Macromolecular interaction studies on FF1-3 of human CA150 and STAT1-importin alpha5 using biophysical and biochemical methods

Macromolecular interactions, such as protein-protein interactions and protein-DNA interactions, play important roles in executing biological functions in cells. However the complexity of such interactions often makes it very challenging to elucidate the structural details of these subjects. In this thesis, two different research strategies were applied on two different two macromolecular systems: X-ray crystallography on three tandem FF domains of transcription regulator CA150 and electron microscopy on STAT1-importin α5 complex. The results from these studies provide novel insights into the function-structure relationships of transcription coupled RNA splicing mediated by CA150 and the nuclear import process of the JAK-STAT signaling pathway. ^ The first project aimed at the protein-protein interaction module FF domain, which often occurs as tandem repeats. Crystallographic structure of the first three FF domains of human CA150 was determined to 2.7 Å resolution. This is the only crystal structure of an FF domain and the only structure on tandem FF domains to date. It revealed a striking connectivity between an FF domain and the next. Peptide binding assay with the potential binding ligand of FF domains was performed using fluorescence polarization. Furthermore, for the first time, FF domains were found to potentially interact with DNA. DNA binding assays were also performed and the results were supportive to this newly proposed functionality of an FF domain. ^ The second project aimed at understanding the molecular mechanism of the nuclear import process of transcription factor STAT1. The first structural model of pSTAT1-importin α5 complex in solution was built from the images of negative staining electron microscopy. Two STAT1 molecules were observed to interact with one molecule of importin α5 in an asymmetric manner. This seems to imply that STAT1 interacts with importin α5 with a novel mechanism that is different from canonical importin α-cargo interactions. Further in vitro binding assays were performed to obtain more details on the pSTAT1-importin α5 interaction. ^

Performance tiers: Implementing comparative effectiveness analysis in the health care setting through operations research and spatial methods

This dissertation develops and tests a comparative effectiveness methodology utilizing a novel approach to the application of Data Envelopment Analysis (DEA) in health studies. The concept of performance tiers (PerT) is introduced as terminology to express a relative risk class for individuals within a peer group and the PerT calculation is implemented with operations research (DEA) and spatial algorithms. The analysis results in the discrimination of the individual data observations into a relative risk classification by the DEA-PerT methodology. The performance of two distance measures, kNN (k-nearest neighbor) and Mahalanobis, was subsequently tested to classify new entrants into the appropriate tier. The methods were applied to subject data for the 14 year old cohort in the Project HeartBeat! study.^ The concepts presented herein represent a paradigm shift in the potential for public health applications to identify and respond to individual health status. The resultant classification scheme provides descriptive, and potentially prescriptive, guidance to assess and implement treatments and strategies to improve the delivery and performance of health systems. ^

SOCIO-ENVIRONMENTAL FACTORS ASSOCIATED WITH THE DISTRIBUTION OF DRACUNCULUS MEDINENSIS (GUINEA WORM DISEASE) AND SUGGESTED METHODS FOR CONTROL, IBARAPA, NIGERIA, 1982 (AFRICA)

A population-based cross-sectional survey of socio-environmental factors associated with the prevalence of Dracunculus medinensis (guinea worm disease) was conducted in Idere, a rural agricultural community in Ibarapa, Oyo state, Nigeria, during 1982.^ The epidemiologic data were collected by household interview of all 501 households. The environmental data were collected by analysis of water samples collected from all domestic water sources and rainfall records.^ The specific objectives of this research were to: (a) Describe the prevalence of guinea worm disease in Idere during 1982 by age, sex, area of residence, drinking water source, religion and weekly amount of money spent by the household to collect potable drinking water. (b) Compare the characteristics of cases with non-cases of guinea worm in order to identify factors associated with high risk of infection. (c) Investigate domestic water sources for the distribution of Cyclops. (d) Determine the extent of potable water shortage with a view to identifying factors responsible for such shortage in the community. (e) Describe the effects of guinea worm on school attendance during 1980/1982 school years by class and location of school from piped water supply.^ The findings of this research indicate that during 1982, 31.8 percent of Idere's 6,527 residents experienced guinea worm infection, with higher prevalence of infection recorded in males in their most productive years and females in their teenage years. The role of sex and age to risk of higher infection rate was explained in the context of water related exposure and water intake due to dehydration from physical occupational actitives of subgroups.^ Potable water available to residents was considerably below the minimum recommended by WHO for tropical climates, with sixty-eight percent of water needs of the residents coming from unprotected surface water which harbour Cyclops, the obligatory intermediate host of Dracunculus medinensis. An association was found between periods of relative high density of Cyclops in domestic water and rainfall.^ Impact of guinea worm infection on educational activities was considerable and its implications were discussed, including the implications of the research findings in relation to control of guinea worm disease in Ibarapa. ^

Phosphorus and Potassium Rates and Placement Methods for Corn and Soybean Managed with No-till or Tillage

No-till management for corn and soybean results in little or no incorporation of crop residues and fertilizer with soil. Subsurface banding phosphorus (P) and potassium (K) fertilizers with planter attachments could be more effective than broadcast fertilization, because in no-till with broadcast fertilizer, both nutrients accumulate at or near the soil surface. A long-term study was initiated in 1994 at the ISU Northwest Research Farm to evaluate P and K fertilizer placement for corn and soybean managed with no-till and chiselplow tillage.

An environmental magnetic study, sedimentological and numerical methods around Tauranga Harbour, New Zealand

Magnetic iron minerals are widespread and indicative sediment constituents in estuarine, coastal and shelf systems. We combine environmental magnetic, sedimentological and numerical methods to identify magnetite-enriched placer-like zones in a complex coastal system and delineate their formation mechanisms. Magnetic susceptibility and remanence measurements on 245 surficial sediment samples collected in and around Tauranga Harbour, the largest barrier-enclosed tidal estuary of New Zealand, reveal several discrete enrichment zones controlled by local hydrodynamic conditions. Active magnetite enrichment takes place in tidal channels, which feed into two coast-parallel nearshore magnetite-enriched belts centered at water depths of 6-10 m and 10-20 m. A close correlation between magnetite content and magnetic grain size was found, where higher susceptibility values are associated within coarser magnetic crystal sizes. Two key mechanisms for magnetite enrichment are identified. First, tide-induced residual currents primarily enable magnetite enrichment within the estuarine channel network. A coast-parallel, fine sand magnetite enrichment belt in water depths of less than 10 m along the barrier island has a strong decrease in magnetite content away from the southern tidal inlet and is apparently related to active coast-parallel transport combined with mobilizing surf zone processes. A second, less pronounced, but more uniform magnetite enrichment belt at 10-20 m water depth is composed of non-mobile, medium-coarse-grained relict sands, which have been reworked during post-glacial sea level transgression. We demonstrate the potential of magnetic methods to reveal and differentiate coastal magnetite enrichment patterns and investigate their formative mechanisms.

The CDG, UDG, and MEL methods for automatic compile-time parallelization of logic programs for independent and-parallelism

There has been significant interest in parallel execution models for logic programs which exploit Independent And-Parallelism (IAP). In these models, it is necessary to determine which goals are independent and therefore eligible for parallel execution and which goals have to wait for which others during execution. Although this can be done at run-time, it can imply a very heavy overhead. In this paper, we present three algorithms for automatic compiletime parallelization of logic programs using IAP. This is done by converting a clause into a graph-based computational form and then transforming this graph into linear expressions based on &-Prolog, a language for IAP. We also present an algorithm which, given a clause, determines if there is any loss of parallelism due to linearization, for the case in which only unconditional parallelism is desired. Finally, the performance of these annotation algorithms is discussed for some benchmark programs.

Complete and efficient methods for supporting side effects in independent/restricted and-parallelism

It has been shown that it is possible to exploit Independent/Restricted And-parallelism in logic programs while retaining the conventional "don't know" semantics of such programs. In particular, it is possible to parallelize pure Prolog programs while maintaining the semantics of the language. However, when builtin side-effects (such as write or assert) appear in the program, if an identical observable behaviour to that of sequential Prolog implementations is to be preserved, such side-effects have to be properly sequenced. Previously proposed solutions to this problem are either incomplete (lacking, for example, backtracking semantics) or they force sequentialization of significant portions of the execution graph which could otherwise run in parallel. In this paper a series of side-effect synchronization methods are proposed which incur lower overhead and allow more parallelism than those previously proposed. Most importantly, and unlike previous proposals, they have well-defined backward execution behaviour and require only a small modification to a given (And-parallel) Prolog implementation.

The application of inverse-dispersion and gradient methods to estimate ammonia emissions from a penguin colony.

Penguin colonies represent some of the most concentrated sources of ammonia emissions to the atmosphere in the world. The ammonia emitted into the atmosphere can have a large influence on the nitrogen cycling of ecosystems near the colonies. However, despite the ecological importance of the emissions, no measurements of ammonia emissions from penguin colonies have been made. The objective of this work was to determine the ammonia emission rate of a penguin colony using inverse-dispersion modelling and gradient methods. We measured meteorological variables and mean atmospheric concentrations of ammonia at seven locations near a colony of Adélie penguins in Antarctica to provide input data for inverse-dispersion modelling. Three different atmospheric dispersion models (ADMS, LADD and a Lagrangian stochastic model) were used to provide a robust emission estimate. The Lagrangian stochastic model was applied both in ‘forwards’ and ‘backwards’ mode to compare the difference between the two approaches. In addition, the aerodynamic gradient method was applied using vertical profiles of mean ammonia concentrations measured near the centre of the colony. The emission estimates derived from the simulations of the three dispersion models and the aerodynamic gradient method agreed quite well, giving a mean emission of 1.1 g ammonia per breeding pair per day (95% confidence interval: 0.4–2.5 g ammonia per breeding pair per day). This emission rate represents a volatilisation of 1.9% of the estimated nitrogen excretion of the penguins, which agrees well with that estimated from a temperature-dependent bioenergetics model. We found that, in this study, the Lagrangian stochastic model seemed to give more reliable emission estimates in ‘forwards’ mode than in ‘backwards’ mode due to the assumptions made.

Multispectral microscopy and quantitative texture

CAMEVA SYSTEM Automated optical identification of ore minerals in polished samples using multispectral digital images Support for basic ore microscopy / ore identification Geometallurgy: Automated system for quantitative mineralogy applications, more efficient than manual methods and less expensive than SEM systems

High speed railroad bridges. Conception, bases of design, typological possibilities and construction methods

Diseño conceptual de puentes de alta velocidad ferroviarios. Railroad bridges, in general, and those for high speed railways, in particular, demand very special conditions. The traffic loads are much higher than for road bridges. Loads due to braking and acceleration determine, due to their magnitude, the structural layout. Because of the speed of the vehicles there are specific dynamic effects which need to be considered. In order to ensure passenger comfort, compatible with speeds of up to 350 km/h, it is necessary to meet very demanding conditions with respect to stiffness, displacements and dynamic behavior. In this paper these conditions are briefly described and different typological possibilities to satisfy them are presented as well as the main construction methods applicable to this kind of bridges.

A comparative analysis between FEM and Boundary Methods in bending of Plates

Two different methods of analysis of plate bending, FEM and BM are discussed in this paper. The plate behaviour is assumed to be represented by using the linear thin plate theory where the Poisson-Kirchoff assumption holds. The BM based in a weighted mean square error technique produced good results for the problem of plate bending. The computational effort demanded in the BM is smaller than the one needed in a FEM analysis for the same level of accuracy. The general application of the FEM cannot be matched by the BM. Particularly, different types of geometry (plates of arbitrary geometry) need a similar but not identical treatment in the BM. However, this loss of generality is counterbalanced by the computational efficiency gained in the BM in the solution achievement

Determination of pH dependent antioxidant activity of Palm (Borassus flabellifer) Polyphenol compounds by Photoluminol and DPPH methods -A Comparison redox-reaction Sensitivity

Palm juice (Borassus flabellifer) is one of the most common and cheap natural juices. Fermented palm juice contains various phytochemical compounds that exhibit antioxidant activity. In the present study, we examined the effects of pH on the production of phytochemicals and their antioxidant activity during the fermentation process. The concentration of total phenolics and flavonoid compounds of fermented palm juice and their antioxidant activity were investigated at various pH. The results showed that total phenolics concentration and antioxidant activity of palm wine and palm vinegar increase as pH increases: 3.54.55.5. Maximum flavonoid concentration was obtained at pH 6.5. Measurements of antioxidant activity by conventional DPPH method and Photochem antioxidant analyzer technique were highly correlated, with a corresponding R2 value of 0.94.

Métodos diferenciales e interferométricos para la evaluación de deformaciones de la corteza terrestre mediante técnicas GNSS e InSAR = Differential and interferometric methods for evaluation of crustal deformation using GNSS and InSAR techniques

La actividad volcánica interviene en multitud de facetas de la propia actividad humana, no siempre negativas. Sin embargo, son más los motivos de peligrosidad y riesgo que incitan al estudio de la actividad volcánica. Existen razones de seguridad que inciden en el mantenimiento del seguimiento y monitorización de la actividad volcánica para garantizar la vida y la seguridad de los asentamientos antrópicos en las proximidades de los edificios volcánicos. En esta tesis se define e implementa un sistema de monitorización de movimientos de la corteza en las islas de Tenerife y La Palma, donde el impacto social que representa un aumento o variación de la actividad volcánica en las islas es muy severo. Aparte de la alta densidad demográfica del Archipiélago, esta población aumenta significativamente, en diferentes periodos a lo largo del año, debido a la actividad turística que representa la mayor fuente de ingresos de las islas. La población y los centros turísticos se diseminan predominantemente a lo largo de las costas y también a lo largo de los flancos de los edificios volcánicos. Quizá el mantenimiento de estas estructuras sociales y socio-económicas son los motivos más importantes que justifican una monitorización de la actividad volcánica en las Islas Canarias. Recientemente se ha venido trabajando cada vez más en el intento de predecir la actividad volcánica utilizando los nuevos sistemas de monitorización geodésica, puesto que la actividad volcánica se manifiesta anteriormente por deformación de la corteza terrestre y cambios en la fuerza de la gravedad en la zona donde más tarde se registran eventos volcánicos. Los nuevos dispositivos y sensores que se han desarrollado en los últimos años en materias como la geodesia, la observación de la Tierra desde el espacio y el posicionamiento por satélite, han permitido observar y medir tanto la deformación producida en el terreno como los cambios de la fuerza de la gravedad antes, durante y posteriormente a los eventos volcánicos que se producen. Estos nuevos dispositivos y sensores han cambiado las técnicas o metodologías geodésicas que se venían utilizando hasta la aparición de los mismos, renovando métodos clásicos y desarrollando otros nuevos que ya se están afianzando como metodologías probadas y reconocidas para ser usadas en la monitorización volcánica. Desde finales de la década de los noventa del siglo pasado se han venido desarrollando en las Islas Canarias varios proyectos que han tenido como objetivos principales el desarrollo de nuevas técnicas de observación y monitorización por un lado y el diseño de una metodología de monitorización volcánica adecuada, por otro. Se presenta aquí el estudio y desarrollo de técnicas GNSS para la monitorización de deformaciones corticales y su campo de velocidades para las islas de Tenerife y La Palma. En su implementación, se ha tenido en cuenta el uso de la infraestructura geodésica y de monitorización existente en el archipiélago a fin de optimizar costes, además de complementarla con nuevas estaciones para dar una cobertura total a las dos islas. Los resultados obtenidos en los proyectos, que se describen en esta memoria, han dado nuevas perspectivas en la monitorización geodésica de la actividad volcánica y nuevas zonas de interés que anteriormente no se conocían en el entorno de las Islas Canarias. Se ha tenido especial cuidado en el tratamiento y propagación de los errores durante todo el proceso de observación, medida y proceso de los datos registrados, todo ello en aras de cuantificar el grado de fiabilidad de los resultados obtenidos. También en este sentido, los resultados obtenidos han sido verificados con otros procedentes de sistemas de observación radar de satélite, incorporando además a este estudio las implicaciones que el uso conjunto de tecnologías radar y GNSS tendrán en un futuro en la monitorización de deformaciones de la corteza terrestre. ABSTRACT Volcanic activity occurs in many aspects of human activity, and not always in a negative manner. Nonetheless, research into volcanic activity is more likely to be motivated by its danger and risk. There are security reasons that influence the monitoring of volcanic activity in order to guarantee the life and safety of human settlements near volcanic edifices. This thesis defines and implements a monitoring system of movements in the Earth’s crust in the islands of Tenerife and La Palma, where the social impact of an increase (or variation) of volcanic activity is very severe. Aside from the high demographic density of the archipelago, the population increases significantly in different periods throughout the year due to tourism, which represents a major source of revenue for the islands. The population and the tourist centres are mainly spread along the coasts and also along the flanks of the volcanic edifices. Perhaps the preservation of these social and socio-economic structures is the most important reason that justifies monitoring volcanic activity in the Canary Islands. Recently more and more work has been done with the intention of predicting volcanic activity, using new geodesic monitoring systems, since volcanic activity is evident prior to eruption because of a deformation of the Earth’s crust and changes in the force of gravity in the zone where volcanic events will later be recorded. The new devices and sensors that have been developed in recent years in areas such as geodesy, the observation of the Earth from space, and satellite positioning have allowed us to observe and measure the deformation produced in the Earth as well as the changes in the force of gravity before, during, and after the volcanic events occur. The new devices and sensors have changed the geodetic techniques and methodologies that were used previously. The classic methods have been renovated and other newer ones developed that are now vouched for as proven recognised methodologies to be used for volcanic monitoring. Since the end of the 1990s, in the Canary Islands various projects have been developed whose principal aim has been the development of new observation and monitoring techniques on the one hand, and the design of an appropriate volcanic monitoring methodology on the other. The study and development of GNSS techniques for the monitoring of crustal deformations and their velocity field is presented here. To carry out the study, the use of geodetic infrastructure and existing monitoring in the archipelago have been taken into account in order to optimise costs, besides complementing it with new stations for total coverage on both islands. The results obtained in the projects, which are described below, have produced new perspectives in the geodetic monitoring of volcanic activity and new zones of interest which previously were unknown in the environment of the Canary Islands. Special care has been taken with the treatment and propagation of errors during the entire process of observing, measuring, and processing the recorded data. All of this was done in order to quantify the degree of trustworthiness of the results obtained. Also in this sense, the results obtained have been verified with others from satellite radar observation systems, incorporating as well in this study the implications that the joint use of radar technologies and GNSS will have for the future of monitoring deformations in the Earth’s crust.