CNS Recruitment of CD8+ T Lymphocytes Specific for a Peripheral Virus Infection Triggers Neuropathogenesis during Polymicrobial Challenge

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]

Accuracy versus precision in boosted top tagging with the ATLAS detector

Abstract The identification of top quark decays where the top quark has a large momentum transverse to the beam axis, known as top tagging, is a crucial component in many measurements of Standard Model processes and searches for beyond the Standard Model physics at the Large Hadron Collider. Machine learning techniques have improved the performance of top tagging algorithms, but the size of the systematic uncertainties for all proposed algorithms has not been systematically studied. This paper presents the performance of several machine learning based top tagging algorithms on a dataset constructed from simulated proton-proton collision events measured with the ATLAS detector at √ s = 13 TeV. The systematic uncertainties associated with these algorithms are estimated through an approximate procedure that is not meant to be used in a physics analysis, but is appropriate for the level of precision required for this study. The most performant algorithms are found to have the largest uncertainties, motivating the development of methods to reduce these uncertainties without compromising performance. To enable such efforts in the wider scientific community, the datasets used in this paper are made publicly available.</jats: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

This paper presents the measurement of the electroweak production of two jets in association with a $Z\gamma$ pair with the $Z$ boson decaying into two neutrinos. It also presents the search for invisible or partially invisible decays of a Higgs boson with a mass of 125 GeV produced through vector-boson fusion with a photon in the final state. These results use data from LHC proton-proton collisions at $\sqrt{s}$ = 13 TeV collected with the ATLAS detector corresponding to an integrated luminosity of 139 fb$^{-1}$. The event signature, shared by all benchmark processes considered for measurements and searches, is characterized by a significant amount of unbalanced transverse momentum and a photon in the final state, in addition to a pair of forward jets. For electroweak production of $Z\gamma$ in association with two jets, the background-only hypothesis is rejected with an observed (expected) significance of 5.2 (5.1) standard deviations. The measured fiducial cross-section for this process is 1.31$\pm$0.29 fb. Observed (expected) upper limit of 0.37 (0.34) at 95% confidence level is set on the branching ratio of a 125 GeV Higgs boson to invisible particles, assuming the Standard Model production cross-section. The signature is also interpreted in the context of decays of a Higgs boson to a photon and a dark photon. An observed (expected) 95% CL upper limit on the branching ratio for this decay is set at 0.018 (0.017), assuming the 125 GeV Standard Model Higgs boson production cross-section

4MOST: 4-metre Multi-Object Spectroscopic Telescope

1134MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the fields of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO and from ground-based facilities like VISTA, VST, DES, LSST and SKA. The 4MOST baseline concept features a 2.5 degree diameter field-of-view with ~2400 fibres in the focal surface that are configured by a fibre positioner based on the tilting spine principle. The fibres feed two types of spectrographs; ~1600 fibres go to two spectrographs with resolution R<5000 (λ~390-930 nm) and ~800 fibres to a spectrograph with R>18,000 (λ~392-437 nm and 515-572 nm and 605-675 nm). Both types of spectrographs are fixed-configuration, three-channel spectrographs. 4MOST will have an unique operations concept in which 5 year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept. 4MOST has been accepted for implementation by ESO with operations expected to start by the end of 2020. This paper provides a top-level overview of the 4MOST facility, while other papers in these proceedings provide more detailed descriptions of the instrument concept[1], the instrument requirements development[2], the systems engineering implementation[3], the instrument model[4], the fibre positioner concepts[5], the fibre feed[6], and the spectrographs[7].nonenonede Jong Roelof S.; Barden Sam; Bellido-Tirado Olga; Brynnel Joar; Chiappini Cristina; Depagne Éric; Haynes Roger; Johl Diana; Phillips Daniel P.; Schnurr Olivier; Schwope Axel D.; Walcher Jakob; Bauer Svend M.; Cescutti G; Cioni Maria-Rosa L.; Dionies Frank; Enke Harry; Haynes Dionne M.; Kelz Andreas; Kitaura Francisco S.; Lamer Georg; Minchev Ivan; Müller Volker; Nuza Sebastián. E.; Olaya Jean-Christophe; Piffl Tilmann; Popow Emil; Saviauk Allar; Steinmetz Matthias; Ural Uǧur; Valentini Monica; Winkler Roland; Wisotzki Lutz; Ansorge Wolfgang R.; Banerji Manda; Gonzalez Solares Eduardo; Irwin Mike; Kennicutt Robert C.; King David M. P.; McMahon Richard; Koposov Sergey; Parry Ian R.; Sun Xiaowei; Walton Nicholas A.; Finger Gert; Iwert Olaf; Krumpe Mirko; Lizon Jean-Louis; Mainieri Vincenzo; Amans Jean-Philippe; Bonifacio Piercarlo; Cohen Matthieu; François Patrick; Jagourel Pascal; Mignot Shan B.; Royer Frédéric; Sartoretti Paola; Bender Ralf; Hess Hans-Joachim; Lang-Bardl Florian; Muschielok Bernard; Schlichter Jörg; Böhringer Hans; Boller Thomas; Bongiorno Angela; Brusa Marcella; Dwelly Tom; Merloni Andrea; Nandra Kirpal; Salvato Mara; Pragt Johannes H.; Navarro Ramón; Gerlofsma Gerrit; Roelfsema Ronald; Dalton Gavin B.; Middleton Kevin F.; Tosh Ian A.; Boeche Corrado; Caffau Elisabetta; Christlieb Norbert; Grebel Eva K.; Hansen Camilla J.; Koch Andreas; Ludwig Hans-G.; Mandel Holger; Quirrenbach Andreas; Sbordone Luca; Seifert Walter; Thimm Guido; Helmi Amina; trager Scott C.; Bensby Thomas; Feltzing Sofia; Ruchti Gregory; Edvardsson Bengt; Korn Andreas; Lind Karin; Boland Wilfried; Colless Matthew; Frost Gabriella; Gilbert James; Gillingham Peter; Lawrence Jon; Legg Neville; Saunders Will; Sheinis Andrew; Driver Simon; Robotham Aaron; Bacon Roland; Caillier Patrick; Kosmalski Johan; Laurent Florence; Richard Johande Jong Roelof, S.; Barden, Sam; Bellido-Tirado, Olga; Brynnel, Joar; Chiappini, Cristina; Depagne, Éric; Haynes, Roger; Johl, Diana; Phillips Daniel, P.; Schnurr, Olivier; Schwope Axel, D.; Walcher, Jakob; Bauer Svend, M.; Cescutti, G; Cioni Maria-Rosa, L.; Dionies, Frank; Enke, Harry; Haynes Dionne, M.; Kelz, Andreas; Kitaura Francisco, S.; Lamer, Georg; Minchev, Ivan; Müller, Volker; Nuza, Sebastián. E.; Olaya, Jean-Christophe; Piffl, Tilmann; Popow, Emil; Saviauk, Allar; Steinmetz, Matthias; Ural, Uǧur; Valentini, Monica; Winkler, Roland; Wisotzki, Lutz; Ansorge Wolfgang, R.; Banerji, Manda; Gonzalez Solares, Eduardo; Irwin, Mike; Kennicutt Robert, C.; King David, M. P.; Mcmahon, Richard; Koposov, Sergey; Parry Ian, R.; Sun, Xiaowei; Walton Nicholas, A.; Finger, Gert; Iwert, Olaf; Krumpe, Mirko; Lizon, Jean-Louis; Mainieri, Vincenzo; Amans, Jean-Philippe; Bonifacio, Piercarlo; Cohen, Matthieu; François, Patrick; Jagourel, Pascal; Mignot Shan, B.; Royer, Frédéric; Sartoretti, Paola; Bender, Ralf; Hess, Hans-Joachim; Lang-Bardl, Florian; Muschielok, Bernard; Schlichter, Jörg; Böhringer, Hans; Boller, Thomas; Bongiorno, Angela; Brusa, Marcella; Dwelly, Tom; Merloni, Andrea; Nandra, Kirpal; Salvato, Mara; Pragt Johannes, H.; Navarro, Ramón; Gerlofsma, Gerrit; Roelfsema, Ronald; Dalton Gavin, B.; Middleton Kevin, F.; Tosh Ian, A.; Boeche, Corrado; Caffau, Elisabetta; Christlieb, Norbert; Grebel Eva, K.; Hansen Camilla, J.; Koch, Andreas; Ludwig, Hans-G.; Mandel, Holger; Quirrenbach, Andreas; Sbordone, Luca; Seifert, Walter; Thimm, Guido; Helmi, Amina; trager Scott, C.; Bensby, Thomas; Feltzing, Sofia; Ruchti, Gregory; Edvardsson, Bengt; Korn, Andreas; Lind, Karin; Boland, Wilfried; Colless, Matthew; Frost, Gabriella; Gilbert, James; Gillingham, Peter; Lawrence, Jon; Legg, Neville; Saunders, Will; Sheinis, Andrew; Driver, Simon; Robotham, Aaron; Bacon, Roland; Caillier, Patrick; Kosmalski, Johan; Laurent, Florence; Richard, Joha

Metal-Ligand Cooperation at Phosphine-Based Acceptor Pincer Ligands

Acceptor ligands, which predominantly withdraw electron density from a transition metal center, often engage in weak metal-ligand interactions. These can be stabilized by flanking the acceptor moiety with strongly binding phosphines in a pincer motif, affording more robust complexes in which bond activation and/or bond-forming events can take place while preserving the integrity of the molecule as a whole. This contribution highlights recent developments in this area. Compounds incorporating a borane at the central position are discussed first, followed by compounds incorporating an electrophilic C = E (E = C, O, N) π-bond. In both cases, recent examples highlight the ability of these ligands to (1) respond to electronic changes at the metal by modifying their binding mode and (2) accept a nucleophilic fragment (e.g., hydride) from substrate molecules. Applications of acceptor pincer ligands as cooperative catalysts are discussed

Tools for estimating fake/non-prompt lepton backgrounds with the ATLAS detector at the LHC

International audienceMeasurements and searches performed with the ATLAS detector at the CERN LHC often involve signatures with one or more prompt leptons. Such analysesare subject to `fake/non-prompt' lepton backgrounds, where either a hadron or a lepton from a hadron decay or an electron from a photon conversion satisfies the prompt-leptonselection criteria. These backgrounds often arise within a hadronic jet because of particle decays in the showering process, particle misidentification or particleinteractions with the detector material. As it is challenging to model these processes with high accuracy in simulation, their estimation typically uses data-driven methods.Three methods for carrying out this estimation are described, along with their implementation in ATLAS and their performance