Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Opportunistic Content-Centric Data Transmission During Short Network Contacts

In this paper, we investigate content-centric data transmission in the context of short opportunistic contacts and base our work on an existing content-centric networking architecture. In case of short interconnection times, file transfers may not be completed and the received information is discarded. Caches in content-centric networks are used for short-term storage and do not guarantee persistence. We implemented a mechanism to extend caching on persistent storage enabling the completion of disrupted content transfers. The mechanisms have been implemented in the CCNx framework and have been evaluated on wireless mesh nodes. Our evaluations using multicast and unicast communication show that the implementation can support content transfers in opportunistic environments without significant processing and storing overhead.

User and Machine Authentication and Authorization Infrastructure for Distributed Wireless Sensor Network Testbeds

The intention of an authentication and authorization infrastructure (AAI) is to simplify and unify access to different web resources. With a single login, a user can access web applications at multiple organizations. The Shibboleth authentication and authorization infrastructure is a standards-based, open source software package for web single sign-on (SSO) across or within organizational boundaries. It allows service providers to make fine-grained authorization decisions for individual access of protected online resources. The Shibboleth system is a widely used AAI, but only supports protection of browser-based web resources. We have implemented a Shibboleth AAI extension to protect web services using Simple Object Access Protocol (SOAP). Besides user authentication for browser-based web resources, this extension also provides user and machine authentication for web service-based resources. Although implemented for a Shibboleth AAI, the architecture can be easily adapted to other AAIs.

Mobile Cloud Networking: Mobile Network, Compute, and Storage as One Service On-Demand

The Future Communication Architecture for Mobile Cloud Services: Mobile Cloud Networking (MCN) is a EU FP7 Large-scale Integrating Project (IP) funded by the European Commission. MCN project was launched in November 2012 for the period of 36 month. In total top-tier 19 partners from industry and academia commit to jointly establish the vision of Mobile Cloud Networking, to develop a fully cloud-based mobile communication and application platform.

Molecular architecture of basement membranes

Basement membranes are specialized extracellular matrices with support, sieving, and cell regulatory functions. The molecular architectures of these matrices are created through specific binding interactions between unique glycoprotein and proteoglycan protomers. Type IV collagen chains, using NH2-terminal, COOH-terminal, and lateral association, form a covalently stabilized polygonal framework. Laminin, a four-armed glycoprotein, self-assembles through terminal-domain interactions to form a second polymer network, Entactin/nidogen, a dumbbell-shaped sulfated glycoprotein, binds laminin near its center and interacts with type IV collagen, bridging the two. A large heparan sulfate proteoglycan, important for charge-dependent molecular sieving, is firmly anchored in the basement membrane and can bind itself through a core-protein interaction to form dimers and oligomers and bind laminin and type IV collagen through its glycosaminoglycan chains. Heterogeneity of structure and function occur in different tissues, in development, and in response to different physiological needs. The molecular architecture of these matrices may be regulated during or after primary assembly through variations in compositions, isoform substitutions, and the modifying influence of exogenous macromolecules such as heparin and heparan sulfate.

Mobility and bandwidth prediction in virtualized LTE systems: Architecture and challenges

Long Term Evolution (LTE) represents the fourth generation (4G) technology which is capable of providing high data rates as well as support of high speed mobility. The EU FP7 Mobile Cloud Networking (MCN) project integrates the use of cloud computing concepts in LTE mobile networks in order to increase LTE's performance. In this way a shared distributed virtualized LTE mobile network is built that can optimize the utilization of virtualized computing, storage and network resources and minimize communication delays. Two important features that can be used in such a virtualized system to improve its performance are the user mobility and bandwidth prediction. This paper introduces the architecture and challenges that are associated with user mobility and bandwidth prediction approaches in virtualized LTE systems.

Network Store: Exploring Slicing in Future 5G Networks

In this paper, we present a revolutionary vision of 5G networks, in which SDN programs wireless network functions, and where Mobile Network Operators (MNO), Enterprises, and Over-The-Top (OTT) third parties are provided with NFV-ready Network Store. The proposed Network Store serves as a digital distribution platform of programmable Virtualized Network Functions (VNFs) that enable 5G application use-cases. Currently existing application stores, such as Apple's App Store for iOS applications, Google's Play Store for Android, or Ubuntu's Software Center, deliver applications to user specific software platforms. Our vision is to provide a digital marketplace, gathering 5G enabling Network Applications and Network Functions, written to run on top of commodity cloud infrastructures, connected to remote radio heads (RRH). The 5G Network Store will be the same to the cloud as the application store is currently to a software platform.

Content-Aware Delivery of Scalable Video in Network Coding Enabled Named Data Networks

In this work, we propose a novel network coding enabled NDN architecture for the delivery of scalable video. Our scheme utilizes network coding in order to address the problem that arises in the original NDN protocol, where optimal use of the bandwidth and caching resources necessitates the coordination of the forwarding decisions. To optimize the performance of the proposed network coding based NDN protocol and render it appropriate for transmission of scalable video, we devise a novel rate allocation algorithm that decides on the optimal rates of Interest messages sent by clients and intermediate nodes. This algorithm guarantees that the achieved flow of Data objects will maximize the average quality of the video delivered to the client population. To support the handling of Interest messages and Data objects when intermediate nodes perform network coding, we modify the standard NDN protocol and introduce the use of Bloom filters, which store efficiently additional information about the Interest messages and Data objects. The proposed architecture is evaluated for transmission of scalable video over PlanetLab topologies. The evaluation shows that the proposed scheme performs very close to the optimal performance

PIN transcriptional regulation shapes root system architecture

Regulation of auxin distribution by PIN transporters is key in the dynamic modulation of root growth and branching. Three novel papers shed light on an intricate network through which several hormones and transcriptional regulators collectively fine-tune the transcriptional level of these auxin transporters in the root.

Functional architecture of mammalian horizontal cells

In the rabbit retina, there are two kinds of horizontal cells (HCs). The A-type HC is a large axonless cell which contacts cones exclusively. The B-type HC is an axon bearing cell. While the somatic dendrites of B-type HCs also contact cones, the axon expands into an elaborately branched structure, the axon terminal (AT), which contacts a large number of rods. It is difficult to label the different HCs selectively by immunochemical methods. Therefore, we developed dye injection methods to label each type of HC. Then it was possible, (1) to describe the detailed structure of the AT (2) to identify the glutamate receptors mediating cone input to A and B-type HCs and rod input to ATs and (3) to test the hypothesis that the B-type HCs are coupled via Cx57 gap junctions. ^ To obtain well filled examples of single HCs, it was necessary to block gap junction coupling to stop the spread of Neurobiotin through the network. We used dye coupling in A-type HCs to screen a series of potential gap junction antagonists. One of these compounds, meclofenamic acid (MFA), was potent, water soluble and easily reversible. This compound may be a useful tool to manipulate gap junction coupling. ^ In the presence of MFA, Neurobiotin passed down the axon of B-type HCs to reveal the detailed structure of the AT. We observed that only one AT ending entered each rod spherule invagination. This observation was confirmed by calculation and two dye injections. ^ Glutamate is the neurotransmitter used by both rods and cones. AMPA receptors were colocalized with the dendrites of A and B-type HCs at each cone pedicle. In addition, AMPA receptors were located on the AT ending at each rod spherule. Thus rod and cone input to HCs is mediated by AMPA receptors. ^ A-type and B-type HCs may express different connexins because they have different dye-coupling properties. Recently, we found that connexin50 (Cx50) is expressed by A-type HCs. B-type HCs and B-type ATs are also independently coupled. Cx57 was expressed in the OPL and double label studies showed that Cx 57 was colocalized with the AT matrix but not with the somatic dendrites of B-type HCs. ^ In summary, we have identified a useful gap junction antagonist, MFA. There is one AT ending at each rod spherule, rods inputs to ATs is mediated by AMPA receptors and coupling in the AT matrix is mediated by Cx57. This confirms that HCs with different properties use distinct connexins. The properties of ATs described in this research are consistent. The connections and properties reported here suggest that ATs functions as rod HCs and provide a negative feedback signal to rods. ^

Inherited structural controls on fault geometry, architecture and hydrothermal activity: an example from Grimsel Pass, Switzerland

Exhumed faults hosting hydrothermal systems provide direct insight into relationships between faulting and fluid flow, which in turn are valuable for making hydrogeological predictions in blind settings. The Grimsel Breccia Fault (Aar massif, Central Swiss Alps) is a late Neogene, exhumed dextral strike-slip fault with a maximum displacement of 25–45 m, and is associated with both fossil and active hydrothermal circulation. We mapped the fault system and modelled it in three dimensions, using the distinctive hydrothermal mineralisation as well as active thermal fluid discharge (the highest elevation documented in the Alps) to reveal the structural controls on fluid pathway extent and morphology. With progressive uplift and cooling, brittle deformation inherited the mylonitic shear zone network at Grimsel Pass; preconditioning fault geometry into segmented brittle reactivations of ductile shear zones and brittle inter-shear zone linkages. We describe ‘pipe’-like, vertically oriented fluid pathways: (1) within brittle fault linkage zones and (2) through alongstrike- restricted segments of formerly ductile shear zones reactivated by brittle deformation. In both cases, low-permeability mylonitic shear zones that escaped brittle reactivation provide important hydraulic seals. These observations show that fluid flow along brittle fault planes is not planar, but rather highly channelised into sub-vertical flow domains, with important implications for the exploration and exploitation of geothermal energy.

Testing a Cloud Provider Network for Hybrid P2P and Cloud Streaming Architectures

The number of online real-time streaming services deployed over network topologies like P2P or centralized ones has remarkably increased in the recent years. This has revealed the lack of networks that are well prepared to respond to this kind of traffic. A hybrid distribution network can be an efficient solution for real-time streaming services. This paper contains the experimental results of streaming distribution in a hybrid architecture that consist of mixed connections among P2P and Cloud nodes that can interoperate together. We have chosen to represent the P2P nodes as Planet Lab machines over the world and the cloud nodes using a Cloud provider's network. First we present an experimental validation of the Cloud infrastructure's ability to distribute streaming sessions with respect to some key streaming QoS parameters: jitter, throughput and packet losses. Next we show the results obtained from different test scenarios, when a hybrid distribution network is used. The scenarios measure the improvement of the multimedia QoS parameters, when nodes in the streaming distribution network (located in different continents) are gradually moved into the Cloud provider infrastructure. The overall conclusion is that the QoS of a streaming service can be efficiently improved, unlike in traditional P2P systems and CDN, by deploying a hybrid streaming architecture. This enhancement can be obtained by strategic placing of certain distribution network nodes into the Cloud provider infrastructure, taking advantage of the reduced packet loss and low latency that exists among its datacenters.

Design and Test of a High QoS Radio Network for CBTC Systems in Subway Tunnels

Communications Based Train Control Systems require high quality radio data communications for train signaling and control. Actually most of these systems use 2.4GHz band with proprietary radio transceivers and leaky feeder as distribution system. All them demand a high QoS radio network to improve the efficiency of railway networks. We present narrow band, broad band and data correlated measurements taken in Madrid underground with a transmission system at 2.4 GHz in a test network of 2 km length in subway tunnels. The architecture proposed has a strong overlap in between cells to improve reliability and QoS. The radio planning of the network is carefully described and modeled with narrow band and broadband measurements and statistics. The result is a network with 99.7% of packets transmitted correctly and average propagation delay of 20ms. These results fulfill the specifications QoS of CBTC systems.

A multi-agent system with distributed bayesian reasoning for network fault diagnosis

In this paper, an innovative approach to perform distributed Bayesian inference using a multi-agent architecture is presented. The final goal is dealing with uncertainty in network diagnosis, but the solution can be of applied in other fields. The validation testbed has been a P2P streaming video service. An assessment of the work is presented, in order to show its advantages when it is compared with traditional manual processes and other previous systems.

A framework for building distributed social network websites

Las redes son la esencia de comunidades y sociedades humanas; constituyen el entramado en el que nos relacionamos y determinan cómo lo hacemos, cómo se disemina la información o incluso cómo las cosas se llevan a cabo. Pero el protagonismo de las redes va más allá del que adquiere en las redes sociales. Se encuentran en el seno de múltiples estructuras que conocemos, desde las interaciones entre las proteínas dentro de una célula hasta la interconexión de los routers de internet. Las redes sociales están presentes en internet desde sus principios, en el correo electrónico por tomar un ejemplo. Dentro de cada cliente de correo se manejan listas contactos que agregadas constituyen una red social. Sin embargo, ha sido con la aparición de los sitios web de redes sociales cuando este tipo de aplicaciones web han llegado a la conciencia general. Las redes sociales se han situado entre los sitios más populares y con más tráfico de la web. Páginas como Facebook o Twitter manejan cifras asombrosas en cuanto a número de usuarios activos, de tráfico o de tiempo invertido en el sitio. Pero las funcionalidades de red social no están restringidas a las redes sociales orientadas a contactos, aquellas enfocadas a construir tu lista de contactos e interactuar con ellos. Existen otros ejemplos de sitios que aprovechan las redes sociales para aumentar la actividad de los usuarios y su involucración alrededor de algún tipo de contenido. Estos ejemplos van desde una de las redes sociales más antiguas, Flickr, orientada al intercambio de fotografías, hasta Github, la red social de código libre más popular hoy en día. No es una casualidad que la popularidad de estos sitios web venga de la mano de sus funcionalidades de red social. El escenario es más rico aún, ya que los sitios de redes sociales interaccionan entre ellos, compartiendo y exportando listas de contactos, servicios de autenticación y proporcionando un valioso canal para publicitar la actividad de los usuarios en otros sitios web. Esta funcionalidad es reciente y aún les queda un paso hasta que las redes sociales superen su condición de bunkers y lleguen a un estado de verdadera interoperabilidad entre ellas, tal como funcionan hoy en día el correo electrónico o la mensajería instantánea. Este trabajo muestra una tecnología que permite construir sitios web con características de red social distribuída. En primer lugar, se presenta una tecnología para la construcción de un componente intermedio que permite proporcionar cualquier característica de gestión de contenidos al popular marco de desarrollo web modelo-vista-controlador (MVC) Ruby on Rails. Esta técnica constituye una herramienta para desarrolladores que les permita abstraerse de las complejidades de la gestión de contenidos y enfocarse en las particularidades de los propios contenidos. Esta técnica se usará también para proporcionar las características de red social. Se describe una nueva métrica de reusabilidad de código para demostrar la validez del componente intermedio en marcos MVC. En segundo lugar, se analizan las características de los sitios web de redes sociales más populares, con el objetivo de encontrar los patrones comunes que aparecen en ellos. Este análisis servirá como base para definir los requisitos que debe cumplir un marco para construir redes sociales. A continuación se propone una arquitectura de referencia que proporcione este tipo de características. Dicha arquitectura ha sido implementada en un componente, Social Stream, y probada en varias redes sociales, tanto orientadas a contactos como a contenido, en el contexto de una asociación vecinal tanto como en proyectos de investigación financiados por la UE. Ha sido la base de varios proyectos fin de carrera. Además, ha sido publicado como código libre, obteniendo una comunidad creciente y está siendo usado más allá del ámbito de este trabajo. Dicha arquitectura ha permitido la definición de un nuevo modelo de control de acceso social que supera varias limitaciones presentes en los modelos de control de acceso para redes sociales. Más aún, se han analizado casos de estudio de sitios de red social distribuídos, reuniendo un conjunto de caraterísticas que debe cumplir un marco para construir redes sociales distribuídas. Por último, se ha extendido la arquitectura del marco para dar cabida a las características de redes sociales distribuídas. Su implementación ha sido validada en proyectos de investigación financiados por la UE. Abstract Networks are the substance of human communities and societies; they constitute the structural framework on which we relate to each other and determine the way we do it, the way information is diseminated or even the way people get things done. But network prominence goes beyond the importance it acquires in social networks. Networks are found within numerous known structures, from protein interactions inside a cell to router connections on the internet. Social networks are present on the internet since its beginnings, in emails for example. Inside every email client, there are contact lists that added together constitute a social network. However, it has been with the emergence of social network sites (SNS) when these kinds of web applications have reached general awareness. SNS are now among the most popular sites in the web and with the higher traffic. Sites such as Facebook and Twitter hold astonishing figures of active users, traffic and time invested into the sites. Nevertheless, SNS functionalities are not restricted to contact-oriented social networks, those that are focused on building your own list of contacts and interacting with them. There are other examples of sites that leverage social networking to foster user activity and engagement around other types of content. Examples go from early SNS such as Flickr, the photography related networking site, to Github, the most popular social network repository nowadays. It is not an accident that the popularity of these websites comes hand-in-hand with their social network capabilities The scenario is even richer, due to the fact that SNS interact with each other, sharing and exporting contact lists and authentication as well as providing a valuable channel to publize user activity in other sites. These interactions are very recent and they are still finding their way to the point where SNS overcome their condition of data silos to a stage of full interoperability between sites, in the same way email and instant messaging networks work today. This work introduces a technology that allows to rapidly build any kind of distributed social network website. It first introduces a new technique to create middleware that can provide any kind of content management feature to a popular model-view-controller (MVC) web development framework, Ruby on Rails. It provides developers with tools that allow them to abstract from the complexities related with content management and focus on the development of specific content. This same technique is also used to provide the framework with social network features. Additionally, it describes a new metric of code reuse to assert the validity of the kind of middleware that is emerging in MVC frameworks. Secondly, the characteristics of top popular SNS are analysed in order to find the common patterns shown in them. This analysis is the ground for defining the requirements of a framework for building social network websites. Next, a reference architecture for supporting the features found in the analysis is proposed. This architecture has been implemented in a software component, called Social Stream, and tested in several social networks, both contact- and content-oriented, in local neighbourhood associations and EU-founded research projects. It has also been the ground for several Master’s theses. It has been released as a free and open source software that has obtained a growing community and that is now being used beyond the scope of this work. The social architecture has enabled the definition of a new social-based access control model that overcomes some of the limitations currenly present in access control models for social networks. Furthermore, paradigms and case studies in distributed SNS have been analysed, gathering a set of features for distributed social networking. Finally the architecture of the framework has been extended to support distributed SNS capabilities. Its implementation has also been validated in EU-founded research projects.