Panels and models for accurate prediction of tumor mutation burden in tumor samples

Immune checkpoint blockade (ICB) is becoming standard-of-care in many types of human malignancies, but patient selection is still imperfect. Tumor mutation burden (TMB) is being evaluated as a biomarker for ICB in clinical trials, but most of the sequencing panels used to estimate it are inadequately designed. Here, we present a bioinformatics-based method to select panels and mathematical models for accurate TMB prediction. Our method is based on tumor-specific, forward-step selection of genes, generation of panels using a linear regression algorithm, and rigorous internal and external validation comparing predicted with experimental TMB. As a result, we propose cancer-specific panels for 14 malignancies which can offer reliable, clinically relevant estimates of TMBs. Our work facilitates a better prediction of TMB that can improve the selection of patients for ICB therapy.Fil: Martinez Perez, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Molina Vila, Miguel Angel. Hospital Universitario Quirón Dexeus; EspañaFil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Search for H alpha emitters in Galaxy Clusters with Tunable Filters

The studies of the evolution of galaxies in Galaxy Clusters have as a traditional complication the difficulty in establishing cluster membership of those sources detected in the field of view. The determination of spectroscopic redshifts involves long exposure times when it is needed to reach the cluster peripherical regions of/or clusters at moderately large redshifts, while photometric redshifts often present uncertainties too large to offer significant conclusions. The mapping of the cluster of galaxies with narrow band tunable filters makes it possible to reach large redshifts intervals with an accuracy high enough to establish the source membership of those presenting emission/absorption lines easily identifiable, as H alpha. Moreover, the wavelength scan can include other lines as [NII], [OIII] or $H_{\beta}$ allowing to distinguish those sources with strong stellar formation activity and those with an active galactic nuclei. All this makes it possible to estimate the stellar formation rate of the galaxies observed. This, together with ancillary data in other wavelengths may lead to a good estimation of the stellar formation histories. It will shed new light over the galaxy evolution in clusters and will improve our understanding of galaxy evolution, especially in the outer cluster regions, usually less studied and with significant unexploited data that can not be correctly interpreted without redshift determination.Comment: 4 pages, 2 figures. "Highlights of Spanish Astrophysics V", Proceedings of the VIII Scientific Meeting of the Spanish Astronomical Society (SEA) held in Santander, 7-11 July, 200

Identification of ovule and seed genes from Citrus clementina

[EN] Seedlessness is a highly desirable trait in fresh fruit. Citrus varieties, such as Clementine mandarin and other related species, show parthenocarpic fruit development without seeds due to self-incompatibility. In spite of that, these fruits frequently contain seeds as a result of cross-pollination by insects with compatible pollen from other citrus cultivars grown nearby. To solve this problem using a biotechnological approach we aim at the destruction of ovules and/or seeds by directing the expression of a toxic gene using the promoter of an ovule and/or seed specific gene. With the purpose of isolating this kind of genes we constructed two cDNA libraries from ovules and seeds at different developmental stages of the Clementine mandarin (Citrus clementina cv. Clemenules). A total of 1,014 ESTs from the ovule library and 1,042 ESTs from the seed library were generated, with a novelty percentage of 27% and 36% among the Spanish Citrus Functional Genomic Project (CFGP) ESTs database, respectively. Quantitative PCR analysis confirmed nearly specific expression in ovule and/or seed of two genes, TRANSPARENT TESTA16 (CcTT16) and TRANSPARENT TESTA7 (CcTT7). Expression of these two genes is restricted to early seed development, and is localized in the embryo sac and endothelium. The promoters of those genes may be useful to genetically engineer citrus species to avoid seed formation in fruits of commercial varieties.The authors thank Dr. L. Navarro and J. Juarez, from the Instituto Valenciano de Investigaciones Agrarias (Generalitat Valenciana), for the use of the Clementine orchard and Fortune pollen; Dr. J Forment and the Genomics Facility at the IBMCP for sequence analysis and maintenance of to the CFGP database; and Drs. F Tadeo and J Carbonell for critical reading of the manuscript. This work was supported by grants from the Conselleria de Agricultura, Pesca y Alimentacion (Generalitat Valenciana) and Spanish Ministerio de Ciencia y Tecnologia (research grant GEN2001-4885-C05). A.G-L. received a PhD fellowship from the Conselleria de Agricultura, Pesca y Alimentacion.García Lor, A.; Garcia Martinez, JL.; Perez Amador, MA. (2012). Identification of ovule and seed genes from Citrus clementina. Tree Genetics and Genomes. 8(2):227-235. doi:10.1007/s11295-011-0435-xS22723582Al-Shahrour F, Diaz-Uriarte R, Dopazo J (2005) Discovering molecular functions significantly related to phenotypes by combining gene expression data and biological information. Bioinformatics 21:2988–2993Al-Shahrour F, Minguez P, Tarraga J, Montaner D, Alloza E, Vaquerizas JMM, Conde L, Blaschke C, Vera J, Dopazo J (2006) BABELOMICS: a systems biology perspective in the functional annotation of genome-scale experiments. Nucleic Acids Res 34:W472–W476Alos E, Cercos M, Rodrigo MJ, Zacarias L, Talon M (2006) Regulation of color break in citrus fruits. Changes in pigment profiling and gene expression induced by gibberellins and nitrate, two ripening retardants. J Agric Food Chem 54:4888–4895Bugos RC, Chiang VL, Zhang XH, Campbell ER, Podila GK, Campbell WH (1995) RNA isolation from plant tissues recalcitrant to extraction in guanidine. Biotechniques 19:734–737Costantini E, Landi L, Silvestroni O, Pandolfini T, Spena A, Mezzetti B (2007) Auxin synthesis-encoding transgene enhances grape fecundity. Plant Physiol 143:1689–1694Debeaujon I, Nesi N, Perez P, Devic M, Grandjean O, Caboche M, Lepiniec L (2003) Proanthocyanidin-accumulating cells in Arabidopsis testa: regulation of differentiation and role in seed development. Plant Cell 15:2514–2531Dorcey E, Urbez C, Blazquez MA, Carbonell J, Perez-Amador MA (2009) Fertilization-dependent auxin response in ovules triggers fruit development through the modulation of gibberellin metabolism in Arabidopsis. Plant J 58:318–332Debeaujon I, Peeters AJ, Léon-Kloosterziel KM, Koornneef M (2001) The TRANSPARENT TESTA12 gene of Arabidopsis encodes a multidrug secondary transporter-like protein required for flavonoid sequestration in vacuoles of the seed coat endothelium. Plant Cell 13:853–571Forment J, Gadea J, Huerta L, Abizanda L, Agusti J, Alamar S, Alos E, Andres F, Arribas R, Beltran JP, Berbel A, Blazquez MA, Brumos J, Canas LA, Cercos M, Colmenero-Flores JM, Conesa A, Estables B, Gandia M, Garcia-Martinez JL, Gimeno J, Gisbert A, Gomez G, Gonzalez-Candelas L, Granell A, Guerra J, Lafuente MT, Madueno F, Marcos JF, Marques MC, Martinez F, Martinez-Godoy MA, Miralles S, Moreno P, Navarro L, Pallas V, Perez-Amador MA, Perez-Valle J, Pons C, Rodrigo I, Rodriguez PL, Royo C, Serrano R, Soler G, Tadeo F, Talon M, Terol J, Trenor M, Vaello L, Vicente O, Vidal C, Zacarias L, Conejero V (2005) Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies. Plant Mol Biol 57:375–391Forment J, Gilabert F, Robles A, Conejero V, Nuez F, Blanca JM (2008) EST2uni: an open, parallel tool for automated EST analysis and database creation, with a data mining web interface and microarray expression data integration. BMC Bioinformatics 9:5Fos M, Nuez F, Garcia-Martinez JL (2000) The gene pat-2, which induces natural parthenocarpy, alters the gibberellin content in unpollinated tomato ovaries. Plant Physiol 122:471–480Fos M, Proaño K, Nuez F, Garcia-Martinez JL (2001) Role of gibberellins in parthenocarpic fruit development induced by the genetic system pat-3/pat-4 in tomato. Physiol Plant 111:545–550Hashimoto JG, Beadles-Bohling AS, Wiren KM (2004) Comparison of RiboGreen and 18S rRNA quantitation for normalizing real-time RT-PCR expression analysis. Biotechniques 36:54–60Haughn G, Chaudhury A (2005) Genetic analysis of seed coat development in Arabidopsis. Trends Plant Sci 10:472–477Hartley RW (1988) Barnase and barstar. Expression of its cloned inhibitor permits expression of a cloned ribonuclease. J Mol Biol 202:913–915Jackson DP (1992) In situ hybridization in plants. In: Bowles DJ, Gurr SJ, Pherenson M (eds) Molecular plant pathology: a practical approach. Oxford University Press, Oxford, UK, pp 163–174Koltunow AM (1993) Isolation and construction of genes to control seed production in Citrus. In: Hyashi T, Omura M, Scott NS (eds) Techniques on gene diagnosis and breeding. Fruit Tree Research Station, Tsukuba, Japan, pp 101–108Koltunow AM, Soltys K, Nito N, Mcclure S (1995) Anther, ovule, seed and nucellar embryo development in Citrus sinensis cv Valencia. Can J Bot 73:1567–1582Koltunow AM, Brennan P, Bond JE, Barker SJ (1998) Evaluation of genes to reduce seed size in Arabidopsis and tobacco and their application to Citrus. Mol Breeding 4:235–251Le BH, Cheng C, Bui AQ, Wagmaister JA, Henry KF, Pelletier J, Kwong L, Belmonte M, Kirkbride R, Horvath S, Drews GN, Fischer RL, Okamuro JK, Harada JJ, Goldberg RB (2010) Global analysis of gene activity during Arabidopsis seed development and identification of seed-specific transcription factors. Proc Natl Acad Sci USA 107:8063–8070Li DD, Shi W, Deng XX (2002) Agrobacterium-mediated transformation of embryogenic calluses of Ponkan mandarin and the regeneration of plants containing the chimeric ribonuclease gene. Plant Cell Rep 21:153–156Marques MC, Alonso-Cantabrana H, Forment J, Arribas R, Alamar S, Conejero V, Perez-Amador MA (2009) A new set of ESTs and cDNA clones from full-length and normalized libraries for gene discovery and functional characterization in citrus. BMC Genomics 10:428Mezzetti B, Landi L, Pandolfini T, Spena A (2004) The DefH9-iaaM auxin-synthesizing gene increases plant fecundity and fruit production in strawberry and raspberry. BMC Biotechnology 4:4Nesi N, Debeaujon I, Jond C, Stewart AJ, Jenkins GI, Caboche M, Lepiniec L (2002) The TRANSPARENT TESTA16 locus encodes the ARABIDOPSIS BSISTER MADS domain protein and is required for proper development and pigmentation of the seed coat. Plant Cell 14:2463–2479Olimpieri I, Siligato F, Caccia R, Mariotti L, Ceccarelli N, Soressi GP, Mazzucato A (2007) Tomato fruit-set driven by pollination or by the parthenocarpic fruit allele are mediated by transcriptionally regulated gibberellin biosynthesis. Planta 226:877–888Peer AW, Brown DE, Tague BW, Muday GK, Taiz L, Murphy AS (2001) Flavonoid accumulation patterns of transparent testa mutants of Arabidopsis. Plant Physiol 126:536–548Rommens CM, Haring MA, Swords K, Davies HV, Belknap WR (2007) The intragenic approach as a new extension to traditional plant breeding. Trends Plant Sci 12:397–403Rotino GL, Acciarri N, Sabatini E, Mennella G, Scalzo RL, Maestrelli A, Molesini B, Pandolfini T, Scalzo J, Mezzetti B, Spena A (2005) Open field trial of genetically modified parthenocarpic tomato: seedlessness and fruit quality. BMC Biotechnol 5:32Schoenbohm C, Martens S, Eder C, Forkmann G, Weisshaar B (2000) Identification of the Arabidopsis thaliana flavonoid 3′-hydroxylase gene and functional expression of the encoded P450 enzyme. Biol Chem 381:749–753Schwabe WW, Mills JJ (1981) Hormones and parthenocarpic fruit set: a literature survey. Hort Abstr 51:661–698Singh DP, Filardo FF, Storey R, Jermakow AM, Yamaguchi S, Swain SM (2010) Overexpression of a gibberellin inactivation gene alters seed development, KNOX gene expression, and plant development in Arabidopsis. Physiol Plant 138:74–90Talon M, Zacarias L, Primo-Millo E (1992) Gibberellins and parthenocarpic ability in developing ovaries of seedless mandarins. Plant Physiol 99:1575–1581Zimmermann P, Hirsch-Hoffmann M, Hennig L, Gruissem W (2004) GENEVESTIGATOR: Arabidopsis microarray database and analysis toolbox. Plant Physiol 136:2621–2632Zhulidov PA, Bogdanova EA, Shcheglov AS, Vagner LL, Khaspekov GL, Kozhemyako VB, Matz MV, Meleshkevitch E, Moroz LL, Lukyanov SA, Shagin DA (2004) Simple cDNA normalization using Kamchatka crab duplex-specific nuclease. Nucleic Acids Res 32:e3

An exploratory analysis of the implementation and use of an intelligent platform for learning in primary education

Smile and Learn is an intelligent platform with more than 4500 educational activities for children aged 3-12. The digital material developed covers all courses of primary education and most of the subjects with the different topic-related worlds with activities in the field of logics and mathematics, science, linguistics and tales, visual-spatial and cognitive skills, emotional intelligence, arts, and multiplayer games. This kind of material supports active learning and new pedagogical models for teachers to use in their lessons. The purpose of this paper is to explore the usage of the platform in three pilot groups schools from different regions of Spain, outlining future directions in the design of such digital materials. Usage is assessed via descriptive analysis and variance analysis, with data collected from users interacting with the intelligent platform. The results show a high use of STEM (Science, Technology, Engineering and Maths) activities among all the activities that could be chosen. Cross-curricular activities are also used. Continuation in the development of such materials is concluded necessary, focusing integration of different fields, accentuating games over quizzes, and the value of teacher training for improving their use in schools.This research was funded by Community of Madrid 'Industrial PhD grants' under project number IND2017/SOC-7874

Wind tunnel experiments to teach physics

Innovative teaching experimental activities for secondary school students have been developed in order to introduce some aerodynamic concepts, with the aim of making science subjects such as mathematics and physics more attractive. Post-graduate students of Universidad Politécnica de Madrid (UPM) and teachers of Deutsche Schule Madrid (DSM) have constructed a small wind tunnel. The main goal has been to provide a tool for secondary school students to become familiar with the scientific method developing curiosity, imagination, initiative, critical thinking and problem-solving skills. Students of DSM have performed wind tunnel experiments, resulting in a successful and amusing experience. The students were able to relate the experimental results obtained with the physic principle of flight, previously explained in class. Evaluations reveal that both, the teacher and the students, considered the experience as interesting and helpful to lead with teaching physics, mathematics and engineering sciences. The teacher observed the strong motivation factor developed for the students to continue learning engineering sciences. Some of the students expressed that this experience had changed their prejudices about physics and mathematics, based only on theoretical approaches

Bronchiectasis-COPD Overlap Syndrome: Role of Peripheral Eosinophil Count and Inhaled Corticosteroid Treatment

Both chronic obstructive pulmonary disease and bronchiectasis are highly prevalent diseases. In both cases, inhaled corticosteroids (ICs) are associated with a decrease in exacerbations in patients with a high peripheral blood eosinophil count (BEC), but it is still not known what occurs in bronchiectasis-COPD overlap syndrome (BCOS). The present study aimed to assess the effect of ICs on various outcomes in patients with BCOS, according to BEC values. We undertook a post-hoc analysis of a cohort of 201 GOLD II-IV COPD patients with a long-term follow-up (median 74 [IQR: 40-106] months). All participants underwent computerized tomography and 115 (57.2%) had confirmed BCOS. A standardized clinical protocol was followed and two sputum samples were collected at each medical visit (every 3-6 months), whenever possible. During follow-up, there were 68 deaths (59.1%), and the mean rate of exacerbations and hospitalizations per year was 1.42 (1.2) and 0.57 (0.83), respectively. A total of 44.3% of the patients presented at least one pneumonic episode per year. The mean value of eosinophils was 402 (112) eosinophils/mu L, with 27 (23.5%), 63 (54.8%), and 25 patients (21.7%) presenting, respectively, less than 100, 101-300, and more than 300 eosinophils/mu L. A total of 84 patients (73.1%) took ICs. The higher the BEC, the higher the annual rate of exacerbations and hospitalizations. Patients with less than 100 eosinophils/mu L presented more infectious events (incident exacerbations, pneumonic episodes, and chronic bronchial infection via pathogenic bacteria). Only those patients with eosinophilia (>300 eosinophils/mu L) treated with ICs decreased the number (1.77 (1.2) vs. 1.08 (0.6), p < 0.001) and the severity (0.67 (0.8) vs. 0.35 (0.5), p = 0.011) of exacerbations, without any changes in the other infectious outcomes or mortality. In conclusion, ICs treatment in patients with BCOS with increased BEC decreased the number and severity of incident exacerbations without any negative influence on other infectious outcomes (incidence of pneumonia or chronic bronchial infection)

Modelado de la sismicidad en Colombia a partir de características de la litosfera terrestre

En el presente artículo se realizó la estimación de modelos del proceso de Poisson no homogéneo, aso- ciado al patrón de sismos en Colombia utilizando covariables descriptivas de la litosfera terrestre tales como la altitud del terreno, anomalías magnéticas e isostáticas, y mediciones de distancia a estructu- ras geológicas tales como fallas, bordes de placa y volcanes. En este estudio se confirmó que los sismos tienden a ocurrir en las cercanías a determinadas es- tructuras geológicas, en zonas con importantes ano- malías gravimétricas, tanto positivas como negativas, y en zonas con valores específicos de anomalías magnéticas y de altitud.

alpha 2-COP is involved in early secretory traffic in Arabidopsis and is required for plant growth

[EN] COP (coat protein) I-coated vesicles mediate intra-Golgi transport and retrograde transport from the Golgi to the endoplasmic reticulum. These vesicles form through the action of the small GTPase ADP-ribosylation factor 1 (ARF1) and the COPI heptameric protein complex (coatomer), which consists of seven subunits (alpha-, beta-, beta' -, gamma-, delta-, epsilon- and xi-COP). In contrast to mammals and yeast, several isoforms for coatomer subunits, with the exception of gamma and delta, have been identified in Arabidopsis. To understand the role of COPI proteins in plant biology, we have identified and characterized a loss-of-function mutant of alpha 2-COP, an Arabidopsis alpha-COP isoform. The alpha 2-cop mutant displayed defects in plant growth, including small rosettes, stems and roots and mislocalization of p24 delta 5, a protein of the p24 family containing a C-terminal dilysine motif involved in COPI binding. The alpha 2-cop mutant also exhibited abnormal morphology of the Golgi apparatus. Global expression analysis of the alpha 2-cop mutant revealed altered expression of plant cell wall-associated genes. In addition, a strong upregulation of SEC31A, which encodes a subunit of the COPII coat, was observed in the alpha 2-cop mutant; this also occurs in a mutant of a gene upstream of COPI assembly, GNL1, which encodes an ARF-guanine nucleotide exchange factor (GEF). These findings suggest that loss of alpha 2-COP affects the expression of secretory pathway genes.Antibody against alpha-COP was kindly provided by Prof. F. Wieland. This work was supported by the Ministerio de Economia y Competitividad (grant number. BFU2012-33883 to FA and MJM; grant numbers BIO2011-26302 and BIO2014-55946-P to MP), the Generalitat Valenciana (grant numbers ISIC/2013/004 and GVACOMP2014-202 to FA and MJM) and the Research Grants Council (grant number AoE/M-05/12 to LJ). NP and CB were recipients of a fellowship from Ministerio de Educacion (FPU program). We thank the Salk Institute Genomic Analysis Laboratory for providing the sequence-indexed Arabidopsis T-DNA insertion mutants and the microscopy and genomics section of SCSIE (University of Valencia).Gimeno-Ferrer, F.; Pastor-Cantizano, N.; Bernat-Silvestre, C.; Selvi-Martinez, P.; Vera Sirera, FJ.; Gao, C.; Perez Amador, MA.... (2017). alpha 2-COP is involved in early secretory traffic in Arabidopsis and is required for plant growth. Journal of Experimental Botany. 68(3):391-401. https://doi.org/10.1093/jxb/erw446S39140168

Diseño de un modelo estratégico integral para el proceso de salud ocupacional con énfasis en gestión del conocimiento empresa Agua el Sol

El presente trabajo; fue realizado como requisito par a obtener el título de administradores de empresas, basados en lo solicitado en el curso del diplomado de profundización en gerencia del talento humano. La investigación realizada fue de tipo cuantitativo y su desarrollo se describe en cinco capítulos: Inicia con un primer capítulo se planteó el problema relacionado con la Salud Ocupacional para el empresa Agua El Sol, el segundo capítulo contiene las teorías relacionadas con la temática, literatura que sirvió de base para la argumentación y descripción del trabajo, en el capítulo tres, se establecieron los procedimientos utilizados para la indagación de los datos necesarios para el estudio, en consecuencia en el capítulo cuarto se presentan los resultados obtenidos mediante el instrumento utilizado en la recolección de la información y finaliza con el capítulo cinco en el que se realizan las recomendaciones del caso frente a los hallazgos encontrados, luego se plantea la propuesta basada en el Modelo de Nonaka y Takeuchi y por último se entregan las conclusiones a que se llegó producto del desarrollo de estudio y para el área indicada.The present work; It was carried out as a requirement to obtain the title of business administrators, based on what was requested in the course of the Diploma of Deepening  in Human Talent Management. The research was quantitative and its development is described in five chapters: Starts with a first chapter the problem related to Occupational Health for the company Agua El Sol was raised, the second chapter contains the theories related to the subject, literature that served as the basis for the argumentation and description of the work, in chapter three, the procedures used for the investigation of the data necessary for the study were established, consequently in the fourth chapter the results obtained through the instrument used in the collection of the information are presented and it ends with chapter five in which the recommendations are made of the case in front of the found findings, then the proposal based on the Nonaka and Takeuchi Model is presented and finally the conclusions reached that were arrived at due to the development of the study and for the indicated area