B cells as a critical node in the microbiota-host immune system network.

Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B-cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut-associated lymphoid tissues to maintain host-microbiota mutualism.

Understanding the Sharing Economy: The Role of Response to Negative Reviews in the Peer-To-Peer Accommodation Sharing Network?

Recognizing the potentially ruinous effect of negative reviews on the reputation of the hosts as well as a subjective nature of the travel experience judgements, peer-to-peer accommodation sharing plat-forms, like Airbnb, have readily embraced the “response” option, empowering hosts with the voice to challenge, deny or at least apologize for the subject of critique. However, the effects of different re-sponse strategies on trusting beliefs towards the host remain unclear. To fill this gap, this study focus-es on understanding the impact of different response strategies and review negativity on trusting be-liefs towards the host in peer-to-peer accommodation sharing setting utilizing experimental methods. Examination of two different contexts, varying in the controllability of the subject of complaint, re-veals that when the subject of complaint is controllable by a host, such strategies as confession / apol-ogy and denial can improve trusting beliefs towards the host. However, when the subject of criticism is beyond the control of the host, denial of the issue does not yield guest’s confidence in the host, where-as confession and excuse have positive influence on trusting beliefs.

From Personal Network to Institution Building: The Lifanyuan and the Formalization of Manchu-Mongol Relations

The Qing emperors, who ruled over China from 1644-1911, managed to bring large parts of Inner Asia under their control and extended the territory of China to an unprecedented degree. This paper maintains that the political technique of patronage with its formalized language, its emphasis on gift exchange and expressions of courtesy is a useful concept for explaining the integration of Inner Asian confederations into the empire. By re-interpreting the obligations of gift exchange, the Qing transformed the network of personal relationships, which had to be reinforced and consolidated permanently into a system with clearly defined rules. In this process of formalization, the Lifanyuan, the Court for the Administration of the Outer Regions, played a key role. While in the early years of the dynasty, it was responsible for collecting and disseminating information concerning the various patronage relationships with Inner Asian leaders, over the course of the 17th and 18th centuries its efforts were directed at standardizing and streamlining the contacts between ethnic minorities and the state. Through the Lifanyuan, the rules and principles of patronage were maintained in a modified form even in the later part of the dynasty, when the Qing exercised control in the outer regions more directly. The paper provides an explanation for the longevity and cohesiveness of the multi-ethnic Qing empire. Based on recently published Manchu and Mongolian language archival material and the Maussian concept of gift exchange the study sheds new light on the changing self-conception of the Qing emperors.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness.

During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Control of the master virulence regulatory gene atxA in Bacillus anthracis

Transcription of the Bacillus anthracis structural genes for the anthrax toxin proteins and biosynthetic operon for capsule are positively regulated by AtxA, a transcription regulator with unique properties. Consistent with the role of atxA in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a murine model for anthrax. In batch culture, multiple signals impact atxA transcript levels, and the timing and steady state level of atxA expression is critical for optimal toxin and capsule synthesis. Despite the apparent complex control of atxA transcription, only one trans-acting protein, the transition state regulator AbrB, has been demonstrated to directly interact with the atxA promoter. The AbrB-binding site has been described, but additional cis-acting control sequences have not been defined. Using transcriptional lacZ fusions, electrophoretic mobility shift assays, and Western blot analysis, the cis-acting elements and trans-acting factors involved in regulation of atxA in B. anthracis strains containing either both virulence plasmids, pXO1 and pXO2, or only one plasmid, pXO1, were studied. This work demonstrates that atxA transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA, and an A+T-rich upstream element (UP-element) for RNA polymerase (RNAP). In addition, the data show that a trans-acting protein(s) other than AbrB negatively impacts atxA transcription when it binds specifically to a 9-bp palindrome within atxA promoter sequences located downstream of P1. Mutation of the palindrome prevents binding of the trans-acting protein(s) and results in a corresponding increase in AtxA and anthrax toxin production in a strain- and culture-dependent manner. The identity of the trans-acting repressor protein(s) remains elusive; however, phenotypes associated with mutation of the repressor binding site have revealed that the trans-acting repressor protein(s) indirectly controls B. anthracis development. Mutation of the repressor binding site results in misregulation and overexpression of AtxA in conditions conducive for development, leading to a marked sporulation defect that is both atxA- and pXO2-61-dependent. pXO2-61 is homologous to the sensor domain of sporulation sensor histidine kinases and is proposed to titrate an activating signal away from the sporulation phosphorelay when overexpressed by AtxA. These results indicate that AtxA is not only a master virulence regulator, but also a modulator of proper B. anthracis development. Also demonstrated in this work is the impact of the developmental regulators AbrB, Spo0A, and SigH on atxA expression and anthrax toxin production in a genetically incomplete (pXO1+, pXO2-) and genetically complete (pXO1+, pXO2+) strain background. AtxA and anthrax toxin production resulting from deletion of the developmental regulators are strain-dependent suggesting that factors on pXO2 are involved in control of atxA. The only developmental deletion mutant that resulted in a prominent and consistent strain-independent increase in AtxA protein levels was an abrB-null mutant. As a result of increased AtxA levels, there is early and increased production of anthrax toxins in an abrB-null mutant. In addition, the abrB-null mutant exhibited an increase in virulence in a murine model for anthrax. In contrast, virulence of the atxA promoter mutant was unaffected in a murine model for anthrax despite the production of 5-fold more AtxA than the abrB-null mutant. These results imply that AtxA is not the only factor impacting pathogenesis in an abrB-null mutant. Overall, this work highlights the complex regulatory network that governs expression of atxA and provides an additional role for AtxA in B. anthracis development.

ADHERENS JUNCTIONS AND THE ACTOMYOSIN NETWORK REGULATE ORGAN GROWTH BY MODULATING HIPPO PATHWAY ACTIVITY IN DROSOPHILA

Adherens junctions (AJs) and basolateral modules are important for the establishment and maintenance of apico-basal polarity. Loss of AJs and basolateral module members lead to tumor formation, as well as poor prognosis for metastasis. Recently, in mammalian studies it has been shown that loss of either AJ or basolateral module members deregulate Yorkie activity, the downstream transcriptional effector of the Hippo pathway. Importantly, it is unclear if AJ and basolateral components act through the same or parallel mechanisms to regulate Yorkie activity. Here, we dissect how loss of AJ and basolateral components affects Hippo signaling in Drosophila. Surprisingly, while scrib knock-down tissue displays increased reporter activity autonomously, α-cat knock-down tissue shows a cell autonomous decrease and a cell non-autonomous increase of Hippo reporter activity. We provided several lines of evidence to show the differential regulation in polarity protein localizations and oncogenic cooperative overgrowth by AJs and basolateral complexes. Finally, we show that Hippo pathway activity is induced in α-cat and scrib double knocked-down tissue. Taken together, our results provide evidence to show that basolateral modules and AJs act in parallel to modulate Hippo pathway activity. Non-muscle myosin II is an actomyosin component that interacts with the actin. Non-muscle myosin II also interacts with lgl, though the function of this interaction is not clear. Our lab demonstrated that modulating F-actin regulates Hippo pathway activity, and lgl also has been described as a Hippo pathway regulator. Therefore we suspect that myosin II is also involved in Hippo pathway regulation. We first characterized non-muscle Myosin II as a novel tumor suppressor gene by affecting Hippo pathway activity. Upstream regulators of Myosin II, members in the Rho signaling pathway, also displayed similar phenotypes as the Myosin II knock-down tissues. Apoptosis is also induced in myosin II knock-down tissues, however, blocking cell death does not affect myosin II knock-down induced Hippo activation. Our data suggested hyperactivating myosin II induced F-actin accumulation so therefore induces Hippo target activation. Unexpectedly, we also observed that reducing F-actin activity induced Hippo target activation in vivo. These controversial data indicated that actomyosin may regulate the Hippo pathway through multiple mechanisms.

Soporte de redes activas para un servicio integrado de multipunto fiable con control de congestión

Las limitaciones de las tecnologías de red actuales, identificadas en la Agencia de Proyectos de Investigación Avanzados para la Defensa (DARPA) durante 1995, han originado recientemente una propuesta de modelo de red denominado Redes Activas. En este modelo, los nodos proporcionan un entorno de ejecución sobre el que se ejecuta el código asociado a cada paquete. El objetivo es disponer de una tecnología de red que permita que nuevos servicios de red sean desarrollados e instalados rápidamente sin modificar los nodos de la red. Un servicio de red que se puede beneficiar de esta tecnología es la transmisión de datos en multipunto con diferentes grados fiabilidad. Las propuestas actuales de servicios de multipunto fiable proporcionan una solución específica para cada clase de aplicaciones, y los protocolos existentes extremo a extremo sufren de limitaciones técnicas relacionadas con una fiabilidad limitada, y con la ausencia de mecanismos de control de congestión efectivos. Esta tesis realiza propuestas originales conducentes a solucionar parte de las limitaciones actuales en el ámbito de Redes Activas y multipunto fiable con control de congestión. En primer lugar, se especificará un servicio genérico de multipunto fiable que, basándose en los requisitos de una serie de aplicaciones consideradas relevantes, proporcione diferentes clases de sesiones y grados de fiabilidad. Partiendo de la definición del servicio genérico especificado, se diseñará un protocolo de comunicaciones sobre la tecnología de Redes Activas que proporcione dicho servicio. El protocolo diseñado estará dotado de un mecanismo de control de congestión para que la fuente ajuste dinámicamente el tráfico inyectado a las condiciones de carga de la red. En esta tesis se pretende también profundizar en el estudio y análisis de la tecnología de Redes Activas, experimentando con dicha tecnología para proporcionar una realimentación a sus diseñadores. Dicha experimentación se realizará en tres ámbitos: el de los servicios y protocolos que puede soportar, el del modelo y arquitectura de las Redes Activas y el de las plataformas de ejecución disponibles. Como aportación adicional de este trabajo, se validarán los objetivos anteriores mediante una implementación piloto de las entidades de protocolo y de su interfaz de servicio sobre uno de los entornos de ejecución disponibles. Abstract The limitations of current networking technologies identified in the Defense Advance Research Projects Agency (DARPA) along 1995 have led to a recent proposal of a new network model called Active Networks. In this model, the nodes provide an execution environment over which the code used to process each packet is executed. The objective is a network technology that allows the fast design and deployment of new network services without requiring the modification of the network nodes. One network service that could benefit from this technology is the transmission of multicast data with different types of loss tolerance. The current proposals for reliable multicast services provide specific solutions for each application class, and existing end-to-end protocols suffer from technical drawbacks related to limited reliability and lack of an effective congestion control mechanism. This thesis contains original proposals that aim to solve part of the current drawbacks in the scope of Active Networks and reliable multicast with congestion control. Firstly, a generic reliable multicast network service will be specified. This service will be designed from the requirements of a relevant set of applications, and will provide different session classes and different types of reliability. Then, a network protocol based on Active Network technology will be designed such that it provides the specified network service. This protocol will incorporate a congestion control mechanism capable of performing an automatic adjustment of the traffic injected by the source to the available network capacity. This thesis will also contribute to a deeper study and analysis of Active Network technology, by experimenting with the technology in order to provide feedback to its designers. This experimentation will be done attending to three different scopes: support of Active Network for services and protocols, Active Network model and architecture, and currently available Active Network execution environments. As an additional contribution of this work, the previous objectives will be validated through a prototype implementation of the protocol entities and the service interface based on one of the current execution environments.

Network convergence and QoS for future multimedia services in the VISION project

The emerging use of real-time 3D-based multimedia applications imposes strict quality of service (QoS) requirements on both access and core networks. These requirements and their impact to provide end-to-end 3D videoconferencing services have been studied within the Spanish-funded VISION project, where different scenarios were implemented showing an agile stereoscopic video call that might be offered to the general public in the near future. In view of the requirements, we designed an integrated access and core converged network architecture which provides the requested QoS to end-to-end IP sessions. Novel functional blocks are proposed to control core optical networks, the functionality of the standard ones is redefined, and the signaling improved to better meet the requirements of future multimedia services. An experimental test-bed to assess the feasibility of the solution was also deployed. In such test-bed, set-up and release of end-to-end sessions meeting specific QoS requirements are shown and the impact of QoS degradation in terms of the user perceived quality degradation is quantified. In addition, scalability results show that the proposed signaling architecture is able to cope with large number of requests introducing almost negligible delay.

Heterogeneous Collaborative Sensor Network for Electrical Management of an Automated House with PV Energy

In this paper we present a heterogeneous collaborative sensor network for electrical management in the residential sector. Improving demand-side management is very important in distributed energy generation applications. Sensing and control are the foundations of the “Smart Grid” which is the future of large-scale energy management. The system presented in this paper has been developed on a self-sufficient solar house called “MagicBox” equipped with grid connection, PV generation, lead-acid batteries, controllable appliances and smart metering. Therefore, there is a large number of energy variables to be monitored that allow us to precisely manage the energy performance of the house by means of collaborative sensors. The experimental results, performed on a real house, demonstrate the feasibility of the proposed collaborative system to reduce the consumption of electrical power and to increase energy efficiency.

NetCDF based data archiving system applied to ITER Fast Plant System Control prototype

EURATOM/CIEMAT and Technical University of Madrid (UPM) have been involved in the development of a FPSC [1] (Fast Plant System Control) prototype for ITER, based on PXIe (PCI eXtensions for Instrumentation). One of the main focuses of this project has been data acquisition and all the related issues, including scientific data archiving. Additionally, a new data archiving solution has been developed to demonstrate the obtainable performances and possible bottlenecks of scientific data archiving in Fast Plant System Control. The presented system implements a fault tolerant architecture over a GEthernet network where FPSC data are reliably archived on remote, while remaining accessible to be redistributed, within the duration of a pulse. The storing service is supported by a clustering solution to guaranty scalability, so that FPSC management and configuration may be simplified, and a unique view of all archived data provided. All the involved components have been integrated under EPICS [2] (Experimental Physics and Industrial Control System), implementing in each case the necessary extensions, state machines and configuration process variables. The prototyped solution is based on the NetCDF-4 [3] and [4] (Network Common Data Format) file format in order to incorporate important features, such as scientific data models support, huge size files management, platform independent codification, or single-writer/multiple-readers concurrency. In this contribution, a complete description of the above mentioned solution is presented, together with the most relevant results of the tests performed, while focusing in the benefits and limitations of the applied technologies.

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.

Neural network controller for active demand side management with PV energy in the residential sector

In this paper, we describe the development of a control system for Demand-Side Management in the residential sector with Distributed Generation. The electrical system under study incorporates local PV energy generation, an electricity storage system, connection to the grid and a home automation system. The distributed control system is composed of two modules: a scheduler and a coordinator, both implemented with neural networks. The control system enhances the local energy performance, scheduling the tasks demanded by the user and maximizing the use of local generation.