7 research outputs found
A Complementary Approach for Adaptive and Adaptable Hypermedia: Intensional Hypertext
No full textIn this paper we describe a methodology and an authoring/publishing tool for adaptable Web documents (user-determined adaptable Web pages) as a complementary approach to Adaptive Hypermedia. Our approach is based on intensional logic, the logic of assertions and expressions, which vary over a collection of contexts or possible worlds. In our approach the contexts are sets of values for parameters which specify the current user profile as supplied by the current Web page URL, and the latest user input. The author produces generic (multi-version) source in the form of HTML with extra markup delimiting parts that are sensitive (in various ways) to the parameters. This source (in what we call Intensional Markup Language) is translated into a Perl-like language called ISE (Intensional Sequential Evaluator). To generate the appropriately adapted individual pages, the server runs the ISE program in the appropriate context. The program produces HTML that, when displayed in the user's browser, is rendered into the desired adaptation of the requested page. Although this intensional approach was originally designed to work without any explicit user model, we can extend it (and make the documents adaptive as well as adaptable) simply by incorporating a user model that monitors the user and computes some of the profile parameters
Inducible expression of RANKL in transgenic pigs under the control of the Tet-On system
No full textBecause of the tremendous need for transgenic large animal models for human diseases, the process of SCNT is a crucial step in transgenic pig production. In our study, we evaluated the particular steps during the production for their impact on the efficiency of cloning transgenic pigs. For this purpose, statistical analysis was performed for all SCNT data from the years 2006 until June 2010. The RANKL transgenic osteoporosis model was chosen for an example for the production steps needed to finally achieve a disease model, to elucidate pitfalls and chances of SCNT procedure. In total 151 in vivo SCNT experiments using different transgenic cell lines were carried out, resulting in 243 piglets and fetuses. Statistical analysis revealed that donor cells treated exclusively in our laboratory had a significant better birth rate than donor cell originated of other laboratories. Furthermore, there was a significant relation between number of transferred NT embryos and later pregnancy checks, birth rate and abortion rate. The more NT embryos were transferred, the more pregnancies finished to terms. It was also elucidated that in our studies a different in vitro culture time of 24 or 48 hours had no significant impact on the outcome like pregnancy or birth rate. Seasonal changes during the years had no significant influence on pregnancy rate, birth or abortion. But there was a strong tendency that autumn showed best performance of all seasons, and most pregnancies were lost after embryo transfers during the summer. All these findings will be integrated in future in vivo SCNT experiments and embryo transfers. For the production of a transgenic osteoporosis model 17 in vivo experiments took place so far, with an outcome of 4 fetuses and 25 piglets. For gaining a controllable expression of RANKL, it was necessary to establish double transgenic pigs to sidestep harmful effects of RANKL overexpression during the fetal development. First attempts to integrate both genes, tetracycline controlled transactivator (Tet-On) and RANKL, in a single step of cell transfection and SCNT, had no satisfying result. We obtained 4 fetuses and stillborn recloned piglets carrying both genes, but they showed only expression of Tet-On and it was impossible to induce RANKL overexpression. Therefore the strategy was changed in favor to two rounds of transfection and nuclear transfer. First Tet-On transgenic piglets were established and screened for integration and expression. Piglet 9894 showed the best expression and severed as donor for next cell transfection step. These Tet-On + TARE RANKL cells were in vitro tested for their inducibility. Thereafter SCNT and embryo transfer of the best candidate were performed and they resulted in 4 pregnancies which all finished to term. One double transgenic piglet could be raised and will be kept until adulthood to establish a line of Tet-On +TARE RANKL transgenic pigs. Importantly, this founder animal showed inducible RANKL overexpression. Other constructs might be based on the existing Tet-On cell line in the future, offering an inducible system for a broad variety of different transgenes. Thus a functional Tet-On system in the pig is reported for the first time.Da es einen enormen Bedarf an transgenen Großtieren als Modelltiere für humane Erkrankungen gibt, wie zum Beispiel für Osteoporose, wurde die Generierung von transgenen Schweinen mittels somatischen Kerntransfers genauer untersucht. Dabei war das Ziel herauszufinden, welchen Einfluss die einzelnen Arbeitsschritte auf die Produktionseffizienz haben. Aus diesem Grund wurde eine statistische Analyse aller in vivo Kerntransfers von Anfang 2006 bis zum Juni 2010 durchgeführt. An dem Beispiel eines RANKL transgenen Osteoporose-Models wurden alle nötigen Produktionsschritte dargestellt und die Schwierigkeiten und Vorteile des somatischen Kerntransfers beschrieben. Die insgesamt 151 in vivo Experimente, wobei unterschiedliche transgene Zelllinien genutzt wurden, resultierten in 243 Ferkeln und Feten. Statistische Analysen zeigten, dass Spenderzellen, die ausschließlich in unserem Labor behandelt wurden, nach Kerntransfer zu einer signifikant höheren Geburtsrate der trächtigen Empfänger führten als Spenderzellen aus anderen Laboren. Weiterhin ergab sich ein Zusammenhang zwischen der Anzahl übertragener Kerntransfer-Embryonen und der späteren Trächtigkeitsrate, Geburtsrate und der Abortrate. Je mehr Embryonen übertragen wurden, desto mehr Trächtigkeiten wurden erfolgreich beendet. Es wurde auch sichtbar, dass in unseren Versuchen eine unterschiedliche in vitro-Kulturdauer der Kerntransfer-Embryonen von 24 bzw. 48 Stunden keinen signifikanten Unterschied in der Trächtigkeits- oder Geburtsrate verursachte. Auch für die verschiedenen Jahreszeiten konnte kein signifikanter Einfluss auf Trächtigkeit oder Geburt nachgewiesen werden. Es zeigte sich aber die Tendenz, dass im Herbst die besten Bedingungen für einen positiven Verlauf der Trächtigkeit herrschen und nach Embryotransfers im Sommer die höchste Abortrate auftritt. All diese Untersuchungsergebnisse werden zukünftig in unseren Arbeitsalltag integriert und der Kerntransfer und Embryotransferablauf optimiert. Zur Erstellung eines transgenen Osteoporosemodells wurden 17 Embryotransfers durchgeführt, die in 4 gewonnenen Feten und 25 geborenen Ferkeln resultierten. Um eine regulierbare RANKL Expression zu erhalten war es notwendig, doppelt transgene Schweine zu erstellen, so dass negative Nebeneffekte der RANKL Überexpression während der Fetalentwicklung vermieden wurden. Die ersten Versuche, Tetrazyklin Transaktivator (Tet-On) und RANKL in einem einzigen Schritt der Zelltransfektion und des in vivo Kerntransfers zu integrieren, führte zu wenig befriedigenden Ergebnissen. Es wurden 4 doppelt transgene Feten und 2 totgeborene Ferkel gewonnen, doch es konnte nur die Expression von Tet-On nachgewiesen werden, da die RANKL Expression nicht induzierbar war. Deswegen wurde die Strategie zu Gunsten von zwei Einzelschritten der Zelltransfektion und in vivo Kerntransfers gewechselt. Zuerst wurden Tet-On transgene Ferkel erstellt und auf Integration und Expression hin untersucht. Das Ferkel 8994 zeigte die beste Expression und seine Zellen wurden für den nächsten Zelltransfektionsschritt verwendet. Die daraus resultierenden Tet-On + TARE RANKL-Zellen wurden in vitro auf ihre Induzierbarkeit getestet. Als Spenderzellen für weitere in vivo Kerntransfers diente der beste Kandidat aus diesen Tests. Alle 4 Embryotransfers resultierten in Trächtigkeiten, die alle auch ausgetragen wurden. Ein doppelt transgenes Ferkel konnte aufgezogen werden, das zum einen nach Erreichen der Geschlechtsreife als Gründer einer transgenen Schweinelinie dienen wird, und im in vivo-Test eine induzierbare Expression von RANKL zeigte. Die regulierbaren Tet-On Zelllinien können auch für weitere zukünftige Konstrukte Verwendung finden, was die Möglichkeit mannigfaltiger genetischer Manipulation durch ein induzierbares System eröffnet. Hiermit wird das erste Mal von einem funktionalen und kontrollierbaren Tet-On System im Schwein berichtet
Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation
No full textRestoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in CftrF508del homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.</p
Don Quijote, humor y gestos
No full textThe present article is about a method of analysis of gestures and movements in literature called kinesic analysis. Its purpose is to develop ways of accounting for a type of humour elicited by narrated corporeal dynamics in interaction, as perceived in the cognitive act of reading literature. When centuries and multiple cultural variations separate corporeal experiences, how does literature enable us to grasp the dynamic sensations narrated by authors to the point of making us laugh? Beyond the undeniable historical divide that calls for the greatest caution, are there shared aspects that allow us to understand the type of embodied experience that an author such as Cervantes conveys through the movements of his writing? In a perspective that is both «narratological» and cognitive, this article provides an approach that takes into account the cognitive process called perceptual simulation, paying a particular attention to the sensorimotor aspect of tonicity.Este artículo trata del análisis kinésico, es decir de un método de análisis de los gestos y de los movimientos en la literatura. Propone desarrollar los medios de dar cuenta de un humor que proviene de las dinámicas corporales en interacción, tal y como se actualizan en la lectura de una obra literaria. Cuando las vivencias corporales se encuentran separadas por siglos y múltiples variaciones culturales, ¿cómo puede la literatura hacernos comprender y sentir las sensaciones dinámicas relatadas por los escritores hasta el punto de hacernos reír? Por encima de las brechas históricas innegables que nos obligan a una gran prudencia, ¿existen aspectos compartidos que nos permiten comprender las vivencias corporales de las que habla un escritor como Cervantes a través de los movimientos que describe en sus relatos? Este artículo trata de la cuestión específica del tono corporal integrado a perspectivas narratológicas y cognitivas
Mirroring cannot account for understanding action
No full textSusan Hurley's shared circuits model (SCM) rightly begins in action and progresses through a series of layers; but it fails to reach action understanding because it relies on mirroring as a driving force, draws on heavily criticized theories, and neglects the need for shared experience in our grasp of social understanding
Multidimensional poverty index (MPI) estimation in Bogotá D.C. and some nearby cities using satellite imagery
No full textilustraciones (principalmente a color), diagramas, fotografíasEn este documento se estudia una alternativa para obtener estimaciones de pobreza utilizando imágenes satelitales de Bogotá, D.C. y algunos municipios cercanos. Para lograr este fin, se comparan las dos metodologías presentadas en este trabajo: un modelo de redes neuronales convolucionales (CNN) y un modelo de regresión tensorial (GTR), los dos modelos aplicados para la clasificación de pixeles. A partir de estos modelos se definen unos criterios o métricas que nos permiten seleccionar el modelo que mejor captura la distribución del Índice de pobreza multidimensional (IPM) a nivel de píxeles. Finalmente, se lleva a cabo una aplicación de estimación de pobreza utilizando las imágenes de Planet Scope (PS) y la información a nivel de manzanas del ´ultimo Censo Nacional de Población y Vivienda (CNPV2018) donde se encuentra que el modelo de GTR presenta mejores métricas de desempeño en comparación del modelo de CNN (Texto tomado de la fuente).This document explores an alternative method to obtain poverty estimates using satellite images of Bogot´a, D.C., and some nearby municipalities. To achieve this goal, the two methodologies proposed in this study are compared: Convolutional Neural Networks (CNN) and a Tensor Regression Model (GTR). Based on these models, criteria or metrics are defined to select the model that best captures the distribution of the Multidimensional Poverty Index (MPI) at the pixel level. Finally, a poverty estimation application is conducted using Planet Scope (PS) images and block-level information from the latest National Population and Housing Census (CNPV2018). The results reveal that the GTR model demonstrates superior performance metrics compared to the CNN model (Texto tomado de la fuente).MaestríaMagíster en Ciencias - EstadísticaAprendizaje Estadístic
Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study
No full textBackground: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis.
Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic.
Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19·8 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6·6 and 2·4 per cent respectively before, but 23·7 and 5·3 per cent, during the pandemic (both P < 0·001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe.
Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2
