1,449 research outputs found

    Factors in Poverty Alleviation: the Globalization, Growth, Inequality, and Growth Nexus

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    Privacy in the Information Age: The Need for Clarity in the ECPA

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    Two dimensional eye tracking: Sampling rate of forcing function

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    A study was conducted to determine the minimum update rate of a forcing function display required for the operator to approximate the tracking performance obtained on a continuous display. In this study, frequency analysis was used to determine whether there was an associated change in the transfer function characteristics of the operator. It was expected that as the forcing function display update rate was reduced, from 120 to 15 samples per second, the operator's response to the high frequency components of the forcing function would show a decrease in gain, an increase in phase lag, and a decrease in coherence

    Head tracking at large angles from the straight ahead position

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    One of the big advantages of a helmet sight in a high performance aircraft is its off-boresight capability in aiming a fire control system. However, tracking data using a target that is moving rapidly and randomly for an extended period of time is missing. This study is intended to provide data in this area that will be of value to engineers in designing head control systems

    Breaking in and Busting out: Cell-penetrating Peptides and the Endosomal Escape Problem

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    Cell-penetrating peptides (CPPs) have long held great promise for the manipulation of living cells for therapeutic and research purposes. They allow a wide array of biomolecules from large, oligomeric proteins to nucleic acids and small molecules to rapidly and efficiently traverse cytoplasmic membranes. With few exceptions, if a molecule can be associated with a CPP, it can be delivered into a cell. However, a growing realization in the field is that CPP-cargo fusions largely remain trapped in endosomes and are eventually targeted for degradation or recycling rather than released into the cytoplasm or trafficked to a desired subcellular destination. This ‘endosomal escape problem’ has confounded efforts to develop CPP-based delivery methods for drugs, enzymes, plasmids, etc. This review provides a brief history of CPP research and discusses current issues in the field with a primary focus on the endosomal escape problem, for which several promising potential solutions have been developed. Are we on the verge of developing technologies to deliver therapeutics such as siRNA, CRISPR/Cas complexes and others that are currently failing because of an inability to get into cells, or are we just chasing after another promising but unworkable technology? We make the case for optimism

    EFN-4 Functions in LAD-2-mediated Axon Guidance in Caenorhabditis elegans

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    During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for theC. elegansephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with theC. elegansdivergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal

    Helicobacter Pylori Hydrogenase Accessory Protein HypA and Urease Accessory Protein UreG Compete with Each Other for UreE Recognition

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    Background: The gastric pathogen Helicobacter pylori relies on nickel-containing urease and hydrogenase enzymes in order to colonize the host. Incorporation of Ni2+ into urease is essential for the function of the enzyme and requires the action of several accessory proteins, including the hydrogenase accessory proteins HypA and HypB and the urease accessory proteins UreE, UreF, UreG and UreH. Methods: Optical biosensing methods (biolayer interferometry and plasmon surface resonance) were used to screen for interactions between HypA, HypB, UreE and UreG. Results: Using both methods, affinity constants were found to be 5nM and 13nM for HypA–UreE and 8μM and 14μM for UreG-UreE. Neither Zn2+ nor Ni2+ had an effect on the kinetics or stability of the HypA–UreE complex. By contrast, addition of Zn2+, but not Ni2+, altered the kinetics and greatly increased the stability of the UreE–UreG complex, likely due in part to Zn2+-mediated oligomerization of UreE. Finally our results unambiguously show that HypA, UreE and UreG cannot form a heterotrimeric protein complex in vitro; instead, HypA and UreG compete with each other for UreE recognition. General significance: Factors influencing the pathogen\u27\u27s nickel budget are important to understand pathogenesis and for future drug design
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