798 research outputs found

    More Than a Wing and a Prayer: Government Indemnification of the Commercial Space Launch Industry

    Get PDF
    Using rockets to launch communications satellites and other spacecraft poses risks to the uninvolved public, including persons and property under the flight path of the launch vehicle. The federal government plays a pivotal technical role during the actual launch by carrying out certain risk-related procedures, thus causing third-party risk to be jointly produced by the company and the government. In addition, under the Commercial Space Launch Act, the government partially indemnifies commercial launch companies for third-party damages. We compare the indemnification policy to optimal liability rules under public-private co-production of risk. Under modest assumptions, shared liability created by the indemnification rules decreases the incentive of both parties to take care relative to the optimum. If care were observable, it would be preferable for the government to fully indemnify companies that take due care. The role of the government as an agent for third parties may qualify these findings.government indemnification, liability, insurance, space transportation

    More Than a Wing and a Prayer: Government Indemnification of the Commercial Space Launch Industry

    Get PDF
    Using rockets to launch communications satellites and other spacecraft poses risks to the uninvolved public, including persons and property under the flight path of the launch vehicle. The federal government plays a pivotal technical role during the actual launch by carrying out certain risk-related procedures, thus causing third-party risk to be jointly produced by the company and the government. In addition, under the Commercial Space Launch Act, the government partially indemnifies commercial launch companies for third-party damages. We compare the indemnification policy to optimal liability rules under public-private co-production of risk. Under modest assumptions, shared liability created by the indemnification rules decreases the incentive of both parties to take care relative to the optimum. If care were observable, it would be preferable for the government to fully indemnify companies that take due care. The role of the government as an agent for third parties may qualify these findings.government indemnification, liability, insurance, space transportation

    The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

    Get PDF
    Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

    On the cyclically fully commutative elements of Coxeter groups

    Get PDF
    Let W be an arbitrary Coxeter group. If two elements have expressions that are cyclic shifts of each other (as words), then they are conjugate (as group elements) in W. We say that w is cyclically fully commutative (CFC) if every cyclic shift of any reduced expression for w is fully commutative (i.e., avoids long braid relations). These generalize Coxeter elements in that their reduced expressions can be described combinatorially by acyclic directed graphs, and cyclically shifting corresponds to source-to-sink conversions. In this paper, we explore the combinatorics of the CFC elements and enumerate them in all Coxeter groups. Additionally, we characterize precisely which CFC elements have the property that powers of them remain fully commutative, via the presence of a simple combinatorial feature called a band. This allows us to give necessary and sufficient conditions for a CFC element w to be logarithmic, that is, ℓ(wk)=k⋅ℓ(w) for all k≥1, for a large class of Coxeter groups that includes all affine Weyl groups and simply laced Coxeter groups. Finally, we give a simple non-CFC element that fails to be logarithmic under these conditions

    Enzymatic Characterization and Inhibition of the Nuclear Variant of Human O-GlcNAcase

    Get PDF
    Increasing cellular O-GlcNAc levels through pharmacological inhibition of O-GlcNAcase, the enzyme responsible for removal of the O-GlcNAc post-translational modification, is being increasingly used to aid in discerning the roles played by this form of intracellular glycosylation. Interestingly, two forms of O-GlcNAcase have been studied; a full-length isoform that is better characterized, and a shorter nuclear-localized variant, arising from failure to splice out one intron, which has not been as well characterized. Given the increasing use of O-GlcNAcase inhibitors as research tools, we felt that a clear understanding of how these inhibitors affect both isoforms of O-GlcNAcase is important for proper interpretation of studies making use of these inhibitors in cell culture and in vivo. Here we describe an enzymatic characterization of the nuclear variant of human O-GlcNAcase. We find that this short nuclear variant of O-GlcNAcase, which has the identical catalytic domain as the full-length enzyme, has similar trends in a pH-rate profile and Taft linear free energy analysis as the full-length enzyme. These findings strongly suggest that both enzymes use broadly similar transition states. Consistent with this interpretation, the short isoform is potently inhibited by several previously described inhibitors of full-length O-GlcNAcase including PUGNAc, NAG-thiazoline, and the selective O-GlcNAcase inhibitor NButGT. These findings contrast with earlier studies and suggest that studies using O-GlcNAcase inhibitors in cultured cells or in vivo can be interpreted with the knowledge that both these forms of O-GlcNAcase are inhibited when present

    Disinfection of Swine Wastewater Using Chlorine, Ultraviolet Light and Ozone

    Get PDF
    Veterinary antibiotics are widely used at concentrated animal feeding operations (CAFOs) to prevent disease and promote growth of livestock. However, the majority of antibiotics are excreted from animals in urine, feces, and manure. Consequently, the lagoons used to store these wastes can act as reservoirs of antibiotics and antibiotic-resistant bacteria. There is currently no regulation or control of these systems to prevent the spread of these bacteria and their genes for antibiotic resistance into other environments. This study was conducted to determine the disinfection potential of chlorine, ultraviolet light and ozone against swine lagoon bacteria. Results indicate that a chlorine dose of 30 mg/L could achieve a 2.2-3.4 log bacteria reduction in lagoon samples. However, increasing the dose of chlorine did not significantly enhance the disinfection activity due to the presence of chlorine-resistant bacteria. The chlorine resistant bacteria were identified to be closely related to Bacillus subtilis and Bacillus licheniformis. A significant percentage of lagoon bacteria were not susceptible to the four selected antibiotics: chlortetracycline, lincomycin, sulfamethazine and tetracycline (TET). However, the presence of both chlorine and TET could inactivate all bacteria in one lagoon sample. The disinfection potential of UV irradiation and ozone was also examined. Ultraviolet light was an effective bacterial disinfectant, but was unlikely to be economically viable due to its high energy requirements. At an ozone dose of 100 mg/L, the bacteria inactivation efficiency could reach 3.3−3.9 log
    corecore