A methodology pruning the search space of six compiler transformations by addressing them together as one problem and by exploiting the hardware architecture details

Today’s compilers have a plethora of optimizations-transformations to choose from, and the correct choice, order as well parameters of transformations have a significant/large impact on performance; choosing the correct order and parameters of optimizations has been a long standing problem in compilation research, which until now remains unsolved; the separate sub-problems optimization gives a different schedule/binary for each sub-problem and these schedules cannot coexist, as by refining one degrades the other. Researchers try to solve this problem by using iterative compilation techniques but the search space is so big that it cannot be searched even by using modern supercomputers. Moreover, compiler transformations do not take into account the hardware architecture details and data reuse in an efficient way. In this paper, a new iterative compilation methodology is presented which reduces the search space of six compiler transformations by addressing the above problems; the search space is reduced by many orders of magnitude and thus an efficient solution is now capable to be found. The transformations are the following: loop tiling (including the number of the levels of tiling), loop unroll, register allocation, scalar replacement, loop interchange and data array layouts. The search space is reduced (a) by addressing the aforementioned transformations together as one problem and not separately, (b) by taking into account the custom hardware architecture details (e.g., cache size and associativity) and algorithm characteristics (e.g., data reuse). The proposed methodology has been evaluated over iterative compilation and gcc/icc compilers, on both embedded and general purpose processors; it achieves significant performance gains at many orders of magnitude lower compilation time

Growth of infants born to HIV-infected women, when fed a biologically acidified starter formula with and without probiotics

Objectives: To compare the growth of HIV-exposed uninfected infants fed a biologically acidified milk formula with or without probiotics (Bifidobacterium lactis) during the first six months of life, with control infants fed a standard starter formula. Design: Multi-centre, double-blinded randomised controlled trial. Setting: Infants born to HIV-infected women delivering at one of three academic hospitals in Johannesburg, South Africa. Subjects: Consenting HIV-positive women, who had previously decided not to breast-feed, were randomised to receive one of three milk formulas for their newborn infants. Outcome measures: Comparisons of growth parameters through the first four months of life were made between infants fed the acidified formula without probiotics and those fed the control formula (“acidification effect”), and between infants fed the acidified formulas with and without added probiotics (“probiotic effect”). Results: Of 131 randomised infants, 33 (25%) did not complete the study and 13 (10%) were HIV infected, leaving 85 infants available for analysis. Infants receiving the acidified formula with probiotics had more rapid head growth (p=0.04) and showed a trend towards more rapid weight gain (p=0.06) over the first four months of life than the infants receiving the acidified formula without probiotics. No other significant differences between the feeding groups were demonstrated. Conclusions: Infants in all study groups grew well, with increased head growth and a trend towards increased weight gain for those receiving probiotics. There were no differences in morbidity between the three study groups and no evidence of adverse effects of the study formulas. SAJCN Vol. 21 (1) 2008: pp. 28-3

Growth of infants born to HIV-positive mothers fed a whey-adapted acidified starter formula with prebiotics and nucleotides

Objectives: The objectives of this study were to evaluate whether infants born to known HIV-positive mothers, but who were not themselves infected with HIV and who were fed a chemically acidified starter formula with prebiotics with or without nucleotides during their first six months, displayed growth rates equal to uninfected infants fed a chemically acidified starter formula without prebiotics or nucleotides.Design: The design was a multi-centre, double-blinded randomised controlled trial.Setting: The study was carried out in four academic hospitals, three in Johannesburg and one in Cape Town, South Africa.Subjects and intervention: The subjects were newborn infants born to consenting HIV-positive women who had previously decided not to breast feed. The infants were randomised to receive one of three milk formulas. The intervention comprised chemically acidified formula without prebiotics or nucleotides, with prebiotics only, or with prebiotics and nucleotides.Outcome measures: The outcome measures were the growth parameters through the first six months of life.Results: Of the 150 randomised infants, 50 did not complete the study and 16 (12.8% of those tested) were infected with HIV, leaving 84 infants available for analysis. All three formulas were tolerated well, with no differences in growth parameters seen with the addition of prebiotics and nucleotides. The growth rates of the study infants up to the age of six months were very good, showing an increase in Z-scores from negative values at the time of enrolment in the first week after birth to around zero for length and > 0.5 for weight.Conclusions: The three chemically acidified formulas were tolerated well and resulted in good growth over the first six months of life. No benefits were seen with the addition of prebiotics or nucleotides. The growth rates were similar to those found in previous studies of ours on biologically acidified formulas. The chemical acidification of infant formulas appears to be a realistic alternative to biological acidification should an acidified formula be required.Keywords: milk formula; acidification; probiotics; nucleotides; infant growt

A Bayesian method for evaluating and discovering disease loci associations

Background: A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed Bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multi-locus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need. Methodology/Findings: We introduce the Bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a Bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found. Conclusions/Significance: We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we conclude that the BNPP is a promising method for discovering disease loci associations. © 2011 Jiang et al

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A

Since cyclosporin A (CsA) is an immuno-suppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3,7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1 + (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1 + DR + cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1 + DR + ), were also reduced after CsA, epidermal non-Langerhans CD1 - DR + cells (macrophages, activated T cells, DR - keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1 + DR + Langerhans cells/non-Langerhans CD1 - DR + epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1 - DR + cells while leaving LC relatively intact in the epidermis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47242/1/403_2004_Article_BF00431054.pd

Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study

<p>Abstract</p> <p>Background</p> <p>DNA-methyltransferase-3B (DNMT3B), which plays a role in DNA methylation, is usually aberrant expression involved in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation in several cancers, thereby modulating the susceptibility to cancer.</p> <p>Methods</p> <p>DNMT3B -579G>T genotypes and -149C>T were determined by PCR-RFLP and sequencing in 137 colorectal cancer patients and 308 controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed colorectal cancer. The association between two SNPs of the <it>DNMT3B </it>promoter and the risk of the development of colorectal cancer was analyzed in a population of Chinese.</p> <p>Results</p> <p>The allele frequency of -149C >T among patients and controls was 0.73% versus 0.65%, respectively. The allele frequency of -597G>T for patients and controls was 6.57% versus 11.53%, respectively. Individuals with at least one -149C>T allele were no at a significantly increase risk of colorectal cancer compared with those having a -149TT genotype. However, Individuals with at least one 579G>T allele were decreased risk of colorectal cancer compared with those having a -579TT genotype.</p> <p>Conclusion</p> <p>The relative distribution of -149C>T <it>DNMT3B </it>SNPs among a Chinese population can not be used as a stratification marker to predict an individual's susceptibility to colorectal cancer. However, the DNMT3B -579G>T polymorphism may contribute to the genetic susceptibility to colorectal cancer.</p

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al