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.

Design of an optimised wheel profile for rail vehicles operating on two track gauges

This paper sets out an optimum synthesis methodology for wheel profiles of railway vehicles in order to secure good dynamic behaviour with different track configurations. Specifically, the optimisation process has been applied to the case of rail wheelsets mounted on double gauge bogies, that move over two different gauges, which also have different types of rail: the Iberian gauge (1668 mm) and the UIC gauge (1435 mm). Optimisation is performed using Genetic Algorithms and traditional optimisation methods in a complementary way. The objective function used is based on an ideal equivalent conicity curve which ensures good stability on straight sections and also proper negotiation of curves. To this end the curve is constructed in such a way that it is constant with a low value for small lateral wheelset displacements (with regard to stability), and increases as the displacements increase (to facilitate negotiation of curved sections). Using this kind of ideal conicity curve also enables a wheel profile to be secured where the contact points have a larger distribution over the active contact areas, making wear more homogeneous and reducing stresses. The result is a wheel profile with a conicity that is closer to the target conicity for both gauges studied, producing better curve negotiation while maintaining good stability on straight sections of track. The paper shows the resultant wheel profile, the contact curves it produces, and a number of dynamic analyses demonstrating better dynamic behaviour of the synthesised wheel on curved sections with respect to the original wheel.

Behavioral profile of adults with Prader-Willi syndrome : correlations with individual and environmental variables

Background: Maladaptive behavior has been reported as a phenotypical feature in Prader–Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. Methods: The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. Results: Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. Conclusions: Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was related to a lower severity of symptoms. Some major behavioral problems, such as hyperphagia, may be well controlled if living circumstances are adapted to the specific requirements of individuals with PWS.

Segmentación de los e-consumidores: un estudio aplicado a partir de las perspectivas de uso de Internet

[ES] La segmentación de mercados se ha utilizado con bastante frecuencia en las investigaciones de marketing tradicionales pero todavía aparece como una materia relativamente novedosa si se busca su aplicación en el uso de las Tecnologías de la Comunicación y de la Información (TIC) en general y de Internet en particular. La presente investigación tiene como objetivo principal analizar el comportamiento del internauta según los principales usos que piensa hacer, en un futuro próximo, de las diferentes aplicaciones de Internet. A partir de una muestra de 700 individuos, se realizó un análisis factorial y cluster para clasificar a los usuarios en tres colectivos. Junto con la información demográfica y las perspectivas de uso de la Red, se hizo posible la elaboración de un perfil diferenciado para cada segmento. El análisis también permite extraer los principales factores en los que se recogen las diferentes actitudes frente al uso de la Red. En las conclusiones se presentan las reflexiones más significativas sobre los segmentos obtenidos y su implicación en la gestión, las limitaciones del estudio y las futuras líneas de investigación.

Understanding Density in an Uneven City, Santiago de Chile: Implications for Social and Environmental Sustainability

Efforts to promote infill development and to raise densities are growing in many cities around the world as a way to encourage urban sustainability. However, in cities polarized along socio-economic lines, the benefits of densification are not so evident. The aim of this paper is to discuss some of the contradictions of densification in Santiago de Chile, a city characterized by socio-spatial disparities. To that end, we first use regression analysis to explain differences in density rates within the city. The regression analysis shows that dwelling density depends on the distance from the city center, socioeconomic conditions, and the availability of urban attributes in the area. After understanding the density profile, we discuss the implications for travel and the distribution of social infrastructures and the environmental services provided by green areas. While, at the metropolitan scale, densification may favor a more sustainable travel pattern, it should be achieved by balancing density rates and addressing spatial differences in the provision of social services and environmental amenities. We believe a metropolitan approach is essential to correct these spatial imbalances and to promote a more sustainable and socially cohesive growth pattern.

Complexity and Uniqueness of the Aromatic Profile of Smoked and Unsmoked Herreno Cheese

In this work, the volatile fraction of unsmoked and smoked Herreno cheese, a type of soft cheese from the Canary Islands, has been characterized for the first time. In order to evaluate if the position in the smokehouse could influence the volatile profile of the smoked variety, cheeses smoked at two different heights were studied. The volatile components were extracted by Solid Phase Microextraction using a divinylbenzene/carboxen/polydimethylsiloxane fiber, followed by Gas Chromatography/Mass Spectrometry. In total, 228 components were detected. The most numerous groups of components in the unsmoked Herreno cheese were hydrocarbons, followed by terpenes and sesquiterpenes, whereas acids and ketones were the most abundant. It is worth noticing the high number of aldehydes and ketones, and the low number of alcohols and esters in this cheese in relation to others, as well as the presence of some specific unsaturated hydrocarbons, terpenes, sesquiterpenes and nitrogenated derivatives. The smoking process enriches the volatile profile of Herreno cheese with ketones and diketones, methyl esters, aliphatic and aromatic aldehydes, hydrocarbons, terpenes, nitrogenated compounds, and especially with ethers and phenolic derivatives. Among these, methylindanones or certain terpenes like a-terpinolene, have not been detected previously in other types of smoked cheese. Lastly, the results obtained suggest a slightly higher smoking degree in the cheeses smoked at a greater height.

Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation

We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.