Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.     

A robot learning from demonstration framework to perform force-based manipulation tasks

This paper proposes an end-to-end learning from demonstration framework for teaching force-based manipulation tasks to robots. The strengths of this work are manyfold. First, we deal with the problem of learning through force perceptions exclusively. Second, we propose to exploit haptic feedback both as a means for improving teacher demonstrations and as a human–robot interaction tool, establishing a bidirectional communication channel between the teacher and the robot, in contrast to the works using kinesthetic teaching. Third, we address the well-known what to imitate? problem from a different point of view, based on the mutual information between perceptions and actions. Lastly, the teacher’s demonstrations are encoded using a Hidden Markov Model, and the robot execution phase is developed by implementing a modified version of Gaussian Mixture Regression that uses implicit temporal information from the probabilistic model, needed when tackling tasks with ambiguous perceptions. Experimental results show that the robot is able to learn and reproduce two different manipulation tasks, with a performance comparable to the teacher’s one.     

Incremental Learning of Skills in a Task-Parameterized Gaussian Mixture Model

Programming by demonstration techniques facilitate the programming of robots. Some of them allow the generalization of tasks through parameters, although they require new training when trajectories different from the ones used to estimate the model need to be added. One of the ways to re-train a robot is by incremental learning, which supplies additional information of the task and does not require teaching the whole task again. The present study proposes three techniques to add trajectories to a previously estimated task-parameterized Gaussian mixture model. The first technique estimates a new model by accumulating the new trajectory and the set of trajectories generated using the previous model. The second technique permits adding to the parameters of the existent model those obtained for the new trajectories. The third one updates the model parameters by running a modified version of the Expectation-Maximization algorithm, with the information of the new trajectories. The techniques were evaluated in a simulated task and a real one, and they showed better performance than that of the existent model.     

Temperature accelerated life test on commercial concentrator III–V triple‐junction solar cells and reliability analysis as a function of the operating temperature

A temperature accelerated life test on commercial concentrator lattice‐matched GaInP/GaInAs/Ge triple‐junction solar cells has been carried out. The acceleration of the aging has been accomplished by subjecting the solar cells at temperatures markedly higher than the nominal working temperature inside a concentrator, and the nominal photo‐current condition (820 X) has been emulated by injecting current in darkness. Three tests at different temperatures have been carried out. The failure distributions across the three test temperatures have been fitted to an Arrhenius–Weibull model. An Arrhenius activation energy of 1.59 eV was determined from the fit. The reliability functions and parameters of these solar cells at two nominal working conditions (80 and 100 °C) have been obtained. In both cases, the instantaneous failure rate function monotonically increases, that is, the failures are of the wear‐out kind. We have also observed that the reliability data are very sensitive to the nominal temperature condition. In fact, at a nominal working condition of 820 X and 80 °C, assuming that the concentration module works 5 h per day, the warranty time obtained for a failure population of 5% has been 113 years. However, for a nominal working condition of 820 X and 100 °C, the warranty time obtained for a failure population of 5% has been 7 years. Therefore, in order to offer a long‐term warranty, the working temperature could be a key factor in the design of the concentration photovoltaic systems. Copyright © 2014 John Wiley & Sons, Ltd.     

High level communication functionalities for wireless sensor networks

In this paper we show how to establish a reliable and efficient high level communication system in a randomly deployed network of sensors equipped with directional antennas. This high level communication system enables the programming of the sensor network using high level communication functionalities without the burden of taking care of their physical capacities (low range, unidirectional links, single frequency, presence of collisions, etc.). The high level communication functionalities we offer include point-to-point communication, point-to-area communication, and one-to-all communication. The basic idea to implement this system is to simulate a virtual network that emerges from the ad-hoc network using self-organization, self-discovery and collaborative methods. We also analyse the efficiency, scalability and robustness of the proposed protocols.     

Selective Green Coupling of Alkynyltins and Allylic Halides to Trienynes via a Tandem Double Stille Reaction

The palladium‐catalyzed reaction of alkynyltin compounds with allylic chlorides leads to a 2:2 coupling to give trienynes by regio‐ and stereoselective formation of three new C C bonds. The reaction can be applied to different alkynyl and allylic fragments, providing a wide range of trienynes with different substitution patterns in very good yields. They can be prepared in a green way using recyclable polymeric tin alkynyls.