490 research outputs found

    Utilization of alkyne bioconjugations to modulate protein function

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    The ability to introduce or modify protein function has widespread application to multiple scientific disciplines. The introduction of unique unnatural amino acids represents an excellent mechanism to incorporate new functionality; however, this approach is limited by ability of the translational machinery to recognize and incorporate the chemical moiety. To overcome this potential limitation, we aimed to exploit the functionality of existing unnatural amino acids to perform bioorthogonal reactions to introduce the desired protein modification, altering its function. Specifically, via the introduction of a terminal alkyne containing unnatural amino acid, we demonstrated chemically programmable protein modification through the Glaser-Hay coupling to other terminal alkynes, altering the function of a protein. In a proof-of-concept experiment, this approach has been utilized to modify the fluorescence spectrum of green fluorescent protein. (C) 2016 Elsevier Ltd. All rights reserved

    Territorial Tactics: The Socio-spatial Significance of Private Policing Strategies in Cape Town

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    This paper analyses the policing strategies of private security companies operating in urban space. An existing literature has considered the variety of ways that territory becomes of fundamental importance in the work of public police forces. However, this paper examines territory in the context of private security companies. Drawing on empirical research in Cape Town, it examines how demarcated territories become key subjects in private policing. Private security companies are responsible for a relatively small section of the city, while in contrast the public police ultimately have to see city space as a whole. Hence, private policing strategy becomes one of displacement, especially of so-called undesirables yielding a patchworked public space associated with private enclaves of consumption. The conclusions signal the historical resonances and comparative implications of these political-legal-security dynamics. © 2013 Urban Studies Journal Limited

    Simple piezoelectric-actuated mirror with 180 kHz servo bandwidth

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    We present a high bandwidth piezoelectric-actuated mirror for length stabilization of an optical cavity. The actuator displays a transfer function with a flat amplitude response and greater than 135^\circ phase margin up to 200 kHz, allowing a 180 kHz unity gain frequency to be achieved in a closed servo loop. To the best of our knowledge, this actuator has achieved the largest servo bandwidth for a piezoelectric transducer (PZT). The actuator should be very useful in a wide variety of applications requiring precision control of optical lengths, including laser frequency stabilization, optical interferometers, and optical communications

    Exascale Deep Learning to Accelerate Cancer Research

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    Deep learning, through the use of neural networks, has demonstrated remarkable ability to automate many routine tasks when presented with sufficient data for training. The neural network architecture (e.g. number of layers, types of layers, connections between layers, etc.) plays a critical role in determining what, if anything, the neural network is able to learn from the training data. The trend for neural network architectures, especially those trained on ImageNet, has been to grow ever deeper and more complex. The result has been ever increasing accuracy on benchmark datasets with the cost of increased computational demands. In this paper we demonstrate that neural network architectures can be automatically generated, tailored for a specific application, with dual objectives: accuracy of prediction and speed of prediction. Using MENNDL--an HPC-enabled software stack for neural architecture search--we generate a neural network with comparable accuracy to state-of-the-art networks on a cancer pathology dataset that is also 16×16\times faster at inference. The speedup in inference is necessary because of the volume and velocity of cancer pathology data; specifically, the previous state-of-the-art networks are too slow for individual researchers without access to HPC systems to keep pace with the rate of data generation. Our new model enables researchers with modest computational resources to analyze newly generated data faster than it is collected.Comment: Submitted to IEEE Big Dat

    A Complex Regulatory Network Coordinating Cell Cycles During C. elegans Development Is Revealed by a Genome-Wide RNAi Screen

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    The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development

    Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

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    Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

    Characterizing genomic alterations in cancer by complementary functional associations.

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    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

    Enantiomerically selective vapochromic sensing

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    a b s t r a c t The double salt materials platinum(II)tetrakis-R-␤-methylphenethylisocyanide tetracyanoplatinate(II) (R-1) and platinum(II)tetrakis-S-␤-methylphenethylisocyanide tetracyanoplatinate(II) (S-1) have been synthesized with highly enantiomerically pure isocyanide ligands. The vapochromic behavior of R-1 and S-1 has been studied in the presence of a chiral probe vapor to determine if enantiomerically selective sensing is possible with these materials. The wavelength of maximum emission values ( max ) for solidstate vapoluminescence spectra of R-1 and S-1 in the presence of enriched R-and S-2-butanol vapor differ by approximately 10 nm while the max values for R-1 and S-1 under nitrogen are nearly identical. Principal component analysis has been performed on datasets that consist of a series of vapoluminescence spectra of R-1 and S-1 as a function of the R/S-2-butanol ratio. Plots of principal component one versus R/S-2-butanol ratio show mirror image trends for R-1 relative to S-1. While care must be taken to control water vapor and monitor R-1 and S-1 for possible decomposition, the reported results nevertheless show that R-1 and S-1 are capable of enantiomerically selective vapochromic sensing
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