Electron-phonon coupling and phonon self-energy in MgB2_2: do we really understand MgB2_2 Raman spectra ?

We consider a model Hamiltonian fitted on the ab-initio band structure to describe the electron-phonon coupling between the electronic $\sigma-$bands and the phonon E$_{2g}$ mode in MgB$_2$. The model allows for analytical calculations and numerical treatments using very large k-point grids. We calculate the phonon self-energy of the E$_{2g}$ mode along two high symmetry directions in the Brillouin zone. We demonstrate that the contribution of the $\sigma$ bands to the Raman linewidth of the E$_{2g}$ mode via the electron-phonon coupling is zero. As a consequence the large resonance seen in Raman experiments cannot be interpreted as originated from the $E_{2g}$ mode at $\Gamma$. We examine in details the effects of Fermi surface singularities in the phonon spectrum and linewidth and we determine the magnitude of finite temperature effects in the the phonon self-energy. From our findings we suggest several possible effects which might be responsible for the MgB$_2$ Raman spectra.Comment: 10 pages, 9 figure

Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis

Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis-infected monocytes degraded collagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein-coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis-infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network-dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration

Total energy global optimizations using non orthogonal localized orbitals

An energy functional for orbital based $O(N)$ calculations is proposed, which depends on a number of non orthogonal, localized orbitals larger than the number of occupied states in the system, and on a parameter, the electronic chemical potential, determining the number of electrons. We show that the minimization of the functional with respect to overlapping localized orbitals can be performed so as to attain directly the ground state energy, without being trapped at local minima. The present approach overcomes the multiple minima problem present within the original formulation of orbital based $O(N)$ methods; it therefore makes it possible to perform $O(N)$ calculations for an arbitrary system, without including any information about the system bonding properties in the construction of the input wavefunctions. Furthermore, while retaining the same computational cost as the original approach, our formulation allows one to improve the variational estimate of the ground state energy, and the energy conservation during a molecular dynamics run. Several numerical examples for surfaces, bulk systems and clusters are presented and discussed.Comment: 24 pages, RevTex file, 5 figures available upon reques

First principles calculation of vibrational Raman spectra in large systems: signature of small rings in crystalline SiO2

We present an approach for the efficient calculation of vibrational Raman intensities in periodic systems within density functional theory. The Raman intensities are computed from the second order derivative of the electronic density matrix with respect to a uniform electric field. In contrast to previous approaches, the computational effort required by our method for the evaluation of the intensities is negligible compared to that required for the calculation of vibrational frequencies. As a first application, we study the signature of 3- and 4-membered rings in the the Raman spectra of several polymorphs of SiO2, including a zeolite having 102 atoms per unit cell.Comment: 4 pages, 2 figures, revtex4 Minor corrections; accepted in Phys. Rev. Let

All-electron magnetic response with pseudopotentials: NMR chemical shifts

A theory for the ab initio calculation of all-electron NMR chemical shifts in insulators using pseudopotentials is presented. It is formulated for both finite and infinitely periodic systems and is based on an extension to the Projector Augmented Wave approach of Bloechl [P. E. Bloechl, Phys. Rev. B 50, 17953 (1994)] and the method of Mauri et al [F. Mauri, B.G. Pfrommer, and S.G. Louie, Phys. Rev. Lett. 77, 5300 (1996)]. The theory is successfully validated for molecules by comparison with a selection of quantum chemical results, and in periodic systems by comparison with plane-wave all-electron results for diamond.Comment: 25 pages, 4 tables, submitted to Physical Review

Acceleration Schemes for Ab-Initio Molecular Dynamics and Electronic Structure Calculations

We study the convergence and the stability of fictitious dynamical methods for electrons. First, we show that a particular damped second-order dynamics has a much faster rate of convergence to the ground-state than first-order steepest descent algorithms while retaining their numerical cost per time step. Our damped dynamics has efficiency comparable to that of conjugate gradient methods in typical electronic minimization problems. Then, we analyse the factors that limit the size of the integration time step in approaches based on plane-wave expansions. The maximum allowed time step is dictated by the highest frequency components of the fictitious electronic dynamics. These can result either from the large wavevector components of the kinetic energy or from the small wavevector components of the Coulomb potential giving rise to the so called {\it charge sloshing} problem. We show how to eliminate large wavevector instabilities by adopting a preconditioning scheme that is implemented here for the first-time in the context of Car-Parrinello ab-initio molecular dynamics simulations of the ionic motion. We also show how to solve the charge-sloshing problem when this is present. We substantiate our theoretical analysis with numerical tests on a number of different silicon and carbon systems having both insulating and metallic character.Comment: RevTex, 9 figures available upon request, to appear in Phys. Rev.

Cellulose production is coupled to sensing of the pyrimidine biosynthetic pathway via c-di-GMP production by the DgcQ protein of Escherichia coli

Production of cellulose, a stress response-mediated process in enterobacteria, is modulated in Escherichia coli by the activity of the two pyrimidine nucleotide biosynthetic pathways, namely, the de novo biosynthetic pathway and the salvage pathway, which relies on the environmental availability of pyrimidine nitrogenous bases. We had previously reported that prevalence of the salvage over the de novo pathway triggers cellulose production via synthesis of the second messenger c-di-GMP by the DgcQ (YedQ) diguanylate cyclase. In this work, we show that DgcQ enzymatic activity is enhanced by UTP, whilst being inhibited by N-carbamoyl-aspartate, an intermediate of the de novo pathway. Thus, direct allosteric control by these ligands allows full DgcQ activity exclusively in cells actively synthesizing pyrimidine nucleotides via the salvage pathway. Inhibition of DgcQ activity by N-carbamoyl-aspartate appears to be favoured by protein-protein interaction between DgcQ and PyrB, a subunit of aspartate transcarbamylase, which synthesizes N-carbamoyl-aspartate. Our results suggest that availability of pyrimidine bases might be sensed, somehow paradoxically, as an environmental stress by E. coli. We hypothesize that this link might have evolved since stress events, leading to extensive DNA/RNA degradation or lysis of neighbouring cells, can result in increased pyrimidine concentrations and activation of the salvage pathway

Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases

The central nervous system is characterized by a high content of sphingolipids and by a high diversity in terms of different structures. Stage- and cell-specific sphingolipid metabolism and expression are crucial for brain development and maintenance toward adult age. On the other hand, deep dysregulation of sphingolipid metabolism, leading to altered sphingolipid pattern, is associated with the majority of neurological and neurodegenerative diseases, even those totally lacking a common etiological background. Thus, sphingolipid metabolism has always been regarded as a promising pharmacological target for the treatment of brain disorders. However, any therapeutic hypothesis applied to complex amphipathic sphingolipids, components of cellular membranes, has so far failed probably because of the high regional complexity and specificity of the different biological roles of these structures. Simpler sphingosine-based lipids, including ceramide and sphingosine 1-phosphate, are important regulators of brain homeostasis, and, thanks to the relative simplicity of their metabolic network, they seem a feasible druggable target for the treatment of brain diseases. The enzymes involved in the control of the levels of bioactive sphingoids, as well as the receptors engaged by these molecules, have increasingly allured pharmacologists and clinicians, and eventually fingolimod, a functional antagonist of sphingosine 1-phosphate receptors with immunomodulatory properties, was approved for the therapy of relapsing-remitting multiple sclerosis. Considering the importance of neuroinflammation in many other brain diseases, we would expect an extension of the use of such analogs for the treatment of other ailments in the future. Nevertheless, many aspects other than neuroinflammation are regulated by bioactive sphingoids in healthy brain and dysregulated in brain disease. In this review, we are addressing the multifaceted possibility to address the metabolism and biology of bioactive sphingosine 1-phosphate as novel targets for the development of therapeutic paradigms and the discovery of new drugs

Approximating Clustering of Fingerprint Vectors with Missing Values

The problem of clustering fingerprint vectors is an interesting problem in Computational Biology that has been proposed in (Figureroa et al. 2004). In this paper we show some improvements in closing the gaps between the known lower bounds and upper bounds on the approximability of some variants of the biological problem. Namely we are able to prove that the problem is APX-hard even when each fingerprint contains only two unknown position. Moreover we have studied some variants of the orginal problem, and we give two 2-approximation algorithm for the IECMV and OECMV problems when the number of unknown entries for each vector is at most a constant.Comment: 13 pages, 4 figure

Ab Initio Molecular Dynamics on the Electronic Boltzmann Equilibrium Distribution

We prove that for a combined system of classical and quantum particles, it is possible to write a dynamics for the classical particles that incorporates in a natural way the Boltzmann equilibrium population for the quantum subsystem. In addition, these molecular dynamics do not need to assume that the electrons immediately follow the nuclear motion (in contrast to any adiabatic approach), and do not present problems in the presence of crossing points between different potential energy surfaces (conical intersections or spin-crossings). A practical application of this molecular dynamics to study the effect of temperature in molecular systems presenting (nearly) degenerate states - such as the avoided crossing in the ring-closure process of ozone - is presented.Comment: published in New J. Phy