Unraveling the Molecular Mechanisms Underlying Complement Dysregulation by Nephritic Factors in C3G and IC-MPGN

Membranoproliferative glomerulonephritis (MPGN) was recently classified as C3 glomerulopathies (C3G), and immune-complex (IC) mediated MPGN. Dysregulation of the complement alternative pathway, driven by acquired and/or genetic defects, plays a pathogenetic role in C3G. However, alternative pathway abnormalities were also found in IC-MPGN. The most common acquired drivers are the C3 nephritic factors (C3NeFs), heterogeneous autoantibodies that stabilize the C3 convertase, C3bBb. C3NeFs are traditionally detected by hemolytic assays based on sheep erythrocyte lysis, which however do not provide a direct molecular estimation of C3bBb formation and decay. We set up a microplate/western blot assay that specifically detects and quantifies C3bBb, and its precursor, the C3 proconvertase C3bB, to investigate the complex mechanistic effects of C3NeFs from patients with primary IC-MPGN (n = 13) and C3G (n = 13). In the absence of properdin, 9/26 patients had C3NeF IgGs stabilizing C3bBb against spontaneous and FH-accelerated decay. In the presence of properdin the IgGs of all but one patient had C3bBb-stabilizing activity. Properdin-independent C3NeFs were identified mostly in DDD patients, while properdin-dependent C3NeFs associated with either C3GN or IC-MPGN and with higher incidence of nephrotic syndrome. When we grouped patients based on our recent cluster analysis, patients in cluster 3, with highly electron-dense intramembranous deposits, low C3, and mostly normal sC5b-9 levels, had a higher prevalence of properdin-independent C3NeFs than patients in clusters 1 and 2. Conversely, about 70% of cluster 1 and 2 patients, with subendothelial, subepithelial, and mesangial deposits, low C3 levels and high sC5b-9 levels, had properdin-dependent C3NeFs. The flexibility of the assay allowed us to get deep insights into C3NeF mechanisms of action, showing that: (1) most C3NeFs bind strongly and irreversibly to C3 convertase; (2) C3NeFs and FH recognize different epitopes in C3 convertase; (3) C3NeFs bind rapidly to C3 convertase and antagonize the decay accelerating activity of FH on newly formed complexes; (4) C3NeFs do not affect formation and stability of the C3 proconvertase. Thus, our study provides a molecular approach to detecting and characterizing C3NeFs. The results highlight different mechanisms of complement dysregulation resulting in different complement profiles and patterns of glomerular injury, and this may have therapeutic implications

Preparazione e caratterizzazione fisico-meccanica di biopolimeri e scaffold polimerici per l'Ingegneria Tissutale

Il presente lavoro di tesi tratta la caratterizzazione meccanica di biopolimeri a base di chitosano e gelatina e di scaffold polimerici a base di poliuretano.La caratterizzazione consiste in prove di swelling e di perdita di peso, prove di stress-strain,e prove di creep-relaxation.I materiali analizzati saranno utilizzati per la ricrescita cellulare

Enhancing predictor analysis for reaction systems.

This thesis focuses on the formalization and analysis of an efficient method to over-approximate a predictor for reaction systems. Alongside this, we have the construction of the MuMa Predictor, a tool that allows the dynamic behaviour of reaction systems to be investigated using this method

Design, Implementation and Performance Evaluation of a Scheduling Algorithm for HSDPA System

The first mobile phone systems, introduced in the early 1980s, were based on analog interface technology with voice-only capabilities. These systems are limited in bandwidth and are low in quality. The increased need for more features was addressed by the introduction of the second generation (2G) network. 2G mobile phone systems, such as Global System for Mobile Communications (GSM), were characterized by digital circuit switched transmission and the introduction of advanced and fast phone to network signaling. However data services that use packet data technology were limited. The data packet service enhancement was introduced with 2.5G systems such as General Packet Radio Service (GPRS). GPRS introduced the packet switched domain to the Core Network (CN) of the GSM. The main features of 2.5G are the possibility to be permanently on line, only paying for the information received and a radio interface that typically provides a maximum data rate of 30-40 kbps with latency of 600 ms. The growing number of applications with quality of service (QoS) requirements, like web browsing, music and game download, mobile TV, Real Time (RT) video sharing, push e-mail, on-line gaming, mobile weblog, Voice over IP (VoIP) and so on, has led to the development of the third generation (3G) mobile telecommunications systems: Universal Mobile Telecommunication System (UMTS). UMTS is standardized by the 3rd Generation Partnership Project (3GPP). The most common form of 3G mobile systems adopts the Wideband Code Division Multiple Access (WCDMA) air interface. WCDMA Release 99 provides data rate of 384 kbps for wide area coverage and up to 2 Mbps, variable data rate on demand, a 5 Mhz bandwidth and a reduction of the network round trip time. The strong demand for multimedia services will require higher data rate than 2 Mbps, particularly for the downlink side, where mobile users data traffic will increase. In order to meet the increasing demand for high data-rate multimedia services, High Speed Downlink Packet Access (HSDPA) has been introduced by 3GPP in Release 5 of UMTS. HSDPA, labeled as 3.5G wireless system, will permit to increase user peak data rate up to 14 Mbps. This enhancement is possible for the introduction of a new downlink time shared channel among access users, that support a transmission time interval (TTI) of 2 ms, an hybrid automatic repeat request (H-ARQ), an adaptive modulation and coding scheme (AMC) and multicode transmissions. A key design feature in HSDPA concepts is packet scheduling, which is implemented in the Node B. A packet scheduler is responsible for sharing the available resources among the users eligible to receive data. Due to its function, the packet scheduler has a direct impact on the HSDPA system performance. It determines the perceived satisfaction among the user in the cell. As a result, it determines the overall behavior of the system. The main focus of this thesis is the design of an HSDPA scheduler aimed at servicing both RT traffic (i.e., VoIP) and BE traffic (i.e., TCP flows). The existing schedulers focus only on a limited subset of the overall HSDPA aspects. In fact, the design of the scheduling algorithm should take into account not only the channel conditions of the users, but also the way in which the HSDPA resources are assigned, the QoS requirements of different traffic types, the priority functions used for user selection and the backlog of each UEs. In order to devise an effective scheduling algorithm for HSDPA, we have first derived a CQI based power control algorithm that set dynamically the resources to allocate, in response to the CQI reports, in order to guaranteeing a BLER no larger than 10%. Then, we have designed and implemented an HSDPA scheduler that takes different decisions based on the traffic type of each UEs, using different priority functions. It considers BE traffic when no more RT traffic can be serviced (either because no RT PDU is waiting for transmission, or because all active RT flows are unable to access the medium, e.g. due to ongoing retransmissions). On the other hand, RT traffic is given as few resources as possible. More specifically the amount of resources involved in transmitting RT PDU is limited to the amount which is strictly necessary in order to guaranteeing a good reception at UE side. Moreover, each newly arrived RT packet in the Node B is associated with a discard timer and it is discarded when its deadline is missed. All the resources not used by RT flows are then allocated to BE traffic. The performance evaluation has been carried out through simulation using an event-driven ad hoc simulator of the HSDPA Release 6 system written for the Network Simulator 2. Comparison results are provided for VoIP services and for different scheduling algorithm, such as Round Robin (RR), MAX-C/I and a scheduler that we implement based on a work of Nokia Networks

Biodiversità dei carabidi e conservazione degli ambienti forestali

Dottorato di Ricerca in Biologia Animale, XXI Ciclo,a.a.2009-20104 Abstract Resilience, stability and resistence of forest ecosystems are the main properties providing the conservation of those habitats and allowing the maintenance of processes essential for the “ecosystem services” supply. In front of climate change and other disturbances coming from human activities, it is of fundamental importance to watch and check stability status of ecosystems. Ground beetles, good bioindicators, by their community composition, functional groups and morphometric sensitivity, provide indicators on habitat conservation evaluation and contribute to identify little changes among areas looking similar. The analisys of biodiversity could be improved by considering the above factors, enhancing the functional role of single species of the community.Università della Calabri

A Scheduling Method and System for Communication

In a method of scheduling transmission services over a high speed packet access communication link such as a HSDPA and/or a HSUPA link a list of queues is created for transmission services to be provided over the link. The queues, which include both Real Time and Non Real Time queues, are allotted respective service priorities based e.g. on a channel quality indicator and/or a Quality of Service indicator to produce an ordered list of queues based on the service priorities. The link resources needed for serving at least one set of queues having higher priorities in the ordered list are estimated and a check is made. If these resources are available, the set of queues having higher priorities in the ordered list are served. If the resources required are not available, at least one queue is removed from the ordered list of queues