SBE13, a newly identified inhibitor of inactive polo-like kinase 1

Poster presentation at 5th German Conference on Cheminformatics: 23. CIC-Workshop Goslar, Germany. 8-10 November 2009 Protein kinases are important targets for drug development. The almost identical protein folding of kinases and the common co-substrate ATP leads to the problem of inhibitor selectivity. Type II inhibitors, targeting the inactive conformation of kinases, occupy a hydrophobic pocket with less conserved surrounding amino acids. Human polo-like kinase 1 (Plk1) represents a promising target for approaches to identify new therapeutic agents. Plk1 belongs to a family of highly conserved serine/threonine kinases, and is a key player in mitosis, where it modulates the spindle checkpoint at metaphase/anaphase transition. Plk1 is over-expressed in all today analyzed human tumors of different origin and serves as a negative prognostic marker in cancer patients. The newly identified inhibitor, SBE13, a vanillin derivative, targets Plk1 in its inactive conformation. This leads to selectivity within the Plk family and towards Aurora A. This selectivity can be explained by docking studies of SBE13 into the binding pocket of homology models of Plk1, Plk2 and Plk3 in their inactive conformation. SBE13 showed anti-proliferative effects in cancer cell lines of different origins with EC50 values between 5 microM and 39 microM and induced apoptosis. Increasing concentrations of SBE13 result in increasing amounts of cells in G2/M phase 13 hours after double thymidin block of HeLa cells. The kinase activity of Plk1 was inhibited with an IC50 of 200 pM. Taken together, we could show that carefully designed structure-based virtual screening is well-suited to identify selective type II kinase inhibitors targeting Plk1 as potential anti-cancer therapeutics

Dynamical measurements of deviations from Newton's 1/r21/r^2 law

In a previous work (arXiv:1609.05654v2), an experimental setup aiming at the measurement of deviations from the Newtonian $1/r^2$ distance dependence of gravitational interactions was proposed. The theoretical idea behind this setup was to study the trajectories of a "Satellite" with a mass $m_{\rm S} \sim {\cal O}(10^{-9})$ $\mathrm{g}$ around a "Planet" with mass $m_{\rm P} \in [10^{-7},10^{-5} ]$ $\mathrm{g}$, looking for precession of the orbit. The observation of such feature induced by gravitational interactions would be an unambiguous indication of a gravitational potential with terms different from $1/r$ and, thus, a powerful tool to detect deviations from Newton's $1/r^2$ law. In this paper we optimize the proposed setup in order to achieve maximal sensitivity to look for {\em Beyond-Newtonian} corrections. We study in detail possible background sources that could induce precession and quantify their impact on the achievable sensitivity. We conclude that a dynamical measurement of deviations from newtonianity can test Yukawa-like corrections to the $1/r$ potential with strength as low as $\alpha \sim 10^{-2}$ for distances as small as $\lambda \sim 10 \, \mu\mathrm{m}$.Comment: Two-column format (26 pages), 18 figure

Coulomb blockade in an atomically thin quantum dot coupled to a tunable Fermi reservoir

Gate-tunable quantum-mechanical tunnelling of particles between a quantum confined state and a nearby Fermi reservoir of delocalized states has underpinned many advances in spintronics and solid-state quantum optics. The prototypical example is a semiconductor quantum dot separated from a gated contact by a tunnel barrier. This enables Coulomb blockade, the phenomenon whereby electrons or holes can be loaded one-by-one into a quantum dot. Depending on the tunnel-coupling strength, this capability facilitates single spin quantum bits or coherent many-body interactions between the confined spin and the Fermi reservoir. Van der Waals (vdW) heterostructures, in which a wide range of unique atomic layers can easily be combined, offer novel prospects to engineer coherent quantum confined spins, tunnel barriers down to the atomic limit or a Fermi reservoir beyond the conventional flat density of states. However, gate-control of vdW nanostructures at the single particle level is needed to unlock their potential. Here we report Coulomb blockade in a vdW heterostructure consisting of a transition metal dichalcogenide quantum dot coupled to a graphene contact through an atomically thin hexagonal boron nitride (hBN) tunnel barrier. Thanks to a tunable Fermi reservoir, we can deterministically load either a single electron or a single hole into the quantum dot. We observe hybrid excitons, composed of localized quantum dot states and delocalized continuum states, arising from ultra-strong spin-conserving tunnel coupling through the atomically thin tunnel barrier. Probing the charged excitons in applied magnetic fields, we observe large gyromagnetic ratios (~8). Our results establish a foundation for engineering next-generation devices to investigate either novel regimes of Kondo physics or isolated quantum bits in a vdW heterostructure platform.Comment: Published in Nature Nanotechnology. 7 pages + 14 supplementary information pages. 14 figure

IMPLEMENTATION OF A PHOTOVOLTAIC FLOATING COVER FOR IRRIGATION RESERVOIRS

[EN] The article presents the main features of a floating photovoltaic cover system (FPCS) for water irrigation reservoirs whose purpose is to reduce the evaporation of water while generating electrical power. The system consists of polyethylene floating modules which are able to adapt to varying reservoir water levels by means of tension bars and elastic fasteners. (C) 2013 Elsevier Ltd. All rights reserved.Redón-Santafé, M.; Ferrer-Gisbert, P.; Sánchez-Romero, F.; Torregrosa Soler, JB.; Ferran Gozalvez, JJ.; Ferrer Gisbert, CM. (2014). IMPLEMENTATION OF A PHOTOVOLTAIC FLOATING COVER FOR IRRIGATION RESERVOIRS. Journal of Cleaner Production. 66:568-570. doi:10.1016/j.jclepro.2013.11.006S5685706

Leonardo da Vinci's Contributions from a Design Perspective

[EN] The figure of Leonardo da Vinci has been extensively studied. In fact, the Leonardiana Library brings together tens of thousands of titles on Leonardo and his work. During the second half of the 20th century, various treaties were published focusing on Leonardo¿s activity as an engineer, and more recently, an increasing number of scientific articles that focus on certain aspects of the prolific work of the genius such as construction, mechanics, strength of materials, etc. have been published. This article analyses the main contributions of the Tuscan genius in the field of design focusing on his processes for generating new solutions, his developments regarding graphic representation techniques, his improvements in plotting and measuring instruments, and how some of his devices were implemented and continue to maintain their usefulness.Cerveró-Meliá, E.; Capuz-Rizo, SF.; Ferrer-Gisbert, P. (2020). Leonardo da Vinci's Contributions from a Design Perspective. Designs. 4(3):1-20. https://doi.org/10.3390/designs4030038S12043Braha, D., & Maimon, O. (1997). The design process: properties, paradigms, and structure. IEEE Transactions on Systems, Man, and Cybernetics - Part A: Systems and Humans, 27(2), 146-166. doi:10.1109/3468.554679Criteria for Accrediting Engineering Programs, 2019–2020 https://www.abet.org/accreditation/accreditation-criteria/criteria-for-accrediting-engineering-programs-2019-2020/#definitionsVeltman, K. H. (2008). Leonardo da Vinci: A Review. Leonardo, 41(4), 381-388. doi:10.1162/leon.2008.41.4.381Innocenzi, P. (2020). Leonardo and the Design of Machines. Advances in Intelligent Systems and Computing, 36-46. doi:10.1007/978-3-030-41018-6_5Oliveira, A. R. E. (2019). The Mechanical Sciences in Leonardo da Vinci’s Work. Advances in Historical Studies, 08(05), 215-238. doi:10.4236/ahs.2019.85016Jaramillo, H. E. (2011). Un Análisis de la Resistencia de Materiales a partir de los Postulados de «Consideraciones y Demostraciones Matemáticas sobre dos Nuevas Ciencias» de Galileo Galilei. Lámpsakos, (5), 53. doi:10.21501/21454086.819Reciprocating machine for weight lifting (Argano), Codex Atlanticus f. 30 v, (1478–1480) https://commons.wikimedia.org/wiki/File:Reproduction_of_page_from_notebook_of_Leonardo_da_Vinci_showing_a_geared_device_assembled_and_disassembled_LCCN2006681098.jpgModel at the Museum of Science and Technology of Milan https://commons.wikimedia.org/wiki/File:Argano_sollevatore_pesi_Leonardo_Museo_scienza_e_tecnologia_Milano.jpgMap of the Val di Chiana, Royal Collection, RLW 12278, (1502–1504) https://commons.wikimedia.org/wiki/File:Val_di_Chiana.jpgReproduction of a compass designed by Leonardo https://commons.wikimedia.org/wiki/File:Compas_Léonard_de_Vinci.JPGProportional or reduction compass. Forster Codex I f. 45 (1485) https://commons.wikimedia.org/wiki/File:Reduction_Compass_Leonardo.jpgParabolic Compass. Codex Atlanticus f. 1093 r https://upload.wikimedia.org/wikipedia/commons/archive/0/03/20171027130237%21Leonardo_parabolic_compass.JPG.Detail of the Codex Atlanticus f. 5 r. Enlarged detail of the prospectograph being used by Leonardo https://commons.wikimedia.org/wiki/File:Codice_Atlantico_-_Perspectograph.jpgStudy ot two odometers. Codex Atlanticus, f. 1b r https://commons.wikimedia.org/wiki/File:Odomètre-Léonard.jpgOdometer model. Museo Nazionale della Scienza e della Tecnologia Leonardo da Vinci. (National Museum of Science and Technology of Milan) https://commons.wikimedia.org/wiki/File:Odometro_a_carriola_-_Museo_scienza_tecnologia_Milano_09908_01.jpgPugno, N. M. (2019). The commemoration of Leonardo da Vinci. Meccanica, 54(15), 2317-2324. doi:10.1007/s11012-019-01099-9Study for the mechanism of a manual lift (1495–1497), Madrid Codex I, f. 9 r https://commons.wikimedia.org/wiki/File:Ascenceur_à_manivelle-Léonard.jpgStudy of a piling machine. Codex Atlanticus, f 785, Ambrosian Library of Milan https://commons.wikimedia.org/wiki/File:Sonnette-Léonard.jpgModel of Leonardo’s pile machine, at the National Museum of Science and Technology of Milan https://commons.wikimedia.org/wiki/File:Battipalo_-_Museo_scienza_tecnologia_Milano_00040_01.jpgDetail of a mechanical jack, Codex Atlanticus, f. 0998 r, Ambrosian Library of Milan https://commons.wikimedia.org/wiki/File:Cric-Léonard.jpgManuscript of the self-propelled vehicle, Codex Atlanticus, f. 812 r (1478-1480), Ambrosiana Library of Milan https://commons.wikimedia.org/wiki/File:Leonardo_da_vinci,_Automobile.jpgModel of the self-propelled vehicle, at the National Museum of Science and Technology of Milan https://commons.wikimedia.org/wiki/File:Carro_semovente_-_Museo_scienza_tecnologia_Milano_09082_02.jp

A new photovoltaic floating cover system for water reservoirs

This paper describes a new photovoltaic floating cover system for water reservoirs developed jointly by the company CELEMIN ENERGY and the Universidad Politecnica de Valencia. The system consists of polyethylene floating modules which, with the use of tension producing elements and elastic fasteners, are able to adapt to varying reservoir water levels. A full-scale plant located near Alicante (Spain) was built in an agriculture reservoir to study the behaviour of the system. The top of the reservoir has a surface area of 4700 m(2) but only 7% of such area has been covered with the fixed solar system. The system also minimizes evaporation losses from water reservoirs. (C) 2013 Elsevier Ltd. All rights reserved.The English revision of this paper was funded by the Universidad Politecnica de Valencia, Spain.Ferrer Gisbert, CM.; Ferran Gozalvez, JJ.; Redón Santafé, M.; Ferrer-Gisbert, P.; Sánchez-Romero, F.; Torregrosa Soler, JB. (2013). A new photovoltaic floating cover system for water reservoirs. Renewable Energy. (60):63-70. doi:10.1016/j.renene.2013.04.007S63706

Project and Design of a Special Agricultural Warehouse Developed in Phases in Valencia (Spain)

[EN] This article describes the developing phases to build warehouses for a Pomelo Company at Valencian County (East of Spain). The warehouses are remarkable because they did not have many intermediate columns. Spatial and lightweight solutions are adopted and described. In the Projects also natural ventilation and lighting have been considered with a successfully result. Erection conditions and Regulations have been taken also account. It has been an inspiration motive for other consultants.Ferrer Gisbert, CM.; Ferrer-Gisbert, P.; Ferran Gozalvez, JJ.; Redón-Santafé, M.; Torregrosa Soler, JB.; Sánchez-Romero, F. (2020). Project and Design of a Special Agricultural Warehouse Developed in Phases in Valencia (Spain). Current Trends in Civil & Structural Engineering. 5(5):1-8. https://doi.org/10.33552/CTCSE.2020.05.000623S185

Texture and mineralogy influence on durability: The Macigno sandstone

The behaviour of ornamental stones in response to environmental changes or interactions is crucial when dealing with the conservation of cultural heritage.Weathering factors affect each rock differently, depending on structure, mineralogy, and extraction and implementation techniques. This work focuses on the Macigno sandstone, a dimension stone often employed in Tuscany over the centuries. A thorough mineralogical (optical microscopy, scanning electron microscopy and X-ray powder diffraction) and petrophysical characterization (i.e. mercury intrusion porosimetry, X-ray computed tomography, hygroscopic adsorption behaviour, ultrasounds, image analysis and capillary uptake) was made of the sandstone type extracted in the area of Greve in Chianti. The lithotype shows mineralogical (i.e. presence of mixed-layer phyllosilicates) and microporosimetric features, leading to a high susceptibility to relative humidity variation. Moreover, the influence of swelling minerals is related to weathering due to saline solution. The joint application of petrographic and petrophysical techniques allows an understanding of the characteristic weathering pattern of exfoliation (i.e. detachment of multiple thin stone layers, centimetre scale, that are sub-parallel to the stone surface)

Analysis of the Impact of Different Variables on the Energy Demand in Office Buildings

[EN] The design of near zero energy offices is a priority, which involves looking to achieve designs which minimise energy consumption and balance energy requirements with an increase in the installation and consumption of renewable energy. In light of this, some authors have used computer software to achieve simulations of the energy behaviour of buildings. Other studies based on regulatory systems which classify and label energy use also generally make their assessments through the use of software. In Spain, there is an authorised procedure for certifying the energy performance of buildings, and software (LIDER-CALENER unified tool) which is used to demonstrate compliance of the performance of buildings both from the point of view of energy demand and energy consumption. The aim of this study is to analyse the energy behaviour of an office building and the variability of the same using the software in terms of the following variables: climate zone, building orientation and certain surrounding wall types and encasements typical of this type of construction.Fuentes Bargues, JL.; Vivancos, J.; Ferrer-Gisbert, P.; Gimeno-Guillem, MÁ. (2020). Analysis of the Impact of Different Variables on the Energy Demand in Office Buildings. Sustainability. 12(13):1-23. https://doi.org/10.3390/su12135347S1231213Pérez-Lombard, L., Ortiz, J., & Pout, C. (2008). A review on buildings energy consumption information. Energy and Buildings, 40(3), 394-398. doi:10.1016/j.enbuild.2007.03.007https://www.google.com.hk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiD95W5-qrqAhVP62EKHaYLCFAQFjADegQIARAB&url=https%3A%2F%2Fec.europa.eu%2Fenergy%2Fsites%2Fener%2Ffiles%2Fdocuments%2F2012_energy_roadmap_2050_en_0.pdf&usg=AOvVaw3tfjm-IvZt9fXrnZuvpohwEuropean Comission Climate Strategies & Targets https://ec.europa.eu/clima/policies/strategies/2030_enEuropean Comission Climate Negotations https://ec.europa.eu/clima/policies/international/negotiations/paris_en2018/844 of the European Parliament and of the Council of 30 May 2018 Amending Directive 2010/31/EU on the Energy Performance of Buildings and Directive 2012/27/EU on Energy Efficiency https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32018L0844&from=ENKurnitski, J., Saari, A., Kalamees, T., Vuolle, M., Niemelä, J., & Tark, T. (2011). Cost optimal and nearly zero (nZEB) energy performance calculations for residential buildings with REHVA definition for nZEB national implementation. Energy and Buildings, 43(11), 3279-3288. doi:10.1016/j.enbuild.2011.08.033Aparicio Ruiz, P., Guadix Martín, J., Salmerón Lissén, J. M., & Sánchez de la Flor, F. J. (2014). An integrated optimisation method for residential building design: A case study in Spain. Energy and Buildings, 80, 158-168. doi:10.1016/j.enbuild.2014.05.020Tourism and Digital Agenda Plan Nacional de Acción de Eficiencia Energética 2017–2020 https://ec.europa.eu/energy/sites/ener/files/documents/es_neeap_2017_es.pdfGuía de Ahorro y Eficiencia Energética en Oficinas http://www.officinaseficientes.es/docs/guia_OFF.pdfCrawley, D. B., Hand, J. W., Kummert, M., & Griffith, B. T. (2008). Contrasting the capabilities of building energy performance simulation programs. Building and Environment, 43(4), 661-673. doi:10.1016/j.buildenv.2006.10.027Pérez-Andreu, V., Aparicio-Fernández, C., Martínez-Ibernón, A., & Vivancos, J.-L. (2018). Impact of climate change on heating and cooling energy demand in a residential building in a Mediterranean climate. Energy, 165, 63-74. doi:10.1016/j.energy.2018.09.015Herrando, M., Cambra, D., Navarro, M., de la Cruz, L., Millán, G., & Zabalza, I. (2016). Energy Performance Certification of Faculty Buildings in Spain: The gap between estimated and real energy consumption. Energy Conversion and Management, 125, 141-153. doi:10.1016/j.enconman.2016.04.037Sinacka, J., & Ratajczak, K. (2018). Analysis of selected input data impact on energy demand in office building - case study. MATEC Web of Conferences, 222, 01015. doi:10.1051/matecconf/201822201015Mikulik, J. (2018). Energy Demand Patterns in an Office Building: A Case Study in Kraków (Southern Poland). Sustainability, 10(8), 2901. doi:10.3390/su10082901Aparicio Ruiz, P., Sánchez de la Flor, F. J., Molina Felix, J. L., Salmerón Lissén, J., & Guadix Martín, J. (2016). Applying the HVAC systems in an integrated optimization method for residential building’s design. A case study in Spain. Energy and Buildings, 119, 74-84. doi:10.1016/j.enbuild.2016.03.023Royal Decree 235/2013, of 5th April, Agreeing to the Procedure Basic for the Certification of the Energy Efficiency of Buildings https://www.boe.es/buscar/pdf/2013/BOE-A-2013-3904-consolidado.pdfUnified Tool LIDER-CALENER (HULC-Tool) https://veredes.es/blog/en/herramienta-unificada-lider-calener-hulc/Rosselló-Batle, B., Ribas, C., Moià-Pol, A., & Martínez-Moll, V. (2015). An assessment of the relationship between embodied and thermal energy demands in dwellings in a Mediterranean climate. Energy and Buildings, 109, 230-244. doi:10.1016/j.enbuild.2015.10.007Sánchez Ramos, J., Guerrero Delgado, Mc., Álvarez Domínguez, S., Molina Félix, J. L., Sánchez de la Flor, F. J., & Tenorio Ríos, J. A. (2019). Systematic Simplified Simulation Methodology for Deep Energy Retrofitting Towards Nze Targets Using Life Cycle Energy Assessment. Energies, 12(16), 3038. doi:10.3390/en12163038Catalogue of Constructive Elements of the TBC 2011 https://itec.cat/cec/Construction Technology of Catalonia (Instituto de Tecnología de la Construcción: ITec) https://en.itec.cat/Ministry of Development Support Document of the DB HE1 for the calculation of Characteristic Parameters of the Building Envelope (DA DB-HE/1) 2015 https://www.codigotecnico.org/images/stories/pdf/ahorroEnergia/DA_DB-HE-1_Calculo_de_parametros_caracteristicos_de_la_envolvente.pdfCondiciones de Aceptación de Procedimientos Alternativos a LIDER y CALENER https://www.idae.es/publicaciones/condiciones-de-aceptacion-de-procedimientos-alternativos-lider-y-calenerDesign Builder Software, ANSI/ASHRAE Standard 140-2004 Building Thermal Envelope and Fabric Load Tests 2006 http://www.designbuilder.co.uk/documents/ANSI_ASHRAE.pdfDatabase 2019 https://www.five.es/productos/herramientas-on-line/visualizador-2019/Haase, M., Marques da Silva, F., & Amato, A. (2009). Simulation of ventilated facades in hot and humid climates. Energy and Buildings, 41(4), 361-373. doi:10.1016/j.enbuild.2008.11.008Lau, A. K. K., Salleh, E., Lim, C. H., & Sulaiman, M. Y. (2016). Potential of shading devices and glazing configurations on cooling energy savings for high-rise office buildings in hot-humid climates: The case of Malaysia. International Journal of Sustainable Built Environment, 5(2), 387-399. doi:10.1016/j.ijsbe.2016.04.004Al-ajmi Farraj F., & Hanby, V. I. (2008). Simulation of energy consumption for Kuwaiti domestic buildings. Energy and Buildings, 40(6), 1101-1109. doi:10.1016/j.enbuild.2007.10.010Raheem, A. A., Issa, R. R., & Olbina, S. (2013). Solar transmittance analysis of different types of sunshades in the Florida climate. Building Simulation, 7(1), 3-11. doi:10.1007/s12273-013-0137-4Valladares-Rendón, L. G., & Lo, S.-L. (2014). Passive shading strategies to reduce outdoor insolation and indoor cooling loads by using overhang devices on a building. Building Simulation, 7(6), 671-681. doi:10.1007/s12273-014-0182-7Huang, Y., Niu, J., & Chung, T. (2014). Comprehensive analysis on thermal and daylighting performance of glazing and shading designs on office building envelope in cooling-dominant climates. Applied Energy, 134, 215-228. doi:10.1016/j.apenergy.2014.07.100Ng, P. K., Mithraratne, N., & Kua, H. W. (2013). Energy analysis of semi-transparent BIPV in Singapore buildings. Energy and Buildings, 66, 274-281. doi:10.1016/j.enbuild.2013.07.029Ihara, T., Gao, T., Grynning, S., Jelle, B. P., & Gustavsen, A. (2015). Aerogel granulate glazing facades and their application potential from an energy saving perspective. Applied Energy, 142, 179-191. doi:10.1016/j.apenergy.2014.12.05