C3b Receptors (CR1) on Peripheral Human Blood Cells

CR1 is the receptor for the activated third component of complement C3b. It is present on the cell membranes of human erythrocytes, lymphocytes, polymorphonuclear leucocytes, mononuclear phagocytes, mast cells, B lymphocytes, some T lymphocytes and kidney podocytes. Purification of CR1 from human erythrocytes using cation exchange and affinity chromatography revealed a single protein with a molecular weight of 230000 daltons. This protein was used to raise a polyclonal antiserum in rabbits, which was then utilised in the development of a radioimmunoassay to quantitate the number of CR1 on human peripheral blood cells. This assay was used successfully to quantitate CR1 levels on erythrocytes. However, it could not be adapted to assess CR1 levels on monocytes, lymphocytes or polymorphonuclear leucocytes . CR1 levels have previously been reported to be reduced on erythrocytes from patients with systemic lupus erythematosus (SLE). However, there has been no agreement in the literature as to whether the reduced erythrocyte CR1 levels observed are acquired as a consequence of the pathological process of the disease or are an inherited defect. The aim of the experiments performed in this thesis was to establish whether CR1 levels are inherited or acquired. To examine this erythrocyte CR1 levels were studied in normal individuals and SLE patients. In addition, patients with rheumatoid arthritis (RA) were investigated. Serial studies were performed on normal individuals, SLE and RA patients to see whether there were temporal changes in CR1 levels. CR1 levels were also assessed in normal families and in families where one or more individuals had SLE to ascertain whether receptor levels were inherited. CR1 levels were quantitated using a radioimmunoassay, which measured the amount of 125I-F(ab')2 anti-CR1 binding to the erythrocytes. From this the number of binding sites per erythrocyte for the F(ab')2 anti-CR1 moiety was calculated (CR1 sites/erythrocyte). Seventy normal erythrocyte specimens were studied; the mean was 3320 CR1 sites/erythrocyte (range 0 to 21692 CR1 sites/ erythrocyte) whilst the mean for the SLE patients was 1541 (n=41, range 0 to 15766 CR1 sites/erythrocyte), significantly lower (p 0. 001) than the normals. Likewise the mean (1410 CR1 sites/erythrocyte, n=25) for the RA patients was also significantly lower (p <0.05). A striking observation was that many of the SLE patients had no receptors (27% as opposed to 1.5% in the normals and 0% in the RA group). When the SLE patients were further subdivided into those who were in an active disease phase or an inactive disease phase, the majority of patients with zero receptors were in an active disease state. When analysed further the mean CR1 level for the patients with active disease (356 CR1 sites/erythrocyte) was significantly lower (p <0.001) than those with inactive disease (2428 CR1 sites/erythrocyte). These levels were not related to any of the serological parameters studied. Serial studies on SLE patients showed that in some individuals the CR1 levels varied with disease activity, decreasing during exacerbations and increasing during remission. Family studies showed a clustering of low, medium or high CR1 levels in individual families. However, where a member of a family had SLE their CR1 levels were not akin to their families suggesting acquisition and not inheritance. Studies of two sets of identical twins showed that they did not have identical CR1 suggesting that they had acquired different levels. Two main conclusions may be drawn from these studies; firstly, genetic factors probably do influence CR1 levels as supported by the clustering of CR1 levels in the families studied and secondly, in some patients with SLE the CR1 levels were acquired, as indicated by the change in CR1 levels with disease activity and the lower levels found in patients with disease exacerbations. Two possible explanations could account for the acquisition of reduced receptor levels, receptor removal or receptor blockade. In support of the latter it was observed that large opsonized immune complexes (formed with thyroglobulin or DNA, with specific antiserum) bound to and totally or partially blocked the erythrocyte CR1. Thus in vivo blockade of CR1 by circulating immune complexes could account for the reduced CR1 levels seen in some SLE patients when their disease is in exacerbation

Digital control of high frequency PWM convertors

The thesis begins with a review of presently available analogue and digital control schemes for high frequency PWM converters. Advantages and disadvantages of each scheme are identified, to determine which features would be desirable in a new digital control scheme. An extensive examination of peak and average current mode control is undertaken, using state-space/sampled data modelling, to gain more detailed information on the properties of current mode control. On the basis of this information, a new digital current mode control scheme is put forward. This uses samples of the inductor current, line voltage and output voltage to implement a control strategy in software. Average inductor current is calculated each switching cycle and compared to the current program level, providing true current mode control. This has some advantages over traditional methods. Accurate inductor current tracking of the current program level is achieved and no slope compensation is required for stable operation over the full range of duty ratios. Line voltage feed-forward is possible in buck derived topologies, which provides an effective null in the audio susceptibility transfer function, independent of compensation parameters. Current loop stability is independent of line voltage or load current in the buck topology, allowing operation with optimum loop compensation under all normal operating conditions. Practical implementation of a digital current mode controlled current-fed converter is described. This includes a modular architecture for the hardware and documentation for the software. Effects of component selection on the achievable converter switching frequency and dynamic performance are discussed. A method is put forward for the direct digital measurement of loop gain and phase in digital control systems. This is used to obtain actual loop responses from a test bed digital current mode controlled current-fed converter. Line and load transient response tests are presented which demonstrate the dynamic characteristics of digital current mode control

Core-periphery organization of complex networks

Networks may, or may not, be wired to have a core that is both itself densely connected and central in terms of graph distance. In this study we propose a coefficient to measure if the network has such a clear-cut core-periphery dichotomy. We measure this coefficient for a number of real-world and model networks and find that different classes of networks have their characteristic values. For example do geographical networks have a strong core-periphery structure, while the core-periphery structure of social networks (despite their positive degree-degree correlations) is rather weak. We proceed to study radial statistics of the core, i.e. properties of the n-neighborhoods of the core vertices for increasing n. We find that almost all networks have unexpectedly many edges within n-neighborhoods at a certain distance from the core suggesting an effective radius for non-trivial network processes

Tax evasion dynamics and Zaklan model on Opinion-dependent Network

Within the context of agent-based Monte-Carlo simulations, we study the well-known majority-vote model (MVM) with noise applied to tax evasion on Stauffer-Hohnisch-Pittnauer (SHP) networks. To control the fluctuations for tax evasion in the economics model proposed by Zaklan, MVM is applied in the neighborhood of the critical noise $q_{c}$ to evolve the Zaklan model. The Zaklan model had been studied recently using the equilibrium Ising model. Here we show that the Zaklan model is robust because this can be studied besides using equilibrium dynamics of Ising model also through the nonequilibrium MVM and on various topologies giving the same behavior regardless of dynamic or topology used here.Comment: 14 page, 4 figure

Network dynamics of ongoing social relationships

Many recent large-scale studies of interaction networks have focused on networks of accumulated contacts. In this paper we explore social networks of ongoing relationships with an emphasis on dynamical aspects. We find a distribution of response times (times between consecutive contacts of different direction between two actors) that has a power-law shape over a large range. We also argue that the distribution of relationship duration (the time between the first and last contacts between actors) is exponentially decaying. Methods to reanalyze the data to compensate for the finite sampling time are proposed. We find that the degree distribution for networks of ongoing contacts fits better to a power-law than the degree distribution of the network of accumulated contacts do. We see that the clustering and assortative mixing coefficients are of the same order for networks of ongoing and accumulated contacts, and that the structural fluctuations of the former are rather large.Comment: to appear in Europhys. Let

Signatures of currency vertices

Many real-world networks have broad degree distributions. For some systems, this means that the functional significance of the vertices is also broadly distributed, in other cases the vertices are equally significant, but in different ways. One example of the latter case is metabolic networks, where the high-degree vertices -- the currency metabolites -- supply the molecular groups to the low-degree metabolites, and the latter are responsible for the higher-order biological function, of vital importance to the organism. In this paper, we propose a generalization of currency metabolites to currency vertices. We investigate the network structural characteristics of such systems, both in model networks and in some empirical systems. In addition to metabolic networks, we find that a network of music collaborations and a network of e-mail exchange could be described by a division of the vertices into currency vertices and others.Comment: to appear in Journal of the Physical Society of Japa

The diplomat's dilemma: Maximal power for minimal effort in social networks

Closeness is a global measure of centrality in networks, and a proxy for how influential actors are in social networks. In most network models, and many empirical networks, closeness is strongly correlated with degree. However, in social networks there is a cost of maintaining social ties. This leads to a situation (that can occur in the professional social networks of executives, lobbyists, diplomats and so on) where agents have the conflicting objectives of aiming for centrality while simultaneously keeping the degree low. We investigate this situation in an adaptive network-evolution model where agents optimize their positions in the network following individual strategies, and using only local information. The strategies are also optimized, based on the success of the agent and its neighbors. We measure and describe the time evolution of the network and the agents' strategies.Comment: Submitted to Adaptive Networks: Theory, Models and Applications, to be published from Springe

Nonlocal evolution of weighted scale-free networks

We introduce the notion of globally updating evolution for a class of weighted networks, in which the weight of a link is characterized by the amount of data packet transport flowing through it. By noting that the packet transport over the network is determined nonlocally, this approach can explain the generic nonlinear scaling between the strength and the degree of a node. We demonstrate by a simple model that the strength-driven evolution scheme recently introduced can be generalized to a nonlinear preferential attachment rule, generating the power-law behaviors in degree and in strength simultaneously.Comment: 4 pages, 4 figures, final version published in PR