Atmospheric emissions of Carbon tetrachloride CCl4 are regulated by the Montreal Protocol due to its role as a strong ozone-depleting substance. The molecule has been the subject of recent increased interest as a consequence of the so called ``mystery of CCl4,'' the discrepancy between atmospheric observations and reported production and consumption. Surface measurements of CCl4 atmospheric concentrations have declined at a rate almost three times smaller than its lifetime-limited rate, suggesting persistent atmospheric emissions despite the ban. In this paper, we study CCl4 vertical and zonal distributions in the upper troposphere and lower stratosphere (including the photolytic loss region, 70-20 hPa), its trend, and its stratospheric lifetime using measurements from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS), which operated onboard the ENVISAT satellite from 2002 to 2012. Specifically, we use the MIPAS data product generated with Version 7 of the Level 2 algorithm operated by the European Space Agency.The CCl4 zonal means show features typical of long-lived species of anthropogenic origin that are destroyed primarily in the stratosphere, with larger quantities in the troposphere and a monotonic decrease with increasing altitude in the stratosphere. In the troposphere, the largest concentrations are observed at the latitudes of major industrial countries (20/50°N). The good agreement we find between MIPAS CCl4 and independent measurements from other satellite and balloon-borne remote sounders proves the reliability of the MIPAS dataset.CCl4 trends are calculated as a function of both latitude and altitude. Negative trends are found at all latitudes in the upper-troposphere / lower-stratosphere region, apart from a region in the Southern mid-latitudes between 50 and 10 hPa where the trend is positive. At the lowest altitudes sounded by MIPAS, we find trends consistent with those determined on the basis of long-term ground-based measurements. For higher altitudes, the trend shows a pronounced asymmetry between Northern and Southern Hemispheres, and the magnitude of the decline rate increases with altitude. At 50 hPa the decline is about 30-35 %/decade, close to the lifetime-limited trend.We use a simplified model assuming tracer-tracer linear correlations to determine CCl4 lifetime in the lower stratosphere. The calculation provides a global average lifetime of 46(38-60) years considering CFC-11 as the reference tracer. This value is consistent with the most recent literature result of 44(36-58) years.

We use high-resolution direct numerical simulations to study the anisotropic contents of a turbulent, statistically homogeneous flow with random transitions among multiple energy containing states. We decompose the velocity correlation functions on different sectors of the three-dimensional group of rotations, SO(3), using a high-precision quadrature. Scaling properties of anisotropic components of longitudinal and transverse velocity fluctuations are accurately measured at changing Reynolds numbers. We show that independently of the anisotropic content of the energy containing eddies, small-scale turbulent fluctuations recover isotropy and universality faster than previously reported in experimental and numerical studies. The discrepancies are ascribed to the presence of highly anisotropic contributions that have either been neglected or measured with less accuracy in the foregoing works. Furthermore, the anomalous anisotropic scaling exponents are devoid of any sign of saturation with increasing order. Our study paves the way to systematically assess persistence of anisotropy in high-Reynolds-number flows.

The Stokes drag force and the gravity force are usually sufficient to describe the behavior of sub-Kolmogorovsize (or pointlike) heavy particles in turbulence, in particular when the particle-to-fluid density ratio rho(p)/rho(integral) greater than or similar to 10(3) (with rho(p) and rho(f) the particle and fluid density, respectively). This is, in general, not the case for smaller particle-to-fluid density ratios, in particular not for rho(p)/rho(f) greater than or similar to 10(2). In that case the pressure gradient force, added mass effects, and the Basset history force also play important roles. In this study we focus on the understanding of the role of these additional forces, all of hydrodynamic origin, in the settling of particles in turbulence. In order to qualitatively elucidate the complex dynamics of such particles in homogeneous isotropic turbulence, we first focus on the case of settling of such particles in the flow field of a single vortex. After having explored this simplified case we extend our analysis to homogeneous isotropic turbulence. In general, we found that the pressure gradient force leads to a decrease in the settling velocity. This can be qualitatively understood by the fact that this force prevents the particles from sweeping out of vortices, a mechanism known as preferential sweeping which causes enhanced settling. Additionally, we found that the Basset history force can both increase and decrease the enhanced settling, depending on the particle Stokes number. Finally, the role of the nonlinear Stokes drag has been explored, confirming that it affects settling of inertial particles in turbulence, but only in a limited way for the parameter settings used in this investigation.

Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells' maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scalphaDEC-205 triggers Th1 T cells' polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis.

Despite numerous important contributions, the investigation of brain connectivity with magnetoencephalography (MEG) still faces multiple challenges. One critical aspect of source-level connectivity, largely overlooked in the literature, is the putative effect of the choice of the inverse method on the subsequent cortico-cortical coupling analysis. We set out to investigate the impact of three inverse methods on source coherence detection using simulated MEG data. To this end, thousands of randomly located pairs of sources were created. Several parameters were manipulated, including inter- and intra-source correlation strength, source size and spatial configuration. The simulated pairs of sources were then used to generate sensor-level MEG measurements at varying signal-to-noise ratios (SNR). Next, the source level power and coherence maps were calculated using three methods (a) L2-Minimum-Norm Estimate (MNE), (b) Linearly Constrained Minimum Variance (LCMV) beamforming, and (c) Dynamic Imaging of Coherent Sources (DICS) beamforming. The performances of the methods were evaluated using Receiver Operating Characteristic (ROC) curves. The results indicate that beamformers perform better than MNE for coherence reconstructions if the interacting cortical sources consist of point-like sources. On the other hand, MNE provides better connectivity estimation than beamformers, if the interacting sources are simulated as extended cortical patches, where each patch consists of dipoles with identical time series (high intra-patch coherence). However, the performance of the beamformers for interacting patches improves substantially if each patch of active cortex is simulated with only partly coherent time series (partial intra-patch coherence). These results demonstrate that the choice of the inverse method impacts the results of MEG source-space coherence analysis, and that the optimal choice of the inverse solution depends on the spatial and synchronization profile of the interacting cortical sources. The insights revealed here can guide method selection and help improve data interpretation regarding MEG connectivity estimation.

We study the conformational freedom of a protein made by two rigid domains connected by a flexible linker. The conformational freedom is represented as an unknown probability distribution on the space of allowed states. A new algorithm for the calculation of the maximum allowable probability is proposed, which can be extended to any type of measurements. In this paper we use pseudo contact shifts and residual dipolar coupling. We reconstruct a single central tendency in the distribution and discuss in depth the results.

In this paper, we propose a new mathematical model describing the effect of phosphocitrate (PC) on sodium sulphate crystallization inside bricks. This model describes salt and water transport, and crystal formation in a one dimensional symmetry. This is a preliminary study that takes into account mathematically the effects of inhibitors inside a porous stone. To this aim, we introduce two model parameters: the crystallization rate coefficient, which depends on the nucleation rate, and the specific volume of precipitated salt. These two parameters are determined by numerical fitting of our model for both the case of the brick treated with PC and non treated one.

A notion of "2D well-balanced" for drift-diffusion is proposed. Exactness at steady-state, typical in 1D, is weakened by aliasing errors when deriving "truly 2D" numerical fluxes from local Green's function. A main ingredient for proving that such a property holds is the optimality of the trapezoidal rule for periodic functions. In accordance with practical evidence, a "Bessel scheme" previously introduced in [SIAM J. Numer. Anal. 56 (2018), pp. 2845-2870] is shown to be "2D well-balanced" (along with former algorithms known as "discrete weighted means" or "tailored schemes". Some L-2 stability estimates are established, too.

Systems medicine holds many promises, but has so far provided only a limited number of proofs of principle. To address this road block, possible barriers and challenges of translating systems medicine into clinical practice need to be identified and addressed. The members of the European Cooperation in Science and Technology (COST) Action CA15120 Open Multiscale Systems Medicine (OpenMultiMed) wish to engage the scientific community of systems medicine and multiscale modelling, data science and computing, to provide their feedback in a structured manner. This will result in follow-up white papers and open access resources to accelerate the clinical translation of systems medicine.

This poster describes some activities developed by CNR and its third party within EoCoE

Lower tropospheric ozone (O3) retrievals from nadir sounders is challenging due to the lack of vertical sensitivity of the measurements and towards the lowest layers. If improvements have been made during the last decade, it is still important to explore possibilities to improve the retrieval algorithms themselves. O3 retrieval from nadir satellite observations is an ill-conditioned problem, which requires regularization using constraint matrices. Up to now, most of the retrieval algorithms rely on a fixed constraint. The constraint is determined and fixed beforehand, on the basis of sensitivity tests. This does not allow ones to take advantage of the entire capabilities of the satellite measurements, which vary with the thermal conditions of the observed scenes. To overcome this limitation, we developed a self-adapting and altitude-dependent regularization scheme. A crucial step is the choice of the strength of the constraint. This choice is done during an iterative process and depends on the measurement errors and on the sensitivity of the measurements to the target parameters at the different altitudes. The challenge is to limit the use of a priori constraints to the minimal amount needed to perform the inversion. The algorithm has been tested on synthetic observations matching the future IASI-NG satellite instrument. IASI-NG measurements are simulated on the basis of O3 concentrations taken from an atmospheric model and retrieved using two retrieval schemes (the standard and self-adapting ones). Comparison of the results shows that the sensitivity of the observations to the O3 amount in the lowest layers (given by the degrees of freedom for the solution) is increased, which allows a better description of the ozone distribution, especially in the case of large ozone plumes. Biases are reduced and the spatial correlation is improved. Tentative of application to real observations from IASI, currently onboard the Metop satellite will also be presented.

This package can be used to compute associations among genes (gene-networks) or between genes and some external traits (i.e. clinical).

This package predicts the gene-gene interaction network and identifies the direct transcriptional targets of the perturbation using an ODE (Ordinary Differential Equation) based method.

eudysbiome a package that permits to annotate the differential genera as harmful/harmless based on their ability to contribute to host diseases (as indicated in literature) or unknown based on their ambiguous genus classification. Further, the package statistically measures the eubiotic (harmless genera increase or harmful genera decrease) or dysbiotic(harmless genera decrease or harmful genera increase) impact of a given treatment or environmental change on the (gut-intestinal, GI) microbiome in comparison to the microbiome of the reference condition.

In Alicandro et al. (J Mech Phys Solids 92:87-104, 2016) a simple discrete scheme for the motion of screw dislocations toward low energy configurations has been proposed. There, a formal limit of such a scheme, as the lattice spacing and the time step tend to zero, has been described. The limiting dynamics agrees with the maximal dissipation criterion introduced in Cermelli and Gurtin (Arch Ration Mech Anal 148, 1999) and predicts motion along the glide directions of the crystal. In this paper, we provide rigorous proofs of the results in [3], and in particular of the passage from the discrete to the continuous dynamics. The proofs are based on ? -convergence techniques.

We show that minimizers of the Heitmann-Radin energy (Heitmann and Radin in J Stat Phys 22(3): 281-287, 1980) are unique if and only if the particle number N belongs to an infinite sequence whose first thirty-five elements are 1, 2, 3, 4, 5, 7, 8, 10, 12, 14, 16, 19, 21, 24, 27, 30, 33, 37, 40, 44, 48, 52, 56, 61, 65, 70, 75, 80, 85, 91, 96, 102, 108, 114, 120 (see the paper for a closed-form description of this sequence). The proof relies on the discrete differential geometry techniques introduced in De Luca and Friesecke (Crystallization in two dimensions and a discrete Gauss-Bonnet Theorem, 2016).

Additionally, it has also come to light an implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape, as demonstrated by the being itself object of epigenetic modifications. An increasing body of data is progressively indicating that the comprehension of the epigenetic landscape, actively integrated with the genetic elements, is crucial to delineate the molecular basis of the inter-individual complexity of ageing process. Indeed, it has emerged that DNA methylation changes occur during ageing, consisting mainly in a progressive process of genome demethylation, in a hypermethylation of gene-specific CpG dinucleotides, as well as in an inter-individual divergence of the epigenome due to stochastic events and environmental exposures throughout life, namely as epigenetic drift.

Degeneration is a hallmark of autoimmune diseases, whose incidence grows worldwide. Currenttherapies attempt to control the immune response to limit degeneration, commonly promotingimmunodepression. Differently, mechanical stimulation is known to trigger healing (regeneration) andit has recently been proposed locally for its therapeutic potential on severely injured areas. As the earlystages of healing consist of altered intra- and inter-cellular fluxes of soluble molecules, we explored thepotential of this early signal to spread, over time, beyond the stimulation district and become systemic,to impact on distributed or otherwise unreachable injured areas. We report in a model of arthritis inrats how stimulations delivered in the subcutaneous dorsal tissue result, over time, in the control andhealing of the degeneration of the paws' joints, concomitantly with the systemic activation of woundhealing phenomena in blood and in correlation with a more eubiotic microbiome in the gut intestinaldistrict.

To exploit this stability and reinforce it, we conducted a meta-analysis on publicly available DNA methylation datasets generated on: normal colorectal, adenoma (ADE) and adenocarcinoma (CRC) samples using the Illumina 450k array, in the systems medicine frame, searching for tumor gene episignatures, to produce a carefully selected list of potential drivers, markers and targets of the disease. The analysis proceeds from a differential meta-analysis of the methylation profiles using an analytical pipeline recently developed by our group [1], through network reconstruction, topological and functional analyses, to finally highlight relevant epigenomic features. Our results show that genes already highlighted for their genetic or transcriptional alteration in colorectal cancer are also differentially methylated, reinforcing-regardless of the level of cellular control-their role in the complex of alterations involved in tumorigenesis. Colorectal cancer is among the leading causes of cancer death worldwide. Despite numerous molecular characterizations of the phenomenon, the exact dynamics of its onset and progression remain elusive. Colorectal cancer onset has been characterized by changes in DNA methylation profiles, that, owing to the stability of their patterns, are promising candidates to shed light on the molecular events laying at the base of this phenomenon.

This package has been developed to evaluate cellular engineering processes for direct differentiation of stem cells or conversion (transdifferentiation) of somatic cells to primary cells based on high throughput gene expression data screened either by DNA microarray or RNA sequencing. The package takes gene expression profiles as inputs from three types of samples: (i) somatic or stem cells to be (trans)differentiated (input of the engineering process), (ii) induced cells to be evaluated (output of the engineering process) and (iii) target primary cells (reference for the output). The package performs differential gene expression analysis for each pair-wise sample comparison to identify and evaluate the transcriptional differences among the 3 types of samples (input, output, reference). The ideal goal is to have induced and primary reference cell showing overlapping profiles, both very different from the original cells.