Nicotinic Acetylcholine Receptor Efficacy And Pharmacological Properties Of 3-(Substituted Phenyl)-2β-Substituted Tropanes

There is a need for different and better aids to tobacco product use cessation. Useful smoking cessation aids, bupropion (2) and varenicline (3), share some chemical features with 3-phenyltropanes (4), which have promise in cocaine dependence therapy. Here we report studies to generate and characterize pharmacodynamic features of 3-phenyltropane analogues. These studies extend our work on the multiple molecular target model for aids to smoking cessation. We identified several new 3-phenyltropane analogues that are superior to 2 in inhibition of dopamine, norepinephrine, and sometimes serotonin reuptake. All of these ligands also act as inhibitors of nicotinic acetylcholine receptor (nAChR) function with a selectivity profile that favors, like 2, inhibition of α3β4*-nAChR. Many of these ligands also block acute effects of nicotine-induced antinociception, locomotor activity, and hypothermia. Importantly, all except one of the analogues tested have better potencies in inhibition of nicotine conditioned place preference than 2. We have identified new compounds that have utility as research tools and possible promise for treatment of nicotine dependence. © 2010 American Chemical Society

The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer

Introduction Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. Methods Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and â\u80\u9cbestâ\u80\u9d stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. Results The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. Conclusions The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts

Search for supersymmetric partners of electrons and muons in proton–proton collisions at s=13TeV

A search for direct production of the supersymmetric (SUSY) partners of electrons or muons is presented in final states with two opposite-charge, same-flavour leptons (electrons and muons), no jets, and large missing transverse momentum. The data sample corresponds to an integrated luminosity of 35.9 fb−1 of proton–proton collisions at s=13TeV, collected with the CMS detector at the LHC in 2016. The search uses the MT2 variable, which generalises the transverse mass for systems with two invisible objects and provides a discrimination against standard model backgrounds containing W bosons. The observed yields are consistent with the expectations from the standard model. The search is interpreted in the context of simplified SUSY models and probes slepton masses up to approximately 290, 400, and 450 GeV, assuming right-handed only, left-handed only, and both right- and left-handed sleptons (mass degenerate selectrons and smuons), and a massless lightest supersymmetric particle. Limits are also set on selectrons and smuons separately. These limits show an improvement on the existing limits of approximately 150 GeV.0info:eu-repo/semantics/publishe

Search for resonant pair production of Higgs bosons decaying to bottom quark-antiquark pairs in proton-proton collisions at 13 TeV

A search for a narrow-width resonance decaying into two Higgs bosons, each decaying into a bottom quark-antiquark pair, is presented. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 35.9 fb$^{-1}$ at $\sqrt{s}=$ 13 TeV recorded by the CMS detector at the LHC. No evidence for such a signal is observed. Upper limits are set on the product of the production cross section for the resonance and the branching fraction for the selected decay mode in the resonance mass range from 260 to 1200 GeV