Development of a critical structure state alarm system based on the instrumentation of the Botafoc breakwater nº 8 caisson

Balearic Port Authority has developed an instrumentation system for the #8 caisson of the Botafoc breakwater that integrates 12 pressure sensors located at three surfaces, two in contact with the sea water and another with the bottom. This design was completed with an inertial system that measures the angular velocities and the accelerations over the three Cartesian axes. Consequently, the system measures actions (pressures) and reactions (movements and accelerations) experimented by the caisson, due to sea waves and/or other service loads. R+D department of the Port Authority and Polytechnic University of Madrid are working on two directions, the development of new theories on vertical breakwater design that go beyond Goda and Sainflou, and on the creation of a real-time critical structure alarm system, based on the instrumentation installed. This alarm system has two main parts: the instrumentation itself that collects data and processes it on real-time (the data processing compares the pressure law suffered by the caisson in every step process with the design critical state of the caisson, in this case the Goda pressure law for a 6.5 m wave), giving a security coefficient that points out the risk level on real-time; and the alarm system consisting of a monitoring panel located in the Port Control Center that shows the risk level and advises in case of an incidental evacuation of this critical portuary installation

Role of voltage-gated proton channel (Hv1) in cancer biology

The acid-base characteristics of tumor cells and the other elements that compose the tumor microenvironment have been topics of scientific interest in oncological research. There is much evidence confirming that pH conditions are maintained by changes in the patterns of expression of certain proton transporters. In the past decade, the voltage-gated proton channel (Hv1) has been added to this list and is increasingly being recognized as a target with onco-therapeutic potential. The Hv1 channel is key to proton extrusion for maintaining a balanced cytosolic pH. This protein-channel is expressed in a myriad of tissues and cell lineages whose functions vary from producing bioluminescence in dinoflagellates to alkalizing spermatozoa cytoplasm for reproduction, and regulating the respiratory burst for immune system response. It is no wonder that in acidic environments such as the tumor microenvironment, an exacerbated expression and function of this channel has been reported. Indeed, multiple studies have revealed a strong relationship between pH balance, cancer development, and the overexpression of the Hv1 channel, being proposed as a marker for malignancy in cancer. In this review, we present data that supports the idea that the Hv1 channel plays a significant role in cancer by maintaining pH conditions that favor the development of malignancy features in solid tumor models. With the antecedents presented in this bibliographic report, we want to strengthen the idea that the Hv1 proton channel is an excellent therapeutic strategy to counter the development of solid tumors

MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML

Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia

Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL). Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL samples at diagnosis (n = 48). We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly, the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect activation of TP53 pathway with 5-aza-29-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of the patients, which significantly correlated with a higher relapse (p = 0.001) and mortality (p,0.001) rate being an independent prognostic factor for disease-free survival (DFS) (p = 0.006) and overall survival (OS) (p = 0.005) in the multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL

Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia

The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor gene Wnt5a, belonging to the non-canonical Wnt signaling pathway, was investigated in a large series of 75 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia by methylationspecific polymerase chain reaction. At least one methylated gene was observed in cells from 66% (49/75) of patients (methylated group). Disease-free survival and overall survival at 9 years were 51 and 40%, respectively, for the unmethylated group and 3 and 2%, respectively, for the methylated group (both P < 0.0001). Multivariate analysis demonstrated that the Wnt methylation profile was an independent prognostic factor predicting disease-free survival (P = 0.007) and overall survival (P = 0.039). Abnormal DNA methylation of promoter-associated CpG islands in the Wnt signaling pathway is very common in Philadelphia chromosome-positive acute lymphoblastic leukemia and potentially defines subgroups with distinct clinical characteristics

Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia

Cancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy. Although CTA genes are expressed in some normal tissues, such as the testis, this immunologically protected site lacks MHC I expression and as such, does not present self antigens to T cells. To date, CTA genes have been shown to be expressed in a range of solid tumors via demethylation of their promoter CpG islands, but rarely in chronic myeloid leukemia (CML) or other hematologic malignancies

Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth

MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34+ cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML

Campañas altimétricas de calibración del Topex y Jason-1 en el Mediterráneo Occidental

Se describen las campañas de calibracion altimétrica realizadas en el Mediterráneo Occidental por la Universidad Politécnica de Cataluña con el soporte del Instituto Cartográfico de Cataluña, el Real Instituto y Observatorio de la Armada y por Puertos del Estado principalmente. Se realizaron tres experiencias en el Cabo de Begur para calibracion altimétrica y mapeo del geoide marino realizadas en 1999, 2000 y 2002. Calibración absoluta directa estimando el bias del Alt‐B del Topex fue realizada durante el overflight del satelite usando boyas GPS. Una contribución española a las experiencias de calibración ha sido el diseño de las Boyas y Catamarán GPS teniendo en cuenta diseños previos de la Universidad de Boulder en Colorado y las de Senetosa/Capraia. Una campaña mas fue realizada en Junio de 2003 en el area de la Isla de Ibiza. Se utilizaron cinco estaciones GPS de referencia localizadas en Ibiza, San Antonio y Portinax, y por dos mareógrafos georeferenciados situados en los puertos de Ibiza y San Antonio. Una calibración directa adicional fue realizada el 14 de Junio. Otro objetivo importante era obtener el perfil de la Superficie Media Marina a lo largo de las trazas del T/P o Jason‐1 con boyas/catamarán GPS. Mapear la superficie marina para la calibración altimetrica indirecta tiene la ventaja de permitir la calibración de cualquier radar que cruce el area estudiada pero, en cambio, la desventaja es reduce la precision de la estimación del bias. Se tiene prevista una nueva campaña a realizar en la misma zona aproximadamente siguiendo las trazas de los atélites Jason‐2 y Altika con lanzamiento previsto en 2011 que permitirá obtener datos altimétricos en zonas róximas a la costa. Three Begur Cape experiences on radar altimeter calibration and marine geoid mapping made on 1999, 2000 and 2002 are overviewed. One campaign has also been made in June 2003 at the Ibiza island area. Direct absolute calibration estimating the Topex Alt‐B bias was performed during the satellite overflight by using GPS buoys. The advantage of that method is that neither geoid modelling nor tidal error is needed. Other main objective was to map the profile of the Mean Sea Surface (mss) along the closest T/P and Jason‐1 groundtrack. Mapping the marine surface for indirect altimeter calibration has de advantage of allowing the calibration of any radar sensor that crosses the studedarea but, in turn, the disadvantage is that the method requires ocean tide and geoid knowledge, which reduces the accuracy of the bias estimate by a factor of 2. A technical Spanish contribution to the calibration experience has been the design of GPS buoys and GPS catamaran taking in account the University of Colorado at Boulder and Senetosa/Capraia. For the mapping of the extended calibration areas centered on satellite ground tracks, the catamaran was tracked by the Patrol Deva, from the Spanish Navy. An additional absolute altimeter direct calibration was performed on June 14. Complementary data came from five GPS reference stations deployed at Ibiza , San Antonio and Portinatx, and from vertically‐referenced tide gauges located at Ibiza and San Antonio. We present first results on Jason‐1 altimeter calibration using the marine geoid derived from data collected during the campaign. Moreover, the geodetic activities (e.g., GPS, leveling) has permitted to build a very accurate (few mm) local network linked to the european one,s (ITRF2000).Postprint (published version

An enduring rapidly moving storm as a guide to Saturn's Equatorial jet's complex structure

This work is licensed under a Creative Commons Attribution 4.0Saturn has an intense and broad eastward equatorial jet with a complex three-dimensional structure mixed with time variability. The equatorial region experiences strong seasonal insolation variations enhanced by ring shadowing, and three of the six known giant planetary-scale storms have developed in it. These factors make Saturn’s equator a natural laboratory to test models of jets in giant planets. Here we report on a bright equatorial atmospheric feature imaged in 2015 that moved steadily at a high speed of 450 ms-1 not measured since 1980–1981 with other equatorial clouds moving within an ample range of velocities. Radiative transfer models show that these motions occur at three altitude levels within the upper haze and clouds. We find that the peak of the jet (latitudes 10ºN to 10º S) suffers intense vertical shears reaching þ2.5 ms-1 km-1, two orders of magnitude higher than meridional shears, and temporal variability above 1 bar altitude level.Peer ReviewedPostprint (published version