Towards a gauge-polyvalent Numerical Relativity code

The gauge polyvalence of a new numerical code is tested, both in harmonic-coordinate simulations (gauge-waves testbed) and in singularity-avoiding coordinates (simple Black-Hole simulations, either with or without shift). The code is built upon an adjusted first-order flux-conservative version of the Z4 formalism and a recently proposed family of robust finite-difference high-resolution algorithms. An outstanding result is the long-term evolution (up to 1000M) of a Black-Hole in normal coordinates (zero shift) without excision.Comment: to appear in Physical Review

Efficient implementation of finite volume methods in Numerical Relativity

Centered finite volume methods are considered in the context of Numerical Relativity. A specific formulation is presented, in which third-order space accuracy is reached by using a piecewise-linear reconstruction. This formulation can be interpreted as an 'adaptive viscosity' modification of centered finite difference algorithms. These points are fully confirmed by 1D black-hole simulations. In the 3D case, evidence is found that the use of a conformal decomposition is a key ingredient for the robustness of black hole numerical codes.Comment: Revised version, 10 pages, 6 figures. To appear in Phys. Rev.

Conformal and covariant formulation of the Z4 system with constraint-violation damping

We present a new formulation of the Einstein equations based on a conformal and traceless decomposition of the covariant form of the Z4 system. This formulation combines the advantages of a conformal decomposition, such as the one used in the BSSNOK formulation (i.e. well-tested hyperbolic gauges, no need for excision, robustness to imperfect boundary conditions) with the advantages of a constraint-damped formulation, such as the generalized harmonic one (i.e. exponential decay of constraint violations when these are produced). We validate the new set of equations through standard tests and by evolving binary black hole systems. Overall, the new conformal formulation leads to a better behavior of the constraint equations and a rapid suppression of the violations when they occur. The changes necessary to implement the new conformal formulation in standard BSSNOK codes are very small as are the additional computational costs.Comment: 12 pages, 7 figures. Version matching the one in press on PR

Fertilization with different soil types in viticulture: a three-year experience in Trentino Alto Adige

6CO.NA.VI. 2020 – 8° Convegno Nazionale di Viticoltura, Udine, Italy, July 5-7, 2021openInternationalItalian coauthor/editorThe work aimed at investigating the impact of various good quality soils of on vineyard productivity. Manure matured with a fast and controlled process and compost obtained from digestate of an organic fraction of municipal solid waste (OFMSW) were applied one time on a grapevine row, in two CAVIT vineyards. A physico-chemical characterization of the soils was carried out and biological quality indices QBS-ar (Arthropodological Biocenosis) were calculated. The vegeto-productive monitoring was performed by foliar nutrients analysis and measuring NDVI and SPAD indices. The organic source had a significant fertilizing effect, especially manure, which determined a nutrient increase in soil (P, K and Mg), a rise in photosynthetically active biomass, available nitrogen and potassium in plants. The effects on the biological community of soils and musts quality were negligible. The use of soil improvers could be an efficient strategy for the nutrition of not vigorous vineyards, which do not require high nitrogen inputs.openPedò, Stefano; Bona, Daniela; Cristoforetti, Andrea; Ippolito, Marco; Porro, Duilio; Trainotti, DiegoPedò, S.; Bona, D.; Cristoforetti, A.; Ippolito, M.; Porro, D.; Trainotti, D

Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation

Macrophages are key targets of HIV-1 infection. We have previously described that the expressionof CC chemokine ligand 2 (CCL2) increases during monocyte differentiation to macrophages and it is furtherup-modulated by HIV-1 exposure. Moreover, CCL2 acts as an autocrine factor that promotes viral replication ininfected macrophages. In this study, we dissected the molecular mechanisms by which CCL2 neutralization inhibitsHIV-1 replication in monocyte-derived macrophages (MDM), and the potential involvement of the innate restrictionfactors protein sterile alpha motif (SAM) histidine/aspartic acid (HD) domain containing 1 (SAMHD1) and apolipoproteinB mRNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family members.Results:CCL2 neutralization potently reduced the number of p24 Gag+cells during the course of either productive orsingle cycle infection with HIV-1. In contrast, CCL2 blocking did not modify entry of HIV-1 based Virus Like Particles, thusdemonstrating that the restriction involves post-entry steps of the viral life cycle. Notably, the accumulation of viralDNA, both total, integrated and 2-LTR circles, was strongly impaired by neutralization of CCL2. Looking for correlates ofHIV-1 DNA accumulation inhibition, we found that the antiviral effect of CCL2 neutralization was independent of themodulation of SAMHD1 expression or function. Conversely, a strong and selective induction of APOBEC3A expression,to levels comparable to those of freshly isolated monocytes, was associated with the inhibition of HIV-1 replicationmediated by CCL2 blocking. Interestingly, the CCL2 neutralization mediated increase of APOBEC3A expression was typeI IFN independent. Moreover, the transcriptome analysis of the effect of CCL2 blocking on global gene expressionrevealed that the neutralization of this chemokine resulted in the upmodulation of additional genes involved in thedefence response to viruses.Conclusions:Neutralization of endogenous CCL2 determines a profound restriction of HIV-1 replication in primaryMDM affecting post-entry steps of the viral life cycle with a mechanism independent of SAMHD1. In addition, CCL2blocking is associated with induction of APOBEC3A expression, thus unravelling a novel mechanism which mightcontribute to regulate the expression of innate intracellular viral antagonistsin vivo. Thus, our study may potentially leadto the development of new therapeutic strategies for enhancing innate cellular defences against HIV-1 and protecting macrophages from infection

Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats

Purpose: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. Methods: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. Results: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. Conclusion: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

<div><p>Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in <i>Cftr^F508del</i> homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the <i>F508del-CFTR</i> mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from <i>F508del</i> homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both <i>in vivo</i>, in mice, and <i>in vitro</i>, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 <i>F508del-CFTR</i> homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells <i>in vivo</i>, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of <i>TNF/TNF-alpha (tumor necrosis factor)</i> and <i>CXCL8</i> (<i>chemokine [C-X-C motif] ligand 8</i>) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the <i>F508del-CFTR</i> mutation.</p></div