Probing the mechanism of electron capture and electron transfer dissociation using tags with variable electron affinity

Electron capture dissociation (ECD) and electron transfer dissociation (ETD) of doubly protonated electron affinity (EA)-tuned peptides were studied to further illuminate the mechanism of these processes. The model peptide FQpSEEQQQTEDELQDK, containing a phosphoserine residue, was converted to EA-tuned peptides via β-elimination and Michael addition of various thiol compounds. These include propanyl, benzyl, 4-cyanobenzyl, perfluorobenzyl, 3,5-dicyanobenzyl, 3-nitrobenzyl, and 3,5-dinitrobenzyl structural moieties, having a range of EA from −1.15 to +1.65 eV, excluding the propanyl group. Typical ECD or ETD backbone fragmentations are completely inhibited in peptides with substituent tags having EA over 1.00 eV, which are referred to as electron predators in this work. Nearly identical rates of electron capture by the dications substituted by the benzyl (EA = −1.15 eV) and 3-nitrobenzyl (EA = 1.00 eV) moieties are observed, which indicates the similarity of electron capture cross sections for the two derivatized peptides. This observation leads to the inference that electron capture kinetics are governed by the long-range electron−dication interaction and are not affected by side chain derivatives with positive EA. Once an electron is captured to high-n Rydberg states, however, through-space or through-bond electron transfer to the EA-tuning tags or low-n Rydberg states via potential curve crossing occurs in competition with transfer to the amide π* orbital. The energetics of these processes are evaluated using time-dependent density functional theory with a series of reduced model systems. The intramolecular electron transfer process is modulated by structure-dependent hydrogen bonds and is heavily affected by the presence and type of electron-withdrawing groups in the EA-tuning tag. The anion radicals formed by electron predators have high proton affinities (approximately 1400 kJ/mol for the 3-nitrobenzyl anion radical) in comparison to other basic sites in the model peptide dication, facilitating exothermic proton transfer from one of the two sites of protonation. This interrupts the normal sequence of events in ECD or ETD, leading to backbone fragmentation by forming a stable radical intermediate. The implications which these results have for previously proposed ECD and ETD mechanisms are discussed

Localization of transverse waves in randomly layered media at oblique incidence

We investigate the oblique incidence of transverse waves on a randomly layered medium in the limit of strong disorder. An approximate method for calculating the inverse localization length based on the assumptions of zero energy flux and complete phase stochastization is presented. Two effects not found at normal incidence have been studied: dependence of the localization length on the polarization, and decrease of the localization length due to the internal reflections from layers with small refractive indexes. The inverse localization length (attenuation rate) for P-polarized radiation is shown to be always smaller than that of S-waves, which is to say that long enough randomly layered sample polarizes transmitted radiation. The localization length for P-polarization depends non-monotonically on the angle of propagation, and under certain conditions turns to infinity at some angle, which means that typical (non-resonant) random realizations become transparent at this angle of incidence (stochastic Brewster effect).Comment: 12 pages, 1 figure, accepted for publication in Physical Review

A Particle Element Approach for Modelling the 3D Printing Process of Fibre Reinforced Polymer Composites

This paper presents a new numerical approach for modelling the 3D printing process of fibre reinforced polymer composites by fused deposition modelling (FDM). The approach is based on the coupling between two particle methods, namely smoothed particle hydrodynamics (SPH) and discrete element method (DEM). The coupled SPH-DEM model has distinctive advantages in dealing with the free surface flow, large deformation of fibres, and/or fibre-fibre interaction that are involved in the FDM process. A numerical feasibility study is carried out to demonstrate its capability for both short and continuous fibre reinforced polymer composites, with promising results achieved for the rheological flow and fibre orientation and deformation. View Full-Tex

A projected approximation to strongly contracted N-electron valence perturbation theory for DMRG wavefunctions

A novel approach to strongly contracted N-electron valence perturbation theory (SC-NEVPT2) as a means of describing dynamic electron correlation for quantum chemical density matrix renormalization group (DMRG) calculations is presented. In this approach the strongly contracted perturber functions are projected onto a renormalized Hilbert space. Compared to a straightforward implementation of SC-NEVPT2 with DMRG wavefunctions, the computational scaling and storage requirements are reduced. This favorable scaling opens up the possibility of calculations with larger active spaces. A specially designed renormalization scheme ensures that both the electronic ground state and the perturber functions are well represented in the renormalized Hilbert space. Test calculations on the N_2 and [Cu_2O_2(en)_2]^(2+) demonstrate some key properties of the method and indicate its capabilities

Piecewise linear transformation in diffusive flux discretization

To ensure the discrete maximum principle or solution positivity in finite volume schemes, diffusive flux is sometimes discretized as a conical combination of finite differences. Such a combination may be impossible to construct along material discontinuities using only cell concentration values. This is often resolved by introducing auxiliary node, edge, or face concentration values that are explicitly interpolated from the surrounding cell concentrations. We propose to discretize the diffusive flux after applying a local piecewise linear coordinate transformation that effectively removes the discontinuities. The resulting scheme does not need any auxiliary concentrations and is therefore remarkably simpler, while being second-order accurate under the assumption that the structure of the domain is locally layered.Comment: 11 pages, 1 figures, preprint submitted to Journal of Computational Physic

Valosin-containing protein regulates the proteasome-mediated degradation of DNA-PKcs in glioma cells.

DNA-dependent protein kinase (DNA-PK) has an important role in the repair of DNA damage and regulates the radiation sensitivity of glioblastoma cells. The VCP (valosine-containing protein), a chaperone protein that regulates ubiquitin-dependent protein degradation, is phosphorylated by DNA-PK and recruited to DNA double-strand break sites to regulate DNA damage repair. However, it is not clear whether VCP is involved in DNA-PKcs (DNA-PK catalytic subunit) degradation or whether it regulates the radiosensitivity of glioblastoma. Our data demonstrated that DNA-PKcs was ubiquitinated and bound to VCP. VCP knockdown resulted in the accumulation of the DNA-PKcs protein in glioblastoma cells, and the proteasome inhibitor MG132 synergised this increase. As expected, this increase promoted the efficiency of DNA repair in several glioblastoma cell lines; in turn, this enhanced activity decreased the radiation sensitivity and prolonged the survival fraction of glioblastoma cells in vitro. Moreover, the VCP knockdown in glioblastoma cells reduced the survival time of the xenografted mice with radiation treatment relative to the control xenografted glioblastoma mice. In addition, the VCP protein was also downregulated in ~25% of GBM tissues from patients (WHO, grade IV astrocytoma), and the VCP protein level was correlated with patient survival (R(2)=0.5222, P<0.05). These findings demonstrated that VCP regulates DNA-PKcs degradation and increases the sensitivity of GBM cells to radiation

Leibniz 2-algebras and twisted Courant algebroids

In this paper, we give the categorification of Leibniz algebras, which is equivalent to 2-term sh Leibniz algebras. They reveal the algebraic structure of omni-Lie 2-algebras introduced in \cite{omniLie2} as well as twisted Courant algebroids by closed 4-forms introduced in \cite{4form}. We also prove that Dirac structures of twisted Courant algebroids give rise to 2-term $L_\infty$-algebras and geometric structures behind them are exactly $H$-twisted Lie algebroids introduced in \cite{Grutzmann}.Comment: 22 pages, to appear in Comm. Algebr

Dynamics of Anderson localization in open 3D media

We develop a self-consistent theoretical approach to the dynamics of Anderson localization in open three-dimensional (3D) disordered media. The approach allows us to study time-dependent transmission and reflection, and the distribution of decay rates of quasi-modes of 3D disordered slabs near the Anderson mobility edge.Comment: 4 pages, 4 figure

Dynamic critical exponents of Swendsen-Wang and Wolff algorithms by nonequilibrium relaxation

With a nonequilibrium relaxation method, we calculate the dynamic critical exponent z of the two-dimensional Ising model for the Swendsen-Wang and Wolff algorithms. We examine dynamic relaxation processes following a quench from a disordered or an ordered initial state to the critical temperature T_c, and measure the exponential relaxation time of the system energy. For the Swendsen-Wang algorithm with an ordered or a disordered initial state, and for the Wolff algorithm with an ordered initial state, the exponential relaxation time fits well to a logarithmic size dependence up to a lattice size L=8192. For the Wolff algorithm with a disordered initial state, we obtain an effective dynamic exponent z_exp=1.19(2) up to L=2048. For comparison, we also compute the effective dynamic exponents through the integrated correlation times. In addition, an exact result of the Swendsen-Wang dynamic spectrum of a one-dimension Ising chain is derived.Comment: 13 pages, 6 figure