243 research outputs found

    Reflection Seismic Imaging for Mineral Exploration in the Sotiel-Coronada Area, Southwest Spain

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    Near Surface Geoscience Conference & Exhibition Online 2020This work explores the first results of the seismic data acquired in the Sotiel-Coronada mine as part of the SIT4ME (Seismic Imaging Techniques for Mineral Exploration) project. In this experiment, a multi-source seismic data-set was acquired at the end of 2018 in the Sotiel- Coronada area of the Iberian Pyrite Belt (IPB) (southwest Spain). In the seismic experiment presented, 653 seismic receivers were deployed distributed in a pseudo 3D grid and six crooked lines across the study area. The sensors recorded c. 900 vibration points produced by a 32 Tn vibrotruck. Here, we present the stack results of the 2D seismic sections. Data from over 100 wells have been incorporating to aid in the structural interpretation. The preliminary interpretation reveals the complexity of this highly faulted ore-bearing area. Correlations between well log data information and 2D seismic profiles, suggest the location of a potentially mineralized area. The SIT4ME project has been funded by EIT Raw Materials (17024)

    MEME Suite: tools for motif discovery and searching

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    The MEME Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as DNA binding sites and protein interaction domains. The popular MEME motif discovery algorithm is now complemented by the GLAM2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms—MAST, FIMO and GLAM2SCAN—allow scanning numerous DNA and protein sequence databases for motifs discovered by MEME and GLAM2. Transcription factor motifs (including those discovered using MEME) can be compared with motifs in many popular motif databases using the motif database scanning algorithm Tomtom. Transcription factor motifs can be further analyzed for putative function by association with Gene Ontology (GO) terms using the motif-GO term association tool GOMO. MEME output now contains sequence LOGOS for each discovered motif, as well as buttons to allow motifs to be conveniently submitted to the sequence and motif database scanning algorithms (MAST, FIMO and Tomtom), or to GOMO, for further analysis. GLAM2 output similarly contains buttons for further analysis using GLAM2SCAN and for rerunning GLAM2 with different parameters. All of the motif-based tools are now implemented as web services via Opal. Source code, binaries and a web server are freely available for noncommercial use at http://meme.nbcr.net

    Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

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    Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel

    Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer.

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    Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer

    SIT4ME: Multidisciplinary techniques for mining exploration in Sotiel (SW-Spain).

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    X Congreso Geológico de España, 5-7 Julio 2021, Vitoria - GasteizLa necesidad de satisfacer la creciente demanda de materia prima de forma segura, sostenible y a bajo coste, es la principal motivación del proyecto SIT4ME, financiado por el programa EIT-Raw Materials. El objetivo principal de SIT4ME es desarrollar una metodología efectiva y eficiente para la exploración de recursos minerales mediante métodos sísmicos. Este proyecto se centra en la adquisición, procesado e interpretación de datos sísmicos (fuente activa y pasiva) en un entorno real: Sotiel-Coronada, ubicada al SO de la Faja Pirítica Ibérica. Estos datos permitirán obtener imágenes de las principales estructuras y de los niveles mineralizados a profundidades de entre 300-500 m. El procesado de los datos sísmicos 2D incluye correcciones estáticas, deconvolución, ecualización de la amplitud, filtro de frecuencia y análisis de velocidad. La correlación entre las imágenes sísmicas, la geología de superficie y los sondeos existentes ha permitido identificar las principales estructuras. Los resultados muestran buena reflectividad hasta los 2000 ms two-way traveltime (TWT), con estructuras buzando al norte. En la zona central del perfil se identifica una zona de alta reflectividad de 385 m de longitud a 130 ms TWT, correspondiente a un nivel mineralizado. En el futuro se incluirán procesos de migración pre-stack, procesado sísmico de los datos en 3D y tomografía de primeras llegadas para obtener un modelo robusto incrementando la probabilidad de éxito en la exploración.The need to satisfy the increasing demand for raw materials in a safe, sustainable and cost-effective manner, is the main motivation of the SIT4ME project, financed by the EIT-Raw Materials program. The main objective of SIT4ME is to develop an effective and efficient methodology to apply seismic techniques in the search of mineral resources. This project focuses on the acquisition, processing and interpretation of seismic data (controlled and natural sources) in a real environment: Sotiel-Coronada, located at the SW of the Iberian Pyrite Belt. These data will allow us to obtain images of the principal structures and mineralized levels at depths of 300-500 m. The 2D seismic data process flow includes static corrections, deconvolution, amplitude equalization, frequency filters and velocity analysis. The correlation between seismic images, surface geology and existing drill cores allowed identifying the main deep structures. The results show good, north-dipping reflectivity up to 2000 ms TWT. A high reflectivity zone, c. 380m long, exists in the center of the profile at 130 ms TWT, related to one of the mineralized areas. Future work will include the pre-stack depth migration, processing of 3D seismic data and first arrivals tomography to obtain a robust model that increases the probability of success in the exploration

    Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

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    The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

    Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting

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    Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson &nbsp;&gt;&nbsp;0·91, P&nbsp;&lt;&nbsp;0·001). Multi-centre testing introduced variation in reported LSC percentages but was found to be below the clinical relevant threshold. Clear gating protocols resulted in all laboratories being able to perform LSC assessment of the validation set. Participating centres were nearly unanimously able to distinguish LSChigh (&gt;0·03% LSC) from LSClow (&lt;0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification

    Dual-functioning transcription factors in the developmental gene network of Drosophila melanogaster

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    Quantitative models for transcriptional regulation have shown great promise for advancing our understanding of the biological mechanisms underlying gene regulation. However, all of the models to date assume a transcription factor (TF) to have either activating or repressing function towards all the genes it is regulating.In this paper we demonstrate, on the example of the developmental gene network in D. melanogaster, that the data-fit can be improved by up to 40% if the model is allowing certain TFs to have dual function, that is, acting as activator for some genes and as repressor for others. We demonstrate that the improvement is not due to additional flexibility in the model but rather derived from the data itself. We also found no evidence for the involvement of other known site-specific TFs in regulating this network. Finally, we propose SUMOylation as a candidate biological mechanism allowing TFs to switch their role when a small ubiquitin-like modifier (SUMO) is covalently attached to the TF. We strengthen this hypothesis by demonstrating that the TFs predicted to have dual function also contain the known SUMO consensus motif, while TFs predicted to have only one role lack this motif.We argue that a SUMOylation-dependent mechanism allowing TFs to have dual function represents a promising area for further research and might be another step towards uncovering the biological mechanisms underlying transcriptional regulation

    Models, measurement and inference in epithelial tissue dynamics

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    The majority of solid tumours arise in epithelia and therefore much research effort has gone into investigating the growth, renewal and regulation of these tissues. Here we review different mathematical and computational approaches that have been used to model epithelia. We compare different models and describe future challenges that need to be overcome in order to fully exploit new data which present, for the first time, the real possibility for detailed model validation and comparison
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