Synergies between operations research and data mining: The emerging use of multi-objective approaches

Operations research and data mining already have a long-established common history. Indeed, with the growing size of databases and the amount of data available, data mining has become crucial in modern science and industry. Data mining problems raise interesting challenges for several research domains, and in particular for operations research, as very large search spaces of solutions need to be explored. Hence, many operations research methods have been proposed to deal with such challenging problems. But the relationships between these two domains are not limited to these natural applications of operations research approaches. The counterpart is also important to consider, since data mining approaches have also been applied to improve operations research techniques. The aim of this article is to highlight the interplay between these two research disciplines. A particular emphasis will be placed on the emerging theme of applying multi-objective approaches in this context.     

Synthesis of polylactide/clay nanocomposites by in situ intercalative polymerization in supercritical carbon dioxide

Polylactide (PLA)/clay nanocomposites have been prepared by in situ ring-opening polymerization in supercritical carbon dioxide. Depending on the type of organoclay used, polylactide chains can be grafted onto the clay surface, leading to an exfoliated morphology. Nanocomposites with high clay contents (30-50 wt.%), called masterbatches, have also been successfully prepared and were recovered as fine powders thanks to the unique properties of the supercritical fluid. Dilution of these masterbatches into commercial l-polylactide by melt blending has led to essentially exfoliated nanocomposites containing 3 wt.% of clay. The mechanical properties of these materials have been assessed by flexion and impact tests. Significant improvements of stiffness and toughness have been observed for the PLA/clay nanocomposites compared to the pure matrix, together with improved impact resistance.     

Computational fragment-based drug design to explore the hydrophobic sub-pocket of the mitotic kinesin Eg5 allosteric binding site

Eg5, a mitotic kinesin exclusively involved in the formation and function of the mitotic spindle has attracted interest as an anticancer drug target. Eg5 is co-crystallized with several inhibitors bound to its allosteric binding pocket. Each of these occupies a pocket formed by loop 5/helix α2 (L5/α2). Recently designed inhibitors additionally occupy a hydrophobic pocket of this site. The goal of the present study was to explore this hydrophobic pocket with our MED-SuMo fragment-based protocol, and thus discover novel chemical structures that might bind as inhibitors. The MED-SuMo software is able to compare and superimpose similar interaction surfaces upon the whole protein data bank (PDB). In a fragment-based protocol, MED-SuMo retrieves MED-Portions that encode protein-fragment binding sites and are derived from cross-mining protein-ligand structures with libraries of small molecules. Furthermore we have excluded intra-family MED-Portions derived from Eg5 ligands that occupy the hydrophobic pocket and predicted new potential ligands by hybridization that would fill simultaneously both pockets. Some of the latter having original scaffolds and substituents in the hydrophobic pocket are identified in libraries of synthetically accessible molecules by the MED-Search software. Ksenia Oguievetskaia and Laetitia Martin-Chanas contributed equally to this work.     

Measurement of the Bs(0) lifetime using semileptonic decays

We report a measurement of the Bs(0) lifetime in the semileptonic decay channel Bs(0) --> Ds- mu+ nuX (and its charge conjugate), using approximately 0.4 fb(-1) of data collected with the D0 detector during 2002-2004. Using 5176 reconstructed Ds- mu+ signal events, we have measured the Bs(0) lifetime to be tau(Bs(0))=1.398+/-0.044(stat)(-0.025)(+0.028)(syst) ps. This is the most precise measurement of the Bs(0) lifetime to date.     

Search for resonant second generation slepton production at the Fermilab Tevatron

We present a search for supersymmetry in the R-parity violating resonant production and decay of smuons and muon sneutrinos in the channels mu-->chi(1)(0)mu, mu-->chi(2,3,4)(0)mu, and nu(mu)-->chi(1,2)(+/-)mu. We analyzed 0.38 fb(-1) of integrated luminosity collected between April 2002 and August 2004 with the D0 detector at the Fermilab Tevatron Collider. The observed number of events is in agreement with the standard model expectation, and we calculate 95% C.L. limits on the slepton production cross section times branching fraction to gaugino plus muon, as a function of slepton and gaugino masses. In the framework of minimal supergravity, we set limits on the coupling parameter lambda(211)('), extending significantly previous results obtained in Run I of the Tevatron and at the CERN LEP collider.     

KRAS Binders Hidden in Nature

Natural products have proven to be a rich source of molecular architectures for drugs. Here, an integrated approach to natural product screening is proposed, which uncovered eight new natural product scaffolds for KRAS—the most frequently mutated oncogenic driver in human cancers, which has remained thus far undrugged. The approach combines aspects of virtual screening, fragment-based screening, structure-activity relationships (SAR) by NMR, and structure-based drug discovery to overcome the limitations in traditional natural product approaches. By using our approach, a new “snugness of fit” scoring function and the first crystal-soaking system of the active form of KRAS^G12D, the protein–ligand X-ray structures of a tricyclic indolopyrrole fungal alkaloid and an indoloisoquinolinone have been successfully elucidated. The natural product KRAS hits discovered provide fruitful ground for the optimization of highly potent natural-product-based inhibitors of the active form of oncogenic RAS. This integrated approach for screening natural products also holds promise for other “undruggable” targets.     

First study of the radiation-amplitude zero in Wgamma production and limits on anomalous WWgamma couplings at sqrt[s]=1.96 TeV

We present results from a study of pp-->Wgamma+X events utilizing data corresponding to 0.7 fb{-1} of integrated luminosity at sqrt[s]=1.96 TeV collected by the D0 detector at the Fermilab Tevatron Collider. We set limits on anomalous WWgamma couplings at the 95% C.L. The one-dimensional 95% C.L. limits are 0.49相似文献   

Precise measurement of the top-quark mass from lepton + jets events

We measure the mass of the top quark using top-quark pair candidate events in the lepton+jets channel from data corresponding to 1 fb;{-1} of integrated luminosity collected by the D0 experiment at the Fermilab Tevatron collider. We use a likelihood technique that reduces the jet energy scale uncertainty by combining an in situ jet energy calibration with the independent constraint on the jet energy scale (JES) from the calibration derived using photon+jets and dijet samples. We find the mass of the top quark to be 171.5+/-1.8(stat.+JES)+/-1.1(syst.) GeV.     

Measurement of the tt[over] production cross section in pp[over] collisions at sqrt(s)=1.96 TeV

We measure the tt[over] production cross section in pp[over] collisions at sqrt(s)=1.96 TeV in the lepton + jets channel. Two complementary methods discriminate between signal and background: b tagging and a kinematic likelihood discriminant. Based on 0.9 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider, we measure sigma(tt[over])=7.62+/-0.85 pb, assuming the current world average m(t)=172.6 GeV. We compare our cross section measurement with theory predictions to determine a value for the top-quark mass of 170+/-7 GeV.     

The pattern of methylcyclopentane and n-hexane reactions on Rh/Al2O3 in catalytic runs of various length

Methylcyclopentane and n-hexane were reacted on a Rh/alumina catalyst in a closed-loop reactor. The product composition was analyzed at different moments of the run. In spite of a slow self-deactivation, the distribution of primary products and the depth of hydrogenolysis showed hardly any dependence on the sampling time in the conversion range of 1.5% and 50%. This is discussed in terms of accumulation of hydrocarbonaceous residues and the low readsorption probability of primary products on rhodium surface.