Lattice-based scheduling for multi-FPGA systems

Accelerators are becoming increasingly prevalent in distributed computation. FPGAs have been shown to be fast and power efficient for particular tasks, yet scheduling on FPGA-based multi-accelerator systems is challenging when workloads vary significantly in granularity in terms of task size and/or number of computational units required. We present a novel approach for dynamically scheduling tasks on networked multi-FPGA systems which maintains high performance, even in the presence of irregular tasks. Our topological ranking-based scheduling allows realistic irregular workloads to be processed while maintaining a significantly higher level of performance than existing schedulers.Postprin

Graduate entry to medicine: widening psychological diversity

At Nottingham University more than 95% of entrants to the traditional 5-year medical course are school leavers. Since 2003 we have admitted graduate entrants (GEM) to a shortened (4-year) course to 'widen access to students from more disadvantaged backgrounds'. We have recently shown that the GEM course widens academic and socio-demographic diversity of the medical student population. This study explored whether GEM students also bring psychological diversity and whether this could be beneficial. We studied: a) 217 and 96 applicants to the Nottingham 5- and 4-year courses respectively, applying in the 2002-3 UCAS cycle, and, b) 246 school leavers starting the 5-year course and 39 graduate entrants to the 4-year course in October 2003. The psychological profiles of the two groups of applicants and two groups of entrants were compared using their performance in the Goldberg 'Big 5' Personality test, the Personal Qualities Assessment (PQA; measuring interpersonal traits and interpersonal values), and the Lovibond and Lovibond measure of depression, anxiety and stress. For the comparison of the Entrants we excluded the 33 school leavers and seven graduates who took the tests as Applicants. Statistical analyses were undertaken using SPSS software (version 16.0). Graduate applicants compared to school leaver applicants were significantly more conscientious, more confident, more self controlled, more communitarian in moral orientation and less anxious. Only one of these differences was preserved in the entrants with graduates being less anxious. However, the graduate entrants were significantly less empathetic and conscientious than the school leavers. This study has shown that school leaver and graduate entrants to medical school differ in some psychological characteristics. However, if confirmed in other studies and if they were manifest in the extreme, not all the traits brought by graduates would be desirable for someone aiming for a medical career

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

INTRODUCTION: Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic–sedative agent employed today and is nontoxic to humans at high levels (50 μg/ml). Clinically relevant concentrations of propofol (3 to 8 μg/ml; 20 to 50 μM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA). METHODS: The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells. RESULTS: At low concentrations (25 μM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells. CONCLUSION: These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer

Fatty Acid and Peptide Profiles in Plasma Membrane and Membrane Rafts of PUFA Supplemented RAW264.7 Macrophages

The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers

Antifungal Activity of Microbial Secondary Metabolites

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi

Interprovincial migration, regional development and state policy in China, 1985-2010

Internal migration in China occurs as a result of both market forces and government interventions. This paper investigates how indicators of migration have changed over the past quarter of a century using data from successive censuses, with particular attention given to the roles of regional economic development and national policy and the effects of age and education on spatial patterns of migration. The results show a surge in migration throughout the period, an increasing concentration of migration destinations and an improvement of migration efficiency prior to 2000, but a decreased focusing of migration during the first decade of the twenty-first century. Widening regional disparity has been responsible for a sharp increase of migration from the interior to the coast, and different national economic growth poles emerged as major migration destinations at different stages of economic reforms. The analyses of age- and education-specific migration flows indicate that young adults were more mobile and more sensitive than older cohorts to interregional economic differentials, and that educated migrants were more concentrated than less-educated migrants since knowledge-based industries were more concentrated than labour-intensive industries. Our findings suggest that massive eastward migration induced by unbalanced economic development and relaxed migration restrictions still persisted in the 2000s, and that the State's recent efforts to alleviate regional inequalities were far from achieving equilibrium in the migration system

Identifying candidate genes affecting developmental time in Drosophila melanogaster: pervasive pleiotropy and gene-by-environment interaction

<p>Abstract</p> <p>Background</p> <p>Understanding the genetic architecture of ecologically relevant adaptive traits requires the contribution of developmental and evolutionary biology. The time to reach the age of reproduction is a complex life history trait commonly known as developmental time. In particular, in holometabolous insects that occupy ephemeral habitats, like fruit flies, the impact of developmental time on fitness is further exaggerated. The present work is one of the first systematic studies of the genetic basis of developmental time, in which we also evaluate the impact of environmental variation on the expression of the trait.</p> <p>Results</p> <p>We analyzed 179 co-isogenic single <it>P[GT1]-</it>element insertion lines of <it>Drosophila melanogaster </it>to identify novel genes affecting developmental time in flies reared at 25°C. Sixty percent of the lines showed a heterochronic phenotype, suggesting that a large number of genes affect this trait. Mutant lines for the genes <it>Merlin </it>and <it>Karl </it>showed the most extreme phenotypes exhibiting a developmental time reduction and increase, respectively, of over 2 days and 4 days relative to the control (a co-isogenic <it>P</it>-element insertion free line). In addition, a subset of 42 lines selected at random from the initial set of 179 lines was screened at 17°C. Interestingly, the gene-by-environment interaction accounted for 52% of total phenotypic variance. Plastic reaction norms were found for a large number of developmental time candidate genes.</p> <p>Conclusion</p> <p>We identified components of several integrated time-dependent pathways affecting egg-to-adult developmental time in <it>Drosophila</it>. At the same time, we also show that many heterochronic phenotypes may arise from changes in genes involved in several developmental mechanisms that do not explicitly control the timing of specific events. We also demonstrate that many developmental time genes have pleiotropic effects on several adult traits and that the action of most of them is sensitive to temperature during development. Taken together, our results stress the need to take into account the effect of environmental variation and the dynamics of gene interactions on the genetic architecture of this complex life-history trait.</p

Alteration of EGFR Spatiotemporal Dynamics Suppresses Signal Transduction

The epidermal growth factor receptor (EGFR), which regulates cell growth and survival, is integral to colon tumorigenesis. Lipid rafts play a role in regulating EGFR signaling, and docosahexaenoic acid (DHA) is known to perturb membrane domain organization through changes in lipid rafts. Therefore, we investigated the mechanistic link between EGFR function and DHA. Membrane incorporation of DHA into immortalized colonocytes altered the lateral organization of EGFR. DHA additionally increased EGFR phosphorylation but paradoxically suppressed downstream signaling. Assessment of the EGFR-Ras-ERK1/2 signaling cascade identified Ras GTP binding as the locus of the DHA-induced disruption of signal transduction. DHA also antagonized EGFR signaling capacity by increasing receptor internalization and degradation. DHA suppressed cell proliferation in an EGFR-dependent manner, but cell proliferation could be partially rescued by expression of constitutively active Ras. Feeding chronically-inflamed, carcinogen-injected C57BL/6 mice a fish oil containing diet enriched in DHA recapitulated the effects on the EGFR signaling axis observed in cell culture and additionally suppressed tumor formation. We conclude that DHA-induced alteration in both the lateral and subcellular localization of EGFR culminates in the suppression of EGFR downstream signal transduction, which has implications for the molecular basis of colon cancer prevention by DHA

Complex I-Associated Hydrogen Peroxide Production Is Decreased and Electron Transport Chain Enzyme Activities Are Altered in n-3 Enriched fat-1 Mice

The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I