Fast algorithms for large scale generalized distance weighted discrimination

High dimension low sample size statistical analysis is important in a wide range of applications. In such situations, the highly appealing discrimination method, support vector machine, can be improved to alleviate data piling at the margin. This leads naturally to the development of distance weighted discrimination (DWD), which can be modeled as a second-order cone programming problem and solved by interior-point methods when the scale (in sample size and feature dimension) of the data is moderate. Here, we design a scalable and robust algorithm for solving large scale generalized DWD problems. Numerical experiments on real data sets from the UCI repository demonstrate that our algorithm is highly efficient in solving large scale problems, and sometimes even more efficient than the highly optimized LIBLINEAR and LIBSVM for solving the corresponding SVM problems

Role of Interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression

Background: The use of TNF inhibitors has been a major progress in the treatment of chronic inflammation. However, not all patients respond. In addition, response will be often lost when treatment is stopped. These clinical aspects indicate that other cytokines might be involved and we focus here on the role of IL-17. In addition, the chronic nature of joint inflammation may contribute to reduced response and enhanced chronicity. Therefore we studied the capacity of IL-17 to regulate synoviolin, an E3 ubiquitin ligase implicated in synovial hyperplasia in human rheumatoid arthritis (RA) FLS and in chronic reactivated streptococcal cell wall (SCW)-induced arthritis.<p></p> Methodology/Principal Findings: Chronic reactivated SCW-induced arthritis was examined in IL-17R deficient and wild-type mice. Synoviolin expression was analysed by real-time RT-PCR, Western Blot or immunostaining in RA FLS and tissue, and p53 assessed by Western Blot. Apoptosis was detected by annexin V/propidium iodide staining, SS DNA apoptosis ELISA kit or TUNEL staining and proliferation by PCNA staining. IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17-RC) or synoviolin inhibition were achieved by small interfering RNA (siRNA) or neutralizing antibodies. IL-17 induced sustained synoviolin expression in RA FLS. Sodium nitroprusside (SNP)-induced RA FLS apoptosis was associated with reduced synoviolin expression and was rescued by IL-17 treatment with a corresponding increase in synoviolin expression. IL-17RC or IL-17RA RNA interference increased SNP-induced apoptosis, and decreased IL-17-induced synoviolin. IL-17 rescued RA FLS from apoptosis induced by synoviolin knockdown. IL-17 and TNF had additive effects on synoviolin expression and protection against apoptosis induced by synoviolin knowndown. In IL-17R deficient mice, a decrease in arthritis severity was characterized by increased synovial apoptosis, reduced proliferation and a marked reduction in synoviolin expression. A distinct absence of synoviolin expressing germinal centres in IL-17R deficient mice contrasted with synoviolin positive B cells and Th17 cells in synovial germinal centre-like structures.<p></p> Conclusion/Significance: IL-17 induction of synoviolin may contribute at least in part to RA chronicity by prolonging the survival of RA FLS and immune cells in germinal centre reactions. These results extend the role of IL-17 to synovial hyperplasia.<p></p&gt

Surface-reconstructed Icosahedral Structures for Lead Clusters

We describe a new family of icosahedral structures for lead clusters. In general, structures in this family contain a Mackay icosahedral core with a reconstructed two-shell outer-layer. This family includes the anti-Mackay icosahedra, which have have a Mackay icosahedral core but with most of the surface atoms in hexagonal close-packed positions. Using a many-body glue potential for lead, we identify two icosahedral structures in this family which have the lowest energies of any known structure in the size range from 900 to 15000 lead atoms. We show that these structures are stabilized by a feature of the many-body glue part of the interatomic potential.Comment: 9 pages, 8 figure

Computer simulations of VANETs using realistic city topologies

Researchers in vehicular ad hoc networks (VANETs) commonly use simulation to test new algorithms and techniques. This is the case because of the high cost and labor involved in deploying and testing vehicles in real outdoor scenarios. However, when determining the factors that should be taken into account in these simulations, some factors such as realistic road topologies and presence of obstacles are rarely addressed. In this paper, we first evaluate the packet error rate (PER) through actual measurements in an outdoor road scenario, and deduce a close model of the PER for VANETs. Secondly, we introduce a topology-based visibility scheme such that road dimension and geometry can be accounted for, in addition to line-of-sight. We then combine these factors to determine when warning messages (i.e., messages that warn drivers of danger and hazards) are successfully received in a VANET. Through extensive simulations using different road topologies, city maps, and visibility schemes, we show these factors can impact warning message dissemination time and packet delivery rate.This work was partially supported by the Ministerio de Educacion y Ciencia, Spain, under Grant TIN2011-27543-C03-01, and by the Diputacion General de Aragon, under Grant "subvenciones destinadas a la formacion y contratacion de personal investigador".Martínez, FJ.; Fogue, M.; Toh, C.; Cano Escribá, JC.; Tavares De Araujo Cesariny Calafate, CM.; Manzoni, P. (2013). Computer simulations of VANETs using realistic city topologies. Wireless Personal Communications. 69(2):639-663. https://doi.org/10.1007/s11277-012-0594-6S639663692Martinez F. J., Toh C.-K., Cano J.-C., Calafate C. T., Manzoni P. (2011) A survey and comparative study of simulators for vehicular ad hoc networks (VANETs). Wireless Communications and Mobile Computing Journal 11(7): 813–828Toh C.-K. (2001) Ad hoc mobile wireless networks: Protocols and systems. Prentice Hall, Englewood Cliffs, NJIEEE 802.11 Working Group. (2010). IEEE standard for information technology—telecommunications and information exchange between systems—local and metropolitan area networks—Specific requirements—Part 11: Wireless LAN medium access control (MAC) and physical layer (PHY) specifications amendment 6: Wireless Access in Vehicular Environments.Sommer, C., Eckhoff, D., German, R., & Dressler F. (2011). A computationally inexpensive empirical model of IEEE 802.11p radio shadowing in urban environments. In Eighth international conference on wireless on-demand network systems and services (WONS), pp. 84–90.Bohm, A., Lidstrom, K., Jonsson, M., & Larsson, T. (2010). Evaluating CALM M5-based vehicle-to-vehicle communication in various road settings through field trials. In Proceedings of the 35th IEEE conference on local computer networks (LCN’10), Denver, Colorado, USA, pp. 613–620.Martinez, F. J., Fogue, M., Coll, M., Cano, J.-C., Calafate, C. T., & Manzoni, P. (2010). Assessing the impact of a realistic radio propagation model on VANET scenarios using real maps. In 9th IEEE international symposium on network computing and applications (NCA), Boston, USA, pp. 132–139.Fall, K., & Varadhan, K. (2000). “ns notes and documents,” The VINT project. UC Berkeley, LBL, USC/ISI, and Xerox PARC, February 2000. Available at http://www.isi.edu/nsnam/ns/ns-documentation.html .Marinoni, S., & Kari, H. H. (2006). Ad hoc routing protocol performance in a realistic environment. In Proceedings of the international conference on networking, international conference on systems and international conference on mobile communications and learning technologies (ICN/ICONS/MCL 2006), Washington, DC, USA.Mahajan, A., Potnis, N., Gopalan, K., & Wang, A. (2007). Modeling VANET deployment in urban settings. In International workshop on modeling analysis and simulation of wireless and mobile systems (MSWiM 2007), Crete Island, Greece.Suriyapaiboonwattana, K., Pornavalai, C., & Chakraborty, G. (2009). An adaptive alert message dissemination protocol for VANET to improve road safety. In IEEE intlernational conference on fuzzy systems, 2009. FUZZ-IEEE 2009, pp. 1639–1644.Bako, B., Schoch, E., Kargl, F., & Weber, M. (2008). Optimized position based gossiping in VANETs. In Vehicular technology conference, 2008. VTC 2008-Fall. IEEE 68th, pp. 1–5.Martinez, F. J., Cano, J.-C., Calafate, C. T., & Manzoni, P. (2008). Citymob: A mobility model pattern generator for VANETs. In IEEE vehicular networks and applications workshop (Vehi-Mobi, held with ICC), Beijing, China.Torrent-Moreno, M., Santi, P., & Hartenstein, H. (2007). Inter-vehicle communications: Assessing information dissemination under safety constraints. In Proceedings of the 4th annual conference on wireless on demand network systems and services (WONS), Oberguyrgl, Austria.Martinez, F. J., Toh, C.-K., Cano, J.-C., Calafate, C. T., & Manzoni, P. (2009). Realistic radio propagation models (RPMs) for VANET simulations. In IEEE wireless communications and networking conference (WCNC), Budapest, Hungary.Martinez, F. J., Toh, C.-K., Cano, J.-C., Calafate, C. T., & Manzoni, P. (2010). A street broadcast reduction scheme (SBR) to mitigate the broadcast storm problem in VANETs. Wireless personal communications, pp. 1–14. doi: 10.1007/s11277-010-9989-4Ni, S.-Y., Tseng, Y.-C., Chen, Y.-S., & Sheu, J.-P. (1999). The broadcast storm problem in a mobile ad hoc network. In ACM/IEEE international conference on mobile computing and networking (MobiCom 1999), Seattle Washington.Krajzewicz, D., & Rossel, C. (2007). “Simulation of urban mobility (SUMO),” Centre for Applied Informatics (ZAIK) and the Institute of Transport Research at the German Aerospace Centre. Available at http://sumo.sourceforge.net/index.shtml .OpenStreetMap Team. (2009). OpenStreetMap, collaborative project to create a free editable map of the world. Available at http://www.openstreetmap.org .U.S. Census Bureau. (2009). TIGER, topologically integrated geographic encoding and referencing. Available at http://www.census.gov/geo/www/tiger .Krauss S., Wagner P., Gawron C. (1997) Metastable states in a microscopic model of traffic flow. Physical Review E 55(5): 5597–5602Krajzewicz, D., Hertkorn, G., Rossel, C., & Wagner, P. (2002). SUMO (Simulation of Urban MObility)—An open-source traffic simulation. In Proceedings of the 4th middle east symposium on simulation and modelling (MESM2002), Sharjah, United Arab Emirates, pp. 183–187

Novel components of the Toxoplasma inner membrane complex revealed by BioID.

UNLABELLED:The inner membrane complex (IMC) of Toxoplasma gondii is a peripheral membrane system that is composed of flattened alveolar sacs that underlie the plasma membrane, coupled to a supporting cytoskeletal network. The IMC plays important roles in parasite replication, motility, and host cell invasion. Despite these central roles in the biology of the parasite, the proteins that constitute the IMC are largely unknown. In this study, we have adapted a technique named proximity-dependent biotin identification (BioID) for use in T. gondii to identify novel components of the IMC. Using IMC proteins in both the alveoli and the cytoskeletal network as bait, we have uncovered a total of 19 new IMC proteins in both of these suborganellar compartments, two of which we functionally evaluate by gene knockout. Importantly, labeling of IMC proteins using this approach has revealed a group of proteins that localize to the sutures of the alveolar sacs that have been seen in their entirety in Toxoplasma species only by freeze fracture electron microscopy. Collectively, our study greatly expands the repertoire of known proteins in the IMC and experimentally validates BioID as a strategy for discovering novel constituents of specific cellular compartments of T. gondii. IMPORTANCE:The identification of binding partners is critical for determining protein function within cellular compartments. However, discovery of protein-protein interactions within membrane or cytoskeletal compartments is challenging, particularly for transient or unstable interactions that are often disrupted by experimental manipulation of these compartments. To circumvent these problems, we adapted an in vivo biotinylation technique called BioID for Toxoplasma species to identify binding partners and proximal proteins within native cellular environments. We used BioID to identify 19 novel proteins in the parasite IMC, an organelle consisting of fused membrane sacs and an underlying cytoskeleton, whose protein composition is largely unknown. We also demonstrate the power of BioID for targeted discovery of proteins within specific compartments, such as the IMC cytoskeleton. In addition, we uncovered a new group of proteins localizing to the alveolar sutures of the IMC. BioID promises to reveal new insights on protein constituents and interactions within cellular compartments of Toxoplasma

Mutually Penetrating Motion of Self-Organized 2D Patterns of Soliton-Like Structures

Results of numerical simulations of a recently derived most general dissipative-dispersive PDE describing evolution of a film flowing down an inclined plane are presented. They indicate that a novel complex type of spatiotemporal patterns can exist for strange attractors of nonequilibrium systems. It is suggested that real-life experiments satisfying the validity conditions of the theory are possible: the required sufficiently viscous liquids are readily available.Comment: minor corrections, 4 pages, LaTeX, 6 figures, mpeg simulations available upon or reques