695 research outputs found

    Tribute to John Pickering

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    This is my homage to John. I ask you to summon up in your imagination today a grand circus, a sort of Cirque du Soleil of lawyers: full of shining talents performing legal feats of wonder, but presided over by a grand ringmaster. This ringmaster knows his performers very well. He knows how to train and stroke them to high achievement. He knows how to groom the younger workers. He can keep his stars in check. He knows when to sit back with a smile, letting his charges perform and claim the applause, even when the applause rightfully belongs to him. When his performers bicker, as they often do, he cajoles them back into their act. When they sulk, he cheers them up. John Pickering is this ringmaster. In my judgment, he was the but-for cause of the firm\u27s great success. Without John, I do not think the firm could have made it past its heady early days. He embodied the firm\u27s conscience, and I hope he still does. Even far beyond the firm, John stood as a model for all lawyers to emulate. I hope he still does

    The Distribution Of Chlorine And Iodine In Soil In The Vicinity Of Lead Mining And Smelting Operations, Bixby Area, S.E. Missouri, U.S.A.

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    Iodine and Cl are enriched in soils in the vicinity of the Magmont and Buick lead mines near Bixby, southeastern Missouri. The enrichments, up to 5.6 ppm I and 305 ppm Cl, are against regional background of 1.26 ppm I and 41 ppm Cl. The area of highest I and Cl is thought to reflect a zone of base metal sulphide mineralization occurring about 400 m below the surface. Iodine and Cl are also enriched in soils immediately adjacent to a tailings pond, hence these elements would appear to be leached from this source. A zone of enhanced I values (up to 2.65 ppm I) to the north of a lead smelter is superimposed on a much larger zone of lead enrichment (up to 12,000 ppm Pb) and is thought to represent I released from sulphide ores on smelting. © 1988

    Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts

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    Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFβ1) and human vascular endothelial growth factor (hVEGF) at 3.2 and 0.6 ng/mm2, respectively. In addition, we demonstrated that retained hTGFβ1 and hVEGF enhanced human dermal fibroblasts (HDFa) average cell surface area and proliferation, respectively, and that exposure to both GFs resulted in up to 1.9-fold higher fraction of area covered relative to the control. After five days in culture, relative to the control surface, non-covalently bound hTGFβ1 significantly increased the expression of collagen type I and hTGFβ1 and downregulated vimentin and matrix metalloproteinase 1 expression. Cumulatively, the response of HDFa to hTGFβ1 aligns well with the expected response of fibroblasts during the early stages of wound healing

    Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland?

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    The specific effects triggered by polypeptide hormone/growth factor stimulation of mammary cells were considered mediated solely by receptor-associated signaling networks. A compelling body of new data, however, clearly indicates that polypeptide ligands and/or their receptors are transported into the nucleus, where they function directly to regulate the expression of specific transcription factors and gene loci. The intranuclear function of these complexes may contribute to the explicit functions associated with a given ligand, and may serve as new targets for pharmacologic intervention

    Effect of sampling rate on acceleration and counts of hip- and wrist-worn ActiGraph accelerometers in children

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    Sampling rate (Hz) of ActiGraph accelerometers may affect processing of acceleration to activity counts when using a hip-worn monitor, but research is needed to quantify if sampling rate affects actual acceleration (mg's), when using wrist-worn accelerometers and during non-locomotive activities. Objective: To assess the effect of ActiGraph sampling rate on total counts/15-sec and mean acceleration and to compare differences due to sampling rate between accelerometer wear locations and across different types of activities. Approach: Children (n=29) wore a hip- and wrist-worn accelerometer (sampled at 100 Hz, downsampled in MATLAB to 30 Hz) during rest/transition periods, active video games, and a treadmill test to volitional exhaustion. Mean acceleration and counts/15-sec were computed for each axis and as vector magnitude. Main Results: There were mostly no significant differences in mean acceleration. However, 100 Hz data resulted in significantly more total counts/15-sec (mean bias 4-43 counts/15-sec across axes) for both the hip- and wrist-worn monitor when compared to 30 Hz data. Absolute differences increased with activity intensity (hip: r=0.46-0.63; wrist: r=0.26-0.55) and were greater for hip- versus wrist-worn monitors. Percent agreement between 100 and 30 Hz data was high (97.4-99.7%) when cut-points or machine learning algorithms were used to classify activity intensity. Significance: Our findings support that sampling rate affects the generation of counts but adds that differences increase with intensity and when using hip-worn monitors. We recommend researchers be consistent and vigilantly report the sampling rate used, but note that classifying data into activity intensities resulted in agreement despite differences in sampling rate

    A Humanized Pattern of Aromatase Expression is Associated with Mammary Hyperplasia in Mice

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    Aromatase is essential for estrogen production and is the target of aromatase inhibitors, the most effective endocrine treatment for postmenopausal breast cancer. Peripheral tissues in women, including the breast, express aromatase via alternative promoters. Female mice lack the promoters that drive aromatase expression in peripheral tissues; thus, we generated a transgenic humanized aromatase (Arom(hum)) mouse line containing a single copy of the human aromatase gene to study the link between aromatase expression in mammary adipose tissue and breast pathology. Arom(hum) mice expressed human aromatase, driven by the proximal human promoters II and I.3 and the distal promoter I.4, in breast adipose fibroblasts and myoepithelial cells. Estrogen levels in the breast tissue of Arom(hum) mice were higher than in wild-type mice, whereas circulating levels were similar. Arom(hum) mice exhibited accelerated mammary duct elongation at puberty and an increased incidence of lobuloalveolar breast hyperplasia associated with increased signal transducer and activator of transcription-5 phosphorylation at 24 and 64 wk. Hyperplastic epithelial cells showed remarkably increased proliferative activity. Thus, we demonstrated that the human aromatase gene can be expressed via its native promoters in a wide variety of mouse tissues and in a distribution pattern nearly identical to that of humans. Locally increased tissue levels, but not circulating levels, of estrogen appeared to exert hyperplastic effects on the mammary gland. This novel mouse model will be valuable for developing tissue-specific aromatase inhibition strategies
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