The Trans-Atlantic Geotraverse hydrothermal field : a hydrothermal system on an active detachment fault

© The Author(s), 2015. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 121 (2015): 8-16, doi:10.1016/j.dsr2.2015.02.015.Over the last ten years, geophysical studies have revealed that the Trans-Atlantic Geotraverse (TAG) hydrothermal field (26°08’N on the Mid-Atlantic Ridge) is located on the hanging wall of an active detachment fault. This is particularly important in light of the recognition that detachment faulting accounts for crustal accretion/extension along a significant portion of the Mid-Atlantic Ridge, and that the majority of confirmed vent sites on this slow-spreading ridge are hosted on detachment faults. The TAG hydrothermal field is one of the largest sites of high-temperature hydrothermal activity and mineralization found to date on the seafloor, and is comprised of active and relict deposits in different stages of evolution. The episodic nature of hydrothermal activity over the last 140 ka provides strong evidence that the complex shape and geological structure of the active detachment fault system exerts first order, but poorly understood, influences on the hydrothermal circulation patterns, fluid chemistry, and mineral deposition. While hydrothermal circulation extracts heat from a deep source region, the location of the source region at TAG is unknown. Hydrothermal upflow is likely focused along the relatively permeable detachment fault interface at depth, and then the high temperature fluids leave the low-angle portion of the detachment fault and rise vertically through the highly fissured hanging wall to the seafloor. The presence of abundant anhydrite in the cone on the summit of the TAG active mound and in veins in the crust beneath provides evidence for a fluid circulation system that entrains significant amounts of seawater into the shallow parts of the mound and stockwork. Given the importance of detachment faulting for crustal extension at slow spreading ridges, the fundamental question that still needs to be addressed is: How do detachment fault systems, and the structure at depth associated with these systems (e.g., presence of plutons and/or high permeability zones) influence the pattern of hydrothermal circulation, mineral deposition, and fluid chemistry, both in space and time, within slowly accreted ocean crust?We acknowledge the National Science Foundation which has supported our research at the TAG hydrothermal field through many awards for cruises, technological advancement of equipment, analytical, and modeling work.2016-02-2

Rare earth element abundances in hydrothermal fluids from the Manus Basin, Papua New Guinea : indicators of sub-seafloor hydrothermal processes in back-arc basins

Author Posting. © The Author(s), 2010. 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 Geochimica et Cosmochimica Acta 74 (2010): 5494-5513, doi:10.1016/j.gca.2010.07.003.Rare earth element (REE) concentrations are reported for a large suite of seafloor vent fluids from four hydrothermal systems in the Manus back–arc basin (Vienna Woods, PACMANUS, DESMOS and SuSu Knolls vent areas). Sampled vent fluids show a wide range of absolute REE concentrations and chondrite–normalized (REEN) distribution patterns (LaN/SmN ~ 0.6 – 11; LaN/YbN ~ 0.6 – 71; EuN/Eu*N ~ 1 – 55). REEN distribution patterns in different vent fluids range from light–REE enriched, to mid– and heavy–REE enriched, to flat, and have a range of positive Eu–anomalies. This heterogeneity contrasts markedly with relatively uniform REEN distribution patterns of mid–ocean ridge hydrothermal fluids. In Manus Basin fluids, aqueous REE compositions do not inherit directly or show a clear relationship with the REE compositions of primary crustal rocks with which hydrothermal fluids interact. These results suggest that the REEs are less sensitive indicators of primary crustal rock composition despite crustal rocks being the dominant source of REEs in submarine hydrothermal fluids. In contrast, differences in aqueous REE compositions are consistently correlated with differences in fluid pH and ligand (chloride, fluoride and sulfate) concentrations. Our results suggest that the REEs can be used as an indicator of the type of magmatic acid volatile (i.e., presence of HF, SO2) degassing in submarine hydrothermal systems. Additional fluid data suggest that near seafloor mixing between high–temperature hydrothermal fluid and locally entrained seawater at many vent areas in the Manus Basin causes anhydrite precipitation. Anhydrite effectively incorporates REE and likely affects measured fluid REE concentrations, but does not affect their relative distributions.This study received financial support from the Ocean Drilling Program Schlanger Fellowship (to P.R. Craddock), the WHOI Deep Ocean Exploration Institute Graduate Fellowship (to E. Reeves) and NSF grant OCE–0327448

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and 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 biomarker driven 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, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but 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 post-platinum therapy

Deducing patterns of fluid flow and mixing within the TAG active hydrothermal mound using mineralogical and geochemical data

The TAG active hydrothermal mound, located 2.4 km east of the neovolcanic zone at 26°N, Mid-Atlantic Ridge, is −200 m in diameter, exhibits 50 m of relief, and is covered entirely by hydrothermal precipitates. Eight different types of vent solids were recovered from the mound by the submersibles Alvin and Mir in 1986, 1990, and 1991. Detailed petrographic and geochemical studies of samples and their distribution are used to deduce patterns of fluid flow and seawater/hydrothermal fluid interaction. Geochemical modeling calculations using fluid composition data corroborate these interpretations. Current activity includes highly focused flow of 363°C fluid from a chimney cluster on the top of the mound and deposition of a high ƒS2-ƒO2 mineral assemblage that reflects low concentrations of H2S in black smoker fluid. Slow percolation of black smoker fluid pooled beneath the black smoker cluster and entrainment of seawater result in formation of massive sulfide crusts and massive anhydrite. These three sample types are enriched in Co and Se. Blocks of sulfide and white smoker chimneys, enriched in Zn, Au, Ag, Sb, Cd, and Pb, are forming on the surface of the mound from black smoker fluid that has been modified by mixing with entrained seawater, precipitation of sulfides and anhydrite, and dissolution of sphalerite within the mound. This is the first time that on-going remobilization, zone refinement, and significant modification of high-temperature fluid in the near surface has been documented in a seafloor hydrothermal system. Deposits of ocherous material and massive sulfide with outer oxidized layers that formed during previous hydrothermal episodes are exposed on the steep outer walls of the mound. Studies of the full range of samples demonstrate that highly focused fluid flow, consequent seawater entrainment, and mixing within the mound can result in formation of a large seafloor hydrothermal deposit exhibiting sample types similar to those observed in Cyprus-type ore bodies

A model for growth of steep-sided vent structures on the Endeavour Segment of the Juan de Fuca Ridge: Results of a petrologic and geochemical study

Petrologic and geochemical studies of vent solids from the Main Endeavour Field (MEF) and the High Rise Field (HRF), Juan de Fuca Ridge, demonstrate that the steep‐sided vent structures characteristic of these sites form dominantly by flange growth, combined with diffuse flow through sealed portions of structures, and incorporation of flanges into structures. Geochemical calculations suggest that the prevalence of amorphous silica and flanges in Endeavour deposits is the result of conductive cooling of vent fluids that have high concentrations of ammonia. At Endeavour, as the temperature of vent fluid decreases, ammonia‐ammonium equilibrium buffers pH and allows more efficient deposition of sulfide minerals and silica from fluids that have a higher pH than conductively cooled ammonia‐poor fluids present at most other unsedimented mid‐ocean ridge vent sites. Deposition of silica stabilizes flanges and allows structures to attain large size. It also leads to diffuse flow and further conductive cooling by reducing the permeability and porosity of the structures and of feeder zones, thus decreasing entrainment of seawater. Most inactive vent samples recovered from areas peripheral to the HRF and MEF are similar to barite + silica rich samples from the Explorer Ridge and Axial Seamount and likely formed from precipitation of silica and barite on a biological substrate. Active white smoker chimneys from the Clam Bed Field, located south of the HRF, are pyrrhotite rich and likely formed from vent fluids that are depleted in Zn and Cd and enriched in Pb and Ba relative to fluids exiting trans‐Atlantic geotraverse (TAG) and Cleft Segment white smoker chimneys

Predictors of quality of life in head and neck cancer survivors up to 5 years after end of treatment:a cross-sectional survey

PURPOSE This study aimed to assess quality of life (QoL) in head and neck cancer (HNC) survivors and determine factors predictive of poor QoL in the first 5 years after the end of treatment. METHODS A cross-sectional survey, including the Quality of Life in Adult Cancer Survivors (QLACS) measure, was sent to HNC survivors in three Scottish health regions, with responses linked to routinely collected clinical data. Independent sample t tests, ANOVAs, Pearson correlations and multiple hierarchical regressions were used to explore associations between and to determine the contribution made by demographic, lifestyle and clinical factors to predicting 'generic' and 'cancer-specific' quality of life. RESULTS Two hundred eighty patients (65 %) returned questionnaires. After adjustment, multivariate analysis showed that younger age, lower socio-economic status, unemployment and self-reported comorbidity independently contributed to poorer generic and cancer-specific quality of life. In addition to these factors, having had a feeding tube or a diagnosis of oral cavity cancer were independently predictive of poorer cancer-specific quality of life. CONCLUSIONS Socio-economic factors and comorbidity are important predictors of QoL in HNC survivors. These factors and the detrimental long-term effects of feeding tubes need further attention in research and practice

Hypermutation In Pancreatic Cancer

© 2017 AGA Institute Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer