ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57-/- hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In mutant NPCs, we observed a reduction of allelic bias of all the 32 genes that were imprinted in wild-type cells, demonstrating that ZFP57-dependent methylation is required for maintaining or acquiring imprinted gene expression during differentiation. Analysis of expression levels showed that imprinted genes expressed from the non-methylated chromosome were generally up-regulated, and those expressed from the methylated chromosome were down-regulated in mutant cells. However, expression levels of several imprinted genes acquiring biallelic expression were not affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neural differentiation was partially impaired in Zfp57-mutant cells, this study also indicates that imprinted genes and/or non-imprinted ZFP57-target genes are required for proper neurogenesis in cultured ESCs.

We consider a one-dimensional, isentropic, hydrodynamical model for a unipolar semiconductor, with the mobility depending on the electric field. The mobility is related to the momentum relaxation time, and field-dependent mobility models are commonly used to describe the occurrence of saturation velocity, that is, a limit value for the electron mean velocity as the electric field increases. For the steady state system, we prove the existence of smooth solutions in the subsonic case, with a suitable assumption on the mobility function. Furthermore, we prove uniqueness of subsonic solutions for sufficiently small currents.

Extended versions of the Bourgain-Brezis-Mironescu theorems on the limit as s->1^- of the Gagliardo-Slobodeckij fractional seminorm are established in the Orlicz space setting. The results hold for fractional Orlicz-Sobolev spaces built upon general Young functions, as well. The case of Young functions with an asymptotic linear growth is also considered in connection with the space of functions of bounded variation. An extended version of the Maz'ya-Shaposhnikova theorem on the limit as s->0^+ of the Gagliardo-Slobodeckij fractional seminorm is established in the Orlicz space setting. The result holds in fractional Orlicz-Sobolev spaces associated with Young functions fulfilling the \Delta_2-condition, and, as shown by counterexamples, it may fail if this condition is dropped. This is a joint work with Andrea Cianchi, Lubos Pick and Lenka Slavikova.

We establish versions for fractional Orlicz-Sobolev seminorms, built upon Young functions, of the Bourgain-Brezis-Mironescu theorem on the limit as s ->1^-, and of the Maz'ya-Shaposhnikova theorem on the limit as s->0^-, dealing with classical fractional Sobolev spaces. As regards the limit as s ->1^-, Young functions with an asymptotic linear growth are also considered in connection with the space of functions of bounded variation. Concerning the limit as s->0^+, Young functions fulfilling the \Delta_2-condition are admissible. Indeed, counterexamples show that our result may fail if this condition is dropped. This is a joint work with Andrea Cianchi, Lubos Pick and Lenka Slavikova.

The optimal Orlicz target space and the optimal rearrangement-invariant tar- get space are exhibited for embeddings of fractional-order Orlicz-Sobolev spaces W^{s,A}(R^n). Related Hardy type inequalities are proposed as well. Versions for frac- tional Orlicz-Sobolev seminorms of the Bourgain-Brezis-Mironescu theorem on the limit as s->1^- and of the Maz'ya-Shaposhnikova theorem on the limit as s ->0^+ are established. This is a joint work with Andrea Cianchi, Lubos Pick and Lenka Slavikova.

The existence of eigenfunctions for a class of fully anisotropic elliptic equations is established. The relevant equations are associated with constrained minimization problems for integral func- tionals depending on the gradient of competing functions through general anisotropic Young functions. In particular, the latter need neither be radial, nor have a polynomial growth, and are not even assumed to satisfy the so called \Delta_2-condition. In particular, our analysis requires the development of some new aspects of the theory of anisotropic Orlicz-Sobolev spaces. This is a joint work with G. di Blasio and F. Feo.

Optimal embeddings for fractional-order Orlicz{Sobolev spaces into Campanato type s- paces are offered. This is a joint work in progress with Andrea Cianchi, Lubos Pick and Lenka Slavikova.

The existence of eigenfunctions for a class of fully anisotropic elliptic equations is estab- lished. The relevant equations are associated with constrained minimization problems for inte- gral functionals depending on the gradient of competing functions through general anisotropic Young functions. In particular, the latter need neither be radial, nor have a polynomial growth, and are not even assumed to satisfy the so called 2-condition. In particular, our analysis re- quires the development of some new aspects of the theory of anisotropic Orlicz-Sobolev spaces. This is a joint work with G. di Blasio and F. Feo [1].

Compact embeddings on domain for fractional Orlicz-Sobolev spaces are exhibited.

The present work is motivated by the development of a mathematical model mimicking the mechanisms observed in lab-on-chip experiments, made to reproduce on microfluidic chips the in vivo reality. Here we consider the Cancer-on-Chip experiment where tumor cells are treated with chemotherapy drug and secrete chemical signals in the environment attracting multiple immune cell species. The in silico model here proposed goes towards the construction of a "digital twin" of the experimental immune cells in the chip environment to better understand the complex mechanisms of immunosurveillance. To this aim, we develop a tumor-immune microfluidic hybrid PDE-ODE model to describe the concentration of chemicals in the Cancer-on-Chip environment and immune cells migration. The development of a trustable simulation algorithm, able to reproduce the immunocompetent dynamics observed in the chip, requires an efficient tool for the calibration of the model parameters. In this respect, the present paper represents a first methodological work to test the feasibility and the soundness of the calibration technique here proposed, based on a multidimensional spline interpolation technique for the time-varying velocity field surfaces obtained from cell trajectories.

Over the last decade, significant attention has been devoted to Closed-Loop Supply Chain (CLSC) design problems. As such, this review aims at assessing whether the current modelling approaches for CLSC problems can support the transition towards a Circular Economy at a supply chain level. The paper comprehensively assesses the extent to which existing modelling approaches evaluate the performance of supply chains across the complete spectrum of sustainability dimensions. Also, the capability of the current approaches of incorporating strategic, tactical, and operational decisions is considered, along with adopted solution methodologies. As a result, a comprehensive analysis was performed on 254 selected articles. This paper emphasises how most of the current literature in the field is affected by a disconnection between supply chain design and the founding principles of Circular Economy. Specifically, the CLSC literature exhibits a reductionist interpretation of the Circular Economy. CLSC studies focusing on all three dimensions of sustainability are relatively rare, and performance measurement approaches appear to be very much focused on monetary issues. While methodological contributions appear adequate to focus on the non-deterministic nature of CLSC design problems, there is paucity of empirically-grounded research. Coherently, a research agenda is proposed, in order to address the mentioned gaps and increase the relevance of this research field to practice.

Recently, many European local authorities have set up Urban Consolidation Centres (UCC) for dealing with challenges arising from the environmental and social impacts of logistical activities in urban contexts through shipment synchronisation and carrier coordination policies. However, the number of successful UCC projects led by local authorities in Europe is low, with most of the UCCs failing to achieve financial sustainability after the initial experimental phase, which is often heavily supported by public funds. In order to propose mechanisms that could favour the economic and financial sustainability of UCC systems, this research develops an adaptation of game-theoretic approaches to the problems of responsibility and cost allocation among stakeholders participating in a UCC delivery network. A solution based on the Shapley Value concept is employed to derive cost allocations; applications of the model to a real-world scenario are evaluated. An extensive sensitivity analysis shows that the proposed cost allocation rules can provide alternative arrangements, based on extended responsibility concepts, which can alleviate the burden on local authorities for the set up of UCCs. As such, results provide useful policy and practice implications on how to safeguard UCCs' viability under different scenarios, including the outsourcing of the last-mile deliveries.

In network analysis, many community detection algorithms have been developed. However, their implementation leaves unaddressed the question of the statistical validation of the results. Here, we present robin (ROBustness In Network), an R package to assess the robustness of the community structure of a network found by one or more methods to give indications about their reliability. The procedure initially detects if the community structure found by a set of algorithms is statistically significant and then compares two selected detection algorithms on the same graph to choose the one that better fits the network of interest. We demonstrate the use of our package on the American College Football benchmark dataset.

Linear solvers for large and sparse systems are a key element of scientific applications, and their efficient implementation is necessary to harness the computational power of current computers. Algebraic Multigrid (AMG) Preconditioners are a popular ingredient of such linear solvers; this is the motivation for the present work where we examine some recent developments in a package of AMG preconditioners to improve efficiency, scalability and robustness on extreme scale problems. The main novelty is the design and implementation of a new parallel coarsening algorithm based on aggregation of unknowns employing weighted graph matching techniques; this is a completely automated procedure, requiring no information from the user, and applicable to general symmetric positive definite (s.p.d.) matrices. The new coarsening algorithm improves in terms of numerical scalability at low operator complexity over decoupled aggregation algorithms available in previous releases of the package. The preconditioners package is built on the parallel software framework PSBLAS, which has also been updated to progress towards exascale. We present weak scalability results on two of the most powerful supercomputers in Europe, for linear systems with sizes up to O(10^{10}) unknowns.

The properties of semiflexible polymers tethered by one end to an impenetrable wall and exposed to oscillatory shear flow are investigated by mesoscale simulations. A polymer, confined in two dimensions, is described by a linear bead-spring chain, and fluid interactions are incorporated by the Brownian multiparticle collision dynamics approach. At small strain, the polymers follow the applied flow field. However, at high strain, we find a strongly nonlinear response with major conformational changes. Polymers are stretched along the flow direction and exhibit U-shaped conformations while following the flow. As a consequence of confinement in the half-space, frequency doubling in the time-dependent polymer properties appears along the direction normal to the wall.

We numerically study by lattice Boltzmann simulations the rheological properties of an active emulsion made of a suspension of an active polar gel embedded in an isotropic passive background. We find that the hexatic equilibrium configuration of polar droplets is highly sensitive to both active injection and external forcing and may either lead to asymmetric unidirectional states which break top-bottom symmetry or symmetric ones. In this latter case, for large enough activity, the system develops a shear thickening regime at low shear rates. Importantly, for larger external forcing a regime with stable negative effective viscosity is found. Moreover, at intermediate activity a region of multistability is encountered and we show that a maximum entropy production principle holds in selecting the most favorable state.

Asymptotically convolution Volterra equations are characterized by kernel functions which exponentiallydecay to convolution ones. Their importance in the applications motivates a numerical analysis of theasymptotic behavior of the solution. Here the quasi-convolution nature of the kernel is exploited in orderto investigate the stability of .; / methods for general systems and in some particular cases.

A prey-predator system with logistic growth of prey and hunting cooperation of predators is studied. The introduction of fractional time derivatives and the related persistent memory strongly characterize the model behavior, as many dynamical systems in the applied sciences are well described by such fractional-order models. Mathematical analysis and numerical simulations are performed to highlight the characteristics of the proposed model. The existence, uniqueness and boundedness of solutions is proved; the stability of the coexistence equilibrium and the occurrence of Hopf bifurcation is investigated. Some numerical approximations of the solution are finally considered; the obtained trajectories confirm the theoretical findings. It is observed that the fractional-order derivative has a stabilizing effect and can be useful to control the coexistence between species.

Background: Probiotics may prevent the allergic response development due to their antiinflammatory and immunomodulatory effects. The aim of this study is to determine if the prophylactic treatment with a mixture of Bifidobacterium animalis subsp. Lactis BB12 and Enterococcus faecium L3 would reduce symptoms and need for drug use in children with allergic rhinitis (AR). Methods: The study included 250 children aged from 6 to 17 years, affected by AR. Patients were randomly assigned to the intervention group (150) or to the placebo group (100). Patients in the intervention group, in addition to conventional therapy (local corticosteroids and/or oral antihistamines), were treated in the 3 months preceding the onset of symptoms related to the presence of the allergen to which the children were most sensitized, with a daily oral administration of a probiotic mixture containing the Bifidobacterium animalis subsp. Lactis BB12 DSM 15954 and the Enterococcus faecium L3 LMG P-27496 strain. We used Nasal Symptoms Score (NSS) to evaluate AR severity before and after the treatment with probiotics or placebo. Results: the patients in the intervention group had a significant reduction in their NSS after probiotic treatment (p-value = 2.2 × 10. Moreover, for the same group of patients, we obtained a significant reduction in the intake of pharmacological therapy. In particular, we obtained a reduction in the use of oral antihistamines (p-value = 2.2 × 10), local corticosteroids (p-value = 2.2 × 10), and of both drugs (p-value 1.5 × 10). Conclusions: When administered as a prophylactic treatment, a mixture of BB12 and L3 statistically decreased signs and symptoms of AR and reduced significantly the need of conventional therapy.

A recently proposed mesoscale approach for the simulation of multicomponent flows with near-contact interactions is employed to investigate the early stage formation and clustering statistics of soft flowing crystals in microfluidic channels. Specifically, we first demonstrate the ability of the aforementioned mesoscale model to accurately reproduce main mechanisms leading to the formation of two basic droplet patterns (triangular and hexagonal), in close agreement with experimental evidence. Next, we quantitatively evaluate the device-scale clustering efficiency of the crystal formation process by introducing a new orientational order parameter, based on the Delaunay triangulation and Voronoi diagrams analysis of the droplet patterns. The mesoscale computational approach employed in this work proves to be an efficient tool to shed new light on the complex dynamics of dense emulsions, from short-scale thin-film hydrodynamics, all the way up to global structure formation and statistics of the resulting droplets ensembles.