Distributed Decision Through Self-Synchronizing Sensor Networks in the Presence of Propagation Delays and Nonreciprocal Channels

In this paper we propose and analyze a distributed algorithm for achieving globally optimal decisions, either estimation or detection, through a self-synchronization mechanism among linearly coupled integrators initialized with local measurements. We model the interaction among the nodes as a directed graph with weights dependent on the radio interface and we pose special attention to the effect of the propagation delays occurring in the exchange of data among sensors, as a function of the network geometry. We derive necessary and sufficient conditions for the proposed system to reach a consensus on globally optimal decision statistics. One of the major results proved in this work is that a consensus is achieved for any bounded delay condition if and only if the directed graph is quasi-strongly connected. We also provide a closed form expression for the global consensus, showing that the effect of delays is, in general, to introduce a bias in the final decision. The closed form expression is also useful to modify the consensus mechanism in order to get rid of the bias with minimum extra complexity.Comment: Conference paper. Journal version submitted to IEEE Transactions on Signal Processing, January 10, 2007. Paper accepted for the publication on the VIII IEEE Workshop on Signal Processing Advances in Wireless Communications, (SPAWC 2007), January 22, 200

Distributed Decision Through Self-Synchronizing Sensor Networks in the Presence of Propagation Delays and Asymmetric Channels

In this paper we propose and analyze a distributed algorithm for achieving globally optimal decisions, either estimation or detection, through a self-synchronization mechanism among linearly coupled integrators initialized with local measurements. We model the interaction among the nodes as a directed graph with weights (possibly) dependent on the radio channels and we pose special attention to the effect of the propagation delay occurring in the exchange of data among sensors, as a function of the network geometry. We derive necessary and sufficient conditions for the proposed system to reach a consensus on globally optimal decision statistics. One of the major results proved in this work is that a consensus is reached with exponential convergence speed for any bounded delay condition if and only if the directed graph is quasi-strongly connected. We provide a closed form expression for the global consensus, showing that the effect of delays is, in general, the introduction of a bias in the final decision. Finally, we exploit our closed form expression to devise a double-step consensus mechanism able to provide an unbiased estimate with minimum extra complexity, without the need to know or estimate the channel parameters.Comment: To be published on IEEE Transactions on Signal Processin

Renal lesions in patients with type 2 diabetes: A puzzle waiting to be solved

Three hundred sixty-six million people worldwide will be living with diabetes mellitus (DM) by 2030 ([1, 2]; http://www.idf.org/global-diabetes-plan-2011-2021). Prospectively, 75–150 million of these patients will develop a diabetic nephropathy (DN) or a non-diabetic renal disease (NDRD), either isolated or superimposed on DN [3, 4]. To date, the differential diagnosis between ND and NDRD remains a challenge that nephrologists are trying to win [5]

The Role of Lysine 63-Linked Ubiquitylation in Health and Disease

A specific subfamily within the E2 protein family is involved in the synthesis of noncanonical poly-ubiquitin chains, linked through lysine 63 residues. The role of lysine 63-linked polyubiquitylation in diseases has emerged only recently. Under physiological conditions, this process does not seem to be involved in the classical protein degradation by the proteasome, but it is involved in the regulation of intracellular signaling, DNA damage response, cellular trafficking, and lysosomal targeting. The alteration of this process has been described in a number of pathological conditions, including immune disorders, diabetes, and cancer. In this chapter, we will describe the role of lysine 63-linked ubiquitylation in the regulation of diverse signaling pathways involved in cell behavior. We will also describe some pathological conditions in which altered lysine 63-linked ubiquitylation has been referred to play an important role

The role of tubular cells in the progression of renal damage: guilty or innocent?

The progressive development of sclerosis in remnant glomeruli after the initial renal damage is caused by hyperfiltration. Thus, there is a progressive decrease in the number of glomeruli connected..

Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease

Abstract In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design of new personalized therapies targeting gut microbiota

Molecular and Genetic Basis of Inherited Nephrotic Syndrome

Nephrotic syndrome is an heterogeneous disease characterized by increased permeability of the glomerular filtration barrier for macromolecules. Podocytes, the visceral epithelial cells of glomerulus, play critical role in ultrafiltration of plasma and are involved in a wide number of inherited and acquired glomerular diseases. The identification of mutations in nephrin and other podocyte genes as causes of genetic forms of nephrotic syndrome has revealed new important aspects of the pathogenesis of proteinuric kidney diseases and expanded our knowledge of the glomerular biology. Moreover, a novel concept of a highly dynamic slit diaphragm proteins is emerging. The most significant discoveries in our understanding of the structure and function of the glomerular filtration barrier are reviewed in this paper

Diabetic kidney disease. new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "the natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function"

Recent epidemiological studies have disclosed heterogeneity in diabetic kidney disease (DKD). In addition to the classical albuminuric phenotype, two new phenotypes have emerged, i.e., “nonalbuminuric renal impairment” and “progressive renal decline”, suggesting that DKD progression toward end-stage kidney disease in diabetic patients may occur through two distinct pathways heralded by a progressive increase in albuminuria and decline in renal function independent of albuminuria, respectively. Besides the natural history of DKD, also the management of hyperglycemia in patients with type 2 diabetes and reduced renal function has profoundly changed in the last two decades. New anti-hyperglycemic drugs have become available for treatment of these individuals and the lowest estimated glomerular filtration rate safety thresholds for some of the old agents have been reconsidered. This joint document of the Italian Diabetes Society (SID) and the Italian Society of Nephrology (SIN) reviews the natural history of DKD in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents in DKD patients

A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications

Diabetic nephropathy (DN), a microvascular complication occurring in approximately 20-40% of patients with type 2 diabetes mellitus (T2DM), is characterized by the progressive impairment of glomerular filtration and the development of KimmelstielWilson lesions leading to end-stage renal failure (ESRD). The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed

Malattia renale policistica autosomica dominante. Nuovi approcci terapeutici "Ottimisti per diritto"

La malattia renale policistica autosomica dominante (Autosomal Dominant Polycystic Kidney Disease, ADPKD), è la più comune forma di malattia renale cistica e rappresenta, nel mondo, la causa di terapia sostitutiva emodialitica nel 7–10% dei pazienti. Sono noti due tipi di malattia policistica: il tipo I è causato da mutazioni del gene PKD1, che codifica per la policistina-1, è la forma più diffusa e aggressiva e colpisce soggetti di età giovane; il tipo II è causato da mutazioni del gene PKD2 che codifica per la policistina-2 e rappresenta il 10–15% dei casi, a evoluzione più lenta. Clinicamente, le cisti si svilup-pano a livello renale, epatico, pancreatico e intestinale. Il dolore cronico, la chirurgia palliativa, l'insufficienza renale, la dialisi, il trapianto, come anche la morte, sono tutte conseguenze di questa malattia genetica che non ha ancora una terapia medica per rallentare o arrestare la sua progressione. Di grande interesse per il suo potenziale terapeutico, è la dimostrazione che la Policistina-1, formando un complesso con la tuberina (la proteina la cui mutazione causa la sclerosi tuberosa), agisce come un inibitore endogeno dell'attività del mammalian Target of Rapamycin (mTOR). Se mutato, come nell'ADPKD, tale meccanismo inibitorio viene compromesso e ciò favorirebbe lo sviluppo delle cisti. I recenti discordanti risultati di alcuni studi nell'uomo sull'uso di un inibitore di mTOR in pazienti affetti da ADPKD, possono generare interrogativi e confusione, ma diverse e molteplici possono essere le ragioni per cui tali studi hanno portato a conclusioni diverse fra di loro. A questo punto, è d'obbligo porsi l'interrogativo se questi risultati siano la fine o possano essere l'inizio di nuovi studi. Agli Autori piace considerare la seconda ipotesi, in quanto tutti gli studi di biologia molecolare, quelli preclinici, e su animali, hanno confermato la "bontà" del percorso intrapreso. Questa rassegna viene proposta per fare chiarezza sui risultati di tali studi e per dare una speranza concreta, secondo l'opinione degli Autori, sulla possibilità di riuscire a scoprire una cura per tale patologia