200 research outputs found

    Corrigendum for the article ''Curved Koszul duality theory''

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    In this corrigendum, we explain and correct a mistake in our article ''Curved Koszul duality theory''. Our definitions of morphisms between semi-augmented properads and between curved coproperads have to be modified.Comment: Mathematische Annalen, 202

    Regulation of Reactive Oxygen Species and the Antioxidant Protein DJ-1 in Mastocytosis

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    Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates with activating mutations in the receptor tyrosine kinase KIT. Constitutive activation of tyrosine kinase oncogenes has been linked to imbalances in oxidant/antioxidant mechanisms in other myeloproliferative disorders. However, the impact of KIT mutations on the redox status in SM and the potential therapeutic implications are not well understood. Here, we examined the regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1 (PARK-7), which increases with cancer progression and acts to lessen oxidative damage to malignant cells, in relationship with SM severity. ROS levels were increased in both indolent (ISM) and aggressive variants of the disease (ASM). However, while DJ-1 levels were reduced in ISM with lower mast cell burden, they rose in ISM with higher mast cell burden and were significantly elevated in patients with ASM. Studies on mast cell lines revealed that activating KIT mutations induced constant ROS production and consequent DJ-1 oxidation and degradation that could explain the reduced levels of DJ-1 in the ISM population, while IL-6, a cytokine that increases with disease severity, caused a counteracting transcriptional induction of DJ-1 which would protect malignant mast cells from oxidative damage. A mouse model of mastocytosis recapitulated the biphasic changes in DJ-1 and the escalating IL-6, ROS and DJ-1 levels as mast cells accumulate, findings which were reversed with anti-IL-6 receptor blocking antibody. Our findings provide evidence of increased ROS and a biphasic regulation of the antioxidant DJ-1 in variants of SM and implicate IL-6 in DJ-1 induction and expansion of mast cells with KIT mutations. We propose consideration of IL-6 blockade as a potential adjunctive therapy in the treatment of patients with advanced mastocytosis, as it would reduce DJ-1 levels making mutation-positive mast cells vulnerable to oxidative damage

    Electrostatic Interactions and Binding Orientation of HIV-1 Matrix Studied by Neutron Reflectivity

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    AbstractThe N-terminal matrix (MA) domain of the HIV-1 Gag protein is responsible for binding to the plasma membrane of host cells during viral assembly. The putative membrane-binding interface of MA was previously mapped by means of mutagenesis and analysis of its trimeric crystal structure. However, the orientation of MA on membranes has not been directly determined by experimental measurements. We present neutron reflectivity measurements that resolve the one-dimensional scattering length density profile of MA bound to a biomimetic of the native viral membrane. A molecular refinement procedure was developed using atomic structures of MA to determine the orientation of the protein on the membrane. The orientation defines a lipid-binding interface consistent with previous mutagenesis results. The MA protein maintains this orientation without the presence of a myristate group, driven only by electrostatic interactions. Furthermore, MA is found to penetrate the membrane headgroup region peripherally such that only the side chains of specific Lys and Arg residues interact with the surface. The results suggest that electrostatic interactions are sufficient to favorably orient MA on viral membrane mimics. The spatial determination of the membrane-bound protein demonstrates the ability of neutron reflectivity to discern orientation and penetration under physiologically relevant conditions

    Interfacing and Verifying ALHAT Safe Precision Landing Systems with the Morpheus Vehicle

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    The NASA Autonomous precision Landing and Hazard Avoidance Technology (ALHAT) project developed a suite of prototype sensors to enable autonomous and safe precision landing of robotic or crewed vehicles under any terrain lighting conditions. Development of the ALHAT sensor suite was a cross-NASA effort, culminating in integration and testing on-board a variety of terrestrial vehicles toward infusion into future spaceflight applications. Terrestrial tests were conducted on specialized test gantries, moving trucks, helicopter flights, and a flight test onboard the NASA Morpheus free-flying, rocket-propulsive flight-test vehicle. To accomplish these tests, a tedious integration process was developed and followed, which included both command and telemetry interfacing, as well as sensor alignment and calibration verification to ensure valid test data to analyze ALHAT and Guidance, Navigation and Control (GNC) performance. This was especially true for the flight test campaign of ALHAT onboard Morpheus. For interfacing of ALHAT sensors to the Morpheus flight system, an adaptable command and telemetry architecture was developed to allow for the evolution of per-sensor Interface Control Design/Documents (ICDs). Additionally, individual-sensor and on-vehicle verification testing was developed to ensure functional operation of the ALHAT sensors onboard the vehicle, as well as precision-measurement validity for each ALHAT sensor when integrated within the Morpheus GNC system. This paper provides some insight into the interface development and the integrated-systems verification that were a part of the build-up toward success of the ALHAT and Morpheus flight test campaigns in 2014. These campaigns provided valuable performance data that is refining the path toward spaceflight infusion of the ALHAT sensor suite

    Curved Koszul duality theory

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    38 pagesInternational audienceWe extend the bar-cobar adjunction to operads and properads, not necessarily augmented. Due to the default of augmentation, the objects of the dual category are endowed with a curvature. We handle the lack of augmentation by extending the category of coproperads to include objects endowed with a curvature. As usual, the bar-cobar construction gives a (large) cofibrant resolution for any properad, such as the properad encoding unital and counital Frobenius algebras, a notion which appears in 2d-TQFT. We also define a curved Koszul duality theory for operads or properads presented with quadratic, linear and constant relations, which provides the possibility for smaller relations. We apply this new theory to study the homotopy theory and the cohomology theory of unital associative algebras

    Benefits and Effects of Interactive Gaming Exercise as Compared to Traditional Exercise Techniques: An Investigation of the Relationship Between Physical Activity Levels and Mode of Activity in College Students

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    Gemstone Team F.I.T.N.E.S.S. (Fun Interactive Techniques for New Exercise and Sport Styles)The objective of this research project was to determine the relationship between mode of activity and motivation to exercise. Specifically, the research aimed to discover if interactive video games are effective in motivating sedentary college students to exercise. The introduction discusses the problems of physical inactivity and obesity, the increased use of video games, and a proposed solution using interactive technology. For a ten-week period, sedentary University of Maryland – College Park students joined either the traditional exercise or interactive gaming group, with heart rates and activity levels documented throughout. Together, quantitative heart rate and activity data and qualitative participant feedback, illustrated that it was too difficult to collect significant data supporting a conclusion that one activity was a significantly better means to raise heart rates and motivate students to exercise. However, the data did support the importance of continuing research on potential benefits of interactive gaming for a sedentary population

    Pairing fluctuations and pseudogaps in the attractive Hubbard model

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    The two-dimensional attractive Hubbard model is studied in the weak to intermediate coupling regime by employing a non-perturbative approach. It is first shown that this approach is in quantitative agreement with Monte Carlo calculations for both single-particle and two-particle quantities. Both the density of states and the single-particle spectral weight show a pseudogap at the Fermi energy below some characteristic temperature T*, also in good agreement with quantum Monte Carlo calculations. The pseudogap is caused by critical pairing fluctuations in the low-temperature renormalized classical regime ω<T\omega < T of the two-dimensional system. With increasing temperature the spectral weight fills in the pseudogap instead of closing it and the pseudogap appears earlier in the density of states than in the spectral function. Small temperature changes around T* can modify the spectral weight over frequency scales much larger than temperature. Several qualitative results for the s-wave case should remain true for d-wave superconductors.Comment: 20 pages, 12 figure

    RAPID: Collaborative Commanding and Monitoring of Lunar Assets

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    RAPID (Robot Application Programming Interface Delegate) software utilizes highly robust technology to facilitate commanding and monitoring of lunar assets. RAPID provides the ability for intercenter communication, since these assets are developed in multiple NASA centers. RAPID is targeted at the task of lunar operations; specifically, operations that deal with robotic assets, cranes, and astronaut spacesuits, often developed at different NASA centers. RAPID allows for a uniform way to command and monitor these assets. Commands can be issued to take images, and monitoring is done via telemetry data from the asset. There are two unique features to RAPID: First, it allows any operator from any NASA center to control any NASA lunar asset, regardless of location. Second, by abstracting the native language for specific assets to a common set of messages, an operator may control and monitor any NASA lunar asset by being trained only on the use of RAPID, rather than the specific asset. RAPID is easier to use and more powerful than its predecessor, the Astronaut Interface Device (AID). Utilizing the new robust middleware, DDS (Data Distribution System), developing in RAPID has increased significantly over the old middleware. The API is built upon the Java Eclipse Platform, which combined with DDS, provides platform-independent software architecture, simplifying development of RAPID components. As RAPID continues to evolve and new messages are being designed and implemented, operators for future lunar missions will have a rich environment for commanding and monitoring assets
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