Importance of hydrothermal vents in scavenging removal of ²³⁰Th in the Nansen Basin

In this study we present dissolved and particulate ²³⁰Th and ²³²Th results, as well as particulate ²³⁴Th data, obtained as part of the GEOTRACES central Arctic Ocean sections GN04 (2015) and IPY11 (2007). Samples were analyzed following GEOTRACES methods and compared to previous results from 1991. We observe significant decreases in ²³⁰Th concentrations in the deep waters of the Nansen Basin. We ascribe this nonsteady state removal process to a variable release and scavenging of trace metals near an ultraslow spreading ridge. This finding demonstrates that hydrothermal scavenging in the deep‐sea may vary on annual time scales and highlights the importance of repeated GEOTRACES sections

Thorium speciation in seawater

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Chemistry 100 (2006): 250-268, doi:10.1016/j.marchem.2005.10.024.Since the 1960’s, thorium isotopes occupy a special place in the oceanographer’s toolbox as tracers for determining rates and mechanisms of oceanic scavenging, particle dynamics, and carbon fluxes. Due to their unique and constant production rates from soluble parent nuclides of uranium and radium, their disequilibrium can be used to calculate rates and time scales of sinking particles. In addition, by ratio-ing particulate 234Th (as well, in principle, other Thnuclides) to carbon (and other elements), and linking this ratio to the parent-daughter disequilibrium in the water column, it is possible to calculate fluxes of carbon and other elements. Most of these applications are possible with little knowledge of the dissolved chemical properties of thorium, other than its oxidation state (IV) and tendency to strongly sorb to surfaces, i.e., its “particle- or surface-activity”. However, the use of any tracer is hindered by a lack of knowledge of its chemical properties. Recent observations in the variability of carbon to 234Th ratios in different particle types, as well as of associations of Th(IV) with various marine organic biomolecules has led to the need for a review of current knowledge and what future endeavors should be taken to understand the marine chemistry of thorium.The writing of this paper was supported, in parts by NSF (OCE-0351559; OCE-0350758, and OCE 0354757)

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

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarkerdriven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. RESULTS: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. CONCLUSIONS: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.Stephan B. Dreyer ... Karin S. Kassahn ... et al

Numerical investigation of 3-D constraint effects on brittle fracture in SE(B) and C(T) specimens

This investigation employs 3-D nonlinear finite element analyses to conduct an extensive parametric evaluation of crack front stress triaxiality for deep notch SE(B) and C(T) specimens and shallow notch SE(B) specimens, with and without side grooves. Crack front conditions are characterized in terms of J-Q trajectories and the constraint scaling model for cleavage fracture toughness proposed previously by Dodds and Anderson. The 3-D computational results imply that a significantly less strict size/deformation limit, relative to the limits indicated by previous plane-strain computations, is needed to maintain small-scale yielding conditions at fracture by a stress- controlled, cleavage mechanism in deep notch SE(B) and C(T) specimens. Additional new results made available from the 3-D analyses also include revised {eta}-plastic factors for use in experimental studies to convert measured work quantities to thickness average and maximum (local) J-values over the crack front

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe