Focus in the structure of concepts in analytic discourse

The primary focus of this thesis was to find out what makes workable topic sentences different from inadequate ones. A group of topic sentences was collected from the author\u27s eight grade students and reviewed

Discovery of AMG 925, a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3

We describe the structural optimization of a lead compound <b>1</b> that exhibits dual inhibitory activities against FLT3 and CDK4. A series of pyrido­[4′,3′:4,5]­pyrrolo­[2,3-<i>d</i>]­pyrimidine derivatives was synthesized, and SAR analysis, using cell-based assays, led to the discovery of <b>28</b> (<b>AMG 925</b>), a potent and orally bioavailable dual inhibitor of CDK4 and FLT3, including many FLT3 mutants reported to date. Compound <b>28</b> inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb⁺) and U937 (FLT3^WT) and induced cell death in MOLM13 (FLT3^ITD) and even in MOLM13 (FLT3^ITD, D835Y), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, compound <b>28</b> leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation

Search for pair-produced vector-like B quarks in proton-proton collisions at s\sqrt{s} = 8 TeV

A search for the production of a heavy B quark, having electric charge -1/3 and vector couplings to W, Z, and H bosons, is carried out using proton-proton collision data recorded at the CERN LHC by the CMS experiment, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The B quark is assumed to be pair-produced and to decay in one of three ways: to tW, bZ, or bH. The search is carried out in final states with one, two, and more than two charged leptons, as well as in fully hadronic final states. Each of the channels in the exclusive final-state topologies is designed to be sensitive to specific combinations of the B quark-antiquark pair decays. The observed event yields are found to be consistent with the standard model expectations in all the final states studied. A statistical combination of these results is performed and upper limits are set on the cross section of the strongly produced B quark-antiquark pairs as a function of the B quark mass. Lower limits on the B quark mass between 740 and 900 GeV are set at a 95% confidence level, depending on the values of the branching fractions of the B quark to tW, bZ, and bH. Overall, these limits are the most stringent to date