Prostaglandins induce early growth response 1 transcription factor mediated microsomal prostaglandin E2 synthase up-regulation for colorectal cancer progression

Cyclooxygenase2 (COX2) has been associated with cell growth, invasiveness, tumor progression and metastasis of colorectal carcinomas. However, the downstream prostaglandin (PG)-PG receptor pathway involved in these effects is poorly characterized. We studied the PG-pathway in gene expression databases and we found that PTGS2 (prostaglandin G/H synthase and cyclooxygenase) and PTGES (prostaglandin E synthase) are co-expressed in human colorectal tumors. Moreover, we detected that COX2 and microsomal Prostaglandin E synthase 1 (mPGES1) proteins are both up-regulated in colorectal human tumor biopsies. Using colon carcinoma cell cultures we found that COX2 overexpression significantly increased mPGES1 mRNA and protein. This up-regulation was due to an increase in early growth response 1 (EGR1) levels and its transcriptional activity. EGR1 was induced by COX2-generated PGF. A PGF receptor antagonist, or EGR1 silencing, inhibited the mPGES1 induction by COX2 overexpression. Moreover, using immunodeficient mice, we also demonstrated that both COX2- and mPGES1- overexpressing carcinoma cells were more efficient forming tumors. Our results describe for the first time the molecular pathway correlating PTGS2 and PTGES in colon cancer progression. We demonstrated that in this pathway mPGES1 is induced by COX2 overexpression, via autocrine PGs release, likely PGF, through an EGR1-dependent mechanism. This signaling provides a molecular explanation to PTGS2 and PTGES association and contribute to colon cancer advance, pointing out novel potential therapeutic targets in this oncological context.Ministerio de Ciencia e Innovación (SAF2010– 18733, SAF2013–42850-R), Comunidad de Madrid S2010/ BMD-2332, RED RICET RD12/0018/004, PIE13/00041 and an institutional grant from Fundación Ramon Areces to MF. FIS PS12/00094 to MLGBPeer Reviewe

Classification and localization of electromagnetic and ultrasonic pulsed emitters

Mención Internacional en el título de doctorThe localization of radiative sources is very important in many fields of work such as: sonar, radar and underwater radar, indoor localization in wireless networks, earthquake epicenter localization, defective assets localization in electrical facilities and so forth. In the process of locating radiative sources exist many issues which can provoke errors in the localization. The signals acquired may belong to different sources or they can be mixed with environmental noise, then, their separation before using localization algorithms is of great interest to be efficient and accurate in the computational process. Furthermore, the geometry and radiation characteristics of the receivers, the nature of the signal or their measuring process may cause deviations in the signal onset calculus and therefore the source localization could be displaced from the actual position. In this thesis, there are three kinds of algorithms to undertake three steps in the emitter localization: signal separation, onset and time delay estimation of the signals and source localization. For each step, in order to reduce the error in the localization, several algorithms are analyzed and compared in each application, to choose the most reliable. As the first step, to separate different kinds of signals is of interest to facilitate further processing. In this thesis, different optimization techniques are presented over the power ratio (PR) maps method. The PR uses a selective spectral signal characterization to extract the features of the analyzed signals. The technique identifies automatically the most representative frequency bands which report a great separation of the different kinds of signals in the PR map. After separating and selecting the signals, it is of interest to compare the algorithms to calculate the onset and time delay of the pulsed signals to know their performance because the time variables are inputs to the most common triangulation algorithms to locate radiative and ultrasonic sources. An overview of the algorithms used to estimate the time of flight (ToF) and time differences of arrival (TDoA) of pulsed signals is done in this thesis. In the comparison, there is also a new algorithm based on statics of high order, which is proposed in this thesis. The survey of their performance is done applied to muscle deep estimation, localization in one dimension (1D), and for the localization of emitters in three dimensions (3D). The results show how the presented algorithm yields great results. As the last step in the radiative source localization, the formulation and principle of work of both iterative and non-iterative triangulation algorithms are presented. A new algorithm is presented as a combination of two already existing improving their performance when working alone. All the algorithms, the proposed and the previous which already exist, are compared in terms of accuracy and computational time. The proposed algorithm reports good results in terms of accuracy and it is one of the fastest in computational time. Once the localization is achieved, it is of great interest to understand how the errors in the determination of the onset of the signals are propagated in the emitter localization. The triangulation algorithms estimate the radiative source position using time variables as inputs: ToF, TDoA or pseudo time of flight (pToF) and the receiver positions. The propagation of the errors in the time variables to the radiative source localization is done in two dimensions (2D) and 3D. New spherical diagrams have been created to represent the directions where the localization is more or less sensible to the errors. This study and their sphere diagrams are presented for several antenna layouts. Finally, how the errors in the positioning of the receivers are propagated to the emitter localization is analyzed. In this study, the effect in the propagation of both the relative distance from the receivers to the emitter and the direction between them has been characterized. The propagation of the error considering the direction is also represented in spherical diagrams. For a preferred direction identified in the spheres, the propagated error in the source localization has been quantified regarding both the source distance and the magnitude of the errors in the receivers positioning.Programa Oficial de Doctorado en Ingeniería Eléctrica, Electrónica y AutomáticaPresidente: Andrea Cavallini.- Secretario: José Antonio García Souto.- Vocal: Iliana Portugués Peter

Influence of the stop/start system on CO2 emissions of a diesel vehicle in urban traffic

This paper presents measurements of CO2 emission and efficiency of stop/start technology on a diesel vehicle in urban traffic. Two four-wheel-drive diesel vehicles with on-board exhaust emission and vehicle activity measurement systems were tested in two urban driving circuits representative of downtown Madrid. The vehicles had similar turbocharged and intercooled diesel engines fulfilling the same Euro 4 emissions regulation; but one had an improved engine incorporating stop/start technology. CO2 emission reduction of more than 20% for the car equipped with the stop/start system was obtained. Regardless of the variability in driving style, the grade and type of streets, traffic congestion, and the engine operating temperature, the car equipped with the stop/start system has intrinsically a lower CO2 emission factor

Involvement of PGE2 and cyclic AMP signaling pathway in the up-regulation of COX-2and mPGES-1 expression in LPS -activated macrophages

The final version of record is available at /http://www.biochemj.org/bj

Opto‑mechanically generated resonant feld enhancement

A link between the resonant cumulative field enhancement experienced by a chain of plasmonic nanoparticles in a light field and the orientation of the chain with respect to the field is obtained. We calculate analytically the optical torque and the equilibrium configuration and we show how stable orientations are triggered by the geometric resonance conditions. Analytical predictions are checked using numerical calculations based on the coupled dipoles method (CDA) for the particular case of a chain of silver nanoparticles. The reported resonance driven optical torque allows for a tuning of the orientation of the chain depending on radiation’s wavelengt

Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy.</p> <p>Results</p> <p>In this study, we tested the ability of a <it>Leishmania infantum </it>deletion mutant, lacking both <it>HSP70-II </it>alleles (ΔHSP70-II), to provide protection against <it>Leishmania </it>infection in the <it>L. major</it>-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-<it>Leishmania </it>IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (<it>Mesocricetus auratus</it>), infected with mutant parasites did not develop any sign of pathology.</p> <p>Conclusions</p> <p>The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis.</p

Separation of radio-frequency sources and localization of partial discharges in noisy environments

The detection of partial discharges (PD) can help in early-warning detection systems to protect critical assets in power systems. The radio-frequency emission of these events can be measured with antennas even when the equipment is in service which reduces dramatically the maintenance costs and favours the implementation of condition-based monitoring systems. The drawback of these type of measurements is the difficulty of having a reference signal to study the events in a classical phase-resolved partial discharge pattern (PRPD). Therefore, in open-air substations and overhead lines where interferences from radio and TV broadcasting and mobile communications are important sources of noise and other pulsed interferences from rectifiers or inverters can be present, it is difficult to identify whether there is partial discharges activity or not. This paper proposes a robust method to separate the events captured with the antennas, identify which of them are partial discharges and localize the piece of equipment that is having problems. The separation is done with power ratio (PR) maps based on the spectral characteristics of the signal and the identification of the type of event is done localizing the source with an array of four antennas. Several classical methods to calculate the time differences of arrival (TDOA) of the emission to the antennas have been tested, and the localization is done using particle swarm optimization (PSO) to minimize a distance function.Tests were done in the High-Voltage Research and Test Laboratory (LINEALT) at Universidad Carlos III de Madrid

A Trypanosoma cruzi monoclonal antibody that recognizes a superficial tubulin-like antigen

A monoclonal antibody (MAB 10), obtained from mice infected with Trypanosoma cruzi, was found to recognize a superficial antigen in living or fixed parasites. It reacted more strongly with T. cruzi than with related parasites such as T. brucei and Leishmania. In immunoblots it recognized a single trypanosoma polypeptide and also brain tubulin, both of which had the same electrophoretic mobility. Further analysis suggested that the α-tubulin subunit contained the epitope recognized by MAB 10. These results suggest that a surface tubulin-like protein is present in T. cruzi.Peer Reviewe

Planar Localization of Radio-Frequency or Acoustic Sources with Two Receivers

Proceeding of: 4th International Electronic Conference on Sensors and Applications (ECSA-4)Spatial localization of emitting sources is especially interesting in different fields of application. The focus of an earthquake, the determination of cracks in solid structures or the position of bones inside a body are some examples of the use of multilateration techniques applied to acoustic and vibratory signals. Radar, GPS and wireless sensors networks location are based on radiofrequency emissions and the techniques are the same as in the case of acoustic emissions. This paper is focused on the determination of the position of sources of partial discharges inside electrical insulation for maintenance based on the condition of the electrical machine. The use of this phenomenon is a mere example of the capabilities of the proposed method because its emission can be electromagnetic in the UHF range or acoustic when the insulation is immersed in oil. Generally, when a pulse is radiated from a source, the wave will arrive to two receivers at different times. One of the advantages of measuring these time differences of arrival or TDOA is that it is not required a common clock as in other localization techniques based on the time of arrival (TOA) of the pulse to the receiver. With only two sensors, all the possible points in the plane that would give the same TDOA describe a hyperbola. Using an independent third receiver and calculating the intersection of the three hyperbolas will give the position of the source. Therefore, planar localization of emitters using multilateration techniques can be solved at least with three receivers. This paper presents a method to locate sources in a plane with only two receivers, one of them in a fixed position and the other is placed describing a circumference around the first one. The TDOA are measured at different angles completing a total turn and obtaining a function, angle versus TDOA, that has all the geometric information needed to locate the source.The work done in this paper has been funded by the Spanish Government under contract DPI2015-66478-C2-1-R (MINECO/FEDER, UE

Radio-Frequency Localization of Multiple Partial Discharges Sources with Two Receivers

Spatial localization of emitting sources is especially interesting in different fields of application. The focus of an earthquake, the determination of cracks in solid structures, or the position of bones inside a body are some examples of the use of multilateration techniques applied to acoustic and vibratory signals. Radar, GPS and wireless sensors networks location are based on radiofrequency emissions and the techniques are the same as in the case of acoustic emissions. This paper is focused on the determination of the position of sources of partial discharges in electrical insulation for maintenance based on the condition of the electrical equipment. The use of this phenomenon is a mere example of the capabilities of the proposed method but it is very representative because the emission can be electromagnetic in the VHF and UHF ranges or acoustic. This paper presents a method to locate more than one source in space with only two receivers, one of them in a fixed position and the other describing a circumference around the first one. The signals arriving from the different sources to the antennas are first separated using a classification technique based on their spectral components. Then, the individualized time differences of arrival (TDOA) from the sources collected at different angles describe a function, angle versus TDOA, that has all the geometric information needed to locate the source. The paper will show how to derive these functions for any source analytically with the position of the source as unknown parameters. Then, it will be demonstrated that it is possible to fit the curve with experimental measurements of the TDOA to obtain the parameters of the position of each source. Finally, the technique is extended to the localization of the emitter in three dimensions.The work done in this paper has been funded by the Spanish Government (MINECO) and the European Regional Development Fund (ERDF) under contract DPI2015-66478-C2-1-R (MINECO/FEDER, UE)