Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective post-sonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements.     

The conceptual evolution of actual mathematical infinity

The different stages in the conceptual evolution of actual infinity are analyzed. We show how this concept occurs in high-school students at a prior, or at best, at the same level, as in Bernard Bolzano's conceptualization (as defined in his work The Paradoxes of Infinity). Furthermore, in terms of the historical development of the concept, the students' conceptualization has intra-objectal stage characteristics. Within the same framework, we show how Cantor's work fits into the inter-objectal stage, as well as presenting the difficulties encountered by students in order to reach this stage, given the current curricular structure. We conclude that such evidence should bring about a reconsideration of Piagetian ideas in education.     

Lo individual y lo social en la construcción del conocimiento

Resumen

En este trabajo se explican los principales principios y teóricos y metodologicos de una línea de investigación que tiene como objetivo el estudio del papel del contexto en la adquisición de ciertos contenidos específicos.

Para ilustrar dicha opción se presentan dos tipos de trabajos. En primer lugar se describe la trayectoria seguida en los trabajos sobre adquisición del lenguaje matemático que hemos venido realizando en los últimos años. En segundo lugar se presentan algunos datos de un trabajo realizado recientemente y orientado a analizar el discurso y la práctica en el aula.     

Decentralized state estimation for the control of network systems

The paper proposes a decentralized state estimation method for the control of network systems, where a cooperative objective has to be achieved. The nodes of the network are partitioned into independent nodes, providing the control inputs, and dependent nodes, controlled by local interaction laws. The proposed state estimation algorithm allows the independent nodes to estimate the state of the dependent nodes in a completely decentralized way. To do that, it is necessary for each independent node of the network to estimate the control input components computed by the other independent nodes, without requiring communication among the independent nodes. The decentralized state estimator, including an input estimator, is developed and the convergence properties are studied. Simulation results show the effectiveness of the proposed approach.     

Characteristics of Successful Collaborations to Produce Educated Software Engineering Professionals

Currently, a large gap exists between the number of open software engineering positions and the number of qualified software engineers to fill those positions. The Industry/University (I/U) subgroup of the Working Group on Software Engineering Education and Training (WGSEET) is investigating active collaborations between companies and universities in which non-software professionals and practitioners without formal software education are reeducated to become software engineers. This paper describes the current status of work performed by the I/U subgroup in the investigation of reeducation collaborations. It is our goal to identify the common characteristics of successful collaborations in order to provide guidance to universities and companies when constructing a collaborative program, as well as to promote future collaborations. In this paper, we report on the current activity of the I/U subgroup, describe the features of successful collaborations identified so far in our research, and provide some conclusions as to the usefulness of such collaborations.     

Aplicación a la escuela de la psicología genética: La pedagogía operatoria

RESUMEN

El sistema de enseñanza actual contribuye a provocar una escisión mental entre los conocimientos teóricos y su conexión con la realidad. La Pedagogía Operatoria, resultado de la experiencia práctica y de las reflexiones teóricas, intenta unir ambos aspectos. Tras analizar los resultados de los sistemas de enseñanza actuales puede afirmarse que todos sus esfuerzos van dirigidos a que el niño desarrolle la capacidad de reproducir conocimientos ya elaborados, y no a desarrollar la facultad de elaborar conocimientos. Se propone como alternativa el aprendizaje operatorio, que supone la construcción o elaboración del conocimiento por parte del individuo. De esta forma es posible la generalización a otras situaciones similares. Si cambia el contexto operacional, la generalización no será inmediata y será necesaria una reconstrucción metodológica. El papel del maestro es fundamental en este tipo de aprendizaje, con la ayuda y orientación del psicólogo escolar.     

Generating suggestions for queries in the long tail with an inverted index

This paper proposes an efficient and effective solution to the problem of choosing the queries to suggest to web search engine users in order to help them in rapidly satisfying their information needs. By exploiting a weak function for assessing the similarity between the current query and the knowledge base built from historical users’ sessions, we re-conduct the suggestion generation phase to the processing of a full-text query over an inverted index. The resulting query recommendation technique is very efficient and scalable, and is less affected by the data-sparsity problem than most state-of-the-art proposals. Thus, it is particularly effective in generating suggestions for rare queries occurring in the long tail of the query popularity distribution. The quality of suggestions generated is assessed by evaluating the effectiveness in forecasting the users’ behavior recorded in historical query logs, and on the basis of the results of a reproducible user study conducted on publicly-available, human-assessed data. The experimental evaluation conducted shows that our proposal remarkably outperforms two other state-of-the-art solutions, and that it can generate useful suggestions even for rare and never seen queries.     

A constructivist approach to studying the bullwhip effect by simulating the supply chain

The Cider Game is a simulator for a supply chain-related learning environment. Its main feature is that it provides support to students in the constructivist discovery process when learning how to make logistics decisions, at the same time as noting the occurrence of the bullwhip phenomenon. This learning environment seeks a balance between direct instruction in the learning process on the part of the tutor, and a suitable and sufficient degree of freedom to regulate independent learning on the part of students. This article describes the basic learning mechanisms using the Cider Game and the graphical learning environments that it provides. We describe the functionality provided by this application, and analyse the effect over the rational understanding of the bullwhip phenomenon by the students and whether they are able to make decisions to minimise its impact, studying the differences when that decision-making learning is done individually or in groups.