The significance of atypical high-silica igneous rocks

The origins of high-silica igneous rocks are debated, as they may be products of high-degree fractional crystallization or low-degree partial melting. They may play a role in the generation of intermediate igneous rocks and are responsible for large, ash-rich volcanic eruptions. High-silica granites and rhyolites in the Sierra Nevada, California, and the Colorado Mineral Belt (CMB) are investigated using isotope geochemistry to better understand how they bear on these questions. Zircon U-Pb geochronology identifies two intrusive suites comprising large volumes of high-silica granites emplaced in the mid-Cretaceous Sierra Nevada batholith: the 106-98 Ma Shaver Intrusive Suite (SIS) in the central part of the batholith, and the 103-100 Ma Kearsarge intrusive suite (KIS) on the Sierra Crest and Owens Valley. High-silica granites in both suites have relatively high concentrations of middle rare earth and high field strength elements. Data for these and other discrete high-silica plutons in the batholith suggest they were derived from titanite-free sources in the deep crust, unlike similarly felsic parts of zoned intrusive suites. Despite similar trace element signatures, SIS and KIS high-silica granites have divergent isotopic compositions. High-silica granites of the SIS have supracrustal O in zircon, crustal Sr and Nd whole rock isotopic compositions, and negative Ce anomalies suggesting the SIS granites may have been derived from oceanic sedimentary sources. In contrast, KIS granites have mantle-like isotopic compositions. The location and geochemistry of the KIS suggests it may have resulted from backarc magmatism in the mid-Cretaceous Sierra. Volcanic and plutonic rocks in the central CMB were emplaced during the Laramide orogeny and subsequent Oligocene-Eocene volcanic flare-up. Strontium and Nd data suggest the 63-39 Ma Twin Lakes pluton and igneous rocks as young as 24 Ma were derived from a persistent mafic lower crust or enriched lithospheric mantle source. In contrast, the ~35 Ma Grizzly Peak Tuff and resurgent plutons are isotopically dissimilar from each other and the CMB as a whole, suggesting derivation by partial melting of ancient felsic lower crust. This distinct source could account for the lack Mo mineralization in the Grizzly Peak caldera relative to other high-silica parts of the CMB.Doctor of Philosoph

Evaluating pluton-volcano relationships: an example from the Mount Givens Granodiorite

Zircon U-Pb geochronology indicates that the Mount Givens Granodiorite (MGG) of the Sierra Nevada batholith, California, was constructed over at least 7 Ma from 98-91 Ma. Chemical and volumetric similarities between homogenous ignimbrites (monotonous intermediates; MIs) and plutons such as the MGG led some to suggest a genetic relationship between the two. However, there are three issues regarding this link: 1) large plutons like the MGG accumulated at estimated rates of 0.001 km3/a, 1-2 orders of magnitude less than fluxes calculated for MIs; 2) zircon dissolution modeling indicates that rejuvenation events thought to affect MIs would not sufficiently dissolve zircon that should record multi-Ma growth of a crystal-rich mush 3) the Sierra Nevada batholith apparently lacks mafic plutons large enough to initiate MI eruptions. I suggest that MI eruptions are caused by high flux events, leaving little behind in the intrusive rock record, whereas low fluxes favor pluton growth.Master of Scienc

A tail-like assembly at the portal vertex in intact herpes simplex type-1 virions

Herpes viruses are prevalent and well characterized human pathogens. Despite extensive study, much remains to be learned about the structure of the genome packaging and release machinery in the capsids of these large and complex double-stranded DNA viruses. However, such machinery is well characterized in tailed bacteriophage, which share a common evolutionary origin with herpesvirus. In tailed bacteriophage, the genome exits from the virus particle through a portal and is transferred into the host cell by a complex apparatus (i.e. the tail) located at the portal vertex. Here we use electron cryo-tomography of human herpes simplex type-1 (HSV-1) virions to reveal a previously unsuspected feature at the portal vertex, which extends across the HSV-1 tegument layer to form a connection between the capsid and the viral membrane. The location of this assembly suggests that it plays a role in genome release into the nucleus and is also important for virion architecture

VLA 1.4 GHz Catalogs of the Abell 370 and Abell 2390 Cluster Fields

We present 1.4 GHz catalogs for the cluster fields Abell 370 and Abell 2390 observed with the Very Large Array. These are two of the deepest radio images of cluster fields ever taken. The Abell 370 image covers an area of 40'x40' with a synthesized beam of ~1.7" and a noise level of ~5.7 uJy near field center. The Abell 2390 image covers an area of 34'x34' with a synthesized beam of ~1.4" and a noise level of ~5.6 uJy near field center. We catalog 200 redshifts for the Abell 370 field. We construct differential number counts for the central regions (radius < 16') of both clusters. We find that the faint (S_1.4GHz < 3 mJy) counts of Abell 370 are roughly consistent with the highest blank field number counts, while the faint number counts of Abell 2390 are roughly consistent with the lowest blank field number counts. Our analyses indicate that the number counts are primarily from field radio galaxies. We suggest that the disagreement of our counts can be largely attributed to cosmic variance.Comment: 13 pages, accepted for publication in ApJ

J1649+2635: A Grand-Design Spiral with a Large Double-Lobed Radio Source

We report the discovery of a grand-design spiral galaxy associated with a double-lobed radio source. J1649+2635 (z = 0.0545) is a red spiral galaxy with a prominent bulge that it is associated with a L$_{1.4{\rm GHz}}\sim$10$^{24}$WHz$^{-1}$ double-lobed radio source that spans almost 100kpc. J1649+2635 has a black hole mass of M$_{\rm BH} \sim$ 3--7 $\times$ 10$^8$M$_{\odot}$ and SFR$\sim$ 0.26 -- 2.6M$_{\odot}$year$^{-1}$. The galaxy hosts a $\sim$96kpc diffuse optical halo, which is unprecedented for spiral galaxies. We find that J1649+2635 resides in an overdense environment with a mass of M$_{dyn} = 7.7^{+7.9}_{-4.3} \times 10^{13}$M$_{\odot}$, likely a galaxy group below the detection threshold of the ROSAT All-Sky Survey. We suggest one possible scenario for the association of double-lobed radio emission from J1649+2635 is that the source may be similar to a Seyfert galaxy, located in a denser-than-normal environment. The study of spiral galaxies that host large-scale radio emission is important because although rare in the local Universe, these sources may be more common at high-redshifts.Comment: 11 pages, 9 figures, Accepted for publication in MNRA

Clinical translation of a click-labeled 18F-octreotate radioligand for imaging neuroendocrine tumors

© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAGTOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts