A study of the effects of the neurokinin peptides on respiratory function in sheep

The respiratory responses, including changes in pulmonary resistance (RL) and dynamic compliance (Cdyn), to the neurokinin peptides substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were assessed in anaesthetised normal Suffolk-cross and conscious Texel-cross asthmatic sheepIn normal sheep (n=l 1) intravenous SP was a more potent bronchoconstrictor than NKA (n=9) and this was similar to findings in sheep with a naturally acquired airway allergy to Ascaris suum antigen (asthmatic) (n=5) where peptides were administered by inhalation. NKB (n=4) was assessed only in normal sheep and caused insignificant changes in bronchomotor tone. Intravenous SP and NKA, in normal anaesthetised sheep, caused a dose-dependent reduction in respiratory rate and this was similar for both peptides.The bronchomotor response to SP in normal sheep demonstrated age-related changes. In sheep under 6 months of age there was a pronounced bronchoconstriction, with a subsequent reduction in the response as animals approach maturity. In old sheep, aged approximately four years, there was minimal bronchomotor response, however, there was dose-dependent apnoea.The bronchomotor response to SP in anaesthetised normal sheep was significantly antagonised after pre-treatment with atropine (lmg/kg; n=6), hexamethonium (20mg/Kg; n=3) and the NK-1 antagonist CP 96,345 (0.1 and 0.5mg/Kg; n=5), but not by the HI receptor antagonist chlorpheniramine (2mg/Kg; n=5) or the neurokinin antagonist spantide (lOug/kg/min; n=3). The anti-asthma drug nedocromil sodium (0.1 and l.Omg/kg; n=4) had a variable effect on the response. In the isolated sheep trachealis muscle preparation the contractile effect of SP was inhibited by atropine (n=4) and the Ml receptor antagonist pirenzepine (n=8), with IC₅₀ values of 5.6xl0⁻⁸ and 5xl0⁻¹⁰ M respectively, while spantide (n=7) and the NK-2 receptor antagonist L-659,874 (n=6) were ineffective.In several normal sheep (n=10) intravenous SP consistently caused augmented breaths. Bilateral vagotomy (n=7) abolished, and cooling of the right cervical vagus (n=7), after section of the left vagus, to temperatures below 7° C significantly attenuated the bronchomotor response to SP in normal sheep.The conclusion of this study is that the order of potency for the bronchomotor effects of the neurokinins is similar to rabbits and pigs but different from that reported for most other species, including man. The mechanism of action of SP is largely indirect, involving activation of vagal reflex mechanisms and/or modulation of ganglionic neurotransmission and acetylcholine release from cholinergic nerve endings

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Measurement of the Differential γ+2 b\gamma+2~b-Jet Cross Section and the Ratio σ\sigma(γ+2 b\gamma+2~b-jets)/σ\sigma(γ+b\gamma+b-jet) in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

We present the first measurements of the differential cross section $d\sigma/dp_{T}^{\gamma}$ for the production of an isolated photon in association with at least two $b$-quark jets. The measurements consider photons with rapidities $|y^\gamma| 15$ GeV and $| y^{jet}| < 1.5$. The ratio of differential production cross sections for $\gamma+2~b$-jets to $\gamma+b$-jet as a function of $p_{T}^{\gamma}$ is also presented. The results are based on the proton-antiproton collision data at $\sqrt{s}=$1.96~\TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next-to-leading order perturbative QCD calculations as well as predictions based on the $k_{T}$-factorization approach and those from the SHERPA and PYTHIA Monte Carlo event generators

Precise measurement of the top quark mass in dilepton decays using optimized neutrino weighting

We measure the top quark mass in dilepton final states of top-antitop events in proton-antiproton collisions at sqrt(s) = 1.96 TeV, using data corresponding to an integrated luminosity of 9.7 fb^-1 at the Fermilab Tevatron Collider. The analysis features a comprehensive optimization of the neutrino weighting method to minimize the statistical uncertainties. We also improve the calibration of jet energies using the calibration determined in top-antitop to lepton+jets events, which reduces the otherwise limiting systematic uncertainty from the jet energy scale. The measured top quark mass is mt = 173.32 +/- 1.36(stat) +/- 0.85(syst) GeV