Effect of irradiation distance on image contrast in epi-optoacoustic imaging of human volunteers

In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.

Temperature dependence of postmortem MR quantification for soft tissue discrimination.

OBJECTIVES To investigate and correct the temperature dependence of postmortem MR quantification used for soft tissue characterization and differentiation in thoraco-abdominal organs. MATERIAL AND METHODS Thirty-five postmortem short axis cardiac 3-T MR examinations were quantified using a quantification sequence. Liver, spleen, left ventricular myocardium, pectoralis muscle and subcutaneous fat were analysed in cardiac short axis images to obtain mean T1, T2 and PD tissue values. The core body temperature was measured using a rectally inserted thermometer. The tissue-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. RESULTS In a 3D plot comprising the combined data of T1, T2 and PD, different organs/tissues could be well differentiated from each other. The quantitative values were influenced by the temperature. T1 in particular exhibited strong temperature dependence. The correction of quantitative values to a temperature of 37 °C resulted in better tissue discrimination. CONCLUSION Postmortem MR quantification is feasible for soft tissue discrimination and characterization of thoraco-abdominal organs. This provides a base for computer-aided diagnosis and detection of tissue lesions. The temperature dependence of the T1 values challenges postmortem MR quantification. Equations to correct for the temperature dependence are provided. KEY POINTS • Postmortem MR quantification is feasible for soft tissue discrimination and characterization • Temperature dependence of the T1 values challenges the MR quantification approach • The results provide the basis for computer-aided postmortem MRI diagnosis • Diagnostic criteria may also be applied for living patients.

Future water quality monitoring--adapting tools to deal with mixtures of pollutants in water resource management.

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring.

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.

Punishing the Innocent along with the Guilty: The Economics of Individual versus Group Punishment

Standard models of law enforcement involve the apprehension and punishment of a single suspect, but in many contexts, punishment is actually imposed on an entire group known to contain the offender. The advantages of .group punishment. are that the offender is punished with certainty and detection costs are saved. The disadvantage is that innocent individuals are punished. We compare individual and group punishment when social welfare depends on fairness, and when it depends on deterrence. We show that group punishment may dominate in the former case if the detection technology is ineffective but never in the latter case. We discuss our results in the context of several examples.

Modelo de indicadores ambientales : observatorio ambiental

Los indicadores ambientales son una herramienta para efectuar el monitoreo de la biodiversidad a través de la recolección sistemática de datos obtenidos mediante mediciones u observaciones en series de tiempo y espacio. Se entiende por indicador ambiental a una variable o suma de variables que proporciona una información sintética sobre un fenómeno ambiental complejo que permite conocer y evaluar el estado y variación de la calidad ambiental. Para la caracterización y detección de indicadores ambientales del litoral de Río Negro se identifican y jerarquizan los conflictos o problemáticas del ambiente, a partir de lo cual se seleccionan las principales variables que componen el sistema de indicadores y por último, se recopilan los niveles de información existentes y los que requieren ser relevados e incorporados a bases de datos relacionales. Los requisitos que deben tener los indicadores seleccio nados son: ser medibles (cuali y cuantitativamente), compresibles, fáciles de usar e interrelacionar, tener dimensión espacial y temporal, ser objetivos sensibles a los cambios y permitir el diagnóstico y pronóstico en función de la detección de situaciones de alerta ambiental. Se realiza una aproximación a la selección de variables e indicadores con el fin de definir el modelo de datos y categorías de agrupamiento. El sistema de indicadores generados se agrupa en función de la disponibilidad de datos existentes y la posibilidad de recopilación para un correcto funcionamiento del prototipo del Observatorio. El modelo adoptado incorpora 3 subsistemas (ambiental, social y económico) interrelacionando con 3 nodos institucionales (que proveen y/o precisan estos datos para la toma de decisiones). Cada indicador se describe en una ficha metodológica, cuyo diseño es normalizado para un correcto funcionamiento del Observatorio. La implementación del modelo de indicadores exige contar con una infraestructura que permita la aplicación de mediciones, observaciones y registros y contar además, con personal idóneo para una correcta manipulación y análisis.

Security devices based on liquid crystals doped with a colour dye

Liquid crystal properties make them useful for the development of security devices in applications of authentication and detection of fakes. Induced orientation of liquid crystal molecules and birefringence are the two main properties used in security devices. Employing liquid crystal and dichroic colorants, we have developed devices that show, with the aid of a polarizer, multiple images on each side of the device. Rubbed polyimide is used as alignment layer on each substrate of the LC cell. By rubbing the polyimide in different directions in each substrate it is possible to create any kind of symbols, drawings or motifs with a greyscale; the more complex the created device is, the more difficult is to fake it. To identify the motifs it is necessary to use polarized light. Depending on whether the polarizer is located in front of the LC cell or behind it, different motifs from one or the other substrate are shown. The effect arises from the dopant colour dye added to the liquid crystal, the induced orientation and the twist structure. In practice, a grazing reflection on a dielectric surface is polarized enough to see the effect. Any LC flat panel display can obviously be used as backlight as well.

Differential invariants of second-order ordinary differential equations

The notion of a differential invariant for systems of second-order differential equations on a manifold M with respect to the group of vertical automorphisms of the projection is de?ned and the Chern connection attached to a SODE allows one to determine a basis for second-order differential invariants of a SODE.

Diseño y fabricación de dispositivos basados en cristal líquido polimérico

Esta tesis se centra en el estudio y desarrollo de dispositivos de aplicación basados en cristal líquido polimérico. Las propiedades de los cristales líquidos los hacen interesantes para su uso en el desarrollo de dispositivos de seguridad para autenticación de productos y marcas, y detección y prevención de falsificaciones. Asimismo, pueden ser muy útiles para fabricar dispositivos basados en CLs dispersos en polímero, los cuales tienen a su vez múltiples aplicaciones. La orientación de las moléculas de cristal líquido y la birrefringencia son las dos características principales que afectan a las propiedades de estos dispositivos. Un dispositivo de cristal líquido estándar consiste en un sándwich formado por dos sustratos de vidrio transparente, dotados con electrodo de ITO (Indium Tin Oxide) en su superficie interna, que confinan el cristal líquido en su interior. En la primera parte de esta tesis se describen las características más importantes que describen una célula de cristal líquido. Esta introducción básica en necesaria para la correcta comprensión de los capítulos posteriores en los que se detalla el desarrollo concreto de los dispositivos desarrollados en la investigación llevada a cabo. Por ejemplo, en el caso de los dispositivos de seguridad se han eliminado los sustratos de vidrio (en la última fase de su desarrollo) para conseguir dispositivos flexibles. En la segunda parte de la tesis se incluye la descripción completa de los dispositivos fabricados, así como de los protocolos de fabricación seguidos y diseñados específicamente para ello. También se detallan en esta parte los resultados obtenidos, así como las propiedades ópticas y electroópticas en cada caso, y el/los equipos de caracterización utilizados. Utilizando cristal líquido nemático y colorante dicroico, se han desarrollado dispositivos que contienen múltiples imágenes latentes en cada cara del mismo. Utilizando distintas técnicas de alineamiento se consigue crear cualquier tipo de motivo latente, ya sean símbolos sencillos, figuras, logotipos o incluso imágenes con escala de gris. Cuanto más complejo es el dispositivo, mayor es la dificultad para reproducirlo en una eventual falsificación. Para visualizar e identificar los motivos es necesario emplear luz polarizada, por ejemplo, con la ayuda de un sencillo polarizador lineal. Dependiendo de si el polarizador está colocado delante del dispositivo o detrás del él, se mostrarán las imágenes generadas en una u otra cara. Este efecto es posible gracias al colorante dicroico añadido al CL, a la orientación inducida sobre las moléculas, y a la estructura de twist utilizada en los dispositivos. En realidad, para ver el efecto de los dispositivos no es necesario el uso de un polarizador, basta con el reflejo de una superficie dielétrica (percialmente polarizado), o la luz emitida por la pantalla de dispositivos de consumo comunes como un televisor LCD, un monitor de ordenador o un “smartphone”. Por otro lado, utilizando una mezcla entre un CL nemático polimérico y un CL nemático no polimérico es posible fabricar dispositivos LCPC (Liquid Crystal Polymer Composite) con propiedades electroópticas muy interesantes, que funcionan a tensiones de conmutación bajas. El CL polimérico conforma una estructura de red en el interior del sándwich que mantiene confinado al CL nemático en pequeños microdominios. Se han fabricado dispositivos LCPC con conmutación inversa utilizando tanto alineamiento homogéneo como homeotrópico. Debido a que tanto la estructura de CL polimérico como el CL nemático que rellena los microdominios están orientados en una misma dirección de alineamiento preinducida, la luz dispersada por el dispositivo se encuentra polarizada. La dirección de polarización coincide con la dirección de alineamiento. La innovación aportada por esta investigación: un nuevo dispositivo LCPC inverso de respuesta ultrarápida y polarizada basado en la mezcla de dos CL nemáticos y, un dispositivo de seguridad y autenticación, patentado internacionalmente, basado en CL nemáticos dopados con colorante dicroico. Abstract This thesis is centered on the availability to use polymerizable liquid crystals to develop non-display application LC devices. Liquid crystal properties make them useful for the development of security devices in applications of authentication and detection of fakes, and also to achieve polymer dispersed LC devices to be used for different applications that will be studied here. Induced orientation of liquid crystal molecules and birefringence are the two main properties used in these devices. A standard liquid crystal device is a sandwich consisting of two parallel glass substrates carrying a thin transparent ITO (Indium‐Tin‐Oxide) electrode on their inner surfaces with the liquid crystal in the middle. The first part of this thesis will describe the most important parameters describing a liquid crystal cell. This basis is necessary for the understanding of later chapters where models of the liquid crystal devices will be discussed and developed. In the case of security devices the standard structure of an LC device has been modified by eliminating the glass substrates in order to achieve plastic and flexible devices. The second part of the thesis includes a detailed description of the devices achieved and the manufacturing protocols that have been developed ad-hoc. The optical and electrooptical properties and the characterization equipment are described here as well. Employing nematic liquid crystal and dichroic colorants, we have developed devices that show, with the aid of a polarizer, multiple images on each side of the device. By different alignment techniques it is possible to create any kind of symbols, drawings or motifs with a grayscale; the more complex the created device is, the more difficult is to fake it. To identify the motifs it is necessary to use polarized light. Depending on whether the polarizer is located in front of the LC cell or behind it, different motifs from one or the other substrate are shown. The effect arises from the dopant color dye added to the liquid crystal, the induced orientation and the twist structure. In practice, a grazing reflection on a dielectric surface is polarized enough to see the effect. Any LC flat panel display (LCD TV, computer, mobile phone) can obviously be used as backlight as well. On the other hand, by using a mixture of polymerizable and non-polymerizable nematics liquid crystals it is also possible to achieve LCPC (Liquid Crystal Polymer Composite) devices that show really interesting electrooptical characteristics using low switching voltages. Polymerizable LC creates a hollow structure inside the sandwich glass cell that keep nematics liquid crystal confined creating microdomains. Homogeneous and homeotropic alignments have been used to develop inverse switching mode LCPCs. Due to the double LC oriented structure, the outgoing scattered light from these devices is already polarized. The polarization axis coincides with LC molecules director, the alignment direction promoted. The novelties derived from the investigation presented here, new ultrafast inverse LCPC with polarized outgoing scattered light based on oriented nematic LC mixture, and an internationally patented security and authentication device based on nematics (doped with dichroic dye) oriented polymerizable LC.

Neutron performance analysis for ESS target proposal

In the course of discussing different target types for their suitability in the European Spallation Source (ESS) one main focus was on neutronics' performance. Diverse concepts have been assessed baselining some preliminary engineering and geometrical details and including some optimization. With the restrictions and resulting uncertainty imposed by the lack of detailed designs optimizations at the time of compiling this paper, the conclusion drawn is basically that there is a little difference in the neutronic yield of the investigated targets. Other criteria like safety, environmental compatibility, reliability and cost will thus dominate the choice of an ESS target.

Vigilancia por análisis de ruido de los sensores de temperatura

En este proyecto se van a aplicar las técnicas de análisis de ruido para caracterizar la respuesta dinámica de varios sensores de temperatura, tanto termorresistencias de platino como de termopares. Estos sensores son imprescindibles para él correcto funcionamiento de las centrales nucleares y requieren vigilancia para garantizar la exactitud de las medidas. Las técnicas de análisis de ruido son técnicas pasivas, es decir, no afectan a la operación de la planta y permiten realizar una vigilancia in situ de los sensores. Para el caso de los sensores de temperatura, dado que se pueden asimilar a sistemas de primer orden, el parámetro fundamental a vigilar es el tiempo de respuesta. Éste puede obtenerse para cada una de las sondas por medio de técnicas en el dominio de la frecuencia (análisis espectral) o por medio de técnicas en el dominio del tiempo (modelos autorregresivos). Además de la estimación del tiempo de respuesta, se realizará una caracterización estadística de las sondas. El objetivo es conocer el comportamiento de los sensores y vigilarlos de manera que se puedan diagnosticar las averías aunque éstas estén en una etapa incipiente. ABSTRACT In this project we use noise analysis technique to study the dynamic response of RTDs (Resistant temperature detectors) and thermocouples. These sensors are essential for the proper functioning of nuclear power plants and therefore need to be monitored to guarantee accurate measurements. The noise analysis techniques do not affect plant operation and allow in situ monitoring of the sensors. Temperature sensors are equivalent to first order systems. In these systems the main parameter to monitor is the response time which can be obtained by means of techniques in the frequency domain (spectral analysis) as well as time domain (autoregressive models). Besides response time estimation the project will also include a statistical study of the probes. The goal is to understand the behavior of the sensors and monitor them in order to detect any anomalies or malfunctions even if they occur in an early stage.

Análisis genómico y funcional de los sistemas de Quorum Sensing en Rhizobium leguminosarum

Rhizobium leguminosarum (Rl) es una alfa-proteobacteria capaz de establecer una simbiosis diazotrófica con distintas leguminosas. A pesar de la importancia de esta simbiosis en el balance global del ciclo del nitrógeno, muy pocos genomas de rhizobios han sido secuenciados, que aporten nuevos conocimientos relacionados con las características genéticas que contribuyen a importantes procesos simbióticos. Únicamente tres secuencias completas de Rl han sido publicadas: Rl bv. viciae 3841 y dos genomas de Rl bv. trifolii (WSM1325 y WSM2304), ambos simbiontes de trébol. La secuencia genómica de Rlv UPM791 se ha determinado por medio de secuenciación 454. Este genoma tiene un tamaño aproximado de 7.8 Mb, organizado en un cromosoma y 5 replicones extracromosómicos, que incluyen un plásmido simbiótico de 405 kb. Este nuevo genoma se ha analizado en relación a las funciones simbióticas y adaptativas en comparación con los genomas completos de Rlv 3841 y Rl bv. trifolii WSM1325 y WSM2304. Mientras que los plásmidos pUPM791a y b se encuentran conservados, el plásmido simbiótico pUPM791c exhibe un grado de conservación muy bajo comparado con aquellos descritos en las otras cepas de Rl. Uno de los factores implicados en el establecimiento de la simbiosis es el sistema de comunicación intercelular conocido como Quorum Sensing (QS). El análisis del genoma de Rlv UPM791 ha permitido la identificación de dos sistemas tipo LuxRI mediados por señales de tipo N-acyl-homoserina lactonas (AHLs). El análisis mediante HPLC-MS ha permitido asociar las señales C6-HSL, C7-HSL y C8-HSL al sistema rhiRI, codificado en el plásmido simbiótico; mientras que el sistema cinRI, localizado en el cromosoma, produce 3OH-C14:1-HSL. Se ha identificado una tercera sintasa (TraI) codificada en el plásmido simbiótico, pero su regulador correspondiente se encuentra truncado debido a un salto de fase. Adicionalmente, se han encontrado tres reguladores de tipo LuxR-orphan que no presentan una sintasa LuxI asociada. El efecto potencial de las señales tipo AHL se ha estudiado mediante una estrategia de quorum quenching, la cual interfiere con los sistemas de QS de la bacteria. Esta estrategia está basada en la introducción del gen aiiA de Bacillus subtilis, que expresa constitutivamente una enzima lactonasa degradadora de AHLs. Para llevar a cabo el análisis en condiciones simbióticas, se ha desarrollado un sistema de doble marcaje que permite la identificación basado en los marcadores gusA y celB, que codifican para una enzima β–glucuronidasa y una β–galactosidasa termoestable, respectivamente. Los resultados obtenidos indican que Rlv UPM791 predomina sobre la cepa Rlv 3841 para la formación de nódulos en plantas de guisante. La baja estabilidad del plásmido que codifica para aiiA, no ha permitido obtener una conclusión definitiva sobre el efecto de la lactonasa AiiA en competitividad. Con el fin de analizar el significado y la regulación de la producción de moléculas señal tipo AHL, se han generado mutantes defectivos en cada uno de los dos sistemas de QS. Se ha llevado a cabo un análisis detallado sobre la producción de AHLs, formación de biofilm y simbiosis con plantas de guisante, veza y lenteja. El efecto de las deleciones de los genes rhiI y rhiR en Rlv UPM791 es más drástico en ausencia del plásmido pUPM791d. Mutaciones en cinI o cinRIS muestran tanto ausencia de señales, como producción exclusivamente de las de bajo peso molecular, respectivamente, producidas por el sistema rhiRI. Estas mutaciones mostraron un efecto importante en simbiosis. El sistema rhiRI se necesita para un comportamiento simbiótico normal. Además, mutantes cinRIS generaron nódulos blancos e ineficientes, mientras que el mutante cinI fue incapaz de producir nódulos en ninguna de las leguminosas utilizadas. Dicha mutación resultó en la inestabilización del plasmido simbiótico por un mecanismo dependiente de cinI que no ha sido aclarado. En general, los resultados obtenidos indican la existencia de un modelo de regulación dependiente de QS significativamente distinto a los que se han descrito previamente en otras cepas de R. leguminosarum, en las cuales no se había observado ningún fenotipo relevante en simbiosis. La regulación de la producción de AHLs Rlv UPM791 es un proceso complejo que implica genes situados en los plásmidos UPM791c y UPM791d, además de la señal 3-OH-C14:1-HSL. Finalmente, se ha identificado un transportador de tipo RND, homologo a mexAB-oprM de P. aeruginosa e implicado en la extrusión de AHLs de cadena larga. La mutación he dicho transportador no tuvo efectos apreciables sobre la simbiosis. ABSTRACT Rhizobium leguminosarum (Rl) is a soil alpha-proteobacterium that establishes a diazotrophic symbiosis with different legumes. Despite the importance of this symbiosis to the global nitrogen cycling balance, very few rhizobial genomes have been sequenced so far which provide new insights into the genetic features contributing to symbiotically relevant processes. Only three complete sequences of Rl strains have been published: Rl bv. viciae 3841, harboring six plasmids (7.75 Mb) and two Rl bv. trifolii (WSM1325 and WSM2304), both clover symbionts, harboring 5 and 4 plasmids, respectively (7.41 and 6.87 Mb). The genomic sequence of Rlv UPM791 was undertaken by means of 454 sequencing. Illumina and Sanger reads were used to improve the assembly, leading to 17 final contigs. This genome has an estimated size of 7.8 Mb organized in one chromosome and five extrachromosomal replicons, including a 405 kb symbiotic plasmid. Four of these plasmids are already closed, whereas there are still gaps in the smallest one (pUPM791d) due to the presence of insertion elements and repeated sequences, which difficult the assembly. The annotation has been carried out thanks to the Manatee pipeline. This new genome has been analyzed as regarding symbiotic and adaptive functions in comparison to the Rlv 3841 complete genome, and to those from Rl bv. trifolii strains WSM1325 and WSM2304. While plasmids pUPM791a and b are conserved, the symbiotic plasmid pUPM791c exhibited the lowest degree of conservation as compared to those from the other Rl strains. One of the factors involved in the symbiotic process is the intercellular communication system known as Quorum Sensing (QS). This mechanism allows bacteria to carry out diverse biological processes in a coordinate way through the production and detection of extracellular signals that regulate the transcription of different target genes. Analysis of the Rlv UPM791 genome allowed the identification of two LuxRI-like systems mediated by N-acyl-homoserine lactones (AHLs). HPLC-MS analysis allowed the adscription of C6-HSL, C7-HSL and C8-HSL signals to the rhiRI system, encoded in the symbiotic plasmid, whereas the cinRI system, located in the chromosome, produces 3OH-C14:1-HSL, previously described as “bacteriocin small”. A third synthase (TraI) is encoded also in the symbiotic plasmid, but its cognate regulator TraR is not functional due to a fameshift mutation. Three additional LuxR orphans were also found which no associated LuxI-type synthase. The potential effect of AHLs has been studied by means of a quorum quenching approach to interfere with the QS systems of the bacteria. This approach is based upon the introduction into the strains Rl UPM791 and Rl 3841 of the Bacillus subtilis gene aiiA expressing constitutively an AHL-degrading lactonase enzyme which led to virtual absence of AHL even when AiiA-expressing cells were a fraction of the total population. No significant effect of AiiA-mediated AHL removal on competitiveness for growth in solid surface was observed. For analysis under symbiotic conditions we have set up a two-label system to identify nodules produced by two different strains in pea roots, based on the markers gusA and celB, encoding a β–glucuronidase and a thermostable β–galactosidase enzymes, respectively. The results obtained show that Rlv UPM791 outcompetes Rlv 3841 for nodule formation in pea plants, and that the presence of the AiiA plasmid does not significantly affect the relative competitiveness of the two Rlv strains. However, the low stability of the pME6863 plasmid, encoding aiiA, did not lead to a clear conclusion about the AiiA lactonase effect on competitiveness. In order to further analyze the significance and regulation of the production of AHL signal molecules, mutants deficient in each of the two QS systems were constructed. A detailed analysis of the effect of these mutations on AHL production, biofilm formation and symbiosis with pea, vetch and lentil plants has been carried out. The effect of deletions on Rlv UPM791 rhiI and rhiR genes is more pronounced in the absence of plasmid pUPM791d, as no signal is detected in UPM791.1, lacking this plasmid. Mutations in cinI or cinRIS show either no signals, or only the small ones produced by the rhiRI system, suggesting that cinR might be regulating the rhiRI system. These mutations had a strong effect on symbiosis. Analysis of rhi mutants revealed that rhiRI system is required for normal symbiotic performance, as a drastic reduction of symbiotic fitness is observed when rhiI is deleted, and rhiR is essential for nitrogen fixation in the absence of plasmid pUPM791d. Furthermore, cinRIS mutants resulted in white and inefficient nodules, whereas cinI mutant was unable to form nodules on any legume tested. The latter mutation is associated to the instabilization of the symbiotic plasmid through a mechanism still uncovered. Overall, the results obtained indicate the existence of a model of QS-dependent regulation significantly different to that previously described in other R. leguminosarum strains, where no relevant symbiotic phenotype had been observed. The regulation of AHL production in Rlv UPM791 is a complex process involving the symbiotic plasmid (pUPM791c) and the smallest plasmid (pUPM791d), with a key role for the 3-OH-C14:1-HSL signal. Finally, we made a search for potential AHL transporters in Rlv UPM791 genome. These signals diffuse freely across membranes, but in the case of the long-chain AHLs an active efflux system might be required, as it has been described for C12-HSL in the case of Pseudomonas aeruginosa. We have identified a putative AHL transporter of the RND family homologous to P. aeruginosa mexAB-oprM. A mutant strain deficient in this transporter has been generated, and TLC analysis shows absence of 3OH-C14:1-HSL in its supernatant. This deficiency was complemented by the reintroduction of an intact copy of the genes via plasmid transfer. The mutation in mexAB genes had no significant effects on the symbiotic performance of R. leguminosarum bv. viciae.

Neutronic analysis of the bi-spectral moderator such as that proposed for ESS

This paper reports on design studies concerning a moderator concept which aims to maximize the time averaged flux. The idea is to provide neutron spectra showing two clear maxima, with peaks at View the MathML source and View the MathML source arising from leakage from both cryogenic and thermal moderators. Such a concept known as a bi-spectral moderator (Mezei, 2006 [1]) while proven on a reactor source has only been examined for the ESS 2003 proposal. Filges et al. (2003 [2]), which featured a different design than the current ESS. This paper thus reports on a baseline design for such a moderator concept and shows that it can provide substantial gains in count rates for those applications not requiring high resolution in time-of-flight.

Conceptual design of the beryllium rotating target for the ESS-Bilbao facility

The ESS-Bilbao facility, hosted by the University of the Basque Country (UPV/EHU), envisages the operation of a high-current proton accelerator delivering beams with energies up to 50 MeV. The time-averaged proton current will be 2.25 mA, delivered by 1.5 ms proton pulses with a repetition rate of 20 Hz. This beam will feed a neutron source based upon the Be (p,n) reaction, which will enable the provision of relevant neutron experimentation capabilities. The neutron source baseline concept consists in a rotating beryllium target cooled by water. The target structure will comprise a rotatable disk made of 6061-T6 aluminium alloy holding 20 beryllium plates. Heat dissipation from the target relies upon a distribution of coolant-flow channels. The practical implementation of such a concept is here described with emphasis put on the beryllium plates thermo-mechanical optimization, the chosen coolant distribution system as well as the mechanical behavior of the assembly.