Complex Networked Systems: Convergence Analysis, Dynamic Behaviour, and Security.

Complex networked systems are a modern reference framework through which very dierent systems from far disciplines, such as biology, computer science, physics, social science, and engineering, can be described. They arise in the great majority of modern technological applications. Examples of real complex networked systems include embedded systems, biological networks, large-scale systems such as power generation grids, transportation networks, water distribution systems, and social network. In the recent years, scientists and engineers have developed a variety of techniques, approaches, and models to better understand and predict the behaviour of these systems, even though several research and industrial challenges are still open. This thesis addresses the study of dierent properties of complex networked systems and their applications. The main contribution of the work can be considered as threefold: the study of interaction among agents and the relative data clustering in small groups, the analysis of convergence conditions towards a common or multiple agreements, and the investigation of security aspects concerning the detection of perturbations that can propagate across network components and subnetworks. Firstly, a novel approach to solve data clustering problems within wireless sensor networks is proposed, including additional constraints on the distance among cluster centroids. A key feature of the presented algorithm is its ability to partition the original raw dataset into a suboptimal set of clusters, without the requirement of a priori specication of the desired cluster number. Secondly, after introducing a mathematical framework describing the dynamic model of a complex network, a set of centralised and distributed conditions are determined, allowing the detection of the connectedness of the network's underlying topological structure, its convergence to a steady state, and even to an agreement. To this purpose, the so-called Hegselmann-Krause opinion dynamics model is adopted, which describes the way agents of a community dynamically in uence with each other. Thirdly, the problem of optimal sensor location within a class of networked systems, which requires the detection of unknown input disturbance, is addressed. To this aim, a measure simultaneously based on the properties of controllability and observability of the network is used, which allows dierent sensor locations to be evaluated with respect to the location of the signal to be detected. These results inform the design of robust networks, and they suggest that sensor location methods based on the network topology alone may lead to poor detection performance

A two-phase problem with Robin conditions on the free boundary

We study for the first time a two-phase free boundary problem in which the solution satisfies a Robin boundary condition. We consider the case in which the solution is continuous across the free boundary and we prove an existence and a regularity result for minimizers of the associated variational problem. Finally, in the appendix, we give an example of a class of Steiner symmetric minimizers

Multidisciplinarity in Transition Pathways for Patients With Kidney Disease: The Current State of Play

In the field of medical care, successful transition from pediatric-centered to adult-oriented healthcare can provide a sense of continuity in the development of youth, and prepare them to accept responsibility for and manage their own chronic kidney condition in complete autonomy. The so-called transition process requires the presence of some basic aspects: a multidisciplinary team, which acts as a bridge between child and adult services; a comprehensive clinical, cognitive, psychological, and social change for the young people; the involvement of family and caregivers. Within the framework of transition and chronicity during the developmental age, we selected international papers explaining models which agreed on some important steps in the transition process, although many differences can be observed between different countries. In fact, in Europe, the situation appears to be heterogeneous as regards certain aspects: the written transition plan, the educational programmes, the timing of transfer to adult services, the presence of a transition coordinator, a dedicated off-site transition clinic. We then analyzed some studies focusing on patients with renal diseases, including the first to contain a standardized protocol for transition which was launched recently in the USA, and which seems to have already achieved important positive, although limited, results. In Italy, the issue of transition is still in its infancy, however important efforts in the management of chronic kidney disease have already been initiated in some regions, including Emila Romagna, which gives us hope for the future of many young people

Immune response to tick-borne hemoparasites: Host adaptive immune response mechanisms as potential targets for therapies and vaccines

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T-and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens

Innate Immune Response to Tick-Borne Pathogens: Cellular and Molecular Mechanisms Induced in the Hosts.

Many pathogens are transmitted by tick bites, including Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species. These pathogens cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen-derived antigens or indirectly by molecules released by host cells binding to these antigens. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. During the infection caused by different microbial agents, very similar profiles of the human innate immune response are observed including secretion of IL-1α, IL-8, and IFN-α, and suppression of superoxide dismutase, IL-1Ra and IL-17A release. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2-5 after tick bite. The ongoing research field of "inflammasome biology" focuses on the interactions among molecules and cells of innate immune response that could be responsible for triggering a protective adaptive immunity. The knowledge of the innate immunity mechanisms, as well as the new targets of investigation arising by bioinformatics analysis, could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections

Vitamin B supplementation and nutritional intake of methyl donors in patients with chronic kidney disease: A critical review of the impact on epigenetic machinery

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo-or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection

Immunological effects of a single hemodialysis treatment

Immune disorders, involving both innate and adaptive response, are common in patients with end-stage renal disease under chronic hemodialysis. Endogenous and exogenous factors, such as uremic toxins and the extracorporeal treatment itself, alter the immune balance, leading to chronic inflammation and higher risk of cardiovascular events. Several studies have previously described the immune effects of chronic hemodialysis and the possibility to modulate inflammation through more biocompatible dialyzers and innovative techniques. On the other hand, very limited data are available on the possible immunological effects of a single hemodialysis treatment. In spite of the lacking information about the immunological reactivity related to a single session, there is evidence to indicate that mediators of innate and adaptive response, above all complement cascade and T cells, are implicated in immune system modulation during hemodialysis treatment. Expanding our understanding of these modulations represents a necessary basis to develop pro-tolerogenic strategies in specific conditions, like hemodialysis in septic patients or the last session prior to kidney transplant in candidates for receiving a graft

Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis

Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl4) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl4 administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI

Vitamin D effects on bone homeostasis and cardiovascular system in patients with chronic kidney disease and renal transplant recipients

Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease–mineral and bone disorder (CKD–MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condi-tion is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes