Scant data exist on the silver isotope composition of native silver specimens because of the relative newness of the technique. This study increases the published dataset by an order of magnitude and presents 80 silver new isotope analyses from native silver originating from a diverse set of worldwide deposits (8 deposit types, 33 mining districts in five continents). The measured isotopic range (defined as 5109Ag/107Ag in per mil units compared to NIST 978 Ag isotope standard) is +2.1 to-0 .86%c (2 a errors less than 0.015); with no apparent systematic correlations to date with deposit type or even within districts. Importantly, the data centering on 0%o all come from high temperature hypogene/primary deposits whereas flanking and overlapping data represent secondary supergene deposits. To investigate the causes for the more fractionated valúes, several laboratory experiments involving oxidation of silver from natural specimens of Ag-rich sulfides and precipitation and adsorption of silver onto reagent grade M n 0 2 and FeOOH were conducted. Simple leach experiments demónstrate little Ag isotope fractionation occurred through oxidation of Ag from native Ag (Asoiution-nativeAg = 0.12%c). In contrast, significant fraction ation occurred through precipitation of native Ag onto M n 0 2 (up to Asoiution-Mn02Ag = 0 .68%c, or 0.3amu). Adsorption of silver onto the M n 0 2 and FeOOH did not produce as lar ge fractionation as precipitation (mean valué of A soiu tio n _M n 0 2 109Ag = 0.10%c). The most likely cause for the isotopic variations seen relates to redox effects such as the reduction of silver from Ag (I) to Ag° that occurs during precipitation onto the mineral surface. Since many Ag deposits have halos dominated by M n 0 2 and FeOOH phases, potential may exist for the silver isotope composition of ores and surrounding geochemical haloes to be used to better understand ore génesis and potential exploration applications. Aside from the Mn oxides, surface fluid silver isotope compositions might provide information about geochemical reactions relevant to both environmental and hydrometallurgical applications.
Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.
Paclitaxel can be added at full dose (200 mg/m2) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Median survival times in both extensive- and limited-stage patients compare favorably with other reported regimens. This regimen merits further investigation, and a randomized trial to compare this regimen with a standard carboplatin/etoposide combination is underway.
Twenty-nine patients with irresectable adenocarcinoma of the pancreas were treated with radiotherapy between 1961 and 1971. I n 6 patients the tumor was widespread. Twenty-three patients had regional malignancy, and were treated with curative intent. Some patients received adjunctive chemotherapy, usually with 5-fluorouracil. The radiotherapeutic technique used when cure was thought possible consisted of 6000 R calculated at the frontal midplane (anterior-posterior diameter) of the pancreas region, using Cobalt 60, in 10 weeks elapsed time. Three series of 2000 R in 10 fractions (2 weeks) were given, spaced by intervals of ,2 weeks. The crude survival figure was 21% at 2% years following diagnosis for all 29 patients. The morbidity of treatment was low; palliative results were encouraging.
This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.
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