Climatology of Mid-latitude Ionospheric Disturbances from the Very Large Array Low-frequency Sky Survey

The results of a climatological study of ionospheric disturbances derived from observations of cosmic sources from the Very Large Array (VLA) Low-frequency Sky Survey (VLSS) are presented. We have used the ionospheric corrections applied to the 74 MHz interferometric data within the VLSS imaging process to obtain fluctuation spectra for the total electron content (TEC) gradient on spatial scales from a few to hundreds of kilometers and temporal scales from less than one minute to nearly an hour. The observations sample nearly all times of day and all seasons. They also span latitudes and longitudes from 28 deg. N to 40 deg. N and 95 deg. W to 114 deg. W, respectively. We have binned and averaged the fluctuation spectra according to time of day, season, and geomagnetic (Kp index) and solar (F10.7) activity. These spectra provide a detailed, multi-scale account of seasonal and intraday variations in ionospheric activity with wavelike structures detected at wavelengths between about 35 and 250 km. In some cases, trends between spectral power and Kp index and/or F10.7 are also apparent. In addition, the VLSS observations allow for measurements of the turbulent power spectrum down to periods of 40 seconds (scales of ~0.4 km at the height of the E-region). While the level of turbulent activity does not appear to have a strong dependence on either Kp index or F10.7, it does appear to be more pronounced during the winter daytime, summer nighttime, and near dusk during the spring.Comment: accepted for publication in Radio Scienc

Functional consequences of seven novel mutations in the CYP11B1 Gene: four mutations associated with nonclassic and three mutations causing classic 11 -Hydroxylase Deficiency

Context: Steroid 11β-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Cases of nonclassic 11OHD are rare compared with the incidence of nonclassic 21-hydroxylase deficiency. Objective: The aim of the study was to analyze the functional consequences of seven novel CYP11B1 mutations (p.M88I, p.W116G, p.P159L, p.A165D, p.K254_A259del, p.R366C, p.T401A) found in three patients with classic 11OHD, two patients with nonclassic 11OHD, and three heterozygous carriers for CYP11B1 mutations. Methods: We conducted functional studies employing a COS7 cell in vitro expression system comparing wild-type (WT) and mutant CYP11B1 activity. Mutants were examined in a computational three-dimensional model of the CYP11B1 protein. Results: All mutations (p.W116G, p.A165D, p.K254_A259del) found in patients with classic 11OHD have absent or very little 11β-hydroxylase activity relative to WT. The mutations detected in patients with nonclassic 11OHD showed partial functional impairment, with one patient being homozygous (p.P159L; 25% of WT) and the other patient compound heterozygous for a novel mild p.M88I (40% of WT) and the known severe p.R383Q mutation. The two mutations detected in heterozygous carriers (p.R366C, p.T401A) also reduced CYP11B1 activity by 23 to 37%, respectively. Conclusion: Functional analysis results allow for the classification of novel CYP11B1 mutations as causative for classic and nonclassic 11OHD, respectively. Four partially inactivating mutations are predicted to result in nonclassic 11OHD. These findings double the number of mild CYP11B1 mutations previously described as associated with mild 11OHD. Our data are important to predict phenotypic expression and provide important information for clinical and genetic counseling i

Ferredoxin 1b (Fdx1b) Is the essential mitochondrial redox partner for cortisol biosynthesis in zebrafish

Mitochondrial cytochrome P450 (CYP) enzymes rely on electron transfer from the redox partner ferredoxin 1 (FDX1) for catalytic activity. Key steps in steroidogenesis require mitochondrial CYP enzymes and FDX1. Over 30 ferredoxin mutations have been explored in vitro; however, no spontaneously occurring mutations have been identified in humans leaving the impact of FDX1 on steroidogenesis in the whole organism largely unknown. Zebrafish are an important model to study human steroidogenesis, because they have similar steroid products and endocrine tissues. This study aimed to characterize the influence of ferredoxin on steroidogenic capacity in vivo by using zebrafish. Zebrafish have duplicate ferredoxin paralogs: fdx1 and fdx1b. Although fdx1 was observed throughout development and in most tissues, fdx1b was expressed after development of the zebrafish interrenal gland (counterpart to the mammalian adrenal gland). Additionally, fdx1b was restricted to adult steroidogenic tissues, such as the interrenal, gonads, and brain, suggesting that fdx1b was interacting with steroidogenic CYP enzymes. By using transcription activator-like effector nucleases, we generated fdx1b mutant zebrafish lines. Larvae with genetic disruption of fdx1b were morphologically inconspicuous. However, steroid hormone analysis by liquid chromatography tandem mass spectrometry revealed fdx1b mutants failed to synthesize glucocorticoids. Additionally, these mutants had an up-regulation of the hypothalamus-pituitary-interrenal axis and showed altered dark-light adaptation, suggesting impaired cortisol signaling. Antisense morpholino knockdown confirmed Fdx1b is required for de novo cortisol biosynthesis. In summary, by using zebrafish, we generated a ferredoxin knockout model system, which demonstrates for the first time the impact of mitochondrial redox regulation on glucocorticoid biosynthesis in vivo

Autoecología, calidad de estación y xilología de "Quercus pyrenaica" Willd. en Galicia

Los rebollares, bosques de Quercus pyrenaica Willd., son un patrimonio natural de gran valor que desempeñan importantes funciones de conservación del suelo y del agua, de la biodiversidad y del paisaje natural, contribuyendo a una satisfacción económica de las poblaciones a partir de actividades como la caza, el turismo, el aprovechamiento de la madera,..., razones por las que se justifica la realización de un estudio sobre estos rebollares. Teniendo en cuenta que los estudios globales realizados sobre esta especie en Galicia son inexistentes hasta la fecha, nos planteamos hacer un trabajo en el que se describan estas masas, intentando dar a conocer su importancia a traves de su caracterización ecológica, delimitación de calidades de estación, estudio de la aptitud tecnológica de la madera y de las propiedades de ésta tanto físicas como mecánicas.Pyrenean oak (Quercus pyrenaica) stands are a very valuable natural heritage and have important functions in the conservation of soil, water, biodiversity and the natural landscape. They are also of economic value to local populations through activities such as hunting, tourism, timber exploitation,… reasons that justify their study. As no detailed studies have been made of this species in Galicia, we proposed describing the stands, attempting to establish their importance by characterising their ecological parameters, defining site index and studying the technological aptitude of the wood as well physical and mechanical properties

Determinación de estrategia de optimización del ciclo de vida de activos de alta capitalización en la industria del gas natural

La combinación del conocimiento humano con la capacidad computacional de los sistemas es uno de los pilares más sólidos y fiables en la gestión de activos actualmente. No cabe duda de que ya se puede vislumbrar un futuro en el que la digitalización va a ser una parte capital en la gestión de las empresas. De hecho, en las compañías que tienen muy definidos sus procesos productivos, lleva siendo una realidad desde hace tiempo. Sin embargo, las empresas de gestión de infraestructuras tienen una serie de retos que no permiten un avance tan claro en este campo. Primero, porque sus activos no responden de manera directa a unas variables claras que permitan tomar decisiones de manera automática. Y segundo, porque aunque se consiguiera definir este “algoritmo” de decisión, se necesitaría de una base sólida de información fiable que alimentara dicho sistema, premisa que a día de hoy está muy lejana. Por lo tanto, todas las aplicaciones digitales con una implantación real en la gestión de activos, tienen a día de hoy una componente de conocimiento especialista muy importante. Debido a esa carencia histórica de datos fiables que ahora se consideran tan necesarios y básicos para la creación de modelos y algoritmos, las soluciones que se están implantando tienden a partir de una base importante de conocimiento humano. Así que, si bien existe un futuro automatizado, no sólo en el proceso productivo, sino el ámbito de gestión, la clave estará en como diseñar el modelo que lo hará funcionar de una manera efectiva. Es justo en ese momento, donde las metodologías de gestión de mantenimiento propuestas en la tesis presentan una forma sencilla e intuitiva de hacer una primera aproximación a la gestión en base a analíticas avanzadas sin necesidad de ceder el control total a un algoritmo. El gran valor de estas técnicas, es ser capaz de transformar de una manera simple el inmenso conocimiento de los especialistas en un ámbito técnico concreto, a formulaciones con criterios objetivos de cálculo, que derivarán en indicadores o valores que ayudarán en la gestión. Por supuesto, estas técnicas también tienen sus detractores, pues incluir como parte esencial el factor humano, es también incluir un factor de subjetividad y de posibilidad de error, mayor que el que aparentemente podría llegar a dar un ordenador. Sin embargo, cualquier ámbito de gestión no puede estar exento del factor humano que de hecho es el mayor factor diferencial que podemos encontrarnos. De esa manera el reto es ser capaces de llevar a valores, fórmulas y datos, las opiniones, sensaciones y aprendizajes que han acumulado los especialistas en torno a los activos industriales que manejan. Debido a su sencilla implantación e interpretación, estas metodologías permiten traducir todo ese conocimiento, y facilitar enormemente la comunicación, entre los especialistas técnicos, los mandos intermedios y la alta dirección. Al tener, gracias a estas técnicas, una comunicación más rápida y un mensaje más comprensible, se consiguen estrategias de gestión más eficiente y con una visión mucho más integral. Es por tanto alcance de la tesis ser capaz de identificar e integrar dentro del modelo actual de gestión de la compañía, herramientas de gestión de mantenimiento que permitan optimizar el ciclo de vida del activo. En concreto se desarrollarán dos técnicas centradas en dos ámbitos de gestión de los activos de gran valor para la compañía; la gestión del riesgo que persigue caracterizar los equipos en función del impacto de un hipotético fallo funcional, y la gestión operativa, que persigue mejorar el rendimiento de dichos activos durante toda su vida útil.The combination of human knowledge with the computational capacity of systems is one of the most solid and reliable pillars in asset management today. There is no doubt that we assume a future in which digitalization will be a key part of company management. In fact, in companies with well-defined production processes, it has been a reality for some time now. However, asset management companies face a series of challenges that do not allow such a clear advance in this field. Firstly, their assets do not respond directly to clear variables that allow automatic decision making. And secondly, even if this decision "algorithm" could be defined, it would require a solid base of reliable information to feed the system, a premise that is still far away. Therefore, all digital applications with a real implementation in asset management today, have a very important component of specialist knowledge. Due to this historical lack of reliable data that is now considered so necessary and basic for the creation of models and algorithms, the solutions that are being implemented tend to start from a significant base of human knowledge. In other words, if there is an automated future, not only in the production process, but also in the management area, the key will be how to design the model that will make it work in an effective way. It is precisely at this point where the maintenance management methodologies proposed in this thesis, present a simple and intuitive way to make a first approach to management based on advanced analytics without the need to let the control to an algorithm. The great value of these techniques is that allow to transform in a simple way the immense knowledge of specialists in a specific technical field, to formulations with objective calculation criteria, which will derive in indicators or values that will help in management. Of course, these techniques also have their detractors. To include the human factor as an essential part of the methodology is also to include a factor of subjectivity and the possibility of error. However, any field of management cannot be exempt from the human factor, which is in fact the greatest differential factor that we can find. Thus, the challenge is to be able to transform into values, formulas and data, the opinions, sensations and learning that specialists have accumulated around the industrial assets they manage. Due to their simple implementation and interpretation, these methodologies make it possible to digitalise all this knowledge and facilitate communication between technical specialists, middle management and top management. By having, thanks to these techniques, a faster communication and a more understandable message, more efficient management strategies with a much more comprehensive vision are achieved. It is the scope of the thesis to be able to identify and integrate within the current management model of the company, maintenance management tools to optimize the life cycle of the asset. Specifically, two techniques will be developed focused on two areas of asset management of great value for the company; risk management, which aims to characterize the equipment according to the impact of a hypothetical functional failure, and operational management, which aims to improve the performance of these assets throughout their useful life

Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort

Context: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking.Objective: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH.Research Design and Methods: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort.Results: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups.Conclusions: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment. (J Clin Endocrinol Metab 98: E346-E354, 2013)</p

Criticality Analysis for optimising OPEX cost lifecycle

3rd IFAC Workshop on Advanced Maintenance Engineering, Services and Technology AMEST 2016: Biarritz, France, 19—21 October 2016. - IFAC-PapersOnLine, Volume 49, Issue 28, 2016, Pages 7-12Identification and quantification of cost and value of industrial assets is a field in which much terminology is mixed. When we try to analyze the importance of an asset for our business, to discuss about its costs should not be separated from the value provided by the asset. Most of the times, managers only use the term “cost” because it seems to be more objective. Value is more subjective and more difficult to define. However, we must try to use definitions as amortization, inflation, replacement value in order to simplify the concept of “value” to improve our decisions. In the case of regulated companies, the economic valuation of the facilities is based on a legal normative, so the concept of “cost” may turn to be quite useless. Therefore, it is important to use a methodology that allows us to estimate the value of our assets. We have developed a criticality analysis of our infrastructures in order to assess the relative value of these items for the company. The target is to optimize the operation and maintenance (O&M) strategies at a corporate level. This must have a relevant impact in the OPEX of our company, and may be also an impact in future CAPEX. This paper discusses the methodology and presents clear examples of how O&M strategy is transformed according to criticality assessments

Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant

Background Hepcidin acts as the main regulator of iron homeostasis through regulation of intestinal absorption and macrophage release. Hepcidin deficiency causes iron overload whereas its overproduction is associated with anaemia of chronic diseases. The aims of the study were: to identify genetic variants in the hepcidin gene (HAMP) promoter, to asses the associations between the variants found and iron status parameters, and to functionally study the role on HAMP expression of the most frequent variant. Results The sequencing of HAMP promoter from 103 healthy individuals revealed two genetic variants: The c.-153C > T with a frequency of 0.014 for allele T, which is known to reduce hepcidin expression and the c.-582A > G with a 0.218 frequency for allele G. In an additional group of 224 individuals, the c.-582A > G variant genotype showed no association with serum iron, transferrin or ferritin levels. The c.-582G HAMP promoter variant decreased the transcriptional activity by 20% compared to c.-582A variant in cells from the human hepatoma cell line HepG2 when cotransfected with luciferase reporter constructs and plasmid expressing upstream stimulatory factor 1 (USF1) and by 12-14% when cotransfected with plasmid expressing upstream stimulatory factor 2 (USF2). Conclusions The c.-582A > G HAMP promoter variant is not associated with serum iron, transferrin or ferritin levels in the healthy population. The in vitro effect of the c.-582A > G variant resulted in a small reduction of the gene transactivation by allele G compared to allele A. Therefore the effect of the variant on the hepcidin levels in vivo would be likely negligible. Finally, the c.-153C > T variant showed a frequency high enough to be considered when a genetic analysis is done in iron overload patientsThis work was supported by a grant from the Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III (PI052249 to LL) and Xunta de Galicia (PGIDIT06PXIC9101136PN)S

Selección del tratamiento óptimo de aguas residuales para poblaciones del medio rural de Galicia

La depuración de aguas residuales en pequeños núcleos debe orientarse hacia alternativas diferentes a las que se suelen aplicar en poblaciones de mayor tamaño. En este sentido, la tecnología actual ofrece un amplio abanico de tratamientos, especialmente los denominados naturales o de bajo coste. Teniendo en cuenta los últimos desarrollos en este campo, en el presente trabajo se aplica una metodología de ayuda a la toma de decisiones para facilitar la elección del sistema de tratamiento más adecuado en núcleos rurales de Galicia. Los núcleos escogidos para el análisis abarcan gran parte de la diversidad del problema en el ámbito rural gallego