Iterative Compilation in a Non-linear Optimisation Space

This paper investigates the applicability of iterative search techniques in program optimisation. Iterative compilation is usually considered too expensive for general purpose computing but is applicable to embedded applications where the cost is easily amortised over the number of embedded systems produced. This paper presents a case study, where an iterative search algorithm is used to investigate a nonlinear transformation space and find the fastest execution time within a fixed number of evaluations. By using execution time as feedback, it searches a large but restricted transformation space and shows performance improvement over existing approaches. We show that in the case of large transformation spaces, we can achieve within 0.3% of the best possible time by visiting less then 0.25% of the space using a simple algorithm and find the minimum after visiting less than 1% of the space

Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity

gem-Disubstituted N-heterocycles are rarely found in drugs, despite their potential to improve the drug-like properties of small molecule pharmaceuticals. Linezolid, a morpholine heterocycle-containing oxazolidinone antibiotic, exhibits significant side effects associated with human mitochondrial protein synthesis inhibition. We synthesized a gem-disubstituted linezolid analogue that when compared to linezolid, maintains comparable (albeit slightly diminished) activity against bacteria, comparable in vitro physicochemical properties, and a decrease in undesired mitochondrial protein synthesis (MPS) inhibition. This research contributes to the structure-activity-relationship data surrounding oxazolidinone MPS inhibition, and may inspire investigations into the utility of gem-disubstituted N-heterocycles in medicinal chemistry

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Enhanced brain connectivity in math-gifted adolescents: An fMRI study using mental rotation

Mathematical giftedness is a form of intelligence related to enhanced mathematical reasoning that can be tested using a variety of numerical and spatial tasks. A number of neurobiological mechanisms related to exceptional mathematical reasoning ability have been postulated, including enhanced brain connectivity. We aimed to further investigate this possibility by comparing a group of mathematically gifted adolescents with an average math ability control group performing mental rotation of complex three-dimensional block figures. Functional magnetic resonance imaging (fMRI) data were collected and differences in intrahemispheric and interhemispheric connectivity between the groups were assessed using structural equation modeling (SEM). The math-gifted showed heightened intrahemispheric frontoparietal connectivity, as well as enhanced interhemispheric frontal connectivity between the dorsolateral prefrontal and premotor cortex. These enhanced connectivity patterns are consistent with previous studies linking increased activation of the frontal and parietal regions with high fluid intelligence, and may be a unique neural characteristic of the mathematically gifted brain. © 2010 Psychology Pres

Mathematically gifted male adolescents activate a unique brain network during mental rotation

Mental rotation involves the creation and manipulation of internal images, with the later being particularly useful cognitive capacities when applied to high-level mathematical thinking and reasoning. Many neuroimaging studies have demonstrated mental rotation to be mediated primarily by the parietal lobes, particularly on the right side. Here, we use fMRI to show for the first time that when performing 3-dimensional mental rotations, mathematically gifted male adolescents engage a qualitatively different brain network than those of average math ability, one that involves bilateral activation of the parietal lobes and frontal cortex, along with heightened activation of the anterior cingulate. Reliance on the processing characteristics of this uniquely bilateral system and the interplay of these anterior/posterior regions may be contributors to their mathematical precocity

Role of TSG101 in uterine cervix cancer

Objective. TSG101 was first described as a possible tumor suppressor gene in breast cancer. To determine whether TSG101 might play a role in cervical carcinogenesis, we examined a panel of cervical cancer cell lines and primary tumor specimens for transcript abnormalities and mutations in TSG101. Methods. Total RNA was derived from cell line cultures or primary tumor specimens. We performed nested reverse transcription polymerase chain reaction (RT-PCR) with eight overlapping primer sets, followed by single- strand conformational polymorphism (SSCP) analysis, to screen for mutations in the TSG101 open reading frame. Representative normal and shifted SSCP bands were sequenced. To identify abnormal-sized transcripts, we performed RT-PCR with primers flanking the open reading frame followed by gel electrophoresis. Results. Mutational analysis was performed on cDNAs from 20 primary cervical tumors and 8 cervical carcinoma cell lines. Two polymorphisms were identified, neither of which resulted in an altered amino acid sequence. Transcript analysis was performed on a subset of 16 primary cervix tumors and 6 cervix carcinoma cell lines. The wild-type transcript (1228 bp) was the dominant transcript expressed in all samples. A transcript measuring 330 bp was detected in 5 of 6 cell lines and 11 of 16 primary tumor specimens. Conclusion. Our results suggest that mutations in TSG101 rarely occur in carcinomas of the uterine cervix. However, the presence of minor aberrant TSG101 transcripts is a common feature. The relationship between aberrant transcription and carcinogenesis should be further investigated

OCEANS: Optimising compilers for embedded applications

Abstract. This paper presents an overview of the activities carried out within the ESPRIT project OCEANS whose objective is to investigate and develop advanced compiler infrastructure for embedded VLIW pro-cessors. This combines high and low-level optimisation approaches within an iterative framework for compilation.