In vivo characterization of renal auto-antigens involved in human auto-immune diseases: the case of membranous glomerulonephritis

Renal auto-immune diseases represent a major source of morbidity in humans. For many years the knowledge on mechanisms of auto-immunity involving the kidney has been uniquely based on animal models. However, these findings often could not be readily translated to humans owing to notably difference in antigen expression by human podocytes. One example is Heymann nephritis (HN), the experimental model of human membranous glomerulonephritis (MGN), which is obtained in rats by injecting antibodies against megalin, a protein that is not present in human glomeruli. Human studies could not be done in the past since sequencing required too much material exceeding what obtainable from tissue biopsies in vivo. Research is now on the way to identify auto-antigens and isolate specific auto-antibodies in humans. New technology developments based on tissue microdissection and proteomical analysis have facilitated the recent discoveries, allowing direct analysis of human tissue in vivo. Major advances on the pathogenesis of MGN, the prototype for the formation and glomerular deposition of auto-antibodies, are now in progress. Two independent groups have, in fact, demonstrated the existence of specific IgG(4) against phospholipase A2 receptor, aldose reductase and Mn-superoxide dismutase in glomerular eluates and in plasma of a prominent part of patients with MGN, suggesting a major role of these proteins as auto-antigens in human MGN. This review will focalize these aspects outlining the contribution of proteomics in most recent developments.     

A declarative two-level framework to specify and verify workflow and authorization policies in service-oriented architectures

The specification of distributed service-oriented applications spans several levels of abstraction, e.g., the protocol for exchanging messages, the set of interface functionalities, the types of the manipulated data, the workflow, the access policy, etc. Many (even executable) specification languages are available to describe each level in separation. However, these levels may interact in subtle ways (for example, the control flow may depend on the values of some data variables) so that a precise abstraction of the application amounts to more than the sum of its per level components. This problem is even more acute in the design phase when automated analysis techniques may greatly help the difficult task of building “correct” applications faced by designers. To alleviate this kind of problems, this paper introduces a framework for the formal specification and automated analysis of distributed service-oriented applications in two levels: one for the workflow and one for the authorization policies. The former allows one to precisely describe the control and data parts of an application with their mutual dependencies. The latter focuses on the specification of the criteria for granting or denying third-party applications the possibility to access shared resources or to execute certain interface functionalities. These levels can be seen as abstractions of one or of several levels of specification mentioned above. The novelty of our proposal is the possibility to unambiguously specify the—often subtle—interplay between the workflow and policy levels uniformly in the same framework. Additionally, our framework allows us to define and investigate verification problems for service-oriented applications (such as executability and invariant checking) and give sufficient conditions for their decidability. These results are non-trivial because their scope of applicability goes well beyond the case of finite state spaces allowing for applications manipulating variables ranging over infinite domains. As proof of concept, we show the suitability and flexibility of our approach on two quite different examples inspired by industrial case studies.     

Mediating debate through on-line large-scale argumentation: Evidence from the field

Web 2.0 technologies, such as forums and wikis, are enabling an explosion of global knowledge sharing through distributed large-scale conversations, but they seem to be less successful at supporting collaborative deliberation around complex and controversial questions. In order to cope with this limitation, many scholars have proposed to adopt on-line argumentation platforms to improve information visualization, organization and reuse. However, such research has mostly focused on the design of adequate argument-based knowledge formalisms. Less attention has been paid to the empirical analysis of actual interactions mediated by argumentation technology with reasonably large user communities. In this paper, we present an in-depth analysis of the data obtained in the empirical test of an argumentation platform where a 160-member community created, in 3 weeks, what is to our knowledge the largest single online argument map ever built (around 5000 posts). Our results show that (i) users were able to quickly and comprehensively explore and map the debate on the selected discussion topic; (ii) substantial moderation was needed to ensure that the argument map was well-organized and users were confident with the argumentation formalism; (iii) considerable out-of-the map communication occurred, possibly as a way to allow for conversational flows inhibited by the argumentation formalism, (iv) formal rating of contributions favored exploration of the map, understanding the debate structure, and improving the quality of content.     

Sound synthesis and evaluation of interactive footsteps and environmental sounds rendering for virtual reality applications

We propose a system that affords real-time sound synthesis of footsteps on different materials. The system is based on microphones, which detect real footstep sounds from subjects, from which the ground reaction force (GRF) is estimated. Such GRF is used to control a sound synthesis engine based on physical models. Two experiments were conducted. In the first experiment, the ability of subjects to recognize the surface they were exposed to was assessed. In the second experiment, the sound synthesis engine was enhanced with environmental sounds. Results show that, in some conditions, adding a soundscape significantly improves the recognition of the simulated environment.     

Performance of One-Round Walks in Linear Congestion Games

We investigate the approximation ratio of the solutions achieved after a one-round walk in linear congestion games. We consider the social functions Sum, defined as the sum of the players’ costs, and Max, defined as the maximum cost per player, as a measure of the quality of a given solution. For the social function Sum and one-round walks starting from the empty strategy profile, we close the gap between the upper bound of \(2+\sqrt{5}\approx 4.24\) given in Christodoulou et al. (Proceedings of the 23rd International Symposium on Theoretical Aspects of Computer Science (STACS), LNCS, vol. 3884, pp. 349–360, Springer, Berlin, 2006) and the lower bound of 4 derived in Caragiannis et al. (Proceedings of the 33rd International Colloquium on Automata, Languages and Programming (ICALP), LNCS, vol. 4051, pp. 311–322, Springer, Berlin, 2006) by providing a matching lower bound whose construction and analysis require non-trivial arguments. For the social function Max, for which, to the best of our knowledge, no results were known prior to this work, we show an approximation ratio of \(\Theta(\sqrt[4]{n^{3}})\) (resp. \(\Theta(n\sqrt{n})\)), where n is the number of players, for one-round walks starting from the empty (resp. an arbitrary) strategy profile.     

On the Convergence of Multicast Games in Directed Networks

We investigate the convergence of the price of anarchy after a limited number of moves in the classical multicast communication game when the underlying communication network is directed. Namely, a subset of nodes of the network are interested in receiving the transmission from a given source node and can share the cost of the used links according to fixed cost sharing methods. At each step, a single receiver is allowed to modify its communication strategy, that is to select a communication path from the source, and assuming a selfish or rational behavior, it will make a best response move, that is it will select a solution yielding the minimum possible payment or shared cost. We determine lower and upper bounds on the price of anarchy, that is the highest possible ratio among the overall cost of the links used by the receivers and the minimum possible cost realizing the required communications, after a limited number of moves under the fundamental Shapley cost sharing method. In particular, assuming that the initial set of connecting paths can be arbitrary, we show an $O(r\sqrt{r})We investigate the convergence of the price of anarchy after a limited number of moves in the classical multicast communication game when the underlying communication network is directed. Namely, a subset of nodes of the network are interested in receiving the transmission from a given source node and can share the cost of the used links according to fixed cost sharing methods. At each step, a single receiver is allowed to modify its communication strategy, that is to select a communication path from the source, and assuming a selfish or rational behavior, it will make a best response move, that is it will select a solution yielding the minimum possible payment or shared cost. We determine lower and upper bounds on the price of anarchy, that is the highest possible ratio among the overall cost of the links used by the receivers and the minimum possible cost realizing the required communications, after a limited number of moves under the fundamental Shapley cost sharing method. In particular, assuming that the initial set of connecting paths can be arbitrary, we show an O(r?r)O(r\sqrt{r}) upper bound on the price of anarchy after 2 rounds, during each of which all the receivers move exactly once, and a matching lower bound, that we also extend to W(r^k?{r})\Omega(r\sqrt[k]{r}) for any number k≥2 rounds, where r is the number of receivers. Similarly, exactly matching upper and lower bounds equal to r are determined for any number of rounds when starting from the empty state in which no path has been selected. Analogous results are obtained also with respect to other three natural cost sharing methods considered in the literature, that is the egalitarian, path-proportional and egalitarian-path proportional ones. Most results are also extended to the undirected case in which the communication links are bidirectional.     

Hybrid dynamics of stochastic programs

We provide Stochastic Concurrent Constraint Programming (sCCP), a stochastic process algebra based on CCP, with a semantics in terms of hybrid automata. We associate with each sCCP program both a stochastic and a non-deterministic hybrid automaton. Then, we compare such automata with the standard stochastic semantics (given by a Continuous Time Markov Chain) and the one based on ordinary differential equations, obtained by a fluid-flow approximation technique. We discuss in detail two case studies: Repressilator and the Circadian Clock, with particular regard to the robustness exhibited by the different semantic models and to the effect of discreteness in dynamical evolution of such systems.     

Logic based methods for SNPs tagging and reconstruction

SNPs are positions of the DNA sequences where the differences among individuals are embedded. The knowledge of such SNPs is crucial for disease association studies, but even if the number of such positions is low (about 1% of the entire sequence), the cost to extract the complete information is actually very high. Recent studies have shown that DNA sequences are structured into blocks of positions, that are conserved during evolution, where there is strong correlation among values (alleles) of different loci. To reduce the cost of extracting SNPs information, the block structure of the DNA has suggested to limit the process to a subset of SNPs, the so-called Tag SNPs, that are able to maintain the most of the information contained in the whole sequence. In this paper, we apply a technique for feature selection based on integer programming to the problem of Tag SNP selection. Moreover, to test the quality of our approach, we consider also the problem of SNPs reconstruction, i.e. the problem of deriving unknown SNPs from the value of Tag SNPs and propose two reconstruction methods, one based on a majority vote and the other on a machine learning approach. We test our algorithm on two public data sets of different nature, providing results that are, when comparable, in line with the related literature. One of the interesting aspects of the proposed method is to be found in its capability to deal simultaneously with very large SNPs sets, and, in addition, to provide highly informative reconstruction rules in the form of logic formulas.