246 research outputs found
High-pressure Partial Melting of Mafic Lithologies in the Mantle
We review experimental phase equilibria associated with partial melting of mafic lithologies (pyroxenites) at high pressures to reveal systematic relationships between bulk compositions of pyroxenite and their melting relations. An important aspect of pyroxenite phase equilibria is the existence of the garnet-pyroxene thermal divide, defined by the enstatite-Ca-Tschermaks pyroxene-diopside plane in CaO-MgO-Al2O3-SiO2 projections. This divide appears at pressures above ∼2 GPa in the natural system where garnet and pyroxenes are the principal residual phases in pyroxenites. Bulk compositions that reside on either side of the divide have distinct phase assemblages from subsolidus to liquidus and produce distinct types of partial melt ranging from strongly nepheline-normative to quartz-normative compositions. Solidus and liquidus locations are little affected by the location of natural pyroxenite compositions relative to the thermal divide and are instead controlled chiefly by bulk alkali contents and Mg-numbers. Changes in phase volumes of residual minerals also influence partial melt compositions. If olivine is absent during partial melting, expansion of the phase volume of garnet relative to clinopyroxene with increasing pressure produces liquids with high Ca/Al and low MgO compared with garnet peridotite-derived partial melt
Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes
Abstract
Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.7%) pediatric gliomas, 8 of 8 (100%) patient derived orthotopic xenograft (PDOX) mouse models, and in both CD133+ and CD133− glioma cells. We demonstrated that lentiviral-shRNA mediated silencing of suppressed cell proliferation in vitro in cells derived from 3 independent PDOX models and eliminated tumor-forming capacity of CD133+ and CD133− cells derived from 2 PDOX models in mouse brains. Gene expression profiling showed that most of the molecular targets of BMI1 ablation in CD133+ cells were different from that in CD133- cells. Importantly, we found that silencing BMI1 in CD133+ cells derived from 3 PDOX models did not affect most of the known genes previously associated with the activated BMI1, but modulated a novel set of core genes, including RPS6KA2, ALDH3A2, FMFB, DTL, API5, EIF4G2, KIF5c, LOC650152, C20ORF121, LOC203547, LOC653308, and LOC642489, to mediate the elimination of tumor formation. In summary, we identified the over-expressed BMI1 as a promising therapeutic target for glioma stem cells, and suggest that the signaling pathways associated with activated BMI1 in promoting tumor growth may be different from those induced by silencing BMI1 in blocking tumor formation. These findings highlighted the importance of careful re-analysis of the affected genes following the inhibition of abnormally activated oncogenic pathways to identify determinants that can potentially predict therapeutic efficacy.http://deepblue.lib.umich.edu/bitstream/2027.42/110124/1/40478_2014_Article_160.pd
Distribution of recycled crust within the upper mantle : insights from the oxygen isotope composition of MORB from the Australian-Antarctic Discordance
Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 10 (2009): Q12004, doi:10.1029/2009GC002728Geochemical heterogeneity within the mantle has long been recognized through the diversity of trace element and radiogenic isotopic compositions of mantle-derived rocks, yet the specific origin, abundance, and distribution of enriched material within the mantle have been difficult to quantify. In particular, the origin of the distinctive geochemical characteristics of Indian mantle has been debated for decades. We present new laser fluorination oxygen isotope measurements of mid-ocean ridge basalt from the Australian-Antarctic Discordance (AAD), an area where a particularly abrupt transition occurs between Pacific-type mid-ocean ridge basalts (MORB) and Atlantic-type MORB. These data show no distinction in average δ18O between Pacific- and Atlantic-type MORB, indicating that the origin of Indian-type mantle cannot be attributed to the presence of pelagic sediment. The combined radiogenic isotope, δ18O, and trace element characteristics of Indian-type MORB at the AAD are consistent with contamination of the Indian upper mantle by lower crustal material. We also present a compilation of available laser fluorination δ18O data for MORB and use these data to evaluate the nature and percentage of enriched material within the upper mantle globally. Data for each ocean basin fit a normal distribution, with indistinguishable means and standard deviations, implying that the variation in δ18O of MORB reflects a stochastic process that operates similarly across all ocean basins. Monte Carlo simulations show that the mean and standard deviation of the MORB data are robust indicators of the mean and standard deviation of the parent distribution of data. Further, although some skewness in the data cannot be ruled out, Monte Carlo results are most consistent with a normal parent distribution. This similarity in characteristics of the δ18O data between ocean basins, together with correlations of δ18O with radiogenic isotope and trace element characteristics of subsets of the data, suggest that the upper mantle globally contains an average of ∼5–10% recycled crustal material and that the depleted mantle in the absence of this component would have δ18O of ∼5.25‰. The Monte Carlo simulations also suggest that additional oxygen isotope data may be used in the future to test the ability of geodynamical models to predict the physical distribution of enriched domains within the upper mantle
Subclinical inflammation in relation to insulin resistance in prediabetic subjects with nonalcoholic fatty liver disease
A multi-targeted approach to suppress tumor-promoting inflammation
Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes
Monte Carlo Simulations of Metasomatic Enrichment in the Lithosphere and Implications for the Source of Alkaline Basalts
One hypothesis for the origin of alkaline lavas erupted on oceanic islands and in intracontinental settings is that they represent the melts of amphibole-rich veins in the lithosphere (or melts of their dehydrated equivalents if metasomatized lithosphere is recycled into the convecting mantle). Amphibole-rich veins are interpreted as cumulates produced by crystallization of low-degree melts of the underlying asthenosphere as they ascend through the lithosphere. We present the results of trace-element modelling of the formation and melting of veins formed in this way with the goal of testing this hypothesis and for predicting how variability in the formation and subsequent melting of such cumulates (and adjacent cryptically and modally metasomatized lithospheric peridotite) would be manifested in magmas generated by such a process. Because the high-pressure phase equilibria of hydrous near-solidus melts of garnet lherzolite are poorly constrained and given the likely high variability of the hypothesized accumulation and remelting processes, we used Monte Carlo techniques to estimate how uncertainties in the model parameters (e.g. the compositions of the asthenospheric sources, their trace-element contents, and their degree of melting; the modal proportions of crystallizing phases, including accessory phases, as the asthenospheric partial melts ascend and crystallize in the lithosphere; the amount of metasomatism of the peridotitic country rock; the degree of melting of the cumulates and the amount of melt derived from the metasomatized country rock) propagate through the process and manifest themselves as variability in the trace-element contents and radiogenic isotopic ratios of model vein compositions and erupted alkaline magma compositions. We then compare the results of the models with amphibole observed in lithospheric veins and with oceanic and continental alkaline magmas. While the trace-element patterns of the near-solidus peridotite melts, the initial anhydrous cumulate assemblage (clinopyroxene ± garnet ± olivine ± orthopyroxene), and the modelled coexisting liquids do not match the patterns observed in alkaline lavas, our calculations show that with further crystallization and the appearance of amphibole (and accessory minerals such as rutile, ilmenite, apatite, etc.) the calculated cumulate assemblages have trace-element patterns that closely match those observed in the veins and lavas. These calculated hydrous cumulate assemblages are highly enriched in incompatible trace elements and share many similarities with the trace-element patterns of alkaline basalts observed in oceanic or continental setting such as positive Nb/La, negative Ce/Pb, and similiar slopes of the rare earth elements. By varying the proportions of trapped liquid and thus simulating the cryptic and modal metasomatism observed in peridotite that surrounds these veins, we can model the variations in Ba/Nb, Ce/Pb, and Nb/U ratios that are observed in alkaline basalts. If the isotopic compositions of the initial low-degree peridotite melts are similar to the range observed in mid-ocean ridge basalt, our model calculations produce cumulates that would have isotopic compositions similar to those observed in most alkaline ocean island basalt (OIB) and continental magmas after ~0·15 Gyr. However, to produce alkaline basalts with HIMU isotopic compositions requires much longer residence times (i.e. 1–2 Gyr), consistent with subduction and recycling of metasomatized lithosphere through the mantle. EM magmas cannot readily be explained without appealing to other factors such as a heterogeneous asthenosphere. These modelling results support the interpretation proposed by various researchers that amphibole-bearing veins represent cumulates formed during the differentiation of a volatile-bearing low-degree peridotite melt and that these cumulates are significant components of the sources of alkaline OIB and continental magmas. The results of the forward models provide the potential for detailed tests of this class of hypotheses for the origin of alkaline magmas worldwide and for interpreting major and minor aspects of the geochemical variability of these magmas
Detailed bathymetry and magnetic anomaly in the Central Ryukyu Arc, Japan: implications for a westward shift of the volcanic front after approximately 2.1 Ma
Concept design of low frequency telescope for CMB B-mode polarization satellite LiteBIRD
LiteBIRD has been selected as JAXA’s strategic large mission in the 2020s, to observe the cosmic microwave background (CMB) B-mode polarization over the full sky at large angular scales. The challenges of LiteBIRD are the wide field-of-view (FoV) and broadband capabilities of millimeter-wave polarization measurements, which are derived from the system requirements. The possible paths of stray light increase with a wider FoV and the far sidelobe knowledge of -56 dB is a challenging optical requirement. A crossed-Dragone configuration was chosen for the low frequency telescope (LFT : 34–161 GHz), one of LiteBIRD’s onboard telescopes. It has a wide field-of-view (18° x 9°) with an aperture of 400 mm in diameter, corresponding to an angular resolution of about 30 arcminutes around 100 GHz. The focal ratio f/3.0 and the crossing angle of the optical axes of 90◦ are chosen after an extensive study of the stray light. The primary and secondary reflectors have rectangular shapes with serrations to reduce the diffraction pattern from the edges of the mirrors. The reflectors and structure are made of aluminum to proportionally contract from warm down to the operating temperature at 5 K. A 1/4 scaled model of the LFT has been developed to validate the wide field-of-view design and to demonstrate the reduced far sidelobes. A polarization modulation unit (PMU), realized with a half-wave plate (HWP) is placed in front of the aperture stop, the entrance pupil of this system. A large focal plane with approximately 1000 AlMn TES detectors and frequency multiplexing SQUID amplifiers is cooled to 100 mK. The lens and sinuous antennas have broadband capability. Performance specifications of the LFT and an outline of the proposed verification plan are presented
Overview of the medium and high frequency telescopes of the LiteBIRD space mission
LiteBIRD is a JAXA-led Strategic Large-Class mission designed to search for the existence of the primordial gravitational waves produced during the inflationary phase of the Universe, through the measurements of their imprint onto the polarization of the cosmic microwave background (CMB). These measurements, requiring unprecedented sensitivity, will be performed over the full sky, at large angular scales, and over 15 frequency bands from 34 GHz to 448 GHz. The LiteBIRD instruments consist of three telescopes, namely the Low-, Medium-and High-Frequency Telescope (respectively LFT, MFT and HFT). We present in this paper an overview of the design of the Medium-Frequency Telescope (89{224 GHz) and the High-Frequency Telescope (166{448 GHz), the so-called MHFT, under European responsibility, which are two cryogenic refractive telescopes cooled down to 5 K. They include a continuous rotating half-wave plate as the first optical element, two high-density polyethylene (HDPE) lenses and more than three thousand transition-edge sensor (TES) detectors cooled to 100 mK. We provide an overview of the concept design and the remaining specific challenges that we have to face in order to achieve the scientific goals of LiteBIRD
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