808 research outputs found

    Conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding.

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    Journal ArticleDifferent isoforms of the full-length protein kinase A (PKA) regulatory subunit homodimer (R2) and the catalytic (C) subunit-bound holoenzyme (R2C2) have very different global structures despite similar molecular weights and domain organization within their primary sequences. To date, it has been the linker sequence between the R subunit dimerization/docking domain and cAMP-binding domain A that has been implicated in modulating domain interactions to give rise to these differences in global structure. The small angle solution scattering data presented here for three different isoforms of PKA heterodimer (deltaR-C) complexes reveal a role for another conformationally dynamic sequence in modulating inter-subunit and domain interactions, the C helix that connects the cAMP-binding domains A and B of the R subunit. The deltaR-C heterodimer complexes studied here were each formed with a monomeric N-terminal deletion mutant of the R subunit (deltaR) that contains the inhibitor sequence and both cAMP-binding domains. The scattering data show that type IIalpha and type IIbeta deltaR-C heterodimers are relatively compact and globular, with the C subunit contacting the inhibitor sequence and both cAMP-binding domains. In contrast, the type Ialpha heterodimer is significantly more extended, with the C subunit interacting with the inhibitor sequence and cAMP-binding domain A, whereas domain B extends out such that its surface is almost completely solvent exposed. These data implicate the C helix of RIalpha in modulating isoform-specific interdomain communication in the PKA holoenzyme, adding another layer of structural complexity to our understanding of signaling dynamics in this multisubunit, multidomain protein kinase

    Retroactive Liability Under the Superfund: Time to Settle the Issue

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    This Article addresses the need for a legislative solution to the issue of retroactive liability under CERCLA. Before suggestion a legislative solution, the authors examine the history of CERCLA. The examination is followed with an analysis of the reasoning applied in the original Olin decision, how courts reacted to this decision, and an analysis of its reversal in Olin II. After examining the ongoing debate in Congress, the authors conclude by suggesting a legislative solution and calling for legislation affirming CERCLA retroactive liability

    Imaging Studies of photodamage and self-healing in disperse orange 11 dye-doped PMMA

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    We report on optical imaging studies of self-healing after laser-induced photodamage in disperse orange 11 dye doped into poly(methyl methacrylate) (PMMA) polymer. In particular, the high spatial-contrast image of the damage track made by a line focus pump laser allows the recovery rates to be measured as a function of burn dose using the relationship between transverse distance and pump intensity profile. The time evolution of the damaged population results in an intensity-independent time constant of {\tau} = 490\pm23 min, in agreement with independent measurements of the time evolution of amplified spontaneous emission. Also observed is a damage threshold above which the material does not fully recover.Comment: 5 pages, 8 figure

    Communications of the Lunar and Planetary Laboratory, volume 8, part 3

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    Infrared photography, mapping, and orbit calculation of natural satellites, comets, and planets in solar syste

    What’s on your keyboard? A systematic review of the contamination of peripheral computer devices in healthcare settings

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    Objective To determine the extent and type of microbial contamination of computer peripheral devices used in healthcare settings, evaluate the effectiveness of interventions to reduce contamination of these devices and establish the risk of patient and healthcare worker infection from contaminated devices. Design Systematic review Methods We searched four online databases: MEDLINE, CINAHL, Embase and Scopus for articles reporting primary data collection on contamination of computer-related equipment (including keyboards, mice, laptops and tablets) and/or studies demonstrating the effectiveness of a disinfection technique. Pooling of contamination rates was conducted where possible, and narrative synthesis was used to describe the rates of device contamination, types of bacterial and viral contamination, effectiveness of interventions and any associations between device contamination and human infections. Results Of the 4432 records identified, a total of 75 studies involving 2804 computer devices were included. Of these, 50 studies reported contamination of computer-related hardware, and 25 also measured the effects of a decontamination intervention. The overall proportion of contamination ranged from 24% to 100%. The most common microbial contaminants were skin commensals, but also included potential pathogens including methicillin-resistantStaphylococcus aureus, Clostridiumdifficile, vancomycin-resistantenterococci and Escherichia coli. Interventions demonstrating effective decontamination included wipes/pads using isopropyl alcohol, quaternary ammonium, chlorhexidine or dipotassium peroxodisulfate, ultraviolet light emitting devices, enhanced cleaning protocols and chlorine/bleach products. However, results were inconsistent, and there was insufficient data to demonstrate comparative effectiveness. We found little evidence on the link between device contamination and patient/healthcare worker colonisation or infection

    Helium, Oxygen, Proton, and Electron (HOPE) Mass Spectrometer for the Radiation Belt Storm Probes Mission

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    The HOPE mass spectrometer of the Radiation Belt Storm Probes (RBSP) mission (renamed the Van Allen Probes) is designed to measure the in situ plasma ion and electron fluxes over 4π sr at each RBSP spacecraft within the terrestrial radiation belts. The scientific goal is to understand the underlying physical processes that govern the radiation belt structure and dynamics. Spectral measurements for both ions and electrons are acquired over 1 eV to 50 keV in 36 log-spaced steps at an energy resolution ΔE FWHM/E≈15 %. The dominant ion species (H+, He+, and O+) of the magnetosphere are identified using foil-based time-of-flight (TOF) mass spectrometry with channel electron multiplier (CEM) detectors. Angular measurements are derived using five polar pixels coplanar with the spacecraft spin axis, and up to 16 azimuthal bins are acquired for each polar pixel over time as the spacecraft spins. Ion and electron measurements are acquired on alternate spacecraft spins. HOPE incorporates several new methods to minimize and monitor the background induced by penetrating particles in the harsh environment of the radiation belts. The absolute efficiencies of detection are continuously monitored, enabling precise, quantitative measurements of electron and ion fluxes and ion species abundances throughout the mission. We describe the engineering approaches for plasma measurements in the radiation belts and present summaries of HOPE measurement strategy and performance

    Cover Crop Effect on Subsequent Wheat Yield in the Central Great Plains

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    Crop production systems in the water-limited environment of the semiarid central Great Plains may not have potential to profitably use cover crops because of lowered subsequent wheat (Triticum asestivum L.) yields following the cover crop. Mixtures have reportedly shown less yield-reducing effects on subsequent crops than single-species plantings. This study was conducted to determine winter wheat yields following both mixtures and single-species plantings of spring-planted cover crops. The study was conducted at Akron, CO, and Sidney, NE, during the 2012–2013 and 2013–2014 wheat growing seasons under both rainfed and irrigated conditions. Precipitation storage efficiency before wheat planting, wheat water use, biomass, and yield were measured and water use efficiency and harvest index were calculated for wheat following four single-species cover crops (flax [Linum usitatissimum L.], oat [Avena sativa L.], pea [Pisum sativum ssp. arvense L. Poir], rapeseed [Brassica napus L.]), a 10-species mixture, and a fallow treatment with proso millet (Panicum miliaceum L.) residue. There was an average 10% reduction in wheat yield following a cover crop compared with following fallow, regardless of whether the cover crop was grown in a mixture or in a single-species planting. Yield reductions were greater under drier conditions. The slope of the wheat water use–yield relationship was not significantly different for wheat following the mixture (11.80 kg ha–1 mm–1) than for wheat following single-species plantings (12.32–13.57 kg ha–1 mm–1). The greater expense associated with a cover crop mixture compared with a single species is not justified

    Temperature-modulated solution-based synthesis of copper oxide nanostructures for glucose sensing

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    Glucose sensors are widely applied in society as an effective way to diagnose and control diabetes by monitoring the blood glucose level. With advantages in stability and efficiency in glucose detection, non-enzymatic glucose sensors are gradually replacing their enzymatic counterparts and copper(ii) oxide (CuO) is a leading material. However, previous work extensively shows that even if the synthesis of CuO nanostructures is performed under nominally similar conditions, entirely different nanostructured products are obtained, resulting in varying physical and chemical properties of the final product, thereby leading to a differing performance in glucose detection. This work investigates the temperature dependence of a wet chemical precipitation synthesis for CuO nanostructures with the resulting samples showing selectivity for glucose in electrochemical tests. X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) demonstrate that all products are predominantly CuO, with some contribution from Cu(OH)2 and other surface species varying across synthesis temperatures. The most important change with increasing synthesis temperature is that the overall nanostructure size changes and the morphology shifts from nanoneedles to nanoparticles between 65 and 70 °C. This work helps to understand the critical relationship between synthesis temperature and final nanostructure and can explain the seemingly random nanostructures observed in the literature. The variations are key to controlling sensor performance and ultimately offering further development in copper oxide-based glucose sensors

    The dawn of the liquid biopsy in the fight against cancer

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    ABSTRACT Cancer is a molecular disease associated with alterations in the genome, which, thanks to the highly improved sensitivity of mutation detection techniques, can be identified in cell-free DNA (cfDNA) circulating in blood, a method also called liquid biopsy. This is a non-invasive alternative to surgical biopsy and has the potential of revealing the molecular signature of tumors to aid in the individualization of treatments. In this review, we focus on cfDNA analysis, its advantages, and clinical applications employing genomic tools (NGS and dPCR) particularly in the field of oncology, and highlight its valuable contributions to early detection, prognosis, and prediction of treatment response
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