1,480 research outputs found

    The Lantern Vol. 30, No. 1, February 1963

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    • Mechanical Duplicity • The Practical Profits of Purism • \u27Tis Better • Misha • Manuel • An American Fairy Tale • The Christ of Christopher Street • Nocturne • Various Reflections • He Came and Gently Lifted Me • Poem, In a Minor Key • World Fell to Ruin • The Map • On Being Jilted • Manna • Traitor • The Leaves Cling • Oh Freedom! • The Insurance Man • Translation - The Vampire • Four Poems • Sanguis • Phoney is the Color of My Love\u27s Life • To a Barmaidhttps://digitalcommons.ursinus.edu/lantern/1083/thumbnail.jp

    The Lantern Vol. 31, No. 1, December 1963

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    • Today\u27s Memory • The Realization • Life Fire • Come Sleep • The Ends Meet • Dawn of Darkness • Closed and Done: With Apologies to No One • A Search • Concern • Obvious Oblivion • Love\u27s Ashes • Silence • To My Dentist • Snow • Wisdom • Look Up • Nepenthe • With Apologies to Charles Schulz • Autumn and You • What is Optimism? • Agnostic? • Potpourri of Beinghttps://digitalcommons.ursinus.edu/lantern/1085/thumbnail.jp

    The Lantern Vol. 31, No. 2, May 1964

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    • The High, Forbidding Wall • Sonnet One • Sceptic • The Witch, the Prince, and the Princess • Portrait in Gold and Black • The Music of the Drum • Sweat It, Jack • Cold Blue and the Moon • Another Carpenter: Circa 1963 • At a Conference of Colonial Historians • Pineland Places • Diasia to Death • Hey!... • The Hour • I\u27ll Not Returnhttps://digitalcommons.ursinus.edu/lantern/1086/thumbnail.jp

    Impact of feeding and housing systems on disease incidence in dairy calves

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    Contentious issues in calf rearing include milk feeding level and single versus group housing. The current study was performed on a high-producing 170 Holstein cow dairy farm to investigate the impact of nutrition and housing on disease incidence. Calves (n=100) were allocated in birth order to one of two commonly used feeding strategies. Group A calves were group housed from birth and fed ad libitum milk replacer (MR) via a computerised machine using a single teat, with weaning commencing at 63 days. Group R calves were initially housed in individual pens receiving 2.5 litres of MR twice daily via a bucket until three weeks of age when they were group housed and fed 3 litres of MR twice daily via a group trough with weaning commencing at 56 days. In total, 80 (80 per cent) calves suffered from at least one incident of disease during the period from birth to 12 weeks. Group A calves had a greater risk of disease than group R calves (diarrhoea: OR 3.86 (95 per cent CI 1.67 to 8.9); pneumonia: OR 5.80 (95 per cent CI 2.33 to 14.44)). There was a 5.1 per cent incidence of failure of passive transfer of Ig assessed via measurement of plasma total protein concentrations at 48 hours of age. It is hypothesised that the increased diarrhoea risk in group A calves was most likely associated with group housing, while the increased pneumonia risk was associated with the use of a single teat allowing increased transmission of pathogens from calf to calf

    What We Talk about When We Talk about Love: A Duoethnographic Exploration of the Dissertation Relationship

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    In the aftermath and mop-up following a successful dissertation defense, an unintended and unexpected data source remained unexplored and unanalyzed: 32 audio-recorded discussions and work sessions documenting the processes, approaches, and decisions made by a dissertation director and his doctoral candidate. What might those conversations reveal about the dissertation relationship? Taking a page from Raymond Carver’s short story, “What We Talk about When We Talk about Love,” we wondered what we might have been talking about when we were talking about dissertation writing. Inspired and shaped by Norris, Sawyer, and Lund’s (2012. Duoethnography: Dialogic methods for social, health, and educational research. Walnut Creek, CA: Left Coast Press.) duoethnographic methods, this study provides opportunity for us to not just look back on the journey, but pushes us into the messiness of “recalling and reconceptualizing” (p. 10). As we each “become the foil for the Other, challenging the Other to reflect on their own life in a deeper, more relational, and authentic manner” (Norris et al., 2012, p. 10) we also interrogate and trouble our own simplistic categories of analysis

    Identification of Direct Target Engagement Biomarkers for Kinase-Targeted Therapeutics

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    Pharmacodynamic (PD) biomarkers are an increasingly valuable tool for decision-making and prioritization of lead compounds during preclinical and clinical studies as they link drug-target inhibition in cells with biological activity. They are of particular importance for novel, first-in-class mechanisms, where the ability of a targeted therapeutic to impact disease outcome is often unknown. By definition, proximal PD biomarkers aim to measure the interaction of a drug with its biological target. For kinase drug discovery, protein substrate phosphorylation sites represent candidate PD biomarkers. However, substrate phosphorylation is often controlled by input from multiple converging pathways complicating assessment of how potently a small molecule drug hits its target based on substrate phoshorylation measurements alone. Here, we report the use of quantitative, differential mass-spectrometry to identify and monitor novel drug-regulated phosphorylation sites on target kinases. Autophosphorylation sites constitute clinically validated biomarkers for select protein tyrosine kinase inhibitors. The present study extends this principle to phosphorylation sites in serine/threonine kinases looking beyond the T-loop autophosphorylation site. Specifically, for the 3′-phosphoinositide-dependent protein kinase 1 (PDK1), two phospho-residues p-PDK1Ser410 and p-PDK1Thr513 are modulated by small-molecule PDK1 inhibitors, and their degree of dephosphorylation correlates with inhibitor potency. We note that classical, ATP-competitive PDK1 inhibitors do not modulate PDK1 T-loop phosphorylation (p-PDK1Ser241), highlighting the value of an unbiased approach to identify drug target-regulated phosphorylation sites as these are complementary to pathway PD biomarkers. Finally, we extend our analysis to another protein Ser/Thr kinase, highlighting a broader utility of our approach for identification of kinase drug-target engagement biomarkers
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