SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Portuguese network for SARS-CoV-2 genomics (Consortium): Agostinho José S Lira, Aida M Sousa Fernandes, Alexandra Estrada, Alexandra Nunes, Alfredo Rodrigues, Ana Caldas, Ana Constança, Ana Margarida Henriques, Ana Miguel Matos, Ana Oliveira, Ana Paula Dias, Ana Pelerito, Ana Rita Couto, Anabela Vilares, António Albuquerque, Baltazar Nunes, Bruna R Gouveia, Carina de Fátima Rodrigues, Carla Feliciano, Carla Roque, Carlos Cardoso, Carlos Sousa, Cathy Paulino, Célia Rodrigues Bettencourt, Claudia C Branco, Cláudia Nunes Dos Santos, Conceição Godinho, Constantino P Caetano, Cristina Correia, Cristina Toscano, Cristina Veríssimo, Daniela Silva, Diana Patrícia Pinto da Silva, Eliana Costa, Elizabeth Pádua, Fátima Martins, Fátima Vale, Fernanda Vilarinho, Fernando Branca, Filomena Caldeira, Filomena Lacerda, Francisca Rocha, Graça Andrade, Helena Ribeiro, Helena Rodrigues, Herberto Jesus, Hugo Sousa, Idalina Ferreira, Inês Baldaque, Inês Costa, Inês Gomes, Inna Slobidnyk, Isabel Albergaria, Isabel Dias, Isabel Fernandes, Isabel Lopes de Carvalho, Ivone Água-Doce, Jácome Bruges Armas, Joana Ramos, João Carlos Sousa, João Costa, João Dias, João Rodrigues, João Sobral, Jorge Machado, Jorge Meneses, José Alves, José Vicente Constantino, Laura Brum, Leonor Silveira, Líbia Zé-Zé, Lidia Santos, Ludivina Freitas, Luís Silva, Luisa Mota-Vieira, Lurdes Lopes, Lurdes Monteiro, Márcia Faria, Margarida Farinha, Margarida Vaz, Maria Alice Pinto, Maria Ana Pessanha, Maria Beatriz Tomaz, Maria Calle Vellés, Maria da Graça Maciel de Soveral, Maria Helena Ramos, Maria Isabel Veiga, Maria João Gargate, Maria João Peres, Maria José Borrego, Maria Matos Figueiredo, Mariana Martins, Mariana Viana, Maurício Melim, Miguel Babarro Jorreto, Miguel Fevereiro, Miguel Pinheiro, Mónica Oleastro, Nair Seixas, Nelson Ventura, Nuno Verdasca, Olga Costa, Patrícia Barros, Patricia Fonseca, Patricia Miguel, Paula Bajanca-Lavado, Paula Branquinho, Paula Palminha, Paula Soares, Paula Valente, Paulo Leandro, Paulo Pereira, Pedro Cardoso, Pedro Pechirra, Pedro Ramos, Raquel Neves, Raquel Rocha, Raquel Rodrigues, Raquel Sabino, Regina Sá, Ricardo Filipe Romão Ferreira, Ricardo Rodrigues, Rita C Veloso, Rita Cordeiro, Rita Côrte-Real, Rita de Sousa, Rita Gralha, Rita Macedo, Rita Matos, Rita Rodrigues, Sandra Paulo, Sara Sousa, Sílvia Lopo, Sónia Marta Santos Magalhães, Sónia Rodrigues, Sónia Silva, Susana Ladeiro, Susana Martins, Susana Silva, Teresa Salvado, Tiago Luís, Valquíria Alves, Vera ManageiroBackground: Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods: By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARS-CoV-2 introductions and early dissemination in Portugal. Results: We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions: Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.Plain language summary: Analysing SARS-CoV-2 genetic material and how it changes over time can help us understand how the virus spreads between countries and determine the impact of control measures. In this study, we investigated SARS-CoV-2 transmission and evolution in the early stages of the COVID-19 pandemic in Portugal. In particular, we reconstructed the routes and timeliness of viral introductions into the country and assessed the relative contribution of each introduction in terms of how the epidemic evolved over time. We detected at least 277 independent introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. This study reflects an unprecedented effort in the field of the infectious diseases in Portugal, highlighting the need for systematic and geographically-representative surveillance to aid public health efforts to control the virus.This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Por tugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-a, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1G1A1004667), Republic of Korea

Resveratrol-Based Nanoformulations as an Emerging Therapeutic Strategy for Cancer

Resveratrol is a polyphenolic stilbene derivative widely present in grapes and red wine. Broadly known for its antioxidant effects, numerous studies have also indicated that it exerts anti-inflammatory and antiaging abilities and a great potential in cancer therapy. Regrettably, the oral administration of resveratrol has pharmacokinetic and physicochemical limitations such as hampering its effects so that effective administration methods are demanding to ensure its efficiency. Thus, the present review explores the published data on the application of resveratrol nanoformulations in cancer therapy, with the use of different types of nanodelivery systems. Mechanisms of action with a potential use in cancer therapy, negative effects, and the influence of resveratrol nanoformulations in different types of cancer are also highlighted. Finally, the toxicological features of nanoresveratrol are also discussed.CR would like to acknowledge the UID/EQU/00511/2020 Project—Laboratory of Process Engineering, Environment, Biotechnology and Energy (LEPABE), financed by national funds through FCT/MCTES (PIDDAC). NC-M acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017). Some of the components of the illustrations are taken from freepik and flaticon

Large-scale instability in interacting dark energy and dark matter fluids

If dark energy interacts with dark matter, this gives a new approach to the coincidence problem. But interacting dark energy models can suffer from pathologies. We consider the case where the dark energy is modelled as a fluid with constant equation of state parameter w. Non-interacting constant-w models are well behaved in the background and in the perturbed universe. But the combination of constant w and a simple interaction with dark matter leads to an instability in the dark sector perturbations at early times: the curvature perturbation blows up on super-Hubble scales. Our results underline how important it is to carefully analyze the relativistic perturbations when considering models of coupled dark energy. The instability that we find has been missed in some previous work where the perturbations were not consistently treated. The unstable mode dominates even if adiabatic initial conditions are used. The instability also arises regardless of how weak the coupling is. This non-adiabatic instability is different from previously discovered adiabatic instabilities on small scales in the strong-coupling regime.Comment: 15 pages, 5 figures. New reference; published versio

Large-scale instability in interacting dark energy and dark matter fluids

If dark energy interacts with dark matter, this gives a new approach to the coincidence problem. But interacting dark energy models can suffer from pathologies. We consider the case where the dark energy is modelled as a fluid with constant equation of state parameter w. Non-interacting constant-w models are well behaved in the background and in the perturbed universe. But the combination of constant w and a simple interaction with dark matter leads to an instability in the dark sector perturbations at early times: the curvature perturbation blows up on super-Hubble scales. Our results underline how important it is to carefully analyze the relativistic perturbations when considering models of coupled dark energy. The instability that we find has been missed in some previous work where the perturbations were not consistently treated. The unstable mode dominates even if adiabatic initial conditions are used. The instability also arises regardless of how weak the coupling is. This non-adiabatic instability is different from previously discovered adiabatic instabilities on small scales in the strong-coupling regime.Comment: 15 pages, 5 figures. New reference; published versio

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

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN