Expansión supervisada de léxicos polarizados adaptable al contexto

El análisis de opiniones es un área en la cual múltiples disciplinas han otorgado diferentes enfoques para elaborar modelos que sean capaces de extraer la polaridad de los textos analizados. En función del dominio o categoría del texto analizado, donde ejemplos de categorías son Deportes o Banca, estos modelos deben ser modificados para obtener un análisis de opinión de calidad. En esta tesis se presenta un modelo que pretende elaborar un análisis de opiniones independiente de la categoría a analizar y un extenso estado del arte sobre análisis de opiniones. Se propone un enfoque cuantitativo que haría uso de un léxico polarizado semilla como único recurso cualitativo del modelo. El enfoque propuesto hace uso de un corpus anotado de textos por polaridad y categoría y el léxico polarizado semilla para producir un modelo capaz de elaborar un análisis de opinión de calidad en las distintas categorías analizadas y expandir el léxico polarizado semilla con términos que se adecúan a las categorías procesadas.---ABSTRACT---Sentiment analysis is an area in which multiple disciplines have given diferent approaches to make models that are able to extract the polarity of the analyzed texts. Depending on the domain or category of the analyzed text, where examples of categories are Sports or Banking, these models should be modified to obtain a good opinion analysis. This thesis presents a model that aims to develop a category independent opinion analysis model and a extensive sentiment analysis state of the art. A quantitative approach is proposed that will use a polarized lexicon as the only qualitative resource. The proposed approach uses an annotated corpus by polarity and category and a polarized lexicon seed to produce a model able to develop a good opinion analysis in the various categories analyzed and to expand the polarized lexicon seed with terms that fit the processed categories.

Hacia un Lexicón Unificado de Sentimientos basado en Unidades de Procesamiento Gráfico

Esta tesis presenta un modelo, una metodología, una arquitectura, varios algoritmos y programas para crear un lexicón de sentimientos unificado (LSU) que cubre cuatro lenguas: inglés, español, portugués y chino. El objetivo principal es alinear, unificar, y expandir el conjunto de lexicones de sentimientos disponibles en Internet y los desarrollados a lo largo de esta investigación. Así, el principal problema a resolver es la tarea de unificar de forma automatizada los diferentes lexicones de sentimientos obtenidos por el crawler CSR, porque la unidad de medida para asignar la intensidad de los valores de la polaridad (de forma manual, semiautomática y automática) varía de acuerdo con las diferentes metodologías utilizadas para la construcción de cada lexicón. La representación codificada de la estructura de datos de los términos presenta también una variación en la estructura de lexicón a lexicón. Por lo que al unificar en un lexicón de sentimientos se hace posible la reutilización del conocimiento recopilado por los diferentes grupos de investigación y se incrementa, a la vez, el alcance, la calidad y la robustez de los lexicones. Nuestra metodología LSU calcula un valor unificado de la intensidad de la polaridad para cada entrada léxica que está presente en al menos dos de los lexicones de sentimientos que forman parte de este estudio. En contraste, las entradas léxicas que no son comunes en al menos dos de los lexicones conservan su valor original. El coeficiente de Pearson resultante permite medir la correlación existente entre las entradas léxicas asignándoles un rango de valores de uno a menos uno, donde uno indica que los valores de los términos están perfectamente correlacionados, cero indica que no existe correlación y menos uno significa que están inversamente correlacionados. Este procedimiento se lleva acabo con la función de MetricasUnificadas tanto en la CPU como en la GPU. Otro problema a resolver es el tiempo de procesamiento que se requiere para realizar la tarea de unificación de la intensidad de la polaridad y con ello alcanzar una cobertura mayor de lemas en los lexicones de sentimientos existentes. Asimismo, la metodología LSU utiliza el procesamiento paralelo para unificar los 155 802 términos. El algoritmo LSU procesa mediante cargas iguales el subconjunto de entradas léxicas en cada uno de los 1344 núcleos en la GPU. Los resultados de nuestro análisis arrojaron un total de 95 430 entradas léxicas donde 35 201 obtuvieron valores positivos, 22 029 negativos y 38 200 neutrales. Finalmente, el tiempo de ejecución fue de 2,506 segundos para el total de las entradas léxicas, lo que permitió reducir el procesamiento de cómputo hasta en una tercera parte con respecto al algoritmo secuencial. De estos resultados se concluye que al lograr un lexicón de sentimientos unificado que permite homogeneizar la intensidad de la polaridad de las unidades léxicas (con valores positivos, negativos y neutrales) deriva no sólo en el análisis semántico del corpus basado en los términos con una mayor carga de polaridad, o del resumen de las valoraciones o las tendencias de neuromarketing, sino también en aplicaciones como el etiquetado subjetivo de sitios web o de portales sintácticos y semánticos, por mencionar algunas. ABSTRACT This thesis presents an approach to create what we have called a Unified Sentiment Lexicon (USL). This approach aims at aligning, unifying, and expanding the set of sentiment lexicons which are available on the web in order to increase their robustness of coverage. One problem related to the task of the automatic unification of different scores of sentiment lexicons is that there are multiple lexical entries for which the classification of positive, negative, or neutral P, N, Z depends on the unit of measurement used in the annotation methodology of the source sentiment lexicon. Our USL approach computes the unified strength of polarity of each lexical entry based on the Pearson correlation coefficient which measures how correlated lexical entries are with a value between 1 and - 1 , where 1 indicates that the lexical entries are perfectly correlated, 0 indicates no correlation, and -1 means they are perfectly inversely correlated and so is the UnifiedMetrics procedure for CPU and GPU, respectively. Another problem is the high processing time required for computing all the lexical entries in the unification task. Thus, the USL approach computes a subset of lexical entries in each of the 1344 GPU cores and uses parallel processing in order to unify 155,802 lexical entries. The results of the analysis conducted using the USL approach show that the USL has 95,430 lexical entries, out of which there are 35,201 considered to be positive, 22,029 negative, and 38,200 neutral. Finally, the runtime was 2.505 seconds for 95,430 lexical entries; this allows a reduction of the time computing for the UnifiedMetrics by 3 times with respect to the sequential implementation. A key contribution of this work is that we preserve the use of a unified sentiment lexicon for all tasks. Such lexicon is used to define resources and resource-related properties that can be verified based on the results of the analysis and is powerful, general and extensible enough to express a large class of interesting properties. Some applications of this work include merging, aligning, pruning and extending the current sentiment lexicons.

Evolución paleoambiental de la Península Ibérica desde hace 1 Ma a partir de los biomarcadores del registro de la Turbera de Padul (Granada)

La Turbera de Padul, en la Provincia de Granada, ofrece unas posibilidades de estudio muy atractivas desde el punto de vista de la reconstrucción paleoambiental. Se trata de una fosa tectónica subsidente de naturaleza detrítica, a cuyo techo aparecen alternantes niveles de turba. El sondeo, de 107 metros, se realizó en un punto donde los estratos de turba aparecen a mayor profundidad, lo que permite obtener un registro geoquímico orgánico con mucho detalle con una antigüedad de hasta 1Ma. Se tomaron muestras cada 20 cm para el análisis de biomarcadores. Estos biomarcadores se obtuvieron mediante extracción Soxhlet, posterior separación de fracciones de diferente polaridad mediante Cromatografía en Columna, con Gel de Sílice y Alúmina, y posteriormente el análisis e identificación por Cromatografía de Gases - Espectrometría de masas, con confirmación de los compuestos químicos identificados por comparación con Bibliotecas de Espectros de Masas. La datación del sondeo se realizó utilizando distintos métodos como datación por 14C, U/Th, y datación por racemización de aminoácidos. Los resultados dataron el muro del sondeo con una antigüedad de 1 millón de años. El estudio de los biomarcadores ha permitido identificar episodios con distintas características en un escenario complejo, como es la Turbera de Padul, donde el aporte de agua por fusión nival complica la interpretación paleoambiental, y es la responsable de la existencia de la lámina de agua en la turbera en periodos secos con temperaturas elevadas. Se han identificado series de n-alcanos, de n-metilcetonas y series de nalcanoles, que han permitido identificar la aportación de materia orgánica de distintas fuentes al sedimento y por tanto la interpretación paleoambiental. La identificación de diterpenoides fenólicos (cis-Totatol, trans-Totarol y Ferruginol) han permitido identificar episodios de clima templado y húmedo con proliferación de cupresáceas, y precipitaciones abundantes. Por otro lado, se han identificado triterpenoides como el Friedelan-3-ona (Friedelin) y el A-norfriedel-8en-10-ona, cuya relación como precursor (Friedelin) y producto (A-norfriedel-8en-10-ona) ha permitido identificar episodios con fluctuaciones del espesor de la lámina de agua y aporte de material vegetal. ABSTRACT The Bog of Padul, in the province of Granada, offers very attractive possibilities for the study of paleoenvironmental reconstruction. It is a subsiding graben of detrital nature, whose upper part appear alternating peat levels. The core of 107 meters, obtained from a borehole drilled in a place where the layers of peat appear deeper, allowing to obtain organic geochemist information along the last 1 million years. Every 20 cm samples for biomarkers analysis were taken. These biomarkers were obtained by Soxhlet extraction, subsequent separation of fractions of different polarity by column chromatography with silica gel and alumina, and then analyzed and identified by gas chromatography - mass spectrometry, with confirmation of the chemicals identified by comparison to mass spectral libraries. The dating of the core was conducted using different methods such as 14C dating, U/Th, and amino acid racemization dating. The results dated the base of the core to be 1 million years old. The study has identified biomarkers episodes with different characteristics in a complex scenario, such as the Bog of Padul, where the contribution of snowmelt water complicates the paleoenvironmental interpretation, and is responsible for the existence of a sheet of water in dry periods with high temperatures. There have been identified series of n-alkanes, n-methyl ketones and series of n-alkanols that have shown the contribution of different organic matter sources to the sediment and therefore allowed to paleo interpretation. The identification of phenolic diterpenoids (cis-Totatol, trans-Totarol and Ferruginol) have identified episodes of mild and humid climate with proliferation of Cupressaceae, and abundant rainfall. In addition, triterpenoids have been identified, as the friedelan-3-one (friedelin) and the A-norfriedel-8en-10-one, whose relationship as precursor (friedelin) and product (A-norfriedel-8en-10-one) has identified episodes with fluctuations on the thickness of the sheet of water and supply of plant material debris.

Diseño de una herramienta para la aplicación de técnicas de minería de textos

El objetivo del presente trabajo es el estudio, diseño e implementación de una herramienta software, con interfaz gráfica de usuario, que permita aplicar diversas técnicas de análisis de textos de forma simple. Las técnicas de análisis, que serán implementadas en la herramienta, extraerán información de textos escritos en un lenguaje humano, es decir un lenguaje no artificial, y se le presentará al usuario. La herramienta permite la obtención de tres tipos de información: categorías a las que pertenece un texto, dentro de un conjunto de categorías predeterminadas; grupos de textos que son similares entre sí; y la polaridad de opinión expresada en un texto hacia el tema u objeto del que trata, que puede ser neutra, positiva o negativa.---ABSTRACT---The aim of this work is to study, design and implement a software tool, with graphical user interface, which will enable a user to easily apply various text analysis techniques. The techniques implemented in the tool will extract information from texts written in natural language, i.e. a non artificial language, and will present it to the user. The tool will extract three different types of information about a given set of texts: their categories (from a predefined set of categories), groups of similar texts, the polarity of the attitude expressed in the texts towards their topic.

El crecimiento, densificación y ordenación de la ciudad difusa en Galicia: desarrollo urbanístico del área urbana de la Ría de Vigo 1990-2010

El área urbana localizada en el contorno de la ría de Vigo se vino comportando hasta finales de los años ochenta del siglo XX como una verdadera "ciudad difusa", entendida la difusión como la forma de urbanización de baja densidad que todavía conserva unas características y una funcionalidad propiamente urbanas, aportadas por la malla tradicional parroquial de caminos y núcleos de población. Esta Tesis demuestra que en el período de veinte años transcurrido entre 1990 y 2010, el área, en la que ya se apreciaban fenómenos de naturaleza metropolitana y policentrismo, experimentó una transformación basada en los factores y formas de urbanización estudiados en otras áreas y ciudades intermedias de similares dimensiones. Para la delimitación del ámbito de estudio se consideraron las diferentes dimensiones y escalas de áreas funcionales utilizadas en distintos estudios y planes territoriales, eligiéndose el que toma como referente principal la Ría de Vigo como soporte de la conurbación polinuclear de su contorno. Para investigar el desarrollo urbanístico operado en el período se estudiaron los factores y formas de urbanización característicos de la urbanización en territorios de baja densidad en esta época, y las variables de densidad es de población y vivienda, primacía y polaridad territorial, ritmos de edificación, planeamiento urbanístico y territorial, actividades económicas, movilidad, desplazamientos residenciatrabajo y vacíos urbanos. Las conclusiones permiten observar como el crecimiento residencial descentralizado, que se ha dado principalmente en el litoral, y la localización periférica de las actividades y dotaciones públicas han introducido elementos de dispersión y fragmentación espacial y social, así como las nuevas y potentes infraestructuras viarias, que han mejorado los desplazamientos a costa de una dependencia abusiva del vehículo privado, y han comenzado a amenazar la sostenibilidad del sistema. La planificación de ordenación territorial a escala metropolitana y el planeamiento urbanístico, que se comenzaron a utilizar con normalidad en esta época, se vislumbran como una oportunidad para reconducir el proceso, integrando los territorios genéricos surgidos entre las nuevas infraestructuras y dotaciones y la malla tradicional, así como los vacíos urbanos susceptibles de compactación, protegiendo aquellos otros vacíos que deben constituir la principal reserva ecológica: Los montes en mano común y la Ría de Vigo. La necesidad de una planificación operativa, sostenible y participativa, que integre la ordenación territorial, la gestión integral de los recursos de la Ría, y articule las diferentes competencias y escalas, la gobernanza , la participación ciudadana y el mercado, se considera la principal conclusión para el futuro. ABSTRACT The urban area located around the Ría de Vigo* used to behave like a “diffused city” until the late 1980s, understanding this difussion as the low-density urbanization that still today exhibits ‘urban’ characteristics and functionality, given by the traditional network of parish paths and town cores. This Thesis shows that during the twenty-year period from 1990 to 2010, this area, which previously showed signals of polycentrism and metropolitan character, started a transformation based on the factors and ways of urbanization studied in other areas and intermediate cities of similar dimensions. In order to demarcate the scope of this study, different dimensions and functional area scales previously used in other studies have been taken into account, choosing the one that takes the Ría de Vigo as the main reference and the basis of the polynuclear conurbation of its surroundings. To research the urban development in this period, factors and ways of urbanization regarding lowdensity territories have been considered, as well as some variables like density of population and housing, territorial primacy and polarity, building rates, territorial planning, economic activities, mobility, home-to-work trips and urban holes. Conclusions allow us to point out how the decentralised residential growing (that occurred mainly on the litoral surface) and the periferic localization of the activities and public facilities, have created elements of “sprawl” and spacial and social fragmentation, which, together with the new and powerfull road infraestructures network (that made the movements easier by means of an abusive dependence on the private vehicle), have started to threaten the sustainability of the system. The planification of the territorial ordinance at metropolitan scale and the urban planning, that in that time started to be established, can be considered as an opportunity to get things back on track, integrating the territories risen up from the new infrastructures and facilities and the traditional network together with the urban holes liable to be compacted, with a special protection of the spaces that must be the main ecological reserve: the communal forests and the Ría de Vigo. The need of a sustainable and participatory operative planification, able to integrate the territory planning, the integral management of resources and the citizen involvement and the market, has to be considered as the main goal for the future.

The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene

The Drosophila gene bicoid functions as the anterior body pattern organizer of Drosophila. Embryos lacking maternally expressed bicoid fail to develop anterior segments including head and thorax. In wild-type eggs, bicoid mRNA is localized in the anterior pole region and the bicoid protein forms an anterior-to-posterior concentration gradient. bicoid activity is required for transcriptional activation of zygotic segmentation genes and the translational suppression of uniformly distributed maternal caudal mRNA in the anterior region of the embryo. caudal genes as well as other homeobox genes or members of the Drosophila segmentation gene cascade have been found to be conserved in animal evolution. In contrast, bicoid homologs have been identified only in close relatives of the schizophoran fly Drosophila. This poses the question of how the bicoid gene evolved and adopted its unique function in organizing anterior–posterior polarity. We have cloned bicoid from a basal cyclorrhaphan fly, Megaselia abdita (Phoridae, Aschiza), and show that the gene originated from a recent duplication of the direct homolog of the vertebrate gene Hox3, termed zerknüllt, which specifies extraembryonic tissues in insects.

The gastrulation defective gene of Drosophila melanogaster is a member of the serine protease superfamily

The establishment of dorsal–ventral polarity in the oocyte involves two sets of genes. One set belongs to the gurken-torpedo signaling pathway and affects the development of the egg chorion as well as the polarity of the embryo. The second set of genes affects only the dorsal–ventral polarity of the embryo but not the eggshell. gastrulation defective is one of the earliest acting of this second set of maternally required genes. We have cloned and characterized the gastrulation defective gene and determined that it encodes a protein structurally related to the serine protease superfamily, which also includes the Snake, Easter, and Nudel proteins. These data provide additional support for the involvement of a protease cascade in generating an asymmetric signal (i.e., asymmetric Spätzle activity) during establishment of dorsal–ventral polarity in the Drosophila embryo.

Heteroduplex joint formation in Escherichia coli recombination is initiated by pairing of a 3′-ending strand

The formation of heteroduplex joints in Escherichia coli recombination is initiated by invasion of double-stranded DNA by a single-stranded homologue. To determine the polarity of the invasive strand, linear molecules with direct terminal repeats were released by in vivo restriction of infecting chimeric phage DNA and heteroduplex products of intramolecular recombination were analyzed. With this substrate, the invasive strand is expected to be incorporated into the circular crossover product and the complementary strand is expected to be incorporated into the reciprocal linear product. Strands of both polarities were incorporated into heteroduplex structures, but only strands ending 3′ at the break were incorporated into circular products. This result indicates that invasion of the 3′-ending strand initiates the heteroduplex joint formation and that the complementary 5′-ending strand is incorporated into heteroduplex structures in the process of reciprocal strand exchange. The polarity of the invasive strand was not affected by recD, recJ, or xonA mutations. However, xonA and recJ mutations increased the proportion of heteroduplexes containing 5′-ending strands. This observation suggests that RecJ exonuclease and exonuclease I may enhance recombination by degrading the displaced strands during branch migration and thereby causing strand exchange to be unidirectional.

Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis

SMAD2 is a member of the transforming growth factor β and activin-signaling pathway. To examine the role of Smad2 in postgastrulation development, we independently generated mice with a null mutation in this gene. Smad2-deficient embryos die around day 7.5 of gestation because of failure of gastrulation and failure to establish an anterior–posterior (A-P) axis. Expression of the homeobox gene Hex (the earliest known marker of the A-P polarity and the prospective head organizer) was found to be missing in Smad2-deficient embryos. Homozygous mutant embryos and embryonic stem cells formed mesoderm derivatives revealing that mesoderm induction is SMAD2 independent. In the presence of wild-type extraembryonic tissues, Smad2-deficient embryos developed beyond 7.5 and up to 10.5 days postcoitum, demonstrating a requirement for SMAD2 in extraembryonic tissues for the generation of an A-P axis and gastrulation. The rescued postgastrulation embryos showed malformation of head structures, abnormal embryo turning, and cyclopia. Our results show that Smad2 expression is required at several stages during embryogenesis.

Chrysanthemum chlorotic mottle viroid: Unusual structural properties of a subgroup of self-cleaving viroids with hammerhead ribozymes

The causal agent of chrysanthemum chlorotic mottle (CChM) disease has been identified, cloned, and sequenced. It is a viroid RNA (CChMVd) of 398–399 nucleotides. In vitro transcripts with the complete CChMVd sequence were infectious and induced the typical symptoms of the CChM disease. CChMVd can form hammerhead structures in both polarity strands. Plus and minus monomeric CChMVd RNAs self-cleaved during in vitro transcription and after purification as predicted by these structures, which are stable and most probably act as single hammerhead structures as in peach latent mosaic viroid (PLMVd), but not in avocado sunblotch viroid (ASBVd). Moreover, the plus CChMVd hammerhead structure also appears to be active in vivo, because the 5′ terminus of the linear plus CChMVd RNA isolated from infected tissue is that predicted by the corresponding hammerhead ribozyme. Both hammerhead structures of CChMVd display some peculiarities: the plus self-cleaving domain has an unpaired A after the conserved A9 residue, and the minus one has an unusually long helix II. The most stable secondary structure predicted for CChMVd is a branched conformation that does not fulfill the rod-like or quasi-rod-like model proposed for the in vitro structure of most viroids with the exception of PLMVd, whose proposed secondary structure of lowest free energy also is branched. The unusual conformation of CChMVd and PLMVd is supported by their insolubility in 2 M LiCl, in contrast to ASBVd and a series of representative non-self-cleaving viroids that are soluble under the same high salt conditions. These results support the classification of self-cleaving viroids into two subgroups, one formed by ASBVd and the other one by PLMVd and CChMVd.

Transmembrane β-barrel of staphylococcal α-toxin forms in sensitive but not in resistant cells

Staphylococcal α-toxin is a 293-residue, single-chain polypeptide that spontaneously assembles into a heptameric pore in target cell membranes. To identify the pore-forming domain, substitution mutants have been produced in which single cysteine residues were introduced throughout the toxin molecule. By attaching the environmentally sensitive dye acrylodan to the sulfhydryl groups, the environment of individual amino acid side chains could be probed. In liposomes, a single 23-amino acid sequence (residues 118–140) was found to move from a polar to a nonpolar environment, indicating that this sequence forms the walls of the pore. However, periodicity in side chain environmental polarity could not be detected in the liposomal system. In the present study, the fluorimetric analyses were extended to physiological target cells. With susceptible cells such as rabbit erythrocytes and human lymphocytes, the 23 central amino acids 118–140 were again found to insert into the membrane; in contrast to the previous study with liposomes, the expected periodicity was now detected. Thus, every other residue in the sequence 126–140 entered a nonpolar environment in a striking display of an amphipathic transmembrane β-barrel. In contrast, human granulocytes were found to bind α-toxin to a similar extent as lymphocytes, but the heptamers forming on these cells failed to insert their pore-forming domain into the membrane. As a consequence, nonfunctional heptamers assembled and the cells remained viable. The data resolve the molecular organization of a pore-forming toxin domain in living cells and reveal that resistant cells can prevent insertion of the functional domain into the bilayer.

Feature integration in pattern perception

The human visual system is able to effortlessly integrate local features to form our rich perception of patterns, despite the fact that visual information is discretely sampled by the retina and cortex. By using a novel perturbation technique, we show that the mechanisms by which features are integrated into coherent percepts are scale-invariant and nonlinear (phase and contrast polarity independent). They appear to operate by assigning position labels or “place tags” to each feature. Specifically, in the first series of experiments, we show that the positional tolerance of these place tags in foveal, and peripheral vision is about half the separation of the features, suggesting that the neural mechanisms that bind features into forms are quite robust to topographical jitter. In the second series of experiment, we asked how many stimulus samples are required for pattern identification by human and ideal observers. In human foveal vision, only about half the features are needed for reliable pattern interpolation. In this regard, human vision is quite efficient (ratio of ideal to real ≈ 0.75). Peripheral vision, on the other hand is rather inefficient, requiring more features, suggesting that the stimulus may be relatively underrepresented at the stage of feature integration.

Revised geochronology of the Casamayoran South American Land Mammal Age: Climatic and biotic implications

Isotopic age determinations (40Ar/39Ar) and associated magnetic polarity stratigraphy for Casamayoran age fauna at Gran Barranca (Chubut, Argentina) indicate that the Barrancan “subage” of the Casamayoran South American Land Mammal “Age” is late Eocene, 18 to 20 million years younger than hitherto supposed. Correlations of the radioisotopically dated magnetic polarity stratigraphy at Gran Barranca with the Cenozoic geomagnetic polarity time scale indicate that Barrancan faunal levels at the Gran Barranca date to within the magnetochronologic interval from 35.34 to 36.62 megannums (Ma) or 35.69 to 37.60 Ma. This age revision constrains the timing of an adaptive shift in mammalian herbivores toward hypsodonty. Specifically, the appearance of large numbers of hypsodont taxa in South America occurred sometime between 36 and 32 Ma (late Eocene–early Oligocene), at approximately the same time that other biotic and geologic evidence has suggested the Southern high latitudes experienced climatic cooling associated with Antarctic glaciation.

Orientation of the transcription preinitiation complex in Archaea

The basal transcription machinery of Archaea corresponds to the minimal subset of factors required for RNA polymerase II transcription in eukaryotes. Using just two factors, Archaea recruit the RNA polymerase to promoters and define the direction of transcription. Notably, the principal determinant for the orientation of transcription is not the recognition of the TATA box by the TATA-box-binding protein. Instead, transcriptional polarity is governed by the interaction of the archaeal TFIIB homologue with a conserved motif immediately upstream of the TATA box. This interaction yields an archaeal preinitiation complex with the same orientation as the analogous eukaryal complex.

Analysis of three structurally related antiviral compounds in complex with human rhinovirus 16

Rhinoviruses are a frequent cause of the common cold. A series of antirhinoviral compounds have been developed that bind into a hydrophobic pocket in the viral capsid, stabilizing the capsid and interfering with cell attachment. The structures of a variety of such compounds, complexed with rhinovirus serotypes 14, 16, 1A, and 3, previously have been examined. Three chemically similar compounds, closely related to a drug that is undergoing phase III clinical trials, were chosen to determine the structural impact of the heteroatoms in one of the three rings. The compounds were found to have binding modes that depend on their electronic distribution. In the compound with the lowest efficacy, the terminal ring is displaced by 1 Å and rotated by 180° relative to the structure of the other two. The greater polarity of the terminal ring in one of the three compounds leads to a small displacement of its position relative to the other compounds in the hydrophobic end of the antiviral compound binding pocket to a site where it makes fewer interactions. Its lower efficacy is likely to be the result of the reduced number of interactions. A region of conserved residues has been identified near the entrance to the binding pocket where there is a corresponding conservation of the mode of binding of these compounds to different serotypes. Thus, variations in residues lining the more hydrophobic end of the pocket are primarily responsible for the differences in drug efficacies.