Many-core bioinformatics platform: development and optimization

Summary This thesis shows the building process of a platform for the execution of bioinformatics algorithms in a massively-parallel environment. The Tile64 microprocessor from Tilera has been used, which is the first commercially available general-purpose many-core microprocessor. It has 64 cores, capable of running a whole standard operating system (a customized Linux version) in each core. Processors integrated in PCI-Express cards have been used, which can be inserted in a standard PC, which pack the processor with 8 GB of RAM and two 10 Gigabit Ethernet connectors. In a first step, the following bioinformatics algorithms have been developed in this platform: i) Needleman-Wunsch (global) and Smith-Waterman (local) pairwise aligners, by the development from scratch of a new wave-front parallel version with a master-worker scheme, as well as its later optimization, to get the most of Tilera’s characteristics; ii) ABySS “de novo” assembler, by porting its open source code and the later parallelization by the adaptation of the original implementation, written for the MPI library to the message passing library available at Tilera; and iii) ClustalW multiple aligner, using the formerly developed pairwise aligners in the first phase of the algorithm. In a second step, a network between these devices has been built, using the available 10G connectors, so constructing a cluster in which the number of available microprocessors can be arbitrarily extended, keeping a unique point of program execution and administration. To achieve this goal, the usual management elements in this kind of systems have been developed, along with a communication library, in order to extend parallelism to the cluster components. Finally, the performance of this network platform has been evaluated; by developing and executing the standard search techniques typically used in heuristic-based alignment algorithms. As main conclusions, the bioinformatics algorithms performance have been remarkably increased by means of an optimized development to achieve a massive parallelization in this new platform. The best results have been obtained with developments from scratch, along with using hybrid-computing techniques. This strategy allows overcoming the limited resources in the card, effectively contributing extra resources from the host computer. These possibilities open new opportunities in nucleic acid and peptide (like proteins) bioinformatics, since it was not possible to apply optimal alignment methods from a mathematical point of view before these developments, being the most usual algorithms based in heuristic approaches.Resumen Esta tesis presenta el proceso de construcción de una plataforma para la ejecución de algoritmos bioinformáticos en un entorno masivamente paralelo. Se ha usado el microprocesador Tile64, del fabricante Tilera, que es el primer microprocesador de propósito general masivamente multi-núcleo disponible comercialmente. Dispone de 64 núcleos capaces de ejecutar un sistema operativo estándar completo (una versión adaptada de Linux) en cada uno de sus núcleos. Se han empleado procesadores integrados en placas PCI-Express, insertables en un PC estándar, que añaden al procesador 8 GB de memoria RAM y dos conectores 10 Gigabit Ethernet. En una primera fase, se han desarrollado sobre esta plataforma los siguientes algoritmos bioinformáticos: i) Alineamientos simples Needleman-Wunsch (global) y Smith-Waterman (local), mediante el desarrollo desde cero de una nueva versión paralelizada, mediante un esquema maestro-trabajadores en frente de onda y su posterior optimización para aprovechar las particularidades de Tilera; ii) Ensamblaje “de novo” ABySS, mediante la migración del código abierto ofrecido por los autores y su paralelización mediante la adaptación de la implementación original, escrita para la biblioteca MPI, a la biblioteca de paso de mensajes disponible en Tilera; y iii) Alineamiento múltiple ClustalW, usando los alineamientos simples desarrollados anteriormente en la primera fase del algoritmo. En una segunda fase, se ha construido una red de estos dispositivos, utilizando los conectores 10G disponibles, según el modelo conocido como “clúster”, de modo que el número de microprocesadores disponibles puede incrementarse a voluntad, manteniendo un único punto de ejecución de programas y de administración. Para conseguirlo se han desarrollado los elementos de gestión habituales en este tipo de sistemas y una biblioteca de comunicaciones para extender el paralelismo a los componentes del “clúster”. Finalmente, se ha evaluado el rendimiento de esta plataforma en red, mediante el desarrollo y ejecución en la misma de las técnicas de búsqueda estándares típicamente utilizadas en algoritmos de alineamiento basados en heurísticos. Como conclusiones principales, estos desarrollos bioinformáticos sobre la nueva plataforma han permitido incrementar el rendimiento de los algoritmos de forma significativa, mediante la paralelización masiva de los mismos. Los mejores resultados se han obtenido cuando se han llevado a cabo desarrollos desde cero, usando además técnicas de computación híbrida. Esta estrategia permite compensar la limitación de recursos en la tarjeta Tilera, usando recursos extra del ordenador en donde se aloja. Estas posibilidades abren nuevas oportunidades en el estudio bioinformático de los ácidos nucleicos y péptidos (como las proteínas), dado que hasta ahora no era posible aplicar métodos de alineamiento óptimos desde el punto de vista matemático, estando basados los algoritmos más habituales en aproximaciones heurísticas

MC64-Cluster: Many-Core CPU Cluster Architecture and Performance Analysis in B-Tree Searches

The MC64-Cluster computer platform was designed, based on many-core CPU microprocessors: Tile64. MC64-Cluster architecture was outlined in terms of both hardware and software, including commands available to manage jobs and provided application programming interfaces to communicate and synchronize tiles, making this system easy to use. Massively, concurrent-searches of keys in B-trees, which are used in many applications, including bioinformatics, were used. Remarkable performance improvements were obtained when the cluster resources were combined with those available in host machine (hybrid or heterogeneous environments). These results were even more outstanding when analyzed in terms of performance-per-watt, highlighting their green-computing advantages. Together with the cluster architecture, they represent the main contributions of this work. To our knowledge, this is the first cluster implementation of this kind being developed

Pilot test for validation of an instrument of Knowledge management in the massive open online context

Knowledge management is a systematic process that deals with looking for, filtering, introducing and using information with the support of information technologies. The objective of using knowledge management depends on the sector that uses it. In companies, it is a value in the balance, in education it is a way to improve the successful of students. The massive open online courses (MOOC) are a topic in which it has been done little researching into the area of knowledge management. In this work, it will be presented a measurement instrument of knowledge management processes on MOOC. The model is based on a previous model used in business who has been adapted to the intercultural, massive and informal context of MOOC. The model was made with the help of an expert panel and its internal consistence was assessing with the Alpha Cronbach technique obtaining general scores over 0.9

Optical coherence tomography in patients with chronic migraine: Literature review and update

Migraine is a chronic disease characterized by unilateral, pulsating, and often moderate-to-severe recurrent episodes of headache with nausea and vomiting. It affects approximately 15% of the general population, yet the underlying pathophysiological mechanisms are not fully understood. Optical coherence tomography (OCT) is a safe and reproducible diagnostic technique that utilizes infrared wavelengths and has a sensitivity of 8-10 µm. It can be used to measure thinning of the retinal nerve fiber layer (RNFL) in some neurological disorders. Although ophthalmologists are often the first specialists to examine patients with migraine, few studies have addressed the involvement of the optic nerve and retino-choroidal structures in this group. We reviewed the literature on the etiological and pathological mechanisms of migraine and the relationship between recurrent constriction of cerebral and retrobulbar vessels and ischemic damage to the optic nerve, retina, and choroid. We also assessed the role of OCT for measuring peripapillary RNFL thickness and macular and choroidal changes in migraine patients. There is considerable evidence of cerebral and retrobulbar vascular involvement in the etiology of migraine. Transitory and recurrent constriction of the retinal and ciliary arteries may cause ischemic damage to the optic nerve, retina, and choroid in patients with migraine. OCT to assess the thickness of the peripapillary RNFL, macula, and choroid might increase our understanding of the pathophysiology of migraine and facilitate diagnosis of retino-choroidal compromise and follow-up of therapy in migraine patients. Future studies should determine the usefulness of OCT findings as a biomarker of migraine

Time lag between metamorphism and crystallization of anatectic granites (Córdoba, Argentina)

SHRIMP and LA-ICP-MS analyses carried out on zircons from the Río de los Sauces granite revealed their metamorphic and igneous nature. The metamorphic zircons yielded an age of 537±4.8 (2σ)Ma that probably predates the onset of the anatexis during the Pampean orogeny. By contrast, the igneous zircons yielded a younger age of 529±6 (2σ)Ma and reflected its crystallization age. These data point to a short time lag of ca. 8Myr between the High Temperature (HT) metamorphic peak and the subsequent crystallization age of the granite. Concordia age of 534±3.8 (2σ)Ma, for both types of zircon populations, can be considered as the mean age of the Pampean HT metamorphism in the Sierras de Córdoba

MC64-ClustalWP2: A Highly-Parallel Hybrid Strategy to Align Multiple Sequences in Many-Core Architectures

We have developed the MC64-ClustalWP2 as a new implementation of the Clustal W algorithm, integrating a novel parallelization strategy and significantly increasing the performance when aligning long sequences in architectures with many cores. It must be stressed that in such a process, the detailed analysis of both the software and hardware features and peculiarities is of paramount importance to reveal key points to exploit and optimize the full potential of parallelism in many-core CPU systems. The new parallelization approach has focused into the most time-consuming stages of this algorithm. In particular, the so-called progressive alignment has drastically improved the performance, due to a fine-grained approach where the forward and backward loops were unrolled and parallelized. Another key approach has been the implementation of the new algorithm in a hybrid-computing system, integrating both an Intel Xeon multi-core CPU and a Tilera Tile64 many-core card. A comparison with other Clustal W implementations reveals the high-performance of the new algorithm and strategy in many-core CPU architectures, in a scenario where the sequences to align are relatively long (more than 10 kb) and, hence, a many-core GPU hardware cannot be used. Thus, the MC64-ClustalWP2 runs multiple alignments more than 18x than the original Clustal W algorithm, and more than 7x than the best x86 parallel implementation to date, being publicly available through a web service. Besides, these developments have been deployed in cost-effective personal computers and should be useful for life-science researchers, including the identification of identities and differences for mutation/polymorphism analyses, biodiversity and evolutionary studies and for the development of molecular markers for paternity testing, germplasm management and protection, to assist breeding, illegal traffic control, fraud prevention and for the protection of the intellectual property (identification/traceability), including the protected designation of origin, among other applications

Trapezius contracture and loss of strength

Musculoskeletal pathology is common in primary care, but not always have a trivial origin. According to the symptoms and comorbidities of the patient, these pathologies have to make us think if is possible to be a guiding symptom of a more severe pathology. That is why we present the case of a young woman with cardiovascular risk factors (hypertension, smoking, obesity and sleep apnea-hypopnea syndrome) with pain at left trapezius and motor and sensory clinical alterations in left upper extremity. These comorbidities have in common their relationship with cerebrovascular pathology so, given the concomitant clinical musculoskeletal, we need to suspect this cause, as was in this case

Time lag between metamorphism and crystallization of anatectic granites (Córdoba, Argentina)

SHRIMP and LA-ICP-MS analyses carried out on zircons from the Río de los Sauces granite revealed their metamorphic and igneous nature. The metamorphic zircons yielded an age of 537±4.8 (2σ)Ma that probably predates the onset of the anatexis during the Pampean orogeny. By contrast, the igneous zircons yielded a younger age of 529±6 (2σ)Ma and reflected its crystallization age. These data point to a short time lag of ca. 8Myr between the High Temperature (HT) metamorphic peak and the subsequent crystallization age of the granite. Concordia age of 534±3.8 (2σ)Ma, for both types of zircon populations, can be considered as the mean age of the Pampean HT metamorphism in the Sierras de Córdoba

Existence of global-in-time solutions to a generalized Dirac-Fock type evolution equation

We consider a generalized Dirac-Fock type evolution equation deduced from no-photon Quantum Electrodynamics, which describes the self-consistent time-evolution of relativistic electrons, the observable ones as well as those filling up the Dirac sea. This equation has been originally introduced by Dirac in 1934 in a simplified form. Since we work in a Hartree-Fock type approximation, the elements describing the physical state of the electrons are infinite rank projectors. Using the Bogoliubov-Dirac-Fock formalism, introduced by Chaix-Iracane ({\it J. Phys. B.}, 22, 3791--3814, 1989), and recently established by Hainzl-Lewin-Sere, we prove the existence of global-in-time solutions of the considered evolution equation.Comment: 12 pages; more explanations added, some final (minor) corrections include