Tips and tricks about financial ratios: how to anticipate unpleasant surprises

Following recent accounting and ethical scandals within the Telecom Industry like Gowex case, old cards are laid on the table: what kind of management and control are we doing on our businesses and what use do we give to the specific tools we have at our disposition? There are indicators, that on a very specific, concise and accurate manner, aside from brief, allow us to analyze and capture the complexity of a business and also they constitute an important support when making optimal decisions. These instruments or indicators show, a priori, all relevant data from a purely economic perspective, while there also exist, the possibility of including factors that are not of this nature strictly. For instance, there are indicators that take into account the customer?s satisfaction, the corporate reputation among others. Both kind of performance indicators form, together, an integral dashboard while the pure economic side of it could be considered as a basic dashboard. Based on DuPont?s methodology, we will be able to calculate the ROI (Return on Investment) of a company from the disaggregation of very useful and much needed indicators like the ROE (Return on Equity) or the ROA (Return on Assets); thereby, we will be able to get to know, to control and, hence, to optimize the company?s leverage level, its liquidity ratio or its solvency ratio, among others; as well as the yield we will be able to obtain if our decisions and management are optimal related to the bodies of assets. Bear in mind and make the most of the abovementioned management tools and indicators that we have at our disposition, allow us to act knowing our path and taking full responsibility, as well as, to obtain the maximum planned benefits, instead of leaving them to be casual. We will be able to avoid errors that can lead the company to an unfortunate and non-desirable situation and, of course, we will detect, way in advance, the actual needs of the business in terms of accounting and financial sanitation before irreversible situations are reached.

Desarrollos metodológicos y aplicaciones hacia el cálculo de la peligrosidad sísmica en el ecuador continental y estudio de riesgo sísmico en la ciudad de Quito

En el presente trabajo de tesis se desarrolla, en primer lugar, un estudio de peligrosidad sísmica en Ecuador continental, siguiendo una metodología probabilista zonificada. El estudio se plantea a escala regional y presenta como principales aportaciones: 1) la elaboración de un Estado del Arte sobre Tectónica y Geología de Ecuador, concluyendo con la identificación de las principales fuentes sísmicas; 2) La confección de un Catálogo Sísmico de proyecto, recopilando información de distintas agencias, que ha sido homogeneizado a magnitud momento, Mw, depurado de réplicas y premonitores y corregido por la falta de completitud para la estimación de tasas en diferentes rangos de magnitud; 3) la propuesta de un nueva zonificación sísmica, definiendo las zonas sismogenéticas en tres regímenes tectónicos: cortical, subducción interfase y subducción in-slab; 4) la caracterización sísmica de cada zona estimando los parámetros de recurrencia y Magnitud Máxima (Mmax), considerando para este último parámetro una distribución de valores posibles en función de la sismicidad y tectónica, tras un exhaustivo análisis de los datos existentes; 5) la generación de mapas de peligrosidad sísmica de Ecuador continental en términos de aceleración pico (PGA) y espectral SA (T= 1s) , en ambos casos para periodos de retorno (PR) de 475, 975 y 2475 años; 6) La estimación de espectros de peligrosidad uniforme (UHS) y sismos de control mediante desagregación de la peligrosidad, para PR de 475 y 2475 años en 4 capitales de provincia: Quito, Esmeraldas, Guayaquil y Loja. Una segunda parte del trabajo se destina al cálculo del riesgo sísmico en el Barrio Mariscal Sucre de Quito, lo que supone incidir ya a una escala municipal. Como principales contribuciones de este trabajo se destacan: 1) definición del escenario sísmico que más contribuye a la peligrosidad en Quito, que actuará como input de cálculo del riesgo; 2) caracterización de la acción sísmica asociada a ese escenario, incluyendo resultados de microzonación y efecto local en la zona de estudio; 3) Elaboración de una Base de Datos partiendo de información catastral e identificación de las tipologías dominantes; 4) Asignación de clases de vulnerabilidad y obtención de porcentajes de daño esperado en cada clase ante la acción sísmica definida previamente, con la consiguiente representación de mapas de vulnerabilidad y daño; 5) mapas de indicadores globales del riesgo sísmico; 6) Base de datos georreferenciada con toda la información generada en el estudio. Cabe destacar que el trabajo, aunque no formula nuevos métodos, si plantea una metodología integral de cálculo del riesgo sísmico, incorporando avances en cada fase abordada, desde la estimación de la peligrosidad o la definición de escenarios sísmicos con carácter hibrido (probabilista-determinista), hasta la asignación de vulnerabilidades y estimación de escenarios de daño. Esta tesis trata de presentar contribuciones hacia el mejor conocimiento de la peligrosidad sísmica en Ecuador y el riesgo sísmico en Quito, siendo uno de los primeros estudios de tesis que se desarrolla sobre estos temas en el país. El trabajo puede servir de ejemplo y punto de partida para estudios futuros; además de ser replicable en otras ciudades y municipios de Ecuador. -------------------- ABSTRACT: ------------------ This thesis first develops a study of seismic hazard in mainland Ecuador, following a zoned, probabilistic methodology. The study considers a regional scale and presents as main contributions: 1) The development of a State of Art on the Tectonics and Geology of Ecuador, concluding with the identification of the main seismic sources; 2) The creation of a Seismic Catalog project, collecting information from different agencies, which has been homogenized to Moment magnitude, Mw, purged from aftershocks and premonitories and corrected for the lack of completeness to estimate rates in different maggnitude ranges; 3) The proposal of a new seismic zoning, defining the seismogenic zones in three tectonic regimes: cortical, subduction interface and subduction in-slab; 4) The seismic characterization of each zone, estimating the parameters of recurrence and Maximum Magnitude (Mmax), considering the latter as a distribution of possible values, depending on the seismicity and tectonics, and after a thorough analysis of the existing data; 5) Seismic hazard maps of continental Ecuador in terms of peak ground acceleration (PGA) and spectral SA(T=1), and return periods (PR) of 475, 975 and 2475 years; 6) Uniform hazard spectra (UHS) and control earthquakes obtained by hazard disaggregation, for PR 475 and 2475 years in four provincial capitals: Quito, Esmeraldas, Guayaquil and Loja. The second section focuses on the calculation of seismic risk in the Quito Mariscal Sucre parish, which is already supposed to be influencing at a municipal level. The main contributions here are the: 1) Definition of the seismic scenario that contributes most to the hazard in Quito, which acts as an input in the risk calculation; 2) Characterization of the seismic action associated with that scenario, including results of micro-zoning and local effect in the study area; 3) Development of a database, based on cadastral data and identification of key typologies; 4) Allocation of vulnerability classes and obtaining percentages of damage expected in each class faced with the seismic action previously defined, with the consequent representation of maps of vulnerability and damage; 5) Global maps of seismic risk indicators; 6) Geo-referenced database with all the information generated in the study. It should be noted that although new methods are not prescribed, this study does set a comprehensive methodology for the calculation of seismic risk, incorporating advances in each phase approached, from the hazard estimation, or definition of seismic scenarios applying a hybrid (deterministic-probabilistic) method, to the allocation of vulnerabilities and estimation of damage scenarios. This thesis aims to present contributions leading to a better understanding of seismic hazard in Ecuador and seismic risk in Quito, and is one of the first studies in the country to develop such themes. This study can serve as an example and starting point for future studies, which could replicate this methodology in other cities and municipalities.

Historia de la protección del patrimonio arquitectónico en España. 1933-1985

El trabajo de investigación que presentamos tiene como principal objetivo, la recopilación, el registro, el análisis y la reflexión sobre una época, tan trascendental como poco estudiada desde el ámbito arquitectónico, como es el período comprendido entre las dos normas de mayor relevancia en relación a la protección del Patrimonio Histórico Español del último siglo. Nos referimos a la Ley sobre Defensa, Conservación y Acrecentamiento del Patrimonio Histórico Nacional de 13 de mayo de 1933 y la Ley 13/1985, de 25 de junio, del Patrimonio Histórico Español. A través de la investigación realizada, se pretende aportar una visión integral de esta etapa, desde el enfoque arquitectónico, fundamentando la misma en el desarrollo de pautas metodológicas, abordadas desde la recopilación exhaustiva del material bibliográfico y documental para su posterior análisis. A partir de esta fase inicial, se han identificado los nexos comunes entre los estudios existentes sobre el patrimonio monumental español previos a la Guerra Civil y las investigaciones dedicadas a la historia de las últimas décadas del siglo XX. De esta forma, se ha procurado trazar un “puente” documental, con el que trasponer virtualmente el vacío bibliográfico existente. Históricamente, la protección del patrimonio histórico edificado y urbano, ha preocupado y ocupado a multitud de profesionales que, desde disciplinas dispares, han emprendido la tarea ímproba de comprender y explicar cuáles han sido los avatares, históricos y legales, que han marcado su evolución. Tal preocupación ha generado una bibliografía ingente y diversa, desde la protección formal y precisa, sobre uno u otro material, pasando por el marco historiográfico de las tendencias conservacionistas y las teorías decimonónicas, las filigranas formadas por las cuantiosas normas promulgadas desde la Novísima Recopilación, hasta la incidencia del planeamiento urbano en la tutela del patrimonio, incluidas la trama de competencias y yuxtaposiciones administrativas. Documentos de toda índole y profundidad científica, que como mosaicos hispanomusulmanes, dibujan el panorama patrimonial en el que la criba de material resulta una tarea, en ocasiones, inextricable. El título de este documento, en sí mismo, circunscribe la materia que ha sido el objeto de análisis durante el proceso de investigación, el Patrimonio Arquitectónico Monumental. El eje o núcleo basal de estudio se sitúa en los bienes inmuebles, los edificados, que, a su vez, ostentan la declaración de Bien de Interés Cultural, y que, por ende, pertenecen al Patrimonio Histórico Español. La metodología de trabajo se ha desarrollado de forma concéntrica, desde aspectos generales de la protección del patrimonio monumental, como el marco legal que antecede a la promulgación de la Ley de 1933, y el estado previo de los bienes susceptibles de ser preservados. Reconocemos en el ámbito legislativo, el fundamento orgánico que regula y dirige la tutela del patrimonio histórico español y la acción conservadora, y que delimita el ámbito a partir del cual se condiciona el devenir de los bienes culturales. Del esquema de situación surgido del análisis previo, se han detectado los factores claves en la transición hacia la Ley de Patrimonio Histórico Español; la evolución conceptual del “Patrimonio”, como apreciación genérica, y el testimonio de este progreso a través de los valores históricos, artísticos y culturales. El presente documento de investigación, consta de una primera fase, correspondiente al Capítulo 1, que se ha desarrollado a partir, principalmente, de la ordenación jurídica que rige el Patrimonio Histórico Español, a través de leyes, decretos, órdenes y disposiciones anexas, complementado con el material bibliográfico dedicado a la revisión histórica del proceso legal de la protección del patrimonio histórico-artístico. Si bien no ha sido nuestro propósito realizar un estudio pormenorizado del volumen jurídico e histórico que precede a la Ley de 1933, y que da inicio al período de estudio de la presente investigación, sí lo ha sido centrarnos en la elaboración de un extracto de aquellos elementos de la doctrina de mayor relevancia y repercusión en la protección del patrimonio histórico-artístico y/o monumental español. A lo largo de este estudio hemos comprobado lo que algunos juristas ya habían planteado, acerca de la profunda dispersión, ramificación, y diversificación de esfuerzos, tanto en la legislación específica como en la urbanística. Esta disgregación se ha extendido al ámbito de las medidas de reconocimiento caracterizado por la elaboración de múltiples catálogos e inventarios, con desigual transcendencia, alcance y utilidad. El resultado ha sido una división de esfuerzos, desdibujando el objetivo y convirtiendo la acción del reconocimiento en múltiples empresas inconexas y de escasa trascendencia. Nuestra investigación avanza en el análisis de la protección del patrimonio, como concepto globalizador, con el desarrollo del Capítulo 2, en el que se incluye una serie de mecanismos directos e indirectos que, individualmente, suelen carecer de la fuerza efectiva que muchos de los monumentos o conjuntos monumentales requieren para sobrevivir al paso del tiempo y sus circunstancias. En primer lugar, en este segundo capítulo nos hemos centrado, específicamente, en el mecanismo regulado por la Ley del Patrimonio Histórico Español, y el régimen general de protección implementado a partir de su promulgación en 1985. En especial, consideraremos la declaración de Interés Cultural como grado máximo de protección y tutela de un bien, y su posterior inscripción en el Registro General correspondiente, dependiente del Ministerio de Educación, Cultura y Deporte. Este mecanismo representa el instrumento por antonomasia que condensa las facultades de tutela del Estado sobre un bien del que se considera poseedor y aglutinador de valores “culturales” —como cohesión de los valores históricos, artísticos, sociales, etc. — representativos de la idiosincrasia española, y sobre el cual no existen dudas sobre la necesidad de garantizar su permanencia a través de su conservación. En segunda instancia, hemos analizado el Planeamiento Urbanístico, como aglutinador de valores culturales contenidos en la ciudad y como contenedor de los efectos generados por el hombre a partir de su interacción con el medio en el que habita y se relaciona. En tercer término, hemos recopilado y estudiado la concepción de los catálogos, como noción genérica de protección. Desde hace siglos, este género ha estado definido como una herramienta capaz de intervenir en la protección del patrimonio histórico, aunque de una manera difícilmente cuantificable, mediante la identificación, enumeración y descripción de una tipología concreta de monumentos o grupos de ellos, contribuyendo al reconocimiento de los valores cualitativos contenidos en éstos. El tercer capítulo analiza el mecanismo directo de tutela que ejerce la Administración en el patrimonio monumental. La declaración de monumentalidad o de Bien de Interés Cultural y su inclusión en el Registro General de Protección. La protección teórica y la protección jurídica de un monumento, analizadas hasta el momento, resultan tan necesarias como pueriles si no van seguidas de su consumación. En el caso de este tipo de patrimonio monumental, toda acción que tenga como objeto resguardar los valores implícitos en un bien mueble o inmueble, y en su materia, implica el cumplimiento de la protección. Por último, el cuarto capítulo se convierte en el punto culminante, y por ende crucial, del proceso de protección del Patrimonio Cultural, el de la consumación de la intervención. La teoría, la crítica, la normativa y hasta las doctrinas más radicales en materia de protección del patrimonio cultural, carecen de sentido si no las suceden los hechos, la acción, en antítesis a la omisión o la desidia. De ello ha dado pruebas elocuentes la propia historia en multitud de ocasiones con la destrucción, por indolencia o desconocimiento, de importantes vestigios del patrimonio arquitectónico español. Por este motivo, y para ser consecuentes con nuestra tesis hemos recuperado, concentrado y analizado la documentación de obra de tres monumentos imprescindibles del patrimonio construido (la Catedral de Burgos, el Palacio-Castillo de la Aljafería en Zaragoza y la Muralla de Lugo). En ocasiones, al examinar retrospectivamente las intervenciones en monumentos de gran envergadura, física y cultural como catedrales o murallas, algunos investigadores han tenido la sospecha o prevención de que las actuaciones no han seguido un plan de actuación premeditado, sino que han sido el resultado de impulsos o arrebatos inconexos producto de la urgencia por remediar algún tipo de deterioro. En oposición a esto, y a través del estudio de las intervenciones llevadas a cabo en los tres monumentos mencionados, hemos podido corroborar que, a excepción de intervenciones de emergencia fruto de circunstancias puntuales, existe coherencia desde el proceso de análisis de situación de un bien a la designación de prioridades, que ha regido el proceso restaurador a lo largo de dos siglos. La evolución de las intervenciones realizadas en los monumentos analizados ha estado definida, además de por su complejidad, magnitud y singularidad constructiva, por el devenir de su estructura y su uso. En conclusión, la efectividad de la protección del patrimonio cultural español, radica en la concomitancia de múltiples aspectos, entre ellos: el cumplimiento acertado de las normas vigentes, específicas y accesorias; el conocimiento del bien y de sus valores históricos, artísticos, y culturales; su catalogación o inclusión en los inventarios correspondientes; el compromiso de los agentes e instituciones de los cuales depende; la planificación de las tareas necesarias que garanticen tanto la salvaguarda estructural como la conservación de sus valores; y la incorporación de un plan de seguimiento que permita detectar eventuales peligros que atenten contra su conservación. Pero, la situación óptima estaría dada por un sistema en el que estos mecanismos —regulaciones específicas y urbanísticas, Declaraciones de Bien de Interés Cultural, Catálogos e Inventarios, etc. — funcionaran, de forma parcial o total, como una maquinaria, donde cada pieza operara con independencia relativa, pero en sintonía con los demás engranajes. Hasta el momento, la realidad dista mucho de esta situación, convirtiendo esta convivencia en una utopía. Tanto los legisladores, como las autoridades y los técnicos involucrados, deben tener presente que, de ellos, de los parámetros asignados por la legislación, de la implementación de los instrumentos estipulados por ésta y de las decisiones tomadas por cada uno de los poderes directivos de los órganos competentes, dependerá el alcance y efectividad de la protección, ya que en cada vertiente existe, en mayor o menor medida, un porcentaje de interpretación y subjetividad. ABSTRACT The research that we present has as the main objective to collect, record, analyzed and reflection on a time, that was little studied from the architectural field. It is the period between the two laws of most relevance to the protection of Spanish Historical Heritage of the last century. We refer to the Law on the Protection and Conservation of National Heritage of 1933 and Law 16/1985 of Spanish Historical Heritage. Through this research, it aims to provide a comprehensive view of the stage from the architectural approach, basing it on the development of methodological guidelines. The investigation was initiated by the bibliography and documentary for further analysis. After this initial phase, we have identified the common links between existing studies on the Spanish architectural heritage prior to the Civil War and dedicated research into the history of the late twentieth century. Thus, we have tried to draw a documental bridge, with which virtually transpose the gap that has existed. Historically, professionals from diverse disciplines have been worried and busy of the protection of the built and urban heritage. They have undertaken the daunting task of understanding and explaining the historical and legal difficulties, which have marked its evolution. This concern has generated an enormous and diverse literature, from formal and precise protection, in the framework of conservation historiographical trends and nineteenth-century theories. Also, they have studied the impact of urban planning in the protection of heritage, including the competences and administrative juxtapositions. They have generated a lot of documents of all kinds and scientific depth. The title of this document, in itself, circumscribes the matter that has been analyzed during this research process, the Monumental Architectural Heritage. The basal studio is located in the historical buildings, which, in turn, hold the declaration of cultural interest, and thus belong to the Spanish Historical Heritage. The work methodology was developed concentrically from general aspects of the protection of monuments, such as the legal framework that predates the enactment of the 1933 Act, and the previous state of the monuments that should be preserved. We recognize in the legislative sphere, the organic base that regulates and directs the tutelage of Spanish heritage and conservative action. The situation scheme emerged from the previous analysis, and we detected the key factors in the transition to the Spanish Historical Heritage Act; the conceptual evolution of the Heritage as a generic assessment, and witness this progress through historical, artistic and cultural values. This research paper consists of a first phase, corresponding to Chapter 1, which has developed from the legal regulation governing the Spanish Historical Heritage, through laws, decrees, orders and related provisions, supplemented the bibliography dedicated to the historical review of the legal process of protecting historical and artistic heritage. While it was not our intention to conduct a detailed study of the legal and historical volume preceding the 1933 Act, and that started the study period of this investigation, yes he has been focusing on the production of an extract from those elements of the doctrine with greater relevance and impact on the protection of Spanish art-historical and / or architectural heritage. Throughout our study we have seen what some jurists had already raised, about the scattering, branching and diversification of efforts, both in specific law and in urban law. This disaggregation has been extended to the field of recognition measures characterized by the development of multiple catalogs and inventories, with varying significance, scope and usefulness. The result has been a division of efforts, blurring the objective and turning the action of the recognition in multiple attempts little consequence. Our research advances in the analysis of heritage protection, as globalization concept in the Chapter 2, which includes a number of direct and indirect mechanisms that individually, often lack the effective force that many of monuments have required to survive the test of time and circumstances. First, in this second chapter we focused specifically on the mechanism regulated by the Spanish Historical Heritage Act, and the general protection regime implemented since its enactment in 1985 . In particular, we consider the declaration of cultural interest as maximum protection and protection of cultural assets, and their subsequent entry in the relevant General Register under the Ministry of Education, Culture and Sports . This mechanism is the instrument par excellence that condenses the powers of state care about a cultural asset, and which represents the cohesion of the historical, artistic, social values , etc. Secondly, we analyzed the Urban Planning, as a unifying cultural value in the city and as a container for the effects caused by man from its interaction with the environment in which he lives and relates. Thirdly, we have collected and studied the origin of catalogs, as generic notion of protection. For centuries, this genre has been defined as a tool to intervene in the protection of historical heritage, although difficult to quantify, through the identification, enumeration and description of a particular typology of monuments, and that contributing to the recognition of qualitative values contained therein. The third chapter analyzes the direct mechanism of protection performed by the Administration in the monuments with the statement of Cultural asset and inclusion in the General Protection Register. The theoretical and legal protection of a monument is as necessary as puerile if they are not followed by intervention. For this type of architectural heritage, any action which has the aim to safeguard the values implicit in the cultural asset involves protection compliance. Finally, the fourth chapter becomes the highlight, because it treated of the end process of the cultural heritage protection, the consummation of the intervention. The theory, the criticism, the rules and even the radical doctrines on the protection of cultural heritage, are meaningless if they do not take place the facts, the action, in antithesis to the omission. The history of the architectural heritage has given eloquent proof by itself. A lot of vestiges have been lost, in many times, for the destruction, through indolence or unknowledge. For this reason, and to be consistent with our thesis, we have collected and analyzed the projects documentation of three monuments (the Burgos Cathedral, the Aljafería Palace-Castle in Zaragoza and the Wall of Lugo). Sometimes, some researchers have suspected that there had not been planning. They suspect that the projects have been the result of different emergency situations. In opposition of this, we confirm that, except for emergency interventions result of specific circumstances, there have been a process of analysis to conclude in the priorities designation, which has guided the restoration process over two centuries. The complexity, magnitude and constructive uniqueness have defined the evolution of intervention. In conclusion, the effectiveness of the protection of Spanish cultural heritage lies in the conjunction of many aspects, including: the successful implementation of existing, specific and ancillary standards; the knowledge of good and its historical, artistic and cultural values; the cataloging and inclusion in the relevant inventories; and the commitment of the actors and institutions on which it depends. These planning tasks are necessary to ensure both structural safeguards as conservation values; and the introduction of a monitoring plan to detect possible dangers that threaten its conservation. But, the optimal situation would be given by a system in which these urban-regulations and specific mechanisms, would work together like a machine, where each piece operated with relative independence, but in tune with the other gears. So far, the reality is far from this situation, turning this coexistence in a utopia. Both legislators and officials and technicians involved must be aware that the effectiveness and scope of protection depends on your insight and commitment.

High pressure fosters protein refolding from aggregates at high concentrations

High hydrostatic pressures (1–2 kbar), combined with low, nondenaturing concentrations of guanidine hydrochloride (GdmHCl) foster disaggregation and refolding of denatured and aggregated human growth hormone and lysozyme, and β-lactamase inclusion bodies. One hundred percent recovery of properly folded protein can be obtained by applying pressures of 2 kbar to suspensions containing aggregates of recombinant human growth hormone (up to 8.7 mg/ml) and 0.75 M GdmHCl. Covalently crosslinked, insoluble aggregates of lysozyme could be refolded to native, functional protein at a 70% yield, independent of protein concentration up to 2 mg/ml. Inclusion bodies containing β-lactamase could be refolded at high yields of active protein, even without added GdmHCl.

Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network

A major activity of molecular chaperones is to prevent aggregation and refold misfolded proteins. However, when allowed to form, protein aggregates are refolded poorly by most chaperones. We show here that the sequential action of two Escherichia coli chaperone systems, ClpB and DnaK-DnaJ-GrpE, can efficiently solubilize excess amounts of protein aggregates and refold them into active proteins. Measurements of aggregate turbidity, Congo red, and 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid binding, and of the disaggregation/refolding kinetics by using a specific ClpB inhibitor, suggest a mechanism where (i) ClpB directly binds protein aggregates, ATP induces structural changes in ClpB, which (ii) increase hydrophobic exposure of the aggregates and (iii) allow DnaK-DnaJ-GrpE to bind and mediate dissociation and refolding of solubilized polypeptides into native proteins. This efficient mechanism, whereby chaperones can catalytically solubilize and refold a wide variety of large and stable protein aggregates, is a major addition to the molecular arsenal of the cell to cope with protein damage induced by stress or pathological states.

Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation

Protein synthesis (PS) has been considered essential to sustain mammalian life, yet was found to be virtually arrested for weeks in brain and other organs of the hibernating ground squirrel, Spermophilus tridecemlineatus. PS, in vivo, was below the limit of autoradiographic detection in brain sections and, in brain extracts, was determined to be 0.04% of the average rate from active squirrels. Further, it was reduced 3-fold in cell-free extracts from hibernating brain at 37°C, eliminating hypothermia as the only cause for protein synthesis inhibition (active, 0.47 ± 0.08 pmol/mg protein per min; hibernator, 0.16 ± 0.05 pmol/mg protein per min, P < 0.001). PS suppression involved blocks of initiation and elongation, and its onset coincided with the early transition phase into hibernation. An increased monosome peak with moderate ribosomal disaggregation in polysome profiles and the greatly increased phosphorylation of eIF2α are both consistent with an initiation block in hibernators. The elongation block was demonstrated by a 3-fold increase in ribosomal mean transit times in cell-free extracts from hibernators (active, 2.4 ± 0.7 min; hibernator, 7.1 ± 1.4 min, P < 0.001). No abnormalities of ribosomal function or mRNA levels were detected. These findings implicate suppression of PS as a component of the regulated shutdown of cellular function that permits hibernating ground squirrels to tolerate “trickle” blood flow and reduced substrate and oxygen availability. Further study of the factors that control these phenomena may lead to identification of the molecular mechanisms that regulate this state.

Biological impact on mineral dissolution: Application of the lichen model to understanding mineral weathering in the rhizosphere

Microorganisms modify rates and mechanisms of chemical and physical weathering and clay growth, thus playing fundamental roles in soil and sediment formation. Because processes in soils are inherently complex and difficult to study, we employ a model based on the lichen–mineral system to identify the fundamental interactions. Fixed carbon released by the photosynthetic symbiont stimulates growth of fungi and other microorganisms. These microorganisms directly or indirectly induce mineral disaggregation, hydration, dissolution, and secondary mineral formation. Model polysaccharides were used to investigate direct mediation of mineral surface reactions by extracellular polymers. Polysaccharides can suppress or enhance rates of chemical weathering by up to three orders of magnitude, depending on the pH, mineral surface structure and composition, and organic functional groups. Mg, Mn, Fe, Al, and Si are redistributed into clays that strongly adsorb ions. Microbes contribute to dissolution of insoluble secondary phosphates, possibly via release of organic acids. These reactions significantly impact soil fertility. Below fungi–mineral interfaces, mineral surfaces are exposed to dissolved metabolic byproducts. Through this indirect process, microorganisms can accelerate mineral dissolution, leading to enhanced porosity and permeability and colonization by microbial communities.

Preparação, caracterização e propriedades de lipossomas contendo o ácido -ciano-4-hidroxicinâmico e o agente fotossenbilizador AICIPc: um novo sistema carreador específico com ação sinérgica aplicado a terapia fotodinâmica

Ftalocianina de alumínio-cloro (AlClPc) é um fotossensibilizador de segunda geração em terapia fotodinâmica (TFD) caracterizado por seu caráter anfifílico e tendência de auto-agregação em meio aquoso, o que prejudica seu potencial de aplicação. O aCHC é um substrato de transportadores de monocarboxilato (MCT) superexpresso em células de MCF-7. Objetivando a solubilização da AlClPc e aumento de internalização em tecidos neoplásicos nos propomos aqui o uso de DSPC e DOPC em diferentes proporções para formar vesículas lipidicas mistas (LV) na presença de aCHC como sistemas veiculadores de fármaco. Lv foi preparado pelo método de injeção etanólica e formou vesículas de dimensões nanométricas (aproximadamente 100 nm) com bom índice de polidispersão, valores negativos de potencial zeta e estáveis em meio aquoso por mais de 50 dias. AlClPc se complexou com o fosfato das LV o que conferiu uma localização interfacial às moléculas de AlClPc como demonstrado pelos resultados de supressão de fluorescência. Medidas de anisotropia, fluorescência estática e resolvida no tempo corroboram com estes resultados e demonstram que a auto-agregação da AlClPc ocorre mesmo em lipossomas. Entretanto, a veiculação da AlClPc por LV em carcinoma de células escamosas oral (OSCC) levou a um processo de desagregação demonstrado por (FLIM). Este incrível comportamento é novo e aumenta o conhecimento científico sobre o mecanismo intracelular de ação de fotossensibilizadores em TFD. Em TFD, ambos os sistemas LVIII+AlClPc e LVIII+AlClPc+aCHC não apresentaram toxicidade no escuro no período de incubação de 3 h com as concentrações de lipídios, AlClPc e aCHC iguais a 0,15 mmol/L, 0,5 umol/L e 10,0 umol/L, respectivamente. De maneira inesperada, o sistema LVIII+AlClPc foi mais eficiente em TFD que o sistema LVIII+AlClPc+aCHC, devido ao caráter antioxidante do aCHC. Estes resultados abrem uma nova perspectiva do potencial uso de LV-AlClPc para o tratamento fotodinâmico.

Homogeneous Spatial Units (HSU) - a Pan-European geographical basis for environmental and socio-economic modelling

The spatial data set delineates areas with similar environmental properties regarding soil, terrain morphology, climate and affiliation to the same administrative unit (NUTS3 or comparable units in size) at a minimum pixel size of 1km2. The scope of developing this data set is to provide a link between spatial environmental information (e.g. soil properties) and statistical data (e.g. crop distribution) available at administrative level. Impact assessment of agricultural management on emissions of pollutants or radiative active gases, or analysis regarding the influence of agricultural management on the supply of ecosystem services, require the proper spatial coincidence of the driving factors. The HSU data set provides e.g. the link between the agro-economic model CAPRI and biophysical assessment of environmental impacts (updating previously spatial units, Leip et al. 2008), for the analysis of policy scenarios. Recently, a statistical model to disaggregate crop information available from regional statistics to the HSU has been developed (Lamboni et al. 2016). The HSU data set consists of the spatial layers provided in vector and raster format as well as attribute tables with information on the properties of the HSU. All input data for the delineation the HSU is publicly available. For some parameters the attribute tables provide the link between the HSU data set and e.g. the soil map(s) rather than the data itself. The HSU data set is closely linked the USCIE data set.

Modelling the growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease

Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of these PrP aggregates is important both in attempting to the elucidate of the pathogenesis of prion disease and in the development of treatments designed to prevent or inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein aggregates. Mathematical models suggest that if aggregation/disaggregation or surface diffusion is the predominant factor, the size frequency distribution of the resulting protein aggregates in the brain should be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different types of PrP deposit, viz., the diffuse and florid-type PrP deposits in patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse plaques were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of plaque deviated significantly from a log-normal model in all brain areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid plaques. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse plaques. These results may be useful in the design of treatments to inhibit the development of protein aggregates in vCJD.

Size frequency distribution of the β-amyloid (aβ) deposits in dementia with Lewy bodies with associated Alzheimer’s disease pathology

The objective is to study beta-amyloid (Abeta) deposition in dementia with Lewy bodies (DLB) with Alzheimer's disease (AD) pathology (DLB/AD). The size frequency distributions of the Abeta deposits were studied and fitted by log-normal and power-law models. Patients were ten clinically and pathologically diagnosed DLB/AD cases. Size distributions had a single peak and were positively skewed and similar to those described in AD and Down's syndrome. Size distributions had smaller means in DLB/AD than in AD. Log-normal and power-law models were fitted to the size distributions of the classic and diffuse deposits, respectively. Size distributions of Abeta deposits were similar in DLB/AD and AD. Size distributions of the diffuse deposits were fitted by a power-law model suggesting that aggregation/disaggregation of Abeta was the predominant factor, whereas the classic deposits were fitted by a log-normal distribution suggesting that surface diffusion was important in the pathogenesis of the classic deposits.

An analysis of costs in institutions of higher education in England

Cost functions are estimated, using random effects and stochastic frontier methods, for English higher education institutions. The article advances on existing literature by employing finer disaggregation by subject, institution type and location, and by introducing consideration of quality effects. Estimates are provided of average incremental costs attached to each output type, and of returns to scale and scope. Implications for the policy of expansion of higher education are discussed.

Size frequency distributions of the florid prion protein aggregates in variant Creutzfeldt-Jakob disease follow a power-law function

The objective was to test the hypothesis that the size frequency distributions of the prion protein (PrP) plaques in cases of variant Creutzfeldt-Jakob disease (vCJD) follow a power-law function. The design was a retrospective neuropathological study. The patients were 11 cases of clinically and neuropathologically verified vCJD. Size distributions of the diffuse and florid-type plaques were measured in several areas of the cerebral cortex and hippocampus from each case and a power-law function fitted to each distribution. The size distributions of the florid and diffuse plaques were fitted successfully by a powerlaw function in 100% and 42% of brain areas investigated respectively. Processes of aggregation/disaggregation may be more important than surface diffusion in the pathogenesis of the florid plaques. By contrast, surface diffusion may be a more significant factor in the development of the diffuse plaques. © Springer-Verlag Italia 2006.

Modelling growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease

Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of PrP aggregates is important both in attempting to elucidate the pathogenesis of prion disease and in the development of treatments designed to inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein deposits. Mathematical models suggest that if either aggregation/disaggregation or surface diffusion is the predominant factor, then the size frequency distribution of the resulting protein aggregates will be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different populations of PrP deposit, viz., the diffuse and florid-type PrP deposits characteristic of patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse deposits were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of aggregate deviated significantly from a log-normal model in all areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid deposits. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse deposits. These results may be useful in the design of treatments to inhibit the development of PrP aggregates in vCJD.

Innovation in the pharmaceutical industry:a study of the effects of regulation on the U.K. pharmaceutical industry

A history of government drug regulation and the relationship between the pharmaceutical companies in the U.K. and the licensing authority is outlined. Phases of regulatory stringency are identified with the formation of the Committees on Safety of Drugs and Medicines viewed as watersheds. A study of the impact of government regulation on industrial R&D activities focuses on the effects on the rate and direction of new product innovation. A literature review examines the decline in new chemical entity innovation. Regulations are cited as a major but not singular cause of the decline. Previous research attempting to determine the causes of such a decline on an empirical basis is given and the methodological problems associated with such research are identified. The U.K. owned sector of the British pharmaceutical industry is selected for a study employing a bottom-up approach allowing disaggregation of data. A historical background to the industry is provided, with each company analysed or a case study basis. Variations between companies regarding the policies adopted for R&D are emphasised. The process of drug innovation is described in order to determine possible indicators of the rate and direction of inventive and innovative activity. All possible indicators are considered and their suitability assessed. R&D expenditure data for the period 1960-1983 is subsequently presented as an input indicator. Intermediate output indicators are treated in a similar way and patent data are identified as a readily-available and useful source. The advantages and disadvantages of using such data are considered. Using interview material, patenting policies for most of the U.K. companies are described providing a background for a patent-based study. Sources of patent data are examined with an emphasis on computerised systems. A number of searches using a variety of sources are presented. Patent family size is examined as a possible indicator of an invention's relative importance. The patenting activity of the companies over the period 1960-1983 is given and the variation between companies is noted. The relationship between patent data and other indicators used is analysed using statistical methods resulting in an apparent lack of correlation. An alternative approach taking into account variations in company policy and phases in research activity indicates a stronger relationship between patenting activity, R&D Expenditure and NCE output over the period. The relationship is not apparent at an aggregated company level. Some evidence is presented for a relationship between phases of regulatory stringency, inventive and innovative activity but the importance of other factors is emphasised.