The idea of an externally corrected singles and doubles coupled cluster (CCSD) method using an independent source for connected triples and quadruples is generalized to open-shell high-spin states and implemented within the framework of the unitary group based CCSD method. New and more efficient programs are designed to perform cluster analysis of ab initio wave functions and to calculate corrections to standard CCSD equations. The method is applied to describe a single bond breaking of OH in the Π2 state, using both double zeta (DZ) and DZ plus polarization (DZP) basis sets. Both full or limited configuration interaction (CI) within small and carefully chosen active spaces (AS) and complete AS self-consistent-field (CASSCF) wave functions are employed as external sources for triple and quadruple corrections. It is shown that the CI or CASSCF corrected CCSD method can effectively account for higher than pair clusters while requiring only a small additional computational effort over that of the standard CCSD approach.

Perturbatively selected configuration interaction (PSCI) is used as a source of higher than pair clusters in the externally corrected coupled cluster method with singles and doubles (ecCCSD). This significantly decreases the dimension of the standard multireference (MR) CISD that is employed by the so-called reduced MR (RMR) CCSD method, thus enabling the use of relatively large active spaces. The performance of the proposed PSCI CCSD method is illustrated by considering the ground state potential energy curves of the HF molecule using DZP and cc-pVTZ basis sets (breaking of a single bond), and of the N2 molecule using a TZ basis set (breaking of a triple bond). It is shown that notwithstanding a large reduction in the dimension of the external source, the accuracy of the resulting ecCCSD energies is almost the same as that obtained when correcting with the full MR CISD wave function.

Ž .The idea of correcting the single-reference coupled cluster CC method truncated at the Ž . pair cluster level CCSD by means of three-and four-body corrections coming from w Ž . some external source J. Paldus, J. Cızek, and M. Takahashi, Phys. Rev. A 30, 2193 1984 ;ˇŽ .x J. Paldus and J. Planelles, Theor. Chim. Acta 89, 13 1994 is explored at the ab initio level using the CAS SCF wave functions as a source of the triply and quadruply excited Ž . cluster amplitudes. The method referred to as CCSD᎐CAS is applied to three simple systems based on minimum basis set and double-zeta models of the BH molecule, in Ž . Ž . which we continuously vary, respectively, i the two electron repulsion, ii the electronic Ž . charge, and iii the internuclear separation in order to explore the performance of the method in quasi-degenerate situations. Both the energies and the higher than pair cluster amplitudes are compared with the corresponding exact full configuration interaction Ž . FCI results. The relative importance of the three-and four-body cluster components is also examined. In all cases considered, the CCSD᎐CAS method provides the best result.

Nearly half of the human genome is made of transposable elements (TEs) whose activity continues to impact its structure and function. Among them, Long INterspersed Element class 1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed and mobilized in different cancers, generating mutagenic insertions that could affect tumor malignancy. Tumor suppressor microRNAs are ∼22nt RNAs that post-transcriptionally regulate oncogene expression and are frequently downregulated in cancer. Here we explore whether they also influence L1 mobilization. We show that downregulation of let-7 correlates with accumulation of L1 insertions in human lung cancer. Furthermore, we demonstrate that let-7 binds to the L1 mRNA and impairs the translation of the second L1-encoded protein, ORF2p, reducing its mobilization. Overall, our data reveals that let-7, one of the most relevant microRNAs, maintains somatic genome integrity by restricting L1 retrotransposition.