Adaptive memory hierarchies for next generation tiled microarchitectures

Les últimes dècades el rendiment dels processadors i de les memòries ha millorat a diferent ritme, limitant el rendiment dels processadors i creant el conegut memory gap. Sol·lucionar aquesta diferència de rendiment és un camp d'investigació d'actualitat i que requereix de noves sol·lucions. Una sol·lució a aquest problema són les memòries “cache”, que permeten reduïr l'impacte d'unes latències de memòria creixents i que conformen la jerarquia de memòria. La majoria de d'organitzacions de les “caches” estan dissenyades per a uniprocessadors o multiprcessadors tradicionals. Avui en dia, però, el creixent nombre de transistors disponible per xip ha permès l'aparició de xips multiprocessador (CMPs). Aquests xips tenen diferents propietats i limitacions i per tant requereixen de jerarquies de memòria específiques per tal de gestionar eficientment els recursos disponibles. En aquesta tesi ens hem centrat en millorar el rendiment i la eficiència energètica de la jerarquia de memòria per CMPs, des de les “caches” fins als controladors de memòria. A la primera part d'aquesta tesi, s'han estudiat organitzacions tradicionals per les “caches” com les privades o compartides i s'ha pogut constatar que, tot i que funcionen bé per a algunes aplicacions, un sistema que s'ajustés dinàmicament seria més eficient. Tècniques com el Cooperative Caching (CC) combinen els avantatges de les dues tècniques però requereixen un mecanisme centralitzat de coherència que té un consum energètic molt elevat. És per això que en aquesta tesi es proposa el Distributed Cooperative Caching (DCC), un mecanisme que proporciona coherència en CMPs i aplica el concepte del cooperative caching de forma distribuïda. Mitjançant l'ús de directoris distribuïts s'obté una sol·lució més escalable i que, a més, disposa d'un mecanisme de marcatge més flexible i eficient energèticament. A la segona part, es demostra que les aplicacions fan diferents usos de la “cache” i que si es realitza una distribució de recursos eficient es poden aprofitar els que estan infrautilitzats. Es proposa l'Elastic Cooperative Caching (ElasticCC), una organització capaç de redistribuïr la memòria “cache” dinàmicament segons els requeriments de cada aplicació. Una de les contribucions més importants d'aquesta tècnica és que la reconfiguració es decideix completament a través del maquinari i que tots els mecanismes utilitzats es basen en estructures distribuïdes, permetent una millor escalabilitat. ElasticCC no només és capaç de reparticionar les “caches” segons els requeriments de cada aplicació, sinó que, a més a més, és capaç d'adaptar-se a les diferents fases d'execució de cada una d'elles. La nostra avaluació també demostra que la reconfiguració dinàmica de l'ElasticCC és tant eficient que gairebé proporciona la mateixa taxa de fallades que una configuració amb el doble de memòria.Finalment, la tesi es centra en l'estudi del comportament de les memòries DRAM i els seus controladors en els CMPs. Es demostra que, tot i que els controladors tradicionals funcionen eficientment per uniprocessadors, en CMPs els diferents patrons d'accés obliguen a repensar com estan dissenyats aquests sistemes. S'han presentat múltiples sol·lucions per CMPs però totes elles es veuen limitades per un compromís entre el rendiment global i l'equitat en l'assignació de recursos. En aquesta tesi es proposen els Thread Row Buffers (TRBs), una zona d'emmagatenament extra a les memòries DRAM que permetria guardar files de dades específiques per a cada aplicació. Aquest mecanisme permet proporcionar un accés equitatiu a la memòria sense perjudicar el seu rendiment global. En resum, en aquesta tesi es presenten noves organitzacions per la jerarquia de memòria dels CMPs centrades en la escalabilitat i adaptativitat als requeriments de les aplicacions. Els resultats presentats demostren que les tècniques proposades proporcionen un millor rendiment i eficiència energètica que les millors tècniques existents fins a l'actualitat.Processor performance and memory performance have improved at different rates during the last decades, limiting processor performance and creating the well known "memory gap". Solving this performance difference is an important research field and new solutions must be proposed in order to have better processors in the future. Several solutions exist, such as caches, that reduce the impact of longer memory accesses and conform the system memory hierarchy. However, most of the existing memory hierarchy organizations were designed for single processors or traditional multiprocessors. Nowadays, the increasing number of available transistors has allowed the apparition of chip multiprocessors, which have different constraints and require new ad-hoc memory systems able to efficiently manage memory resources. Therefore, in this thesis we have focused on improving the performance and energy efficiency of the memory hierarchy of chip multiprocessors, ranging from caches to DRAM memories. In the first part of this thesis we have studied traditional cache organizations such as shared or private caches and we have seen that they behave well only for some applications and that an adaptive system would be desirable. State-of-the-art techniques such as Cooperative Caching (CC) take advantage of the benefits of both worlds. This technique, however, requires the usage of a centralized coherence structure and has a high energy consumption. Therefore we propose the Distributed Cooperative Caching (DCC), a mechanism to provide coherence to chip multiprocessors and apply the concept of cooperative caching in a distributed way. Through the usage of distributed directories we obtain a more scalable solution and, in addition, has a more flexible and energy-efficient tag allocation method. We also show that applications make different uses of cache and that an efficient allocation can take advantage of unused resources. We propose Elastic Cooperative Caching (ElasticCC), an adaptive cache organization able to redistribute cache resources dynamically depending on application requirements. One of the most important contributions of this technique is that adaptivity is fully managed by hardware and that all repartitioning mechanisms are based on distributed structures, allowing a better scalability. ElasticCC not only is able to repartition cache sizes to application requirements, but also is able to dynamically adapt to the different execution phases of each thread. Our experimental evaluation also has shown that the cache partitioning provided by ElasticCC is efficient and is almost able to match the off-chip miss rate of a configuration that doubles the cache space. Finally, we focus in the behavior of DRAM memories and memory controllers in chip multiprocessors. Although traditional memory schedulers work well for uniprocessors, we show that new access patterns advocate for a redesign of some parts of DRAM memories. Several organizations exist for multiprocessor DRAM schedulers, however, all of them must trade-off between memory throughput and fairness. We propose Thread Row Buffers, an extended storage area in DRAM memories able to store a data row for each thread. This mechanism enables a fair memory access scheduling without hurting memory throughput. Overall, in this thesis we present new organizations for the memory hierarchy of chip multiprocessors which focus on the scalability and of the proposed structures and adaptivity to application behavior. Results show that the presented techniques provide a better performance and energy-efficiency than existing state-of-the-art solutions

A Mediterranean identity? The activity of the Mediterranean Cities Program

Postprint (published version

The hang air city

Postprint (published version

Lipophilicity in drug design: an overview of lipophilicity descriptors in 3D-QSAR studies

The pharmacophore concept is a fundamental cornerstone in drug discovery, playing a critical role in determining the success of in silico techniques, such as virtual screening and 3D-QSAR studies. The reliability of these approaches is influenced by the quality of the physicochemical descriptors used to characterize the chemical entities. In this context, a pivotal role is exerted by lipophilicity, which is a major contribution to host-guest interaction and ligand binding affinity. Several approaches have been undertaken to account for the descriptive and predictive capabilities of lipophilicity in 3D-QSAR modeling. Recent efforts encode the use of quantum mechanical-based descriptors derived from continuum solvation models, which open novel avenues for gaining insight into structure-activity relationships studies

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued e orts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature

La soledad y el sonido

Sin resume

Screening the antioxidant activity of thermal or non-thermally treated fruit juices by in vitro and in vivo assays

The health benefits of fruit juices have been associated with their high content of antioxidant compounds. Commercial juice has been traditionally heat-processed to destroy microorganisms and enzymes. However, high temperatures induce undesirable changes in the nutritional value of the juice. High-intensity pulsed electric fields (HIPEF) are being studied as an alternative to heat treatments. In addition, in vitro and in vivo methods have been recommended to determine the antioxidant potential of juices in a complementary manner. Thus, the antioxidant activity of untreated, high-intensity pulsed electric fields (HIPEF) or heat-treated fruit juices (tomato, apple, pineapple and orange) was studied using in vitro (TEAC, DPPH, FRAP and Folin-Ciocalteu) and in vivo assays (Saccharomyces cerevisiae). Vitamin C and total phenolic compounds in these juices were determined. The highest antioxidant activities (12.01 mmol of Trolox/L) were obtained through the Folin-Ciocalteu assay in orange juices. The lowest values (0.119 mmol of Trolox/L) were found in apple juice analysed by the FRAP assay. Vitamin C content varied from 10 mg/L (orange juice) to 344 mg/L (orange juice). The highest concentration of total phenolic compounds was determined in orange juice (1238 mg/L), whereas the lowest value was found in tomato juices (149 mg/L). The effect of HIPEF and thermal processing on the antioxidant potential of juices depended on the fruits used to prepare the juices and the antioxidant activity assay conducted. Vitamin C concentration was directly related to the antioxidant activity analysed by Folin-Ciocalteu and FRAP methods and the S. cerevisiae growth rate. S. cerevisiae yeast can be used as a feasible in vivo assay to further determine the antioxidant activity of fruit juices.This study has been carried out with financial support from Universitat de Lleida through a joint Agrotecnio/IRBLleida grant. This work was also supported by the Ministerio de Economia y Competividad (Spain) through the Project BFU2010-17656 and by the Generalitat de Catalunya (2014SGR/1000). Judit Puigpinos thanks University of Lleida for the predoctoral grant

ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins

BACKGROUND: Annotations of completely sequenced genomes reveal that nearly half of the genes identified are of unknown function, and that some belong to uncharacterized gene families. To help resolve such issues, information can be obtained from the comparative analysis of homologous genes in model organisms. RESULTS: While characterizing genes from the retinitis pigmentosa locus RP26 at 2q31-q33, we have identified a new gene, ORMDL1, that belongs to a novel gene family comprising three genes in humans (ORMDL1, ORMDL2 and ORMDL3), and homologs in yeast, microsporidia, plants, Drosophila, urochordates and vertebrates. The human genes are expressed ubiquitously in adult and fetal tissues. The Drosophila ORMDL homolog is also expressed throughout embryonic and larval stages, particularly in ectodermally derived tissues. The ORMDL genes encode transmembrane proteins anchored in the endoplasmic reticulum (ER). Double knockout of the two Saccharomyces cerevisiae homologs leads to decreased growth rate and greater sensitivity to tunicamycin and dithiothreitol. Yeast mutants can be rescued by human ORMDL homologs. CONCLUSIONS: From protein sequence comparisons we have defined a novel gene family, not previously recognized because of the absence of a characterized functional signature. The sequence conservation of this family from yeast to vertebrates, the maintenance of duplicate copies in different lineages, the ubiquitous pattern of expression in human and Drosophila, the partial functional redundancy of the yeast homologs and phenotypic rescue by the human homologs, strongly support functional conservation. Subcellular localization and the response of yeast mutants to specific agents point to the involvement of ORMDL in protein folding in the ER

Nonideal optical response of liquid crystal variable retarders and its impact on their performance as polarization modulators

Liquid crystal variable retarders (LCVRs) will be used for the first time in a space instrument, the Solar Orbiter mission of the European Space Agency, as polarization states analyzers (PSAs). These devices will determine the Stokes parameters of the light coming from the Sun by temporal polarization modulation, using the so-called modulation matrix O. This is a matrix constituted by the first rows of properly selected PSA Mueller matrices. Calibrating a space instrument, in particular, finding O, is a critical point because in a spacecraft there is no possibility of physical access. Due to the huge difficulty in calibrating the complete instruments in all possible scenarios, a more complete calibration of the individual components has been done in ground in order to make extrapolations to obtain O in-flight. Nevertheless, apart from the individual calibrations, the experimental errors and nonideal effects that inhibit the system to reach the designed and theoretical values must be known. In this work, description and study of these effects have been done, focusing on the nonideal effects of the LCVRs and the azimuthal misalignments between the optical components of the PSA during the mechanical assembly. The Mueller matrix of a representative LCVR has been measured and mathematically decomposed by logarithm decomposition, looking for values of circular birefringence and fast axis angle variations as a function of voltage. These effects, in the absence of other nonidealities, affect the polarimetric performance, reducing the polarimetric efficiencies in some cases until 11%. Nevertheless, in this case, they are negligible if compared to the other nonideality studied, which are the azimuthal misalignments between the PSA optical components. The study presented in this work is key to extrapolate the PSA O matrix if the expected instrumental set-point temperatures are not reached in flight and can be used for the design and implementation of other polarimetric instruments