1,571 research outputs found

    Eternal God: Divine Atemporality in Thomas Aquinas

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    The recent trend among many philosophers of religion has been to interpret divine eternity as an everlasting temporality in which an omnitemporal God exists in and throughout the whole of time. This is in contrast to the classical account of divine eternity as atemporal, immutable existence. In this paper, Aquinas' use of Boethius's definition of eternity as “the whole, perfect, and simultaneous possession of endless life” is analyzed and explained in contradistinction to Aristotle's definition of time. This analysis is then used to respond to Nicholas Wolterstroff's argument in "God Everlasting" that God's knowledge of temporal events infects God with temporality and mutability. The argument concludes by introducing an important distinction between absolute simultaneity and temporal simultaneity, which allows us to hold God is omniscient because he is absolutely simultaneous with all events but is not temporally simultaneous with any event

    Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis

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    AbstractMethionine at position 184 of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) was changed to valine, isoleucine, threonine, or alanine in an HIV-1-based vector. The vectors were analyzed for replication capacity and for resistance to the nucleoside analog 2′,3′-dideoxy-3′thiacytidine (3TC) using a single-cycle assay. Viruses containing the valine or isoleucine mutations were highly resistant to 3TC and replicated almost as well as the wild-type virus. The virus containing the threonine mutation was resistant to 3TC, but replicated about 30% as well as the wild-type. The alanine mutation conferred partial resistance to 3TC, but replicated poorly. The amounts of viral DNA synthesized decreased in 3TC-treated cells when the cells were infected with wild-type virus and the M184A mutant. The effect of these mutations on the generation of the ends of the linear viral DNA was determined using the sequence of the 2-LTR circle junctions. The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT

    Assessing the invertebrate fauna trajectories in remediation sites of Winstone Aggregates Hunua quarry in Auckland

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    This study monitored the invertebrates in restoration plantings in the Winstone Aggregates Hunua Quarry. This was to assess the re-establishment of invertebrates in the restoration planting sites and compare them with unplanted control and mature sites. This study follows on from a baseline study carried out in 2014-2015 measuring the restoration trajectory of invertebrates in the Winstone Aggregate Hunua quarry site. A range of entomological monitoring techniques were used and found that dung beetles, millipedes, foliage moths, leaf litter moths and some mite species increased in numbers from the control sites through to the mature sites, while ants, rove beetles, grass moths, some carabid beetles, and worms showed a downwards trend from the mature sites to the control sites. Further monitoring of invertebrates in the restoration area should be carried out

    Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials

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    Background: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy. Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE). Findings: All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted. Interpretation: Despite a universal ADA response post-pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile. Fund: BioMarin Pharmaceutical Inc. Keywords: Enzyme replacement therapy, Antidrug antibody, Circulating immune complex, Hypersensitivity, Phenylalanin

    Ferroelectricity in Perovskitelike NaCaF3 Predicted Ab Initio

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    The ability of zero-stress simulations, using Gordon-Kim pair potentials, to describe the structures and transformations of known fluoride-based perovskites is demonstrated for the case of KCaF3. When K+ is replaced by Na+ a new ferroelectric crystal isomorphous with LiNbO3 is predicted. The equivalent relationships of the ferroelectric lithium niobate structure with the perovskite and antiperovskite structures are examined. A polarization of 21 jµC/cm2 at room temperature and a transition temperature of 550 K are predicted for NaCaF3. Surface effects are examined in simulations of a 1080-ion cluster

    Double diffusion, shear instabilities, and heat impacts of a pacific summer water intrusion in the Beaufort Sea

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    © The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Fine, E., MacKinnon, J., Alford, M., Middleton, L., Taylor, J., Mickett, J., Cole, S., Couto, N., Boyer, A., & Peacock, T. Double diffusion, shear instabilities, and heat impacts of a pacific summer water intrusion in the Beaufort Sea. Journal of Physical Oceanography, 52(2), (2022): 189–203, https://doi.org/10.1175/jpo-d-21-0074.1.Pacific Summer Water eddies and intrusions transport heat and salt from boundary regions into the western Arctic basin. Here we examine concurrent effects of lateral stirring and vertical mixing using microstructure data collected within a Pacific Summer Water intrusion with a length scale of ∼20 km. This intrusion was characterized by complex thermohaline structure in which warm Pacific Summer Water interleaved in alternating layers of O(1) m thickness with cooler water, due to lateral stirring and intrusive processes. Along interfaces between warm/salty and cold/freshwater masses, the density ratio was favorable to double-diffusive processes. The rate of dissipation of turbulent kinetic energy (ε) was elevated along the interleaving surfaces, with values up to 3 × 10−8 W kg−1 compared to background ε of less than 10−9 W kg−1. Based on the distribution of ε as a function of density ratio Rρ, we conclude that double-diffusive convection is largely responsible for the elevated ε observed over the survey. The lateral processes that created the layered thermohaline structure resulted in vertical thermohaline gradients susceptible to double-diffusive convection, resulting in upward vertical heat fluxes. Bulk vertical heat fluxes above the intrusion are estimated in the range of 0.2–1 W m−2, with the localized flux above the uppermost warm layer elevated to 2–10 W m−2. Lateral fluxes are much larger, estimated between 1000 and 5000 W m−2, and set an overall decay rate for the intrusion of 1–5 years.This work was supported by ONR Grant N00014-16-1-2378 and NSF Grants PLR 14-56705 and PLR-1303791, NSF Graduate Research Fellowship Grant DGE-1650112, as well as by the Postdoctoral Scholar Program at Woods Hole Oceanographic Institution, with funding provided by the Weston Howland Jr. Postdoctoral Scholarship

    Formulation, Casting, and Evaluation of Paraffin-Based Solid Fuels Containing Energetic and Novel Additives for Hybrid Rockets

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    This investigation studied the inclusion of various additives to paraffin wax for use in a hybrid rocket motor. Some of the paraffin-based fuels were doped with various percentages of LiAlH4 (up to 10%). Addition of LiAlH4 at 10% was found to increase regression rates between 7 - 10% over baseline paraffin through tests in a gaseous oxygen hybrid rocket motor. Mass burn rates for paraffin grains with 10% LiAlH4 were also higher than those of the baseline paraffin. RDX was also cast into a paraffin sample via a novel casting process which involved dissolving RDX into dimethylformamide (DMF) solvent and then drawing a vacuum on the mixture of paraffin and RDX/DMF in order to evaporate out the DMF. It was found that although all DMF was removed, the process was not conducive to generating small RDX particles. The slow boiling generated an inhomogeneous mixture of paraffin and RDX. It is likely that superheating the DMF to cause rapid boiling would likely reduce RDX particle sizes. In addition to paraffin/LiAlH4 grains, multi-walled carbon nanotubes (MWNT) were cast in paraffin for testing in a hybrid rocket motor, and assorted samples containing a range of MWNT percentages in paraffin were imaged using SEM. The fuel samples showed good distribution of MWNT in the paraffin matrix, but the MWNT were often agglomerated, indicating that a change to the sonication and mixing processes were required to achieve better uniformity and debundled MWNT. Fuel grains with MWNT fuel grains had slightly lower regression rate, likely due to the increased thermal conductivity to the fuel subsurface, reducing the burning surface temperature

    An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis

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    Establishment of angiogenic circuits that orchestrate blood vessel development and remodeling requires an exquisite balance between the activities of pro- and antiangiogenic factors. However, the logic that permits complex signal integration by vascular endothelium is poorly understood. We demonstrate that a “neuropeptide,” neurokinin-B (NK-B), reversibly inhibits endothelial cell vascular network assembly and opposes angiogenesis in the chicken chorioallantoic membrane. Disruption of endogenous NK-B signaling promoted angiogenesis. Mechanistic analyses defined a multicomponent pathway in which NK-B signaling converges upon cellular processes essential for angiogenesis. NK-B−mediated ablation of Ca2+ oscillations and elevation of 3′–5′ cyclic adenosine monophosphate (cAMP) reduced cellular proliferation, migration, and vascular endothelial growth factor receptor expression and induced the antiangiogenic protein calreticulin. Whereas NK-B initiated certain responses, other activities required additional stimuli that increase cAMP. Although NK-B is a neurotransmitter/ neuromodulator and NK-B overexpression characterizes the pregnancy-associated disorder preeclampsia, NK-B had not been linked to vascular remodeling. These results establish a conserved mechanism in which NK-B instigates multiple activities that collectively oppose vascular remodeling

    Viloxazine in the Treatment of Attention Deficit Hyperactivity Disorder

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    Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Over the past twenty years, research on the disease and its characteristics and treatment options has grown exponentially. The first-line pharmacologic treatment of ADHD is stimulants, which have a response rate of ~70%. With the support of four phase 3 studies involving more than 1,000 pediatric patients 6–17 years old, the FDA has approved the non-stimulant, serotonin-norepinephrine modulating agent (SNMA) viloxazine in an extended-release capsule (viloxazine ER) for treatment of ADHD in children aged 6–17. Viloxazine modulates serotonergic activity as a selective 5-HT22B receptor antagonist and 5-HT2C receptor agonist and moderately inhibits norepinephrine transporter (NET), thus blocking the reuptake of norepinephrine. A phase 2 study by Johnson et al. found that once-daily dosing of viloxazine ER in 200, 300, or 400 mg dosages in children with ADHD for eight weeks resulted in a statistically significant reduction of ADHD-RS-IV total score. A post hoc analysis of data from four phase 3, randomized, placebo-controlled, double-blind, three-arm, clinical trials by Faraone et al. found that early response to viloxazine treatment, defined as a change in ADHD-RS-5 total score at week 2, best predicted the treatment response at week 6 [75% positive predictive power (PPP), 75% sensitivity]. Proper treatment of the symptoms and comorbidities associated with ADHD is crucial in improving a patient\u27s quality of life, cognitive function, and overall therapeutic outcomes. Viloxazine\u27s mechanism of action, clinical effects, and limited side effect profile point toward the drug\u27s relevance in the treatment of ADHD

    Trafficking

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    In cities the world over we are able to determine stability in daily existence, to identify with our social spaces, because modes of transport have become essential components of subjective autonomy. But would it not be just as accurate to say that in transit modern life puts the self in abeyance? I argue that the ways we allow ourselves to be moved around in ‘traffic space’ creates a passivity that renders almost invisible the complex mechanics of movement, which we only become alert to at the moment of breakdown, precisely when they become a threat to autonomy. Our trafficking, I conclude, has an almost narcotic effect, rendering us immobile against the continual movements that constitute urban life, one that also magnifies out of all proportion the accidents or aberrations that sometimes disturb our traffic space, making it seem as if we may easily descend into an uncontrollable chaos
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