4,651 research outputs found

    Chemical shift assignments of the N-terminal domain of PSD95 (PSD95-NT)

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    Postsynaptic density protein-95 (PSD95) contributes to the postsynaptic architecture of neuronal synapses and plays an important role in controlling synaptic plasticity. The N-terminal domain of PSD95 (residues 1–71, called PSD95-NT) interacts with target proteins (calmodulin, α-actinin-1 and CDKL5), which regulate the Ca2+-dependent degradation of glutamate receptors. We report complete backbone NMR chemical shift assignments of PSD95-NT (BMRB No. 50752)

    The causes and prevention of cancer.

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    Structural and functional conservation of key domains in InsP3 and ryanodine receptors.

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    Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6 Å) and without (3.0 Å) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-ÎČ and IBC-α, identifies two discrete interfaces (α and ÎČ) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the ÎČ-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-ÎČ or B domain), to gate the pore

    Guaranteed clustering and biclustering via semidefinite programming

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    Identifying clusters of similar objects in data plays a significant role in a wide range of applications. As a model problem for clustering, we consider the densest k-disjoint-clique problem, whose goal is to identify the collection of k disjoint cliques of a given weighted complete graph maximizing the sum of the densities of the complete subgraphs induced by these cliques. In this paper, we establish conditions ensuring exact recovery of the densest k cliques of a given graph from the optimal solution of a particular semidefinite program. In particular, the semidefinite relaxation is exact for input graphs corresponding to data consisting of k large, distinct clusters and a smaller number of outliers. This approach also yields a semidefinite relaxation for the biclustering problem with similar recovery guarantees. Given a set of objects and a set of features exhibited by these objects, biclustering seeks to simultaneously group the objects and features according to their expression levels. This problem may be posed as partitioning the nodes of a weighted bipartite complete graph such that the sum of the densities of the resulting bipartite complete subgraphs is maximized. As in our analysis of the densest k-disjoint-clique problem, we show that the correct partition of the objects and features can be recovered from the optimal solution of a semidefinite program in the case that the given data consists of several disjoint sets of objects exhibiting similar features. Empirical evidence from numerical experiments supporting these theoretical guarantees is also provided

    Complementary Aerodynamic Performance Datasets for Variable Speed Power Turbine Blade Section from Two Independent Transonic Turbine Cascades

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    Two independent experimental studies were conducted in linear cascades on a scaled, two-dimensional mid-span section of a representative Variable Speed Power Turbine (VSPT) blade. The purpose of these studies was to assess the aerodynamic performance of the VSPT blade over large Reynolds number and incidence angle ranges. The influence of inlet turbulence intensity was also investigated. The tests were carried out in the NASA Glenn Research Center Transonic Turbine Blade Cascade Facility and at the University of North Dakota (UND) High Speed Compressible Flow Wind Tunnel Facility. A large database was developed by acquiring total pressure and exit angle surveys and blade loading data for ten incidence angles ranging from +15.8deg to 51.0deg. Data were acquired over six flow conditions with exit isentropic Reynolds number ranging from 0.05106 to 2.12106 and at exit Mach numbers of 0.72 (design) and 0.35. Flow conditions were examined within the respective facility constraints. The survey data were integrated to determine average exit total-pressure and flow angle. UND also acquired blade surface heat transfer data at two flow conditions across the entire incidence angle range aimed at quantifying transitional flow behavior on the blade. Comparisons of the aerodynamic datasets were made for three "match point" conditions. The blade loading data at the match point conditions show good agreement between the facilities. This report shows comparisons of other data and highlights the unique contributions of the two facilities. The datasets are being used to advance understanding of the aerodynamic challenges associated with maintaining efficient power turbine operation over a wide shaft-speed range

    Virtual Constraints and Hybrid Zero Dynamics for Realizing Underactuated Bipedal Locomotion

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    Underactuation is ubiquitous in human locomotion and should be ubiquitous in bipedal robotic locomotion as well. This chapter presents a coherent theory for the design of feedback controllers that achieve stable walking gaits in underactuated bipedal robots. Two fundamental tools are introduced, virtual constraints and hybrid zero dynamics. Virtual constraints are relations on the state variables of a mechanical model that are imposed through a time-invariant feedback controller. One of their roles is to synchronize the robot's joints to an internal gait phasing variable. A second role is to induce a low dimensional system, the zero dynamics, that captures the underactuated aspects of a robot's model, without any approximations. To enhance intuition, the relation between physical constraints and virtual constraints is first established. From here, the hybrid zero dynamics of an underactuated bipedal model is developed, and its fundamental role in the design of asymptotically stable walking motions is established. The chapter includes numerous references to robots on which the highlighted techniques have been implemented.Comment: 17 pages, 4 figures, bookchapte

    Uncoupling growth from phosphorus uptake in Lemna: Implications for use of duckweed in wastewater remediation and P recovery in temperate climates

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    Phosphorus (P) is an essential nutrient for crop growth and the second most limiting after N. Current supplies rely on P‐rich rocks that are unevenly distributed globally and exploited unsustainably, leading to concerns about future availability and therefore food security. Duckweeds (Lemnaceae) are aquatic macrophytes used in wastewater remediation with the potential for nutrient recycling as feed or fertilizer. The use of duckweeds in this way is confined to tropical regions as it has previously been assumed that growth in the colder seasons of the temperate regions would be insufficient. In this study, the combined effects of cool temperatures and short photoperiods on growth and P uptake and accumulation in Lemna were investigated under controlled laboratory conditions. Growth and P accumulation in Lemna can be uncoupled, with significant P removal from the medium and accumulation within the plants occurring even at 8°C and 6‐hr photoperiods. Direct measurement of radiolabeled phosphate uptake confirmed that while transport is strongly temperature dependent, uptake can still be measured at 5°C. Prior phosphate starvation of the duckweed and use of nitrate as the nitrogen (N) source also greatly increased the rate of P removal and in‐cell accumulation. These results form the basis for further examination of the feasibility of duckweed‐based systems for wastewater treatment and P recapture in temperate climates, particularly in small, rural treatment works

    MUSTANG: 90 GHz Science with the Green Bank Telescope

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    MUSTANG is a 90 GHz bolometer camera built for use as a facility instrument on the 100 m Robert C. Byrd Green Bank radio telescope (GBT). MUSTANG has an 8 by 8 focal plane array of transition edge sensor bolometers read out using time-domain multiplexed SQUID electronics. As a continuum instrument on a large single dish MUSTANG has a combination of high resolution (8") and good sensitivity to extended emission which make it very competitive for a wide range of galactic and extragalactic science. Commissioning finished in January 2008 and some of the first science data have been collected.Comment: 9 Pages, 5 figures, Presented at the SPIE conference on astronomical instrumentation in 200
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