156 research outputs found

    Liveness-based garbage collection

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    Liveness-Based Garbage Collection for Lazy Languages

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    We consider the problem of reducing the memory required to run lazy first-order functional programs. Our approach is to analyze programs for liveness of heap-allocated data. The result of the analysis is used to preserve only live data---a subset of reachable data---during garbage collection. The result is an increase in the garbage reclaimed and a reduction in the peak memory requirement of programs. While this technique has already been shown to yield benefits for eager first-order languages, the lack of a statically determinable execution order and the presence of closures pose new challenges for lazy languages. These require changes both in the liveness analysis itself and in the design of the garbage collector. To show the effectiveness of our method, we implemented a copying collector that uses the results of the liveness analysis to preserve live objects, both evaluated (i.e., in WHNF) and closures. Our experiments confirm that for programs running with a liveness-based garbage collector, there is a significant decrease in peak memory requirements. In addition, a sizable reduction in the number of collections ensures that in spite of using a more complex garbage collector, the execution times of programs running with liveness and reachability-based collectors remain comparable

    Anti-A1Leb: a mind boggler

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    Formation of Nano-Bio-Complex as Nanomaterials Dispersed in a Biological Solution for Understanding Nanobiological Interactions

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    Information on how cells interface with nanomaterials in biological environments has important implications for the practice of nanomedicine and safety consideration of nanomaterials. However, our current understanding of nanobiological interactions is still very limited. Here, we report the direct observation of nanomaterial bio-complex formation (other than protein corona) from nanomaterials dispersed in biologically relevant solutions. We observed highly selective binding of the components of cell culture medium and phosphate buffered saline to ZnO and CuO nanoparticles, independent of protein molecules. Our discoveries may provide new insights into the understanding of how cells interact with nanomaterials

    PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer

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    Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN- loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies

    Attaching DNA to Nanoceria: Regulating Oxidase Activity and Fluorescence Quenching

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Applied Materials and Interfaces copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Pautler, R., Kelly, E. Y., Huang, P.-J. J., Cao, J., Liu, B., & Liu, J. (2013). Attaching DNA to Nanoceria: Regulating Oxidase Activity and Fluorescence Quenching. ACS Applied Materials & Interfaces, 5(15), 6820–6825. https://doi.org/10.1021/am4018863Cerium oxide nanoparticles (nanoceria) have recently emerged as a nanozyme with oxidase activity. In this work, we present a few important interfacial properties of nanoceria. First, the surface charge of nanoceria can be controlled not only by adjusting pH but also by adsorption of simple inorganic anions. Adsorption of phosphate and citrate gives negatively charged surface over a broad pH range. Second, nanoceria adsorbs DNA via the DNA phosphate backbone in a sequence-independent manner; DNA adsorption inhibits its oxidase activity. Other anionic polymers display much weaker inhibition effects. Adsorption of simple inorganic phosphate does not have the inhibition effect. Third, nanoceria is a quencher for many fluorophores. These discoveries provide an important understanding for further use of nanoceria in biosensor development, materials science, and nanotechnology.University of Waterloo || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

    Immunomodulation by Different Types of N-Oxides in the Hemocytes of the Marine Bivalve Mytilus galloprovincialis

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    The potential toxicity of engineered nanoparticles (NPs) for humans and the environment represents an emerging issue. Since the aquatic environment represents the ultimate sink for NP deposition, the development of suitable assays is needed to evaluate the potential impact of NPs on aquatic biota. The immune system is a sensitive target for NPs, and conservation of innate immunity represents an useful basis for studying common biological responses to NPs. Suspension-feeding invertebrates, such as bivalves, are particularly at risk to NP exposure, since they have extremely developed systems for uptake of nano and microscale particles integral to intracellular digestion and cellular immunity. Evaluation of the effects of NPs on functional parameters of bivalve immunocytes, the hemocytes, may help understanding the major toxic mechanisms and modes of actions that could be relevant for different NP types in aquatic organisms.In this work, a battery of assays was applied to the hemocytes of the marine bivalve Mytilus galloprovincialis to compare the in vitro effects of different n-oxides (n-TiO2, n-SiO2, n-ZnO, n-CeO2) chosen on the basis of their commercial and environmental relevance. Physico-chemical characterization of both primary particles and NP suspensions in artificial sea water-ASW was performed. Hemocyte lysosomal and mitochondrial parameters, oxyradical and nitric oxide production, phagocytic activity, as well as NP uptake, were evaluated. The results show that different n-oxides rapidly elicited differential responses hemocytes in relation to their chemical properties, concentration, behavior in sea water, and interactions with subcellular compartments. These represent the most extensive data so far available on the effects of NPs in the cells of aquatic organisms. The results indicate that Mytilus hemocytes can be utilized as a suitable model for screening the potential effects of NPs in the cells of aquatic invertebrates, and may provide a basis for future experimental work for designing environmentally safer nanomaterials
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