Morphological Features of Dysplastic Progression in Epithelium: Quantification of Cytological, Microendoscopic, and Second Harmonic Generation Images

Advances in imaging technology have led to a variety of available clinical and investigational systems. In this collection of studies, we tested the relevance of morphological image feature quantification on several imaging systems and epithelial tissues. Quantification carries the benefit of creating numerical baselines and thresholds of healthy and abnormal tissues, to potentially aid clinicians in determining a diagnosis, as well as providing researchers with standardized, unbiased results for future dissemination and comparison. Morphological image features in proflavine stained oral cells were compared qualitatively to traditional Giemsa stained cells, and then we quantified the nuclear to cytoplasm ratio. We determined that quantification of proflavine stained cells matched our hypothesis, as the nuclei in oral carcinoma cells were significantly larger than healthy oral cells. Proflavine has been used in conjunction with translational fluorescence microendoscopy of the gastrointestinal tract, and we demonstrated the ability of our custom algorithm to accurately (up to 85% sensitivity) extract colorectal crypt area and circularity data, which could minimize the burden of training on clinicians. In addition, we proposed fluorescein as an alternative fluorescent dye, providing comparable crypt area and circularity information. In order to investigate the morphological changes of crypts via the supporting collagen structures, we adapted our quantification algorithm to analyze crypt area, circularity, and an additional shape parameter in second harmonic generation images of label-free freshly resected murine epithelium. Murine models of colorectal cancer (CRC) were imaged at early and late stages of tumor progression, and we noted significant differences between the Control groups and the late cancer stages, with some differences between early and late stages of CRC progression

Technical Contributions to the Quality of Telerehabilitation Platforms: Case Study—ePHoRt Project

This chapter proposes three main technical contributions for the development of a telerehabilitation platform, named ePHoRT, for patients recovering from hip surgery. The first contribution is the application of a diffuse 3D model for the detection of rehabilitation exercises after hip surgery. The model applies fuzzy logic, which allows identifying in real time if a patient is performing a right or wrong movement, assisted by an avatar in 3D. The avatar copies the movements of the patient through a Kinect camera. The second contribution involves the proposal of an iterative method to improve the usability of telerehabilitation platforms along the development life cycle. The proposed method involves the use of an inspection method and includes protocols and instruments. This method has been validated in the ePHoRT project. Finally, the chapter describes accessibility guidelines for educational resources. It proposes accessibility standards for the content of educational resources in video and PDF formats in the telerehabilitation platform according to the Web Content Accessibility Guidelines (WCAG)

Serviços de sincronização e armazenamento de arquivos para ambientes educativos em caso de desastre

1 recurso en línea (páginas 81-91).Las nubes computacionales son una solución emergente que responden al concepto de Smart University, para proporcionar un entorno inteligente de continuidad del negocio para los actores de un centro educativo. Esta investigación propone un plan de recuperación de servicios educativos en caso de desastres, aplicando la metodología de Investigación-Acción, que incluye un análisis de nubes computacionales de software libre, al enfocarse en los sistemas de Sincronización y Uso Compartido de Archivos Empresariales (EFSS). Para llevarlo a cabo se diseñó e implementó un escenario local (Linux Apache, MySQL, y PHP, LAMP). Para su evaluación y validación se realizaron varias pruebas de estrés en tres aplicativos: Nextcloud, Seafile y Pydio. Entre los hallazgos se evidenció que Nextcloud tuvo resultados consistentes por encima de las dos opciones restantes; sin embargo, esta solución no tiene un sistema que le permita sincronizar dos instancias de Nextcloud. Para solucionarlo, se desarrolló una rutina con el objetivo de proporcionar un ambiente que monitoree un hot site donde está alojado el aplicativo en producción y, cada cierto tiempo, realice sincronizaciones de la instancia para evitar la pérdida de información en caso de desastres. Luego, se configuró un segundo aplicativo en un cold site que está atento ante una posible caída del servicio, para su respuesta y alerta inmediata. Por último, se evalúo la usabilidad de la rutina y se ensambló un plan de recuperación de desastres para las EFSS, a fin de ofrecer una continuidad de los servicios educativos que se gestan en estos entornos.Cloud computing is an emerging solution that responds to the concept of Smart University; it aims at offering an intelligent environment of business continuity for the actors of an educational center. This research offers a recovery plan of educational services in case of disaster, through an action research, which analyzed free software for cloud computing, focusing on Enterprise File Synchronization and Sharing (EFSS). To achieve this, the implementation was placed in a local scenario (Linux Apache, MySQL, PHP, LAMP), and stress tests were performed on three applications: Nextcloud, Seafile and Pydio. Nextcloud had more consistent and better results than the other two applications; however, it lacks a system that allows synchronizing two Nextcloud instances. To solve this, we developed a routine aimed at providing an environment that monitors the hot site where the application is hosted and, from time to time, synchronize the instance to avoid data loss during disaster events. Afterwards, we configured a second application on a cold site that is alert to a possible service breakdown, so it can respond and sent immediate alerts. Finally, the usability of the routine was evaluated, and the disaster recovery plan for the EFSS was assembled, to offer a continuity of the educational services that are running in these environments.As nuvens computacionais são uma solução emergente que respondem ao conceito de Smart University, para proporcionar um ambiente inteligente de continuidade do negócio para os atores de um centro educativo. Esta pesquisa propõe um plano de recuperação de serviços educativos em caso de desastres, aplicando a metodologia de Pesquisa-Ação, que inclui uma análise de nuvens computacionais de software livre, ao enfocar-se nos sistemas de Sincronização e Uso Compartilhado de Arquivos Empresariais (EFSS). Para levá-lo a cabo desenhou-se e implementou-se um cenário local (Linux Apache, MySQL, e PHP, LAMP). Para sua avaliação e validação realizaram-se várias provas de estresse em três aplicativos: Nextcloud, Seafile e Pydio. Entre os achados evidenciou-se que Nextcloud teve resultados consistentes acima das duas opções restantes; porém, esta solução não tem um sistema que lhe permita sincronizar duas instâncias de Nextcloud. Para solucioná-lo, desenvolveu-se uma rotina com o objetivo de proporcionar um ambiente que monitore um hot site onde está alojado o aplicativo em produção e, cada certo tempo, realize sincronizações da instância para evitar a perda de informação em caso de desastres. Logo, configurou-se um segundo aplicativo em um cold site que está atento ante uma possível queda do serviço, para sua resposta e alerta imediata. Por último, avaliou-se a usabilidade da rotina e elaborou-se um plano de recuperação de desastres para as EFSS, a fim de oferecer uma continuidade dos serviços educativos que se gestam nestes ambientes.Bibliografía: páginas 90-91

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

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

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

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO