Reactivity of neonicotinoid insecticides with carbonate radicals

“NOTICE: this is the author’s version of a work that was accepted for publication in Water Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in WATER RESEARCH, [VOL46, ISSUE11, jul 2012] DOI10.1016/j.watres.2012.03.051¨ ©IWA Publishing 2012. The definitive peer-reviewed and edited version of this article is published in Water Research 46 11 3476-3489 2012 10.1016/j.watres.2012.03.051 and is available at www.iwapublishing.comThe reaction of three chloronicotinoid insecticides, namely Imidacloprid (IMD), Thiacloprid (THIA) and Acetamiprid (ACT), with carbonate radicals (CO3 center dot-) was investigated. The second order rate constants (4 +/- 1) x 10(6), (2.8 +/- 0.5) x 10(5), and (1.5 +/- 1) x 10(5) M-1 s(-1) were determined for IMD, THIA and ACT, respectively. The absorption spectra of the organic intermediates formed after CO3 center dot- is approximately equal to attack to IMD is in line with those reported for alpha-aminoalkyl radicals. A reaction mechanism involving an initial charge transfer from the amidine nitrogen of the insecticides to CO3 center dot- is proposed and further supported by the identified reaction products. The pyridine moiety of the insecticides remains unaffected until nicotinic acid is formed. CO3 center dot- radical reactivity towards IMD, ACT, and THIA is low compared to that of HO center dot radicals, excited triplet states, and O-1(2), and is therefore little effective in depleting neonicotinoid insecticides. (C) 2012 Elsevier Ltd. All rights reserved.This research was financially supported by Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Agencia Nacional de Promocion Cientifica y Tecnologica (Argentina, project PICT 2007 number 00308), and Agencia Espanola de Cooperacion Internacional (project A/8199/07). M.L.D. thanks CONICET for a graduate studentship. M.C.G. is a research member of CONICET. D.O.M. is a research member of Comision de Investigaciones Cientificas de la Provincia de Buenos Aires (CIC), Argentina. L.S.J. acknowledges Ministerio de Ciencia e Innovacion for his Juan de la Cierva scholarship.Dell'arciprete, ML.; Soler Escoda, JM.; Santos-Juanes Jordá, L.; Arques Sanz, A.; Martire, DO.; Furlong, JP.; González, MC. (2012). Reactivity of neonicotinoid insecticides with carbonate radicals. Water Research. 46(11):3476-3489. https://doi.org/10.1016/j.watres.2012.03.051S34763489461

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

10.1371/journal.pone.0068759PLoS ONE87-POLN

The PREVIEW intervention study : Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes

Aim To compare the impact of two long-term weight-maintenance diets, a high protein (HP) and low glycaemic index (GI) diet versus a moderate protein (MP) and moderate GI diet, combined with either high intensity (HI) or moderate intensity physical activity (PA), on the incidence of type 2 diabetes (T2D) after rapid weight loss. Materials and Methods A 3-year multicentre randomized trial in eight countries using a 2 x 2 diet-by-PA factorial design was conducted. Eight-week weight reduction was followed by a 3-year randomized weight-maintenance phase. In total, 2326 adults (age 25-70 years, body mass index >= 25 kg/m(2)) with prediabetes were enrolled. The primary endpoint was 3-year incidence of T2D analysed by diet treatment. Secondary outcomes included glucose, insulin, HbA1c and body weight. Results The total number of T2D cases was 62 and the cumulative incidence rate was 3.1%, with no significant differences between the two diets, PA or their combination. T2D incidence was similar across intervention centres, irrespective of attrition. Significantly fewer participants achieved normoglycaemia in the HP compared with the MP group (P <.0001). At 3 years, normoglycaemia was lowest in HP-HI (11.9%) compared with the other three groups (20.0%-21.0%, P <.05). There were no group differences in body weight change (-11% after 8-week weight reduction; -5% after 3-year weight maintenance) or in other secondary outcomes. Conclusions Three-year incidence of T2D was much lower than predicted and did not differ between diets, PA or their combination. Maintaining the target intakes of protein and GI over 3 years was difficult, but the overall protocol combining weight loss, healthy eating and PA was successful in markedly reducing the risk of T2D. This is an important clinically relevant outcome.Peer reviewe

Analyses of the yeast Rad51 recombinase A265V mutant reveal different in vivo roles of Swi2-like factors

The Saccharomyces cerevisiae Swi2-like factors Rad54 and Rdh54 play multifaceted roles in homologous recombination via their DNA translocase activity. Aside from promoting Rad51-mediated DNA strand invasion of a partner chromatid, Rad54 and Rdh54 can remove Rad51 from duplex DNA for intracellular recycling. Although the in vitro properties of the two proteins are similar, differences between the phenotypes of the null allele mutants suggest that they play different roles in vivo. Through the isolation of a novel RAD51 allele encoding a protein with reduced affinity for DNA, we provide evidence that Rad54 and Rdh54 have different in vivo interactions with Rad51. The mutant Rad51 forms a complex on duplex DNA that is more susceptible to dissociation by Rdh54. This Rad51 variant distinguishes the in vivo functions of Rad54 and Rdh54, leading to the conclusion that two translocases remove Rad51 from different substrates in vivo. Additionally, we show that a third Swi2-like factor, Uls1, contributes toward Rad51 clearance from chromatin in the absence of Rad54 and Rdh54, and define a hierarchy of action of the Swi2-like translocases for chromosome damage repair

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?

[EN] Academic spin-offs (ASOs) help universities transfer knowledge or technology through business projects developed by academic staff. This investigation aims at analyzing the critical factors for spin-off creation at universities operating in crisis-raven, entrepreneurship-unfriendly environments. Such factors revolve around four types of resources: environmental, institutional, organizational, and personal. Focusing on a Southern European context, as an example of an unfriendly environment affected by economic crisis, an entrepreneurial university (the Technical University of Valencia in Spain, UPV) is our research setting. Through a case study approach, we examine the potential of UPV as a springboard for ASOs. Our results show an adverse local environment, a rather favorable influence of institutional and organizational drivers, and a mixed role of personal factors. Our findings illustrate that UPV consistently supports spin-off creation due to a greater (rather positive) reflexivity from its institutional, organizational and personal resources than the (negative) imprinting of the unfriendly environment. This helps counter-balance the structural unfriendliness for academic entrepreneurship, and trigger a crisis-led risk-taking attitude by academic staff. Hence, UPV should continue with its current strategy of supporting academic entrepreneurship, and might transfer best practices to other universities also affected by unfavorable environmental conditions. Generally speaking, we would advise universities facing adverse circumstances to develop rules and mechanisms for academic entrepreneurship, carefully revise and improve malfunctions, and become involved throughout the whole process of spin-off development. All in all, our study advances understanding of how the different drivers for ASO creation can be revamped by universities located in unfriendly environments, having in mind the key role that universities play in fostering social and economic development through academic entrepreneurship in such environments.The authors would like to thank the Universitat Politecnica de Valencia (grant PAID-06-12-0916), and the Spanish Ministry of Economy and Competitiveness (grant ECO2011-29863), for their financial support for this research.Seguí-Mas, E.; Oltra, V.; Tormo-Carbó, G.; Sarrión Viñes, F. (2017). Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?. International Entrepreneurship and Management Journal. 1-42. doi:10.1007/s11365-017-0478-zS142Acs, Z. J., Audretsch, D. B., & Lehmann, E. E. (2013). The knowledge spillover theory of entrepreneurship. Small Business Economics, 41, 757–774.Alemany, L. (2011). Libro blanco de la iniciativa emprendedora en España. Resource document. ISEAD. http://idl.isead.edu.es:8080/jspui/bitstream/123456789/859/1/658ALElib.pdf . Accessed 31 October 2015.Algieri, B., Aquino, A., & Succurro, M. (2013). Technology transfer offices and academic spin-off creation: the case of Italy. Journal of Technology Transfer, 38(4), 382–400.ARWU (2017). Academic Ranking of World Universities 2017. Resource document. http://www.shanghairanking.com/ARWU2017.html . Accesed 15 August 2017.Ashcroft, B., Holden, D., & Low, K. (2004). Potential entrepreneurs and the self employment choice decision. In Strathclyde Discussion papers in Economics, 4–16. Glasglow: University of Strathclyde.Autio, E., & Kauranen, I. (1994). Technologist-entrepreneurs versus nonentrepreneurial technologists: Analysis of motivational triggering factors. Entrepreneurship & Regional Development, 6, 315–328.Autio, E., Kenney, M., Mustar, P., Siegel, D., & Wright, M. (2014). Entrepreneurial innovation: The importance of context. Research Policy, 43, 1097–1108.Bonnacorsi, A., Colombo, M. G., Guerini, M., & Rossi-Lamastra, C. (2013). University specialization and new firm creation across industries. Small Business Economics, 41, 837–863.Bruneel, J., Van de Velde, E., & Clarysse, B. (2013). Impact of the type of corporate spin-off on growth. Entrepreneurship Theory and Practice, 37, 943–959.CampusHabitat5U (2017). International Campus of Excellence. Resource document. UPV. http://campushabitat5u.es/?lang=en . Accessed 5 October 2017.Chiesa, V., & Piccaluga, A. (2000). Exploitation and diffusion of public research: The chase of academic spin-offs companies in Italy. R&D Management, 30, 329–339.Clark, B. R. (1998). Creating entrepreneurial universities: Organizational pathways of transformation. New York: IAU Press.Clarysse, B., & Moray, N. (2004). A process study of entrepreneurial team formation: The case of research-based spin-off. Journal of Business Venturing, 19, 55–79.Cohen, M., Nelson, R., & Walsh, J. (2002). Links and impacts: The influence of public research on industrial R&D. Management Science, 48, 1–23.Creswell, J.W. & Clark, V. (2011). Designing and Conducting Mixed Methods Research. SAGE Publications.De Cleyn, S. H., Braet, J., & Klofsten, M. (2015). How human capital interacts with the early development of academic spin-offs. International Entrepreneurship and Management Journal, 11(3), 599–621.Doutriaux, J., & Peterman, D. (1982). Technology transfer and academic entrepreneurship. Babson Park: Frontiers of Entrepreneurship Research, Babson College Entrepreneurship Research Conference (BCERC).Eisenhardt, K. M. (1989). Building Theories from Case Study Research. Academy of Management Review, 14(4), 532–550.European Commission (2017). Erasmus 2013–14. Top 500 higher education institutions receiving Erasmus students. Resource document. EC. http://ec.europa.eu/dgs/education_culture/repository/education/library/statistics/2014/erasmus-receiving-institutions_en.pdf Accessed 5 October 2017.Eurovoc (2017). Mutilingual Thesaurus of the European Union. Resource document. http://eurovoc.europa.eu Accessed 03 February 2017.Franzoni, C. & Lissoni, F. (2006). Academic entrepreneurship, patents and spinoffs: Critical issues and lessons for Europe. CESPRI, Università Commerciale “Luigi Bocconi”. Working Paper No. 80.Fritsch, M., & Aamoucke, R. (2013). Regional public research, higher education, and innovative start-ups: An empirical investigation. Small Business Economics, 41, 865–885.Gartner, W. B. (1985). A conceptual framework for describing the phenomenon of new venture creation. The Academy of Management Review, 10, 696–706.Gartner, W. B. (1988). Who is an entrepreneur? is the wrong question. American Journal of Small Business, 12, 11–32.Geuna, A., & Nesta, L. J. J. (2006). University Patenting and its Effects on Academic Research: The merging European Evidence. Research Policy, 35, 790–807.Gibbert, M., & Ruigrok, W. (2010). The “What” and “How” of the case Study Rigor: Three Strategies based on Published Work. Organizational Research Methods, 13(4), 710–737.Gómez Gras, J. M., Galiana Lapera, D. R., Mira Solves, I., Verdú Jover, A. J., & Sancho Azuar, J. (2008). An empirical approach to the organisational determinants of spin-off creation in European universities. International Entrepreneurship and Management Journal, 4(2), 187–198.Grandi, A., & Grimaldi, R. (2005). Academics' organizational characteristics and the generation of successful business ideas. Journal of Business Venturing, 20(6), 821–845.Güemes, J.J. (2011), “Global Entrepreneurship Monitor. Informe GEM España 2010”. Resource document. GEM España. http://www.gemconsortium.org/docs/download/616. Accessed 15 January 2015 .Guerrero, M., & Urbano, D. (2012). The development of an entrepreneurial university. Journal of Technology Transfer, 37(1), 43–74.Guerrero, M., Urbano, D., Cunningham, J., & Organ, D. (2014). Entrepreneurial universities in two European regions: a case study comparison. Journal of Technology Transfer, 39(3), 415–434.Hoang, H., & Antoncic, B. (2003). Network-based research in entrepreneurship: A critical review. Journal of Business Venturing, 18(2), 165–187.Hofstede, G. (1980). Culture’s Consequences. International differences in work-related values. Beverly Hills: Sage.Hofstede, G. (2001). Culture’s consequences: Comparing values, behaviours, institutions, and organizations across nations (2nd ed.). Thousand Oaks: Sage.Hülsbeck, M., & Pickavé, E. N. (2014). Regional knowledge production as determinant of high-technology entrepreneurship: Empirical evidence for Germany. International Entrepreneurship and Management Journal, 10, 121–138.INE (2016). INEbase: Operaciones estadísticas. Instituto Nacional de Estadística (National [Spanish] Statistical Institute). Resource document. INE. http://www.ine.es/inebmenu/indice.htm . Accessed 2 July 2016.Kalar, B., & Antoncic, B. (2015). The entrepreneurial university, academic activities and technology and knowledge transfer in four European countries. Technovation, 36-37, 1–11.Kroll, H. (2009). Demonstrating the instrumentality of motivation oriented approaches for the explanation of academic spin-off formation—an application based on the Chinese case. International Entrepreneurship and Management Journal, 5, 97–116.LAEI (2013). Ley 14/2013, de 27 de septiembre, de Apoyo a Emprendedores y su Internacionalización (‘Act of Support to Entrepreneurs and their Internationalization’). Government of Spain, 27 September. Resource document: http://www.boe.es/boe/dias/2013/09/28/pdfs/BOE-A-2013-10074.pdf . Accessed 10 March 2016.Lam, A., & De Campos, A. (2015). Content to be sad’ or ‘runaway apprentice’? The psychological contract and career agency of young scientists in the entrepreneurial university. Human Relations, 68(5), 811–841.LCTI (2011). Ley 14/2011, de 1 de junio, de la Ciencia, la Tecnología y la Innovación (‘Science, Technology and Innovation Act’). Government of Spain, 1 June. Resource document: http://www.boe.es/boe/dias/2011/06/02/pdfs/BOE-A-2011-9617.pdf . Accessed 10 March 2016.León-Darder, F. (2016). La internacionalització de l’empresa valenciana. In E. Seguí-Mas (Ed.), Una nova via per a l’empresa valenciana (pp. 61–80). Catarroja: Editorial Afers & Fundació Nexe.LES (2011). Ley 2/2011, de 4 de marzo, de Economía Sostenible (‘Sustainable Economy Act’). Government of Spain, 4 March, Resource document. http://www.boe.es/boe/dias/2011/03/05/pdfs/BOE-A-2011-4117.pdf. Accessed 10 March 2016 .Leyden, D. P., & Link, A. N. (2013). Knowledge spillovers, collective entrepreneurship, and economic growth: The role of universities. Small Business Economics, 41, 797–817.Lindelöf, P., & Löfsten, H. (2006). Environmental hostility and firm behavior – An empirical examination of new technology-based firms on science parks. Journal of Small Business Management, 44(3), 386–406.Link, N., & Scott, T. (2005). Opening the ivory’s tower door: An analysis of the determinants of the formation of US university spin-off companies. Research Policy, 34, 1106–1112.Lockett, A., & Wright, M. (2005). Resources, capabilities, risk capital and the creation of university spin-out companies. Research Policy, 34, 1043–1057.LOMLOU (2007). Ley Orgánica 4/2007, de 12 de abril, por la que se modifica la Ley Orgánica 6/2011, de 21 de diciembre, de Universidades (‘Act of Modification of the University Act’). Government of Spain, 12 April. Resource document. https://www.boe.es/boe/dias/2007/04/13/pdfs/A16241-16260.pdf (accessed 11 March 2016).LOU (2001). Ley Orgánica 6/2001, de Universidades (‘University Act’). Government of Spain, 21 December. Resource document: https://www.boe.es/boe/dias/2001/12/24/pdfs/A49400-49425.pdf . Accessed 11 March 2016.Martinelli, A., Meyer, M., & Von Tunzelmann, N. (2008). Becoming an entrepreneurial university? A case study of knowledge exchange relationships and faculty attitudes in a medium-sized, research-oriented university. Journal of Technology Transfer, 33, 259–283.Martínez Carrascal, C. & Mulino Ríos, M. (2014). La evolución del crédito bancario a las empresas españolas según su tamaño. Un análisis basado en la explotación conjunta de la información de la CIR y de la CBI, Boletín Económico - Banco de España, Enero (January), pp. 117–125.Mathias, B. D., Williams, D. W., & Smith, A. R. (2015). Entrepreneurial inception: The role of imprinting in entrepreneurial action. Journal of Business Venturing, 30(1), 11–28.MIET (Spanish Ministry of Industry, Energy and Tourism) (2012). Estadísticas Pyme. Evolución e indicadores. No. 10″, Resource document. http://www.ipyme.org/Publicaciones/ESTADISTICAS_PYME_N10_2011.pdf. Accessed 2 May 2016 .Miles, M.B. & Huberman, A.M. (2008). Qualitative Data Analysis: an expanded sourcebook. Sage Publications.Morales-Gualdrón, S. Y., Gutiérrez-Gracias, & Roig Dobón, S. (2009). The entrepreneurial motivation in academia: A multidimensional construct. International Entrepreneurship and Management Journal, 6, 301–317.Mosey, S., & Wright, M. (2007). From human capital to social capital: A longitudinal study of technology-based academic entrepreneurs. Entrepreneur, 31, 909–936.Mosey, S., Lockett, A., & Westhead, P. (2006). Creating network bridges for university technology transfer: The Medici fellowship programme. Technology Analysis and Strategic Management, 18, 71–91.Mosey, S., Wright, M., & Clarysse, B. (2012a). Transforming traditional university structures for the knowledge economy through multidisciplinary institutes. Cambridge Journal of Economics, 36, 587–607.Mosey, S., Noke, H., & Binks, M. (2012b). The influence of human and social capital upon the entrepreneurial intentions and destinations of academics. Technology Analysis and Strategic Management, 24, 893–910.Moutinho, R., Au-Yong-Oliveira, M., Coelho, A., & Manso, J. P. (2016). Determinants of knowledge-based entrepreneurship: an exploratory approach. International Entrepreneurship and Management Journal, 12(1), 171–197.Mowery, D. C., Nelson, R. R., Sampat, B. N., & Ziedonis, A. A. (2001a). The growth of patenting and licensing by US universities: an assessment of the effects of Bayle-Dole Act of 1980. Research Policy, 30(1), 99–119.Mowery, D. C., Sampat, B. N., & Ziedonis, A. A. (2001b). Learning to patent: institutional experience, learning, and the characyeristics of US university Patents after the Bayle-Dole Act, 1981-1992. Management Science, 48(1), 73–89.O’Shea, R., Allen, J., Chevalier, A., & Roche, F. (2005). Entrepreneurial orientation, technology transfer and spinoff performance of US universities. Research Policy, 34, 994–1009.O’Shea, R., Allen, T., Morse, K., O’Gorman, C., & Roche, F. (2007). Delineating the anatomy of an entrepreneurial university: the Massachusetts Institute of Technology Experience. R&D Management, 37(1), 1–16.O’Shea, R., Chugh, H., & Allen, T. (2008). Determinants and consequences of university spinoff activity: A conceptual framework. Journal of Technology Transfer, 33, 653–666.Ortín, P., Salas, V., Trujillo, M.V., & Vendrell, F. (2007). El spin-off universitario en España como modelo de creación de empresas intensivas en tecnología. Ministerio de Industria, Turismo y Comercio. Secretaría General de Industria. Dirección General de Política de la Pyme. Resource document. http://www.ipyme.org/Publicaciones/Informe spinnoff.pdf . Accessed 2 October 2016.Papaoikonomou, E., Segarra, P., & Li, X. (2012). Entrepreneurship in the context of crisis: Identifying barriers and proposing strategies. International Advances in Economic Research, 18, 111–119.Piperopoulos, P., & Piperopoulos, G. (2010). Is Greece finally on the right path toward entrepreneurship, innovation, and business clusters? International Journal of Public Administration, 33(1), 55–59.Powers, B., & McDougall, P. (2005). University startup formation and technology licensing with firms that go public: A resource-based view of academic entrepreneurship. Journal of Business Venturing, 20, 291–311.Red OTRI (2016). Informe de la Encuesta de Investigación y Transferencia 2014 de las universidades españolas. Resource document. http://www.redotriuniversidades.net/index.php/informa-encuesta/6-encuesta-redotri/informa-encuesta-2014/download . Accessed 22 June 2016.Redero San-Román, M. (2002). Origen y desarrollo de la universidad franquista. Studia Zamorensia, 6, 337–352.Rodríguez-Gulías, M. J., Rodeiro-Pazos, D., & Fernández-López, S. (2017). The effect of university and regional knowledge spillovers on firms’ performance: an analysis of the Spanish USOs. International Entrepreneurship and Management Journal, 13(1), 191–209.Rodríguez-San Pedro, L.E. (2014). Las universidades españolas en su contexto historic. Resource document. Universia. http://universidades.universia.es/universidades-de-pais/historia-de-universidades/historia-universidad-espanola/pasado-reciente/pasado-reciente-multiplicidad-regimen-autonomico.html . Accessed 28 July 2015.Samsom, K., & Gurdon, M. (1990). Entrepreneurial scientist: Organizational performance in scientist-started high technology firms. Forest Park: Frontiers of Entrepreneurship Research, Babson College Entrepreneurship Research Conference (BCERC).Schmitz, A., Urbano, D., Dandolini, G. A., de Souza, J. A., & Guerrero, M. (2017). Innovation and entrepreneurship in the academic setting: A systematic literature review. International Entrepreneurship and Management Journal, 13(2), 369–395.Shane, S., & Khurana, R. (2003). Bringing individuals back in: The effects of career experience on new firm founding. Industrial and Corporate Change, 12, 519–543.Shapero, A., & Sokol, L. (1982). The social dimensions of entrepreneurship. In C. A. Kent, D. L. Sexton, & K. H. Vesper (Eds.), Encyclopaedia of entrepreneurship (pp. 72–90). Englewood Cliffs: Prentice Hall.Smilor, R. W., Gibson, D. V., & Dietrich, G. B. (1990). University spin-out companies: technology start-ups from UT-Austin. Journal of Business Venturing, 5(1), 63–76.Soler i Marco, V. (2009). Creixement i canvi estructural. In V. Soler (Ed.), Economia espanyola i del País Valencià. Valencia: Publicacions de la Universitat de València.Suddaby, R., Bruton, G. D., & Si, S. X. (2015). Entrepreneurship through a qualitative lens: Insights on the construction and/or discovery of entrepreneurial opportunity. Journal of Business Venturing, 30(1), 1–10.Tech Transfer UPV FCR (2016). Air Nostrum, Caixa Popular e IVI entran en el fondo de la UPV. Resource document. TTUPV FCR. http://www.techtransferupv.com/noticias/air-nostrum-caixa-popular-e-ivi-entran-en-el-fondo-de-la-upv/ (4 April) Accessed 10 July 2016.The Times Higher Education (2017). 100 Under 50 Ranking 2017. Resource document. THE. https://www.timeshighereducation.com/world-university-rankings/2017/young-university-rankings#!/page/0/length/-1/sort_by/rank/sort_order/asc/cols/stats . Accessed 15 august 2017.UPV (2007). Instituto IDEAS 15 aniversario (1992–2007). Resource document. UPV. http://www.upv.es/entidades/IDEAS/menu_urlv.html?http://www.upv.es/entidades/IDEAS/info/memoria15a%F1os.pdf . Accessed 10 April 2016.UPV (2011). Corporación empresarial. Resource document. UPV. http://www.upv.es/noticias-upv/noticia-4904-corporacion-emp-es.html . Accessed 10 April 2016.UPV (2014). Plan de emprendimiento global. Resource document. UPV. https://www.upv.es/noticias-upv/noticia-6846-plan-de-emprend-es.html . Accessed 10 April 2016.UPV (2015). Jornadas de Puertas Abiertas 2015–16. Resource document. UPV. www.upv.es/contenidos/ORIENTA/info/jpa_ciclos_2015-16.ppt . Accessed 10 April 2016.UPV (2017a). Spin-Off UPV. Resource document. UPV. http://www.upv.es/entidades/I2T/info/891434normalc.html . Accessed 5 October 2017.UPV (2017b). Ciudad Politécnica de la Innovación. Parque Científico en Red de la Universidad Politécnica de Valencia. Quienes Somos. Presentación. Resource document. UPV. http://cpi.upv.es/quienes-somos/presentacion . Accessed 5 October 2017.UPV (2017c). Servicio de Promoción y Apoyo a la Investigación, la Innovación y la Transferencia. Presentación. Resource document. UPV. http://i2t.webs.upv.es/i2t/presentacion.php. Accessed 5 October 2017 .UPV. (2017d). Tech Transfer UPV. UPV: Resource document http://www.upv.es/noticias-upv/noticia-8355-tech-transfer-u-es.html. Accessed 5 October 2017 .UPV (2017e). Mission statement, vision and values. Resource document. UPV. https://www.upv.es/organizacion/la-institucion/misionvisionvalores-plan-upv-en.html Accessed 17 October 2017.Vargas Vasserot, C. (2012). Las spin-offs académicas y su posible configuración como empresas de economía social. REVESCO. Revista de Estudios Cooperativos, 107, 186–205.VLC/Campus (2017). VLC/Campus. Valencia, International Campus of Excellence. Resource document. UPV. http://www.vlc-campus.com/en . Accessed 5 October 2017.Walter, A., Auer, M., & Ritter, T. (2006). The impact of network capabilities and entrepreneurial orientation on university spin-off performance. Journal of Business Venturing, 21(4), 541–567.Weatherston, J. (1995). Academic Entrepreneurs: Is a spin-off Company too risky. Proceedings of the 40th International Council on Small Business, Sydney, 18–21.Willoughby, M., Talon, J., Millet, J., & Ayats, C. (2013). University services for fostering creativity in hi-tech firms. The Service Industries Journal, 33, 1103–1116.Wright, M., & Mosey, S. (2012). Strategic entrepreneurship, resource orchestration and growing spin-offs from universities. Technology Analysis and Strategic Management, 24, 911–927.Wright, M., Clarysse, B., Mustar, P., & Lockett, A. (2007). Academic Entrepreneurship in Europe. Cheltenham: Edward Elgar.Yin, R. K. (1994). Case study research: Design and methods (2nd ed.). Sage: Thousand Oaks.Yusof, M., & Jain, K. J. (2010). Categories of university-level entrepreneurship: A literature survey. International Entrepreneurship and Management Journal, 6(1), 81–86

Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group

Dynamics of Co-Transcriptional Pre-mRNA Folding Influences the Induction of Dystrophin Exon Skipping by Antisense Oligonucleotides

Antisense oligonucleotides (AONs) mediated exon skipping offers potential therapy for Duchenne muscular dystrophy. However, the identification of effective AON target sites remains unsatisfactory for lack of a precise method to predict their binding accessibility. This study demonstrates the importance of co-transcriptional pre-mRNA folding in determining the accessibility of AON target sites for AON induction of selective exon skipping in DMD. Because transcription and splicing occur in tandem, AONs must bind to their target sites before splicing factors. Furthermore, co-transcriptional pre-mRNA folding forms transient secondary structures, which redistributes accessible binding sites. In our analysis, to approximate transcription elongation, a “window of analysis” that included the entire targeted exon was shifted one nucleotide at a time along the pre-mRNA. Possible co-transcriptional secondary structures were predicted using the sequence in each step of transcriptional analysis. A nucleotide was considered “engaged” if it formed a complementary base pairing in all predicted secondary structures of a particular step. Correlation of frequency and localisation of engaged nucleotides in AON target sites accounted for the performance (efficacy and efficiency) of 94% of 176 previously reported AONs. Four novel insights are inferred: (1) the lowest frequencies of engaged nucleotides are associated with the most efficient AONs; (2) engaged nucleotides at 3′ or 5′ ends of the target site attenuate AON performance more than at other sites; (3) the performance of longer AONs is less attenuated by engaged nucleotides at 3′ or 5′ ends of the target site compared to shorter AONs; (4) engaged nucleotides at 3′ end of a short target site attenuates AON efficiency more than at 5′ end

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- A nd middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs