Application of liquid pre-column capillary electrophoresis technique to the study of interaction between drug enantiomers and human serum albumin

Based on the chiral separation of several basic drugs, dimetindene, tetryzoline, theodrenaline and verapamil, the liquid pre-column capillary electrophoresis (LPC-CE) technique was established. It was used to determine free concentrations of drug enantiomers in mixed solutions with human serum albumin (HSA). To prevent HSA entering the CE chiral separation zone, the mobility differences between HSA and drugs under a specific pH condition were employed in the LPC. Thus, the detection confusion caused by protein was totally avoided. Further study of binding constants determination and protein binding competitions was carried out. The study proves that the LPC technique could be used for complex media, particularly the matrix of protein coexisting with a variety of drugs.

Base pairing interaction between 5′- and 3′-UTRs controls icaR mRNA translation in Staphylococcus aureus

UPNa. Instituto de Agrobiotecnología. Laboratorio de Biofilms Microbianos.

Iterative Linearized Density Matrix Propagation for Modeling Coherent Energy Transfer in Photosynthetic Light Harvesting

We present results of calculations [1] that employ a new mixed quantum classical iterative density matrix propagation approach (ILDM , or so called Is‐Landmap) [2] to explore the survival of coherence in different photo synthetic models. Our model studies confirm the long lived quantum coherence , while conventional theoretical tools (such as Redfield equation) fail to describe these phenomenon [3,4]. Our ILDM method is a numerical exactly propagation scheme and can be served as a bench mark calculation tools[2]. Result get from ILDM and from other recent methods have been compared and show agreement with each other[4,5]. Long lived coherence plateau has been attribute to the shift of harmonic potential due to the system bath interaction, and the harvesting efficiency is a balance between the coherence and dissipation[1]. We use this approach to investigate the excitation energy transfer dynamics in various light harvesting complex include Fenna‐Matthews‐Olsen light harvesting complex[1] and Cryptophyte Phycocyanin 645 [6]. [1] P.Huo and D.F.Coker ,J. Chem. Phys. 133, 184108 (2010) . [2] E.R. Dunkel, S. Bonella, and D.F. Coker, J. Chem. Phys. 129, 114106 (2008). [3] A. Ishizaki and G.R. Fleming, J. Chem. Phys. 130, 234111 (2009). [4] A. Ishizaki and G.R. Fleming, Proc. Natl. Acad. Sci. 106, 17255 (2009). [5] G. Tao and W.H. Miller, J. Phys. Chem. Lett. 1, 891 (2010). [6] P.Huo and D.F.Coker in preparation

Interaction strengths and net effects in food web models

Understanding how dynamic ecological communities respond to anthropogenic drivers of change such as habitat loss and fragmentation, climate change and the introduction of alien species requires that there is a theoretical framework able to predict community dynamics. At present there is a lack of empirical data that can be used to inform and test predictive models, which means that much of our knowledge regarding the response of ecological communities to perturbations is obtained from theoretical analyses and simulations. This thesis is composed of two strands of research: an empirical experiment conducted to inform the scaling of intraspecific and interspecific interaction strengths in a three species food chain and a series of theoretical analyses on the changes to equilibrium biomass abundances following press perturbations. The empirical experiment is a consequence of the difficulties faced when parameterising the intraspecific interaction strengths in a Lotka-Volterra model. A modification of the dynamic index is used alongside the original dynamic index to estimate intraspecific interactions and interspecific interaction strengths in a three species food. The theoretical analyses focused on the effect of press perturbations to focal species on the equilibrium biomass densities of all species in the community; these perturbations allow for the quantification of a species total net effect. It was found that there is a strong and consistent positive relationship between a species body size and its total net effect for a set of 97 synthetic food webs and also for the Ythan Estuary and Tuesday Lake food webs (empirically described food webs). It is shown that ecological constraints (due to allometric scaling) on the magnitude of entries in the community matrix cause the patterns observed in the inverse community matrix and thus explain the relationship between a species body mass and its total net effect in a community.

Infrared spectra of C2H2 under jet-cooled and para-H2 matrix conditions

In spectra of jet-cooled C2H2 recorded with an FTIR spectrometer, the ν5, ν4 + ν5, ν3 and ν2 + ν4 + ν5 bands all exhibit an intensity distribution corresponding to ∼6 K for rotation, with no evidence of nuclear spin conversion. Spectra of C2H2 isolated in solid p-H2 show no evidence of rotation of C2H2. The strong interaction between ν3 and ν2 + ν4 + ν5 in the gas phase is diminished in solid p-H2. Lines associated with dimer, trimer and tetramer of C2H2 are identified. Spectral features characteristic of solid state acetylene are observed under jet-cooled conditions. © 2007 Elsevier B.V. All rights reserved.

Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4.

Pulmonary fibrosis is a progressive, dysregulated response to injury culminating in compromised lung function due to excess extracellular matrix production. The heparan sulfate proteoglycan syndecan-4 is important in mediating fibroblast-matrix interactions, but its role in pulmonary fibrosis has not been explored. To investigate this issue, we used intratracheal instillation of bleomycin as a model of acute lung injury and fibrosis. We found that bleomycin treatment increased syndecan-4 expression. Moreover, we observed a marked decrease in neutrophil recruitment and an increase in both myofibroblast recruitment and interstitial fibrosis in bleomycin-treated syndecan-4-null (Sdc4-/-) mice. Subsequently, we identified a direct interaction between CXCL10, an antifibrotic chemokine, and syndecan-4 that inhibited primary lung fibroblast migration during fibrosis; mutation of the heparin-binding domain, but not the CXCR3 domain, of CXCL10 diminished this effect. Similarly, migration of fibroblasts from patients with pulmonary fibrosis was inhibited in the presence of CXCL10 protein defective in CXCR3 binding. Furthermore, administration of recombinant CXCL10 protein inhibited fibrosis in WT mice, but not in Sdc4-/- mice. Collectively, these data suggest that the direct interaction of syndecan-4 and CXCL10 in the lung interstitial compartment serves to inhibit fibroblast recruitment and subsequent fibrosis. Thus, administration of CXCL10 protein defective in CXCR3 binding may represent a novel therapy for pulmonary fibrosis.

Assessment of LD matrix measures for the analysis of biological pathway association.

Complex diseases will have multiple functional sites, and it will be invaluable to understand the cross-locus interaction in terms of linkage disequilibrium (LD) between those sites (epistasis) in addition to the haplotype-LD effects. We investigated the statistical properties of a class of matrix-based statistics to assess this epistasis. These statistical methods include two LD contrast tests (Zaykin et al., 2006) and partial least squares regression (Wang et al., 2008). To estimate Type 1 error rates and power, we simulated multiple two-variant disease models using the SIMLA software package. SIMLA allows for the joint action of up to two disease genes in the simulated data with all possible multiplicative interaction effects between them. Our goal was to detect an interaction between multiple disease-causing variants by means of their linkage disequilibrium (LD) patterns with other markers. We measured the effects of marginal disease effect size, haplotype LD, disease prevalence and minor allele frequency have on cross-locus interaction (epistasis). In the setting of strong allele effects and strong interaction, the correlation between the two disease genes was weak (r=0.2). In a complex system with multiple correlations (both marginal and interaction), it was difficult to determine the source of a significant result. Despite these complications, the partial least squares and modified LD contrast methods maintained adequate power to detect the epistatic effects; however, for many of the analyses we often could not separate interaction from a strong marginal effect. While we did not exhaust the entire parameter space of possible models, we do provide guidance on the effects that population parameters have on cross-locus interaction.

Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics.

Tools for analysing configuration interaction wavefunctions

The configuration interaction (CI) approach to quantum chemical calculations is a well-established means of calculating accurately the solution to the Schrodinger equation for many-electron systems. It represents the many-body electron wavefunction as a sum of spin-projected Slater determinants of orthogonal one-body spin-orbitals. The CI wavefunction becomes the exact solution of the Schrodinger equation as the length of the expansion becomes infinite, however, it is a difficult quantity to visualise and analyse for many-electron problems. We describe a method for efficiently calculating the spin-averaged one- and two-body reduced density matrices rho(psi)((r) over bar; (r) over bar' ) and Gamma(psi)((r) over bar (1), (r) over bar (2); (r) over bar'(1), (r) over bar'(2)) of an arbitrary CI wavefunction Psi. These low-dimensional functions are helpful tools for analysing many-body wavefunctions; we illustrate this for the case of the electron-electron cusp. From rho and Gamma one can calculate the matrix elements of any one- or two-body spin-free operator (O) over cap. For example, if (O) over cap is an applied electric field, this field can be included into the CI Hamiltonian and polarisation or gating effects may be studied for finite electron systems. (C) 2003 Elsevier B.V. All rights reserved.

Ultrafast Laser-Driven Excitation Dynamics in Ne: An Ab Initio Time-Dependent R-Matrix Approach

An attosecond pump-probe scheme that combines the use of a free-electron laser pulse with an ultrashort pulse is applied in order to explore the ultrafast excitation dynamics in Ne. We describe the multielectron dynamics using a new nonperturbative time-dependent R-matrix theory. This theory enables the interaction of ultrashort light fields with multielectron atoms and atomic ions to be determined from first principles. By probing the emission of an inner 2s electron from Ne we are also able to study the bound state population dynamics during the free-electron laser pulse.

Time-dependent R -matrix theory for ultrafast atomic processes

We describe an ab initio nonperturbative time-dependent R-matrix theory for ultrafast atomic processes. This theory enables investigations of the interaction of few-femtosecond and -attosecond pulse lasers with complex multielectron atoms and atomic ions. A derivation and analysis of the basic equations are given, which propagate the atomic wave function in the presence of the laser field forward in time in the internal and external R-matrix regions. To verify the accuracy of the approach, we investigate two-photon ionization of Ne irradiated by an intense laser pulse and compare current results with those obtained using the R-matrix Floquet method and an alternative time-dependent method. We also verify the capability of the current approach by applying it to the study of two-dimensional momentum distributions of electrons ejected from Ne due to irradiation by a sequence of 2 as light pulses in the presence of a 780 nm laser field.

Breit-Pauli R-matrix calculation of fine-structure effective collision strengths for the electron impact excitation of Mg V

Context. Electron-impact excitation collision strengths are required for the analysis and interpretation of stellar observations.
Aims. This calculation aims to provide effective collision strengths for the Mg V ion for a larger number of transitions and for a greater temperature range than previously available, using collision strength data that include contributions from resonances.
Methods. A 19-state Breit-Pauli R-matrix calculation was performed. The target states are represented by configuration interaction wavefunctions and consist of the 19 lowest LS states, having configurations 2s22p4, 2s2p5, 2p6, 2s22p33s, and 2s22p33p. These target states give rise to 37 fine-structure levels and 666 possible transitions. The effective collision strengths were calculated by averaging the electron collision strengths over a Maxwellian distribution of electron velocities.
Results. The non-zero effective collision strengths for transitions between the fine-structure levels are given for electron temperatures in the range = 3.0 - 7.0. Data for transitions among the 5 fine-structure levels arising from the 2s22p4 ground state configurations, seen in the UV range, are discussed in the paper, along with transitions in the EUV range – transitions from the ground state 3P levels to 2s2p5?3P levels. The 2s22p4?1D–2s2p5?1P transition is also noted. Data for the remaining transitions are available at the CDS.

Structural change in multipartite entanglement sharing: A random matrix approach

We study the typical entanglement properties of a system comprising two independent qubit environments interacting via a shuttling ancilla. The initial preparation of the environments is modeled using random matrix techniques. The entanglement measure used in our study is then averaged over many histories of randomly prepared environmental states. Under a Heisenberg interaction model, the average entanglement between the ancilla and one of the environments remains constant, regardless of the preparation of the latter and the details of the interaction. We also show that, upon suitable kinematic and dynamical changes in the ancillaenvironment subsystems, the entanglement-sharing structure undergoes abrupt modifications associated with a change in the multipartite entanglement class of the overall system's state. These results are invariant with respect to the randomized initial state of the environments.

Eigenvalues of the time-delay matrix in overlapping resonances

We discuss the properties of the lifetime or the time-delay matrix Q(E) for multichannel scattering, which is related to the scattering matrix S(E) by Q = i?S(dS†/dE). For two overlapping resonances occurring at energies E with widths G(? = 1, 2), with an energy-independent background, only two eigenvalues of Q(E) are proved to be different from zero and to show typical avoided-crossing behaviour. These eigenvalues are expressible in terms of the four resonance parameters (E , G) and a parameter representing the strength of the interaction of the resonances. An example of the strong and weak interaction in an overlapping double resonance is presented for the positronium negative ion. When more than two resonances overlap (? = 1, ..., N), no simple representation of each eigenvalue has been found. However, the formula for the trace of the Q-matrix leads to the expression d(E) = -?arctan[(G/2)/(E - E)] + d(E) for the eigenphase sum d(E) and the background eigenphase sum d(E), in agreement with the known form of the state density. The formulae presented in this paper are useful in a parameter fitting of overlapping resonances. © 2006 IOP Publishing Ltd.

Configuration-interaction effects in and intensity dependence of F- multiphoton detachment

Two- and three-photon detachment rates have been obtained for F- using several expansions in the R-matrix Floquet approach. These rates are compared with other theoretical and experimental results. The use of Hartree-Fock wavefunctions for the ground state of F with addition of continuum electrons does not lead to agreement with experiment for two- and three-photon detachment. By adding correlation terms, agreement with experiment and other theoretical results is improved considerably, demonstrating the importance of electron correlation effects. However, convergence with respect to the wavefunction expansion cannot be established, we also study the intensity dependence of multiphoton detachment rates for F- at the Nd-YAG frequency. Due to the ponderomotive shift the three-photon detachment channel closes at an intensity of 8.5 x 10(11) W cm(-2) and the influence of this channel closure on the multiphoton detachment peaks is illustrated by determining the heights of the excess-photon peaks obtained using a Gaussian laser pulse.