Photoemission Spectra from the Extended Koopman's Theorem, Revisited.

The Extended Koopman's Theorem (EKT) provides a straightforward way to compute charged excitations from any level of theory. In this work we make the link with the many-body effective energy theory (MEET) that we derived to calculate the spectral function, which is directly related to photoemission spectra. In particular, we show that at its lowest level of approximation the MEET removal and addition energies correspond to the so-called diagonal approximation of the EKT. Thanks to this link, the EKT and the MEET can benefit from mutual insight. In particular, one can readily extend the EKT to calculate the full spectral function, and choose a more optimal basis set for the MEET by solving the EKT secular equation. We illustrate these findings with the examples of the Hubbard dimer and bulk silicon.

Accurate nonrelativistic ground-state energies of 3d transition metal atoms.

We present accurate nonrelativistic ground-state energies of the transition metal atoms of the 3d series calculated with Fixed-Node Diffusion Monte Carlo (FN-DMC). Selected multi-determinantal expansions obtained with the CIPSI (Configuration Interaction using a Perturbative Selection made Iteratively) method and including the most prominent determinants of the full configuration interaction expansion are used as trial wavefunctions. Using a maximum of a few tens of thousands determinants, fixed-node errors on total DMC energies are found to be greatly reduced for some atoms with respect to those obtained with Hartree-Fock nodes. To the best of our knowledge, the FN-DMC/(CIPSI nodes) ground-state energies presented here are the lowest variational total energies reported so far. They differ from the recently recommended non-variational values of McCarthy and Thakkar [J. Chem. Phys. 136, 054107 (2012)] only by a few percents of the correlation energy. Thanks to the variational property of FN-DMC total energies, our results provide exact lower bounds for the absolute value of all-electron correlation energies, |Ec|.

Constitutive activation of JAK2 in mammary epithelium elevates Stat5 signalling, promotes alveologenesis and resistance to cell death, and contributes to tumourigenesis.

Signalling through the janus kinase (JAK)/signal transducer and activator of transcription (Stat) pathway is required at different stages of mammary gland development, and this pathway is frequently hyper-activated in cancer, including tumours of the breast. Stats 3, 5 and 6 have important roles in the differentiation and survival of mammary alveolar cells, but somewhat paradoxically, both Stat3 and 5 can have oncogenic activity in the mammary gland. Constitutive activation of JAK2 could be anticipated to result in hyper-activation of Stats 1, 3, 5 and 6 with concomitant cell transformation, although the outcome is difficult to envisage, particularly since Stats 3 and 5 play opposing roles in normal mammary gland development. Here, we show that expression of a constitutively active JAK2 mutant, JAK2 V617F, leads to hyper-activation of Stat5 in mammary epithelial cells (MECs), and transgenic mice expressing JAK2 V617F specifically in the mammary gland exhibit accelerated alveologenesis during pregnancy and delayed post-lactational regression. Overexpressing JAK2 V617F in MECs in vitro results in elevated proliferation and resistance to cell death. Furthermore, constitutively active JAK2 enhances anchorage-independent cell growth in the presence of a co-operating oncogene and accelerates tumourigenesis in a xenograft model. Taken together, our results provide insights into signalling downstream of constitutively active JAK2 and could be important for understanding the molecular mechanisms of breast tumourigenesis.

On the stability of Be3: a benchmark complete active space self-consistent field + averaged quadratic coupled cluster study.

The optimized geometries and binding energies for the linear and triangular isomers of the beryllium trimer have been obtained through benchmark multireference averaged quadratic coupled cluster (AQCC) calculations using very large complete active space SCF (CASSCF) references (12 active electrons in 13 and 14 orbitals). Geometries were optimized with the cc-pV5Z basis, while the binding energies (including counterpoise correction) were obtained with the significantly larger aug-cc-pV5Z basis set. The binding energies (27.3 and 16.3 kcal/mol for the equilateral and linear isomers, respectively) are larger than the previous full CI benchmark values, while the corresponding Be-Be equilibrium distances of 4.101 and 4.088 a.u. are smaller. In view of the near-size consistency character of the CASSCF + AQCC method, the fact that all 12 electrons are fully correlated, the active reference space includes 14 orbitals, and the very large basis set used here, we propose to consider these results as reference data for Be(3). Using the electron pair localization function obtained at the CASSCF(12,15) level, it is clearly illustrated that the 2p orbitals lying in the molecular plane play a dominant role in the bonding pattern for the equilateral isomer.

The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK.

GPR55 is an orphan G protein-coupled receptor that may be engaged by some lipid ligands such as lysophosphatidylinositol and cannabinoid-type compounds. Very little is known about its expression pattern and physio-pathological relevance, and its pharmacology and signaling are still rather controversial. Here we analyzed the expression and function of GPR55 in cancer cells. Our data show that GPR55 expression in human tumors from different origins correlates with their aggressiveness. Moreover, GPR55 promotes cancer cell proliferation, both in cell cultures and in xenografted mice, through the overactivation of the extracellular signal-regulated kinase cascade. These findings reveal the importance of GPR55 in human cancer, and suggest that it could constitute a new biomarker and therapeutic target in oncology.

JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells.

It has been recently shown that cannabinoids, the active components of marijuana and their derivatives, inhibit cell cycle progression of human breast cancer cells. Here we studied the mechanism of Delta(9)-tetrahydrocannabinol (THC) antiproliferative action in these cells, and show that it involves the modulation of JunD, a member of the AP-1 transcription factor family. THC activates JunD both by upregulating gene expression and by translocating the protein to the nuclear compartment, and these events are accompanied by a decrease in cell proliferation. Of interest, neither JunD activation nor proliferation inhibition was observed in human non-tumour mammary epithelial cells exposed to THC. We confirmed the importance of JunD in THC action by RNA interference and genetic ablation. Thus, in both JunD-silenced human breast cancer cells and JunD knockout mice-derived immortalized fibroblasts, the antiproliferative effect exerted by THC was significantly diminished. Gene array and siRNA experiments support that the cyclin-dependent kinase inhibitor p27 and the tumour suppressor gene testin are candidate JunD targets in cannabinoid action. In addition, our data suggest that the stress-regulated protein p8 participates in THC antiproliferative action in a JunD-independent manner. In summary, this is the first report showing not only that cannabinoids regulate JunD but, more generally, that JunD activation reduces the proliferation of cancer cells, which points to a new target to inhibit breast cancer progression.

Diffusion monte carlo methods with a fixed number of walkers

In this paper we discuss various aspects of diffusion Monte Carlo methods using a fixed number of walkers. First, a rigorous proof of the divergence of pure diffusion Monte Carlo (PDMC) methods (DMC without branching in which the weights are carried along trajectories) is given. Second, a bias-free Monte Carlo method combining DMC and PDMC approaches, and based on a minimal stochastic reconfiguration of the population, is discussed. Finally, some illustrative calculations for a system of coupled quantum rotators are presented.