828 research outputs found

    ASPs: Applications for Rent

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    ASSESSMENT AND POTENTIAL ADJUSTMENTS TO THE SNOW-RELATED ALGORITHMS IN BIOME-BGC, v4.2

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    Many watersheds throughout the mountain west are snow-melt dominated. Recent studies suggest that climatic shifts throughout the 20th century have diminished snowpack around the west, a trend that may accelerate in the future. Loss of critical snowpack could negatively affect the ecosystems and communities that have come to depend on it. Process models offer a way to illuminate the effects of climate change on snowpack. BIOME-BGC, a well established eco-system process model, contains a simple snow melt model for predicting daily snow water equivalent (SWE). The model requires standard daily meteorological data and can, therefore, be extrapolated over long periods of record. This research evaluated the effectiveness of BIOME-BGC (v4.2) at predicting SWE, snowpack evolution, and soil temperature. Then, several physically based algorithms were incorporated into current model logic and model behavior was evaluated. Finally, a new degree-day algorithm was presented and assessed for inclusion into future versions of BIOME-BGC. The study concluded that the new degree-day algorithm should be investigated further as it offered the best results

    A theory of group technic in Christian education.

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    Thesis (Ph.D.)--Boston UniversityAlthough, in theory, the chUrch has laid stress upon democratic methods in group education, it has consistently relied in its technic upon educative systems designed to transmit information and help the individual gain sufficient information concerning the Christian tradition and culture. This procedure has been questioned by George A. Coe, W. C. Bower, Harrison Elliott, E. J. Chave, and others. Following the lead of Dewey, Froebel, and Pestalozzi, they translated a theory of social and functional education for the church. Theoretically, their findings hold with the Christian view of the religious life. However, they set forth no technic through which their basic theories could function, and as a consequence, learning groups in the church have continued to employ technics that are authoritarian and highly indifferent to the dynamics resident in group interaction. [TRUNCATED

    Reciprocal regulation of PKA and rac signaling

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    Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

    An open-label multi-center phase 1 safety study of BXQ-350 in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors

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    BACKGROUND: BXQ-350 is a novel anti-neoplastic agent composed of saposin C (SapC) and phospholipid dioleoylphosphatidyl-serine sodium (DOPS) that selectively binds tumor cell phosphatidylserine (PS), inducing apoptosis. BXQ-350 has demonstrated preclinical antitumor effects in high-grade gliomas (HGG) and clinical activity in adult patients with recurrent HGG. METHODS: A phase 1 study was conducted in pediatric patients with relapsed/refractory solid tumors, including recurrent brain tumors. Primary objectives were to characterize safety and determine maximum tolerated dose (MTD) and preliminary antitumor activity. Sequential dose cohorts were assessed up to 3.2 mg/kg using an accelerated titration design. Each cycle was 28 days; dosing occurred on days 1-5, 8, 10, 12, 15, and 22 of cycle 1, and day 1 of subsequent cycles, until disease progression or toxicity. RESULTS: Nine patients, median age 10 years (range: 4-23), were enrolled. Seven patients (78%) had central nervous system (CNS) and two (22%) had non-CNS tumors. Eight patients completed cycle 1. No dose limiting toxicity (DLT) or BXQ-350-related serious adverse events (SAEs) were observed. Six patients experienced at least one adverse event (AE) considered possibly BXQ-350-related, most were grade ≤2. One patient with diffuse intrinsic pontine glioma experienced stable disease for 5 cycles. The study was terminated after part 1 to focus development on the frontline setting. CONCLUSION: No DLTs or BXQ-350-related SAEs were reported, and the maximal planned dose of 3.2 mg/kg IV was tolerable. Limited safety and efficacy data support continued BXQ-350 development in pediatric HGG; however, early discontinuations for progression suggest novel therapies be assessed at earlier disease stages

    Ursinus College Alumni Journal, Spring 1946

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    Farewells to Ursinus • Education for veterans • Alumni Day • President\u27s page • Faculty and staff changes announced • Exhibits to be shown Commencement week • College pastor retires after 18 years\u27 service • Loyalty Fund grows • Professor and Mrs. Sheeder to leave Ursinus • Enrollments remain at high peak • Warren K. Hess \u2731, elected Berks judge • Wounded veterans attend courses • Ursinus and World War II • Store displays mural of college • News from the campus • Athletic policy defined • Sports revue • Secretary\u27s letter • Ensminger \u2714, receives Legion of Merit medal • Former professor invents electronic computer • Control of nuclear energy • News about ourselves • Necrology • Dr. DeWire aided in atom bomb experiments • Alumni Association nomineeshttps://digitalcommons.ursinus.edu/alumnijournal/1027/thumbnail.jp

    Rhesus monkey rhadinovirus (RRV): construction of a RRV-GFP recombinant virus and development of assays to assess viral replication

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    Rhesus monkey rhadinovirus (RRV) is a gamma-2-herpesvirus that is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). Lack of an efficient culture system to grow high titers of virus, and the lack of an in vivo animal model system, has hampered the study of KSHV replication and pathogenesis. RRV is capable of replicating to high titers on fibroblasts, thus facilitating the construction of recombinant rhadinoviruses. In addition, the ability to experimentally infect naïve rhesus macaques with RRV makes it an excellent model system to study gamma-herpesvirus replication. Our study describes, for the first time, the construction of a GFP-expressing RRV recombinant virus using a traditional homologous recombination strategy. We have also developed two new methods for determining viral titers of RRV including a traditional viral plaque assay and a quantitative real-time PCR assay. We have compared the replication of wild-type RRV with that of the RRV-GFP recombinant virus in one-step growth curves. We have also measured the sensitivity of RRV to a small panel of antiviral drugs. The development of both the recombination strategy and the viral quantitation assays for RRV will lay the foundation for future studies to evaluate the contribution of individual genes to viral replication both in vitro and in vivo

    Differential β-arrestin2 requirements for constitutive and agonist-induced internalization of the CB1 cannabinoid receptor

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    CB1 cannabinoid receptor (CB1R) undergoes both constitutive and agonist-induced internalization, but the underlying mechanisms of these processes and the role of beta-arrestins in the regulation of CB1R function are not completely understood. In this study, we followed CB1R internalization using confocal microscopy and bioluminescence resonance energy transfer measurements in HeLa and Neuro-2a cells. We found that upon activation CB1R binds beta-arrestin2 (beta-arr2), but not beta-arrestin1. Furthermore, both the expression of dominant-negative beta-arr2 (beta-arr2-V54D) and siRNA-mediated knock-down of beta-arr2 impaired the agonist-induced internalization of CB1R. In contrast, neither beta-arr2-V54D nor beta-arr2-specific siRNA had a significant effect on the constitutive internalization of CB1R. However, both constitutive and agonist-induced internalization of CB1R were impaired by siRNA-mediated depletion of clathrin heavy chain. We conclude that although clathrin is required for both constitutive and agonist-stimulated internalization of CB1R, beta-arr2 binding is only required for agonist-induced internalization of the receptor suggesting that the molecular mechanisms underlying constitutive and agonist-induced internalization of CB1R are different
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