Overview of heavy-flavour measurements in ALICE

ALICE is devoted to the study of the properties of the Quark-Gluon Plasma (QGP). This state of matter is created in ultra-relativistic heavy-ion collisions at the LHC. Heavy quarks are considered effective probes of the QGP since, due to their large masses, they are produced in hard scattering processes and experience the full evolution of the hot and dense medium while interacting with its constituents. The heavy-quark measurements provide insights on processes like in-medium energy loss and hadronization. Measurements in proton-proton collisions provide the baseline for interpreting heavy-ion collision results and constitute an excellent test of pQCD calculations. In addition, proton-nucleus collisions allow separating cold nuclear matter effects from those due to the deconfined strongly interacting matter created in heavy-ion collisions. In this contribution, an overview of recent ALICE results for open heavy flavours, quarkonia, and heavy-flavour jets is presented.Comment: Proceedings of Excited QCD 2020, 2-8 February 2020, Krynica Zdr\'oj, Polan

Receptor binding properties, cell tropism and transmission of influenza A virus

The first influenza pandemic of the 21st century was caused by the influenza A (H1N1) 2009 virus (A(H1N1)pdm09) that emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported intermittently in the past decade, none went on to cause a pandemic or sustained human-to-human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA) protein of influenza have been associated with the ability of the virus to transmit between humans. In this thesis the effect of mutations at residue 227 in HA on cell tropism and transmission of A(H1N1)pdm09 is described. In A(H1N1)pdm09 and previous seasonal H1N1 viruses this residue is glutamic acid (E), whereas in swine influenza it is alanine (A). Using human airway epithelium, a differential cell tropism of A(H1N1)pdm09 compared to A(H1N1)pdm09 E227A and swine influenza was shown suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, multi-cycle viral growth of both A(H1N1)pdm09 E227A and swine influenza was found to be attenuated in comparison to A(H1N1)pdm09 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of A(H1N1)pdm09 E227A in ferrets. This suggests that acquisition of 227E was not solely responsible for the ability of A(H1N1)pdm09 to transmit between humans. Because the work with the E227A mutant showed that small differences in cell tropism that may affect influenza virus transmissibility could be detected in human airway cells, a receptor binding assay was developed for laboratory surveillance using commercial human airway epithelium cultures, to screen for zoonotic influenza strains of particular concern for human health. To further investigate adaptations by influenza virus for infection of the human host, the cell tropism determined by the HA protein of an avian H7N7 and human H7N3 isolate was compared. Binding to non-ciliated human airway cells was increased for the human isolate. This human case of H7N3 infection yielded two isolates from different sites (eye and throat) from the same patient on the same day. A whole genome sequencing assay was designed for H7 isolates and both eye and throat isolate were fully sequenced. One synonymous nucleotide change was found in the NS gene segment and one synonymous and two non-synonymous nucleotide changes were found in the PB2 gene segment. Comparison of the non-synonymous changes in the protein sequence of PB2 to available avian and human virus PB2 sequences revealed that the substitutions in the eye isolate were comparatively uncommon. Interestingly, these changes resulted in an increased viral growth in human airway epithelial cells at 32ºC when compared to the throat isolate, a phenomenon which was not observed at 37ºC. Finally, the use of a lung model maintained by the ex-vivo lung perfusion (EVLP) technique for study of virus infection was tested. This technique allows the use of both human and porcine lungs up to 24 hours after abstraction and is a potential model for respiratory pathogens and novel treatments. Porcine lungs were infected with A(H1N1)pdm09. Physiological and virological parameters were measured in two separate experiments and infection was demonstrated by increased viral loads in samples obtained at late time points after infection

Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution

On the Use of Iterative Approximations in Queueing Networks; with Simple Applications

Networks of queues which have a productform solution can be analyzed easily by the convolution method or with mean value analysis. Regrettably, however, many practical queueing network models do not possess a productform solution. In this paper the following approach is advocated for models with alight deviations from the productform conditions: approximate the model interatively by a sequence of models which satisfy conditions for simple analysis. Quite often aggregation and mean value analysis provide the natural approach for de signing an iteration step. Applications which are mentioned are: two-phase servers where the first phase is a preparatory one; a type of priorities; blocking; many-chains networks; FCFS-servers with different workloads for different types of customers