Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells

Background -- N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. Methods -- CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. Results -- No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. Conclusions -- In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.

Tension and Ampacity Monitoring System for Overhead Lines

Real time monitoring allows the determination of the line state and the calculation of the actual rating value. The real time monitoring systems measure sag, conductor tension, conductor temperature or weather related magnitudes. In this paper, a new ampacity monitoring system for overhead lines, based on the conductor tension, the ambient temperature, the solar radiation and the current intensity, is presented. The measurements are transmitted via GPRS to a control center where a software program calculates the ampacity value. The system takes into account the creep deformation experienced by the conductors during their lifetime and calibrates the tension-temperature reference and the maximum allowable temperature in order to obtain the ampacity. The system includes both hardware implementation and remote control software.

Visual SLAM using straight lines

The present thesis is focuses on the problem of Simultaneous Localisation and Mapping (SLAM) using only visual data (VSLAM). This means to concurrently estimate the position of a moving camera and to create a consistent map of the environment. Since implementing a whole VSLAM system is out of the scope of a degree thesis, the main aim is to improve an existing visual SLAM system by complementing the commonly used point features with straight line primitives. This enables more accurate localization in environments with few feature points, like corridors. As a foundation for the project, ScaViSLAM by Strasdat et al. is used, which is a state-of-the-art real-time visual SLAM framework. Since it currently only supports Stereo and RGB-D systems, implementing a Monocular approach will be researched as well as an integration of it as a ROS package in order to deploy it on a mobile robot. For the experimental results, the Care-O-bot service robot developed by Fraunhofer IPA will be used.

Enhanced Operation of Electricity Distribution Grids Through Smart Metering PLC Network Monitoring, Analysis and Grid Conditioning

Low Voltage (LV) electricity distribution grid operations can be improved through a combination of new smart metering systems' capabilities based on real time Power Line Communications (PLC) and LV grid topology mapping. This paper presents two novel contributions. The first one is a new methodology developed for smart metering PLC network monitoring and analysis. It can be used to obtain relevant information from the grid, thus adding value to existing smart metering deployments and facilitating utility operational activities. A second contribution describes grid conditioning used to obtain LV feeder and phase identification of all connected smart electric meters. Real time availability of such information may help utilities with grid planning, fault location and a more accurate point of supply management.

The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

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Rhythm Analysis during Cardiopulmonary Resuscitation: Past, Present, and Future

Survival from out-of-hospital cardiac arrest depends largely on two factors: early cardiopulmonary resuscitation (CPR) and early defibrillation. CPR must be interrupted for a reliable automated rhythm analysis because chest compressions induce artifacts in the ECG. Unfortunately, interrupting CPR adversely affects survival. In the last twenty years, research has been focused on designing methods for analysis of ECG during chest compressions. Most approaches are based either on adaptive filters to remove the CPR artifact or on robust algorithms which directly diagnose the corrupted ECG. In general, all the methods report low specificity values when tested on short ECG segments, but how to evaluate the real impact on CPR delivery of continuous rhythm analysis during CPR is still unknown. Recently, researchers have proposed a new methodology to measure this impact. Moreover, new strategies for fast rhythm analysis during ventilation pauses or high-specificity algorithms have been reported. Our objective is to present a thorough review of the field as the starting point for these late developments and to underline the open questions and future lines of research to be explored in the following years.

Mateda-2.0: Estimation of Distribution Algorithms in MATLAB

This paper describes Mateda-2.0, a MATLAB package for estimation of distribution algorithms (EDAs). This package can be used to solve single and multi-objective discrete and continuous optimization problems using EDAs based on undirected and directed probabilistic graphical models. The implementation contains several methods commonly employed by EDAs. It is also conceived as an open package to allow users to incorporate different combinations of selection, learning, sampling, and local search procedures. Additionally, it includes methods to extract, process and visualize the structures learned by the probabilistic models. This way, it can unveil previously unknown information about the optimization problem domain. Mateda-2.0 also incorporates a module for creating and validating function models based on the probabilistic models learned by EDAs.

Extending Distance-based Ranking Models In Estimation of Distribution Algorithms

Recently, probability models on rankings have been proposed in the field of estimation of distribution algorithms in order to solve permutation-based combinatorial optimisation problems. Particularly, distance-based ranking models, such as Mallows and Generalized Mallows under the Kendall’s-t distance, have demonstrated their validity when solving this type of problems. Nevertheless, there are still many trends that deserve further study. In this paper, we extend the use of distance-based ranking models in the framework of EDAs by introducing new distance metrics such as Cayley and Ulam. In order to analyse the performance of the Mallows and Generalized Mallows EDAs under the Kendall, Cayley and Ulam distances, we run them on a benchmark of 120 instances from four well known permutation problems. The conducted experiments showed that there is not just one metric that performs the best in all the problems. However, the statistical test pointed out that Mallows-Ulam EDA is the most stable algorithm among the studied proposals.