The effect of exposure to antibiotics on incidence and spontaneous clearance of childhood Helicobacter pylori infection

It is claimed often in the H. pylori literature that spontaneous clearance (infection loss without attempts to treat) is uncommon, though little evidence supports this claim. Emerging evidence suggests that spontaneous clearance may be frequent in young children; however, factors that determine persistence of untreated H. pylori infection in childhood are not well understood. The author hypothesized that antibiotics taken for common infections cause spontaneous clearance of H. pylori infection in children. The Pasitos Cohort Study (19982005) investigated predictors of acquisition and persistence of H. pylori infection in children from El Paso, Texas, and Juarez, Mexico, enrolled prenatally at maternal-child clinics. Children were screened for infection at target intervals of 6 months from 6-84 months of age by the 13C-urea breath test corrected for body-size-dependent variation in CO2 production. This dissertation aimed to estimate the risk of spontaneous clearance at the next test following an initial detected H. pylori infection (first detected clearance), estimate the effect of antibiotic exposure on the risk of first detected clearance (risk difference), and estimate the effect of antibiotic exposure on the rate of first detected infection (rate ratio). Data on infection status and medication history were available for 608 children followed for a mean of 3.5 years. Among 265 subjects with a first detected infection, 218 had a subsequent test, and among them, the risk of first detected clearance was 68% (95% CI: 61-74%). Children who took antibiotics during the interval between first detected infection and next test had an increased probability (risk difference of 10 percentage points) of a first detected clearance. However, there was also a similar effect of average antibiotic use >0 courses across all intervals preceding the next test. Average antibiotic exposure across all intervals preceding the first detected infection appeared to have a much stronger protective effect than interval/specific exposure when estimating incidence rate ratios (0.45 vs. 1.0). Incidental antibiotic exposure appears to influence the acquisition and duration of childhood H. pylori infection, however, given that many exposed children acquired the infection and many unexposed children cleared the infection, antibiotic exposure does not explain all infection events. ^

The role of reactive astrocytes in the resistance of melanoma brain metastasis to chemotherapy

Brain metastasis is resistant to chemotherapy while the leaky blood-brain-barrier in brain metastasis can not be the underlying reason. Metastatic tumor cells (“seed”) exploit the host microenvironment (“soil”) for survival advantages. Astrocytes which maintain the homeostasis of the brain microenvironment become reactive subsequent to brain damages and protect neurons from various injuries. We observed reactive astrocytes surrounding and infiltrating into brain metastasis in both clinical specimen and experimental animal model, thus raising a possibility that reactive astrocytes may protect tumor cells from cytotoxic chemotherapeutic drugs. ^ To test this hypothesis, we first generated an immortalized astrocyte cell line from H-2Kb-tsA58 mice. The immortal mouse astrocytes expressed specific markers including GFAP. Scanning electron microscopy demonstrated that astrocytes formed direct physical contact with tumor cells. Moreover, the expression of GFAP by astrocytes was up-regulated subsequent to co-culture with tumor cells, indicating that the co-culture of astrocytes and tumor cells may serve as a model to recapitulate the pathophysiological situation of brain metastasis. ^ In co-culture, astrocytes dramatically reduced apoptosis of tumor cells produced by various chemotherapeutic drugs. This protection effect was not because of culturing cells from different species since mouse fibroblasts did not protect tumor cells from chemotherapy. Furthermore, the protection by astrocytes was completely dependent on a physical contact. ^ Gap junctional communication (GJC) served as this physical contact. Tumor cells and astrocytes both expressed the major component of gap junctional channel—connexin 43 and formed functional GJC as evidenced by the “dye transfer” assay. The blockage of GJC between tumor cells and astrocytes by either specific chemical blocker carbenoxolone (CBX) or by genetically knocking down connexin 43 on astrocytes reversed the chemo-protection. ^ Calcium was the signal molecule transmitted through GJC that rescued tumor cells from chemotherapy. Accumulation of cytoplasmic calcium preceded the progress of apoptosis in tumor cells treated with chemotherapeutic drugs. Furthermore, chelation of accumulated cytoplasmic calcium inhibited the apoptosis of tumor cells treated with chemotherapeutic drugs. Most importantly, astrocytes could “shunt” the accumulated cytoplasmic calcium from tumor cells (treated with chemotherapeutic drug) through GJC. We also used gene expression micro-array to investigate global molecular consequence of tumor cells forming GJC with astrocytes. The data demonstrated that astrocytes (but not fibroblasts), through GJC, up-regulated the expressions of several well known survival genes in tumor cells. ^ In summary, this dissertation provides a novel mechanism underlying the resistance of brain metastasis to chemotherapy, which is due to protection by astrocytes through GJC. Interference with the GJC between astrocytes and tumor cells holds great promise in sensitizing brain metastasis to chemotherapy and improving the prognosis for patients with brain metastasis. ^

Laboratory investigation of flow structure and resistance of high- and low-angle dunes

A prominent control on the flow over subaqueous dunes is the slope of the downstream leeside. While previous work has focused on steep (~30°), asymmetric dunes with permanent flow separation, little is known about dunes with lower lee-slope angles for which flow separation is absent or intermittent. Here, we present a laboratory investigation where we systematically varied the dune lee-slope, holding other geometric parameters and flow hydraulics constant, to explore effects on the turbulent flow field and flow resistance. Three sets of fixed dunes (lee-slopes of 10°, 20° and 30°) were separately installed in a 15 m long and 1 m wide flume and subjected to 0.20 m deep flow. Measurements consisted of high-frequency, vertical profiles collected with a Laser Doppler Velocimeter (LDV). We show that the temporal and spatial occurrence of flow separation decreases with dune lee-slope. Velocity gradients in the dune leeside depict a free shear layer downstream of the 30° dunes and a weaker shear layer closer to the bed for the 20° and 10° dunes. The decrease in velocity gradients leads to lower magnitude of turbulence production for gentle lee-slopes. Aperiodic, strong ejection events dominate the shear layer, but decrease in strength and frequency for low-angle dunes. Flow resistance of dunes decreases with lee-slope; the transition being non-linear. Over the 10°, 20° and 30° dunes, shear stress is 8%, 33% and 90 % greater than a flat bed, respectively. Our results demonstrate that dune lee-slope plays an important, but often ignored role in flow resistance.

Geochemistry of last glacial sediments of Isla de los Estados, southeastern Tierra del Fuego

The island of Isla de los Estados is situated at 54.5°S, 64°W, east of Argentinian Tierra del Fuego, and is located in a sensitive geographic position in relation to the zonal circulation between Antarctica and South America. Its terrestrial records of the last deglaciation, recording atmospheric conditions but within an oceanic setting, can help to clarify changes of regional circulation patterns, both atmospheric and marine. Here, we present geochemical analyses from 16-10 ka cal BP of a peat core from Lago Galvarne Bog at the northern coast of the island, and a lake sediment core from Laguna Cascada 3 km further south. The data comprise TC, TN, loss on ignition analyses and continuous XRF scanning on both cores as well as age-depth modeling based on AMS-14C dating. Deglaciation and onset of peat formation in the coastal areas began before 16 ka cal BP followed by a rapid glacial retreat and the start of lacustrine sedimentation further inland. Data suggest initially windy conditions with permafrost succeeded by gradually warmer and wetter conditions until ca 14.5 ka cal BP. The warming trend slows down until ca 13.5 ka cal BP, followed by arid conditions culminating around 12.8 ka cal BP. Our data suggest fairly warm conditions and the establishment of denser peat and forest vegetation ca 10.6 ka cal BP, contemporaneous with the onset of the Antarctic thermal optimum. This indicates large-scale shifts in the placement of zonal flow and the Westerlies at the beginning of the Holocene.

Pacific-wide contrast highlights resistance of reef calcifiers to ocean acidification

Ocean acidification (OA) and its associated decline in calcium carbonate saturation states is one of the major threats that tropical coral reefs face this century. Previous studies of the effect of OA on coral reef calcifiers have described a wide variety of outcomes for studies using comparable partial pressure of CO2 (pCO2) ranges, suggesting that key questions remain unresolved. One unresolved hypothesis posits that heterogeneity in the response of reef calcifiers to high pCO2 is a result of regional-scale variation in the responses to OA. To test this hypothesis, we incubated two coral taxa (Pocillopora damicornis and massive Porites) and two calcified algae (Porolithon onkodes and Halimeda macroloba) under 400, 700 and 1000 µatm pCO2 levels in experiments in Moorea (French Polynesia), Hawaii (USA) and Okinawa (Japan), where environmental conditions differ. Both corals and H. macroloba were insensitive to OA at all three locations, while the effects of OA on P. onkodes were location-specific. In Moorea and Hawaii, calcification of P. onkodes was depressed by high pCO2, but for specimens in Okinawa, there was no effect of OA. Using a study of large geographical scale, we show that resistance to OA of some reef species is a constitutive character expressed across the Pacific.

Global compilation of last glacial maximum oxygen isotopic ratios for planktonic and benthic foraminifera

We use the fully coupled atmosphere-ocean three-dimensional model of intermediate complexity iLOVECLIM to simulate the climate and oxygen stable isotopic signal during the Last Glacial Maximum (LGM, 21 000 yr). By using a model that is able to explicitly simulate the sensor (d18O), results can be directly compared with data from climatic archives in the different realms. Our results indicate that iLOVECLIM reproduces well the main feature of the LGM climate in the atmospheric and oceanic components. The annual mean d18O in precipitation shows more depleted values in the northern and southern high latitudes during the LGM. The model reproduces very well the spatial gradient observed in ice core records over the Greenland ice-sheet. We observe a general pattern toward more enriched values for continental calcite d18O in the model at the LGM, in agreement with speleothem data. This can be explained by both a general atmospheric cooling in the tropical and subtropical regions and a reduction in precipitation as confirmed by reconstruction derived from pollens and plant macrofossils. Data-model comparison for sea surface temperature indicates that iLOVECLIM is capable to satisfyingly simulate the change in oceanic surface conditions between the LGM and present. Our data-model comparison for calcite d18O allows investigating the large discrepancies with respect to glacial temperatures recorded by different microfossil proxies in the North Atlantic region. The results argue for a trong mean annual cooling between the LGM and present (>6°C), supporting the foraminifera transfer function reconstruction but in disagreement with alkenones and dinocyst reconstructions. The data-model comparison also reveals that large positive calcite d18O anomaly in the Southern Ocean may be explained by an important cooling, although the driver of this pattern is unclear. We deduce a large positive d18Osw anomaly for the north Indian Ocean that contrasts with a large negative d18Osw anomaly in the China Sea between the LGM and present. This pattern may be linked to changes in the hydrological cycle over these regions. Our simulation of the deep ocean suggests that changes in d18Osw between the LGM and present are not spatially homogenous. This is supported by reconstructions derived from pore fluids in deep-sea sediments. The model underestimates the deep ocean cooling thus biasing the comparison with benthic calcite d18O data. Nonetheless, our data-model comparison support a heterogeneous cooling of few degrees (2-4°C) in the LGM Ocean.

Evaluation of the trading development in the Iberian Energy Derivatives Market

The efficiency of the Iberian Energy Derivatives Market in its first five and a half years is assessed in terms of volume, open interest and price. The continuous market shows steady liquidity growth. Its volume is strongly correlated to that of the Over The Counter (OTC) market, the amount of market makers, the enrolment of financial agents and generation companies belonging to the integrated group of last resort suppliers, and the OTC cleared volume in its clearing house. The hedging efficiency, measured through the ratio between the final open interest and the cleared volume, shows the lowest values for the Spanish base load futures as they are the most liquid contracts. The ex-post forward risk premium has diminished due to the learning curve and the effect of the fixed price retributing the indigenous coal fired generation. This market is quite less developed than the European leaders headquartered in Norway and Germany. Enrolment of more traders, mainly international energy companies, financial agents, energy intensive industries and renewable generation companies is desired. Market monitoring reports by the market operator providing post-trade transparency, OTC data access by the energy regulator, and assessment of the regulatory risk can contribute to efficiency gains.

Relations between resistance of fruit and skin characteristics in tomato varieties.

Varietal differences in physical properties of processing tomato fruits related with resistance are determined. Mean values of skin resistance and firmness are highly correlated with rupture of the fruits by quasi-static compression and by impact. Skin resistance is dependent on the features of the epidermis, studied microscopically.

Fruit firmness and skin resistance of processing tomato varieties tested in Badajoz (Spain), related to mechanical harvesting.

Determinations of resistance to damage were carried out in a total of 31 tomato varieties for processing, with the purpose of choosing the most suitable ones for mechanical harvesting. The characteristics studied include: puncture, deformation and rupture of the fruits, the ease of detachment of the fruits also being determined. Seventeen varieties were chosen, for further tests, with values 0.76 to 1.7 2 N of resistance to puncture; 3 to 9 N/mm of resistance to compression and 2.16 to 29.40 N resistance to detachment.

Effect of strain and magnetic field on the critical current and electric resistance of the joints between HTS coated conductors

Engineering of devices and systems such as magnets, fault current limiters or cables, based on High Temperature Superconducting wires requires a deep characterization of the possible degradation of their properties by handling at room temperature as well as during the service life thus establishing the limits for building up functional devices and systems. In the present work we report our study regarding the mechanical behavior of spliced joints between commercial HTS coated conductors based on YBCO at room temperature and service temperature, 77 K. Tensile tests under axial stress and the evolution of the critical current and the electric resistance of the joints have been measured. The complete strain contour for the tape and the joint has been obtained by using Digital Image Correlation. Also, tensile tests under external magnetic field have been performed and the effect of the applied field on the critical current and the electric resistance of the joints has been studied. Finally, a preliminary numerical study by means of Finite Element Method (FEM) of the mechanical behavior of the joints between commercial HTS is presented.

Effect of strain and magnetic field on the critical current and electric resistance of the joints between HTS coated conductors

Engineering of devices and systems such as magnets, fault current limiters or cables, based on High Temperature Superconducting wires requires a deep characterization of the possible degradation of their properties by handling at room temperature as well as during the service life thus establishing the limits for building up functional devices and systems. In the present work we report our study regarding the mechanical behavior of spliced joints between commercial HTS coated conductors based on YBCO at room temperature and service temperature, 77 K. Tensile tests under axial stress and the evolution of the critical current and the electric resistance of the joints have been measured. The complete strain contour for the tape and the joints has been obtained by using Digital Image Correlation. Also, tensile tests under external magnetic field have been performed and the effect of the applied field on the critical current and the electric resistance of the joints has been studied. Additionally, fatigue tests under constant cyclic stress and loading-unloading ramps have been carried out in order to evaluate the electromechanical behavior of the joints and the effect of maximum applied stress on the critical current. Finally, a preliminary numerical study by means of the Finite Element Method (FEM) of the electromechanical behavior of the joints between commercial HTS is presented.

Propuestas regulatorias para el diseño de un mercado ibérico a plazo eficiente de la energía = Regulatory proposals for the development of an efficient iberian energy forward market

El mercado ibérico de futuros de energía eléctrica gestionado por OMIP (“Operador do Mercado Ibérico de Energia, Pólo Português”, con sede en Lisboa), también conocido como el mercado ibérico de derivados de energía, comenzó a funcionar el 3 de julio de 2006. Se analiza la eficiencia de este mercado organizado, por lo que se estudia la precisión con la que sus precios de futuros predicen el precio de contado. En dicho mercado coexisten dos modos de negociación: el mercado continuo (modo por defecto) y la contratación mediante subasta. En la negociación en continuo, las órdenes anónimas de compra y de venta interactúan de manera inmediata e individual con órdenes contrarias, dando lugar a operaciones con un número indeterminado de precios para cada contrato. En la negociación a través de subasta, un precio único de equilibrio maximiza el volumen negociado, liquidándose todas las operaciones a ese precio. Adicionalmente, los miembros negociadores de OMIP pueden liquidar operaciones “Over-The-Counter” (OTC) a través de la cámara de compensación de OMIP (OMIClear). Las cinco mayores empresas españolas de distribución de energía eléctrica tenían la obligación de comprar electricidad hasta julio de 2009 en subastas en OMIP, para cubrir parte de sus suministros regulados. De igual manera, el suministrador de último recurso portugués mantuvo tal obligación hasta julio de 2010. Los precios de equilibrio de esas subastas no han resultado óptimos a efectos retributivos de tales suministros regulados dado que dichos precios tienden a situarse ligeramente sesgados al alza. La prima de riesgo ex-post, definida como la diferencia entre los precios a plazo y de contado en el periodo de entrega, se emplea para medir su eficiencia de precio. El mercado de contado, gestionado por OMIE (“Operador de Mercado Ibérico de la Energía”, conocido tradicionalmente como “OMEL”), tiene su sede en Madrid. Durante los dos primeros años del mercado de futuros, la prima de riesgo media tiende a resultar positiva, al igual que en otros mercados europeos de energía eléctrica y gas natural. En ese periodo, la prima de riesgo ex-post tiende a ser negativa en los mercados de petróleo y carbón. Los mercados de energía tienden a mostrar niveles limitados de eficiencia de mercado. La eficiencia de precio del mercado de futuros aumenta con el desarrollo de otros mecanismos coexistentes dentro del mercado ibérico de electricidad (conocido como “MIBEL”) –es decir, el mercado dominante OTC, las subastas de centrales virtuales de generación conocidas en España como Emisiones Primarias de Energía, y las subastas para cubrir parte de los suministros de último recurso conocidas en España como subastas CESUR– y con una mayor integración de los mercados regionales europeos de energía eléctrica. Se construye un modelo de regresión para analizar la evolución de los volúmenes negociados en el mercado continuo durante sus cuatro primeros años como una función de doce indicadores potenciales de liquidez. Los únicos indicadores significativos son los volúmenes negociados en las subastas obligatorias gestionadas por OMIP, los volúmenes negociados en el mercado OTC y los volúmenes OTC compensados por OMIClear. El número de creadores de mercado, la incorporación de agentes financieros y compañías de generación pertenecientes a grupos integrados con suministradores de último recurso, y los volúmenes OTC compensados por OMIClear muestran una fuerte correlación con los volúmenes negociados en el mercado continuo. La liquidez de OMIP está aún lejos de los niveles alcanzados por los mercados europeos más maduros (localizados en los países nórdicos (Nasdaq OMX Commodities) y Alemania (EEX)). El operador de mercado y su cámara de compensación podrían desarrollar acciones eficientes de marketing para atraer nuevos agentes activos en el mercado de contado (p.ej. industrias consumidoras intensivas de energía, suministradores, pequeños productores, compañías energéticas internacionales y empresas de energías renovables) y agentes financieros, captar volúmenes del opaco OTC, y mejorar el funcionamiento de los productos existentes aún no líquidos. Resultaría de gran utilidad para tales acciones un diálogo activo con todos los agentes (participantes en el mercado, operador de mercado de contado, y autoridades supervisoras). Durante sus primeros cinco años y medio, el mercado continuo presenta un crecimento de liquidez estable. Se mide el desempeño de sus funciones de cobertura mediante la ratio de posición neta obtenida al dividir la posición abierta final de un contrato de derivados mensual entre su volumen acumulado en la cámara de compensación. Los futuros carga base muestran la ratio más baja debido a su buena liquidez. Los futuros carga punta muestran una mayor ratio al producirse su menor liquidez a través de contadas subastas fijadas por regulación portuguesa. Las permutas carga base liquidadas en la cámara de compensación ubicada en Madrid –MEFF Power, activa desde el 21 de marzo de 2011– muestran inicialmente valores altos debido a bajos volúmenes registrados, dado que esta cámara se emplea principalmente para vencimientos pequeños (diario y semanal). Dicha ratio puede ser una poderosa herramienta de supervisión para los reguladores energéticos cuando accedan a todas las transacciones de derivados en virtud del Reglamento Europeo sobre Integridad y Transparencia de los Mercados de Energía (“REMIT”), en vigor desde el 28 de diciembre de 2011. La prima de riesgo ex-post tiende a ser positiva en todos los mecanismos (futuros en OMIP, mercado OTC y subastas CESUR) y disminuye debido a la curvas de aprendizaje y al efecto, desde el año 2011, del precio fijo para la retribución de la generación con carbón autóctono. Se realiza una comparativa con los costes a plazo de generación con gas natural (diferencial “clean spark spread”) obtenido como la diferencia entre el precio del futuro eléctrico y el coste a plazo de generación con ciclo combinado internalizando los costes de emisión de CO2. Los futuros eléctricos tienen una elevada correlación con los precios de gas europeos. Los diferenciales de contratos con vencimiento inmediato tienden a ser positivos. Los mayores diferenciales se dan para los contratos mensuales, seguidos de los trimestrales y anuales. Los generadores eléctricos con gas pueden maximizar beneficios con contratos de menor vencimiento. Los informes de monitorización por el operador de mercado que proporcionan transparencia post-operacional, el acceso a datos OTC por el regulador energético, y la valoración del riesgo regulatorio pueden contribuir a ganancias de eficiencia. Estas recomendaciones son también válidas para un potencial mercado ibérico de futuros de gas, una vez que el hub ibérico de gas –actualmente en fase de diseño, con reuniones mensuales de los agentes desde enero de 2013 en el grupo de trabajo liderado por el regulador energético español– esté operativo. El hub ibérico de gas proporcionará transparencia al atraer más agentes y mejorar la competencia, incrementando su eficiencia, dado que en el mercado OTC actual no se revela precio alguno de gas. ABSTRACT The Iberian Power Futures Market, managed by OMIP (“Operador do Mercado Ibérico de Energia, Pólo Português”, located in Lisbon), also known as the Iberian Energy Derivatives Market, started operations on 3 July 2006. The market efficiency, regarding how well the future price predicts the spot price, is analysed for this energy derivatives exchange. There are two trading modes coexisting within OMIP: the continuous market (default mode) and the call auction. In the continuous trading, anonymous buy and sell orders interact immediately and individually with opposite side orders, generating trades with an undetermined number of prices for each contract. In the call auction trading, a single price auction maximizes the traded volume, being all trades settled at the same price (equilibrium price). Additionally, OMIP trading members may settle Over-the-Counter (OTC) trades through OMIP clearing house (OMIClear). The five largest Spanish distribution companies have been obliged to purchase in auctions managed by OMIP until July 2009, in order to partly cover their portfolios of end users’ regulated supplies. Likewise, the Portuguese last resort supplier kept that obligation until July 2010. The auction equilibrium prices are not optimal for remuneration purposes of regulated supplies as such prices seem to be slightly upward biased. The ex-post forward risk premium, defined as the difference between the forward and spot prices in the delivery period, is used to measure its price efficiency. The spot market, managed by OMIE (Market Operator of the Iberian Energy Market, Spanish Pool, known traditionally as “OMEL”), is located in Madrid. During the first two years of the futures market, the average forward risk premium tends to be positive, as it occurs with other European power and natural gas markets. In that period, the ex-post forward risk premium tends to be negative in oil and coal markets. Energy markets tend to show limited levels of market efficiency. The price efficiency of the Iberian Power Futures Market improves with the market development of all the coexistent forward contracting mechanisms within the Iberian Electricity Market (known as “MIBEL”) – namely, the dominant OTC market, the Virtual Power Plant Auctions known in Spain as Energy Primary Emissions, and the auctions catering for part of the last resort supplies known in Spain as CESUR auctions – and with further integration of European Regional Electricity Markets. A regression model tracking the evolution of the traded volumes in the continuous market during its first four years is built as a function of twelve potential liquidity drivers. The only significant drivers are the traded volumes in OMIP compulsory auctions, the traded volumes in the OTC market, and the OTC cleared volumes by OMIClear. The amount of market makers, the enrolment of financial members and generation companies belonging to the integrated group of last resort suppliers, and the OTC cleared volume by OMIClear show strong correlation with the traded volumes in the continuous market. OMIP liquidity is still far from the levels reached by the most mature European markets (located in the Nordic countries (Nasdaq OMX Commodities) and Germany (EEX)). The market operator and its clearing house could develop efficient marketing actions to attract new entrants active in the spot market (e.g. energy intensive industries, suppliers, small producers, international energy companies and renewable generation companies) and financial agents as well as volumes from the opaque OTC market, and to improve the performance of existing illiquid products. An active dialogue with all the stakeholders (market participants, spot market operator, and supervisory authorities) will help to implement such actions. During its firs five and a half years, the continuous market shows steady liquidity growth. The hedging performance is measured through a net position ratio obtained from the final open interest of a month derivatives contract divided by its accumulated cleared volume. The base load futures in the Iberian energy derivatives exchange show the lowest ratios due to good liquidity. The peak futures show bigger ratios as their reduced liquidity is produced by auctions fixed by Portuguese regulation. The base load swaps settled in the clearing house located in Spain – MEFF Power, operating since 21 March 2011, with a new denomination (BME Clearing) since 9 September 2013 – show initially large values due to low registered volumes, as this clearing house is mainly used for short maturity (daily and weekly swaps). The net position ratio can be a powerful oversight tool for energy regulators when accessing to all the derivatives transactions as envisaged by European regulation on Energy Market Integrity and Transparency (“REMIT”), in force since 28 December 2011. The ex-post forward risk premium tends to be positive in all existing mechanisms (OMIP futures, OTC market and CESUR auctions) and diminishes due to the learning curve and the effect – since year 2011 – of the fixed price retributing the indigenous coal fired generation. Comparison with the forward generation costs from natural gas (“clean spark spread”) – obtained as the difference between the power futures price and the forward generation cost with a gas fired combined cycle plant taking into account the CO2 emission rates – is also performed. The power futures are strongly correlated with European gas prices. The clean spark spreads built with prompt contracts tend to be positive. The biggest clean spark spreads are for the month contract, followed by the quarter contract and then by the year contract. Therefore, gas fired generation companies can maximize profits trading with contracts of shorter maturity. Market monitoring reports by the market operator providing post-trade transparency, OTC data access by the energy regulator, and assessment of the regulatory risk can contribute to efficiency gains. The same recommendations are also valid for a potential Iberian gas futures market, once an Iberian gas hub – currently in a design phase, with monthly meetings amongst the stakeholders in a Working Group led by the Spanish energy regulatory authority since January 2013 – is operating. The Iberian gas hub would bring transparency attracting more shippers and improving competition and thus its efficiency, as no gas price is currently disclosed in the existing OTC market.

Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the Idd5 diabetes susceptibility region

Defects in lymphocyte apoptosis may lead to autoimmune disorders and contribute to the pathogenesis of type 1 diabetes. Lymphocytes of nonobese diabetic (NOD) mice, an animal model of autoimmune diabetes, have been found resistant to various apoptosis signals, including the alkylating drug cyclophosphamide. Using an F2 intercross between the apoptosis-resistant NOD mouse and the apoptosis-susceptible C57BL/6 mouse, we define a major locus controlling the apoptosis-resistance phenotype and demonstrate its linkage (logarithm of odds score = 3.9) to a group of medial markers on chromosome 1. The newly defined gene cannot be dissociated from Ctla4 and Cd28 and in fact marks a 20-centimorgan region encompassing Idd5, a previously postulated diabetes susceptibility locus. Interestingly, we find that the CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) and the CD28 costimulatory molecules are defectively expressed in NOD mice, suggesting that one or both of these molecules may be involved in the control of apoptosis resistance and, in turn, in diabetes susceptibility.

Structural origins of the exonuclease resistance of a zwitterionic RNA

Nuclease resistance and RNA affinity are key criteria in the search for optimal antisense nucleic acid modifications, but the origins of the various levels of resistance to nuclease degradation conferred by chemical modification of DNA and RNA are currently not understood. The 2′-O-aminopropyl (AP)-RNA modification displays the highest nuclease resistance among all phosphodiester-based analogues and its RNA binding affinity surpasses that of phosphorothioate DNA by 1°C per modified residue. We found that oligodeoxynucleotides containing AP-RNA residues at their 3′ ends competitively inhibit the degradation of single-stranded DNA by the Escherichia coli Klenow fragment (KF) 3′-5′ exonuclease and snake venom phosphodiesterase. To shed light on the origins of nuclease resistance brought about by the AP modification, we determined the crystal structure of an A-form DNA duplex with AP-RNA modifications at 1.6-Å resolution. In addition, the crystal structures of complexes between short DNA fragments carrying AP-RNA modifications and wild-type KF were determined at resolutions between 2.2 and 3.0 Å and compared with the structure of the complex between oligo(dT) and the D355A/E357A KF mutant. The structural models suggest that interference of the positively charged 2′-O-substituent with the metal ion binding site B of the exonuclease allows AP-RNA to effectively slow down degradation.