Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture

Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter

We present a study of showers initiated by electrons, pions, kaons, and protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE scintillator-tungsten analogue hadronic calorimeter. The data were recorded at the CERN Super Proton Synchrotron in 2011. The analysis includes measurements of the calorimeter response to each particle type as well as measurements of the energy resolution and studies of the longitudinal and radial shower development for selected particles. The results are compared to Geant4 simulations (version 9.6.p02). In the study of the energy resolution we include previously published data with beam momenta from 1 GeV to 10 GeV recorded at the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table

The Time Structure of Hadronic Showers in highly granular Calorimeters with Tungsten and Steel Absorbers

The intrinsic time structure of hadronic showers influences the timing capability and the required integration time of hadronic calorimeters in particle physics experiments, and depends on the active medium and on the absorber of the calorimeter. With the CALICE T3B experiment, a setup of 15 small plastic scintillator tiles read out with Silicon Photomultipliers, the time structure of showers is measured on a statistical basis with high spatial and temporal resolution in sampling calorimeters with tungsten and steel absorbers. The results are compared to GEANT4 (version 9.4 patch 03) simulations with different hadronic physics models. These comparisons demonstrate the importance of using high precision treatment of low-energy neutrons for tungsten absorbers, while an overall good agreement between data and simulations for all considered models is observed for steel.Comment: 24 pages including author list, 9 figures, published in JINS

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503

Immigrant fertility in West Germany: is there a socialization effect in transitions to second and third births?

In this paper on immigrant fertility in West Germany, we estimate the transition rates to second and third births, using intensity-regression models. The data come from the German Socio-Economic Panel Study. We distinguish women of the first and the second immigrant generations originating from Turkey, the former Yugoslavia, Greece, Italy, and Spain, and compare their fertility levels to those of West German women. In the theoretical framework, we discuss competing hypotheses on migrant fertility. The findings support mainly the socialization hypothesis: the transition rates of first-generation immigrants vary by country of origin, and the fertility patterns of migrant descendants resemble more closely those of West Germans than those of the first immigrant generation. In addition, the analyses show that fertility differentials between immigrants and women of the indigenous population can largely, though not in full, be explained by compositional differences.Dans cet article relatif à la fécondité des immigrées en Allemagne, le passage du premier au deuxieme enfant et dans celui du deuxieme au troisieme enfant est estimé à partir de modèles de régression à risques instantanés. Les données utilisées proviennent de l’étude de Panel socio-économique allemand. On distingue les femmes immigrées de première ou de seconde génération originaires de Turquie, d’ex-Yougoslavie, de Grèce, d’Italie et d’Espagne, et leurs niveaux de fécondité sont comparés à ceux des femmes ouest-allemandes d’origine. Des hypothèses concurrentes sur la fécondité des immigrés sont discutées dans le cadre théorique. Les résultats vérifient principalement l’hypothèse de la socialisation : le passage au deuxieme et au troisieme enfant de la première génération d’immigrés varie selon le pays d’origine, et le profil de fécondité par âge des descendantes d’immigrées se rapproche plus de celui des femmes ouest-allemandes que de celui des immigrées de première génération. De plus, les analyses montrent que les différences de fécondité entre les immigrées et les femmes ouest-allemandes peuvent être en grande partie, mais pas totalement, expliquées par des différences de structure

Global Genomic Analysis of SARS-CoV-2 RNA Dependent RNA Polymerase Evolution and Antiviral Drug Resistance.

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima's D = -2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic