Cellular excitability and the regulation of functional neuronal identity: from gene expression to neuromodulation

The intrinsic properties of a neuron determine the translation of synaptic input to axonal output. It is this input– output relationship that is the heart of all nervous system activity. As such, the overall regulation of the intrinsic excitability of a neuron directly determines the output of that neuron at a given point in time, giving the cell a unique “functional identity.” To maintain this distinct functional output, neurons must adapt to changing patterns of synaptic excitation. These adaptations are essential to prevent neurons from either falling silent as synaptic excitation falls or becoming saturated as excitation increases. In the absence of stabilizing mechanisms, activity-dependent plasticity could drive neural activity to saturation or quiescence. Furthermore, as cells adapt to changing patterns of synaptic input, presumably the overall balance of intrinsic conductances of the cell must be maintained so that reliable output is achieved (Daoudal and Debanne, 2003; Turrigiano and Nelson, 2004; Frick and Johnston, 2005). Although these regulatory phenomena have been well documented, the molecular and physiological mechanisms involved are poorly understood

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies

Bubble-Mediated Gas Transfer and Gas Transfer Suppression of DMS and CO2

Direct dimethyl sulfide (DMS) flux measurements using eddy covariance have shown a suppression of gas transfer at medium to high wind speed. However, not all eddy covariance measurements show evidence of this suppression. Processes, such as wave-wind interaction and surfactants, have been postulated to cause this suppression. We measured DMS and carbon dioxide eddy covariance fluxes during the Asian summer monsoon in the western tropical Indian Ocean (July and August 2014). Both fluxes and their respective gas transfer velocities show signs of a gas transfer suppression above 10 m/s. Using a wind-wave interaction, we describe a flow separation process that could be responsible for a suppression of gas transfer. As a result we provide a Reynolds number-based parameterization, which states the likelihood of a gas transfer suppression for this cruise and previously published gas transfer data. Additionally, we compute the difference in the gas transfer velocities of DMS and CO2 to estimate the bubble-mediated gas transfer using a hybrid model with three whitecap parameterizations

First normal stress difference and crystallization in a dense sheared granular fluid

The first normal stress difference (${\mathcal N}_1$) and the microstructure in a dense sheared granular fluid of smooth inelastic hard-disks are probed using event-driven simulations. While the anisotropy in the second moment of fluctuation velocity, which is a Burnett-order effect, is known to be the progenitor of normal stress differences in {\it dilute} granular fluids, we show here that the collisional anisotropies are responsible for the normal stress behaviour in the {\it dense} limit. As in the elastic hard-sphere fluids, ${\mathcal N}_1$ remains {\it positive} (if the stress is defined in the {\it compressive} sense) for dilute and moderately dense flows, but becomes {\it negative} above a critical density, depending on the restitution coefficient. This sign-reversal of ${\mathcal N}_1$ occurs due to the {\it microstructural} reorganization of the particles, which can be correlated with a preferred value of the {\it average} collision angle $\theta_{av}=\pi/4 \pm \pi/2$ in the direction opposing the shear. We also report on the shear-induced {\it crystal}-formation, signalling the onset of fluid-solid coexistence in dense granular fluids. Different approaches to take into account the normal stress differences are discussed in the framework of the relaxation-type rheological models.Comment: 21 pages, 13 figure

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector