Dynamics of Brokerage Positions in Clusters: Evidence from the Spanish Foodstuffs Industry

[EN] Shifting away from traditional approaches orientated towards the analysis of the benefits associated with brokerage, this paper provides valuable insights into the dynamics of this network position and the opportunities to innovate that it provides. Using fine grain micro data collected in a foodstuff Spanish cluster, the evolution of different brokerage profiles is analyzed in depth. It was particularly evident how firm-level characteristics (status, former mediating experience and external openness) and their interactions may generate changes in the different brokerage roles over a period of time. The findings of this work partially validate expectations based on the network dynamics approaches. Status and previous mediating experience facilitate the creation of partnerships, fostering brokerage. Conversely, interaction effects demote brokerage activity at the intra-cluster level, suggesting the selective nature of brokers¿ relational behavior.Financial support from the Spanish Ministry of Economy and Competitiveness (ECO2015-67122-R) is gratefully acknowledged.Belso-Martínez, JA.; Expósito-Langa, M.; Mas-Verdú, F.; Molina-Morales, F. (2017). Dynamics of Brokerage Positions in Clusters: Evidence from the Spanish Foodstuffs Industry. Sustainability. 9(2):1-18. https://doi.org/10.3390/su9020290S1189

VE-Cadherin modulates ß-catenin/TCF-4 to enhance Vasculogenic Mimicry

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that ß-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VEcadherin upon FAK disabling resulted in VE-Cadherin/ß-catenin complex dissociation, increased ß-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses ß-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of ß-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of ß-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness SAF2015-70520-R, the Spanish Ministry of Science and Technology RTI2018-098968-B-I00, CIBERONC ISCIII CB16/12/00421 and Junta de Andalucía, a project of Excellence from Junta de Andalucía P10-CTS-0662, P12-CTS-383 to FJO. Fundación Domingo Martínez to FJO. Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (PAIDI 2020, POSTDOC_21_00865) to DD-B. Fundación Getthi ONC18PE01/2022 to DAE, AT

Cambio climático, aridez y sequías en Canarias

Ponencia presentada en: XII Congreso de la Asociación Española de Climatología celebrado en Santiago de Compostela entre el 19 y el 21 de octubre de 2022.[ES]El cambio climático supone un factor de gran incertidumbre en cuanto a la posible evolución de los niveles de aridez y de sequía. Por una parte, se prevé un aumento de la evapotranspiración y por otra, el comportamiento de la precipitación presenta importantes diferencias regionales. En este trabajo se han analizado las proyecciones de la aridez y de las futuras sequías en las Islas Canarias, en términos de frecuencia, duración y severidad, utilizando el modelo Weather Research and Forecasting (WRF) para el periodo 2070-2099, y para los escenarios Representative Concentration Pathways (RCPs) 4.5 y 8.5. Las condiciones iniciales y de contorno se definieron mediante tres modelos incluidos en el Coupled Model Intercomparison Project 5 (CMIP5): GFDL-ESM2M, MIROC-ESM e IPSL-CM5. Los cambios futuros de la aridez se obtuvieron empleando el cambio en el índice de aridez (ACI), basado en la relación entre el cambio fraccional de la evaporación potencial y de la precipitación respecto al periodo de referencia 1981-2009. En el caso de la sequía, se utilizó el índice estandarizado de precipitación (SPI) para las escalas de tiempo de 3 y 12 meses. Asimismo, se consideraron eventos de sequía extrema (eventos extremos húmedos) cuando el SPI toma valores por debajo (por encima) de -2 (2). A partir de los resultados obtenidos, podemos destacar que la aridez y los eventos de sequía extrema aumentarán a finales de siglo respecto al periodo de referencia, para ambos escenarios.[EN]Climate change is a great relevance factor in the evolution of aridity and droughts due to increase of evapotranspiration and the behavior of precipitation. In this work, we analyses climate change projections in terms of frequency, duration, and severity of future aridity and drought in the Canary Island with the Weather Research and Forecasting (WRF) model driven by some Coupled Models Intercomparison Project phase 5 (CMIP5) simulations, for the period 2070-2099 and for two Representative Concentration Pathways (RCP) scenarios (RCP4.5 and RCP8.5). Initial and boundary conditions were defined using three models of the Coupled Model Intercomparison Project 5 (CMIP5): GFDL-ESM2M, MIROC-ESM and IPSL-CM5. Aridity change index was obtained to assessment future changes of aridity, which is based on the fractional change of potential evapotranspiration and precipitation with respect to the reference period (1981-2009). To evaluate droughts, the Standardized Precipitation Index (SPI) was applied at the 3 and 12-month time scales. In addition, extreme drought (wet) events are considered when SPI is lower (higher) than -2 (2). The results show an increase of extreme aridity and drought events by the end of this century with respect to the reference period for both emission scenarios.Este estudio se ha realizado en el marco del proyecto VidDATA (RTC2019-006948-7), cofinanciado por el Programa Estatal de I+D+i Orientada a los Retos de la Sociedad del Ministerio de Ciencia e Innovación, España. Agradecemos el apoyo del Proyecto PLANCLIMAC (MAC / 3.5b / 244), el cual está financiado por el Programa INTERREG MAC 2014-2020 de la Unión Europea, cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER-FEDER)

Aerosol concentration at two heights (2550 and 650 m a.s.l.) in SE Spain

Ponencia presentada en: XXXV Jornadas Científicas de la AME y el XIX Encuentro Hispano Luso de Meteorología celebrado en León, del 5 al 7 de marzo de 2018.The simultaneous aerosol sampling at two heights in southern Spain may provide valuable information on the vertical structure of the dust transport from North Africa to the Iberian Peninsula. It also allows the characterization of the ambient air at two sites with distinct anthropogenic impact. This work presents the results obtained from the first field campaign of the FRESA project (Impact of dust-laden African air masses and of stratospheric air masses in the Iberian Peninsula. Role of the Atlas Mountains), performed in the period July-November 2017 at El Albergue Universitario in Sierra Nevada (2550 m a.s.l.) and the city of Granada (650 m a.s.l.). The two sites were instrumented with a low-volume sampler with PM10 inlet for daily sampling and mass and chemical composition characterization, a high-volume sampler for total suspended particles (TSP) for weekly sampling and radionuclide activity determination, and with a GRIMM 365 optical particle counter that provides continuously the aerosol size distribution

Ultrasonography in rheumatology: time to learn from patient views

Objective: The objective of this observational, descriptive, cross-sectional, multicentre study was to assess the perceived quality and grade of satisfaction expressed by patients with chronic arthropathies regarding the use of musculoskeletal (MSK) ultrasonography by rheumatologists as an integrated clinical care tool. Methods: All Spanish rheumatology departments with MSK ultrasonography incorporated in their healthcare services were invited to participate in the study. A Spanish-language survey was offered to fill out anonymously to all consecutive patients with chronic arthropathies under follow-up in the rheumatology outpatient clinics who attended their centre for a period of 3 months. The survey consisted of three sections. The first section contained patients’ demographics, disease data, frequency of performing rheumatological ultrasound and information about who performed their ultrasound assessments. The second section consisted of 14 questions about patient’s experience and opinion on different aspects of the management, performance and perceived usefulness of performing ultrasound, to be answered on a Likert scale 1–5. The third section of the survey was addressed to the rheumatologist ultrasonographers. Results: Nine hundred and four patients from 16 university hospital rheumatology departments completed the survey. All questions reached an overall favourable response ≥ 80%. Patients who reported usual ultrasound examinations in their rheumatology care and those in which it was their attending rheumatologist who performed the ultrasound assessments responded more favourably. Conclusion: Our encouraging patient-centred results may be useful in facilitating the implementation of rheumatological ultrasound in rheumatology care worldwide. Key Points • This is the largest multicentre survey carried out in patients with chronic joint diseases designed to assess their experience and perceived benefits with the use of ultrasonography performed by rheumatologists in daily practice. • Musculoskeletal ultrasound incorporated into rheumatology care was very well accepted and valued by most patients. • The patients perceived that ultrasonography helps not only their rheumatologist but also themselves to better understand their condition. • The patients believed that ultrasonography helps them accept and comply with the proposed treatmen

Aerosol radiative forcing efficiency in the UV region over southeastern Mediterranean: VELETA2002 campaign

Atmospheric aerosol effects on spectral global UV irradiance were evaluated during the VELETA2002 field campaign between 8 and 19 July 2002 in southeast Spain. In the first stage, seven UV spectroradiometer and six CIMEL Sun photometer measurements were carried out simultaneously, allowing them to be calibrated and intercompared. The mean ratio obtained for the global irradiance between the spectroradiometers, with regards to a reference instrument, ranges from 0.98 up to 1.04 with standard deviations that oscillate between ±0.01 and ±0.17. In particular, the two spectroradiometers used to obtain the aerosol forcing efficiencies have a ratio of 1.000 ± 0.001. The aerosol optical depth (AOD) obtained with the CIMEL Sun photometers has a standard deviation of lower than ±0.01 for all the channels. Under clear sky conditions, the diurnal aerosol forcing efficiency (DDFe) and fractional diurnal forcing efficiency (DFDFe) was calculated for two Mediterranean stations: Armilla (691 m.a.s.l.) within the boundary layer and Sabinas (2200 m.a.s.l) on the lower limit of the free troposphere and 25 km away from the first station. The DDFe values obtained at Armilla range between _2.72 ± 0.45 W m_2/t380 and _2.88 ± 0.45 W m_2/t440 and between _3.22 ± 0.61 W m_2/t380 and _3.40 ± 0.62 W m_2/t440 at Sabinas station; the DFDFe values range from _8.0 ± 1.4%/t380 to _8.6 ± 1.3%/t440 and _12.0 ± 2.3%/t380 to _12.6 ± 2.3%/t440 at the two stations, respectively. Also, an experimental aerosol transmittance factor, CT, used to obtain UV satellite derived products was found as a result of the dependence of the global irradiance with the AOD, under cloudless conditions. The average aerosol attenuation factor, h, obtained from the CT, is 6 ± 2% under weakly absorbing aerosols, with a negligible spectral dependence.This work was supported by CICYT–MCYT through the coordinated projects CGL2004-05984-C07-05 and CGL2005-03428-C04-02

Peripheral organ equivalent dose estimation procedure in proton therapy

The aim of this work is to present a reproducible methodology for the evaluation of total equivalent doses in organs during proton therapy facilities. The methodology is based on measuring the dose equivalent in representative locations inside an anthropomorphic phantom where photon and neutron dosimeters were inserted. The Monte Carlo simulation was needed for obtaining neutron energy distribution inside the phantom. The methodology was implemented for a head irradiation case in the passive proton beam of iThemba Labs (South Africa). Thermoluminescent dosimeter (TLD)-600 and TLD-700 pairs were used as dosimeters inside the phantom and GEANT code for simulations. In addition, Bonner sphere spectrometry was performed inside the treatment room to obtain the neutron spectra, some relevant neutron dosimetric quantities per treatment Gy, and a percentual distribution of neutron fluence and ambient dose equivalent in four energy groups, at two locations. The neutron spectrum at one of those locations was also simulated so that a reasonable agreement between simulation and measurement allowed a validation of the simulation. Results showed that the total out-of-field dose equivalent inside the phantom ranged from 1.4 to 0.28 mSv/Gy, mainly due to the neutron contribution and with a small contribution from photons, 10% on average. The order of magnitude of the equivalent dose in organs was similar, displaying a slow reduction in values as the organ is farther from the target volume. These values were in agreement with those found by other authors in other passive beam facilities under similar irradiation and measurement conditions

Identification of novel synthetic lethal vulnerability in non small cell lung cancer by co targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci

We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.This work was supported by CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil, Junta de Andalucía, project of Excellence from Junta de Andalucía P12-CTS-383 to FJO, Spanish Ministry of Economy and Competitiveness SAF2015-70520-R to FJO and JMRdA, RTICC RD12/0036/0026 and CIBER Cáncer ISCIII CB16/12/00421 to FJO

Estimation of neutron-equivalent dose in organs of patients undergoing radiotherapy by the use of a novel online digital detector.

Neutron peripheral contamination in patients undergoing high-energy photon radiotherapy is considered as a risk factor for secondary cancer induction. Organ-specific neutron-equivalent dose estimation is therefore essential for a reasonable assessment of these associated risks. This work aimed to develop a method to estimate neutron-equivalent doses in multiple organs of radiotherapy patients. The method involved the convolution, at 16 reference points in an anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy spectra with the kerma and energy-dependent radiation weighting factor. This was then scaled with the total neutron fluence measured with passive detectors, at the same reference points, in order to obtain the equivalent doses in organs. The latter were correlated with the readings of a neutron digital detector located inside the treatment room during phantom irradiation. This digital detector, designed and developed by our group, integrates the thermal neutron fluence. The correlation model, applied to the digital detector readings during patient irradiation, enables the online estimation of neutron-equivalent doses in organs. The model takes into account the specific irradiation site, the field parameters (energy, field size, angle incidence, etc) and the installation (linac and bunker geometry). This method, which is suitable for routine clinical use, will help to systematically generate the dosimetric data essential for the improvement of current risk-estimation models