4-Amino-1,2,4-triazole-3-thione as a Promising Scaffold for the Inhibition of Serine and Metallo-\u3b2-Lactamases

The emergence of bacteria that co-express serine- and metallo- carbapenemases is a threat to the efficacy of the available \u3b2-lactam antibiotic armamentarium. The 4-amino-1,2,4-triazole-3-thione scaffold has been selected as the starting chemical moiety in the design of a small library of \u3b2-Lactamase inhibitors (BLIs) with extended activity profiles. The synthesised compounds have been validated in vitro against class A serine \u3b2 12Lactamase (SBLs) KPC-2 and class B1 metallo \u3b2 12Lactamases (MBLs) VIM-1 and IMP-1. Of the synthesised derivatives, four compounds showed cross-class micromolar inhibition potency and therefore underwent in silico analyses to elucidate their binding mode within the catalytic pockets of serine- and metallo-BLs. Moreover, several members of the synthesised library have been evaluated, in combination with meropenem (MEM), against clinical strains that overexpress BLs for their ability to synergise carbapenems

Employment Expectations and Gross Flows by Type of Work Contract

There is growing interest in understanding firms’ temporary and permanent employment practices and how institutional changes shape them. Using data on Spanish establishments, we examine: (a) how employers adjust temporary and permanent job and worker flows to prior employment expectations, and (b) how the 1994 and 1997 labour reforms promoting permanent employment affected establishments’ employment practices. Generally, establishments’ prior employment expectations are realized through changes in all job and worker flows. However, establishments uniquely rely on temporary hires as a buffer to confront diminishing long-run employment expectations. None of the reforms significantly affected establishments’ net temporary or permanent employment flows.http://deepblue.lib.umich.edu/bitstream/2027.42/40032/3/wp646.pd

Procesos y riesgos volcánicos

Magmas are generated in four well-defined geodynamic settings: a) constructive plate margins, including mid-ocean ridges and back-ac basins; b) destructive plate margins, such as island arcs and active continental margins; c) oceanic intraplate areas, and d) continental intraplate areas. <br>In mid-ocean ridges, intraoceanic island-arcs and oceanic islands, magmas can only be generated at the upper mantle due to the absence of continental crust. On the contrary, the crust can play an important role in continental settings. Additionally, the generation of magma in the upper mantle can be located in the asthenosphere and the lithosphere. <br>The mechanisms of magma generation in each geodynamic setting is different. In constructive plate margins, the asthenosphere rises adiabatically and melts. In destructive margins, melting is linked to subduction. Finally, in continental intraplate areas melting is associated to extensional processes, which can be linked to various phenomena such as indentation, delamination or mantle plumes, as in the case of oceanic intraplate settings. <br>The eruptive mode depends strongly on the magma composition, and more precisely of its temperature, viscosity and gas content. In general, basaltic magmas (characterised by SiO2 abundances between 45 to 52%, temperatures of 1.000-1.200 &#194;&#176;C, viscosities of 10-102 Pa&#194;&#183;s and low gas content) erupt in a quiet or moderately explosive way, producing hawaiian- or strombolian-type eruptions. On the other hand, acid magmas(with SiO2 higher than 53%, temperatures of 700-900 &#194;&#176;C, viscosities between 106 and 108 Pa&#194;&#183;s and high gas contents) are characterised by explosive, vulcanian- to plinian-type eruptions. <br>At global scale, the volcanic eruptions and their associated phenomena are less frequent and involve less victims and damage than other natural disasters. According to the recent database by Witham (2005), from the 176 considered volcanoes and volcanic areas, only a half are related to more than one incident in the 20th century. Additionally, from the 491 eruptions produced in that period, about 50% resulted in deaths. Considering the type of materials erupted, pyroclastic density currents were the main death causes, followed by lahars, which are the main cause of injuring. On the contrary, lava flows and pyroclastic falls involved a relatively low number of deaths and injuries even though pyroclastic falls were responsible of a great number of people losing their homes or being evacuated. Since the eruptions of the volcanoes associated to subduction areas are in general of greater explosivity and therefore more dangerous than intraplate volcanoes, the regions where more deaths are linked to volcanic activity in the 20th century were the Caribbean, South and Central America, and SE Asia.<br><br>Los magmas se generan en cuatro ambientes geodin&#225;micos diferentes: a) en los m&#225;rgenes de placa constructivos, en los que se incluyen las dorsales centro-oce&#225;nicas y las cuencas tras-arco; b) en los m&#225;rgenes de placa destructivos, como los arcos-isla y los m&#225;rgenes continentales activos; c) en zonas de intraplaca oce&#225;nica, y d) en zonas de intraplaca continental. <br>En las dorsales, en los arcos-isla intraoce&#225;nicos y en las islas oce&#225;nicas los magmas s&#243;lo se pueden generar en el manto superior, ya que en estas &#225;reas no existe corteza continental, pero en los m&#225;rgenes continentales activos y en las &#225;reas de intraplaca continental la corteza puede jugar un papel m&#225;s o menos importante. A su vez, las dos zonas del manto superior en las que potencialmente se pueden originar magmas son la litosfera y la astenosfera. <br>El mecanismo por el que se originan los magmas en cada uno de estos ambientes geodin&#225;micos es diferente. En los m&#225;rgenes de placa constructivos la astenosfera asciende adiab&#225;ticamente y funde. En los m&#225;rgenes destructivos la generaci&#243;n de magmas est&#225; relacionada con la subducci&#243;n. Finalmente, en &#225;reas de intraplaca continental el magmatismo est&#225; asociado a fen&#243;menos de extensi&#243;n producidos por fen&#243;menos tales como la indentaci&#243;n y la delaminaci&#243;n o bien est&#225; relacionado con plumas mant&#233;licas, como ocurre en general en &#225;reas de intraplaca oce&#225;nica. <br>El tipo de erupci&#243;n depende de la composici&#243;n del magma, y sobre todo de su temperatura, viscosidad y contenido en gases. En general, los magmas bas&#225;lticos (que tienen contenidos en SiO2 comprendidos entre 45 y 52%, temperaturas de 1.000-1.200 &#194;&#176;C, viscosidades del orden de 10-102 Pa&#194;&#183;s y baja abundancia de gases) extruyen de forma tranquila o moderadamente explosiva, dando lugar a erupciones de tipo hawaiano o estromboliano. Por el contrario, los magmas &#225;cidos (que tienen contenidos en SiO2 superiores al 63%, temperaturas de 700 a 900 &#194;&#176;C, viscosidades entre 106 y 108 Pa&#194;&#183;s y elevado contenido en gases) y los traqu&#237;tico-fonol&#237;ticos lo hacen de forma explosiva, generando erupciones de tipo vulcaniano y pliniano. <br>A escala global las erupciones volc&#225;nicas y los fen&#243;menos asociados son m&#225;s infrecuentes y generan menos v&#237;ctimas y da&#241;os que otros riesgos naturales. Seg&#250;n la informaci&#243;n recopilada en la m&#225;s reciente y completa base de datos (Witham, 2005), de los 176 volcanes/&#225;reas volc&#225;nicas que se incluyen en la misma, m&#225;s de la mitad han sido responsables de m&#225;s de un incidente en el siglo XX, y de las 491 erupciones que han tenido lugar en este per&#237;odo de tiempo del orden del 50% han producido muertes. De los diferentes materiales emitidos, las coladas y oleadas pirocl&#225;sticas fueron las principales causas de muerte, seguidas de los lahares, que a su vez fueron la principal causa de heridos. Por el contrario, las lavas y los piroclastos de ca&#237;da generaron un n&#250;mero relativamente peque&#241;o de muertes y heridos, si bien los piroclastos de ca&#237;da fueron responsables del mayor n&#250;mero de personas que perdieron su casa y que tuvieron que ser evacuadas. Por otra parte, como las erupciones de los volcanes asociados a zonas de subducci&#243;n son, en general, m&#225;s explosivas y por ende m&#225;s peligrosas que las de los volcanes de &#225;reas de intraplaca, las regiones en las que m&#225;s muertes se produjeron en el siglo XX fueron el Caribe, Sudam&#233;rica, Am&#233;rica Central y el Sudeste asi&#225;tico

Modelizaci&#243;n geoqu&#237;mica de los procesos de diferenciaci&#243;n por cristalizaci&#243;n

During crystallization processes, major and trace elements and stable isotopes fractionate, whereas radiogenic isotopes do not change. The different equations proposed allow us to reproduce the variation in major and trace elements during these differentiation processes. In the case of simple fractional crystallization, the residual liquid is impoverished in compatible elements faster than it is enriched in incompatible elements as crystallization proceeds. During in situ crystallization the highly incompatible elements evolve in a similar way to the case of simple fractional crystallization but the enrichment rate of the moderately incompatible elements is slower and the compatible element; do not suffer a depletion as strong as the one observed during simple fractional crystallization, even for higher <i>f</i> values. In a periodically replenished magma chamber if all the liquid present is removed at the end of each cycle, the magma follows patterns similar to those generated by simple fractional crystallization. On the contrary, if the liquid fraction that crystallizes during each cycle and the one that is extruded at the end of the cycle are small, the residual liquid shows compositions similar to those that would be obtained by equilibrium crystallization. Crystallization processes modelling is in general less difficult than (or partial melting. If a rock series is the result of simple fractional crystallization, a el Cⁱ_L - C^j_L plot in which <i>i</i> is a compatible element and <i>j</i> is highly incompatible, allows us to obtain a good approximation to the initial liquid composition. Additionally, log Cⁱ_L -log C^j_L diagrams in which <i>i</i> is a highly incompatible element, allow us to identify steps in the process and to calculate the bulk distribution coefficients of the trace elements during each step.<br><br>Durante los procesos de diferenciaci&#243;n por cristalizaci&#243;n los elementos mayores y traza y los is&#243;topos estables sufren fraccionaci&#243;n, mientras que los is&#243;topos radiog&#233;nicos no var&#237;an. Las ecuaciones propuestas parlO_ los diferentes procesos de diferenciaci&#243;n permiten establecer las pautas de variaci&#243;n de los elementos mayores y traza durante cada uno de estos procesos. En la cristalizaci&#243;n fraccionada simple el l&#237;quido residual se empobrece r&#225;pidamente en elementos compatibles y se enriquece en elementos incompatibles, a medida que progresa la cristalizaci&#243;n. En la cristalizaci&#243;n in situ el l&#237;quido evoluciona de forma id&#233;ntica a la cristalizaci&#243;n fraccionada simple por lo que respecta a los elementos altamente incompatibles, pero experimenta un menor incremento en lo que concierne a los elementos moderadamente incompatibles; en cuanto a los elementos compatibles, los l&#237;quidos residuales tambi&#233;n se empobrecen, aunque mucho m&#225;s suavemente que en los derivados por cristalizaci&#243;n fraccionada simple, incluso para valores de <i>f</i> altos. Si tiene lugar el rellenado c&#237;clico de la c&#225;mara y todo el l&#237;quido presente en la misma desaparece al final de cada ciclo, el magma sigue las mismas pautas que en la cristalizaci&#243;n fraccionada simple. Por el contrario, si la fracci&#243;n de l&#237;quido que cristaliza en cada ciclo y la del l&#237;quido eruptado al final de cada ciclo son peque&#241;as, la composici&#243;n del l&#237;quido residual se aproxima a la que se obtiene por cristalizaci&#243;n en equilibrio. La modelizaci&#243;n de los proceses de cristalizaci&#243;n plantea menos dificultades que la de la fusi&#243;n parcial. Si una serie de rocas se ha generado por cristalizaci&#243;n fraccionada simple, su proyecci&#243;n en diagramas el Cⁱ_L - C^j_L si <i>i</i> es un elemento compatible y <i>j</i> un elemento altamente incompatible, permite una buena aproximaci&#243;n a la composici&#243;n del magma inicial. Asimismo la proyecci&#243;n en diagramas log Cⁱ_L -log C^j_L, en la que el elemento <i>i</i> es altamente incompatible, permite identificar las distintas etapas del proceso y calcular los coeficientes de distribuci&#243;n global de los elementos traza del sistema