Screening of Synergic Interactions of Anti-Angiogenic and Anti-Tumor Compounds

Solid cancers have several common characteristics that Hanahan & Weinberg named as the hallmarks of cancer. Angiogenesis is an essential hallmark of cancer because tumor cells need oxygen and nutrients delivered by the vascular system. In fact, tumor growth and metastasis are angiogenesis dependent, and microvascular endothelial cells recruited by tumors have become an important target in cancer therapy. Combinations of drugs with different modes of action may lead to enhanced antitumor and antiangiogenic effects without injuring the host. The combined use of two drugs may sometimes produce enhanced, unchanged or diminished effects in comparison with their individual effects. These three different types of behaviour of the interacting drugs are called synergy, additive/indifferent and antagonistic effects. In the present work, we analyze 105 paired combinations of 15 compounds, some described by our research group as potent antiangiogenic compounds, and others currently used in clinical therapy. Our results show synergistic effects of several paired combinations using the MTT assay. [Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)].This communication has the support of a travel grant "Universidad de Málaga.Campus de Excelencia Internacional Andalucía Tech".Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Millimeter-wave aperture synthesis radiometry for snow and ice mapping

An outline design for a dual-band mm-wave polarimetric SAIR has been presented and is considered to be tractable. The envisaged application is for snow and ice mapping and ocean wind vector measurement. The vastly increased complexity of the high-frequency waveband may not be justified by the scientific benefit and operation at an additional lower frequency such as 18 GHz may give improved classification, though with reduced spatial resolution. The authors describe the outline design for a polarimetric, mm-wave SAIR. One-dimensional aperture synthesis employs a hybrid technique in which a long linear array of real-aperture stick antennas form over-lapping fan beams on the ground and aperture synthesis within the fan beams enables synthesis of the mm-wave image. Critical aspects for building a high-resolution, mm-wave ESTAR are system calibration and the construction of stick antennas that will be 3 m long and about half a wavelength wide.Peer ReviewedPostprint (published version

Síndrome compartimental en joven con alteración hemática

El síndrome compartimental es una patología bien conocida que se produce por un aumento de la presión dentro de un compartimiento miofascial. Presentamos el caso de un paciente con trombopenia que sufrió un traumatismo banal. Necesitó fasciotomía del compartimiento anteroexterno de la pierna y, más tarde, esplenectomía. El diagnóstico y tratamiento tardíos de esta complicación, así como una descomprensión inadecuada, pueden conducir a la pérdida de función en una extremidad.The compartment syndrome is a well described cli- nical entity that results from increased pressure within a myo- fascial compartment. An unusual case of a patient with thrombopenia and a minimal traumatism, is reported. He required fasciotomy of the anterolateral compartment of the leg and, later, splenectomy. Late recognition and treatment of this complication, as well as inadequate decompression, can lead to loss of limb

Cosmological bounds on sub-MeV mass axions

Axions with mass greater than 0.7 eV are excluded by cosmological precision data because they provide too much hot dark matter. While for masses above 20 eV the axion lifetime drops below the age of the universe, we show that the cosmological exclusion range can be extended from 0.7 eV till 300 keV, primarily by the cosmic deuterium abundance: axion decays would strongly modify the baryon-to-photon ratio at BBN relative to the one at CMB decoupling. Additional arguments include neutrino dilution relative to photons by axion decays and spectral CMB distortions. Our new cosmological constraints complement stellar-evolution limits and laboratory bounds.Comment: 19 pages, 10 figure

Estudio de la validez del concepto de material equivalente para predecir la rotura producida por entallas en U

El presente trabajo analiza los límites de aplicabilidad del concepto de material equivalente para predecir la rotura producida por entallas en U. El concepto de material equivalente simplifica el estudio de materiales elastoplásticos reduciéndolos al caso elástico lineal, introduciendo una tensión de rotura ficticia tal que en un ensayo de tracción la energía de deformación es igual al del material real. Esta aproximación combinada con un criterio de rotura permite calcular la carga máxima que resiste un sólido entallado en forma de U. La metodología ha sido aplicada a diferentes materiales elastoplásticos, configuraciones y temperaturas distinguiendo entre casos válidos e inválidos. Estos dos grupos diferenciados han permitido establecer los límites de validez y determinar una condición de aplicabilidad basada en el factor de intensidad de tensiones en entallas en U adimensionalizado, el radio adimensional y el ratio entre la carga máxima y la carga de colapso plástico.The authors wish to express their gratitude to the European Union’s H2020 research and innovation programme for their financial support under the LightCoce project (No 814632)

Proyecto EMULCELL: nuevas emulsiones bituminosas fabricadas con nanocelulosas. Resultados preliminares

Versión dos/as autores/as.[Resumen:] En la presente investigación se detallan los resultados de la investigación preliminar llevada a cabo en el marco del proyecto EMULCELL. Este proyecto nace con el objetivo de desarrollar nuevos tipos de emulsiones bituminosas mediante el empleo de nanocelulosas como agentes emulgentes. La finalidad de la presente investigación es la de minimizar los impactos ambientales asociados a la producción de este tipo de materiales de construcción y fomentar el uso de mezclas en frío, que presentan menores emisiones de gases de efecto invernadero y son de puesta en obra más sencilla y segura para los operarios. Para llevan a cabo la presente investigación se ha utilizado un molino coloidal con el fin de fabricar diferentes emulsiones bituminosas, de tipo C60B5, pero sustituyendo parte del agente emulgente comercial por nanocelulosa. Con las emulsiones así fabricadas, se han llevado a cabo ensayos de envuelta con el fin de determinar la cantidad más adecuada de agua de envuelta y de comprobar la mayor o menor facilidad de estas emulsiones para recubrir toda la superficie del árido durante el proceso de fabricación de mezclas bituminosas en frío. Los resultados se han comparado con los obtenidos para una emulsión de control de tipo C60B5 comercial. En general, cabe destacar la dificultad encontrada para obtener una emulsión catiónica. Finalmente, puede decirse que, en cuanto a envuelta, los resultados obtenidos son, en buena parte de los casos, similares a los obtenidos con la emulsión convencional. Sin embargo, se aprecia a simple viste una mayor cantidad de sedimento en las emulsiones fabricadas con nanocelulosa. Por tanto, para obtener resultados concluyentes, se requiere profundizar en la investigación. En fases posteriores se realizará un detallado análisis de la sensibilidad al agua de las mezclas fabricadas con estas emulsiones, así como un análisis de su rigidez, deformación permanente y susceptibilidad térmica.Ministerio de Economía y Competitividad; IDI-2017109

Quantum dots coordinated with conjugated organic ligands: new nanomaterials with novel photophysics

CdSe quantum dots functionalized with oligo-(phenylene vinylene) (OPV) ligands (CdSe-OPV nanostructures) represent a new class of composite nanomaterials with significantly modified photophysics relative to bulk blends or isolated components. Single-molecule spectroscopy on these species have revealed novel photophysics such as enhanced energy transfer, spectral stability, and strongly modified excited state lifetimes and blinking statistics. Here, we review the role of ligands in quantum dot applications and summarize some of our recent efforts probing energy and charge transfer in hybrid CdSe-OPV composite nanostructures

Results from MAGIC's first observation cycle on galactic sources

During its Cycle I, the MAGIC telescope targeted about 250 hours several galactic sources sought to be, or detected previously by other experiments in the same energy domain, gamma-ray emitters. This paper reviews some results of such MAGIC observations covering, among others, supernova remnants, the Galactic Center and microquasars. We will concentrate on the recent discovery at very high energy gamma-rays of the microquasar LS I +61 303.Comment: 6 pages, 8 figures. Prepared for "The Multi-messenger Approach to High-energy Gamma-ray Sources", Barcelona (Spain) 4-7 July 200

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

Short-term local expression of a PD-L1 blocking antibody from a self-replicating RNA vector induces potent antitumor responses

Immune checkpoint blockade has shown anti-cancer efficacy, but requires systemic administration of monoclonal antibodies (mAbs), often leading to adverse effects. To avoid toxicity, mAbs could be expressed locally in tumors. We developed adeno-associated virus (AAV) and Semliki Forest virus (SFV) vectors expressing anti-programmed death ligand 1 (aPDL1) mAb. When injected intratumorally in MC38 tumors, both viral vectors led to similar local mAb expression at 24 h, diminishing quickly in SFV-aPDL1-treated tumors. However, SFV-aPDL1 induced >40% complete regressions and was superior to AAV-aPDL1, as well as to aPDL1 mAb given systemically or locally. SFV-aPDL1 induced abscopal effects and was also efficacious against B16-ovalbumin (OVA). The higher SFV-aPDL1 antitumor activity could be related to local upregulation of interferon-stimulated genes because of SFV RNA replication. This was confirmed by combining local SFV-LacZ administration and systemic aPDL1 mAb, which provided higher antitumor effects than each separated agent. SFVaPDL1 promoted tumor-specific CD8 T cells infiltration in both tumor models. In MC38, SFV-aPDL1 upregulated co-stimulatory markers (CD137/OX40) in tumor CD8 T cells, and its combination with anti-CD137 mAb showed more pronounced antitumor effects than each single agent. These results indicate that local transient expression of immunomodulatory mAbs using non-propagative RNA vectors inducing type I interferon (IFN-I) responses represents a potent and