Papel de los esfingolipidos en la senalizacion celular

Este trabajo ha recibido financiación del Ministerio de Educación\ud y Ciencia (SAF-2005-00602

Multiview mm-Wave Imaging With Augmented Depth Camera Information

This work was supported in part by Ayudas Fundacion BBVA a Investigadores y Creadores Culturales 2016, in part by the Ministerio de Ciencia e Innovacion of Spain /FEDER under Project TEC2014-55290-JIN and Project TEC2014-54005-P, and in part by the Gobierno del Principado de Asturias (PCTI)/FEDER-FSE under Project GRUPIN14-114

Synthesis of phased arrays in complex environments with the multilevel characteristic basis function method

The aim of this paper is to present a method to carry out the synthesis of large phased arrays when they are affected by complex environments which can influence the radiation pattern. The synthesis is performed with the help of the Multilevel Characteristic Basis Function Method to calculate a matrix relating input voltages and the far field pattern samples. The method is illustrated with the synthesis of a Secondary Surveillance Radar antenna on a turret containing multiple obstacle

Misuse of derivatives : considerations for internal control

Derivatives are nowadays widely used globally both for speculative and hedging purposes. However, as experience shows, inadequate use of derivatives may cause severe problems and even bankruptcy of firms. Thus, it is essential to help organizations design a robust proactive governance and internal control structure, which will help to prevent new financial debacles and scandals when using derivatives. Taking into account the frequent use and the growing fraud caused by derivatives, the aim of the paper is to identify considerations for internal control important to ensure better governance of firms using derivatives. The main findings are based on an analysis of interviews that were conducted with experts directly or indirectly involved with derivatives from different European countries. The interviews were semistructured following the approach proposed by Patton (1990). An analysis of the data collected from the interviews was carried out using a thematic approach. The paper identifies and analyzes the main “sources” of derivatives misuse, including poor design and mis-categorization of instruments, convenience to blame derivatives, unsophisticated players, insufficient regulatory environment, poorly designed internal controls, inadequate communication, poor firm culture, etc. It also provides an extensive analysis of the main recommendation for internal control concerning awareness of derivatives design, the human aspects, regulations, communication, knowledge, and training. Sound internal controls could avoid new debacles without adding other restrictions to the market. Moreover, it provides recommendations for internal control important to ensure better governance of firms using derivatives.peer-reviewe

Phaseless characterization of Broadband Antennas

A new efficient method for broadband antenna characterization from phaseless acquisitions in the frequency-domain (FD) is presented. The phase-retrieval technique is based on an extrapolation of the off-axis indirect holography. In common with the conventional approach, the power of the interferometric field of the antenna under test (AUT) and a reference antenna, whose field is known in advance, as well as the power of the AUT alone, is measured at the desired frequencies. Nevertheless, the phase retrieval is accomplished independently at each spatial point by filtering in the time-domain (TD) rather than in the k-space. Thus, the dependency of the phase retrieval on the position accuracy is reduced and it can be accomplished simultaneously at all frequencies without resorting to iterative schemes. Moreover, it yields a less dense sampling and a phase-retrieval algorithm not dependent on the geometry of the acquisition. The method is illustrated with a numerical example in the W-band as well as with two near-field (NF) measurement examples in the Ka- and W-band

Detección de objetos mediante un radar compacto en banda de milimétricas

XXXII Simposium Nacional de la Unión Científica Internacional de Radio, 6 a 8 de septiembre de 2017, Cartagena (España)El artículo testeará las características de un radar compacto de nueva generación que trabaja en la banda milimétrica y su capacidad para identificar blancos. Se comentarán los fundamentos de un radar FMCW usando formulas matemáticas y un diagrama de bloques. Se explicará el procesado de las medidas cuyo objetivo es identificar blancos utilizando una técnica de imagen. Se presentará el set-up de medida. Por último, se mostrará la gran calidad de imagen y la precisión en la identificación de los blancos que se consigue al utilizar este radar y el procesado comentado en este artículoEste trabajo ha sido financiado por el Ministerio de Ciencia e Innovación de España/FEDER bajo los proyectos PortEMVision (TEC2014-55290-JIN) and MIRIIEM (TEC2014-54005-P); por el Gobierno del Principado de Asturias a través del proyecto PCTI 2013-2017 GRUPIN14-114; y por las Ayudas Fundación BBVA a Investigadores Creadores Culturales 201

Targeting AMP-activated kinase impacts hepatocellular cancer stem cells induced by long-term treatment with sorafenib

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. HCC treatment is hindered by the frequent emergence of chemoresistance to the multikinase inhibitor sorafenib, which has been related to the presence of cancer stem cells (CSCs) that self‐renew and often escape therapy. The key metabolic sensor AMP‐activated kinase (AMPK) has recently been recognized as a tumour growth regulator. In this study, we aimed to elucidate the role of AMPK in the development of a stem cell phenotype in HCC cells. To this end, we enriched the CSC population in HCC cell lines that showed increased expression of drug resistance (ALDH1A1, ABCB1A) and stem cell (CD133, Nanog, Oct4, alpha fetoprotein) markers and demonstrated their stemness phenotype. These cells were refractory to sorafenib‐induced cell death. We report that sorafenib‐resistant cells had lower levels of total and phosphorylated AMPK as well as its downstream substrate, ACC, compared with the parental cells. Interestingly, AMPK knockdown with siRNA or inhibition with dorsomorphin increased the expression of stem cell markers in parental cells and blocked sorafenib‐induced cell death. Conversely, the upregulation of AMPK, either by transfection or by pharmacological activation with A‐769662, decreased the expression of ALDH1A1, ABCB1A, CD133, Nanog, Oct4, and alpha fetoprotein, and restored sensitivity to sorafenib. Analysis of the underlying mechanism points to hypoxia‐inducible factor HIF‐1α as a regulator of stemness. In vivo studies in a xenograft mouse model demonstrated that stem‐like cells have greater tumourigenic capacity. AMPK activation reduced xenograft tumour growth and decreased the expression of stem cell markers. Taken together, these results indicate that AMPK may serve as a novel target to overcome chemoresistance in HCC

Direct evidence for microdomain-specific localization and remodeling of functional L-type calcium channels in rat and human atrial myocytes

Background—Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). Methods and Results—Isolated rat and human AMs were characterized by scanning ion conductance, confocal, and electron microscopy. Half of AMs possessed T-tubules and structured topography, proportional to cell width. A bigger proportion of myocytes in the left atrium had organized T-tubules and topography than in the right atrium. Super-resolution scanning patch clamp showed that LTCCs distribute equally in T-tubules and crest areas of the sarcolemma, whereas, in ventricular myocytes, LTCCs primarily cluster in T-tubules. Rat, but not human, T-tubule LTCCs had open probability similar to crest LTCCs, but exhibited ≈40% greater current. Optical mapping of Ca2+ transients revealed that rat AMs presented ≈3-fold as many spontaneous Ca2+ release events as ventricular myocytes. Occurrence of crest LTCCs and spontaneous Ca2+ transients were eliminated by either a caveolae-targeted LTCC antagonist or disrupting caveolae with methyl-β-cyclodextrin, with an associated ≈30% whole-cell ICa,L reduction. Heart failure (16 weeks post–myocardial infarction) in rats resulted in a T-tubule degradation (by ≈40%) and significant elevation of spontaneous Ca2+ release events. Although heart failure did not affect LTCC occurrence, it led to ≈25% decrease in T-tubule LTCC amplitude. Conclusions—We provide the first direct evidence for the existence of 2 distinct subpopulations of functional LTCCs in rat and human AMs, with their biophysical properties modulated in heart failure in a microdomain-specific manner

The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells

BACKGROUND: Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer. The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells.METHODS: NE differentiation of prostate cancer LNCaP cells was induced by serum deprivation or by incubation with interleukin-6, for 6 days. Levels of NE markers and signaling proteins were determined by western blotting. Levels of cannabinoid receptors were determined by quantitative PCR. The involvement of signaling cascades was investigated by pharmacological inhibition and small interfering RNA.RESULTS: The differentiated LNCaP cells exhibited neurite outgrowth, and increased the expression of the typical NE markers neuron-specific enolase and βIII tubulin (βIII Tub). Treatment with 3 μM WIN inhibited NK differentiation of LNCaP cells. The cannabinoid WIN downregulated the PI3K/Akt/mTOR signaling pathway, resulting in NE differentiation inhibition. In addition, an activation of AMP-activated protein kinase (AMPK) was observed in WIN-treated cells, which correlated with a decrease in the NE markers expression. Our results also show that during NE differentiation the expression of cannabinoid receptors CB1 and CB2 dramatically decreases.CONCLUSIONS: Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.Prostate Cancer and Prostatic Diseases advance online publication, 21 June 2016; doi:10.1038/pcan.2016.19.</p