Sistema de Visión Estereoscópica para Navegación Autónoma de vehículos no tripulados

La visión estereoscópica constituye un campo de la inteligencia artificial que se basa en la composición de imágenes 3D mediante visión binocular. De esta manera, un autómata equipado con un sistema de dos cámaras a la misma altura y desplazadas a cierta distancia, podría reconstruir el entorno que le rodea tridimensionalmente. El presente proyecto está enfocado a este fin: obtener, a partir de las imágenes, un mapa del entorno que, de la manera más aproximada, represente la distancia a la que se encuentran los objetos en la escena respecto del robot. Con dicha reconstrucción, un robot es capaz de poder detectar y esquivar los obstáculos que se puede encontrar en su camino, pudiendo así planificar distintas rutas seguras que le lleven hasta su objetivo. [ABSTRACT] Stereoscopic vision is a field of artificial intelligence based on the composition of 3Dimages by binocular vision. In this way, a robot equipped with a system of two cameras at the same height and displaced at a distance among them, could rebuild the tridimensional surrounding environment. This project is aimed for this purpose: to obtain images from the environment that, as nearly, represents the distance at which objects are located on with respect the robot. With this reconstruction of the scene, the stereovision system in the robot could be able to detect and avoid obstacles that can be found on its path, thus being able to plan different routes that lead to secure targets

Huntington's disease-specific mis-splicing unveils key effector genes and altered splicing factors

Correction of mis-splicing events is a growing therapeutic approach for neurological diseases such as spinal muscular atrophy or neuronal ceroid lipofuscinosis 7, which are caused by splicing-affecting mutations. Mis-spliced effector genes that do not harbour mutations are also good candidate therapeutic targets in diseases with more complex aetiologies such as cancer, autism, muscular dystrophies or neurodegenerative diseases. Next-generation RNA sequencing (RNA-seq) has boosted investigation of global mis-splicing in diseased tissue to identify such key pathogenic mis-spliced genes. Nevertheless, while analysis of tumour or dystrophic muscle biopsies can be informative on early stage pathogenic mis-splicing, for neurodegenerative diseases, these analyses are intrinsically hampered by neuronal loss and neuroinflammation in post-mortem brains. To infer splicing alterations relevant to Huntington's disease pathogenesis, here we performed intersect-RNA-seq analyses of human post-mortem striatal tissue and of an early symptomatic mouse model in which neuronal loss and gliosis are not yet present. Together with a human/mouse parallel motif scan analysis, this approach allowed us to identify the shared mis-splicing signature triggered by the Huntington's disease-causing mutation in both species and to infer upstream deregulated splicing factors. Moreover, we identified a plethora of downstream neurodegeneration-linked mis-spliced effector genes that-together with the deregulated splicing factors-become new possible therapeutic targets. In summary, here we report pathogenic global mis-splicing in Huntington's disease striatum captured by our new intersect-RNA-seq approach that can be readily applied to other neurodegenerative diseases for which bona fide animal models are available.Extremadura Research Centre for Advanced Technologies (CETA-CIEMAT), funded by the European Regional Development Fund (ERDF). CETA-CIEMAT belongs to CIEMAT and the Government of Spai

Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression

Chromosomal instability (CIN) lies at the core of cancer development leading to aneuploidy, chromosomal copy-number heterogeneity (chr-CNH) and ultimately, unfavorable clinical outcomes. Despite its ubiquity in cancer, the presence of CIN in childhood B-cell acute lymphoblastic leukemia (cB-ALL), the most frequent pediatric cancer showing high frequencies of aneuploidy, remains unknown. Here, we elucidate the presence of CIN in aneuploid cB-ALL subtypes using single-cell whole-genome sequencing of primary cB-ALL samples and by generating and functionally characterizing patient-derived xenograft models (cB-ALL-PDX). We report higher rates of CIN across aneuploid than in euploid cB-ALL that strongly correlate with intraclonal chr-CNH and overall survival in mice. This association was further supported by in silico mathematical modeling. Moreover, mass-spectrometry analyses of cB-ALL-PDX revealed a "CIN signature" enriched in mitotic-spindle regulatory pathways, which was confirmed by RNA-sequencing of a large cohort of cB-ALL samples. The link between the presence of CIN in aneuploid cB-ALL and disease progression opens new possibilities for patient stratification and offers a promising new avenue as a therapeutic target in cB-ALL treatment.</p

Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, and high-hyperdiploidy (HyperD) identifies the most common subtype of pediatric B-ALL. Despite HyperD is an initiating oncogenic event affiliated to childhood B-ALL, the mitotic and chromosomal defects associated to HyperD B-ALL (HyperD-ALL) remain poorly characterized. Here, we have used 54 primary pediatric B-ALL samples to characterize the cellular-molecular mechanisms underlying the mitotic/chromosome defects predicated to be early pathogenic contributors in HyperD-ALL. We report that HyperD-ALL blasts are low proliferative and show a delay in early mitosis at prometaphase, associated to chromosome alignment defects at the metaphase plate leading to robust chromosome segregation defects and non-modal karyotypes. Mechanistically, biochemical, functional and mass-spectrometry assays revealed that condensin complex is impaired in HyperD-ALL cells, leading to chromosome hypocondensation, loss of centromere stiffness and mis-localization of the chromosome passenger complex proteins Aurora B Kinase (AURKB) and Survivin in early mitosis. HyperD-ALL cells show chromatid cohesion defects and impaired spindle assembly checkpoint (SAC) thus undergoing mitotic slippage due to defective AURKB and impaired SAC activity, downstream of condensin complex defects. Chromosome structure/condensation defects and hyperdiploidy were reproduced in healthy CD34+ stem/progenitor cells upon inhibition of AURKB and/or SAC. Collectively, hyperdiploid B-ALL is associated to defective condensin complex, AURKB and SAC

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V

Characterization of clinically relevant RNA alterations for personalized cancer medicine

The following thesis tries to answer the question of wheter RNA processing alterations are informative for the clinical management of cancer patients. For this, the work is focused on solve two main issues: the development of computational tools to study RNA profiles from multiple tumors and the identification of RNA-related signatures that may be predictive of prognosis and therapy. The thesis is divided in three chapters: First, the development a new tool for fast quantification of differential splicing: SUPPA2. Second, a new methodology for elucidating the prognostic potential of alternative transcript isoforms across human tumours. And third, a new method for the detection of aberrant tumor splicing junctions and their antigenic evaluation.La presente tesis intenta arrojar luz sobre la pregunta de si las alteraciones del ARN son informativas para el tratamiento clínico de pacientes con cancer. Para ello, este trabajo se centra en resolver dos cuestiones principales: el desarrollo de metodos computaciones para el estudio de perfiles de ARN en multiples tumores y la identificación de marcadores que puedan ser predictivos de prognosis y terapia. La tesis está dividida en tres capítulos: Primero, el desarollo de un nuevo método para la cuantificación rápida de splicing diferencial: SUPPA2. Segundo, una nueva metodologia para dilucidar el potencial prognóstico de tránscritos alternativos en tumores humanos. Y tercero, un nuevo método para la detección de junctions aberrantes tumorales y su evaluacion antigénic

Characterization of clinically relevant RNA alterations for personalized cancer medicine

The following thesis tries to answer the question of wheter RNA processing alterations are informative for the clinical management of cancer patients. For this, the work is focused on solve two main issues: the development of computational tools to study RNA profiles from multiple tumors and the identification of RNA-related signatures that may be predictive of prognosis and therapy. The thesis is divided in three chapters: First, the development a new tool for fast quantification of differential splicing: SUPPA2. Second, a new methodology for elucidating the prognostic potential of alternative transcript isoforms across human tumours. And third, a new method for the detection of aberrant tumor splicing junctions and their antigenic evaluation.La presente tesis intenta arrojar luz sobre la pregunta de si las alteraciones del ARN son informativas para el tratamiento clínico de pacientes con cancer. Para ello, este trabajo se centra en resolver dos cuestiones principales: el desarrollo de metodos computaciones para el estudio de perfiles de ARN en multiples tumores y la identificación de marcadores que puedan ser predictivos de prognosis y terapia. La tesis está dividida en tres capítulos: Primero, el desarollo de un nuevo método para la cuantificación rápida de splicing diferencial: SUPPA2. Segundo, una nueva metodologia para dilucidar el potencial prognóstico de tránscritos alternativos en tumores humanos. Y tercero, un nuevo método para la detección de junctions aberrantes tumorales y su evaluacion antigénic

Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. We applied automated sequential-iFISH coupled with single-cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD-B-ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD-B-ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD-B-ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)-negative childhood HHD-B-ALL patients: relapse-free survival beyond 5 years: 22.1% versus 87.9%, P < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-B-ALL patients.This work is supported by the Spanish Ministry of Science and Innovation (PID2019-108160RB-I00/AEI/10.13039/501100011033, the European Research Council (CoG-2014-646903), the Spanish Ministry of Economy and Competitiveness (SAF2016-80481-R and SAF-2019-108160-R), the Leo Messi Foundation, the Health Institute Carlos III (ISCIII) (RICORS, RD21/0017/0029) within the Next Generation EU program (plan de recuperación, transformación y resilencia), and the Fundación Uno entre Cienmil (PM). Additional funding was provided by the ISCIII (FEDER PI17/01028 and PI20/00822) (CB), the Generalitat de Catalunya (2017/SGR-503) and the Universitat Autònoma de Barcelona (UAB/CF-180034) (JB) and the Blood Cancer UK (CJH). JLT was supported by a Juan de la Cierva fellowship by the Spanish Ministry of Science and Innovation (FJC2019-040868-I), BL-M was supported by the Asociación Española Contra el Cáncer (AECC; INVES20011LÓPE). AB was supported by the Fundación Española de Hematología y Hemoterapia (FEHH). OM was supported by a Beatriu de Pinós Postdoctoral Fellowship (BP2016-00048) from AGAUR (Generalitat de Catalunya), a 2017 Lady Tata Memorial Trust International Award, and the AECC (INVES211226MOLI). PM is an investigator of the Spanish Cell Therapy cooperative network (TERCEL)

The prognostic potential of alternative transcript isoforms across human tumors

Background: Phenotypic changes during cancer progression are associated with alterations in gene expression, which can be exploited to build molecular signatures for tumor stage identification and prognosis. However, it is not yet known whether the relative abundance of transcript isoforms may be informative for clinical stage and survival. Methods: Using information theory and machine learning methods, we integrated RNA sequencing and clinical data from The Cancer Genome Atlas project to perform the first systematic analysis of the prognostic potential of transcript isoforms in 12 solid tumors to build new signatures for stage and prognosis. This study was also performed in breast tumors according to estrogen receptor (ER) status and melanoma tumors with proliferative and invasive phenotypes. Results: Transcript isoform signatures accurately separate early from late-stage groups and metastatic from non-metastatic tumors, and are predictive of the survival of patients with undetermined lymph node invasion or metastatic status. These signatures show similar, and sometimes better, accuracies compared with known gene expression signatures in retrospective data and are largely independent of gene expression changes. Furthermore, we show frequent transcript isoform changes in breast tumors according to ER status, and in melanoma tumors according to the invasive or proliferative phenotype, and derive accurate predictive models of stage and survival within each patient subgroup. Conclusions: Our analyses reveal new signatures based on transcript isoform abundances that characterize tumor phenotypes and their progression independently of gene expression. Transcript isoform signatures appear especially relevant to determine lymph node invasion and metastasis and may potentially contribute towards current strategies of precision cancer medicine.This work was supported by grants BIO2014-52566-R and Consolider RNAREG (CSD2009-00080) from the MINECO (Spanish Government) and FEDER, by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013)