Linking mineralisation process and sedimentary product in terrestrial carbonates using a solution thermodynamic approach

Determining the processes which generate terrestrial carbonate deposits (tufas, travertines and to a lesser extent associated chemical sediments such as calcretes and speleothems) is a long-standing problem. Precipitation of mineral products from solution reflects a complex combination of biological, equilibrium and kinetic processes, and the different morphologies of carbonate sediment produced by different processes have yet to be clearly demarked. Building on the groundbreaking work of previous authors, we propose that the underlying control on the processes leading to the deposition of these products can be most parsimoniously understood from the thermodynamic properties of their source solutions. Here, we report initial observations of the differences in product generated from spring and lake systems spanning a range of temperature–supersaturation space. We find that at high supersaturation, biological influences are masked by high rates of physico-chemical precipitation, and sedimentary products from these settings infrequently exhibit classic "biomediated" fabrics such as clotted micrite. Likewise, at high temperature (>40 °C) exclusion of vascular plants and complex/diverse biofilms can significantly inhibit the magnitude of biomediated precipitation, again impeding the likelihood of encountering the "bio-type" fabrics. <br></br> Conversely, despite the clear division in product between extensive tufa facies associations and less spatially extensive deposits such as oncoid beds, no clear division can be identified between these systems in temperature–supersaturation space. We reiterate the conclusion of previous authors, which demonstrate that this division cannot be made on the basis of physico-chemical characteristics of the solution alone. We further provide a new case study of this division from two adjacent systems in the UK, where tufa-like deposition continuous on a metre scale is happening at a site with lower supersaturation than other sites exhibiting only discontinuous (oncoidal) deposition. However, a strong microbiological division is demonstrated between these sites on the basis of suspended bacterial cell distribution, which reach a prominent maximum where tufa-like deposits are forming. <br></br> We conclude that at high supersaturation, the thermodynamic properties of solutions provide a highly satisfactory means of linking process and product, raising the opportunity of identifying water characteristics from sedimentological/petrological characteristics of ancient deposits. At low supersaturation, we recommend that future research focuses on geomicrobiological processes rather than the more traditional, inorganic solution chemistry approach dominant in the past

Interaction of temperature, salinity and extracellular polymeric substances controls trace element incorporation into tufa calcite

The influence of extracellular polymeric substances on carbonate mineral growth in natural settings remains one of the most poorly understood contributors to the growth of non-marine carbonate sediments. The influences of these materials are complicated by their association with living cells creating local microenvironments via metabolism and enzyme production, and by our uncertainty about the extracellular polymeric substances materials themselves. Different mixtures of extracellular polymeric substance molecules may behave in different ways, and differences in the local physical environment may alter how the mixtures influence mineral formation, and even result in different patterns of polymerization. Here, the influence of extracellular polymeric substances on calcite precipitation rate and Mg/Cacalcite in the absence of cells is investigated using extracts of extracellular polymeric substances from temperate fluvial tufa biofilm. The influence is complex, with the concentration of extracellular polymeric substances in solution altering deposition rate and trace element incorporation. Moreover, the results show interaction of the presence/absence of extracellular polymeric substances and both temperature and salinity. However, despite extracting extracellular polymeric substances from the same parent sample, a uniform influence was not found in these experiments, implying that the mixture is sufficiently variable within a sample for microenvironments within the biofilm to either promote or inhibit mineralization. As sedimentologists, we can no longer take the view that extracellular polymeric substances are a bystander material, or that they have a single set of coherent and predictable or intuitive influences. Rather, the emphasis must be on investigating the specific mixtures present in nature, and their complex and dynamic interaction with both mineral surfaces and hydrochemical conditions

A participatory methodology for future scenario analysis of sub-national water and sanitation access: case study of Kisumu, Kenya

This study pilots a participatory methodology for sub-national spatial planning of urban and peri-urban water and sanitation services. Three groups of key informants were presented with evidence on national historic and future service provision trajectories and asked to map water and sanitation access in the city of Kisumu, Kenya, by 2030, assuming current trends continue. Comparison of the groups’ outputs suggests greater certainty among participants regarding service access in Kisumu’s urban core compared to peri-urban areas. We discuss extensions to this preliminary methodology, including the potential benefits of its application to Kenya’s rapidly expanding small towns as suggested by participants

Forests from the grass: Natural regeneration of woody vegetation in temperate marginal hill farmland under minimum interference management

Marginal hill farmland is a key target for the restoration of temperate indigenous forest, which can help mitigate climate change and biodiversity loss. Reliance on natural regeneration and minimum interference management (MIM) is a low-cost restoration strategy for farmers, with the transition from pasture to woody scrub vegetation (whether indigenous or exotic) an important early successional phase. However, few studies have determined the key factors that influence the regeneration of woody vegetation on pastoral farmland, nor the rate at which regeneration occurs. Using a geospatial analysis of a New Zealand pastoral hill farm subject to variable grazing and MIM, this study found that only 3.8% of grassland experienced detectable regeneration of woody vegetation over 16 years. The key factor influencing natural regeneration was proximity to existing woody vegetation, with the probability of regeneration decreasing as distance increased. Cattle grazing had a significant negative impact, with regeneration more likely to occur in areas free from cattle. Sheep grazing exhibited no significant positive or negative relationship with regeneration. To support natural regeneration of woody vegetation, landowners should prioritize areas with a higher presence of existing woody vegetation and exclude cattle. To increase the rate of regeneration, landowners should consider active management regimes and supplemental restoration strategies, such as applied nucleation and the introduction of nurse species. Given the increased cost and complexity of such approaches, effective government incentive programmes may be needed to provide landowners with financial support and expertise

Oxygen Concentration Flammability Thresholds of Selected Aerospace Materials Considered for the Constellation Program

Materials selection for spacecraft is based on an upward flammability test conducted in a quiescent environment in the highest expected oxygen concentration environment. The test conditions and its pass/fail test logic do not provide sufficient quantitative materials flammability information for an advanced space exploration program. A modified approach has been suggested determination of materials self-extinguishment limits. The flammability threshold information will allow NASA to identify materials with increased flammability risk from oxygen concentration and total pressure changes, minimize potential impacts, and allow for development of sound requirements for new spacecraft and extraterrestrial landers and habitats. This paper provides data on oxygen concentration self-extinguishment limits under quiescent conditions for selected materials considered for the Constellation Program

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

&lt;b&gt;Background:&lt;/b&gt; Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2–3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objective:&lt;/b&gt; To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Design, setting, and participants:&lt;/b&gt; RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Outcome measurements and statistical analysis:&lt;/b&gt; We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results and limitations:&lt;/b&gt; We identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions:&lt;/b&gt; RNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.&lt;p&gt;&lt;/p&gt

Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material

An antibody-directed enzyme prodrug therapy (ADEPT) system against CEA-positive tumours is currently in phase I clinical trials. It consists of a prodrug, 4-[N,N-bis(2-iodoethyl) amino] phenoxycarbonyl L -glutamic acid (ZD2767P) and a conjugate of the F(ab')2 anti-CEA antibody A5B7 and the bacterial enzyme carboxypeptidase G2 (CPG2). ZD2767P is converted by antibody-targeted CPG2 into an active bifunctional alkylating drug (ZD2767) at the tumour site. The IC 50 value of the prodrug against the human colorectal tumour LS174T cell line was 55 ± 9 μM following a 1 h exposure. In contrast, co-incubation of ZD2767P with CPG2 resulted in 229-fold increase in activity. Using a modified comet assay, DNA interstrand cross links (ISC) were detected within 1 h of ZD2767P + CPG2 treatment and were repaired by 24 h. A clear dose–response was seen between the level of ISC, growth inhibition and ZD2767 concentration. Administration of a therapeutic dose of ZD2767P 72 h after the F(ab′)2 A5B7 conjugate to mice bearing LS147T xenografts resulted in extensive ISC in the tumour after 1 h; repair was seen at 24 h. Tumour biopsies and peripheral lymphocytes were studied in 5 patients on the ADEPT phase I clinical trial. In 4 patients no ISC were detected. These patients also demonstrated poor localization of conjugate and no tumour response was seen. However a significant level of ISC was detected in one tumour biopsy, which also showed evidence of conjugate localization and clinical response. These studies demonstrate the application of the comet assay in the measurement of ISC in vitro and in clinical material and confirm that activation of ZD2767P results in the formation of DNA crosslinks. © 2001 Cancer Research Campaign http://www.bjcancer.co