Two Amino Acid Residues Contribute to a Cation-π Binding Interaction in the Binding Site of an Insect GABA Receptor

Cys-loop receptor binding sites characteristically possess an "aromatic box," where several aromatic amino acid residues surround the bound ligand. A cation-π interaction between one of these residues and the natural agonist is common, although the residue type and location are not conserved. Even in the closely related vertebrate GABA_A and GABA_C receptors, residues in distinct locations perform this role: in GABA_A receptors, a Tyr residue in loop A forms a cation-π interaction with GABA, while in GABA_C receptors it is a loop B residue. GABA-activated Cys-loop receptors also exist in invertebrates, where they have distinct pharmacologies and are the target of a range of pesticides. Here we examine the location of GABA in an insect binding site by incorporating a series of fluorinated Phe derivatives into the receptor binding pocket using unnatural amino acid mutagenesis, and evaluating the resulting receptors when expressed in Xenopus oocytes. A homology model suggests that two aromatic residues (in loops B and C) are positioned such that they could contribute to a cation-π interaction with the primary ammonium of GABA, and the data reveal a clear correlation between the GABA EC_(50) and the cation-π binding ability both at Phe206 (loop B) and Tyr254 (loop C), demonstrating for the first time the contribution of two aromatic residues to a cation-π interaction in a Cys-loop receptor

Experimental and finite element dynamic analysis of incrementally loaded reinforced concrete structures

This work investigates influence of damage in reinforced concrete (RC) structures on their dynamic properties through modal testing and non-linear finite element (FE) analysis. Five RC beams were designed with the fundamental flexural mode frequencies in the range of 6.5–18.0 Hz for the uncracked state. Mechanical properties of concrete, such as static and dynamic elastic moduli were determined from standard tests and ultra-sonic pulse velocity readings. The beams were incrementally loaded until the span/250 deflection limit was reached and their natural frequencies were measured from the free decay vibrations. The progressive damage reduced fundamental frequencies of tested beams by up to 25%. The non-linear FE analysis was carried out for RC beams and one two-span slab and the calculated reduced frequencies of the 1st and 2nd vibration modes were in excellent agreement with measurements. This led to the conclusion that, given that the non-linear analysis can capture degradation of dynamic stiffness due to cracking, the future dynamic performance and damage identification on the RC structure can be reliably determined from the same FE model. The results reveal potential of the combined modal testing and FE analysis to improve inspection and assessment of the in-service RC structures

Performance of the ATLAS Level-1 topological trigger in Run 2

During LHC Run&nbsp;2 (2015&ndash;2018) the ATLAS Level-1 topological trigger allowed efficient data-taking by the ATLAS experiment at luminosities up to 2.110&nbsp;cms, which exceeds the design value by a factor of two. The system was installed in 2016 and operated in 2017 and 2018. It uses Field Programmable Gate Array processors to select interesting events by placing kinematic and angular requirements on electromagnetic clusters, jets, -leptons, muons and the missing transverse energy. It allowed to significantly improve the background event rejection and signal event acceptance, in particular for Higgs and B-physics processes.</p

Modelling and computational improvements to the simulation of single vector-boson plus jet processes for the ATLAS experiment

This paper presents updated Monte Carlo configurations used to model the production of single electroweak vector bosons (W, Z/&gamma;&lowast;) in association with jets in proton-proton collisions for the ATLAS experiment at the Large Hadron Collider. Improvements pertaining to the electroweak input scheme, parton-shower splitting kernels and scale-setting scheme are shown for multi-jet merged configurations accurate to next-to-leading order in the strong and electroweak couplings. The computational resources required for these set-ups are assessed, and approximations are introduced resulting in a factor three reduction of the per-event CPU time without affecting the physics modelling performance. Continuous statistical enhancement techniques are introduced by ATLAS in order to populate low cross-section regions of phase space and are shown to match or exceed the generated effective luminosity. This, together with the lower per-event CPU time, results in a 50% reduction in the required computing resources compared to a legacy set-up previously used by the ATLAS collaboration. The set-ups described in this paper will be used for future ATLAS analyses and lay the foundation for the next generation of Monte Carlo predictions for single vector-boson plus jets production. &nbsp;</p

Observation of electroweak production of two jets in association with an isolated photon and missing transverse momentum, and search for a Higgs boson decaying into invisible particles at 13 TeV with the ATLAS detector

his paper presents a measurement of the elec-troweak production of two jets in association with a Z &gamma; pair,with the Z boson decaying into two neutrinos. It also presentsa search for invisible or partially invisible decays of a Higgsboson with a mass of 125 GeV produced through vector-boson fusion with a photon in the final state. These results usedata from LHC proton&ndash;proton collisions at &radic;s = 13 TeV col-lected with the ATLAS detector and corresponding to an inte-grated luminosity of 139 fb&minus;1 . The event signature, sharedby all benchmark processes considered for the measurementsand searches, is characterized by a significant amount ofunbalanced transverse momentum and a photon in the finalstate, in addition to a pair of forward jets. Electroweak Z &gamma;production in association with two jets is observed in thisfinal state with a significance of 5.2 (5.1 expected) standarddeviations. The measured fiducial cross-section for this pro-cess is 1.31 &plusmn; 0.29 fb. An observed (expected) upper limitof 0.37 (0.34+0.15&minus;0.10 ) at 95% confidence level is set on thebranching ratio of a 125 GeV Higgs boson to invisible parti-cles, assuming the Standard Model production cross-section.The signature is also interpreted in the context of decays ofa Higgs boson into a photon and a dark photon. An observed(expected) 95% CL upper limit on the branching ratio forthis decay is set at 0.018 (0.017+0.007&minus;0.005 ), assuming the Stan-dard Model production cross-section for a 125 GeV Higgsboson.</p

Search for type-III seesaw heavy leptons in leptonic final states in pp collisions at root s=13 TeV with the ATLAS detector

A search for the pair production of heavy leptons as predicted by the type-III seesaw mechanism is presented. The search uses proton&ndash;proton collision data at a centre-of-mass energy of 13&nbsp;TeV, corresponding to 139fb&minus;1 of integrated luminosity recorded by the ATLAS detector during Run 2 of the Large Hadron Collider. The analysis focuses on final states with three or four electrons or muons from the possible decays of new heavy leptons via intermediate electroweak bosons. No significant deviations above the Standard Model expectation are observed; upper and lower limits on the heavy lepton production cross-section and masses are derived respectively. These results are then combined for the first time with the ones already published by ATLAS using the channel with two leptons in the final state. The observed lower limit on the mass of the type-III seesaw heavy leptons combining two, three and four lepton channels together is 910 GeV at the 95% confidence level.</p

Biomechanical Tolerance of Whole Lumbar Spines in Straightened Posture Subjected to Axial Acceleration

Quantification of biomechanical tolerance is necessary for injury prediction and protection of vehicular occupants. This study experimentally quantified lumbar spine axial tolerance during accelerative environments simulating a variety of military and civilian scenarios. Intact human lumbar spines (T12‐L5) were dynamically loaded using a custom‐built drop tower. Twenty‐three specimens were tested at sub‐failure and failure levels consisting of peak axial forces between 2.6 and 7.9 kN and corresponding peak accelerations between 7 and 57 g. Military aircraft ejection and helicopter crashes fall within these high axial acceleration ranges. Testing was stopped following injury detection. Both peak force and acceleration were significant (p \u3c 0.0001) injury predictors. Injury probability curves using parametric survival analysis were created for peak acceleration and peak force. Fifty‐percent probability of injury (95%CI) for force and acceleration were 4.5 (3.9–5.2 kN), and 16 (13–19 g). A majority of injuries affected the L1 spinal level. Peak axial forces and accelerations were greater for specimens that sustained multiple injuries or injuries at L2–L5 spinal levels. In general, force‐based tolerance was consistent with previous shorter‐segment lumbar spine testing (3–5 vertebrae), although studies incorporating isolated vertebral bodies reported higher tolerance attributable to a different injury mechanism involving structural failure of the cortical shell. This study identified novel outcomes with regard to injury patterns, wherein more violent exposures produced more injuries in the caudal lumbar spine. This caudal migration was likely attributable to increased injury tolerance at lower lumbar spinal levels and a faster inertial mass recruitment process for high rate load application. Published 2017. This article is a U.S. Government work and is in the public domain in the USA

Adaptive State Estimation for Nonminimum-Phase Systems with Uncertain Harmonic Inputs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90727/1/AIAA-2011-6315-484.pd