ZnO-mesoporous glass scaffolds loaded with osteostatin and mesenchymal cells improve bone healing in a rabbit bone defect.

The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2–10.3CaO–3.3P2O5–4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN+MSC, 4ZN+OST or 4ZN+MSC+OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice

Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus

8 páginas, 2 figuras, 2 tablas.The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants. © 2022, The Author(s).Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and MICINN/AEI (PID2020- 119035RB-100). EVG was funded by FPU17/00627, FPU17/05346; VCGA, MAB, MCP and LGP are recipients of Junta de Castilla y León (JCyL) (LE082-18, LE051-18, LE135-19, LE096-20, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y competitividad; MMV, RYC-2015-18368).Peer reviewe

Oval Domes. The Case of the Basílica de la Virgen de los Desamparados of Valencia

[EN] The dome of the Basilica de la Virgen de los Desamparados of Valencia is an emblematic example of Valencian baroque architecture and painting. Its shape, oval or elliptical, has been the subject of controversy in various studies. The study of oval domes throughout history is a very interesting field of research because, among other things, the determination of the exact shape is important in order to conclude how it was built. We approach the problem from a new mathematical point of view, calculating the distances between the points that make up the real data cloud and the hypothetical form considered, oval or ellipse. The use of modern graphic surveying techniques, carried out with a 3D laser scanner, and computation with the powerful symbolic and numerical mathematical solver, Mathematica, has allowed us to accurately determine the shape of the dome and determine that its sections are not well-described by ellipses. A better fit is obtained assuming that sections are ovals. The programming and generalization of the mathematical method employed in this work will allow it to be applied to determine the exact geometry of other oval or ellipsoidal vaults.Calvo Roselló, V.; Capilla Tamborero, E.; Navarro Fajardo, JC. (2020). Oval Domes. The Case of the Basílica de la Virgen de los Desamparados of Valencia. Nexus Network Journal. 22(2):393-409. https://doi.org/10.1007/s00004-019-00465-0S393409222Arphe i Villafañe, Juan de. 1585. Tratado De varia conmmensuracion para la Escultura y Architectura. Sevilla: imprenta de Andrea Pescioni i Juan de León.Barrallo J. 2011. Ovals and Ellipses in Architecture. Proceedings of ISAMA 2011, Columbia College, Chicago, Illinois; p. 9–18.Bérchez Gómez, J. 1995. Basílica de Nuestra Señora de los Desamparados (Valencia). In: Monumentos de la Comunidad Valenciana. Catálogo de Monumentos declarados y conjuntos históricos incoados. Tomo X. Valencia. Arquitectura Religiosa. Valencia: Conselleria de Cultura, Educació i Ciència—Generalitat Valenciana, 204–217.Borngässer, B. 1997a. Arquitectura barroca en España y Portugal. In Toman R. (ed.) El barroco. Arquitectura-escultura-pintura. Köln: Könemann, 78–119.Borngässer, B. 1997b. Arquitectura barroca en Francia. In Toman R. (ed.) El barroco. Arquitectura-escultura-pintura. Köln: Könemann, 122–151.Bosch Reig, I., Roig Picazo, P. 1999. El proyecto de restauración arquitectónica de las cúpulas, tambor y linterna de la Basílica de la Virgen de los Desamparados de Valencia. In: Restauración de Pintura Mural aplicada a la Basílica de la Virgen de los Desamparados de Valencia, Roig Picazo, P. y Bosch Reig, I. Valencia: Servicio de Publicaciones de la U.P.V., 21–74.Calvo López, J., Alonso Rodríguez, M.A., Rabasa Díaz, E.; López Mozo, A. 2005. Cantería Renacentista en la Catedral de Murcia. Murcia: Colegio Oficial de Arquitectos.Capilla Tamborero E., Calvo Roselló, V. 2014. Chapter 8: La cúpula interior de la Basílica de la Virgen de los Desamparados de Valencia. Análisis geométrico y matemático. In: J. C. Navarro (ed.) Bóvedas Valencianas. Arquitecturas ideales, reales y virtuales en época medieval y moderna. Valencia: ed. UPV (Scientia), 196–237. ISBN: 978-84-9048-188-2.Connors, J. 1999. Un teorema sacro: San Carlo alle Quattro Fontane. In Il giovane Borromini. Dagli esordi a San Carlo alle Quattro Fontane. Milano: Skira, 459–512.Dotto, E. 2001. Note sulle costruzioni degli ovali a quattro centri. Vecchie e nuove costruzioni dell’ovale. Disegnare Idee Immagini; XII 23: 7–14.Duvernoy, Sylvie. 2015. Baroque Oval Churches: Innovative Geometrical Patterns in Early Modern Sacred Architecture. Nexus Network Journal 17 (2): 425–456.Fernández Gómez M. 1996. La planta oval. Traza y símbolo. Loggia. Arquitectura & Restauración 3: 16–21.García Jara F. 2008. Las cúpulas de la arquitectura religiosa de la provincia de Alicante: del Renacimiento al siglo XIX. Ph.D. Thesis.García Jara F. 2010. La estereotomía de las cúpulas sobre base oval. In: X Congreso Internacional de Expresión Gráfica aplicada a la Edificación, APEGA 2010, Alicante: 767–780.Gentil Baldrich, J. M. 1994. Planta oval y traza elíptica en la arquitectura: Consideraciones geométricas y un ejemplo español. Valladolid.Gentil Baldrich J.M. 1996. La traza oval y la Sala Capitular de la catedral de Sevilla. Una aproximación geométrica. In: J. A. Ruiz de la Rosa et al. Quatro edificios sevillanos. Sevilla: Colegio Oficial de Arquitectos de Andalucía, Demarcación Occidental, 73–147.Gómez-Collado, M.C.; Calvo Roselló, V; Capilla Tamborero, E. 2018. Mathematical modeling of oval arches. A study of the George V and Neuilly Bridges. Journal of Cultural Heritage Vol. 32: 144–155; https://doi.org/10.1016/j.culher.2018.01.012Hatch, John G. 2015. The Science Behind Francesco Borromini’s Divine Geometry. In: Architecture and Mathematics from Antiquity to the Future, eds. Kim Williams and Michael J. Oswald, vol. II, ch. 61, 217–228. Basel: Birkhäuser.Hill, Michael. 2013. Practical and Symbolic Geometry in Borromini’s San Carlo alle Quattro Fontane. Journal of the Society of Architectural Historians 72 (4): 555–583.Huerta Fernández, S. 2002. Informe sobre la estabilidad de la cúpula interior de la Basílica de la Virgen de los Desamparados de Valencia. Valencia. Conselleria Cultura, Educació y Ciència de la Generalitat Valenciana, 20 páginas.Huerta Fernández, S. 2007. Oval domes, geometry and mechanics. Nexus Network Journal 9(2), 211–248.Huerta Fernández, S. 2012a. Análisis estructural de cúpulas tabicadas: la cúpula interior de la Basílica de la Virgen de los Desamparados en Valencia. Construyendo Bóvedas Tabicadas. In: Actas del Simposio Internacional sobre bóvedas tabicadas. Valencia, 26 y 27 de mayo de 2011. Valencia: Editorial Universitat Politècnica de València, 318–335.Huerta Fernández, S. 2012b. Structural Analysis of Thin Tile Vaults and Domes: The Inner Oval Dome of the Basílica de la Virgen de los Desamparados in Valencia. In: Carvais et al (ed.) Nuts and Bolts of construction history. Culture, technology and society. Vol. 1. Paris: Picard, 375–383.Jung, W. 1997.) Arquitectura y ciudad en Italia. In Toman R. (ed.) El barroco. Arquitectura-escultura-pintura. Köln: Könemann, 12–75.Kluckert, E. 1997. Arquitectura barroca en Alemania, Suiza, Austria y Europa oriental. In Toman R. (ed.) El barroco. Arquitectura-escultura-pintura. Köln: Könemann, 184–273.López Manzanares, G. 2005. La contribución de R. G. Boscovich al desarrollo de la teoría de cúpulas: el informe sobre la Biblioteca Cesarea de Viena. In: Huerta, S. (ed.) Actas del Cuarto Congreso Nacional de Historia de la Construcción. Cádiz, 27–29 January 2005. Madrid: Instituto Juan de Herrera, 655–665.López Mozo A. 2011. Ovals for Any Given Proportion in Architecture: A Layout Possibly Known in the Sixteenth Century. Nexus Network Journal Vol. 13: 569–597.Mazzotti, A. 2014a. A Euclidean Approach to Eggs and Polycentric Curves. Nexus Network Journal, 16, 345–387. DOI https://doi.org/10.1007/s00004-014-0189-5Mazzotti, A. 2014b. What Borromini Might Have Known About Ovals. Ruler and Compass Constructions. Nexus Network Journal. https://doi.org/10.1007/s00004-014-0190-z .Mazzotti, A. 2017. All sides to an oval. Properties, Parameters, and Borromini’s Mysterious Construction. Springer. DOI https://doi.org/10.1007/978-3-319-39375-9Montoliu Soler, V. 2012. La Real Capilla de la Virgen de los Desamparados de Valencia: sus orígenes histórico-artísticos. Valencia: Real Academia de Cultura Valenciana.Navascués Palacio, P. 1974. El libro de arquitectura de Hernán Ruiz el Joven. Estudio y edición crítica por Pedro Navascues Palacio. Madrid: Escuela Técnica Superior de Arquitectura.Petrovic, Maja et al. 2019. A Focal Curve Approximation of a Borromini Oval Contour. Nexus Network Journal 21:19–31 https://doi.org/10.1007/s00004-018-00421-4Rabasa, E. 2009. Soluciones innecesariamente complicadas de la estereotomía clásica. In: AA.VV. El arte de la piedra, teoría y prática de la cantería. Madrid: CEU Ediciones, 50–69.Ragazzo, F. 1995, Geometria delle figure ovoidali, In Disegnare: 11, 17-24.Rosin P. 2001. On Serlio’s construction of ovals. The Mathematical Intelligencer 23(1): 58–69.Serlio S. 1552. Tercero y cuarto libro de Architectura de Sebastiano Serlio Boloñes. Translated by Francisco de Villalpando Architecto. Toledo: Casa de Iván de Ayala, 1552. (Edición facs. Barcelona: Serie Arte y Arquitectura, Editorial Alta Fulla, 1990.) (Edición digitalizada en Huerta, S. 2004. Selección de Tratados españoles de Arquitectura y Construcción de los siglos XVI al XX).Simona, M. 2005. Ovals in Borromini’s Geometry. In: Emmer, M., (ed.) Mathematics and Culture II. Visual Perfection: Mathematics and Creativity. Springer. 45–52. springeronline.comSoler Verdú, R. 1995. La cúpula en la arquitectura moderna valenciana. Siglos XVI a XVIII. Metodologías de estudios previos, para las arquitecturas de sistemas abovedados. Ph.D. Thesis. Universitat Politècnica de València.VV.AA. 2001. Real Basílica de la Virgen de los Desamparados de Valencia. Restauración de los fondos pictóricos y escultóricos. 1998–2001. I. Bosch (ed.) Valencia: Fundación para la Restauración de la Basílica de la Mare de Déu dels Desamparats

Oval Domes: History, Geometry and Mechanics

An oval dome may be defined as a dome whose plan or profile (or both) has an oval form. The word Aoval@ comes from the latin Aovum@, egg. Then, an oval dome has an egg-shaped geometry. The first buildings with oval plans were built without a predetermined form, just trying to close an space in the most economical form. Eventually, the geometry was defined by using arcs of circle with common tangents in the points of change of curvature. Later the oval acquired a more regular form with two axis of symmetry. Therefore, an “oval” may be defined as an egg-shaped form, doubly symmetric, constructed with arcs of circle; an oval needs a minimum of four centres, but it is possible also to build polycentric ovals. The above definition corresponds with the origin and the use of oval forms in building and may be applied without problem until, say, the XVIIIth century. Since then, the teaching of conics in the elementary courses of geometry made the cultivated people to define the oval as an approximation to the ellipse, an “imperfect ellipse”: an oval was, then, a curve formed with arcs of circles which tries to approximate to the ellipse of the same axes. As we shall see, the ellipse has very rarely been used in building. Finally, in modern geometrical textbooks an oval is defined as a smooth closed convex curve, a more general definition which embraces the two previous, but which is of no particular use in the study of the employment of oval forms in building. The present paper contains the following parts: 1) an outline the origin and application of the oval in historical architecture; 2) a discussion of the spatial geometry of oval domes, i. e., the different methods employed to trace them; 3) a brief exposition of the mechanics of oval arches and domes; and 4) a final discussion of the role of Geometry in oval arch and dome design

Design, characterization and installation of the NEXT-100 cathode and electroluminescence regions

NEXT-100 is currently being constructed at the Laboratorio Subterr\'aneo de Canfranc in the Spanish Pyrenees and will search for neutrinoless double beta decay using a high-pressure gaseous time projection chamber (TPC) with 100 kg of xenon. Charge amplification is carried out via electroluminescence (EL) which is the process of accelerating electrons in a high electric field region causing secondary scintillation of the medium proportional to the initial charge. The NEXT-100 EL and cathode regions are made from tensioned hexagonal meshes of 1 m diameter. This paper describes the design, characterization, and installation of these parts for NEXT-100. Simulations of the electric field are performed to model the drift and amplification of ionization electrons produced in the detector under various EL region alignments and rotations. Measurements of the electrostatic breakdown voltage in air characterize performance under high voltage conditions and identify breakdown points. The electrostatic deflection of the mesh is quantified and fit to a first-principles mechanical model. Measurements were performed with both a standalone test EL region and with the NEXT-100 EL region before its installation in the detector. Finally, we describe the parts as installed in NEXT-100, following their deployment in Summer 2023.Comment: 35 pages, 25 Figures, update includes accepted version in JINS

Production and processing of graphene and related materials

© 2020 The Author(s). We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resourceconsuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown

Production and processing of graphene and related materials

© 2020 The Author(s). We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resourceconsuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown

Detection of persistent VHE gamma-ray emission from PKS 1510-089 by the MAGIC telescopes during low states between 2012 and 2017

PKS 1510-089 is a flat spectrum radio quasar strongly variable in the optical and GeV range. To date, very high-energy (VHE, > 100 GeV) emission has been observed from this source either during long high states of optical and GeV activity or during short flares. Aims. We search for low-state VHE gamma-ray emission from PKS 1510-089. We characterize and model the source in a broadband context, which would provide a baseline over which high states and flares could be better understood. Methods. PKS 1510-089 has been monitored by the MAGIC telescopes since 2012. We use daily binned Fermi-LAT flux measurements of PKS 1510-089 to characterize the GeV emission and select the observation periods of MAGIC during low state of activity. For the selected times we compute the average radio, IR, optical, UV, X-ray, and gamma-ray emission to construct a low-state spectral energy distribution of the source. The broadband emission is modeled within an external Compton scenario with a stationary emission region through which plasma and magnetic fields are flowing. We also perform the emission-model-independent calculations of the maximum absorption in the broad line region (BLR) using two different models. Results. The MAGIC telescopes collected 75 hr of data during times when the Fermi-LAT flux measured above 1 GeV was below 3? × 10 -8 ? cm -2 ? s -1 , which is the threshold adopted for the definition of a low gamma-ray activity state. The data show a strongly significant (9.5¿) VHE gamma-ray emission at the level of (4.27 ± 0.61 stat ) × 10 -12 ? cm -2 ? s -1 above 150 GeV, a factor of 80 lower than the highest flare observed so far from this object. Despite the lower flux, the spectral shape is consistent with earlier detections in the VHE band. The broadband emission is compatible with the external Compton scenario assuming a large emission region located beyond the BLR. For the first time the gamma-ray data allow us to place a limit on the location of the emission region during a low gamma-ray state of a FSRQ. For the used model of the BLR, the 95% confidence level on the location of the emission region allows us to place it at a distance > 74% of the outer radius of the BLR. © ESO 2018.The financial support of the German BMBF and MPG, the Italian INFN and INAF, the Swiss National Fund SNF, the ERDF under the Spanish MINECO (FPA2015-69818-P, FPA2012-36668, FPA2015-68378-P, FPA2015-69210-C6-2-R, FPA2015-69210-C6-4-R, FPA2015-69210-C6-6-R, AYA2015-71042-P, AYA2016-76012-C3-1-P, ESP2015-71662-C2-2-P, CSD2009-00064), and the Japanese JSPS and MEXT is gratefully acknowledged. This work was also supported by the Spanish Centro de Exce-lencia “Severo Ochoa” SEV-2012-0234 and SEV-2015-0548, and Unidad de Excelencia “María de Maeztu” MDM-2014-0369, by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02, by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3, the Polish National Research Centre grant UMO-2016/22/M/ST9/00382, and by the Brazilian MCTIC, CNPq and FAPERJ. IA acknowledges support from a Ramón y Cajal grant of the Ministerio de Economía, Industria, y Competitividad (MINECO) of Spain. Acquisition and reduction of the POLAMI and MAPCAT data was supported in part by MINECO through grants AYA2010-14844, AYA2013-40825-P, and AYA2016-80889-P, and by the Regional Government of Andalucía through grant P09-FQM-4784.Peer Reviewe

A Compact Dication Source for Ba2+^{2+} Tagging and Heavy Metal Ion Sensor Development

We present a tunable metal ion beam that delivers controllable ion currents in the picoamp range for testing of dry-phase ion sensors. Ion beams are formed by sequential atomic evaporation and single or multiple electron impact ionization, followed by acceleration into a sensing region. Controllability of the ionic charge state is achieved through tuning of electrode potentials that influence the retention time in the ionization region. Barium, lead, and cobalt samples have been used to test the system, with ion currents identified and quantified using a quadrupole mass analyzer. Realization of a clean $\mathrm{Ba^{2+}}$ ion beam within a bench-top system represents an important technical advance toward the development and characterization of barium tagging systems for neutrinoless double beta decay searches in xenon gas. This system also provides a testbed for investigation of novel ion sensing methodologies for environmental assay applications, with dication beams of Pb$^{2+}$ and Cd$^{2+}$ also demonstrated for this purpose

Clinical standards for the diagnosis and management of asthma in low- and middle-income countries

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs). METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards. RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94–98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3–5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0–3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6–11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12–18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS. The following standards (14–18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual’s lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available. CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings