Connecticut Poison Control Center . 2004 and 2005 Bi-Annual Report on Poisoning in Connecticut

For the past 49 years, the Connecticut Poison Control Center (CTPCC) based at the University of Connecticut Health Center (UCHC), has managed human exposures and poisonings throughout the state and continues to serve as a toxicologic center of excellence. A human exposure may be defined as contact by skin, eye, mouth or inhalation to any substance: animal, mineral or vegetable, including: bites, commercial products, chemicals, drugs, natural remedies and plants among others. A poisoning is any injury to the body resulting from an exposure. Toxicology is the scientific study of the adverse effects of any substance on the body.

Impact of elevated pCO2 on paralytic shellfish poisoning toxin content and composition in Alexandrium tamarense

Ocean acidification is considered a major threat to marine ecosystems and may particularly affect primary producers. Here we investigated the impact of elevated pCO2 on paralytic shellfish poisoning toxin (PST) content and composition in two strains of Alexandrium tamarense, Alex5 and Alex2. Experiments were carried out as dilute batch to keep carbonate chemistry unaltered over time. We observed only minor changes with respect to growth and elemental composition in response to elevated pCO2. For both strains, the cellular PST content, and in particular the associated cellular toxicity, was lower in the high CO2 treatments. In addition, Alex5 showed a shift in its PST composition from a nonsulfated analogue towards less toxic sulfated analogues with increasing pCO2. Transcriptomic analyses suggest that the ability of A. tamarense to maintain cellular homeostasis is predominantly regulated on the post-translational level rather than on the transcriptomic level. Furthermore, genes associated to secondary metabolite and amino acid metabolism in Alex5 were down-regulated in the high CO2 treatment, which may explain the lower PST content. Elevated pCO2 also induced up-regulation of a putative sulfotransferase sxtN homologue and a substantial down-regulation of several sulfatases. Such changes in sulfur metabolism may explain the shift in PST composition towards more sulfated analogues. All in all, our results indicate that elevated pCO2 will have minor consequences for growth and elemental composition, but may potentially reduce the cellular toxicity of A. tamarense.

Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

Marine phytoplankton has developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 µmol /l in the presence of seawater Ca2+ concentrations of 10 mmol/1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, phytoplankton taxonomic groups appear to have evolved different strategies, which may affect their ability to cope with changes in seawater Ca2+ concentrations in their environment on geological time scales. For example, the Cretaceous (145 to 66 Ma ago), an era known for the high abundance of coccolithophores and the production of enormous calcium carbonate deposits, exhibited seawater calcium concentrations up to four times present-day levels. We show that calcifying coccolithophore species (Emiliania huxleyi, Gephyrocapsa oceanica and Coccolithus braarudii) are able to maintain their relative fitness (in terms of growth rate and photosynthesis) at simulated Cretaceous seawater calcium concentrations, whereas these rates are severely reduced under these conditions in some non-calcareous phytoplankton species (Chaetoceros sp., Ceratoneis closterium and Heterosigma akashiwo). Most notably, this also applies to a non-calcifying strain of E. huxleyi which displays a calcium-sensitivity similar to the non-calcareous species. We hypothesize that the process of calcification in coccolithophores provides an efficient mechanism to alleviate cellular calcium poisoning and thereby offered a potential key evolutionary advantage, responsible for the proliferation of coccolithophores during times of high seawater calcium concentrations. The exact function of calcification and the reason behind the highly-ornate physical structures of coccoliths remain elusive.

Remarks on Compositionality (with reference to Gennadij Zeldoviè's article “On Russian Dative Reflexive Constructions: Accidental or Compositional”)

Zeldovič’s article “On Russian Dative Reflexive Constructions: Accidental or Compositional” is very interesting. It contains a good deal of insightful observations and is painstakingly argued. Its research object is the Russian dative reflexive construction (DRC) like Ивану не работается ‘Ivan does not feel like reading’. The aim of the article is to show that the DRC is fully compositional. Like many other works by Zeldovič, the article is written from the radical-pragmatic perspective and constitutes a very good illustration of this trend in linguistic research. The language material that it analyzes has often been investigated within more traditional frameworks, especially in Russian linguistics, which makes Zeldovič’s novel approach to the old problem particularly interesting. In this short note I would like (by way of discussion) to address two problems connected not so much with the DRC itself as with methodological issues concerning compositionality. I will dwell on two aspects: on the question of how we understand the very concept of compositionality, and what instruments we employ to demonstrate it.

Mejora de la seguridad de las presas de escollera frente a percolación accidental mediante protecciones tipo repié

Esta tesis doctoral es el fruto de un trabajo de investigación cuyo objetivo principal es definir criterios de diseño de protecciones en forma de repié en presas de materiales sueltos cuyo espaldón de aguas abajo esté formado por escollera. La protección propuesta consiste en un relleno de material granular situado sobre el pie de aguas abajo de la presa y formado a su vez por una escollera con características diferenciadas respecto de la escollera que integra el espaldón de la presa. La función de esta protección es evitar que se produzcan deslizamientos en masa cuando una cantidad de agua anormalmente elevada circula accidentalmente por el espaldón de aguas abajo de la presa por distintos motivos como pueden ser el vertido por coronación de la presa o la pérdida de estanqueidad del elemento impermeable o del cimiento. Según los datos de la International Commission on Large Dams (ICOLD 1995) el 70% de las causas de rotura o avería grave en presas de materiales sueltos en el mundo están dentro de las que se han indicado con anterioridad. Esta circulación accidental de agua a través del espaldón de escollera, típicamente turbulenta, se ha denominado en esta tesis percolación (“through flow”, en inglés) para diferenciarla del término filtración, habitualmente utilizada para el flujo laminar a través de un material fino. El fenómeno físico que origina la rotura de presas de materiales sueltos sometidas a percolación accidental es complejo, entrando en juego diversidad de parámetros, muchas veces no deterministas, y con acoplamiento entre procesos, tanto de filtración como de arrastre y deslizamiento. En esta tesis se han realizado diferentes estudios experimentales y numéricos con objeto de analizar el efecto sobre el nivel de protección frente al deslizamiento en masa que producen los principales parámetros geométricos que definen el repié: la anchura de la berma, el talud exterior y su altura máxima desde la base. También se han realizado estudios sobre factores con gran influencia en el fenómeno de la percolación como son la anisotropía del material y el incremento de los caudales unitarios en el pie de presa debidos a la forma de la cerrada. A partir de los resultados obtenidos en las distintas campañas de modelación física y numérica se han obtenido conclusiones respecto a la efectividad de este tipo de protección para evitar parcial o totalmente los daños provocados por percolación accidental en presas de escollera. El resultado final de la tesis es un procedimiento de diseño para este tipo de protecciones. Con objeto de completar los criterios de dimensionamiento, teniendo en cuenta los mecanismos de rotura por erosión interna y arrastre, se han incluido dentro del procedimiento recomendaciones adicionales basadas en investigaciones existentes en la bibliografía técnica. Finalmente, se han sugerido posibles líneas de investigación futuras para ampliar el conocimiento de fenómenos complejos que influyen en el comportamiento de este tipo de protección como son el efecto de escala, la anisotropía de la escollera, las leyes de resistencia que rigen la filtración turbulenta a través de medios granulares, los efectos de cimentaciones poco competentes o la propia caracterización de las propiedades de la escollera de presas. This thesis is the result of a research project that had the main objective of defining criteria to design rockfill toe protections for dams with a highly‐permeable downstream shoulder. The proposed protection consists of a rockfill toe berm situated downstream from the dam with specific characteristics with respect to the rockfill that integrates the shoulder of the main dam. The function of these protections is to prevent mass slides due to an abnormally high water flow circulation through the dam shoulder. This accidental seepage flow may be caused by such reasons as overtopping or the loss of sealing at the impervious element of the dam or its foundation. According to data from the International Commission on Large Dams (ICOLD 1995), 70% of the causes of failure or serious damage in embankment dams in the world are within that described previously. This accidental seepage of water through the rockfill shoulder, typically turbulent, is usually called through‐flow. The physical phenomenon which causes the breakage of the rockfill shoulder during such through‐flow processes is complex, involving diversity of parameters (often not deterministic) and coupling among processes, not only seepage but also internal erosion, drag or mass slide. In this thesis, numerical and experimental research is conducted in order to analyze the effects of the main parameters that define the toe protection, i.e. the toe crest length, its slope and maximum height. Additional studies on significant factors which influence the seepage, such as the anisotropy of the material and the increase of the unit flows at the dam toe due to the valley shape are also performed. In addition, conclusions regarding the effectiveness of this type of protection are obtained based on the results of physical and numerical models. The main result of the thesis is a design procedure for this type of protection to avoid mass sliding. In order to complete the design criteria, additional recommendations about internal and external erosion based on the state of the art are included. Finally, new lines of research are suggested for the future to expand the level of knowledge of the complex phenomena that influence the behavior of this type of protection, such as the effects of scale, rockfill anisotropy, non‐linear seepage laws in turbulent seepage through granular media, effects of erodible foundations, or new procedures to characterize the properties of dam rockfill as a construction material.

Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections

This work was supported by the European Research Council (http://erc.europa.eu/: STRIFE Advanced Grant ERC-2009-AdG-249793). A.J.P.B. was also supported by the UK Biotechnology and Biological Research Council (www.bbsrc.ac.uk: Research Grants BB/F00513X/1, BB/K017365/1), the UK Medical Research Council (www.mrc.ac.uk: Programme Grant MR/M026663/1; Centre Grant MR/ N006364/1), and the Wellcome Trust (www.wellcome.ac.uk: Strategic Award 097377)

A terbenzimidazole that preferentially binds and conformationally alters structurally distinct DNA duplex domains: A potential mechanism for topoisomerase I poisoning

The terbenzimidazoles are a class of synthetic ligands that poison the human topoisomerase I (TOP1) enzyme and promote cancer cell death. It has been proposed that drugs of this class act as TOP1 poisons by binding to the minor groove of the DNA substrate of TOP1 and altering its structure in a manner that results in enzyme-mediated DNA cleavage. To test this hypothesis, we characterize and compare the binding properties of a 5-phenylterbenzimidazole derivative (5PTB) to the d(GA4T4C)2 and d(GT4A4C)2 duplexes. The d(GA4T4C)2 duplex contains an uninterrupted 8-bp A⋅T domain, which, on the basis of x-ray crystallographic data, should induce a highly hydrated “A-tract” conformation. This duplex also exhibits anomalously slow migration in a polyacrylamide gel, a feature characteristic of a noncanonical global conformational state frequently described as “bent.” By contrast, the d(GT4A4C)2 duplex contains two 4-bp A⋅T tracts separated by a TpA dinucleotide step, which should induce a less hydrated “B-like” conformation. This duplex also migrates normally in a polyacrylamide gel, a feature further characteristic of a global, canonical B-form duplex. Our data reveal that, at 20°C, 5PTB exhibits an ≈2.3 kcal/mol greater affinity for the d(GA4T4C)2 duplex than for the d(GT4A4C)2 duplex. Significantly, we find this sequence/conformational binding specificity of 5PTB to be entropic in origin, an observation consistent with a greater degree of drug binding-induced dehydration of the more solvated d(GA4T4C)2 duplex. By contrast with the differential duplex affinity exhibited by 5PTB, netropsin and 4′,6-diamidino-2-phenylindole (DAPI), two AT-specific minor groove binding ligands that are inactive as human TOP1 poisons, bind to both duplexes with similar affinities. The electrophoretic behaviors of the ligand-free and ligand-bound duplexes are consistent with 5PTB-induced bending and/or unwinding of both duplexes, which, for the d(GA4T4C)2 duplex, is synergistic with the endogenous sequence-directed electrophoretic properties of the ligand-free duplex state. By contrast, the binding to either duplex of netropsin or DAPI induces little or no change in the electrophoretic mobilities of the duplexes. Our results demonstrate that the TOP1 poison 5PTB binds differentially to and alters the structures of the two duplexes, in contrast to netropsin and DAPI, which bind with similar affinities to the two duplexes and do not significantly alter their structures. These results are consistent with a mechanism for TOP1 poisoning in which drugs such as 5PTB differentially target conformationally distinct DNA sites and induce structural changes that promote enzyme-mediated DNA cleavage.

Juan Antonio Fernández (1752-1814), el epigrafista accidental

En 1789, a instancias del prior Antonio Tavira, Juan Antonio Fernández se trasladó a Uclés (Cuenca) para llevar a cabo la ordenación y clasificación del archivo de la Orden de Santiago. Allí supo de la existencia de las ruinas romanas de Cabeza del Griego (Segobriga) y llevó a cabo con Tavira las primeras excavaciones. Durante ese tiempo, descubrieron un buen número de inscripciones romanas y Juan Antonio Fernández llevó a cabo la primera recopilación de las inscripciones de Segobriga. Después de su muerte en 1814, muchos de los documentos fueron comprados por la Real Academia de la Historia.