Matrix metalloproteinase-13 refines pathological staging of precancerous colorectal lesions

An exact classification of precancerous stages of colorectal polyps might improve therapy and patients´ outcome. Here we investigate the association between grade of dysplasia and Matrix metalloproteinase-13 (MMP-13) expression in 137 biopsies from patients with cancerous and non-cancerous colorectal adenomas. A reproducible staining procedure for histologic MMP-13 analysis in routinely fixed colorectal biopsy specimens has been established. A newly adopted immunoreactive scoring system for MMP-13 was demonstrated as reliable readout. The strength of the association between pathologic stage and immunoreactive MMP-13 scoring emphasizes its eligibility for diagnosis in precancerous colorectal lesions

IMPACTO DE LA CAMPAÑA PUBLICITARIA “EL RETO DE LIMPIEZA” DE LA MARCA ARIEL, EN LOS HÁBITOS DE COMPRA DE LAS AMAS DE CASA DE LA VICTORIA

Las campañas publicitarias son un conjunto de estrategias que se elaboran con la finalidad de dar a conocer el producto o servicio; sus objetivos son la mayor participación de clientes, lograr o cambiar el posicionamiento; lanzamiento y promoción de productos, además de poder condicionar la decisión de compra del público objetivo de la empresa. La efectividad de las campañas publicitarias se midió a través de la eficacia publicitaria la cual no es más que el impacto ya sea positivo o negativo que la campaña produzca en el mercado. El presente estudio se enfocó en determinar el impacto de la campaña publicitaria “El reto de limpieza” de la marca Ariel, en los hábitos de compra de las amas de casa de La Victoria. Con la finalidad de alcanzar el objetivo el estudio fue abordado desde una perspectiva cuantitativa con un alcance correlacional – causal, tomando un diseño de contrastación de hipótesis no experimental de corte transversal. Se trabajó con una población de 18004 amas de casa del distrito de la Victoria, de donde se extrajo una muestra de 384 participantes del estudio. Para recoger los datos se trabajó con una encuesta y se aplicó un cuestionario que constaba de 22 ítems basados en una escala cualitativa ordinal para medir la actitud de las amas de casa frente a las variables de estudio. Según la prueba de hipótesis se concluyó que la campaña publicitaria “El reto de Limpieza” de la marca Ariel, no generaba un impacto significativo sobre los hábitos de compra de las amas de casa de la Victoria. Sin embargo, según el coeficiente de correlación de Spearman de 0.075 existe la posibilidad de que la campaña publicitaria de la marca ejerza efectos mínimos sobre los hábitos de compra.Tesi

LUVMI: an innovative payload for the sampling of volatiles at the Lunar poles

The ISECG identifies one of the first exploration steps as in situ investigations of the moon or asteroids. Europe is developing payload concepts for drilling and sample analysis, a contribution to a 250kg rover as well as for sample return. To achieve these missions, ESA depends on international partnerships. Such missions will be seldom, expensive and the drill/sample site selected will be based on observations from orbit not calibrated with ground truth data. Many of the international science community’s objectives can be met at lower cost, or the chances of mission success improved and the quality of the science increased by making use of an innovative, low mass, mobile robotic payload following the LEAG recommendations. LUVMI provides a smart, low mass, innovative, modular mobile payload comprising surface and subsurface sensing with an in-situ sampling technology capable of depth-resolved extraction of volatiles, combined with a volatile analyser (mass spectrometer) capable of identifying the chemical composition of the most important volatiles. This will allow LUVMI to: traverse the lunar surface prospecting for volatiles; sample subsurface up to a depth of 10 cm (with a goal of 20 cm); extract water and other loosely bound volatiles; identify the chemical species extracted; access and sample permanently shadowed regions (PSR). The main innovation of LUVMI is to develop an in situ sampling technology capable of depth-resolved extraction of volatiles, and then to package within this tool, the analyser itself, so as to maximise transfer efficiency and minimise sample handling and its attendant mass requirements and risk of sample alteration. By building on national, EC and ESA funded research and developments, this project will develop to TRL6 instruments that together form a smart modular mobile payload that could be flight ready in 2020. The LUVMI sampling instrument will be tested in a highly representative environment including thermal, vacuum and regolith simulant and the integrated payload demonstrated in a representative environment

Reseñas

Quattuor libri principiorum, ed. M. A. SÁNCHEZ MANZANO. B. BAYONA AZNAR, Religión y poder. Marsilio de Padua: ¿La primera teoría laica del Estado? K.G. SCHON (ed), Die Capitula Angilramni. Eine prozessrechtiliche Falschung Pseudoisidors. C. JOSTMANN, Sibilla Erithea Babilonica: Papsttum und Prophetie im 13. Jahrhundert. H. RODRÍGUEZ PENELAS, Ética y sistemática del contrato en el Siglo de Oro. La obra de Francisco García en su contexto jurídico-moral. J. ESCOTO ERIÚGENA, Sobre las naturalezas (Periphyseon), trad. LORENZO VELÁZQUEZ. MARKUS RIEDENAUER, Pluralität und Rationalität. Die Herausforderung der Vernunft durch religiöse und kulturelle Vielfalt nach Nikolaus Cusanus. E.P. BOS, Logica modernorum in Prague about 1400. The sophistria disputations ‘quoniam quatuor’ with a partial reconstruction of Thomas of Cleves’ Logica. SAN AGUSTÍN, Confesiones, trad. A. UÑA JUÁREZ. JUAN CRUZ CRUZ / MA. JESÚS SOTO-BRUNA (eds), Metafísica y Dialéctica en los períodos carolingios y franco (s. IX-XI). DIONISIO AREOPAGITA, Los nombres divinos, estudio filológico-lingüístico, trad. P. A. CAVALLERO. YSABEL DE ANDÍA, Denys L’Aréopagite. Tradition et Métamorphoses. S. CAROTI / R. IMBACH / Z. KALUZA / G. STABILE / L. STURLESE (eds), “Ad ingenii acuitionem”. Studies in honour of Alfonso Maierù. SAN AGUSTÍN, Interpretación literal del Génesis, trad. C. CALABRESE. W. V. HARRIS (ed), The Spread of Christianity in the First Four Centuries. Essays in Explanation. M. C. PACHECO / J. F. MEIRINHOS (eds), Intellect et imagination dans la Philosophie Médiévale. J. HAMESSE / O. WEIJERS (ed), Écriture et Réécriture des textes philosophiques médiévaux. S. GERSH / D. MORAN (eds), Eriugena, Berkeley and the Idealist Tradition. CLAUDIA D’AMICO (ed), Todo y nada de todo. Selección de textos del Neoplatonismo latino medieval

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic die