The top quark is the heaviest known elementary particle, with a mass about 40 times larger than the mass of its isospin partner, the bottom quark. It decays almost 100% of the time to a W boson and a ...bottom quark. Using top-antitop pairs at the Tevatron proton-antiproton collider, the CDF and D0 Collaborations have measured the top quark's mass in different final states for integrated luminosities of up to 5.8 fb super(-1). This paper reports on a combination of these measurements that results in a more precise value of the mass than any individual decay channel can provide. It describes the treatment of the systematic uncertainties and their correlations. The mass value determined is 173.18 + or - 0.56(stat) + or - 0.75(syst) GeV or 173.18 + or - 0.94 GeV, which has a precision of + or -0.54%, making this the most precise determination of the top-quark mass.
We present the first measurement of the integrated forward-backward charge asymmetry in top-quark-top-antiquark pair (tt) production in proton-antiproton (pp) collisions in the lepton+jets final ...state. Using a b-jet tagging algorithm and kinematic reconstruction assuming tt + X production and decay, a sample of 0.9 fb(-1) of data, collected by the D0 experiment at the Fermilab Tevatron Collider, is used to measure the asymmetry for different jet multiplicities. The result is also used to set upper limits on tt+X production via a Z' resonance.
Poly-ADP-ribose-polymerase (PARP) inhibitors have achieved regulatory approval in oncology for homologous recombination repair deficient tumors including BRCA mutation. However, some have failed in ...combination with first-line chemotherapies, usually due to overlapping hematological toxicities. Currently approved PARP inhibitors lack selectivity for PARP1 over PARP2 and some other 16 PARP family members, and we hypothesized that this could contribute to toxicity. Recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for driving efficacy in a BRCA mutant background. Herein, we describe the structure- and property-based design of
(AZD5305), a potent and selective PARP1 inhibitor and PARP1-DNA trapper with excellent in vivo efficacy in a BRCA mutant HBCx-17 PDX model. Compound
is highly selective for PARP1 over other PARP family members, with good secondary pharmacology and physicochemical properties and excellent pharmacokinetics in preclinical species, with reduced effects on human bone marrow progenitor cells in vitro.
A CDK9 inhibitor having short target engagement would enable a reduction of Mcl-1 activity, resulting in apoptosis in cancer cells dependent on Mcl-1 for survival. We report the optimization of a ...series of amidopyridines (from compound 2), focusing on properties suitable for achieving short target engagement after intravenous administration. By increasing potency and human metabolic clearance, we identified compound 24, a potent and selective CDK9 inhibitor with suitable predicted human pharmacokinetic properties to deliver transient inhibition of CDK9. Furthermore, the solubility of 24 was considered adequate to allow i.v. formulation at the anticipated effective dose. Short-term treatment with compound 24 led to a rapid dose- and time-dependent decrease of pSer2-RNAP2 and Mcl-1, resulting in cell apoptosis in multiple hematological cancer cell lines. Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematological tumors. Compound 24 is currently in clinical trials for the treatment of hematological malignancies.
A dedicated sample of Large Hadron Collider proton-proton collision data at centre-of-mass energy $ \sqrt{s} $ = 8 TeV is used to study inclusive single diffractive dissociation, pp → X p. The intact ...final-state proton is reconstructed in the ATLAS ALFA forward spectrometer, while charged particles from the dissociated system X are measured in the central detector components. The fiducial range of the measurement is −4.0 < log$_{10}$ξ < −1.6 and 0.016 < |t| < 0.43 GeV$^{2}$, where ξ is the proton fractional energy loss and t is the squared four-momentum transfer. The total cross section integrated across the fiducial range is 1.59 ± 0.13 mb. Cross sections are also measured differentially as functions of ξ, t, and ∆η, a variable that characterises the rapidity gap separating the proton and the system X . The data are consistent with an exponential t dependence, dσ/dt ∝ e$^{Bt}$ with slope parameter B = 7.65 ± 0.34 GeV$^{−2}$. Interpreted in the framework of triple Regge phenomenology, the ξ dependence leads to a pomeron intercept of α(0) = 1.07 ± 0.09.graphic not available: see fulltext
Optimization of a series of azabenzimidazoles identified from screening hit 2 and the information gained from a co-crystal structure of the azabenzimidazole-based lead 6 bound to CDK9 led to the ...discovery of azaindoles as highly potent and selective CDK9 inhibitors. With the goal of discovering a highly selective and potent CDK9 inhibitor administrated intravenously that would enable transient target engagement of CDK9 for the treatment of hematological malignancies, further optimization focusing on physicochemical and pharmacokinetic properties led to azaindoles 38 and 39. These compounds are highly potent and selective CDK9 inhibitors having short half-lives in rodents, suitable physical properties for intravenous administration, and the potential to achieve profound but transient inhibition of CDK9 in vivo.
We extract the total width of the top quark, Γ(t), from the partial decay width Γ(t → Wb) measured using the t-channel cross section for single top-quark production and from the branching fraction ...B(t → Wb) measured in tt events using up to 2.3 fb(-1) of integrated luminosity collected by the D0 Collaboration at the Tevatron pp Collider. The result is Γ(t) = 1.99(-0.55)(+0.69) GeV, which translates to a top-quark lifetime of τ(t) = (3.3(-0.9)(+1.3)) × 10(-25) s. Assuming a high mass fourth generation b' quark and unitarity of the four-generation quark-mixing matrix, we set the first upper limit on |V(tb')| < 0.63 at 95% C.L.
We present a search for charged Higgs bosons in decays of top quarks, in the mass range 80 < m(H+) < 155 GeV, assuming the subsequent decay H(+) -> tau(+)nu(tau) (and its charge conjugate). ...Using 0.9 fb(-1) of lepton + jets data collected with the D0 detector at the Fermilab Tevatron p (p) over bar collider, operating at a center of mass energy root s = 1.96 TeV, we find no evidence for a H(+/-) signal. Hence we exclude branching ratios B(t -> H(+)b) > 0.24 for m(H+) 80 GeV and B(t -> H(+)b) > 0.19 for m(H+) = 155 GeV at the 95% C.L.
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