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See detailStages of COVID-19 pandemic and paths to herd immunity by vaccination: dynamical model comparing Austria, Luxembourg and Sweden
Kemp, Francoise UL; Proverbio, Daniele UL; Aalto, Atte UL et al

E-print/Working paper (2021)

Background. Worldwide more than 72 million people have been infected and 1.6 million died with SARS-CoV-2 by 15th December 2020. Non-pharmaceutical interventions which decrease social interaction have ... [more ▼]

Background. Worldwide more than 72 million people have been infected and 1.6 million died with SARS-CoV-2 by 15th December 2020. Non-pharmaceutical interventions which decrease social interaction have been implemented to reduce the spread of SARS-CoV-2 and to mitigate stress on healthcare systems and prevent deaths. The pandemic has been tackled with disparate strategies by distinct countries resulting in different epidemic dynamics. However, with vaccines now becoming available, the current urgent open question is how the interplay between vaccination strategies and social interaction will shape the pandemic in the next months. Methods. To address this question, we developed an extended Susceptible-Exposed-Infectious-Removed (SEIR) model including social interaction, undetected cases and the progression of patients trough hospitals, intensive care units (ICUs) and death. We calibrated our model to data of Luxembourg, Austria and Sweden, until 15th December 2020. We incorporated the effect of vaccination to investigate under which conditions herd immunity would be achievable in 2021. Results. The model reveals that Sweden has the highest fraction of undetected cases, Luxembourg displays the highest fraction of infected population, and all three countries are far from herd immunity as of December 2020. The model quantifies the level of social interactions, and allows to assess the level which would keep Reff(t) below 1. In December 2020, this level is around 1/3 of what it was before the pandemic for all the three countries. The model allows to estimate the vaccination rate needed for herd immunity and shows that 2700 vaccinations/day are needed in Luxembourg to reach it by mid of April and 45,000 for Austria and Sweden. The model estimates that vaccinating the whole country’s population within 1 year could lead to herd immunity by July in Luxembourg and by August in Austria and Sweden. Conclusion. The model allows to shed light on the dynamics of the epidemics in different waves and countries. Our results emphasize that vaccination will help considerably but not immediately and therefore social measures will remain important for several months before they can be fully alleviated. [less ▲]

Detailed reference viewed: 51 (1 UL)
See detailCausal dynamical modelling predicts novel regulatory genes of FOXP3 in human regulatory T cells
Sawlekar, Rucha UL; Magni, Stefano UL; Chapelle, Christophe et al

E-print/Working paper (2020)

Detailed reference viewed: 67 (5 UL)
See detailCOVID-19 Crisis Management in Luxembourg: Insights from an Epidemionomic Approach
burzynski, Michal; Machado, Joel; Aalto, Atte UL et al

E-print/Working paper (2020)

We develop an epidemionomic model that jointly analyzes the health and economic responses to the COVID-19 crisis and to the related containment and public health policy measures implemented in Luxembourg ... [more ▼]

We develop an epidemionomic model that jointly analyzes the health and economic responses to the COVID-19 crisis and to the related containment and public health policy measures implemented in Luxembourg and in the Greater Region. The model has a weekly structure and covers the whole year 2020. With a limited number of parameters, the model is calibrated to depict the pre-crisis evolution of the Luxembourg economy, and to match post-lockdown leading economic indicators and industry-specific infection curves. The nowcasting part of our analysis reveals that each week of lockdown reduces national output by about 28% (and annual GDP by 0.54%). A first peak of the infection curve was observed at the very beginning of April. If the lockdown measures had been permanent, annual GDP would have decreased by 22% in 2020, the number of COVID-19 cases would have reached zero around mid-June, and the proportion of recovered people would have reached 1.4% of the population. In an economy heavily relying on skill-intensive services, we show that the role of teleworking has been instrumental to limiting the weekly economic output loss (almost by one half) and the propagation of the virus. In the forecasting part of the analysis, we quantify the epidemiological and economic responses to gradual deconfinement measures under various public health scenarios. If the post-lockdown transmission rates could be kept constant throughout the deconfinement period, restarting all sectors would have huge effects on the economy (limiting the annual GDP loss to about 7%) and no effect on the aggregate infection curve. While it is a good time for lifting containment measures, there is also a risk that increasing the density of employees at the workplace and resuming social activities would induce a rebound in the infection curve. Preventing such a relapse is possible with PCR testing of both national and cross-border workers, and with accompanying measures such as (i) maintaining teleworking practices, (ii) reopening hotels, restaurants and cafes at half of their full capacity or with equivalent physical distancing measures and last but not least, (iii) sustaining distancing measures in social activities. Overall, in our worst-case scenario, combining bi-monthly testing with contact tracing and quarantining measures appear to be a suficient (perhaps not necessary) policy option in the aftermath of the deconfinement plan. [less ▲]

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See detailSingle-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids
Smits, Lisa UL; Magni, Stefano UL; Kinugawa, Kaoru et al

in Cell and Tissue Research (2020)

Detailed reference viewed: 66 (6 UL)
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See detailAssessing suppression strategies against epidemicoutbreaks like COVID-19: the SPQEIR model
Proverbio, Daniele UL; Kemp, Francoise UL; Magni, Stefano UL et al

E-print/Working paper (2020)

The current COVID-19 outbreak represents a most serious challenge for societies worldwide. It isendangering the health of millions of people, and resulting in severe socioeconomic challenges dueto lock ... [more ▼]

The current COVID-19 outbreak represents a most serious challenge for societies worldwide. It isendangering the health of millions of people, and resulting in severe socioeconomic challenges dueto lock-down measures. Governments worldwide aim to devise exit strategies to revive the economywhile keeping the pandemic under control. The problem is that the effects of distinct measures arenot well quantified. This paper compares several suppression approaches and potential exit strategiesusing a new extended epidemic SEIR model. It concludes that while rapid and strong lock-down isan effective pandemic suppression measure, a combination of other strategies such as social distanc-ing, active protection and removal can achieve similar suppression synergistically. This quantitativeunderstanding will support the establishment of mid- and long-term interventions. Finally, the paperprovides an online tool that allows researchers and decision makers to interactively simulate diversescenarios with our model. [less ▲]

Detailed reference viewed: 103 (3 UL)
See detailFrom Diagnosing Diseases to Predicting Diseases
Balling, Rudi UL; Goncalves, Jorge UL; Magni, Stefano UL et al

in Betz, Ulrich A.K. (Ed.) Curious2018 (2019)

Chronic diseases can be considered as perturbations of complex adaptive systems. Transitions from healthy states to chronic diseases are often characterized by sudden and unexpected onset of diseases ... [more ▼]

Chronic diseases can be considered as perturbations of complex adaptive systems. Transitions from healthy states to chronic diseases are often characterized by sudden and unexpected onset of diseases. These critical transitions or catastrophic shifts have been studied in theoretical and applied physics, ecology, social science, economics and recently also in biomedical applications. If we could understand the underlying mechanisms and the dynamics of critical transitions involved in the development of diseases, we would be better equipped to predict and eventually prevent them from arising. The current paper gives an overview of the potential application of the concept of critical transitions to biomedical applications. [less ▲]

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See detailSingle-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids
Smits, Lisa UL; Magni, Stefano UL; Grzyb, Kamil UL et al

E-print/Working paper (2019)

Human stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organisation and function of a respective organ or part of an ... [more ▼]

Human stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organisation and function of a respective organ or part of an organ. Human midbrain organoids (hMOs) have been described to contain midbrain-specific dopaminergic neurons that release the neurotransmitter dopamine. However, the human midbrain contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means of single-cell RNA-sequencing (scRNA-seq), imaging and electrophysiology to unravel cell heterogeneity. Our findings demonstrate that hMOs show essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, and glutamatergic neurons. Recapitulating these in vivo features makes hMOs an excellent tool for in vitro disease phenotyping and drug discovery. [less ▲]

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See detailData-driven dynamical model indicates that the heat shock response in Chlamydomonas reinhardtii is tailored to handle natural temperature variation
Magni, Stefano UL; Succurro, Antonella; Skupin, Alexander UL et al

in Journal of the Royal Society, Interface (2018), 15(142), 20170965

Global warming exposes plants to severe heat stress, with consequent crop yield reduction. Organisms exposed to high temperature stresses typically protect themselves with a heat shock response (HSR ... [more ▼]

Global warming exposes plants to severe heat stress, with consequent crop yield reduction. Organisms exposed to high temperature stresses typically protect themselves with a heat shock response (HSR), where accumulation of unfolded proteins initiates the synthesis of heat shock proteins through the heat shock transcription factor HSF1. While the molecular mechanisms are qualitatively well characterized, our quantitative understanding of the under- lying dynamics is still very limited. Here, we study the dynamics of HSR in the photosynthetic model organism Chlamydomonas reinhardtii with a data-driven mathematical model of HSR. We based our dynamical model mostly on mass action kinetics, with a few nonlinear terms. The model was parametrized and validated by several independent datasets obtained from the literature. We demonstrate that HSR quantitatively and significantly differs if an increase in temperature of the same magnitude occurs abruptly, as often applied under laboratory conditions, or gradually, which would rather be expected under natural conditions. In contrast to rapid temperature increases, under gradual changes only negligible amounts of misfolded proteins accumulate, indicating that the HSR of C. reinhardtii efficiently avoids the accumulation of misfolded proteins under conditions most likely to prevail in nature. The mathematical model we developed is a flexible tool to simulate the HSR to different conditions and complements the current experimental approaches. [less ▲]

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See detailA systems-wide understanding of photosynthetic acclimation in algae and higher plants
Wanjiku Moejes, Fiona; Matuszyńska, Anna; Adhikari, Kailash et al

in Journal of Experimental Botany (2017), 68(11), 26672681

The ability of phototrophs to colonise different environments relies on robust protection against oxidative stress, a critical requirement for the successful evolutionary transition from water to land ... [more ▼]

The ability of phototrophs to colonise different environments relies on robust protection against oxidative stress, a critical requirement for the successful evolutionary transition from water to land. Photosynthetic organisms have developed numerous strategies to adapt their photosynthetic apparatus to changing light conditions in order to optimise their photosynthetic yield, which is crucial for life on Earth to exist. Photosynthetic acclimation is an excellent example of the complexity of biological systems, where highly diverse processes, ranging from electron excitation over protein protonation to enzymatic processes coupling ion gradients with biosynthetic activity, interact on drastically different timescales from picoseconds to hours. Efficient functioning of the photosynthetic apparatus and its protection is paramount for efficient downstream processes, including metabolism and growth. Modern experimental techniques can be successfully integrated with theoretical and mathematical models to promote our understanding of underlying mechanisms and principles. This review aims to provide a retrospective analysis of multidisciplinary photosynthetic acclimation research carried out by members of the Marie Curie Initial Training Project, AccliPhot, placing the results in a wider context. The review also highlights the applicability of photosynthetic organisms for industry, particularly with regards to the cultivation of microalgae. It intends to demonstrate how theoretical concepts can successfully complement experimental studies broadening our knowledge of common principles in acclimation processes in photosynthetic organisms, as well as in the field of applied microalgal biotechnology. [less ▲]

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See detailAstrophysical aspects of dark matter direct detection
Magni, Stefano UL

Doctoral thesis (2015)

Detailed reference viewed: 99 (18 UL)
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See detailMaking sense of the local Galactic escape speed estimates in direct dark matter searches
Lavalle, Julien; Magni, Stefano UL

in Physical Review. D. (2015), 91(2), 023510

Direct detection (DD) of dark matter (DM) candidates in the ≲10 GeV mass range is very sensitive to the tail of their velocity distribution. The important quantity is the maximum weakly interacting ... [more ▼]

Direct detection (DD) of dark matter (DM) candidates in the ≲10 GeV mass range is very sensitive to the tail of their velocity distribution. The important quantity is the maximum weakly interacting massive particle speed in the observer's rest frame, i.e. in average the sum of the local Galactic escape speed v[SUB]esc[/SUB] and of the circular velocity of the Sun v[SUB]c[/SUB]. While the latter has been receiving continuous attention, the former is more difficult to constrain. The RAVE Collaboration has just released a new estimate of v[SUB]esc[/SUB] [T. Piffl et al., Astron. Astrophys. 562, A91 (2014)] that supersedes the previous one [M. C. Smith, et al. Mon. Not. R. Astron. Soc. 379, 755 (2007)], which is of interest in the perspective of reducing the astrophysical uncertainties in DD. Nevertheless, these new estimates cannot be used blindly as they rely on assumptions in the dark halo modeling which induce tight correlations between the escape speed and other local astrophysical parameters. We make a self-consistent study of the implications of the RAVE results on DD assuming isotropic DM velocity distributions, both Maxwellian and ergodic. Taking as references the experimental sensitivities currently achieved by LUX, CRESST-II, and SuperCDMS, we show that (i) the exclusion curves associated with the best-fit points of P14 may be more constraining by up to ˜40 % with respect to standard limits, because the underlying astrophysical correlations induce a larger local DM density, and (ii) the corresponding relative uncertainties inferred in the low weakly interacting massive particle mass region may be moderate, down to 10-15% below 10 GeV. We finally discuss the level of consistency of these results with other independent astrophysical constraints. This analysis is complementary to others based on rotation curves. [less ▲]

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See detailOn the use of the escape speed estimates in setting dark matter direct detection limits
Magni, Stefano UL; Lavalle, J.

in Proceedings, International Conference: "50th Rencontres de Moriond Electroweak Interactions and Unified Theories" La Thuile, Italy, March 14-21 (2015)

The knowledge of the high velocity tail of the WIMP velocity distribution has a strong impact on the way direct detection (DD) may constrain or discover light WIMPs in the GeV mass range. Recently, there ... [more ▼]

The knowledge of the high velocity tail of the WIMP velocity distribution has a strong impact on the way direct detection (DD) may constrain or discover light WIMPs in the GeV mass range. Recently, there have been important observational efforts to estimate the so-called Galactic escape speed at the position of the Earth, for instance the analysis published in early 2014 by the RAVE Collaboration ' , which is of interest in the perspective of reducing the astrophysical uncertainties in DD. Nevertheless, these new estimates cannot be used blindly as they rely on assumptions in the dark halo modeling, which induce tight correlations between the escape speed and other local astrophysical parameters (e.g. the local circular speed and dark matter density). We make a self-consistent study of the implications of the RAVE results on DD assuming isotropic DM velocity distributions, both Maxwellian and ergodic. Taking as reference the experimental sensitivities currently achieved by LUX, CRESST2, and SuperCDMS, we show that the DD constraints on WIMPs (and associated uncertainties) are slightly stronger (moderate). [less ▲]

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See detailRevisiting the escape speed impact on dark matter direct detection
Magni, Stefano UL; Lavalle, J.

in Proceedings, International Conference: "Frontiers of Fundamental Physics '14", Marseille, France, July 15-18 (2014)

The knowledge of the high velocity tail of the WIMP (Weakly Interacting Massive Particles) velocity distribution has a strong impact on the way dark matter direct detection (DMDD) may constrain or ... [more ▼]

The knowledge of the high velocity tail of the WIMP (Weakly Interacting Massive Particles) velocity distribution has a strong impact on the way dark matter direct detection (DMDD) may constrain or discover light WIMPs in the GeV mass range. Recently, there have been important observational efforts to estimate the Galactic escape speed at the position of the Earth, like for instance the analysis published in early 2014 by the RAVE Collaboration (Piffl et al., 2014), which is of interest in the perspective of reducing the astrophysical uncertainties in DMDD. Nevertheless, these new estimates cannot be used blindly as they rely on assumptions on the Milky Way mass distribution, which induce tight correlations between the escape speed and other local astrophysical parameters (circular speed and dark matter density). We make a self-consistent study of the implications of the RAVE results on DMDD assuming isotropic DM velocity distributions, both Maxwellian and ergodic. Taking as reference the experimental sensitivities currently achieved by LUX, CRESST2, and SuperCDMS, we show that the uncertainties inferred for the exclusion curves in the low WIMP mass region are moderate, ranging from 10% to 20% , and that the RAVE results imply large values of r , and so correspond to exclusion curves that are more constraining than the standard ones by 40%. [less ▲]

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See detailBackreaction and the Covariant Formalism of General Relativity
Magni, Stefano UL

Bachelor/master dissertation (2012)

This thesis is a review of backreaction, which is a possible alternative to dark energy and modified gravity. We describe in detail the 3+1 covariant formalism and Frobenius' theorem. We present the ... [more ▼]

This thesis is a review of backreaction, which is a possible alternative to dark energy and modified gravity. We describe in detail the 3+1 covariant formalism and Frobenius' theorem. We present the averaging procedure developed by Buchert, the Buchert equations and the generalization of these equations to the case of general matter. We then generalize to arbitrary number of spatial dimensions. We focus on the case of 2+1 dimensions, where the relation between the topology and the geometry of a surface imposes a global constraint on backreaction. [less ▲]

Detailed reference viewed: 42 (8 UL)