120 research outputs found

    beta-decay study of Cu-77

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    A beta-decay study of Cu-77 has been performed at the ISOLDE mass separator with the aim to deduce its beta-decay properties and to obtain spectroscopic information on Zn-77. Neutron-rich copper isotopes were produced by means of proton- or neutron-induced fission reactions on U-238. After the production, Cu-77 was selectively laser ionized, mass separated and sent to different detection systems where beta-gamma and beta-n coincidence data were collected. We report on the deduced half-live, decay scheme, and possible spin assignment of 77Cu

    PARP inhibitors as P-glyoprotein substrates

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    The cytotoxicity of PARP inhibitors olaparib, veliparib, and CEP-8983 were investigated in two P-glycoprotein (P-gp) overexpressing drug-resistant cell models (IGROVCDDP and KB-8-5-11). IGROVCDDP and KB-8-5-11 were both resistant to olaparib and resistance was reversible with the P-gp inhibitors elacridar, zosuquidar, and valspodar. In contrast, the P-gp overexpressing models were not resistant to veliparib or CEP-8983. Olaparib and veliparib did not induce protein expression of P-gp in IGROVCDDP or KB-8-5-11 at doses that successfully inhibit PARP. Olaparib therefore appears to be a P-gp substrate. Veliparib and CEP-8983 do not appear to be substrates. Veliparib and CEP-8983 may therefore be more useful in combined chemotherapy regimens with P-gp substrates and may be active in platinum and taxane-resistant ovarian cancer

    Earthquake Rupture in Fault Zones With Along‐Strike Material Heterogeneity

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    Geological and geophysical observations reveal along‐strike fault zone heterogeneity on major strike‐slip faults, which can play a significant role in earthquake rupture propagation and termination. I present 2‐D dynamic rupture simulations to demonstrate rupture characteristics in such heterogeneous fault zone structure. The modeled rupture is nucleated in a damaged fault zone and propagates on a preexisting fault toward the zone of intact rocks. There is an intermediate range of nucleation lengths that only allow rupture to spontaneously propagate in the damaged fault zone but not in a homogeneous medium given the same stresses and frictional parameters. Rupture with an intermediate nucleation length tends to stop when it reaches the zone of intact rocks for uniform fault stress conditions, especially when the rupture propagation distance in the damaged fault zone is relatively short and when the damaged fault zone is relatively narrow or smooth in the fault‐normal direction. Pronounced small‐scale heterogeneity within the damaged fault zone also contributes to such early rupture termination. In asymmetric fault zones bisected by a bimaterial fault, rupture moving in the direction of slip of faster rocks tends to terminate under the same conditions as in symmetric fault zones, whereas rupture moving in the direction of slip of slower rocks can penetrate into the zone of intact rocks. A sufficiently large asperity located at the edge of the zone of intact rocks also allows break‐through rupture. The results suggest that the along‐strike fault zone heterogeneity can play a critical role in seismicity distribution.Plain Language SummaryNatural faults are surrounded by a zone of deformed rocks to accommodate strain localization. Such fault zone is not continuous along the fault, but rather includes segments of relatively damaged rocks adjacent to segments of relatively intact rocks. By simulating the dynamic interactions between fault stress, friction, and fault zone heterogeneities during the earthquake rupture process, I show that rupture is more likely to spontaneously propagate inside the damaged fault zone and stop when it reaches the relatively intact zone for uniform fault stress conditions. This phenomenon is less pronounced when the damaged fault zone becomes wider, sharper, and more damaged, indicating a higher likelihood of having large earthquakes that can penetrate into the relatively intact zone on more mature faults. The results suggest that a priori knowledge of the fault zone heterogeneity is critical for understanding the spatial distribution of earthquakes and the likelihood of having large earthquakes.Key PointsRupture nucleated in a damaged fault zone tends to terminate when it propagates along strike to an intact zone for uniform fault stressesRupture tends to penetrate into the relatively intact zone when the damaged fault zone becomes wider, sharper, and more damagedAn asperity at the edge of the relatively intact zone can facilitate rupture when its size is comparable to the nucleation half‐lengthPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147204/1/jgrb53125_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147204/2/jgrb53125.pd

    Changes in the geographical distribution and abundance of the tick Ixodes ricinus during the past 30 years in Sweden

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    <p>Abstract</p> <p>Background</p> <p><it>Ixodes ricinus </it>is the main vector in Europe of human-pathogenic Lyme borreliosis (LB) spirochaetes, the tick-borne encephalitis virus (TBEV) and other pathogens of humans and domesticated mammals. The results of a previous 1994 questionnaire, directed at people living in Central and North Sweden (Svealand and Norrland) and aiming to gather information about tick exposure for humans and domestic animals, suggested that <it>Ixodes ricinus </it>ticks had become more widespread in Central Sweden and the southern part of North Sweden from the early 1980s to the early 1990s. To investigate whether the expansion of the tick's northern geographical range and the increasing abundance of ticks in Sweden were still occurring, in 2009 we performed a follow-up survey 16 years after the initial study.</p> <p>Methods</p> <p>A questionnaire similar to the one used in the 1994 study was published in Swedish magazines aimed at dog owners, home owners, and hunters. The questionnaire was published together with a popular science article about the tick's biology and role as a pathogen vector in Sweden. The magazines were selected to get information from people familiar with ticks and who spend time in areas where ticks might be present.</p> <p>Results</p> <p>Analyses of data from both surveys revealed that during the near 30-year period from the early 1980s to 2008, <it>I. ricinus </it>has expanded its distribution range northwards. In the early 1990s ticks were found in new areas along the northern coastline of the Baltic Sea, while in the 2009 study, ticks were reported for the first time from many locations in North Sweden. This included locations as far north as 66°N and places in the interior part of North Sweden. During this 16-year period the tick's range in Sweden was estimated to have increased by 9.9%. Most of the range expansion occurred in North Sweden (north of 60°N) where the tick's coverage area doubled from 12.5% in the early 1990s to 26.8% in 2008. Moreover, according to the respondents, the abundance of ticks had increased markedly in LB- and TBE-endemic areas in South (Götaland) and Central Sweden.</p> <p>Conclusions</p> <p>The results suggest that <it>I. ricinus </it>has expanded its range in North Sweden and has become distinctly more abundant in Central and South Sweden during the last three decades. However, in the northern mountain region <it>I. ricinus </it>is still absent. The increased abundance of the tick can be explained by two main factors: First, the high availability of large numbers of important tick maintenance hosts, i.e., cervids, particularly roe deer (<it>Capreolus capreolus</it>) during the last three decades. Second, a warmer climate with milder winters and a prolonged growing season that permits greater survival and proliferation over a larger geographical area of both the tick itself and deer. High reproductive potential of roe deer, high tick infestation rate and the tendency of roe deer to disperse great distances may explain the range expansion of <it>I. ricinus </it>and particularly the appearance of new TBEV foci far away from old TBEV-endemic localities. The geographical presence of LB in Sweden corresponds to the distribution of <it>I. ricinus</it>. Thus, LB is now an emerging disease risk in many parts of North Sweden. Unless countermeasures are undertaken to keep the deer populations, particularly <it>C. capreolus </it>and <it>Dama dama</it>, at the relatively low levels that prevailed before the late 1970s - especially in and around urban areas where human population density is high - by e.g. reduced hunting of red fox (<it>Vulpes vulpes</it>) and lynx (<it>Lynx lynx</it>), the incidences of human LB and TBE are expected to continue to be high or even to increase in Sweden in coming decades.</p

    <i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

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    BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

    Interactive Effects of Climate Change with Nutrients, Mercury, and Freshwater Acidification on Key Taxa in the North Atlantic Landscape Conservation Cooperative Region

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    The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public–private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using a case study approach, we focused on 3 stressors with sufficient NA LCC regionspecific information for an informed discussion. We describe GCC interactions with a contaminant (Hg) and 2 complex environmental phenomena—freshwater acidification and eutrophication. We also prepared taxa case studies on GCCand GCC-contaminant/nutrient/process effects on amphibians and freshwater mussels. Several avian species of high conservation concern have blood Hg concentrations that have been associated with reduced nesting success. Freshwater acidification has adversely affected terrestrial and aquatic ecosystems in the Adirondacks and other areas of the region that are slowly recovering due to decreased emissions of N and sulfur oxides. Eutrophication in many estuaries within the region is projected to increase from greater storm runoff and less denitrification in riparian wetlands. Estuarine hypoxia may be exacerbated by increased stratification. Elevated water temperature favors algal species that produce harmful algal blooms (HABs). In several of the region\u27s estuaries, HABs have been associated with bird die-offs. In the NA LCC region, amphibian populations appear to be declining. Some species may be adversely affected by GCC through higher temperatures and more frequent droughts. GCC may affect freshwater mussel populations via altered stream temperatures and increased sediment loading during heavy storms. Freshwater mussels are sensitive to un-ionized ammonia that more toxic at higher temperatures. We recommend studying the interactive effects of GCC on generation and bioavailability of methylmercury and how GCC-driven shifts in bird species distributions will affect avian exposure to methylmercury. Research is needed on how decreases in acid deposition concurrent with GCC will alter the structure and function of sensitive watersheds and surface waters. Studies are needed to determine how GCC will affect HABs and avian disease, and how more severe and extensive hypoxia will affect fish and shellfish populations. Regarding amphibians, we suggest research on 1) thermal tolerance and moisture requirements of species of concern, 2) effects of multiple stressors (temperature, desiccation, contaminants, nutrients), and 3) approaches to mitigate impacts of increased temperature and seasonal drought. We recommend studies to assess which mussel species and populations are vulnerable and which are resilient to rising stream temperatures, hydrological shifts, and ionic pollutants, all of which are influenced by GCC

    Capture et dissipation dans la région des noyaux superlourds

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    Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

    Capture et dissipation dans la région des noyaux superlourds

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    Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe
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