63 research outputs found

    Characterization of a potential CO2 storage complex in the Cambay Basin, India

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    Introduction High-level studies have identified that there is potential for subsurface storage of CO2 in India (Holloway et al., 2009; Vishal et al., 2021). A major challenge to the deployment of CO2 storage in India is the lack of detailed technical appraisals aimed at understanding and de-risking the storage resource. The vast majority of India’s CO2 storage resource is therefore considered to be undiscovered as per the Society of Petroleum Engineers CO2 Storage Resource Management System (SRMS) scale (SPE, 2017). Given the need to rapidly appraise India’s storage resource to support emission reductions targets, one pragmatic approach would be to first define representative storage complexes in key regions of interest for future CO2 storage developments. Theory and/or Method The notion of a CO2 storage complex is embedded in European legislation, where it provides a means of defining the storage site and surrounding geological domain which can have an effect on overall storage integrity and security, including secondary containment formations (EC, 2009). Defining a storage complex can therefore be a key starting point in identifying the specific site appraisal studies required to gain insight into the likely dynamic behavior of sites during CO2 injection, including the long-term post-injection period. This presentation will investigate how storage projects developed in NW Europe have considered the subsurface lithostratigraphy and structure to define storage complex boundaries. Through interpretation of legacy datasets acquired during legacy oil and gas exploration and development, these principles will then be applied to an area on the flank of the brownfield Gandhar Oil Field in the Cambay Basin, Gujarat. Example The lithostratigraphic determination of a potential storage complex within the Anklesvar Formation is illustrated in Figure 1. The stratigraphy of the Cambay Basin presents the possibility for several different storage concepts. Firstly, hydrocarbon-bearing sandstones of the Mid-Eocene Hazad Member may be suitable for CO2 storage, either following cessation of production, and/or as a beneficial by-product of CO2-enhanced oil recovery. The Hazad Member is sealed by shales of the Kanwa Member. Secondly, marine shales of the overlying Ardol Member provide an additional top seal, while deltaic sandstones are also present over part of the area which present an opportunity for saline aquifer storage. The sand-prone sequences within the Ardol Member may be considered as a storage opportunity in their own right, or in the context of secondary storage in the event of CO2 storage in the Hazad Member. The storage complex is capped by shales of the Telwa Member, which exhibits a variable thickness distribution across the region. The regionally extensive Y Marker in the Upper part of the Cambay Shale provides a reliable seismic reflector which can conveniently be used to define the lower storage complex boundary. In this way, thin impersistent sandstones in the upper part of the Cambay Shale are also incorporated within the storage complex. Evaluation of legacy oil and gas datasets have enabled mapping of the distribution, thickness and structural disposition of the reservoir and top seal units. This has enabled a high-level assessment of the storage potential and associated storage risks to be determined. The spatial arrangement of reservoir sands in the Hazad and Ardol Members is controlled by frequent fluctuations between transgressive and regressive sequences, and the direction of sediment input. The deltaic sands of the Hazad Member are mainly sourced from the Northeast, and are covered by transgressive shales of the Kanwa Member. Changes in baselevel and sediment input direction have influenced the distribution of the Ardol Member, leading to an uneven distribution of sands. The Telwa shale, acting as the regional seal, experiences occasional erosion beneath a second-order erosional unconformity. No major faults offset the storage complex in the study area, with the primary risk being the presence of down-cutting sandstone units affecting the Kanwa and/or Telwa member top seals. A number of key recommendations for further detailed appraisal have been identified, including the requirement to accurately determine the volumes of sandstone available for CO2 storage capacity estimations, and the requirement to carefully characterize the thickness of the Telwa Member as the ultimate top seal. Finally, the high number of legacy oil and gas wells in the region will necessitate detailed well integrity studies. Conclusions We have demonstrated for the first time how application of the storage complex concept can be applied to an onshore sedimentary basin in India. The study has enabled identification of specific activities that will be required to fully understand the CO2 storage potential of the region. These measures relate to the quantification of storage capacity, the likely dynamic behavior of the site, and the understanding of containment risk and natural barriers

    A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma

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    Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. It is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs. We engineered an implantable poly(lactic-co-glycolic)-based biodegradable device that is able to linearly release high doses of chemotherapeutic drugs for up to 60 days. We created five patient-derived PDAC cell lines and tested their sensitivity to approved chemotherapeutic compounds. These in vitro experiments showed that paclitaxel was the most effective single agent across all cell lines. We compared the efficacy of systemic and local paclitaxel therapy on the patient-derived cell lines in an orthotopic xenograft model in mice (PDX). In this model, we found up to a 12-fold increase in suppression of tumor growth by local therapy in comparison to systemic administration and reduce retention into off-target organs. Herein, we highlight the efficacy of a local therapeutic approach to overcome PDAC chemoresistance and reduce the need for repeated interventions and biliary obstruction by preventing local tumor growth. Our results underscore the urgent need for an implantable drug-eluting platform to deliver cytotoxic agents directly within the tumor mass as a novel therapeutic strategy for patients with pancreatic cancer. Keywords: Pancreatic cancer; Chemoresistance; Local delivery; Patient-derived xenograft; Paclitaxel; Poly(lactic-co-glycolic acid)National Institutes of Health (U.S.) (Grant P30-CA14051

    EWS-FLI1 Utilizes Divergent Chromatin Remodeling Mechanisms to Directly Activate or Repress Enhancer Elements in Ewing Sarcoma

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    SummaryThe aberrant transcription factor EWS-FLI1 drives Ewing sarcoma, but its molecular function is not completely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements, which lack evolutionary conservation and regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors. These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets, such as the kinase VRK1. Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation

    Science with the Daksha High Energy Transients Mission

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    We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to >1>1~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

    Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

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    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
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