampshire skin cancer study.

PubMed

Gossai, Anala; Waterboer, Tim; Hoen, Anne G; Farzan, Shohreh F; Nelson, Heather H; Michel, Angelika; Willhauck-Fleckenstein, Martina; Christensen, Brock C; Perry, Ann E; Pawlita, Michael; Karagas, Margaret R

2016-06-01

Squamous cell carcinoma (SCC) of the skin is a malignancy arising from epithelial keratinocytes. Experimental and epidemiologic evidence raise the possibility that human polyomaviruses (PyV) may be associated with the occurrence of SCC. To investigate whether the risk for SCC was associated with PyV infection, seropositivity to 10 PyV types was assessed following diagnosis in a population-based case-control study conducted in the United States. A total of 253 SCC cases and 460 age group and gender-matched controls were included. Antibody response against each PyV was measured using a multiplex serology-based glutathione S-transferase capture assay of recombinantly expressed VP1 capsid proteins. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using logistic regression, with adjustment for potentially confounding factors. SCC cases were seropositive for a greater number of PyVs than controls (P = 0.049). Those who were JC seropositive had increased odds of SCC when compared to those who were JC seronegative (OR = 1.37, 95% CI: 0.98-1.90), with an increasing trend in SCC risk with increasing quartiles of seroreactivity (P for trend = 0.04). There were no clear associations between SCC risk and serostatus for other PyV types. This study provides limited evidence that infection with certain PyVs may be related to the occurrence of SCC in the general population of the United States. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Boiling-Water Reactor internals aging degradation study. Phase 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luk, K.H.

1993-09-01

This report documents the results of an aging assessment study for boiling water reactor (BWR) internals. Major stressors for BWR internals are related to unsteady hydrodynamic forces generated by the primary coolant flow in the reactor vessel. Welding and cold-working, dissolved oxygen and impurities in the coolant, applied loads and exposures to fast neutron fluxes are other important stressors. Based on results of a component failure information survey, stress corrosion cracking (SCC) and fatigue are identified as the two major aging-related degradation mechanisms for BWR internals. Significant reported failures include SCC in jet-pump holddown beams, in-core neutron flux monitor drymore » tubes and core spray spargers. Fatigue failures were detected in feedwater spargers. The implementation of a plant Hydrogen Water Chemistry (HWC) program is considered as a promising method for controlling SCC problems in BWR. More operating data are needed to evaluate its effectiveness for internal components. Long-term fast neutron irradiation effects and high-cycle fatigue in a corrosive environment are uncertainty factors in the aging assessment process. BWR internals are examined by visual inspections and the method is access limited. The presence of a large water gap and an absence of ex-core neutron flux monitors may handicap the use of advanced inspection methods, such as neutron noise vibration measurements, for BWR.« less

The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB.

PubMed

Tsapara, Anna; Matter, Karl; Balda, Maria S

2006-03-01

The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional activity. Here, we identify a new binding partner of the SH3 domain that modulates ZO-1-ZONAB signaling. Expression screening of a cDNA library with a fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in Madin-Darby canine kidney cells inhibits G(1)/S phase progression. Apg-2 coimmunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain in vitro and regulates ZONAB's transcriptional activity in reporter gene assays. Our data hence support a model in which Apg-2 regulates ZONAB function by competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions as a regulator of ZO-1-ZONAB signaling in epithelial cells in response to cellular stress.

The Heat-Shock Protein Apg-2 Binds to the Tight Junction Protein ZO-1 and Regulates Transcriptional Activity of ZONAB

PubMed Central

Tsapara, Anna; Matter, Karl; Balda, Maria S.

2006-01-01

The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional activity. Here, we identify a new binding partner of the SH3 domain that modulates ZO-1–ZONAB signaling. Expression screening of a cDNA library with a fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in Madin-Darby canine kidney cells inhibits G1/S phase progression. Apg-2 coimmunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain in vitro and regulates ZONAB's transcriptional activity in reporter gene assays. Our data hence support a model in which Apg-2 regulates ZONAB function by competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions as a regulator of ZO-1–ZONAB signaling in epithelial cells in response to cellular stress. PMID:16407410

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

PubMed

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review.

PubMed

Nguyen, Kim P; Peppelman, Malou; Hoogedoorn, Lisa; Van Erp, Piet E J; Gerritsen, Marie-Jeanne P

2016-12-01

Clinical differentiation between actinic keratosis (AK), squamous cell carcinoma (SCC) in situ, and invasive SCC and its variants may be difficult. Reflectance confocal microscopy (RCM) is a non-invasive technique for in vivo skin imaging. To explicate the diagnostic and monitoring use of RCM within the spectrum of AK and SCC, and evaluate the accuracy of RCM for these diagnoses relative to histopathology. A systematic literature search was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases. The quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Twenty-five eligible studies were included. Different diagnostic RCM features have been described for AK, actinic cheilitis (AC), erythroplasia of Queyrat, Bowen disease, invasive SCC, and keratoacanthoma (KA). The overall range of sensitivity and specificity of RCM for the diagnosis of SCC, AK, SCC in situ, and KA was 79-100% and 78-100%, respectively. The current literature describes the use of RCM for diagnosing AK, AC, erythroplasia of Queyrat, Bowen disease, invasive SCC, and KA, as well as for monitoring treatments of AK, with good accuracy. Unfortunately, studies with high methodological quality are lacking. Pre-treatment of hyperkeratotic lesions and uniform definitions of RCM features are required to simplify the differentiation between AKs, SCC in situ, and SCC and its variants in clinical practice.

Quantum Mechanics/Molecular Mechanics Simulations Identify the Ring-Opening Mechanism of Creatininase.

PubMed

Jitonnom, Jitrayut; Mujika, Jon I; van der Kamp, Marc W; Mulholland, Adrian J

2017-12-05

Creatininase catalyzes the conversion of creatinine (a biosensor for kidney function) to creatine via a two-step mechanism: water addition followed by ring opening. Water addition is common to other known cyclic amidohydrolases, but the precise mechanism for ring opening is still under debate. The proton donor in this step is either His178 or a water molecule bound to one of the metal ions, and the roles of His178 and Glu122 are unclear. Here, the two possible reaction pathways have been fully examined by means of combined quantum mechanics/molecular mechanics simulations at the SCC-DFTB/CHARMM22 level of theory. The results indicate that His178 is the main catalytic residue for the whole reaction and explain its role as proton shuttle during the ring-opening step. In the first step, His178 provides electrostatic stabilization to the gem-diolate tetrahedral intermediate. In the second step, His178 abstracts the hydroxyl proton of the intermediate and delivers it to the cyclic amide nitrogen, leading to ring opening. The latter is the rate-limiting step with a free energy barrier of 18.5 kcal/mol, in agreement with the experiment. We find that Glu122 must be protonated during the enzyme reaction, so that it can form a stable hydrogen bond with its neighboring water molecule. Simulations of the E122Q mutant showed that this replacement disrupts the H-bond network formed by three conserved residues (Glu34, Ser78, and Glu122) and water, increasing the energy barrier. Our computational studies provide a comprehensive explanation for previous structural and kinetic observations, including why the H178A mutation causes a complete loss of activity but the E122Q mutation does not.

Hypothyroidism Potentially Linked to Cutaneous Squamous Cell Carcinoma: Retrospective Study at a Single Tertiary Academic Medical Center.

PubMed

Ahadiat, Omeed; Higgins, Shauna; Trodello, Cameron; Talmor, Guy; Kokot, Niels; Wysong, Ashley

2018-01-01

There are multiple known risk factors for the development of cutaneous squamous cell carcinoma (SCC). To determine whether patients with cutaneous SCC have a higher prevalence of hypothyroidism than the general US population. A retrospective review was performed for patients seen at the University of Southern California with cutaneous SCC. Chart review was performed for the presence of hypothyroidism and thyroid replacement therapy before the diagnosis of SCC for each patient. Multiple prevalence studies were gathered from the literature for comparison, reporting the prevalence of overt and subclinical hypothyroidism in the general US population and/or elderly US population. Of the 265 patients diagnosed with SCC of the skin, 61 (23%) of patients were found to have a preceding diagnosis of hypothyroidism. The prevalence of hypothyroidism among the population of SCC patients was significantly greater than the prevalence of hypothyroidism (overt and subclinical) in any general and/or elderly US population reported. Patients with SCC of skin are more likely to have a history of hypothyroidism than the general population. The authors conclude that hypothyroidism may be linked to the development of cutaneous SCC.

Quantitative frequency-domain fluorescence spectroscopy in tissues and tissue-like media

NASA Astrophysics Data System (ADS)

Cerussi, Albert Edward

1999-09-01

In the never-ending quest for improved medical technology at lower cost, modern near-infrared optical spectroscopy offers the possibility of inexpensive technology for quantitative and non-invasive diagnoses. Hemoglobin is the dominant chromophore in the 700-900 nm spectral region and as such it allows for the optical assessment of hemoglobin concentration and tissue oxygenation by absorption spectroscopy. However, there are many other important physiologically relevant compounds or physiological states that cannot be effectively sensed via optical methods because of poor optical contrast. In such cases, contrast enhancements are required. Fluorescence spectroscopy is an attractive component of optical tissue spectroscopy. Exogenous fluorophores, as well as some endogenous ones, may furnish the desperately needed sensitivity and specificity that is lacking in near-infrared optical tissue spectroscopy. The main focus of this thesis was to investigate the generation and propagation of fluorescence photons inside tissues and tissue-like media (i.e., scattering dominated media). The standard concepts of fluorescence spectroscopy have been incorporated into a diffusion-based picture that is sometimes referred to as photon migration. The novelty of this work lies in the successful quantitative recovery of fluorescence lifetimes, absolute fluorescence quantum yields, fluorophore concentrations, emission spectra, and both scattering and absorption coefficients at the emission wavelength from a tissue-like medium. All of these parameters are sensitive to the fluorophore local environment and hence are indicators of the tissue's physiological state. One application demonstrating the capabilities of frequency-domain lifetime spectroscopy in tissue-like media is a study of the binding of ethidium bromide to bovine leukocytes in fresh milk. Ethidium bromide is a fluorescent dye that is commonly used to label DNA, and hence visualize chromosomes in cells. The lifetime of ethidium bromide increases by an order of magnitude upon binding to DNA. In this thesis, I demonstrated that the fluorescence photon migration model is capable of accurately determining the somatic cell count (SCC) in a milk sample. Although meant as a demonstration of fluorescence tissue spectroscopy, this specific problem has important implications for the dairy industry's warfare against subclinical mastitis (i.e., mammary gland inflammation), since the SCC is often used as an indication of bovine infection.

Pseudo-magnetic fields of strongly-curved graphene nanobubbles

NASA Astrophysics Data System (ADS)

Liu, Li-Chi

2018-04-01

We use the π-orbital axis vector (POAV) analysis to deal with large curvature effect of graphene in the tight-binding model. To test the validities of pseudo-magnetic fields (PMFs) derived from the tight-binding model and the model with Dirac equation coupled to a curved surface, we propose two types of spatially constant-field topographies for strongly-curved graphene nanobubbles, which correspond to these two models, respectively. It is shown from the latter model that the PMF induced by any spherical graphene nanobubble is always equivalent to the magnetic field caused by one magnetic monopole charge distributed on a complete spherical surface with the same radius. Such a PMF might be attributed to the isometry breaking of a graphene layer attached conformably to a spherical substrate with adhesion.

Energy-efficient constellations design and fast decoding for space-collaborative MIMO visible light communications

NASA Astrophysics Data System (ADS)

Zhu, Yi-Jun; Liang, Wang-Feng; Wang, Chao; Wang, Wen-Ya

2017-01-01

In this paper, space-collaborative constellations (SCCs) for indoor multiple-input multiple-output (MIMO) visible light communication (VLC) systems are considered. Compared with traditional VLC MIMO techniques, such as repetition coding (RC), spatial modulation (SM) and spatial multiplexing (SMP), SCC achieves the minimum average optical power for a fixed minimum Euclidean distance. We have presented a unified SCC structure for 2×2 MIMO VLC systems and extended it to larger MIMO VLC systems with more transceivers. Specifically for 2×2 MIMO VLC, a fast decoding algorithm is developed with decoding complexity almost linear in terms of the square root of the cardinality of SCC, and the expressions of symbol error rate of SCC are presented. In addition, bit mappings similar to Gray mapping are proposed for SCC. Computer simulations are performed to verify the fast decoding algorithm and the performance of SCC, and the results demonstrate that the performance of SCC is better than those of RC, SM and SMP for indoor channels in general.

Surface buffing and its effect on chloride induced SCC of 304L austenitic stainless steel

NASA Astrophysics Data System (ADS)

kumar, Pandu Sunil; Ghosh Acharyya, Swati; Ramana Rao, S. V.; Kapoor, Komal

2018-02-01

The study focuses on the impact of buffing operation on the stress corrosion cracking (SCC) susceptibility of 304L austenitic stainless steel (SS). The SCC susceptibility of the buffed surfaces were determined by testing in boiling magnesium chloride (MgCl2) environment as per ASTM G 36. Test was conducted for 3hr, 9hr and 72hr to study the SCC susceptibility. Buffed surfaces were resistant to SCC even after 72hr of exposure to boiling MgCl2. The surface and cross section of the samples were examined for both before and after exposure to boiling MgCl2 and was characterized using optical microscopy. The study revealed that buffing operation induces compressive residual stresses on the surface, which helps in protecting the surface from SCC.

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway.

PubMed

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-10-01

We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of 'fanconizing' cancer cells in order to make them more sensitive to other anti-tumour drugs. © 2013 The British Pharmacological Society.

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway

PubMed Central

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-01-01

BACKGROUND AND PURPOSE We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. EXPERIMENTAL APPROACH Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. KEY RESULTS While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. CONCLUSIONS AND IMPLICATIONS Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of ‘fanconizing’ cancer cells in order to make them more sensitive to other anti-tumour drugs. PMID:23937566

Evaluation of milk cathelicidin for detection of bovine mastitis.

PubMed

Addis, M F; Tedde, V; Puggioni, G M G; Pisanu, S; Casula, A; Locatelli, C; Rota, N; Bronzo, V; Moroni, P; Uzzau, S

2016-10-01

Mastitis due to intramammary infection is one of the most economically relevant diseases in dairy cows, causing reductions in milk quality and quantity. Currently, mastitis monitoring is based on somatic cell count (SCC) and bacteriologic culture (BC) of milk. Nevertheless, inflammation-specific protein markers might provide more sensitive and reliable assays, enabling immunoassay-based screening strategies. Cathelicidin is an inflammatory protein released in milk that has recently demonstrated fair reliability and diagnostic potential for ewe mastitis. To assess its performance in cows, 531 quarter milk samples from 2 herds were tested using cathelicidin ELISA, SCC, and BC. We found that 29.0% of samples were positive for cathelicidin, 18.8% had SCC >200,000 cells/mL, and 13.7% were BC-positive. Cathelicidin showed a strong positive correlation with SCC as demonstrated by receiver operating characteristics curve analysis and by the clustering of cathelicidin-negative and cathelicidin-positive samples in association with low and high SCC values, respectively. For evaluating the diagnostic performance of a novel test, BC cannot be considered a reliable gold standard for true disease status because of its known limitations. Therefore, we assessed the sensitivity (Se) and specificity (Sp) of the milk cathelicidin ELISA using a latent class analysis approach together with BC and SCC by considering different diagnostic thresholds to identify the preferred Se/Sp combination. We modeled conditional dependence of cathelicidin and SCC to account for their close association. The cathelicidin ELISA showed higher Se than SCC and BC for almost all threshold combinations. In fact, at the best-performing threshold combination, the Se of cathelicidin was 80.6%, 6.2 percentage points higher than that of SCC >200,000 cells/mL (74.4%) and similar to that of SCC >100,000 cells/mL (80.2%). Most importantly, this Se was obtained with a loss in Sp of only 1.4 percentage points compared with SCC >200,000 cells/mL (94.9% Sp for cathelicidin vs. 96.3% for SCC >200,000). The limited Se of BC (38.8%) was also confirmed in this study, and BC showed a slightly lower Sp than both cathelicidin and SCC for most of threshold combinations. This study confirmed that cathelicidin is released in the milk of cows with mastitis and that its presence is highly correlated with SCC. The measurement of cathelicidin by ELISA may hold significant potential for improving the sensitivity of mastitis detection in dairy cows while maintaining high specificity. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Perspectives from ab-initio and tight-binding: Applications to transition metal compounds and superlattices

NASA Astrophysics Data System (ADS)

Venkataraman, Vijay Shankar

The experimental and theoretical study of transition metal compounds have occupied condensed matter physicists for the best part of the last century. The rich variety of physical behaviour exhibited by these compounds owes its origin to the subtle balance of the energy scales at play for the d orbitals. In this thesis, we study three different systems comprised of transition metal atoms from the third, the fourth, and the fifth group of the periodic table using a combination of ab-initio density functional theory (DFT) computations and effective tight-binding models for the electronic properties. We first consider the electronic properties of artificially fabricated perovskite superlattices of the form [(SrIrO3)m / SrTiO3] with integer m denoting the number of layers of SrIrO3. After discussing the results of experiments undertaken by our collaborators, we present the results of our DFT calculations and build tight-binding models for the m = 1 and m = 2 superlattices. The active ingredient is found to be the 5d orbitals with significant spin-orbit coupling. We then study the energies of magnetic ground states within DFT and compare and contrast our results with those obtained for the bulk Ruddlesden-Popper iridates. Together with experimental measurements, our results suggest that these superlattices are an exciting venue to probe the magnetism and metal-insulator transitions that occur from the intricate balance of the spin-orbit coupling and electron interactions, as has been reported for their bulk counterparts. Next, we consider alpha-RuCl3, a honeycomb lattice compound. We first show using DFT calculations in conjunction with experiments performed by our collaborators, how spin-orbit coupling in the 4d orbitals of Ru is essential to understand the insulating state realized in this compound. Then, in the latter half of the chapter, we study the magnetic ground states of a two-dimensional analogue of alpha-RuCl3 in weak and strong-coupling regimes obtained from a tight-binding model for the 4d orbitals. We further compare these results with energies obtained from DFT calculations. We obtain a zig-zag magnetic ground state for this compound, in all the three approaches. Within DFT, we find that correlations enhance the spin-orbit coupling in this compound and that the anisotropic Kitaev interactions between the spins are dominant in a strong-coupling model. Then, we move on to study the electronic band structures of the higher manganese silicides, which are good thermoelectric materials. Using results from DFT calculations on Mn4Si7 and structural arguments, we construct an effective tight-binding model for the first three members of this series - Mn4Si7, Mn11Si19, and Mn15Si26.

Stress Corrosion Cracking of Aluminum Alloys

DTIC Science & Technology

2012-09-10

Hossain and B. J, O’Toole: Stress Corrosion Cracking of Martensitic Stainless Steel for Transmutation Application, Presented at 2003 International...SCC of marternsitic stainless steel by Roy,[12] and learn the annealing effect on SCC of carbon steel by Haruna.[13] The application of slow...observations. In his study on SCC of AISI 304 stainless steel , Roychowdhury[3] detected no apparent SCC in solutions containing 1 ppm thiosulfate and

Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?

PubMed

Balci, Ugur; Ozer, Kutan; Gorgel, Sacit Nuri; Sefik, Ertugrul; Girgin, Cengiz; Dincel, Cetin

2013-10-01

The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.

Geographic Distribution of Trauma Burden, Mortality, and Services in the United States: Does Availability Correspond to Patient Need?

PubMed

Rios-Diaz, Arturo J; Metcalfe, David; Olufajo, Olubode A; Zogg, Cheryl K; Yorkgitis, Brian; Singh, Mansher; Haider, Adil H; Salim, Ali

2016-12-01

The association between the need for trauma care and trauma services has not been characterized previously. We compared the distribution of trauma admissions with state-level availability of trauma centers (TCs), surgical critical care (SCC) providers, and SCC fellowships, and assessed the association between trauma care provision and state-level trauma mortality. We obtained 2013 state-level data on trauma admissions, TCs, SCC providers, SCC fellowship positions, per-capita income, population size, and age-adjusted mortality rates. Normalized densities (per million population [PMP]) were calculated and generalized linear models were used to test associations between provision of trauma services (higher-level TCs, SCC providers, and SCC fellowship positions) and trauma burden, per-capita income, and age-adjusted mortality rates. There were 1,345,024 trauma admissions (4,250 PMP), 2,496 SCC providers (7.89 PMP), and 1,987 TCs across the country, of which 521 were Level I or II (1.65 PMP). There was considerable variation between the top 5 and bottom 5 states in terms of Level I/Level II TCs and SCC surgeon availability (approximately 8.0/1.0), despite showing less variation in trauma admission density (1.5/1.0). Distribution of trauma admissions was positively associated with SCC provider density and age-adjusted trauma mortality (p ≤ 0.001), and inversely associated with per-capita income (p < 0.001). Age-adjusted mortality was inversely associated with the number of SCC providers PMP. For every additional SCC provider PMP, there was a decrease of 618 deaths per year. There is an inequitable distribution of trauma services across the US. Increases in the density of SCC providers are associated with decreases in mortality. There was no association between density of trauma admissions and location of Level I/Level II TCs. In the wake of efforts to regionalize TCs, additional efforts are needed to address disparities in the provision of quality care to trauma patients. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

In vitro investigation of head and neck cancer stem cell proportions and their changes following X-ray irradiation as a function of HPV status.

PubMed

Reid, Paul; Wilson, Puthenparampil; Li, Yanrui; Marcu, Loredana G; Staudacher, Alexander H; Brown, Michael P; Bezak, Eva

2017-01-01

Some head and neck squamous cell carcinomas (HNSCC) have a distinct aetiology, which depends on the presence of oncogenic human papilloma virus (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater radioresistance and capacity to change replication dynamics in response to irradiation compared to non-clonogenic cells. Since there is limited data on CSCs in HNSCC as a function of HPV status, better understanding of their radiobiology may enable improved treatment outcome. Baseline and post-irradiation changes in CSC proportions were investigated by flow cytometry in a HPV-negative (UM-SCC-1) and a HPV-positive (UM-SCC-47) HNSCC cell line, using fluorescent staining with CD44/ALDH markers. CSC proportions in both irradiated and unirradiated cultures were compared for the two cell lines at various times post-irradiation. To assess repopulation of CSCs, untreated cultures were depleted of CD44+/ALDH+ cells and re-cultured for 3 weeks before flow cytometry analysis. CSC proportions in untreated cell lines were 0.57% (UM-SCC-1) and 2.87% (UM-SCC-47). Untreated cell lines depleted of CD44+/ALDH+ repopulated this phenotype to a mean of 0.15% (UM-SCC-1) and 6.76% (UM-SCC-47). All UM-SCC-47 generations showed elevated CSC proportions after irradiation, with the most significant increase at 2 days post-irradiation. The highest elevation in UM-SCC-1 CSCs was observed at 1 day post-irradiation in the 2nd generation and at 3 days after irradiation in the 3rd generation. When measured after 10 days, only the 3rd generation of UM-SCC-1 showed elevated CSCs. CSC proportions in both cell lines were elevated after exposure and varied with time post irradiation. UM-SCC-47 displayed significant plasticity in repopulating the CSC phenotype in depleted cultures, which was not seen in UM-SCC-1.

Effectiveness of the WHO SCC on improving adherence to essential practices during childbirth, in resource constrained settings.

PubMed

Kumar, Somesh; Yadav, Vikas; Balasubramaniam, Sudharsanam; Jain, Yashpal; Joshi, Chandra Shekhar; Saran, Kailash; Sood, Bulbul

2016-11-08

India accounts for 27 % of world's neonatal deaths. Although more Indian women deliver in facilities currently than a decade ago, early neonatal mortality has not declined, likely because of insufficient quality of care. The WHO Safe Childbirth Checklist (SCC) was developed to support health workers to perform essential practices known to reduce preventable maternal and new-born deaths around the time of childbirth. Despite promising early research many outstanding questions remain about effectiveness of the SCC in low-resource settings. In collaboration with the Ministry of Health SCC was modified for Indian context and introduced in 101 intervention facilities in Rajasthan, India and 99 facilities served as comparison to study if it reduces mortality. This Quasi experimental Observational intervention-comparison was embedded in this larger program to test whether a program for introduction of SCC with simple implementation package was associated with increased adherence to 28 evidence-based practices. This study was conducted in 8 intervention and 8 comparison sites. Program interventions to promote appropriate use of the SCC included orienting providers to the checklist, modest modifications of the SCC to promote provider uptake and accountability, ensuring availability of essential supplies, and providing supportive supervision for helping providers in using the SCC. The SCC was used by providers in 86 % of 240 deliveries observed in the eight intervention facilities. Providers in the intervention group significantly adhered to practices included in the SCC than providers in the comparison group controlling for baseline scores and confounders. Women delivering in the intervention facilities received on an average 11.5 more of the 28 practices included compared with women in the comparison facilities. For selected practices provider performance in the intervention group increased as much as 93 % than comparison sites. Use of the SCC and provider performance of best practices increased in intervention facilities reflecting improvement in quality of facility childbirth care for women and new-born in low resource settings.

Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

PubMed

Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

2014-02-01

Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value <0.05 was considered statistically significant. 196 patients with SCC of the oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

1,25D3 potentiates cisplatin antitumor activity by p73 induction in a squamous cell carcinoma model

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Hershberger, Pamela A.; Flynn, Geraldine; Kong, Rui-Xian; Trump, Donald L.; Johnson, Candace S.

2008-01-01

1,25D3 exhibits anti-tumor activity in a variety of cancers including squamous cell carcinoma (SCC). Intrinsic resistance of SCC cells to cisplatin was observed and led to the investigation into whether 1,25D3 sensitizes SCC cells to cisplatin. Pretreatment with 1,25D3 followed by cisplatin enhanced growth inhibition in SCC cells compared with 1,25D3 alone, as assessed by cytotoxicity and in vitro clonogenic assays. In addition, 1,25D3 sensitized SCC cells to cisplatin-mediated apoptosis. Treatment of tumor-bearing C3H mice with 1,25D3 prior to cisplatin reduced clonogenic survival using in vivo excision clonogenic assay. These results were not observed in a 1,25D3-resistant SCC variant, indicating the critical role of 1,25D3 in sensitizing SCC cells to cisplatin. Further, a marked decrease in fractional tumor volume was observed when SCC tumor-bearing mice were treated with 1,25D3 prior to cisplatin as compared to either agent administered alone. Cisplatin has been shown to modulate p73 protein level in certain cancer cells. Our data showed that p73 level was not affected by cisplatin, but increased by 1,25D3 in SCC cells. Knocking down p73 by siRNA protected SCC cells against 1,25D3 and cisplatin-mediated clonogenic cell kill and apoptosis. Increasing p73 protein level by knocking down UFD2a, which mediates p73 degradation, promoted 1,25D3 and cisplatin-mediated clonogenic cell kill. These results suggest that 1,25D3 potentiates cisplatin anti-tumor activity in vitro and in vivo in a SCC model system, possibly through p73 induction and apoptosis. The combination treatment may provide a more effective therapeutic regimen in cancer treatment. PMID:18790784

Dynamic CRM occupancy reflects a temporal map of developmental progression.

PubMed

Wilczyński, Bartek; Furlong, Eileen E M

2010-06-22

Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression.

Structure of an E. coli integral membrane sulfurtransferase and its structural transition upon SCN- binding defined by EPR-based hybrid method

NASA Astrophysics Data System (ADS)

Ling, Shenglong; Wang, Wei; Yu, Lu; Peng, Junhui; Cai, Xiaoying; Xiong, Ying; Hayati, Zahra; Zhang, Longhua; Zhang, Zhiyong; Song, Likai; Tian, Changlin

2016-01-01

Electron paramagnetic resonance (EPR)-based hybrid experimental and computational approaches were applied to determine the structure of a full-length E. coli integral membrane sulfurtransferase, dimeric YgaP, and its structural and dynamic changes upon ligand binding. The solution NMR structures of the YgaP transmembrane domain (TMD) and cytosolic catalytic rhodanese domain were reported recently, but the tertiary fold of full-length YgaP was not yet available. Here, systematic site-specific EPR analysis defined a helix-loop-helix secondary structure of the YagP-TMD monomers using mobility, accessibility and membrane immersion measurements. The tertiary folds of dimeric YgaP-TMD and full-length YgaP in detergent micelles were determined through inter- and intra-monomer distance mapping and rigid-body computation. Further EPR analysis demonstrated the tight packing of the two YgaP second transmembrane helices upon binding of the catalytic product SCN-, which provides insight into the thiocyanate exportation mechanism of YgaP in the E. coli membrane.

Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix.

PubMed

Fregnani, José H T G; Soares, Fernando A; Novik, Pablo R; Lopes, Ademar; Latorre, Maria R D O

2008-02-01

(1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence. This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (IB and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson's chi(2)-test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan-Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p<0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p=0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p<0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p=0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p=0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors. The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted.

Mediation analysis to estimate direct and indirect milk losses associated with bacterial load in bovine subclinical mammary infections.

PubMed

Detilleux, J; Theron, L; Duprez, J-N; Reding, E; Moula, N; Detilleux, M; Bertozzi, C; Hanzen, C; Mainil, J

2016-08-01

Milk losses associated with mastitis can be attributed to either effects of pathogens per se (i.e. direct losses) or to effects of the immune response triggered by the presence of mammary pathogens (i.e. indirect losses). Test-day milk somatic cell counts (SCC) and number of bacterial colony forming units (CFU) found in milk samples are putative measures of the level of immune response and of the bacterial load, respectively. Mediation models, in which one independent variable affects a second variable which, in turn, affects a third one, are conceivable models to estimate direct and indirect losses. Here, we evaluated the feasibility of a mediation model in which test-day SCC and milk were regressed toward bacterial CFU measured at three selected sampling dates, 1 week apart. We applied this method on cows free of clinical signs and with records on up to 3 test-days before and after the date of the first bacteriological samples. Most bacteriological cultures were negative (52.38%), others contained either staphylococci (23.08%), streptococci (9.16%), mixed bacteria (8.79%) or were contaminated (6.59%). Only losses mediated by an increase in SCC were significantly different from null. In cows with three consecutive bacteriological positive results, we estimated a decreased milk yield of 0.28 kg per day for each unit increase in log2-transformed CFU that elicited one unit increase in log2-transformed SCC. In cows with one or two bacteriological positive results, indirect milk loss was not significantly different from null although test-day milk decreased by 0.74 kg per day for each unit increase of log2-transformed SCC. These results highlight the importance of milk losses that are mediated by an increase in SCC during mammary infection and the feasibility of decomposing total milk loss into its direct and indirect components.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients

PubMed Central

Bae, Su-Mi; Min, Hyun-Jin; Ding, Guo Hua; Kwak, Sun-Young; Cho, Young-Lae; Nam, Kye-Hyun; Park, Choong Hak; Kim, Yong-Wan; Kim, Chong-Kook; Han, Byoung-Don; Lee, Young-Joo; Kim, Do Kang

2006-01-01

Purpose Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two- dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI- TOF) mass spectrometer. Materials and Methods Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software™. The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. Results A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, α-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. Conclusion 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC. PMID:19771267

Three-dimensional potential energy surface of selected carbohydrates' CH/π dispersion interactions calculated by high-level quantum mechanical methods.

PubMed

Kozmon, Stanislav; Matuška, Radek; Spiwok, Vojtěch; Koča, Jaroslav

2011-05-09

In this study we present the first systematic computational three-dimensional scan of carbohydrate hydrophobic patches for the ability to interact through CH/π dispersion interactions. The carbohydrates β-d-glucopyranose, β-d-mannopyranose and α-l-fucopyranose were studied in a complex with a benzene molecule, which served as a model of the CH/π interaction in carbohydrate/protein complexes. The 3D relaxed scans were performed at the SCC-DFTB-D level with 3 757 grid points for both carbohydrate hydrophobic sides. The interaction energy of all grid points was recalculated at the DFT-D BP/def2-TZVPP level. The results obtained clearly show highly delimited and separated areas around each CH group, with an interaction energy up to -5.40 kcal mol(-1) . The results also show that with increasing H⋅⋅⋅π distance these delimited areas merge and form one larger region, which covers all hydrogen atoms on that specific carbohydrate side. Simultaneously, the interaction becomes weaker with an energy of -2.5 kcal mol(-1) . All local energy minima were optimized at the DFT-D BP/def2-TZVPP level and the interaction energies of these complexes were refined by use of the high-level ab initio computation at the CCSD(T)/CBS level. Results obtained from the optimization suggest that the CH group hydrogen atoms are not equivalent and the interaction energy at the CCSD(T)/CBS level range from -3.54 to -5.40 kcal mol(-1) . These results also reveal that the optimal H⋅⋅⋅π distance for the CH/π dispersion interaction is approximately (2.310±0.030) Å, and the angle defined as carbon-hydrogen-benzene geometrical centre is (180±30)°. These results reveal that whereas the dispersion interactions with the lowest interaction energies are quite strictly located in space, the slightly higher interaction energy regions adopt a much larger space. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Incidence, demographics and surgical outcomes of cutaneous squamous cell carcinoma diagnosed in Northland, New Zealand.

PubMed

Elliott, Brodie M; Douglass, Benjamin R; McConnell, Daniel; Johnson, Blair; Harmston, Christopher

2018-05-18

Non-melanoma skin cancer (NMSC) is the most commonly diagnosed and most costly cancer in Australasia. Cutaneous squamous cell carcinoma (cSCC) accounts for approximately 25% of NMSC. Despite this, reporting of cSCC is not mandatory in Australasia. This creates difficulties in planning, resourcing and improving outcomes in cSCC. Previous studies in New Zealand have lacked data on ethnicity. The aim of this study was to define the incidence and demographics of cSCC diagnosed in Northland, New Zealand, including data on ethnicity. A 12-month retrospective study was carried out of all primary cSCC histologically diagnosed in Northland for one year. The cohort was identified by searching the Northland District Health Board pathology database. Data on outcomes and ethnicity were obtained from the hospital results system. Primary outcome of interest was the incidence of cSCC in Northland. Secondary outcomes of interest were lesion characteristics and positive margin rate. 1,040 cSCC were identified in 890 patients. Mean age of patients was 75. Crude incidence of primary cSCC was 668/100,000 patient years. Age standardised incidence was 305/100,000 patient years. An estimate of New Zealand incidence adjusted for age and ethnicity is 580/100,000 patient years. Overall positive margin rate in excised lesions was 9.5%. This study has defined the rate of cSCC in a large, well defined New Zealand population, and estimated age and ethnicity adjusted incidence in New Zealand. It has demonstrated the highest incidence of cSCC in the world outside Australia. Overall positive margin rate of excised lesions was acceptable.

Alcohol intake is associated with increased risk of squamous cell carcinoma of the skin: three US prospective cohort studies

PubMed Central

Siiskonen, Satu; Han, Jiali; Li, Tricia; Cho, Eunyoung

2016-01-01

The association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RR) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13 to 1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09 to 1.59). We found no increased risk of cSCC with other alcoholic beverages. The population attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC. PMID:27145335

Alcohol Intake is Associated with Increased Risk of Squamous Cell Carcinoma of the Skin: Three US Prospective Cohort Studies.

PubMed

Siiskonen, Satu; Han, Jiali; Li, Tricia; Cho, Eunyoung; Nijsten, Tamar; Qureshi, Abrar

2016-01-01

The association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RRs) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13-1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09-1.59). We found no increased risk of cSCC with other alcoholic beverages. The population-attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC.

Density-functional tight-binding investigation of the structure, stability and material properties of nickel hydroxide nanotubes

NASA Astrophysics Data System (ADS)

Jahangiri, Soran; Mosey, Nicholas J.

2018-01-01

Nickel hydroxide is a material composed of two-dimensional layers that can be rolled up to form cylindrical nanotubes belonging to a class of inorganic metal hydroxide nanotubes that are candidates for applications in catalysis, energy storage, and microelectronics. The stabilities and other properties of this class of inorganic nanotubes have not yet been investigated in detail. The present study uses self-consistent-charge density-functional tight-binding calculations to examine the stabilities, mechanical properties, and electronic properties of nickel hydroxide nanotubes along with the energetics associated with the adsorption of water by these systems. The tight-binding model was parametrized for this system based on the results of first-principles calculations. The stabilities of the nanotubes were examined by calculating strain energies and performing molecular dynamics simulations. The results indicate that single-walled nickel hydroxide nanotubes are stable at room temperature, which is consistent with experimental investigations. The nanotubes possess size-dependent mechanical properties that are similar in magnitude to those of other inorganic nanotubes. The electronic properties of the nanotubes were also found to be size-dependent and small nickel oxyhydroxide nanotubes are predicted to be semiconductors. Despite this size-dependence, both the mechanical and electronic properties were found to be almost independent of the helical structure of the nanotubes. The calculations also show that water molecules have higher adsorption energies when binding to the interior of the nickel hydroxide nanotubes when compared to adsorption in nanotubes formed from other two-dimensional materials such as graphene. The increased adsorption energy is due to the hydrophilic nature of nickel hydroxide. Due to the broad applications of nickel hydroxide, the nanotubes investigated here are also expected to be used in catalysis, electronics, and clean energy production.

Resonant scattering due to adatoms in graphene: Top, bridge, and hollow positions

NASA Astrophysics Data System (ADS)

Irmer, Susanne; Kochan, Denis; Lee, Jeongsu; Fabian, Jaroslav

2018-02-01

We present a theoretical study of resonance characteristics in graphene from adatoms with s or pz character binding in top, bridge, and hollow positions. The adatoms are described by two tight-binding parameters: on-site energy and hybridization strength. We explore a wide range of different magnitudes of these parameters by employing T -matrix calculations in the single adatom limit and by tight-binding supercell calculations for dilute adatom coverage. We calculate the density of states and the momentum relaxation rate and extract the resonance level and resonance width. The top position with a large hybridization strength or, equivalently, small on-site energy, induces resonances close to zero energy. The bridge position, compared to top, is more sensitive to variation in the orbital tight-binding parameters. Resonances within the experimentally relevant energy window are found mainly for bridge adatoms with negative on-site energies. The effect of resonances from the top and bridge positions on the density of states and momentum relaxation rate is comparable and both positions give rise to a power-law decay of the resonant state in graphene. The hollow position with s orbital character is affected from destructive interference, which is seen from the very narrow resonance peaks in the density of states and momentum relaxation rate. The resonant state shows no clear tendency to a power-law decay around the impurity and its magnitude decreases strongly with lowering the adatom content in the supercell calculations. This is in contrast to the top and bridge positions. We conclude our study with a comparison to models of pointlike vacancies and strong midgap scatterers. The latter model gives rise to significantly higher momentum relaxation rates than caused by single adatoms.

Structural, physicochemical characterization, theoretical studies of carboxamides and their Cu(II), Zn(II) complexes having antibacterial activities against E. coli

NASA Astrophysics Data System (ADS)

Aktan, Ebru; Gündüzalp, Ayla Balaban; Özmen, Ümmühan Özdemir

2017-01-01

The carboxamides; N,N‧-bis(thiophene-2-carboxamido)-1,3-diaminopropanol (L1) and N,N‧-bis(furan-2-carboxamido)-1,3-diaminopropanol (L2) were synthesized and characterized using 1H NMR, 13C NMR, LC-MS and FT-IR spectrum. The molecular geometries of these molecules were optimized by DFT/B3LYP method with 6-311G(d,p) basis set in Gaussian 09 software. The geometrical parameters, frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) mapped surfaces were calculated by the same basis set. Dinuclear Cu(II) and Zn(II) complexes having general formula as [MLCl]2Cl2.nH2O (in which M = Cu(II),Zn(II); n = 0,2) were also synthesized and characterized using LC-MS and FT-IR spectrum, thermogravimetric analysis (TGA/DTA curves), magnetic moments and molar conductivities. Coordination was found to be through carbonyl oxygen and two chlorine atoms as bridging in distorted tetrahedral geometry. The optimized structures, geometrical parameters, frontier molecular orbitals (FMOs) and dipole moments of metal complexes were also obtained by DFT/B3LYP method with LanL2DZ basis set. Antibacterial activities of the compounds were screened against E. coli using microdilution method (MIC's in μg/mL). The activity results show that the corresponding compounds exhibit good to moderate antibacterial effects when compared with sulfamethoxazole and sulfisoxazole antibiotics as positive controls. Also, metal complexes have remarkable increase in their activities than parent ligands against E. coli which is mostly effected by [Cu(L2)Cl]2Cl2 complex as potential antibacterial agent.

Basaloid Squamous Cell Carcinoma of the Anus Revisited.

PubMed

Graham, Rondell P; Arnold, Christina A; Naini, Bita V; Lam-Himlin, Dora M

2016-03-01

Basaloid squamous cell carcinoma (SCC) of the anus, previously called cloacogenic carcinoma, is a subtype of SCC. There are very few data on the morphologic variation within basaloid SCC of the anus, which may contribute to misdiagnosis. We retrospectively evaluated cases originally diagnosed as basaloid SCC for histologic characterization. We retrieved and reviewed cases of basaloid SCC from 1994 to 2013. Ten (27%) cases were reclassified after review, including basal cell carcinoma (n=6), melanoma (n=2), and neuroendocrine carcinoma (n=2). The final group of basaloid SCC (n=27) showed a female predominance (median age=60 y; range, 42 to 92 y). Morphologically, basaloid SCC could be categorized into 4 groups: transitional carcinoma like (n=10), basaloid with peripheral palisade (n=13), adenoid cystic carcinoma like (n=3), and mucinous microcystic (n=1). In 19 cases the histologic patterns were pure and were mixed in the remainder. CK5/6, p16, and high-risk HPV were positive in all cases (n=27). SOX2 was positive in 18/22 cases. Clinical follow-up was available on 60% of cases; 9 patients (53%) developed local recurrence or metastasis, and 5 (29%) died of disease. Basaloid SCC of the anus is characterized by 4 major histologic patterns and is consistently HPV driven.

Self-Concept Clarity in Adolescents and Parents: A Six-Wave Longitudinal and Multi-Informant Study on Development and Intergenerational Transmission.

PubMed

Crocetti, Elisabetta; Rubini, Monica; Branje, Susan; Koot, Hans M; Meeus, Wim

2016-10-01

The purpose of this study was twofold: (a) to disentangle patterns of change and stability in self-concept clarity (SCC) in adolescents and in their parents and (b) to examine processes of intergenerational transmission of SCC in families with adolescents. Participants were 497 Dutch families including the father (baseline Mage  = 46.74), the mother (baseline Mage  = 44.41), and their adolescent child (56.9% males; baseline Mage  = 13.03). Each family member completed the SCC scale for six waves, with a one-year interval between each wave. Latent growth curve analyses indicated that adolescent boys reported higher SCC than girls. Furthermore, fathers and mothers reported higher SCC than their children, and it increased over time. Indices of SCC rank-order stability were high and increased from T1 to T2, T2 to T3, etc., for each family member, especially for adolescents. Multivariate latent growth curve analyses and cross-lagged models highlighted a unidirectional transmission process, with fathers' and mothers' SCC influencing adolescents' SCC. This result was not moderated by adolescent gender. These findings indicate that self-concept clarity is transmitted from parents to children. © 2015 Wiley Periodicals, Inc.

Medicare claims data reliably identify treatments for basal cell carcinoma and squamous cell carcinoma: a prospective cohort study.

PubMed

Thompson, Bridie S; Olsen, Catherine M; Subramaniam, Padmini; Neale, Rachel E; Whiteman, David C

2016-04-01

To investigate the accuracy of Medical Benefit Schedule (MBS) item numbers to identify treatments for basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). We linked records from QSkin Study participants (n=37,103) to Medicare. We measured the proportion of Medicare claims for primary excision of BCC/SCC that had corresponding claims for histopathology services. In subsets of participants, we estimated the sensitivity and external concordance of MBS item numbers for identifying BCC/SCC diagnoses by comparing against 'gold-standard' histopathology reports. A total of 2,821 (7.6%) participants had 4,830 separate Medicare claims for BCC/SCC excision; almost all (97%) had contemporaneous Medicare claims for histopathology services. Among participants with BCC/SCC confirmed by histology reports, 76% had a corresponding Medicare claim for primary surgical excision of BCC/SCC. External concordance for Medicare claims for primary BCC/SCC excision was 68%, increasing to 97% when diagnoses for intra-epidermal carcinomas and keratoacanthomas were included. MBS item numbers for primary excision of BCC/SCC are reasonably reliable for determining incident cases of keratinocyte skin cancers, but may underestimate incidence by up to 24%. Medicare claims data may have utility in monitoring trends in conditions for which there is no mandatory reporting. © 2015 Public Health Association of Australia.

Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

PubMed

Asgari, Maryam M; Warton, E Margaret; Whittemore, Alice S

2015-04-01

The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients.

PubMed

Herms, Florian; Kramkimel, Nora; Regnier-Rosencher, Elodie; Carlotti, Agnès; Chanal, Johan; Boitier, Françoise; Aractingi, Selim; Dupin, Nicolas; Avril, Marie-Françoise

2016-10-01

Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08-12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.

Self-consolidating concrete (SCC) for infrastructure elements.

DOT National Transportation Integrated Search

2012-09-01

Because of its unique nature, self-consolidating concrete (SCC) has the potential to significantly reduce costs associated with : transportation-related infrastructure, benefiting both MoDOT and the residents of Missouri. SCC is a highly flowable, no...

Self-consolidating concrete (SCC) for infrastructure elements.

DOT National Transportation Integrated Search

2012-07-01

Because of its unique nature, self-consolidating concrete (SCC) has the potential to significantly reduce costs associated with : transportation-related infrastructure, benefiting both MoDOT and the residents of Missouri. SCC is a highly flowable, : ...

Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma

PubMed Central

Li, Fei; Fang, Zhaoyuan; Zhang, Jian; Li, Chen; Liu, Hongyan; Xia, Jufeng; Zhu, Hongwen; Guo, Chenchen; Qin, Zhen; Li, Fuming; Han, Xiangkun; Wang, Yuetong; Feng, Yan; Wang, Ye; Zhang, Wenjing; Wang, Zuoyun; Jin, Yujuan; Sun, Yihua; Wei, Wenyi; Zeng, Rong; Chen, Haiquan; Ji, Hongbin

2016-01-01

Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer. Our current knowledge of oncogenic drivers in this specific subtype of lung cancer is largely limited compared with lung adenocarcinoma (ADC). Through exon array analyses, molecular analyses and functional studies, we here identify the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC. We found that this gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Through mechanistic studies, we further revealed that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2-MMP1 signaling axis. We show that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression. These findings improve our current knowledge of oncogenic drivers in lung SCC and provide a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion. PMID:27670699

PWSCC Susceptibility in Heat Affected Zones of Alloy 600

NASA Astrophysics Data System (ADS)

Couvant, Thierry; Brossier, Thomas; Cossange, Christian

The recent field experience and several experimental results have shown the possible deleterious effect of a heat affected zone (HAZ) induced by welding on the susceptibility to the stress corrosion cracking (SCC) of Alloy 600 of bottom penetrations exposed to primary water of PWRs. This work tried to quantify the increasing susceptibility to initiation and crack propagation in 600/182 HAZ. The rolled plate did not exhibit any susceptibility to SCC except for a cold work higher than 10% typically. By contrast, the weld metal was well known for its high susceptibility to SCC. Metallurgical and mechanical characterizations of the HAZ indicated a slight gradient of Vickers micro hardness close to the fusion line (up to few mm) and a lack of intergranular precipitates up to 500 µm from the fusion line. SCC tests clearly demonstrated that a non-susceptible plate may exhibit a significant susceptibility to SCC propagation in the HAZ. Results of initiation tests did not allow to observe any SCC in the base metal, due to the high susceptibility to SCC of the weld.

A Review of Supply Chain Collaboration Practices for Small and Medium-sized Manufacturers

NASA Astrophysics Data System (ADS)

Wee, SY; Thoo, AC; Z, Sulaiman; FM, Muharam

2016-05-01

For the decades, organizations have endeavored to look for external sources for opportunities to achieve efficient and responsive supply chain with their partners especially for small and medium manufacturers (SMM). In this scenario, supply chain collaboration (SCC) is an interaction between supply chain members with the purpose of utilizes the knowledge and resources of customers and suppliers, and integrates the flows of products and information in order to achieve a common goal and obtain mutual benefit. The essential SCC dimensions for SMMs comprised of information sharing, joint knowledge creation, joint decision making, goal congruence and incentive sharing. The successful implementation of SCC can give SMMs an edge over their competitors. This paper aims to introduce a review of SCC practices for SMM. Overall, the findings provide managerial insights for the SMM in SCC implementation owing to resource scarcity and the need to draw SCC in order to ensure a sustainable competitive advantage.

Tight-Binding Study of Polarons in Two-Dimensional Systems: Implications for Organic Field-Effect Transistor Materials

NASA Astrophysics Data System (ADS)

Lei, Jie

2011-03-01

In order to understand the electronic and transport properties of organic field-effect transistor (FET) materials, we theoretically studied the polarons in two-dimensional systems using a tight-binding model with the Holstein type and Su--Schrieffer--Heeger type electron--lattice couplings. By numerical calculations, it was found that a carrier accepts four kinds of localization, which are named the point polaron, two-dimensional polaron, one-dimensional polaron, and the extended state. The degree of localization is sensitive to the following parameters in the model: the strength and type of electron--lattice couplings, and the signs and relative magnitudes of transfer integrals. When a parameter set for a single-crystal phase of pentacene is applied within the Holstein model, a considerably delocalized hole polaron is found, consistent with the bandlike transport mechanism.

Improved nonorthogonal tight-binding Hamiltonian for molecular-dynamics simulations of silicon clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ordejon, P.; Lebedenko, D.; Menon, M.

1994-08-15

We present an improvement over the nonorthogonal tight-binding molecular-dynamics scheme recently proposed by Menon and Subbaswamy [Phys. Rev. B 47, 12 754 (1993)]. The proper treatment of the nonorthogonality and its effect on the Hamiltonian matrix elements has been found to obviate the need for a bond-counting term, leaving only two adjustable parameters in the formalism. With the improved parametrization we obtain values of the energies and bonding distances which are in better agreement with the available [ital ab] [ital initio] results for clusters of size up to [ital N]=10. Additionally, we have identified a lowest energy structure for themore » Si[sub 9] cluster, which to our knowledge has not been considered to date. We show that this structure (a distorted tricapped trigonal prism with [ital C][sub 2[ital v

A Model for Predicting Thermoelectric Properties of Bi2Te3

NASA Technical Reports Server (NTRS)

Lee, Seungwon; VonAllmen, Paul

2009-01-01

A parameterized orthogonal tight-binding mathematical model of the quantum electronic structure of the bismuth telluride molecule has been devised for use in conjunction with a semiclassical transport model in predicting the thermoelectric properties of doped bismuth telluride. This model is expected to be useful in designing and analyzing Bi2Te3 thermoelectric devices, including ones that contain such nano - structures as quantum wells and wires. In addition, the understanding gained in the use of this model can be expected to lead to the development of better models that could be useful for developing other thermoelectric materials and devices having enhanced thermoelectric properties. Bi2Te3 is one of the best bulk thermoelectric materials and is widely used in commercial thermoelectric devices. Most prior theoretical studies of the thermoelectric properties of Bi2Te3 have involved either continuum models or ab-initio models. Continuum models are computationally very efficient, but do not account for atomic-level effects. Ab-initio models are atomistic by definition, but do not scale well in that computation times increase excessively with increasing numbers of atoms. The present tight-binding model bridges the gap between the well-scalable but non-atomistic continuum models and the atomistic but poorly scalable ab-initio models: The present tight-binding model is atomistic, yet also computationally efficient because of the reduced (relative to an ab-initio model) number of basis orbitals and flexible parameterization of the Hamiltonian.

Density function theory study of the adsorption and dissociation of carbon monoxide on tungsten nanoparticles.

PubMed

Weng, Meng-Hsiung; Ju, Shin-Pon; Chen, Hsin-Tsung; Chen, Hui-Lung; Lu, Jian-Ming; Lin, Ken-Huang; Lin, Jenn-Sen; Hsieh, Jin-Yuan; Yang, Hsi-Wen

2013-02-01

The adsorption and dissociation properties of carbon monoxide (CO) molecule on tungsten W(n) (n = 10-15) nanoparticles have been investigated by density-functional theory (DFT) calculations. The lowest-energy structures for W(n) (n = 10-15) nanoparticles are found by the basin-hopping method and big-bang method with the modified tight-binding many-body potential. We calculated the corresponding adsorption energies, C-O bond lengths and dissociation barriers for adsorption of CO on nanoparticles. The electronic properties of CO on nanoparticles are studied by the analysis of density of state and charge density. The characteristic of CO on W(n) nanoparticles are also compared with that of W bulk.

Visualization of atomic-scale phenomena in superconductors: application to FeSe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choubey, Peayush; Berlijn, Tom; Kreisel, Andreas

Here we propose a simple method of calculating inhomogeneous, atomic-scale phenomena in superconductors which makes use of the wave function information traditionally discarded in the construction of tight-binding models used in the Bogoliubov-de Gennes equations. The method uses symmetry- based first principles Wannier functions to visualize the effects of superconducting pairing on the distribution of electronic states over atoms within a crystal unit cell. Local symmetries lower than the global lattice symmetry can thus be exhibited as well, rendering theoretical comparisons with scanning tunneling spectroscopy data much more useful. As a simple example, we discuss the geometric dimer states observedmore » near defects in superconducting FeSe.« less

Visualization of atomic-scale phenomena in superconductors: application to FeSe

DOE PAGES

Choubey, Peayush; Berlijn, Tom; Kreisel, Andreas; ...

2014-10-31

Here we propose a simple method of calculating inhomogeneous, atomic-scale phenomena in superconductors which makes use of the wave function information traditionally discarded in the construction of tight-binding models used in the Bogoliubov-de Gennes equations. The method uses symmetry- based first principles Wannier functions to visualize the effects of superconducting pairing on the distribution of electronic states over atoms within a crystal unit cell. Local symmetries lower than the global lattice symmetry can thus be exhibited as well, rendering theoretical comparisons with scanning tunneling spectroscopy data much more useful. As a simple example, we discuss the geometric dimer states observedmore » near defects in superconducting FeSe.« less

PFKFB3 Control of Cancer Growth by Responding to Circadian Clock Outputs

PubMed Central

Chen, Lili; Zhao, Jiajia; Tang, Qingming; Li, Honggui; Zhang, Chenguang; Yu, Ran; Zhao, Yan; Huo, Yuqing; Wu, Chaodong

2016-01-01

Circadian clock dysregulation promotes cancer growth. Here we show that PFKFB3, the gene that encodes for inducible 6-phosphofructo-2-kinase as an essential supporting enzyme of cancer cell survival through stimulating glycolysis, mediates circadian control of carcinogenesis. In patients with tongue cancers, PFKFB3 expression in both cancers and its surrounding tissues was increased significantly compared with that in the control, and was accompanied with dys-regulated expression of core circadian genes. In the in vitro systems, SCC9 tongue cancer cells displayed rhythmic expression of PFKFB3 and CLOCK that was distinct from control KC cells. Furthermore, PFKFB3 expression in SCC9 cells was stimulated by CLOCK through binding and enhancing the transcription activity of PFKFB3 promoter. Inhibition of PFKFB3 at zeitgeber time 7 (ZT7), but not at ZT19 caused significant decreases in lactate production and in cell proliferation. Consistently, PFKFB3 inhibition in mice at circadian time (CT) 7, but not CT19 significantly reduced the growth of implanted neoplasms. Taken together, these findings demonstrate PFKFB3 as a mediator of circadian control of cancer growth, thereby highlighting the importance of time-based PFKFB3 inhibition in cancer treatment. PMID:27079271