Do we see what we should see? Describing non-covalent interactions in protein structures including precision

The power of X-ray crystal structure analysis as a technique is to `see where the atoms are'. The results are extensively used by a wide variety of research communities. However, this `seeing where the atoms are' can give a false sense of security unless the precision of the placement of the atoms has been taken into account. Indeed, the presentation of bond distances and angles to a false precision (i.e. to too many decimal places) is commonplace. This article has three themes. Firstly, a basis for a proper representation of protein crystal structure results is detailed and demonstrated with respect to analyses of Protein Data Bank entries. The basis for establishing the precision of placement of each atom in a protein crystal structure is non-trivial. Secondly, a knowledge base harnessing such a descriptor of precision is presented. It is applied here to the case of salt bridges, i.e. ion pairs, in protein structures; this is the most fundamental place to start with such structure-precision representations since salt bridges are one of the tenets of protein structure stability. Ion pairs also play a central role in protein oligomerization, molecular recognition of ligands and substrates, allosteric regulation, domain motion and alpha-helix capping. A new knowledge base, SBPS (Salt Bridges in Protein Structures), takes these structural precisions into account and is the first of its kind. The third theme of the article is to indicate natural extensions of the need for such a description of precision, such as those involving metalloproteins and the determination of the protonation states of ionizable amino acids. Overall, it is also noted that this work and these examples are also relevant to protein three-dimensional structure molecular graphics software.

Preparation and study of magnetic thin film based sub-micron structures

Due to its high Curie temperature of 420K and band structure calculations predicting 100% spin polarisation, Sr2FeMoO6 is a potential candidate for spintronic devices. However, the preparation of good quality thin films has proven to be a non-trivial task. Epitaxial Sr2FeMoO6 thin films were prepared by pulsed laser deposition on different substrates. Differing from previous reports a post-deposition annealing step at low oxygen partial pressure (10-5 mbar) was introduced and enabled the fabrication of reproducible, high quality samples. According to the structural properties of the substrates the crystal structure and morphology of the thin films are modified. The close interrelation between the structural, magnetic and electronic properties of Sr2FeMoO6 was studied. A detailed evaluation of the results allowed to extract valuable information on the microscopic nature of magnetism and charge transport. Smooth films with a mean roughness of about 2 nm have been achieved, which is a pre-requisite for a possible inclusion of this material in future devices. In order to establish device-oriented sub-micron patterning as a standard technique, electron beam lithography and focussed ion beam etching facilities have been put into operation. A detailed characterisation of these systems has been performed. To determine the technological prospects of new spintronics materials, the verification of a high spin polarisation is of vital interest. A popular technique for this task is point contact Andreev reflection (PCAR). Commonly, the charge transport in a transparent metal-superconductor contact of nanometer dimensions is attributed solely to coherent transport. If this condition is not fulfilled, inelastic processes in the constriction have to be considered. PCAR has been applied to Sr2FeMoO6 and the Heusler compound Co2Cr0.6Fe0.4Al. Systematic deviations between measured spectra and the standard models of PCAR have been observed. Therefore existing approaches have been generalised, in order to include the influence of heating. With the extended model the measured data was successfully reproduced but the analysis has revealed grave implications for the determination of spin polarisation, which was found to break down completely in certain cases.

Time-resolved evolution of coherent structures in turbulent channels

El objetivo de esta tesis es estudiar la dinámica de la capa logarítmica de flujos turbulentos de pared. En concreto, proponemos un nuevo modelo estructural utilizando diferentes tipos de estructuras coherentes: sweeps, eyecciones, grupos de vorticidad y streaks. La herramienta utilizada es la simulación numérica directa de canales turbulentos. Desde los primeros trabajos de Theodorsen (1952), las estructuras coherentes han jugado un papel fundamental para entender la organización y dinámica de los flujos turbulentos. A día de hoy, datos procedentes de simulaciones numéricas directas obtenidas en instantes no contiguos permiten estudiar las propiedades fundamentales de las estructuras coherentes tridimensionales desde un punto de vista estadístico. Sin embargo, la dinámica no puede ser entendida en detalle utilizando sólo instantes aislados en el tiempo, sino que es necesario seguir de forma continua las estructuras. Aunque existen algunos estudios sobre la evolución temporal de las estructuras más pequeñas a números de Reynolds moderados, por ejemplo Robinson (1991), todavía no se ha realizado un estudio completo a altos números de Reynolds y para todas las escalas presentes de la capa logarítmica. El objetivo de esta tesis es llevar a cabo dicho análisis. Los problemas más interesantes los encontramos en la región logarítmica, donde residen las cascadas de vorticidad, energía y momento. Existen varios modelos que intentan explicar la organización de los flujos turbulentos en dicha región. Uno de los más extendidos fue propuesto por Adrian et al. (2000) a través de observaciones experimentales y considerando como elemento fundamental paquetes de vórtices con forma de horquilla que actúan de forma cooperativa para generar rampas de bajo momento. Un modelo alternativo fué ideado por del Álamo & Jiménez (2006) utilizando datos numéricos. Basado también en grupos de vorticidad, planteaba un escenario mucho más desorganizado y con estructuras sin forma de horquilla. Aunque los dos modelos son cinemáticamente similares, no lo son desde el punto de vista dinámico, en concreto en lo que se refiere a la importancia que juega la pared en la creación y vida de las estructuras. Otro punto importante aún sin resolver se refiere al modelo de cascada turbulenta propuesto por Kolmogorov (1941b), y su relación con estructuras coherentes medibles en el flujo. Para dar respuesta a las preguntas anteriores, hemos desarrollado un nuevo método que permite seguir estructuras coherentes en el tiempo y lo hemos aplicado a simulaciones numéricas de canales turbulentos con números de Reynolds lo suficientemente altos como para tener un rango de escalas no trivial y con dominios computacionales lo suficientemente grandes como para representar de forma correcta la dinámica de la capa logarítmica. Nuestros esfuerzos se han desarrollado en cuatro pasos. En primer lugar, hemos realizado una campaña de simulaciones numéricas directas a diferentes números de Reynolds y tamaños de cajas para evaluar el efecto del dominio computacional en las estadísticas de primer orden y el espectro. A partir de los resultados obtenidos, hemos concluido que simulaciones con cajas de longitud 2vr y ancho vr veces la semi-altura del canal son lo suficientemente grandes para reproducir correctamente las interacciones entre estructuras coherentes de la capa logarítmica y el resto de escalas. Estas simulaciones son utilizadas como punto de partida en los siguientes análisis. En segundo lugar, las estructuras coherentes correspondientes a regiones con esfuerzos de Reynolds tangenciales intensos (Qs) en un canal turbulento han sido estudiadas extendiendo a tres dimensiones el análisis de cuadrantes, con especial énfasis en la capa logarítmica y la región exterior. Las estructuras coherentes han sido identificadas como regiones contiguas del espacio donde los esfuerzos de Reynolds tangenciales son más intensos que un cierto nivel. Los resultados muestran que los Qs separados de la pared están orientados de forma isótropa y su contribución neta al esfuerzo de Reynolds medio es nula. La mayor contribución la realiza una familia de estructuras de mayor tamaño y autosemejantes cuya parte inferior está muy cerca de la pared (ligada a la pared), con una geometría compleja y dimensión fractal « 2. Estas estructuras tienen una forma similar a una ‘esponja de placas’, en comparación con los grupos de vorticidad que tienen forma de ‘esponja de cuerdas’. Aunque el número de objetos decae al alejarnos de la pared, la fracción de esfuerzos de Reynolds que contienen es independiente de su altura, y gran parte reside en unas pocas estructuras que se extienden más allá del centro del canal, como en las grandes estructuras propuestas por otros autores. Las estructuras dominantes en la capa logarítmica son parejas de sweeps y eyecciones uno al lado del otro y con grupos de vorticidad asociados que comparten las dimensiones y esfuerzos con los remolinos ligados a la pared propuestos por Townsend. En tercer lugar, hemos estudiado la evolución temporal de Qs y grupos de vorticidad usando las simulaciones numéricas directas presentadas anteriormente hasta números de Reynolds ReT = 4200 (Reynolds de fricción). Las estructuras fueron identificadas siguiendo el proceso descrito en el párrafo anterior y después seguidas en el tiempo. A través de la interseción geométrica de estructuras pertenecientes a instantes de tiempo contiguos, hemos creado gratos de conexiones temporales entre todos los objetos y, a partir de ahí, definido ramas primarias y secundarias, de tal forma que cada rama representa la evolución temporal de una estructura coherente. Una vez que las evoluciones están adecuadamente organizadas, proporcionan toda la información necesaria para caracterizar la historia de las estructuras desde su nacimiento hasta su muerte. Los resultados muestran que las estructuras nacen a todas las distancias de la pared, pero con mayor probabilidad cerca de ella, donde la cortadura es más intensa. La mayoría mantienen tamaños pequeños y no viven mucho tiempo, sin embargo, existe una familia de estructuras que crecen lo suficiente como para ligarse a la pared y extenderse a lo largo de la capa logarítmica convirtiéndose en las estructuras observas anteriormente y descritas por Townsend. Estas estructuras son geométricamente autosemejantes con tiempos de vida proporcionales a su tamaño. La mayoría alcanzan tamaños por encima de la escala de Corrsin, y por ello, su dinámica está controlada por la cortadura media. Los resultados también muestran que las eyecciones se alejan de la pared con velocidad media uT (velocidad de fricción) y su base se liga a la pared muy rápidamente al inicio de sus vidas. Por el contrario, los sweeps se mueven hacia la pared con velocidad -uT y se ligan a ella más tarde. En ambos casos, los objetos permanecen ligados a la pared durante 2/3 de sus vidas. En la dirección de la corriente, las estructuras se desplazan a velocidades cercanas a la convección media del flujo y son deformadas por la cortadura. Finalmente, hemos interpretado la cascada turbulenta, no sólo como una forma conceptual de organizar el flujo, sino como un proceso físico en el cual las estructuras coherentes se unen y se rompen. El volumen de una estructura cambia de forma suave, cuando no se une ni rompe, o lo hace de forma repentina en caso contrario. Los procesos de unión y rotura pueden entenderse como una cascada directa (roturas) o inversa (uniones), siguiendo el concepto de cascada de remolinos ideado por Richardson (1920) y Obukhov (1941). El análisis de los datos muestra que las estructuras con tamaños menores a 30η (unidades de Kolmogorov) nunca se unen ni rompen, es decir, no experimentan el proceso de cascada. Por el contrario, aquellas mayores a 100η siempre se rompen o unen al menos una vez en su vida. En estos casos, el volumen total ganado y perdido es una fracción importante del volumen medio de la estructura implicada, con una tendencia ligeramente mayor a romperse (cascada directa) que a unirse (cascade inversa). La mayor parte de interacciones entre ramas se debe a roturas o uniones de fragmentos muy pequeños en la escala de Kolmogorov con estructuras más grandes, aunque el efecto de fragmentos de mayor tamaño no es despreciable. También hemos encontrado que las roturas tienen a ocurrir al final de la vida de la estructura y las uniones al principio. Aunque los resultados para la cascada directa e inversa no son idénticos, son muy simétricos, lo que sugiere un alto grado de reversibilidad en el proceso de cascada. ABSTRACT The purpose of the present thesis is to study the dynamics of the logarithmic layer of wall-bounded turbulent flows. Specifically, to propose a new structural model based on four different coherent structures: sweeps, ejections, clusters of vortices and velocity streaks. The tool used is the direct numerical simulation of time-resolved turbulent channels. Since the first work by Theodorsen (1952), coherent structures have played an important role in the understanding of turbulence organization and its dynamics. Nowadays, data from individual snapshots of direct numerical simulations allow to study the threedimensional statistical properties of those objects, but their dynamics can only be fully understood by tracking them in time. Although the temporal evolution has already been studied for small structures at moderate Reynolds numbers, e.g., Robinson (1991), a temporal analysis of three-dimensional structures spanning from the smallest to the largest scales across the logarithmic layer has yet to be performed and is the goal of the present thesis. The most interesting problems lie in the logarithmic region, which is the seat of cascades of vorticity, energy, and momentum. Different models involving coherent structures have been proposed to represent the organization of wall-bounded turbulent flows in the logarithmic layer. One of the most extended ones was conceived by Adrian et al. (2000) and built on packets of hairpins that grow from the wall and work cooperatively to gen- ´ erate low-momentum ramps. A different view was presented by del Alamo & Jim´enez (2006), who extracted coherent vortical structures from DNSs and proposed a less organized scenario. Although the two models are kinematically fairly similar, they have important dynamical differences, mostly regarding the relevance of the wall. Another open question is whether such a model can be used to explain the cascade process proposed by Kolmogorov (1941b) in terms of coherent structures. The challenge would be to identify coherent structures undergoing a turbulent cascade that can be quantified. To gain a better insight into the previous questions, we have developed a novel method to track coherent structures in time, and used it to characterize the temporal evolutions of eddies in turbulent channels with Reynolds numbers high enough to include a non-trivial range of length scales, and computational domains sufficiently long and wide to reproduce correctly the dynamics of the logarithmic layer. Our efforts have followed four steps. First, we have conducted a campaign of direct numerical simulations of turbulent channels at different Reynolds numbers and box sizes, and assessed the effect of the computational domain in the one-point statistics and spectra. From the results, we have concluded that computational domains with streamwise and spanwise sizes 2vr and vr times the half-height of the channel, respectively, are large enough to accurately capture the dynamical interactions between structures in the logarithmic layer and the rest of the scales. These simulations are used in the subsequent chapters. Second, the three-dimensional structures of intense tangential Reynolds stress in plane turbulent channels (Qs) have been studied by extending the classical quadrant analysis to three dimensions, with emphasis on the logarithmic and outer layers. The eddies are identified as connected regions of intense tangential Reynolds stress. Qs are then classified according to their streamwise and wall-normal fluctuating velocities as inward interactions, outward interactions, sweeps and ejections. It is found that wall-detached Qs are isotropically oriented background stress fluctuations, common to most turbulent flows, and do not contribute to the mean stress. Most of the stress is carried by a selfsimilar family of larger wall-attached Qs, increasingly complex away from the wall, with fractal dimensions « 2. They have shapes similar to ‘sponges of flakes’, while vortex clusters resemble ‘sponges of strings’. Although their number decays away from the wall, the fraction of the stress that they carry is independent of their heights, and a substantial part resides in a few objects extending beyond the centerline, reminiscent of the very large scale motions of several authors. The predominant logarithmic-layer structures are sideby- side pairs of sweeps and ejections, with an associated vortex cluster, and dimensions and stresses similar to Townsend’s conjectured wall-attached eddies. Third, the temporal evolution of Qs and vortex clusters are studied using time-resolved DNS data up to ReT = 4200 (friction Reynolds number). The eddies are identified following the procedure presented above, and then tracked in time. From the geometric intersection of structures in consecutive fields, we have built temporal connection graphs of all the objects, and defined main and secondary branches in a way that each branch represents the temporal evolution of one coherent structure. Once these evolutions are properly organized, they provide the necessary information to characterize eddies from birth to death. The results show that the eddies are born at all distances from the wall, although with higher probability near it, where the shear is strongest. Most of them stay small and do not last for long times. However, there is a family of eddies that become large enough to attach to the wall while they reach into the logarithmic layer, and become the wall-attached structures previously observed in instantaneous flow fields. They are geometrically self-similar, with sizes and lifetimes proportional to their distance from the wall. Most of them achieve lengths well above the Corrsin’ scale, and hence, their dynamics are controlled by the mean shear. Eddies associated with ejections move away from the wall with an average velocity uT (friction velocity), and their base attaches very fast at the beginning of their lives. Conversely, sweeps move towards the wall at -uT, and attach later. In both cases, they remain attached for 2/3 of their lives. In the streamwise direction, eddies are advected and deformed by the local mean velocity. Finally, we interpret the turbulent cascade not only as a way to conceptualize the flow, but as an actual physical process in which coherent structures merge and split. The volume of an eddy can change either smoothly, when they are not merging or splitting, or through sudden changes. The processes of merging and splitting can be thought of as a direct (when splitting) or an inverse (when merging) cascade, following the ideas envisioned by Richardson (1920) and Obukhov (1941). It is observed that there is a minimum length of 30η (Kolmogorov units) above which mergers and splits begin to be important. Moreover, all eddies above 100η split and merge at least once in their lives. In those cases, the total volume gained and lost is a substantial fraction of the average volume of the structure involved, with slightly more splits (direct cascade) than mergers. Most branch interactions are found to be the shedding or absorption of Kolmogorov-scale fragments by larger structures, but more balanced splits or mergers spanning a wide range of scales are also found to be important. The results show that splits are more probable at the end of the life of the eddy, while mergers take place at the beginning of the life. Although the results for the direct and the inverse cascades are not identical, they are found to be very symmetric, which suggests a high degree of reversibility of the cascade process.

Clone Detection in Repositories of Business Process Models

Business process model repositories capture precious knowledge about an organization or a business domain. In many cases, these repositories contain hundreds or even thousands of models and they represent several man-years of effort. Over time, process model repositories tend to accumulate duplicate fragments, as new process models are created by copying and merging fragments from other models. This calls for methods to detect duplicate fragments in process models that can be refactored as separate subprocesses in order to increase readability and maintainability. This paper presents an indexing structure to support the fast detection of clones in large process model repositories. Experiments show that the algorithm scales to repositories with hundreds of models. The experimental results also show that a significant number of non-trivial clones can be found in process model repositories taken from industrial practice.

Clone detection in repositories of business process models

As organizations reach to higher levels of business process management maturity, they often find themselves maintaining repositories of hundreds or even thousands of process models, representing valuable knowledge about their operations. Over time, process model repositories tend to accumulate duplicate fragments (also called clones) as new process models are created or extended by copying and merging fragments from other models. This calls for methods to detect clones in process models, so that these clones can be refactored as separate subprocesses in order to improve maintainability. This paper presents an indexing structure to support the fast detection of clones in large process model repositories. The proposed index is based on a novel combination of a method for process model decomposition (specifically the Refined Process Structure Tree), with established graph canonization and string matching techniques. Experiments show that the algorithm scales to repositories with hundreds of models. The experimental results also show that a significant number of non-trivial clones can be found in process model repositories taken from industrial practice.

Fast detection of exact clones in business process model repositories

As organizations reach higher levels of business process management maturity, they often find themselves maintaining very large process model repositories, representing valuable knowledge about their operations. A common practice within these repositories is to create new process models, or extend existing ones, by copying and merging fragments from other models. We contend that if these duplicate fragments, a.k.a. ex- act clones, can be identified and factored out as shared subprocesses, the repository’s maintainability can be greatly improved. With this purpose in mind, we propose an indexing structure to support fast detection of clones in process model repositories. Moreover, we show how this index can be used to efficiently query a process model repository for fragments. This index, called RPSDAG, is based on a novel combination of a method for process model decomposition (namely the Refined Process Structure Tree), with established graph canonization and string matching techniques. We evaluated the RPSDAG with large process model repositories from industrial practice. The experiments show that a significant number of non-trivial clones can be efficiently found in such repositories, and that fragment queries can be handled efficiently.

A Matlab toolbox for parametric identification of radiation-force models of ships and offshore structures

This article describes a Matlab toolbox for parametric identification of fluid-memory models associated with the radiation forces ships and offshore structures. Radiation forces are a key component of force-to-motion models used in simulators, motion control designs, and also for initial performance evaluation of wave-energy converters. The software described provides tools for preparing non-parmatric data and for identification with automatic model-order detection. The identification problem is considered in the frequency domain.

Efficiency of parallelisation of genetic algorithms in the data analysis context

Most real-life data analysis problems are difficult to solve using exact methods, due to the size of the datasets and the nature of the underlying mechanisms of the system under investigation. As datasets grow even larger, finding the balance between the quality of the approximation and the computing time of the heuristic becomes non-trivial. One solution is to consider parallel methods, and to use the increased computational power to perform a deeper exploration of the solution space in a similar time. It is, however, difficult to estimate a priori whether parallelisation will provide the expected improvement. In this paper we consider a well-known method, genetic algorithms, and evaluate on two distinct problem types the behaviour of the classic and parallel implementations.

Archiving primary data: Solutions for long-term studies

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.

Grad–Shafranov Reconstruction of Magnetic Clouds: Overview and Improvements

The Grad–Shafranov reconstruction is a method of estimating the orientation (invariant axis) and cross section of magnetic flux ropes using the data from a single spacecraft. It can be applied to various magnetic structures such as magnetic clouds (MCs) and flux ropes embedded in the magnetopause and in the solar wind. We develop a number of improvements of this technique and show some examples of the reconstruction procedure of interplanetary coronal mass ejections (ICMEs) observed at 1 AU by the STEREO, Wind, and ACE spacecraft during the minimum following Solar Cycle 23. The analysis is conducted not only for ideal localized ICME events but also for non-trivial cases of magnetic clouds in fast solar wind. The Grad–Shafranov reconstruction gives reasonable results for the sample events, although it possesses certain limitations, which need to be taken into account during the interpretation of the model results.

Generating Efficient Data Movement Code for Heterogeneous Architectures with Distributed-Memory

Programming for parallel architectures that do not have a shared address space is extremely difficult due to the need for explicit communication between memories of different compute devices. A heterogeneous system with CPUs and multiple GPUs, or a distributed-memory cluster are examples of such systems. Past works that try to automate data movement for distributed-memory architectures can lead to excessive redundant communication. In this paper, we propose an automatic data movement scheme that minimizes the volume of communication between compute devices in heterogeneous and distributed-memory systems. We show that by partitioning data dependences in a particular non-trivial way, one can generate data movement code that results in the minimum volume for a vast majority of cases. The techniques are applicable to any sequence of affine loop nests and works on top of any choice of loop transformations, parallelization, and computation placement. The data movement code generated minimizes the volume of communication for a particular configuration of these. We use a combination of powerful static analyses relying on the polyhedral compiler framework and lightweight runtime routines they generate, to build a source-to-source transformation tool that automatically generates communication code. We demonstrate that the tool is scalable and leads to substantial gains in efficiency. On a heterogeneous system, the communication volume is reduced by a factor of 11X to 83X over state-of-the-art, translating into a mean execution time speedup of 1.53X. On a distributed-memory cluster, our scheme reduces the communication volume by a factor of 1.4X to 63.5X over state-of-the-art, resulting in a mean speedup of 1.55X. In addition, our scheme yields a mean speedup of 2.19X over hand-optimized UPC codes.

Bottle and Pumpcast Data from the 1988 Black Sea Expedition

This report contains inorganic nutrient chemistry, sulfide and oxygen data collected during cruises 2 through 5 of the 1988 Black Sea Oceanographic Expedition aboard the R/V Knorr. Continuous nutrient and sulfide data were obtained in the upper 375 m using a pumped profiling system. Discrete samples were collected from rosette-CTD casts. The corresponding physical oceanographic data have been presented by White et al. (1989). Although all of the data reported has been edited at least twice, errors may remain. We encourage queries and plan to distribute updates on electronic media if there are any non-trivial changes.

An artificial immune system for data analysis

Timmis J and Neal M J. An artificial immune system for data analysis. In Proceedings of 3rd international workshop on information processing in cells and tissues (IPCAT), Indianapolis, U.S.A., 1999.

Data mining the yeast genome in a lazy functional language

Clare, A. and King R.D. (2003) Data mining the yeast genome in a lazy functional language. In Practical Aspects of Declarative Languages (PADL'03) (won Best/Most Practical Paper award).

Gene Network Inference using Machine Learning and Graph Algorithms on Big Biomedical Data

Thesis (Master's)--University of Washington, 2016-03