Correlated ab-initio calculations for ground-state properties of II-VI semiconductors

Correlated ab-initio ground-state calculations, using relativistic energy-consistent pseudopotentials, are performed for six II-VI semiconductors. Valence ($ns,np$) correlations are evaluated using the coupled cluster approach with single and double excitations. An incremental scheme is applied based on correlation contributions of localized bond orbitals and of pairs and triples of such bonds. In view of the high polarity of the bonds in II-VI compounds, we examine both, ionic and covalent embedding schemes for the calculation of individual bond increments. Also, a partitioning of the correlation energy according to local ionic increments is tested. Core-valence ($nsp,(n-1)d$) correlation effects are taken into account via a core-polarization potential. Combining the results at the correlated level with corresponding Hartree-Fock data we recover about 94% of the experimental cohesive energies; lattice constants are accurate to \sim 1%; bulk moduli are on average 10% too large compared with experiment.Comment: 10 pages, twocolumn, RevTex, 3 figures, accepted Phys. Rev.

Resonant inelastic soft-x-ray scattering spectra at the N1s and C1s edges of poly(pyridine-2,5-diyl)

Resonant inelastic scattering measurements of poly(pyridine-2,5-diyl) have been performed at the N1s and C1s edges using synchrotron radiation. For comparison, molecular orbital calculations of the spectra have been carried out with the repeat unit as a model molecule of the polymer chain. The resonant emission spectra show depletion of the p electron bands which is consistent with symmetry selection and momentum conservation rules. The depletion is most obvious in the resonant inelastic scattering spectra of carbon while the nitrogen spectra are dominated by lone pair n orbital emission of s symmetry and are less excitation energy dependent. By comparing the measurements to calculations an isomeric dependence of the resonant spectra is found giving preference to two of the four possible isomers in the polymer.Comment: 6 pages, 3 figures, http://www.sciencedirect.com/science/article/pii/S036820489800354

The electronic structure of poly(pyridine-2,5-diyl) investigated by soft x-ray absorption and emission spectroscopies

The electronic structure of the poly-pyridine conjugated polymer has been investigated by resonant and nonresonant inelastic X-ray scattering and X-ray absorption spectroscopies using synchrotron radiation. The measurements were made for both the carbon and nitrogen contents of the polymer. The analysis of the spectra has been carried out in comparison with molecular orbital calculations taking the repeat-unit cell as a model molecule of the polymer chain. The simulations indicate no significant differences in the absorption and in the non-resonant X-ray scattering spectra for the different isomeric geometries, while some isomeric dependence of the resonant spectra is predicted. The resonant emission spectra show depletion of the {\pi} electron bands in line with symmetry selection and momentum conservation rules. The effect is most vizual for the carbon spectra; the nitrogen spectra are dominated by lone pair n orbital emission of {\sigma} symmetry and are less frequency dependent.Comment: 11 pages, 7 figures, 1 table, http://www.sciencedirect.com/science/article/pii/S030101049800262

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.info:eu-repo/semantics/publishedVersio

TBP Binding-Induced Folding of the Glucocorticoid Receptor AF1 Domain Facilitates Its Interaction with Steroid Receptor Coactivator-1

The precise mechanism by which glucocorticoid receptor (GR) regulates the transcription of its target genes is largely unknown. This is, in part, due to the lack of structural and functional information about GR's N-terminal activation function domain, AF1. Like many steroid hormone receptors (SHRs), the GR AF1 exists in an intrinsically disordered (ID) conformation or an ensemble of conformers that collectively appears to be unstructured. The GR AF1 is known to recruit several coregulatory proteins, including those from the basal transcriptional machinery, e.g., TATA box binding protein (TBP) that forms the basis for the multiprotein transcription initiation complex. However, the precise mechanism of this process is unknown. We have earlier shown that conditional folding of the GR AF1 is the key for its interactions with critical coactivator proteins. We hypothesize that binding of TBP to AF1 results in the structural rearrangement of the ID AF1 domain such that its surfaces become easily accessible for interaction with other coactivators. To test this hypothesis, we determined whether TBP binding-induced structure formation in the GR AF1 facilitates its interaction with steroid receptor coactivator-1 (SRC-1), a critical coactivator that is important for GR-mediated transcriptional activity. Our data show that stoichiometric binding of TBP induces significantly higher helical content at the expense of random coil configuration in the GR AF1. Further, we found that this induced AF1 conformation facilitates its interaction with SRC-1, and subsequent AF1-mediated transcriptional activity. Our results may provide a potential mechanism through which GR and by large other SHRs may regulate the expression of the GR-target genes

Calculation of molecular thermochemical data and their availability in databases

Thermodynamic properties of molecules can be obtained by experiment, by statistical mechanics in conjunction with electronic structure theory and by empirical rules like group additivity. The latter two methods are briefly re-viewed in this chapter. The overview of electronic structure methods is intended for readers less experienced in electronic structure theory and focuses on concepts without going into mathematical details. This is followed by a brief description of group additivity schemes; finally, an overview of databases listing reliable thermochemical data is given

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Development of a chemical probe against NUDT15

The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues