On the Finite-Time Stabilization of Uncertain Nonlinear Systems With Relative Degree Three

This technical note discusses a finite-time stabilization problem in a nonlinear, uncertain, environment. The main result of the present note is presented making reference to a triple integrator affected by bounded uncertainties and subject to ldquohardrdquo measurement nonlinearities such that the sign of the state variables is the only reliable information available for feedback. We propose a discontinuous control scheme guaranteeing the practical finite-time annihilation of the three state variables. Constructive proof and computer simulations, as well as guidelines for practical implementations, are provided throughout this technical note.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

The AFLATOX® Project: Approaching the Development of New Generation,Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox^® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem.     

Surface modification of ultra‐high‐molecular‐weight polyethylene. II. Effect on the physicomechanical and tribological properties of ultra‐high‐molecular‐weight polyethylene/poly(ethylene terephthalate) composites

We performed surface modification of ultra‐high‐molecular‐weight polyethylene (UHMWPE) through chromic acid etching, with the aim of improving the performance of its composites with poly(ethylene terephthalate) (PET) fibers. In this article, we report on the morphology and physicomechanical and tribological properties of modified UHMWPE/PET composites. Composites containing chemically modified UHMWPE had higher impact properties than those based on unmodified UHMWPE because of improved interfacial bonding between the polymer matrix and the fibers and better dispersion of the fibers within the modified UHMWPE matrix. Chemical modification of UHMWPE before the introduction of PET fibers resulted in composites exhibiting improved wear resistance compared to the base material and compared to unmodified UHMWPE/PET composites. On the basis of the morphological studies of worn samples, microploughing and fatigue failure associated with microcracking were identified as the principle wear mechanisms. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection‐based delivery of insulin. Neonatal Fc receptor (FcRn)‐mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn‐targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH‐responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH‐sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn‐targeted NPs. Overall, these FcRn‐targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.     

eCRM 2.0 applications and trends: The use and perceptions of Greek tourism firms of social networks and intelligence

Although previous CRM studies treat eCRM as a synonymous with 1:1 communications and personalised service at an individual basis, web 2.0 further enables firms and users to generate customer value and build customer relations through social networking, co-learning, co-production and collaboration. The paper advocates the development of eCRM 2.0 strategies aiming at exploiting both the networking and social/customer intelligence of web 2.0 by integrating and engaging customers and communities along firms’ value chain operations. The usage and readiness of Greek tourism firms to embark on eCRM 2.0 strategies was examined by conducting an e-mail survey and focused groups with tourism professionals. Despite the low adoption rates of eCRM 2.0, respondents were aware and greatly concerned about the practical implications of this field, which in turn elucidated an agenda for future research studies.     

On the second-order sliding mode control of nonlinear systems with uncertain control direction

This note deals with the implementation of a second-order sliding mode control algorithm for a class of nonlinear systems in which the sign of the high-frequency gain, though constant, is unknown. A specific second-order sliding mode control algorithm, the “Suboptimal” algorithm, is properly modified in order to face the uncertainty in the control direction. It is shown that after a finite time the uncertain sign is identified and the standard finite time convergence takes place from that time on. Simulation results are provided.     

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.