The second will be first: competition on directed networks

Multiple sinks competition is investigated for a walker diffusing on directed complex networks. The asymmetry of the imposed spatial support makes the system non transitive. As a consequence, it is always possible to identify a suitable location for the second absorbing sink that screens at most the flux of agents directed against the first trap, whose position has been preliminarily assigned. The degree of mutual competition between pairs of nodes is analytically quantified through apt indicators that build on the topological characteristics of the hosting graph. Moreover, the positioning of the second trap can be chosen so as to minimize, at the same time the probability of being in turn shaded by a thirdly added trap. Supervised placing of absorbing traps on a asymmetric disordered and complex graph is hence possible, as follows a robust optimization protocol. This latter is here discussed and successfully tested against synthetic data

Global topological control for synchronized dynamics on networks

A general scheme is proposed and tested to control the symmetry breaking instability of a homogeneous solution of a spatially extended multispecies model, defined on a network. The inherent discreteness of the space makes it possible to act on the topology of the inter-nodes contacts to achieve the desired degree of stabilization, without altering the dynamical parameters of the model. Both symmetric and asymmetric couplings are considered. In this latter setting the web of contacts is assumed to be balanced, for the homogeneous equilibrium to exist. The performance of the proposed method are assessed, assuming the Complex Ginzburg-Landau equation as a reference model. In this case, the implemented control allows one to stabilize the synchronous limit cycle, hence time-dependent, uniform solution. A system of coupled real Ginzburg-Landau equations is also investigated to obtain the topological stabilization of a homogeneous and constant fixed point

Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa environment interaction

Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. METHODS: We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase "home-made" ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). RESULTS: We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). CONCLUSIONS: This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor

La diagnostica per la conoscenza storica e artistica delle opere d'arte. Il ruolo delle analisi sui pigmenti nel restauro degli affreschi di Michelangelo nella Cappella Sistina

Il pensiero inerente la tutela delle opere d’arte ha subito una notevole evo- luzione nel corso della storia ed oggi è diventato indispensabile affiancare la scienza della conservazione alle consuete metodologie di restauro. Le scienze applicate ai Beni Culturali coinvolgono studiosi provenienti da diversi campi di ricerca e la collaborazione diventa una prerogativa imprescindibile per il successo dell’intervento conservativo e, soprattutto, per la conoscenza approfondita dell’opera in tutti i suoi aspetti, dai materiali costitutivi alla tecnica di realizzazione. Nell’articolo illustreremo quanto detto soffermandoci tra l’altro sul restauro degli affre- schi di Michelangelo della Cappella Sistina. Questo è stato definito come il primo restauro moderno, proprio perché le analisi hanno accompagnato ogni intervento tecnico sugli affre- schi, i quali sono tornati allo splendore originario nel rispetto dei principi teorici del restauro. In questo e in altri casi la diagnostica è diventata quindi un importante ausilio per lo stu- dio dei Beni Culturali, anche se la scelta della tecnica analitica deve essere relazionata sempre alla domanda alla quale si cerca la risposta. Le scienze applicate permettono di approfondire la storia dell’opera, la tecnica dell’artista, caratterizzano i materiali, ricostruendone le antiche rotte commerciali; tutte queste informazioni permettono di raggiungere una conoscenza senza pari, indispensabile per la valorizzazione, la tutela e la conservazione dei Beni Culturali.he approach to the protection of artwork has considerably evolved through- out history; placing side by side the conservation science and the usual methods of restoration has today become unavoidable. Science Applied to Cultural Heritage involves scholars from different research fields making their collaboration of paramount importance for the success of the conservation process and, above all, for the in-depth knowledge of the artwork in all its aspects, from the constituent materials to the realization technique. This article will discuss this topic taking into particular account the restoration of Michelangelo’s frescoes in the Sistine Chapel. This was defined as the first modern restoration, because scientific tests have accompanied for the first time any technical intervention on the frescoes, which were returned to their original splendor in respect of the theoretical principles of restoration. In this specific case and in other ones, the diagnostics has therefore become an important aid in Cultural Heritage studies, provided that the choice of the analytical technique is always related to the answer that one is trying to pursue. Applied sciences provide an insight into the history of the artworks, the artists’ techniques, the knowledge of employed materials – that allow one to reconstruct the ancient trade routes; all this information can accomplish an unsurpassed knowledge, which is becoming essential for the development, protection and conservation of Cultural Heritage

Response to 'Is there a future for hydroxychloroquine/chloroquine in prevention of SARS-CoV-2 infection (COVID-19)?' by Moiseev <i>et al</i>

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Immunohistochemical Expression of p62 in Feline Mammary Carcinoma and Non-Neoplastic Mammary Tissue

The p62 protein, also called sequestosome 1 (SQSTM1), is a ubiquitin-binding scaffold protein. In human oncology, although the interest in the function of this protein is recent, the knowledge is now numerous, but its role in tumorigenesis is not yet clear. This preliminary study aims to evaluate the immunohistochemical expression of p62 in 38 cases of feline mammary carcinoma with different grades of differentiation and in 12 non-neoplastic mammary gland tissues, to assess the expression level and a possible correlation with malignancy. The expression of p62 was statistically higher in carcinoma compared to non-neoplastic mammary glands: 28 feline mammary carcinomas (73.7%) had a high p62 expression score, three (7.9%) had a moderate expression, while seven cases (18.4%) had a low expression. The grade of the differentiation of the carcinoma was not correlated with the p62 expression. This study represents the first approach in feline oncology that correlates p62 expression in feline mammary carcinoma. Our results, although preliminary, are similar to the results of human breast cancer, therefore, also in the cat, p62 could be considered a possible oncotarget

Autophagy and rheumatoid arthritis: Current knowledges and future perspectives

Autophagy is a degradation mechanism by which cells recycle cytoplasmic components to generate energy. By influencing lymphocyte development, survival, and proliferation, autophagy regulates the immune responses against self and non-self antigens. Deregulation of autophagic pathway has recently been implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Indeed, autophagy seems to be involved in the generation of citrullinated peptides, and also in apoptosis resistance in RA. In this review, we summarize the current knowledge on the role of autophagy in RA and discuss the possibility of a clinical application of autophagy modulation in this disease

Morning Blood Pressure Surge, Dipping, and Risk of Coronary Events in Elderly Treated Hypertensive Patients

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