75 research outputs found

    Predicción lineal de la parte causal de la autocorrelación para la identificación del locutor en ambientes ruidosos

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    Recently, a new parametrization technique based on the AR modelling of the one-sided autocorrelation sequence (OSALPC) has shown to be attractive for speech recognition because of its simplicity and its high recognition perfomance in noisy conditions. In this paper, that new parametrization technique is proposed to speaker identification in noisy enviroment. Experimental results obtained with a new speaker identification system based on the statistics of the cepstrals vectors show that OSALPC also achieves much better results than standard parametrization techniques.Peer ReviewedPostprint (published version

    Movilización de carbono orgánico por distintos procesos erosivos en la conexión ladera-cauce

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    21 páginas, 5 figuras, 2 tablas.[ES] Con el fin de caracterizar la cantidad y tipo (lábil o recalcitrante) de carbono orgánico (CO) movilizado por distintos procesos erosivos identificados en las conexiones ladera-cauce, se estudiaron las características de los depósitos de erosión concentrada en cárcavas, erosión hídrica laminar, erosión lateral-gravitacional y erosión por laboreo en el contacto ladera-cauce de una cuenca de pequeño tamaño (10 ha) y se relacionaron con las características de los suelos-fuentes originales de donde procedían. La selectividad en el arranque y transporte de suelo de los distintos procesos se pudo asociar a diferentes contenidos y tipos de CO en los depósitos. Las razones de enriquecimiento de carbono orgánico sedimento/suelo fueron bajas (~0,40 ± 0,26), a pesar de haber un ligero enriquecimiento en partículas finas (correlacionadas positivamente con el CO) en los depósitos. Todo ello se atribuyó a los efectos de la mineralización en un cauce muy activo con pocas zonas de deposición y abundantes procesos de erosión no selectiva.[EN] With the purpose of analysing the type (labile or stable) and quantity of organic carbon (OC) mobilized by different erosive processes identified at the slope-bed connection, the erosion deposits of gullies, sheet erosion, bank erosion and tillage erosion were studied in a small catchment (10 ha) and compared to the characteristics of the catchment soils. Selectivity upon soil detachment and transport was associated to different OC content and types in the erosion deposits. Enrichment ratios of organic carbon sediment/soil were low (~0,40 ± 0,26), even though a slight enrichment was described for fine particles (positively correlated to CO). These results were attributed to mineralization processes prevailing over OC burial in a very active channel where depositional sites are scarce.Este trabajo ha sido financiado por los proyectos ERCO (CGL-2007- 62590/BTE) del Ministerio de Ciencia e Innovación y el proyecto PROBASE (CGL2006-11619). La primera autora tiene el apoyo económico de una ayuda FPI del Ministerio de Ciencia e Innovación (BES-2008-002379).Peer reviewe

    Movilización de carbono orgánico por distintos procesos erosivos en la conexión ladera-cauce

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    With the purpose of analysing the type (labile or stable) and quantity of organic carbon (OC) mobilized by different erosive processes identified at the slope-bed connection, the erosion deposits of gullies, sheet erosion, bank erosion and tillage erosion were studied in a small catchment (10 ha) and compared to the characteristics of the catchment soils. Selectivity upon soil detachment and transport was associated to different OC content and types in the erosion deposits. Enrichment ratios of organic carbon sediment/soil were low (~0,40 ± 0,26), even though a slight enrichment was described for fine particles (positively correlated to CO). These results were attributed to mineralization processes prevailing over OC burial in a very active channel where depositional sites are scarce.Con el fin de caracterizar la cantidad y tipo (lábil o recalcitrante) de carbono orgánico (CO) movilizado por distintos procesos erosivos identificados en las conexiones ladera-cauce, se estudiaron las características de los depósitos de erosión concentrada en cárcavas, erosión hídrica laminar, erosión lateral-gravitacional y erosión por laboreo en el contacto ladera-cauce de una cuenca de pequeño tamaño (10 ha) y se relacionaron con las características de los suelos-fuentes originales de donde procedían. La selectividad en el arranque y transporte de suelo de los distintos procesos se pudo asociar a diferentes contenidos y tipos de CO en los depósitos. Las razones de enriquecimiento de carbono orgánico sedimento/suelo fueron bajas (~0,40 ± 0,26), a pesar de haber un ligero enriquecimiento en partículas finas (correlacionadas positivamente con el CO) en los depósitos. Todo ello se atribuyó a los efectos de la mineralización en un cauce muy activo con pocas zonas de deposición y abundantes procesos de erosión no selectiva

    Minimal residual disease is an independent predictor for 10-year survival in CLL

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    Minimal residual disease (MRD) negativity, defined as <1 chronic lymphocytic leukemia (CLL) cell detectable per 10 000 leukocytes, has been shown to independently predict for clinical outcome in patients receiving combination chemoimmunotherapy in the frontline setting. However, the long-term prognostic value of MRD status in other therapeutic settings remains unclear. Here, we retrospectively analyzed, with up to 18 years follow-up, all patients at our institution who achieved at least a partial response (PR) with various therapies between 1996 and 2007, and received a bone marrow MRD assessment at the end of treatment according to the international harmonized approach. MRD negativity correlated with both progression-free survival (PFS) and overall survival (OS) independent of the type and line of treatment, as well as known prognostic factors including adverse cytogenetics. The greatest impact of achieving MRD negativity was seen in patients receiving frontline treatment, with 10-year PFS of 65% vs 10% and 10-year OS of 70% vs 30% for MRD-negative vs MRD-positive patients, respectively. Our results demonstrate the long-term benefit of achieving MRD negativity, regardless of the therapeutic setting and treatment modality, and support its use as a prognostic marker for long-term PFS and as a potential therapeutic goal in CLL

    Signatures of TOP1 transcription-associated mutagenesis in cancer and germline

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    The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair1. In microorganisms, transcription has been demonstrated to be mutagenic2,3; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes4. Here we show that ID4—a cancer insertion–deletion (indel) mutation signature of unknown aetiology5 characterized by short (2 to 5 base pair) deletions —is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activity at sites of genome-embedded ribonucleotides as a mechanistic basis. Such TOP1-mediated deletions occur somatically in cancer, and the ID-TOP1 signature is also found in physiological settings, contributing to genic de novo indel mutations in the germline. Thus, although topoisomerases protect against genome instability by relieving topological stress6, their activity may also be an important source of mutations in the human genome.We thank S. Jinks-Robertson for suggesting the traffic light reporter approach; H. Klein for guidance on fluctuation assays; R. van Boxtel for sharing sequencing data for MLH1-KO organoids; A. Bretherick, O. B. Reina and G. Kudla for advice on HygroR re-coding; staff at the IGC core services (L. Murphy, C. Nicol, C. Warnock, E. Freyer, S. Brown and J. Joseph), C. Logan, A. Fluteau, A. Robertson and the staff at Edinburgh Genomics for technical assistance; staff at Liverpool CLL Biobank (funded by Blood Cancer UK) for samples used to generate GEL WGS data; A. Ewing, C.-A. Martin, N. Hastie and W. Bickmore for discussions. Funding for this work: UK Medical Research Council Human Genetics Unit core grants (MC_UU_00007/5 to A.P.J., MC_UU_00007/11 to M.S.T.); Edinburgh Clinical Academic Track PhD programme (Wellcome Trust 204802/Z/16/Z) to T.C.W.; 2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research (grant number 21-40-11-NADE) to F.N.; a CRUK Brain Tumour Centre of Excellence Award (C157/A27589) to M.D.N.; EKFS research grant (2019_A09), Wilhelm Sander-Stiftung (2019.046.1) to K.A., CRUK programme grant (C20807/A2864) to T.S.; La Caixa Foundation (CLLEvolution-LCF/PR/HR17/52150017, Health Research 2017 Program HR17-00221) to E.C.; E.C. is an Academia Researcher of the Institució Catalana de Recerca i Estudis Avançats of the Generalitat de Catalunya. Edinburgh Genomics is partly supported by NERC (R8/H10/56), MRC (MR/K001744/1) and BBSRC (BB/J004243/1). This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support.Peer Reviewed"Article signat per 22 autors/es: Martin A. M. Reijns, David A. Parry, Thomas C. Williams, Ferran Nadeu, Rebecca L. Hindshaw, Diana O. Rios Szwed, Michael D. Nicholson, Paula Carroll, Shelagh Boyle, Romina Royo, Alex J. Cornish, Hang Xiang, Kate Ridout, The Genomics England Research Consortium, Colorectal Cancer Domain UK 100,000 Genomes Project, Anna Schuh, Konrad Aden, Claire Palles, Elias Campo, Tatjana Stankovic, Martin S. Taylor & Andrew P. Jackson "Postprint (published version

    Intravascular Large B-Cell Lymphoma Genomic Profile Is Characterized by Alterations in Genes Regulating NF-κB and Immune Checkpoints.

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    Intravascular large B-cell lymphoma (IVLBCL) is an uncommon lymphoma with an aggressive clinical course characterized by selective growth of tumor cells within the vessels. Its pathogenesis is still uncertain and there is little information on the underlying genomic alterations. In this study, we performed a clinicopathologic and next-generation sequencing analysis of 15 cases of IVLBCL using a custom panel for the detection of alterations in 68 recurrently mutated genes in B-cell lymphomagenesis. Six patients had evidence of hemophagocytic syndrome. Four patients presented concomitantly a solid malignancy. Tumor cells outside the vessels were observed in 7 cases, 2 with an overt diffuse large B-cell cell lymphoma. In 4 samples, tumor cells infiltrated lymphatic vessel in addition to blood capillaries. Programmed death-ligand 1 (PD-L1) was positive in tumor cells in 4 of 11 evaluable samples and in macrophages intermingled with tumor cells in 8. PD-L1 copy number gains were identified in a higher proportion of cases expressing PD-L1 than in negative tumors. The most frequently mutated gene was PIM1 (9/15, 60%), followed by MYD88L265P and CD79B (8/15, 53% each). In 6 cases, MYD88L265P and CD79B mutations were detected concomitantly. We also identified recurrent mutations in IRF4 , TMEM30A , BTG2 , and ETV6 loci (4/15, 27% each) and novel driver mutations in NOTCH2 , CCND3 , and GNA13 , and an IRF4 translocation in 1 case each. The mutational profile was similar in patients with and without evidence of hemophagocytic syndrome and in cases with or without dissemination of tumor cells outside the vessels. Our results confirm the relevance of mutations in B-cell receptor/nuclear factor-κB signaling and immune escape pathways in IVLBCL and identify novel driver alterations. The similar mutational profile in tumors with extravascular dissemination suggests that these cases may also be considered in the spectrum of IVLBCL

    Signatures of TOP1 transcription-associated mutagenesis in cancer and germline

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    The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair1. In microorganisms, transcription has been demonstrated to be mutagenic2,3; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes4. Here we show that ID4—a cancer insertion–deletion (indel) mutation signature of unknown aetiology5 characterized by short (2 to 5 base pair) deletions —is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activity at sites of genome-embedded ribonucleotides as a mechanistic basis. Such TOP1-mediated deletions occur somatically in cancer, and the ID-TOP1 signature is also found in physiological settings, contributing to genic de novo indel mutations in the germline. Thus, although topoisomerases protect against genome instability by relieving topological stress6, their activity may also be an important source of mutations in the human genome

    Impacts of selected Ecological Focus Area options in European farmed landscapes on climate regulation and pollination services: a systematic map protocol

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    Background: This systematic map protocol responds to an urgent policy need to evaluate key environmental benefits of new compulsory greening measures in the European Union’s Common Agricultural Policy (CAP), with the aim of building a policy better linked to environmental performance. The systematic map will focus on Ecological Focus Areas (EFAs), in which larger arable farmers must dedicate 5% of their arable land to ecologically beneficial habitats, landscape features and land uses. The European Commission’s Joint Research Centre has used a software tool called the ‘EFA calculator’ to inform the European Commission about environmental benefits of EFA implementation. However, there are gaps in the EFA calculator’s coverage of ecosystem services, especially ‘global climate regulation’, and an opportunity to use systematic mapping methods to enhance its capture of evidence, in advance of forthcoming CAP reforms. We describe a method for assembling a database of relevant, peer-reviewed research conducted in all agricultural landscapes in Europe and neighbouring countries with similar biogeography, addressing the primary question: what are the impacts of selected EFA features in agricultural land on two policy-relevant ecosystem service outcomes—global climate regulation and pollination? The method is streamlined to allow results in good time for the current, time-limited opportunity to influence reforms of the CAP greening measures at European and Member State level. Methods: We will search four bibliographic databases in English, using a predefined and tested search string that focuses on a subset of EFA options and ecosystem service outcomes. The options and outcomes are selected as those with particular policy relevance and traction. Only articles in English will be included. We will screen search results at title, abstract and full text levels, recording the number of studies deemed non-relevant (with reasons at full text). A systematic map database that displays the meta-data (i.e. descriptive summary information about settings and methods) of relevant studies will be produced following full text assessment. The systematic map database will be published as a MS-Excel database. The nature and extent of the evidence base will be discussed, and the applicability of methods to convert the available evidence into EFA calculator scores will be assessed

    Molecular map of chronic lymphocytic leukemia and its impact on outcome

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    Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the ‘CLL map,’ we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication
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