An Impedimetric Biosensing Strategy Based on Bicyclic Peptides as Bioreceptors for Monitoring huPA Cancer Biomarker

In the era of liquid biopsies, the reliable and cost-effective detection and screening of cancer biomarkers has become of fundamental importance, thus paving the way for the advancement of research in the field of point-of-care testing and the development of new methodologies and technologies. Indeed, the latter ones can help designing advanced diagnostic tools that can offer portability, ease of use with affordable production and operating costs. In this respect, impedance-based biosensing platforms might represent an attractive alternative. In this work, we describe a proof-of-concept study aimed at designing portable impedimetric biosensors for the monitoring of human urokinase-type plasminogen activator (h-uPA) cancer biomarker by employing small synthetic receptors. Aberrant levels of h-uPA were correlated with different types of cancers. Herein, we report the use of two bicyclic peptides (P2 and P3) which have been engineered to bind h-uPA with high affinity and exquisite specificity. The synthetic receptors were immobilized via biotin-streptavidin chemistry on the surface of commercial screen-printed electrodes. The impedimetric changes in the electrode/solution interface upon incubation of spiked h-uPA samples in the presence of a redox probe were followed via electrochemical impedance spectroscopy. The P3-based impedimetric assay showed the best outcomes in terms of dynamic range and linearity (0.01–1 μg mL−1) and sensitivity (LOD = 9 ng mL−1). To fully assess the performances of P3 over P2, and to compare the label-free architecture vs. labelled architecture, a voltammetric assay was also developed

Dipole Moment Effect on the Electrochemical Desorption of Self-Assembled Monolayers of 310-Helicogenic Peptides on Gold

AbstractThe front cover artwork is provided by Pierangelo Gobbo and Flavio Maran, University of Padova (Italy). The image highlights how the orientation of the dipole moment associated with helical peptides affects the electrodesorption potential of the corresponding self‐assembled monolayers. Read the full text of the Article at 10.1002/celc.201600573

Expressing aspectual interactions in requirements engineering: Experiences, problems and solutions

Aspect Oriented Requirements Engineering (AORE) provides support for modularizing crosscutting requirements. In the context of an industrial project in the domain of Slot Machines we needed to perform AORE, with a special emphasis on dependencies and interactions among concerns. We were however unable to find any report of large-scale industrial applications of AORE approaches that treat dependencies and interactions. We therefore evaluated two AORE approaches: Theme/Doc and MDSOCRE, to establish their applicability in our setting. In this paper we report on the limitations of both approaches we encountered and propose extensions that allow them to cope with concern interactions. We also show how these extensions provide the needed expressiveness by applying them to our industrial case study.Laboratorio de Investigación y Formación en Informática Avanzad

Una arquitectura para manejar datos continuos en SIG

Las aplicaciones geográficas en muchos casos implican la definición y manipulación de información continua. Esto es de suma relevancia en áreas como meteorología y aplicaciones ambientales. Los sistemas de información geográfica carecen de herramientas que permitan el uso de este tipo de información, lo que muchas veces impide contar con un análisis completo. En este trabajo se describe una arquitectura orientada a objetos que permite el diseño y manipulación de datos continuos

Addressing aspect interactions in an industrial setting: experiences, problems and solutions

Aspect oriented programming (AOP) introduces new and powerful modularization constructs. The aspect module is used to encapsulate crosscutting concerns, which otherwise would remain tangled and scattered. The idea of encapsulating crosscutting concerns rapidly expanded to earlier phases in the development cycle, including requirement analysis (aspect oriented requirement engineering, AORE) and design (aspect oriented modeling, AOM). The overall application of aspect orientation concepts is known as aspect oriented software development (AOSD). AOP is not yet a mainstream practice. Particularly AOSD is still in its early stages. This is reflected in the lack of reports of full development cycles using aspect oriented approaches, especially using industrial case studies. Furthermore, the power of aspects comes at the price of new challenges, one of them is that systems built using aspects are more difficult to understand. The crosscutting nature of aspects allows them to alter the behavior of many other modules. As a result, aspects may interact in unintended and unanticipated ways. This problem is known as aspect interactions. In this work we deal with the aspect interaction problem in the context of an industrial domain: slots machines. We perform a complete development cycle of the slot machine software. This is, to the best of our knowledge, the first complete industrial case of study of aspect orientation. Through this experience we discovered the limitations with regard to aspect interactions, of some emblematic aspect oriented approaches for requirement engineering, design and implementation. The contribution of this work is threefold. Firstly, we contribute with the evaluation and extensions to some of AORE and AOM approaches, in order to provide explicit support for aspect interactions in requirement analysis and design phases. We also evaluate the implementation of interactions using a static and a dynamic AOP language, and propose an AspectJ extension that copes with aspect interactions. Secondly, this work is the first report of a complete aspect oriented development cycle of an industrial case study. Thirdly, this work provides a complex case study that presents several business logic crosscutting concerns, which in turn exhibit numerous aspect interactions, that serves as a challenging test bed for upcoming AOSD approaches.Facultad de Informátic

Integrando sensibilidad al contexto mediante Aspect Oriented Programming

La complejidad de los sistemas sensibles al contexto implica un gran número de concerns de software que deben ser modelados e implementados. Estos concerns normalmente se entremezclan con el resto de los módulos produciendo código esparcido y enredado que, por consiguiente, es muy difícil de evolucionar y mantener. Para atacar este problema en el presente trabajo se estudia la utilización de Aspect Oriented Programming. Se relevan las características principales de las aplicaciones móviles sensibles al contexto y los principales enfoques de separación de concerns. Se describe una arquitectura basada en Aspect Oriented Programming que permite lograr un alto grado modularización, separando los concerns que no pertenecen a la dimensión principal de la aplicación. Dicha arquitectura es estudiada desde el punto de vista del reuso de los concerns de sensibilidad al contexto. Además se estudian los conflictos que surgen de la integración de los diversos concerns implementados como aspectos, proponiendo un mecanismo que permite resolverlos conservando a la vez la escencia modular de Aspect Oriented Programming.Facultad de Informátic

Paneth and Intestinal Stem Cells Preserve their Functional Integrity during Worsening of Acute Cellular Rejection in Small Bowel Transplantation

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67+ IL-22R+ stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R+ Ki-67+ stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients.Fil: Pucci Molineris, Melisa Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Gonzalez Polo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Pérez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ramisch, D.. Fundación Favaloro; ArgentinaFil: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Gondolesi, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Meier, D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67+ IL-22R+ stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R+ Ki-67+ stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients.Instituto de Estudios Inmunológicos y Fisiopatológico

Manipulación de campos continuos y su aplicación a los sistemas de información geográfica

Se está haciendo un considerable progreso en la integración de los sistemas de información espacial, GIS y los modelos matemáticos que rigen en medioambiente. Para la mayoría de los proyectos de modelos ambientales, los GISs son vistos como bases de datos apropiadas y bien estructuradas para el manejo de grandes cantidades de datos espaciales. La herramientas GIS tradicionales, como los overlays y buffering son también importantes para el desarrollo de juegos de datos derivados (derivative datasets) que sirven para generar vistas sobre variables. Muchos expertos esperan que pronto se incorporen mejores métodos de análisis espacial a los GIS actuales, la tecnología GIS se convertirá en una herramienta importante en todos los aspectos del modelamiento, incluyendo construcción de modelos, validación y operación. Sin embargo, existen grandes incompatibilidades que obstruyen la verdadera integración. Los GIS manejan datos estáticos y discretos mientras los modelos ambientales tratan fenómenos dinámicos y continuos. Las BD GIS manipulan datos en términos de ubicación, distribución y relaciones espaciales, mientras que los modelos ambientales trabajan con la transferencia masa y energía. Para lograr una integración total de ambos necesitamos agregar el dinamismo y la continuidad a nuestro concepto de datos espaciales; e interacción espacial y funcionalidad a los modelos ambientales. Este trabajo de investigación apunta a la primera de estas necesidades, considerando lo que implica trabajar con fenómenos continuos directamente en el contexto de GIS. Se tendrá en cuenta cómo los fenómenos espacialmente distribuidos se caracterizan en los modelos ambientales, una estrategia para trabajar con dichos fenómenos de manera que puedan ser eficientes y convincentemente incorporados en aplicaciones GIS. Ya que la mayoría de los fenómenos ambientales tratan con fenómenos que son continuos en el espacio, es necesario proveer formas en las que los modeladores puedan trabajar directamente con los fenómenos continuos, en vez de verse forzados a trabajar con datos espaciales discretos. Debemos reconocer que los datos espaciales son representaciones de la realidad, no la realidad en sí, por lo que deberíamos concentrarnos en lograr un análisis que no dependa de la representación, sino de la realidad en sí (frame free analysis).Facultad de Informátic