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This Technical Design Report presents a detailed description of all aspects of the LUXE (Laser Und XFEL Experiment), an experiment that will combine the high-quality and high-energy electron beam of the European XFEL with a high-intensity laser, to explore the uncharted terrain of strong-field quantum electrodynamics characterised by both high energy and high intensity, reaching the Schwinger field and beyond. The further implications for the search of physics beyond the Standard Model are also discussed.

In this paper, we obtain some important variants of the Lions and Chabrowski Concentration-compactness principle, in the context of fractional Sobolev spaces with variable exponents, especially for nonlinear systems. As an application of the results, we show the existence and assymptotic behaviour of nontrivial solutions for elliptic systems involving a new class of general nonlocal integrodifferential operators with exponent variables and critical growth conditions in $\mathbb{R}^{N}$.

In this manuscript, we will study the asymptotic behavior for a class of nonlocal diffusion equations associated with the weighted fractional $\wp(\cdot)-$Laplacian operator involving constant/variable exponent. In the case of constant exponents, under some appropriate conditions, we will study the existence of solutions and asymptotic behavior of solutions by employing the subdifferential approach and we will study the problem when $\wp$ goes to $\infty$. Already, for case the weighted fractional $\wp(\cdot)$-Laplacian operator, we will also study the asymptotic behavior of the problem solution when $\wp(\cdot)$ goes to $\infty$, in the whole or in a subset of the domain (the problem involving the fractional $\wp(\cdot)$-Laplacian presents a discontinuous exponent). To obtain the results of the asymptotic behavior in both problems it will be via Mosco convergence.

In the context of Mediterranean aquaculture little attention has been paid to the manipulation of feeding frequency at the on-growing phase. The effects of different feeding frequencies: one meal per day, two meals per day, three meals per day on growth, digestive enzyme activity, feed digestibility and plasma biochemistry were studied in gilthead sea bream (Sparus aurata, L. 1758) fed with high and low fishmeal and fish oil levels. Isonitrogenous and isolipidic extruded diets were fed to triplicate fish groups by a fixed ration over 109 days. No significant effects of feeding frequency on overall performance, feed efficiency and feed digestibility during the on-growing of gilthead sea bream fed high or low fishmeal and fish oil dietary level were observed. Pepsin activity showed an apparent decrease in fish receiving more than one meal a day which was not compensated by an increased production of alkaline proteases particularly in fish fed on low FM. Although there were no effects on growth and feed utilisation at increasing feeding frequency, trypsin decreased significantly with an increasing number of meals only under low FMFO diet. Thus, it seemed that consecutive meals could have amplified the potential trypsin inhibitor effect of the vegetable meal-based diet adopted. Results of the plasma parameters related to nutritional and physiological conditions were not affected by feeding frequency. The higher level of plasma creatinine detected in fish fed a single daily meal with high FMFO level seems to be within physiological values in relation to the higher protein efficiency observed with this diet. According to the results, gilthead sea bream seems able to maximise feed utilisation regardless of the number of meals, and this could be a useful indicator for planning feeding activity at farm level to optimise growth of fish and costs of feeding procedures.

The steep climbing of victims caused by the new coronavirus disease 2019 (COVID-19) throughout the planet is sparking an unprecedented effort to identify effective therapeutic regimens to tackle the pandemic. The SARS-CoV-2 virus is known to gain entry into various cell types through the binding of one of its surface proteins (spike) to the host Angiotensin-Converting Enzyme 2 (ACE2). Thus, spike-ACE2 interaction represents a major target for vaccines and antiviral drugs. A novel method has been recently described by some of the authors to pharmacologically downregulate the expression of target proteins at the post-translational level. This technology builds on computational advancements in the simulation of folding mechanisms to rationally block protein expression by targeting folding intermediates, hence hampering the folding process. Here, we report the all-atom simulations of the entire sequence of events underlying the folding pathway of ACE2. Our data revealed the existence of a folding intermediate showing two druggable pockets hidden in the native conformation. Both pockets were targeted by a virtual screening repurposing campaign aimed at quickly identifying drugs capable to decrease the expression of ACE2. We identified four compounds capable of lowering ACE2 expression in Vero cells in a dose-dependent fashion. All these molecules were found to inhibit the entry into cells of a pseudotyped retrovirus exposing the SARS-CoV-2 spike protein. Importantly, the antiviral activity has been tested against live SARS-CoV-2 (MEX-BC2/2020 strain). One of the selected drugs (Artefenomel) could completely prevent cytopathic effects induced by the presence of the virus, thus showing antiviral activity against SARS-CoV-2. Ongoing studies are further evaluating the possibility of repurposing these drugs for the treatment of COVID-19., Comment: Manuscript has extended to include the experimental evidence for anti-viral effects on cell colonies

In Mediterranean aquaculture little research has examined the interaction between rearing density and dietary composition on main key performance indicators, physiological processes and gut bacterial community. A study was undertaken, therefore to assess growth response, digestive enzyme activity, humoral immunity on skin mucus, plasma biochemistry and gut microbiota of gilthead sea bream (Sparus aurata, L. 1758) reared at high (HD) and low (LD) final stocking densities and fed high (FM30FO15, 30 % fishmeal FM, 15 % fish oil, FO) and low (FM10FO3; 10 % FM and 3 % FO) FM and FO levels. Isonitrogenous and isolipidic extruded diets were fed to triplicate fish groups (initial weight: 96.2 g) to overfeeding over 98 days. The densities tested had no major effects on overall growth and feed efficiency of sea bream reared at high or low FM and FO dietary level. Results of digestive enzyme activity indicated a comparable digestive efficiency among rearing densities and within each dietary treatment. Plasma parameters related to nutritional and physiological conditions were not affected by rearing densities under both nutritional conditions a similar observation was also achieved through the study of lysozyme, protease, antiprotease and total protein determination in skin mucus, For the first time on this species, the effect of rearing density on gut bacterial community was studied. Different response in relation to dietary treatment under HD and LD were detected. Low FM-FO diet maintained steady the biodiversity of the gut bacterial community between LD and HD conditions while fish fed high FM-FO level showed a reduced biodiversity at HD. According to the results, it seems feasible to rear gilthead sea bream at the on-growing phase at a density up to 36-44 kg m3 with low or high FM-FO diet without negatively affecting growth, feed efficiency, welfare condition and gut bacterial community.

In this paper, we study the existence and multiplicity of weak solutions for a general class of elliptic equations (\mathscr{P}_{\lambda}) in a smooth bounded domain, driven by a nonlocal integrodifferential operator \mathscr{L}_{\mathcal{A}K} with Dirichlet boundary conditions involving variable exponents without Ambrosetti and Rabinowitz type growth conditions. Using different versions of the Mountain Pass Theorem, as well as, the Fountain Theorem and Dual Fountain Theorem with Cerami condition, we obtain the existence of weak solutions for the problem (\mathscr{P}_{\lambda}) and we show that the problem treated has at least one nontrivial solution for any parameter \lambda>0 small enough as well as that the solution blows up, in the fractional Sobolev norm, as \lambda \to 0. Moreover, for the case sublinear, by imposing some additional hypotheses on the nonlinearity f(x,\cdot), by using a new version of the symmetric Mountain Pass Theorem due to Kajikiya [36], we obtain the existence of infinitely many weak solutions which tend to be zero, in the fractional Sobolev norm, for any parameter \lambda>0. As far as we know, the results of this paper are new in the literature., Comment: arXiv admin note: text overlap with arXiv:2003.13646

In this paper, we investigate the existence of nontrivial weak solutions to a class of elliptic equations ($\mathscr{P}$) involving a general nonlocal integrodifferential operator $\mathscr{L}_{\mathcal{A}K}$, two real parameters, and two weight functions, which can be sign-changing. Considering different situations concerning the growth of the nonlinearities involved in the problem ($\mathscr{P}$), we prove the existence of two nontrivial distinct solutions and the existence of a continuous family of eigenvalues. The proofs of the main results are based on ground state solutions using the Nehari method, Ekelands variational principle, and the direct method of the calculus of variations. The difficulties arise from the fact that the operator $\mathscr{L}_{\mathcal{A}K}$ is nonhomogeneous and the nonlinear term is undefined.