1,014 research outputs found

    A Report of the Geology of the Golden Sunlight Mining District

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    This paper is a report of a geological survey made of an area of approximately fifty square miles lying Northeast of Whitehall, Montana, in the region of the Golden Sun­light Mine. The survey was made by a field party consisting of twenty-three members of the senior class of the Montana School of Mines

    Chapter 8: Domestic Relations

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    A novel design methodology accounting for ramping and field inhomogeneities in dreMR imaging

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    Delta relaxation enhanced magnetic resonance (dreMR) is a field cycled magnetic resonance imaging method for quantitative molecular imaging. DreMR uses an insertable field cycling coil to exploit longitudinal dispersion of contrast agents producing signal proportional to their concentration. Assumptions in the development of dreMR included instantaneous ramping of the insert coil and perfectly homogeneous field shifts. Here we discard these assumptions and show that finite ramping and field inhomogeneities can impair proportionality to agent concentration and produce significant signal from background tissues. To mitigate these effects, a novel dreMR coil design method is developed employing a boundary element method designed layer to the system which corrects field inhomogeneities, maximizing the usable dreMR imaging region. While a dreMR coil has not yet been constructed for use on humans, with these improvements it is expected that human designs will be much more feasible allowing the extension of this method to clinical studies

    Altered Cortical Microarchitecture and Bone Metabolism in Patients with Monoclonal Gammopathy of Undetermined Significance

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    Patients with monoclonal gammopathy of undetermined significance (MGUS) are at increased fracture risk, and we have previously shown that MGUS patients have altered trabecular bone microarchitecture compared with controls. However, there are no data on whether the porosity of cortical bone, which may play a greater role in bone strength and the occurrence of fractures, is increased in MGUS. Thus, we studied cortical porosity and bone strength (apparent modulus) using high-resolution peripheral quantitative computed tomography imaging of the distal radius in 50 MGUS patients and 100 age-, gender-, and body mass index–matched controls. Compared with controls, MGUS patients had both significantly higher cortical porosity (+16.8%; P < .05) and lower apparent modulus (–8.9%; P < .05). Despite their larger radial bone size, MGUS patients have significantly increased cortical bone porosity and reduced bone strength relative to controls. This increased cortical porosity may explain the increased fracture risk seen in MGUS patients

    An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

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    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion

    UV irradiation induces homologous recombination genes in the model archaeon, Halobacterium sp. NRC-1

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    BACKGROUND: A variety of strategies for survival of UV irradiation are used by cells, ranging from repair of UV-damaged DNA, cell cycle arrest, tolerance of unrepaired UV photoproducts, and shielding from UV light. Some of these responses involve UV-inducible genes, including the SOS response in bacteria and an array of genes in eukaryotes. To address the mechanisms used in the third branch of life, we have studied the model archaeon, Halobacterium sp. strain NRC-1, which tolerates high levels of solar radiation in its natural hypersaline environment. RESULTS: Cells were irradiated with 30–70 J/m(2 )UV-C and an immunoassay showed that the resulting DNA damage was largely repaired within 3 hours in the dark. Under such conditions, transcriptional profiling showed the most strongly up-regulated gene was radA1, the archaeal homolog of rad51/recA, which was induced 7-fold. Additional genes involved in homologous recombination, such as arj1 (recJ-like exonuclease), dbp (eukaryote-like DNA binding protein of the superfamily I DNA and RNA helicases), and rfa3 (replication protein A complex), as well as nrdJ, encoding for cobalamin-dependent ribonucleotide reductase involved in DNA metabolism, were also significantly induced in one or more of our experimental conditions. Neither prokaryotic nor eukaryotic excision repair gene homologs were induced and there was no evidence of an SOS-like response. CONCLUSION: These results show that homologous recombination plays an important role in the cellular response of Halobacterium sp. NRC-1 to UV damage. Homologous recombination may permit rescue of stalled replication forks, and/or facilitate recombinational repair. In either case, this provides a mechanism for the observed high-frequency recombination among natural populations of halophilic archaea

    The rad18 Gene of Schizosaccharomyces pombe Defines a New Subgroup of the SMC Superfamily Involved in DNA Repair

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    The rad18 mutant of Schizosaccharomyces pombe is very sensitive to killing by both UV and Âż radiation. We have cloned and sequenced the rad18 gene and isolated and sequenced its homolog from Saccharomyces cerevisiae, designated RHC18. The predicted Rad18 protein has all the structural properties characteristic of the SMC family of proteins, suggesting a motor function- the first implicated in DNA repair. Gene deletion shows that both rad18 and RHC18 are essential for proliferation. Genetic and biochemical analyses suggest that the product of the rad18 gene acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair. This second repair pathway involves the products of the rhp51 gene (the homolog of the RAD51 gene of S. cerevisiae) and the rad2 gene

    Editorial: The History and Evolution of the Journal of Sorority and Fraternity Life Research and Practice

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    Individuals involved in the founding of the Oracle: The Research Journal of the Association of Fraternity/Sorority Advisors (Oracle), former Oracle editors and Adam M. McCready, Editor of Journal of Sorority and Fraternity Life Research and Practice share the history and evolution of the journal over the past two decades
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