Production and loss of high-density batholithic root, southern Sierra Nevada, California

Eclogites are commonly believed to be highly susceptible to delamination and sinking into the mantle from lower crustal metamorphic environments. We discuss the production of a specific class of eclogitic rocks that formed in conjunction with the production of the Sierra Nevada batholith. These high-density eclogitic rocks, however, formed by crystal-liquid equilibria and thus contrast sharply in their petrogenesis and environment of formation from eclogite facies metamorphic rocks. Experimental studies show that when hydrous mafic to intermediate composition assemblages are melted in excess of 1 GPa, the derivative liquids are typical of Cordilleran-type batholith granitoids, and garnet + clinopyroxene, which is an eclogitic mineralogy, dominate the residue assemblage. Upper mantle-lower crustal xenolith suites that were entrained in mid-Miocene volcanic centers erupted through the central Sierra Nevada batholith are dominated by such garnet clinopyroxenites, which are shown further by geochemical data to be petrogenetically related to the overlying batholith as its residue assemblage. Petrogenetic data on garnet pyroxenite and associated peridotite and granulite xenoliths, in conjunction with a southward deepening oblique crustal section and seismic data, form the basis for the synthesis of a primary lithospheric column for the Sierra Nevada batholith. Critical aspects of this column are the dominance of felsic batholithic rocks to between 35 and 40 km depths, a thick (∼35 km) underlying garnet clinopyroxenite residue sequence, and interlayered spinel and underlying garnet peridotite extending to ∼125 km depths. The peridotites appear to be the remnants of the mantle wedge from beneath the Sierran arc. The principal source for the batholith was a polygenetic hydrous mafic to intermediate composition lower crust dominated by mantle wedge-derived mafic intrusions. Genesis of the composite batholith over an ∼50 m.y. time interval entailed the complete reconstitution of the Sierran lithosphere. Sierra Nevada batholith magmatism ended by ∼80 Ma in conjunction with the onset of the Laramide orogeny, and subsequently, its underlying mantle lithosphere cooled conductively. In the southernmost Sierra-northern Mojave Desert region the subbatholith mantle lithosphere was mechanically delaminated by a shallow segment of the Laramide slab and was replaced by underthrust subduction accretion assemblages. Despite these Laramide events, the mantle lithosphere of the greater Sierra Nevada for the most part remained intact throughout much of Cenozoic time. A pronounced change in xenolith suites sampled by Pliocene-Quaternary lavas to garnet absent, spinel and plagioclase peridotites, whose thermobarometry define an asthenosphere adiabat, as well as seismic data, indicate that much of the remaining sub-Sierran lithosphere was removed in Late Miocene to Pliocene time. Such removal is suggested to have arisen from a convective instability related to high-magnitude extension in the adjacent Basin and Range province and to have worked in conjunction with the recent phase of Sierran uplift and a change in regional volcanism to more primitive compositions. In both the Mio-Pliocene and Late Cretaceous lithosphere removal events the base of the felsic batholith was the preferred locus of separation

Sobolev spaces

Master of ScienceDepartment of MathematicsMarianne KortenThe goal for this paper is to present material from Gilbarg and Trudinger’s Elliptic Partial Differential Equations of Second Order chapter 7 on Sobolev spaces, in a manner easily accessible to a beginning graduate student. The properties of weak derivatives and there relationship to conventional concepts from calculus are the main focus, that is when do weak and strong derivatives coincide. To enable the progression into the primary focus, the process of mollification is presented and is widely used in estimations. Imbedding theorems and compactness results are briefly covered in the final sections. Finally, we add some exercises at the end to illustrate the use of the ideas presented throughout the paper

Spanning tree modulus: deflation and a hierarchical graph structure

Doctor of PhilosophyDepartment of MathematicsNathan AlbinThe concept of discrete $p$-modulus provides a general framework for understanding arbitrary families of objects on a graph. The $p$-modulus provides a sense of ``structure'' of the underlying graph, with different families of objects leading to different insight into the graph's structure. This dissertation builds on this idea, with an emphasis on the family of spanning trees and the underlying graph structure that spanning tree modulus exposes. This dissertation provides a review of the probabilistic interpretation of modulus. In the context of spanning trees, this interpretation rephrases modulus as the problem of choosing a probability mass function on the spanning trees so that two independent, identically distributed random spanning trees have expected overlap as small as possible. A theoretical lower bound on the expected overlap is shown. Graphs that attain this lower bound are called homogeneous and have the property that there exists a probability mass function that gives every edge equal likelihood to appear in a random tree. Moreover, any nonhomogeneous graph necessarily has a homogeneous subgraph (called a homogeneous core), which is shown to split the modulus problem into two smaller subproblems through a process called deflation. Spanning tree modulus and the process of deflation establish a type of hierarchical structure in the underlying graph that is similar to the concept of core-periphery structure found in the literature. Using this, one can see an alternative way of decomposing a graph into its hierarchical community components using homogeneous cores and a related concept: minimum feasible partitions. This dissertation also introduces a simple greedy algorithm for computing the spanning tree modulus that utilizes any efficient algorithm for finding minimum spanning trees. A theoretical proof of the convergence rate is provided, along with computational examples

Seasonal variation in hospital encounters with hypoglycaemia and hyperglycaemia

Aim To assess whether rates of hospital encounters with hypoglycaemia and hyperglycaemia display seasonal variation. Methods Time series analyses of the monthly rates of hospital encounters (emergency room visits or inpatient admissions) with hypoglycaemia and hyperglycaemia from 2003 to 2012 using linked healthcare databases in Ontario, Canada. Results Over the study period, there were 129 887 hypoglycaemia and 79 773 hyperglycaemia encounters. The characteristics of people at the time of their encounters were similar across the seasons in 2008 (median age 68 years for hypoglycaemia encounters and 53 years for hyperglycaemia encounters; 50% female; 90% with diabetes). We observed moderate seasonality in both types of encounters (R2 autoregression coefficient 0.58 for hypoglycaemia; 0.59 for hyperglycaemia). The rate of hypoglycaemia encounters appeared to peak between April and June, when on average, there was an additional 49 encounters per month (0.36 encounters per 100 000 persons per month) compared with the other calendar months (5% increase). The rate of hyperglycaemia encounters appeared to peak in January, when on average, there was an additional 69 encounters per month (0.50 encounters per 100 000 persons per month) compared with the other calendar months (11% increase). Conclusions In our region, there is seasonal variation in the rate of hospital encounters with hypoglycaemia and hyperglycaemia. Our findings may help to highlight periods of vulnerability for people, may inform future epidemiological studies and may aid in the appropriate planning of healthcare resources

Evaluating the association between extreme heat and mortality in urban Southwestern Ontario using different temperature data sources

Urban areas have complex thermal distribution. We examined the association between extreme temperature and mortality in urban Ontario, using two temperature data sources: high-resolution and weather station data. We used distributed lag non-linear Poisson models to examine census division-specific temperature–mortality associations between May and September 2005–2012. We used random-effect multivariate meta-analysis to pool results, adjusted for air pollution and temporal trends, and presented risks at the 99th percentile compared to minimum mortality temperature. As additional analyses, we varied knots, examined associations using different temperature metrics (humidex and minimum temperature), and explored relationships using different referent values (most frequent temperature, 75th percentile of temperature distribution). Weather stations yielded lower temperatures across study months. U-shaped associations between temperature and mortality were observed using both high-resolution and weather station data. Temperature–mortality relationships were not statistically significant; however, weather stations yielded estimates with wider confidence intervals. Similar findings were noted in additional analyses. In urban environmental health studies, high-resolution temperature data is ideal where station observations do not fully capture population exposure or where the magnitude of exposure at a local level is important. If focused upon temperature–mortality associations using time series, either source produces similar temperature–mortality relationships

Computer-aided discovery of a metal-organic framework with superior oxygen uptake.

Current advances in materials science have resulted in the rapid emergence of thousands of functional adsorbent materials in recent years. This clearly creates multiple opportunities for their potential application, but it also creates the following challenge: how does one identify the most promising structures, among the thousands of possibilities, for a particular application? Here, we present a case of computer-aided material discovery, in which we complete the full cycle from computational screening of metal-organic framework materials for oxygen storage, to identification, synthesis and measurement of oxygen adsorption in the top-ranked structure. We introduce an interactive visualization concept to analyze over 1000 unique structure-property plots in five dimensions and delimit the relationships between structural properties and oxygen adsorption performance at different pressures for 2932 already-synthesized structures. We also report a world-record holding material for oxygen storage, UMCM-152, which delivers 22.5% more oxygen than the best known material to date, to the best of our knowledge

KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively—laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT