292 research outputs found

    The three-stage petrochemical evolution of the Steens Basalt [southeast Oregon, USA] compared to large igneous provinces and layered mafic intrusions

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    The Steens Basalt, southeast Oregon, USA, initiated at 17 Ma as the earliest pulse of the Columbia River Flood Basalt of the northwestern USA. New and existing stratigraphically controlled data reveal temporal changes in lava flow character, and whole-rock and mineral compositions, which we use to evaluate how the balance of magma differentiation processes change in time. Temporal petrochemical variations in the Steens Basalt are analogous to the transition from Imnaha Basalt to Grande Ronde Basalt units of the Columbia River Flood Basalt and have parallels to the temporal evolution of the Deccan and Siberian traps, in India and Russia, respectively, as well as to the stratigraphic sequences of the Bushveld, of South Africa, and Stillwater, in southern Montana, USA, layered mafic intrusions. The excellent stratigraphic control from the Steens Basalt provides a detailed record for comparison across this variety of large mafic systems, providing ability to focus on commonalities among differentiation processes in time. Chemostratigraphic excursions and volcanological characteristics in the Steens Basalt record a three-stage history. A minimally exposed early stage preserved in the lower A Steens Basalt section is characterized by heterogeneity (3–8 wt% MgO) collapsing to homogeneity (~5 wt% MgO), suggesting crystal fractionation outpaces recharge. Sparse weathering horizons indicate some time elapses between eruptions. The second stage, lower B Steens Basalt, is volumetrically dominant and represents waxing of the basaltic pulse. Flows are stacked immediately upon one another without evidence of weathering or intervening sedimentary horizons, indicating high-eruptive frequency. Compositions oscillate over a ΔMgO of ~4–5 wt% between low- and high- MgO basalt, both of which become more magnesian up section, signaling a period dominated by recharge. This stage closes with declining oscillations to produce homogeneous compositions (6–8 wt% MgO). The waning stage of eruption is represented by the upper Steens Basalt section, where thin intercalated weathering horizons occur especially high in the section. The upper Steens Basalt is characterized by overall declining MgO and increasing incompatible element concentrations confirming the dominance of crystal fractionation accompanied by crustal assimilation. In detail, the upper Steens Basalt initiates with a small stack of heterogeneous flows (5–8 wt% MgO), followed by a period of relatively homogeneous flows (~6 wt% MgO) and closes with highly variable basalts to trachybasaltic andesites. These compositional characteristics coupled with a change in average flow thickness from lower to upper Steens Basalt of5–10 m illustrate a shift to more silicic compositions and higher viscosity up section. The chemical changes up section in other large igneous provinces record similar variations in differentiation processes through time, suggesting that these large volume systems share similar evolutionary histories: the earliest records suggest the magmatic systems are initially more ephemeral and compositionally variable as magma traverses relatively cool crust. With waxing, a transition to regimes of high thermal and mass input results in a stage where recharge outpaces crystal fractionation. Thermal priming of the crust during these events coupled with waning input yields magmas in which fractionation plus crustal assimilation dominates over recharge late in the system; pulses of later stage felsic magmatism in many large mafic provinces are consistent with this evolution. Using layered mafic intrusions as an analog for intrusive, cumulus-dominated residua of voluminous fractionation, as well as oceanic large igneous provinces as an analog for total magma volumes in continental flood basalt regimes, leads to the suggestion that 50%–85% of the total magma volume in a flood basalt remains in the crust, effectively remaking the crust in these regions

    Changing Mantle Sources and the Effects of Crustal Passage on the Steens Basalt, SE Oregon: Chemical and Isotopic Constraints

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    Continental flood basalts are more prone to compositional modification from passage through thicker and (or) more felsic crust in comparison to their oceanic counterparts. The Steens Basalt in southeast Oregon (~17 Ma) is among the oldest and most mafic members of the Columbia River Basalt Group and provides a record of the early stages of flood basalt volcanism. We evaluate the balance of mantle sources in time during the onset of Columbia River Basalt Group magmatism and assess the effect of crustal passage using stratigraphically controlled Sr, Nd, Pb, Hf, Os, and O isotopic compositions, as well as whole rock major and trace element data. Mixing models indicate that depleted and enriched mantle sources identified by previous workers contribute in varying proportions during the life of the magmatic system, with the greatest contribution by depleted mantle when eruption rate and presumed intrusion rate increase. During waxing, enrichment of δ18O in some flows signals cryptic deep fractionation of abundant clinopyroxene followed by shallow fractionation of olivine ± clinopyroxene ± plagioclase. Os concentrations are among the highest worldwide at a given MgO (0.29–0.86 ppb at 6.0 to 10.9 wt.%). We argue that high Os results from scavenging of sulfides by recharging magmas passing through earlier crystallized magmas. Elevated 87Sr/86Sr in the latest stage supports modest assimilation of partial melts from mafic accreted terranes, facilitated by thermal priming of crust by persistent magmatism. This work provides a more detailed schematic view of the Steens Basalt magmatic system, from mantle origin through crustal staging

    Income in Adult Survivors of Childhood Cancer.

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    INTRODUCTION: Little is known about the impact of childhood cancer on the personal income of survivors. We compared income between survivors and siblings, and determined factors associated with income. METHODS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to survivors, aged ≥18 years, registered in the Swiss Childhood Cancer Registry (SCCR), diagnosed at age 4'500 CHF), even after we adjusted for socio-demographic and educational factors (OR = 0.46, p<0.001). Older age, male sex, personal and parental education, and number of working hours were associated with high income. Survivors of leukemia (OR = 0.40, p<0.001), lymphoma (OR = 0.63, p = 0.040), CNS tumors (OR = 0.22, p<0.001), bone tumors (OR = 0.24, p = 0.003) had a lower income than siblings. Survivors who had cranial irradiation, had a lower income than survivors who had no cranial irradiation (OR = 0.48, p = 0.006). DISCUSSION: Even after adjusting for socio-demographic characteristics, education and working hours, survivors of various diagnostic groups have lower incomes than siblings. Further research needs to identify the underlying causes

    Structural versus Electrical Functionalization of Oligo(phenyleneethynylene) Diamine Molecular Junctions

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    We explore both experimentally and theoretically the conductance and packing of molecular junctions based on oligo(phenyleneethynylene) (OPE) diamine wires, when a series of functional groups are incorporated into the wires. Using the scanning tunnelling microscopy break-junction (STM BJ) technique, we study these compounds in two environments (air and 1,2,4-trichlorobenzene) and explore different starting molecular concentrations. We show that the electrical conductance of the molecular junctions exhibits variations among different compounds, which are significant at standard concentrations but become unimportant when working at a low enough concentration. This shows that the main effect of the functional groups is to affect the packing of the molecular wires, rather than to modify their electrical properties. Our theoretical calculations consistently predict no significant changes in the conductance of the wires due to the electronic structure of the functional groups, although their ability to hinder ring rotations within the OPE backbone can lead to higher conductances at higher packing densities

    A Comprehensive Peptidome Profiling Technology for the Identification of Early Detection Biomarkers for Lung Adenocarcinoma

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    The mass spectrometry-based peptidomics approaches have proven its usefulness in several areas such as the discovery of physiologically active peptides or biomarker candidates derived from various biological fluids including blood and cerebrospinal fluid. However, to identify biomarkers that are reproducible and clinically applicable, development of a novel technology, which enables rapid, sensitive, and quantitative analysis using hundreds of clinical specimens, has been eagerly awaited. Here we report an integrative peptidomic approach for identification of lung cancer-specific serum peptide biomarkers. It is based on the one-step effective enrichment of peptidome fractions (molecular weight of 1,000–5,000) with size exclusion chromatography in combination with the precise label-free quantification analysis of nano-LC/MS/MS data set using Expressionist proteome server platform. We applied this method to 92 serum samples well-managed with our SOP (standard operating procedure) (30 healthy controls and 62 lung adenocarcinoma patients), and quantitatively assessed the detected 3,537 peptide signals. Among them, 118 peptides showed significantly altered serum levels between the control and lung cancer groups (p<0.01 and fold change >5.0). Subsequently we identified peptide sequences by MS/MS analysis and further assessed the reproducibility of Expressionist-based quantification results and their diagnostic powers by MRM-based relative-quantification analysis for 96 independently prepared serum samples and found that APOA4 273–283, FIBA 5–16, and LBN 306–313 should be clinically useful biomarkers for both early detection and tumor staging of lung cancer. Our peptidome profiling technology can provide simple, high-throughput, and reliable quantification of a large number of clinical samples, which is applicable for diverse peptidome-targeting biomarker discoveries using any types of biological specimens

    Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review

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    Abstract BACKGROUND: The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder. METHODS: A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed, with the combination of the words 'aripiprazole' and 'bipolar'. RESULTS: The search returned 184 articles and was last updated on 15 April 2009. An additional search included repositories of clinical trials and previous systematic reviews specifically in order to trace unpublished trials. There were seven placebo-controlled randomised controlled trials (RCTs), six with comparator studies and one with add-on studies. They assessed the usefulness of aripiprazole in acute mania, acute bipolar depression and during the maintenance phase in comparison to placebo, lithium or haloperidol. CONCLUSION: Aripiprazole appears effective for the treatment and prophylaxis against mania. The data on bipolar depression are so far negative, however there is a need for further study at lower dosages. The most frequent adverse effects are extrapyramidal signs and symptoms, especially akathisia, without any significant weight gain, hyperprolactinaemia or laboratory test changes

    The Interaction between the First Transmembrane Domain and the Thumb of ASIC1a Is Critical for Its N-Glycosylation and Trafficking

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    Acid-sensing ion channel-1a (ASIC1a), the primary proton receptor in the brain, contributes to multiple diseases including stroke, epilepsy and multiple sclerosis. Thus, a better understanding of its biogenesis will provide important insights into the regulation of ASIC1a in diseases. Interestingly, ASIC1a contains a large, yet well organized ectodomain, which suggests the hypothesis that correct formation of domain-domain interactions at the extracellular side is a key regulatory step for ASIC1a maturation and trafficking. We tested this hypothesis here by focusing on the interaction between the first transmembrane domain (TM1) and the thumb of ASIC1a, an interaction known to be critical in channel gating. We mutated Tyr71 and Trp287, two key residues involved in the TM1-thumb interaction in mouse ASIC1a, and found that both Y71G and W287G decreased synaptic targeting and surface expression of ASIC1a. These defects were likely due to altered folding; both mutants showed increased resistance to tryptic cleavage, suggesting a change in conformation. Moreover, both mutants lacked the maturation of N-linked glycans through mid to late Golgi. These data suggest that disrupting the interaction between TM1 and thumb alters ASIC1a folding, impedes its glycosylation and reduces its trafficking. Moreover, reducing the culture temperature, an approach commonly used to facilitate protein folding, increased ASIC1a glycosylation, surface expression, current density and slowed the rate of desensitization. These results suggest that correct folding of extracellular ectodomain plays a critical role in ASIC1a biogenesis and function

    Diversity of Cl− Channels

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    Cl− channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl− channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca2+-activated Cl− channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl− channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl− channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl−-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles
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