Primitive CaO-rich, silica-undersaturated melts in island arcs: Evidence for the involvement of clinopyroxene-rich lithologies in the petrogenesis of arc magmas

On the basis of the study of olivine-hosted melt inclusions in a calc-alkaline basalt from Batan Island (Philippines) we define a distinctive type of primitive, nepheline-normative island arc magma characterized by unusually high CaO contents (up to 19.0 wt %) that cannot be simply explained by melting of the metasomatized peridotitic mantle wedge above subducting oceanic lithosphere. CaO-rich melt inclusions with these characteristics are preserved in Fo85-90 olivine, and compositional variations among the inclusions are interpreted to reflect mixing between melts such as those found in the most CaO-rich inclusions (present in Fo90 olivine) and melts similar to primitive "normal" island arc magmas (trapped in Fo85 olivine). Compilation of primitive island arc magmas from the literature shows that whole rocks and olivine-hosted melt inclusions with CaO contents >13 wt % are found in many arc volcanoes from all over the world in addition to Batan. These inclusions occur in lavas ranging from CaO-rich ankaramites to basaltic andesites with low-CaO contents (i.e., <13 wt %). The globally occurring CaO-rich inclusions and whole rocks comprise a group that although defined on the basis of their CaO contents is compositionally distinctive when compared to island arc lavas that have lower CaO contents; for example, they have lower FeO at a given SiO2 content than most arc lavas, and they are all nepheline normative, with normative nepheline contents positively correlated with CaO contents. Variations in CaO content and normative compositions of experimental partial melts of lherzolite related to changes of pressure, temperature, and source composition suggest that there are no conditions under which partial melting of peridotite can generate melts having CaO contents and other properties comparable to those observed for the primitive, CaO-rich arc-derived melts identified here. Although melting of peridotite at high pressure in the presence of CO2 can produce CaO-rich, silica-poor liquids, we consider it unlikely that this is responsible for producing the CaO-rich, silica-undersaturated melts considered in this study because there are significant differences in nearly all other compositional characteristics between the CaO-rich arc magmas and melts known or thought to be produced by melting of carbonated peridotite. Model major element compositions of partial melts of clinopyroxene-rich lithologies (mantle pyroxenites, lower crustal pyroxenites, and eclogites) calculated using the MELTS algorithm suggest that the most CaO-rich, nepheline-normative melt inclusions and whole rocks identified here could represent intermediate to high degree (~10-40 wt %) partial melts of pyroxenites at lower crustal to upper mantle pressures. Such a hypothesis is supported by the comparison between the trace element compositions of model pyroxenite sources of the Batan CaO-rich melt inclusions and naturally occurring pyroxenites. The most likely source of the primitive CaO-rich, silica-undersaturated arc melts identified here is lower crustal and shallow upper mantle pyroxene-rich cumulates from arc environments because these cumulates have CaO concentrations at the upper end of the range observed for mantle pyroxenites. They are therefore more likely to yield partial melts with the restricted range of remarkably high CaO contents of the most CaO-rich inclusions and whole rocks identified here. Moreover, these cumulates often contain amphibole, which would lower their solidus temperatures relative to the anhydrous pyroxenite equivalents to values more consistent with those expected in deep crustal or shallow subarc environments

Access and metro network convergence for flexible end-to-end network design

This paper reports on the architectural, protocol, physical layer, and integrated testbed demonstrations carried out by the DISCUS FP7 consortium in the area of access - metro network convergence. Our architecture modeling results show the vast potential for cost and power savings that node consolidation can bring. The architecture, however, also recognizes the limits of long-reach transmission for low-latency 5G services and proposes ways to address such shortcomings in future projects. The testbed results, which have been conducted end-to-end, across access - metro and core, and have targeted all the layers of the network from the application down to the physical layer, show the practical feasibility of the concepts proposed in the project

Zonation of H_(2)O and F Concentrations around Melt Inclusions in Olivines

Studies of both naturally quenched and experimentally reheated melt inclusions have established that they can lose or gain H_(2)O after entrapment in their host mineral, before or during eruption. Here we report nanoSIMS analyses of H2O, Cl and F in olivine around melt inclusions from two natural basaltic samples: one from the Sommata cinder cone on Vulcano Island in the Aeolian arc and the other from the Jorullo cinder cone in the Trans-Mexican Volcanic Belt. Our results constrain olivine/basaltic melt partition coefficients and allow assessment of mechanisms of volatile loss from melt inclusions in natural samples. Cl contents in olivine from both samples are mostly below detection limits (≤0·03 ± 0·01 ppm), with no detectable variation close to the melt inclusions. Assuming a maximum Cl content of 0·03 ppm for all olivines, maximum estimates for Cl partition coefficients between olivine and glass are 0·00002 ± 0·00002. Olivines from the two localities display contrasting H_(2)O and F compositions: Sommata olivines contain 27 ± 11 ppm H_(2)O and 0·28 ± 0·07 ppm F, whereas Jorullo olivines have lower and proportionately more variable H_(2)O and F (11 ± 12 ppm and 0·12 ± 0·09 ppm, respectively; uncertainties are two standard deviations for the entire population). The variations of H_(2)O and F contents in the olivines exhibit clear zonation patterns, increasing with proximity to melt inclusions. This pattern was most probably generated during transfer of volatiles out of the inclusions through the host olivine. H_(2)O concentration gradients surrounding melt inclusions are roughly concentric, but significantly elongated parallel to the crystallographic a-axis of olivine. Because of this preferential crystallographic orientation, this pattern is consistent with H_(2)O loss that is rate-limited by the ‘proton–polaron’ mechanism of H diffusion in olivine. Partition coefficients based on olivine compositions immediately adjacent to melt inclusions are 0·0007 ± 0·0003 for H_(2)O and 0·0005 ± 0·0003 for F. The H_(2)O and F diffusion profiles most probably formed in response to a decrease in the respective fugacities in the external melt, owing to either degassing or mixing with volatile-poor melt. Volatile transport out of inclusions might also have been driven in part by increases in the fugacity within the inclusion owing to post-entrapment crystallization. In the case of F, because of the lack of data on F diffusion in olivine, any interpretation of the measured F gradients is speculative. In the case of H_(2)O, we model the concentration gradients using a numerical model of three-dimensional anisotropic diffusion of H, where initial conditions include both H2O decrease in the external melt and post-entrapment enrichment of H_(2)O in the inclusions. The model confirms that external degassing is the dominant driving force, showing that the orientation of the anisotropy in H diffusion is consistent with the proton–polaron diffusion mechanism in olivine. The model also yields an estimate of the initial H_(2)O content of the Sommata melt inclusions before diffusive loss of 6 wt % H_(2)O. The findings provide new insights on rapid H_(2)O loss during magma ascent and improve our ability to assess the fidelity of the H_(2)O record from melt inclusions

Predictive modeling of die filling of the pharmaceutical granules using the flexible neural tree

In this work, a computational intelligence (CI) technique named flexible neural tree (FNT) was developed to predict die filling performance of pharmaceutical granules and to identify significant die filling process variables. FNT resembles feedforward neural network, which creates a tree-like structure by using genetic programming. To improve accuracy, FNT parameters were optimized by using differential evolution algorithm. The performance of the FNT-based CI model was evaluated and compared with other CI techniques: multilayer perceptron, Gaussian process regression, and reduced error pruning tree. The accuracy of the CI model was evaluated experimentally using die filling as a case study. The die filling experiments were performed using a model shoe system and three different grades of microcrystalline cellulose (MCC) powders (MCC PH 101, MCC PH 102, and MCC DG). The feed powders were roll-compacted and milled into granules. The granules were then sieved into samples of various size classes. The mass of granules deposited into the die at different shoe speeds was measured. From these experiments, a dataset consisting true density, mean diameter (d50), granule size, and shoe speed as the inputs and the deposited mass as the output was generated. Cross-validation (CV) methods such as 10FCV and 5x2FCV were applied to develop and to validate the predictive models. It was found that the FNT-based CI model (for both CV methods) performed much better than other CI models. Additionally, it was observed that process variables such as the granule size and the shoe speed had a higher impact on the predictability than that of the powder property such as d50. Furthermore, validation of model prediction with experimental data showed that the die filling behavior of coarse granules could be better predicted than that of fine granules

Visual similarity effects on short-term memory for order: The case of verbally labeled pictorial stimuli

Four experiments examined the effect of visual similarity on immediate memory for order. Experiments 1 and 2 used easily nameable line drawings. Following a sequential presentation in either silent or suppression conditions, participants were presented with the drawings in a new, random order and were required to remember their original serial position. In Experiment 3, participants first learned to associate a verbal label with an abstract matrix pattern. Then they completed an immediate memory task in which they had to name the matrices aloud during presentation. At recall, the task required remembering either the order of the matrices or the order of their names. In Experiment 4, participants learned to associate nonword labels with schematic line drawings of faces; the phonemic similarity of the verbal labels was also manipulated. All four experiments indicate that the representations supporting performance comprise both verbal and visual features. The results are consistent with a multiattribute encoding view

An intermediate-effect size variant in UMOD confers risk for chronic kidney disease

The kidney-specific gene UMOD encodes for uromodulin, the most abundant protein excreted in normal urine. Rare large-effect variants in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), while common low-impact variants strongly associate with kidney function and the risk of chronic kidney disease (CKD) in the general population. It is unknown whether intermediate-effect variants in UMOD contribute to CKD. Here, candidate intermediate-effect UMOD variants were identified using large-population and ADTKD cohorts. Biological and phenotypical effects were investigated using cell models, in silico simulations, patient samples, and international databases and biobanks. Eight UMOD missense variants reported in ADTKD are present in the Genome Aggregation Database (gnomAD), with minor allele frequency (MAF) ranging from 10(−5) to 10(−3). Among them, the missense variant p.Thr62Pro is detected in ∼1/1,000 individuals of European ancestry, shows incomplete penetrance but a high genetic load in familial clusters of CKD, and is associated with kidney failure in the 100,000 Genomes Project (odds ratio [OR] = 3.99 [1.84 to 8.98]) and the UK Biobank (OR = 4.12 [1.32 to 12.85). Compared with canonical ADTKD mutations, the p.Thr62Pro carriers displayed reduced disease severity, with slower progression of CKD and an intermediate reduction of urinary uromodulin levels, in line with an intermediate trafficking defect in vitro and modest induction of endoplasmic reticulum (ER) stress. Identification of an intermediate-effect UMOD variant completes the spectrum of UMOD-associated kidney diseases and provides insights into the mechanisms of ADTKD and the genetic architecture of CKD

Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin

Background Uromodulin, the most abundant protein excreted in normal urine, plays major roles in kidney physiology and disease. The mechanisms regulating the urinary excretion of uromodulin remain essentially unknown. Methods We conducted a meta-analysis of genome-wide association studies for raw (uUMOD) and indexed to creatinine (uUCR) urinary levels of uromodulin in 29,315 individuals of European ancestry from 13 cohorts. We tested the distribution of candidate genes in kidney segments and investigated the effects of keratin-40 (KRT40) on uromodulin processing. Results Two genome-wide significant signals were identified for uUMOD: a novel locus (P 1.24E-08) over the KRT40 gene coding for KRT40, a type 1 keratin expressed in the kidney, and the UMOD-PDILT locus (P 2.17E-88), with two independent sets of single nucleotide polymorphisms spread over UMOD and PDILT. Two genome-wide significant signals for uUCR were identified at the UMOD-PDILT locus and at the novel WDR72 locus previously associated with kidney function. The effect sizes for rs8067385, the index single nucleotide polymorphism in the KRT40 locus, were similar for both uUMOD and uUCR. KRT40 colocalized with uromodulin and modulating its expression in thick ascending limb (TAL) cells affected uromodulin processing and excretion. Conclusions Common variants in KRT40,WDR72, UMOD, and PDILT associate with the levels of uromodulin in urine. The expression of KRT40 affects uromodulin processing in TAL cells. These results, although limited by lack of replication, provide insights into the biology of uromodulin, the role of keratins in the kidney, and the influence of the UMOD-PDILT locus on kidney function

Research specialties as emergent phenomena: Connecting emergence theory and scientometrics

This short paper represents an initial effort to connect the emergence theory literature with the bibliometric, informetric, and scientometic literatures. It begins with a prominent definition of emergence, and then connects each of the components of this definition with the relevant insights about the development of new scientific and technical concepts or research specialties. Finally, it concludes with a discussion of the relationship between these two distinct areas of scholarly inquiry and the need for further exploration of this intersection.Intelligence Advanced Research Projects Activity (IARPA) viapublished or submitted for publicationis peer reviewe

Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

Testing a dynamic field account of interactions between spatial attention and spatial working memory

Studies examining the relationship between spatial attention and spatial working memory (SWM) have shown that discrimination responses are faster for targets appearing at locations that are being maintained in SWM, and that location memory is impaired when attention is withdrawn during the delay. These observations support the proposal that sustained attention is required for successful retention in SWM: if attention is withdrawn, memory representations are likely to fail, increasing errors. In the present study, this proposal is reexamined in light of a neural process model of SWM. On the basis of the model’s functioning, we propose an alternative explanation for the observed decline in SWM performance when a secondary task is performed during retention: SWM representations drift systematically toward the location of targets appearing during the delay. To test this explanation, participants completed a color-discrimination task during the delay interval of a spatial recall task. In the critical shifting attention condition, the color stimulus could appear either toward or away from the memorized location relative to a midline reference axis. We hypothesized that if shifting attention during the delay leads to the failure of SWM representations, there should be an increase in the variance of recall errors but no change in directional error, regardless of the direction of the shift. Conversely, if shifting attention induces drift of SWM representations—as predicted by the model—there should be systematic changes in the pattern of spatial recall errors depending on the direction of the shift. Results were consistent with the latter possibility—recall errors were biased toward the location of discrimination targets appearing during the delay