The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model.

BACKGROUND The effects of the com quorum sensing system during colonisation and invasion of Streptococcus pneumoniae (Spn) are poorly understood. METHODS We developed an ex vivo model of differentiated human airway epithelial (HAE) cells with beating ciliae, mucus production and tight junctions to study Spn colonisation and translocation. HAE cells were inoculated with Spn wild-type TIGR4 (wtSpn) or its isogenic ΔcomC quorum sensing-deficient mutant. RESULTS Colonisation density of ΔcomC mutant was lower after 6 h but higher at 19 h and 30 h compared to wtSpn. Translocation correlated inversely with colonisation density. Transepithelial electric resistance (TEER) decreased after pneumococcal inoculation and correlated with increased translocation. Confocal imaging illustrated prominent microcolony formation with wtSpn but disintegration of microcolony structures with ΔcomC mutant. ΔcomC mutant showed greater cytotoxicity than wtSpn, suggesting that cytotoxicity was likely not the mechanism leading to translocation. There was greater density- and time-dependent increase of inflammatory cytokines including NLRP3 inflammasome-related IL-18 after infection with ΔcomC compared with wtSpn. ComC inactivation was associated with increased pneumolysin expression. CONCLUSIONS ComC system allows a higher organisational level of population structure resulting in microcolony formation, increased early colonisation and subsequent translocation. We propose that ComC inactivation unleashes a very different and possibly more virulent phenotype that merits further investigation

Quantitative nanoscale vortex-imaging using a cryogenic quantum magnetometer

Microscopic studies of superconductors and their vortices play a pivotal role in our understanding of the mechanisms underlying superconductivity. Local measurements of penetration depths or magnetic stray-fields enable access to fundamental aspects of superconductors such as nanoscale variations of superfluid densities or the symmetry of their order parameter. However, experimental tools, which offer quantitative, nanoscale magnetometry and operate over the large range of temperature and magnetic fields relevant to address many outstanding questions in superconductivity, are still missing. Here, we demonstrate quantitative, nanoscale magnetic imaging of Pearl vortices in the cuprate superconductor YBCO, using a scanning quantum sensor in form of a single Nitrogen-Vacancy (NV) electronic spin in diamond. The sensor-to-sample distance of ~10nm we achieve allows us to observe striking deviations from the prevalent monopole approximation in our vortex stray-field images, while we find excellent quantitative agreement with Pearl's analytic model. Our experiments yield a non-invasive and unambiguous determination of the system's local London penetration depth, and are readily extended to higher temperatures and magnetic fields. These results demonstrate the potential of quantitative quantum sensors in benchmarking microscopic models of complex electronic systems and open the door for further exploration of strongly correlated electron physics using scanning NV magnetometry.Comment: Main text (5 pages, 4 figures) plus supplementary material (5 pages, 6 figures). Comments welcome. Further information under http://www.quantum-sensing.c

Restoring the valence-shell stabilization in Nd-140

A projectile Coulomb-excitation experiment was performed at the radioactive-ion beam facility HIE-ISOLDE at CERN to obtain E2 and M1 transition matrix elements of Nd-140 using the multistep Coulomb-excitation code GOSIA. The absolute M1 strengths, B(M1; 2(2)(-) -> 2(1)(+)) = 0.033(8)mu(2)(N), B(M1 ; 2(3)(+) -> 2(1)(+)) = 0.26(-0.10)(+0.11)mu(2)(N), and B(M1; 2(4)+ -> 2(1)(+)) <0.04 mu(2)(N) identify the 2(3)(+) state as the main fragment of the one-quadrupole-phonon proton-neutron mixed-symmetry state of Nd-140. The degree of F-spin mixing in Nd-140 was quantified with the determination of the mixing matrix element VF-mix <7(-7)(-13) keV.Peer reviewe

The Neurotoxicity of DOPAL: Behavioral and Stereological Evidence for Its Role in Parkinson Disease Pathogenesis

BACKGROUND: The etiology of Parkinson disease (PD) has yet to be fully elucidated. We examined the consequences of injections of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the substantia nigra of rats on motor behavior and neuronal survival. METHODS/PRINCIPAL FINDINGS: A total of 800 nl/rat of DOPAL (1 µg/200 nl) was injected stereotaxically into the substantia nigra over three sites while control animals received similar injections of phosphate buffered saline. Rotational behavior of these rats was analyzed, optical density of striatal tyrosine hydroxylase was calculated, and unbiased stereological counts of the substantia nigra were made. The rats showed significant rotational asymmetry ipsilateral to the lesion, supporting disruption of dopaminergic nigrostriatal projections. Such disruption was verified since the density of striatal tyrosine hydroxylase decreased significantly (p<0.001) on the side ipsilateral to the DOPAL injections when compared to the non-injected side. Stereological counts of neurons stained for Nissl in pars compacta of the substantia nigra significantly decreased (p<0.001) from control values, while counts of those in pars reticulata were unchanged after DOPAL injections. Counts of neurons immunostained for tyrosine hydroxylase also showed a significant (p=0.032) loss of dopaminergic neurons. In spite of significant loss of dopaminergic neurons, DOPAL injections did not induce significant glial reaction in the substantia nigra. CONCLUSIONS: The present study provides the first in vivo quantification of substantia nigra pars compacta neuronal loss after injection of the endogenous toxin DOPAL. The results demonstrate that injections of DOPAL selectively kills SN DA neurons, suggests loss of striatal DA terminals, spares non-dopaminergic neurons of the pars reticulata, and triggers a behavioral phenotype (rotational asymmetry) consistent with other PD animal models. This study supports the "catecholaldehyde hypothesis" as an important link for the etiology of sporadic PD

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe