José Ignacio Gómez

Polyhedral parallel code generation for CUDA

This article addresses the compilation of a sequential program for parallel execution on a modern GPU. To this end, we present a novel source-to-source compiler called PPCG. PPCG singles out for its ability to accelerate computations from any static control loop nest, generating multiple CUDA kernels when necessary. We introduce a multilevel tiling strategy and a code generation scheme for the parallelization and locality optimization of imperfectly nested loops, managing memory and exposing concurrency according to the constraints of modern GPUs. We evaluate our algorithms and tool on the entire PolyBench suite.

Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver

Dietary restriction (DR) lowers mitochondrial reactive oxygen species (ROS) generation and oxidative damage and increases maximum longevity in rodents. Protein restriction (PR) or methionine restriction (MetR), but not lipid or carbohydrate restriction, also cause those kinds of changes. However, previous experiments of MetR were performed only at 80% MetR, and substituting dietary methionine with glutamate in the diet. In order to clarify if MetR can be responsible for the lowered ROS production and oxidative stress induced by standard (40%) DR, Wistar rats were subjected to 40% or 80% MetR without changing other dietary components. It was found that both 40% and 80% MetR decrease mitochondrial ROS generation and percent free radical leak in rat liver mitochondria, similarly to what has been previously observed in 40% PR and 40% DR. The concentration of complexes I and III, apoptosis inducing factor, oxidative damage to mitochondrial DNA, five different markers of protein oxidation, glycoxidation or lipoxidation and fatty acid unsaturation were also lowered. The results show that 40% isocaloric MetR is enough to decrease ROS production and oxidative stress in rat liver. This suggests that the lowered intake of methionine is responsible for the decrease in oxidative stress observed in DR.

Effects of fasting on oxidative stress in rat liver mitochondria

While moderate caloric restriction has beneficial effects on animal health state, fasting may be harmful. The present investigation was designed to test how fasting affects oxidative stress, and to find out whether the effects are opposite to those previously found in caloric restriction studies. We have focused on one of the main determinants of aging rate: the rate of mitochondrial free radical generation. Different parameters related to lipid and protein oxidative damage were also analyzed. Liver mitochondria from rats subjected to 72 h of fasting leaked more electrons per unit of O2 consumed at complex III, than mitochondria from ad libitum fed rats. This increased leak led to a higher free radical generation under state 3 respiration using succinate as substrate. Regarding lipids, fasting altered fatty acid composition of hepatic membranes, increasing the double bond and the peroxidizability indexes. In accordance with this, we observed that hepatic membranes from the fasted animals were more sensitive to lipid peroxidation. Hepatic protein oxidative damage was also increased in fasted rats. Thus, the levels of oxidative modifications, produced either indirectly by reactive carbonyl compounds (Nepsilon- malondialdehyde-lysine), or directly through amino acid oxidation (glutamic and aminoadipic semialdehydes) were elevated due to the fasting treatment in both liver tissue and liver mitochondria. The current study shows that severe food deprivation increases oxidative stress in rat liver, at least in part, by increasing mitochondrial free radical generation during state 3 respiration and by increasing the sensitivity of hepatic membranes to oxidative damage, suggesting that fasting and caloric restriction have different effects on liver mitochondrial oxidative stress.

Forty Percent Methionine Restriction Decreases Mitochondrial Oxygen Radical Production and Leak at Complex I During Forward Electron Flow and Lowers Oxidative Damage to Proteins and Mitochondrial DNA in Rat Kidney and Brain Mitochondria

Eighty percent dietary methionine restriction (MetR) in rodents (without calorie restriction), like dietary restriction (DR), increases maximum longevity and strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative stress. Eighty percent MetR also lowers the degree of membrane fatty acid unsaturation in rat liver. Mitochondrial ROS generation and the degree of fatty acid unsaturation are the only two known factors linking oxidative stress with longevity in vertebrates. However, it is unknown whether 40% MetR, the relevant methionine restriction degree to clarify the mechanisms of action of standard (40%) DR can reproduce these effects in mitochondria from vital tissues of strong relevance for aging. Here we study the effect of 40% MetR on ROS production and oxidative stress in rat brain and kidney mitochondria. Male Wistar rats were fed during 7 weeks semipurified diets differing only in their methionine content: control or 40% MetR diets. It was found that 40% MetR decreases mitochondrial ROS production and percent free radical leak (by 62-71%) at complex I during forward (but not during reverse) electron flow in both brain and kidney mitochondria, increases the oxidative phosphorylation capacity of brain mitochondria, lowers oxidative damage to kidney mitochondrial DNA, and decreases specific markers of mitochondrial protein oxidation, lipoxidation, and glycoxidation in both tissues. Forty percent MetR also decreased the amount of respiratory complexes I, III, and IV and apoptosis-inducing factor (AIF) in brain mitochondria and complex IV in kidney mitochondria, without changing the degree of mitochondrial membrane fatty acid unsaturation. Forty percent MetR, differing from 80% MetR, did not inhibit the increase in rat body weight. These changes are very similar to the ones previously found during dietary and protein restriction in rats. We conclude that methionine is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in DR.

Effect of 8.5% and 25% caloric restriction on mitochondrial free radical production and oxidative stress in rat liver

Previous studies have consistently shown that 40% caloric restriction (CR) decreases the rate of mitochondrial ROS production and steady-state levels of markers of oxidative damage to macromolecules including mitochondrial DNA. However, few investigations have studied whether these changes also occur in lower CR regimes. This is of potential interest since moderate levels of dietary restriction are more practicable for humans. In this investigation male Wistar rats were subjected to 8.5% and 25% caloric restriction. Neither 8.5% nor 25% CR changed mitochondrial ROS production, oxygen consumption or mtDNA oxidative damage in rat liver mitochondria. However, both 8.5% and 25% CR significantly decreased the five different markers of protein oxidation, glycoxidation and lipoxidation measured, aminoadipic and glutamic semialdehyde, carboxyethyl-lysine, carboxymethyl-lysine, and malondialdehyde-lysine. The fatty acid composition of liver mitochondria was also affected and led to a moderate decrease in the degree of membrane unsaturation in both 8.5% and 25% CR. While 8.5% CR only affected complex I concentration (which was decreased), 25% CR decreased complexes I and IV and increased complexes II and III of the respiratory chain. Apoptosis-inducing factor (AIF) significantly decreased in 25% CR but not in 8.5% CR. The results show that moderate levels of caloric restriction can have beneficial effects including decreases in oxidative protein modification and a lower sensitivity of membranes to lipid peroxidation, in association with a reprogramming of the respiratory chain complexes and AIF content.

kNN query processing in metric spaces using GPUs

Information retrieval from large databases is becoming crucial for many applications in different fields such as content searching in multimedia objects, text retrieval or computational biology. These databases are usually indexed off-line to enable an acceleration of on-line searches. Furthermore, the available parallelism has been exploited using clusters to improve query throughput. Recently some authors have proposed the use of Graphic Processing Units (GPUs) to accelerate bruteforce searching algorithms for metric-space databases. In this work we improve existing GPU brute-force implementations and explore the viability of GPUs to accelerate indexing techniques. This exploration includes an interesting discussion about the performance of both bruteforce and indexing-based algorithms that takes into account the intrinsic dimensionality of the element of the database.

Mitochondrial DNA sequences are present inside nuclear DNA in rat tissues and increase with age.

Mitochondrial DNA (mtDNA) mutations increase with age. However, the number of cells with predominantly mutated mtDNA is small in old animals. Here a new hypothesis is proposed: mtDNA fragments may insert into nuclear DNA contributing to aging and related diseases by alterations in the nucleus. Real-time PCR quantification shows that sequences of cytochrome oxidase III and 16S rRNA from mtDNA are present in highly purified nuclei from liver and brain in young and old rats. The sequences of these insertions revealed that they contain single nucleotide polymorphisms identical to those present in mtDNA of the same animal. Interestingly, the amount of mitochondrial sequences in nuclear DNA increases with age in both tissues. In situ hybridization of mtDNA to nuclear DNA confirms the presence of mtDNA sequences inside nuclear DNA in rat hepatocytes. Bone marrow metaphase cells from both young and old rats show mtDNA at centromeric regions in 20 out of the 2n=40 chromosomes. Consequently, mitochondria can be a major trigger of aging but the final target could also be the nucleus.

SDRAM-Energy-Aware Memory Allocation for Dynamic Multi-Media Applications on Multi-Processor Platforms

Heterogeneous multi-processors platforms are an interesting option to satisfy the computational performance of dynamic multi-media applications at a reasonable energy cost. Today, almost no support exists to energy-efficiently manage the data of a multi-threaded application on these platforms. In this paper we show that the assignment of data of dynamically created/deleted tasks to the shared memory has a large impact on the energy consumption. We present two dynamic memory allocators which solve the bank assignment problem for shared multi-banked SDRAM memories. Both allocators assign the tasksý data to the available SDRAM banks such that the number of page-misses is reduced. We have measured large energy savings with these allocators compared to existing dynamic memory allocators for several task-sets based on MediaBench[5].

Methionine and homocysteine modulate the rate of ROS generation of isolated mitochondria in vitro

Dietary methionine restriction and supplementation in mammals have beneficial (antiaging) and detrimental effects respectively, which have been related to chronic modifications in the rate of mitochondrial ROS generation. However it is not known if methionine or its metabolites can have, in addition, direct effects on the rate of mitochondrial ROS production. This is studied here for the methionine cycle metabolites S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine and methionine itself in isolated rat liver, kidney, heart, and brain mitochondria. The results show that methionine increases ROS production in liver and kidney mitochondria, homocysteine increases it in kidney and decreases it in the other three organs, and SAM and SAH have no effects. The variations in ROS production are localized at complexes I or III. These changes add to previously described chronic effects of methionine restriction and supplementation in vivo.

Cysteine dietary supplementation reverses the decrease in mitochondrial ROS production at complex I induced by methionine restriction

It has been described that dietary cysteine reverses many of the beneficial changes induced by methionine restriction in aging rodents. In this investigation male Wistar rats were subjected to diets low in methionine, supplemented with cysteine, or simultaneously low in methionine and supplemented with cysteine. The results obtained in liver showed that cysteine supplementation reverses the decrease in mitochondrial ROS generation induced by methionine restriction at complex I. Methionine restriction also decreased various markers of oxidative and non-oxidative stress on mitochondrial proteins which were not reversed by cysteine. Instead, cysteine supplementation also lowered protein damage in association with decreases in mTOR activation. The results of the present study add the decrease in mitochondrial ROS production to the various beneficial changes induced by methionine restriction that are reversed by cysteine dietary supplementation.