Elementary landscape decomposition of the 0-1 unconstrained quadratic optimization

Journal of Heuristics, 19(4), pp.711-728Landscapes’ theory provides a formal framework in which combinatorial optimization problems can be theoretically characterized as a sum of an especial kind of landscape called elementary landscape. The elementary landscape decomposition of a combinatorial optimization problem is a useful tool for understanding the problem. Such decomposition provides an additional knowledge on the problem that can be exploited to explain the behavior of some existing algorithms when they are applied to the problem or to create new search methods for the problem. In this paper we analyze the 0-1 Unconstrained Quadratic Optimization from the point of view of landscapes’ theory. We prove that the problem can be written as the sum of two elementary components and we give the exact expressions for these components. We use the landscape decomposition to compute autocorrelation measures of the problem, and show some practical applications of the decomposition.Spanish Ministry of Sci- ence and Innovation and FEDER under contract TIN2008-06491-C04-01 (the M∗ project). Andalusian Government under contract P07-TIC-03044 (DIRICOM project)

Das Zusammenspiel zwischen Wasserstoffbrücken und Präorganisation in der Entwicklung von selbstassemblierenden Systemen

Cooperative pi–pi interactions and H-bonding are frequently exploited in supramolecular polymerization; however, close scrutiny of their mutual interplay has been largely unexplored. Herein, we compare the self-assembly behavior of a series of C2- and C3-symmetrical oligophenyleneethynylenes differing in their amide topology (N- or C-centered). This subtle structural modification brings about drastic changes in their photophysical and supramolecular properties, highlighting the reciprocal impact of H-bonding vs. preorganization on the evolution and final outcome of supramolecular systems.Kooperative pi-pi-Wechselwirkungen und Wasserstoffbrückenbindungen werden häufig in supramolekularen Polymerisationen genutzt. Nähere Untersuchungen zu deren Zusammenspiel wurden in der Vergangenheit jedoch weitestgehend vernachlässigt. In dieser Arbeit wird das Aggregationsverhalten einer Reihe von C2- und C3- symmetrischen Oligophenylenethinylenen, die sich in der Topologie des Amids (N- oder C-zentriert) unterscheiden, verglichen. Diese geringe strukturelle Veränderung bewirkt drastische Unterschiede in den photophysikalischen und supramolekularen Eigenschaften. Somit wird der gegenseitige Einfluss von Wasserstoffbrückenbindungen und geometrischer Präorganisation auf den Assemblierungsprozess und dessen Endresultat in supramolekularen Systemen hervorgehoben

A SNP in Steroid Receptor Coactivator-1 Disrupts a GSK3β Phosphorylation Site and Is Associated with Altered Tamoxifen Response in Bone

The coregulator steroid receptor coactivator (SRC)-1 increases transcriptional activity of the estrogen receptor (ER) in a number of tissues including bone. Mice deficient in SRC-1 are osteopenic and display skeletal resistance to estrogen treatment. SRC-1 is also known to modulate effects of selective ER modulators like tamoxifen. We hypothesized that single nucleotide polymorphisms (SNP) in SRC-1 may impact estrogen and/or tamoxifen action. Because the only nonsynonymous SNP in SRC-1 (rs1804645; P1272S) is located in an activation domain, it was examined for effects on estrogen and tamoxifen action. SRC-1 P1272S showed a decreased ability to coactivate ER compared with wild-type SRC-1 in multiple cell lines. Paradoxically, SRC-1 P1272S had an increased protein half-life. The Pro to Ser change disrupts a putative glycogen synthase 3 (GSK3)β phosphorylation site that was confirmed by in vitro kinase assays. Finally, knockdown of GSK3β increased SRC-1 protein levels, mimicking the loss of phosphorylation at P1272S. These findings are similar to the GSK3β-mediated phospho-ubiquitin clock previously described for the related coregulator SRC-3. To assess the potential clinical significance of this SNP, we examined whether there was an association between SRC-1 P1272S and selective ER modulators response in bone. SRC-1 P1272S was associated with a decrease in hip and lumbar bone mineral density in women receiving tamoxifen treatment, supporting our in vitro findings for decreased ER coactivation. In summary, we have identified a functional genetic variant of SRC-1 with decreased activity, resulting, at least in part, from the loss of a GSK3β phosphorylation site, which was also associated with decreased bone mineral density in tamoxifen-treated women