Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs.

We studied the actions of geldanamycin (GA) and herbimycin A (HMA), inhibitors of the chaperone proteins Hsp90 and GRP94, on B chronic lymphocytic leukemia (CLL) cells in vitro. Both drugs induced apoptosis of the majority of CLL isolates studied. Whereas exposure to 4-hour pulses of 30 to 100 nM GA killed normal B lymphocytes and CLL cells with similar dose responses, T lymphocytes from healthy donors as well as those present in the CLL isolates were relatively resistant. GA, but not HMA, showed a modest cytoprotective effect toward CD34+ hematopoietic progenitors from normal bone marrow. The ability of bone marrow progenitors to form hematopoietic colonies was unaffected by pulse exposures to GA. Both GA and HMA synergized with chlorambucil and fludarabine in killing a subset of CLL isolates. GA- and HMA-induced apoptosis was preceded by the up-regulation of the stress-responsive chaperones Hsp70 and BiP. Both ansamycins also resulted in down-regulation of Akt protein kinase, a modulator of cell survival. The relative resistance of T lymphocytes and of CD34+ bone marrow progenitors to GA coupled with its ability to induce apoptosis following brief exposures and to synergize with cytotoxic drugs warrant further investigation of ansamycins as potential therapeutic agents in CLL

Entrepreneurial intentions and entrepreneurship education to University students in Portugal

[EN] This article analyzes entrepreneurial intentions and motivations that encourage university students of Tourism to create their own company. Methodology is based on an empirical study, using a questionnaire adapted from a model of Veciana and Urbano (Actitudes de los estudiantes universitarios hacia la creación de empresas: un estudio empírico comparativo entre Catalunya y Puerto Rico. El emprendedor innovador y la creación de empresas de I + D + I, University of Valencia, pp 35 58, 2004), including the desirability and viability concepts. One hundred and sixty students answered the questionnaire from a total study population of 243 official Tourism degree students of the Superior Institute of Accounting and Management of Porto. This research finds out that the university students have a very positive perception about the desire to create their own company; a 90 % of students express their desire to do it, and 83.5 % express their intention. Moreover, a 57.5 % think that within actual crisis it is more difficult to do than before it. This research lets us get an in-depth study of a student of Tourism degree, finding out his entrepreneurial attitudes. It can be the first step to wake up and encourage students interest for starting up their own business.Del Rio-Rama, MDLC.; Peris-Ortiz, M.; Álvarez García, J.; Rueda Armengot, C. (2016). Entrepreneurial intentions and entrepreneurship education to University students in Portugal. Technology, Innovation and Education. 2(7):1-11. doi:10.1186/s40660-016-0013-5S11127Ajzen I (1991) The theory of plannes behavior. Organ Behav Hum Decis Process 50:179–211Aponte M (2002) Factores condicionantes de la creación de empresas en Puerto Rico: un enfoque institucional. Doctoral dissertation, Autonomous University of BarcelonaAponte M, Urbano D, Veciana JM (2006) Actitudes hacia la creación de empresas: un estudio comparativo entre Catalunya y Puerto Rico. Centro de Investigaciones Comerciales e Iniciativas Académicas de la Facultad de Administración de Empresas. Forum Empresarial 11(2):52–75Bae TJ, Qian S, Miao C, Fiet JO (2014) The relationship between entrepreneurship education and entrepreneurial intentions: a meta-analytic review. Entrep Theory Pract 38(2):217–254Brice J (2004) The role of personality dimensions on the formation of entrepreneurial intentions. USASBE Small Business Advancement National Center. University of Central Arkansas, USACabana-Villca R, Cortes-Castillo I, Plaza-Pasten D, Castillo-Vergara M, Alvarez-Marin A (2013) Análisis de las capacidades emprendedoras potenciales y efectivas en alumnos de centros de educación superior. J Technol Manag Innov 8(1):65–75Davidsson P (1989) Continued entrepreneurship and small firm business. Stockholm School of Economics, StockholmDavidsson P (1995) Culture, structure and regional levels of entrepreneurship. Entrep Reg Dev 7(1):41–62De Jorge-Moreno J, Castillo LL, Triguero MS (2012) The effect of business and economics education programs on students’ entrepreneurial intention. Eur J Train Dev 36(4):409–425Díaz JC, Hernández RM, Barata ML (2007) Estudiantes universitarios y creación de empresas. Un análisis comparativo entre España y Portugal. In Ayala, J.C. (coord.) Conocimiento, innovación y emprendedores: camino al futuro. Grupo FEDRA, MadridDo Paço AMF, Ferreira JM, Raposo M, Rodrigues RG, Dinis A (2011) Behaviours and entrepreneurial intention: empirical findings about secondary students. J Int Entrep 9(1):20–38Dohse D, Walter SG (2010) The role of entrepreneurship education and regional context in forming entrepreneurial intentions (No. 2010, 18). Document de treball de l’IEBEuropean Commission (2006). Entrepreneurship education in Europe: Fostering entrepreneurial mindsets through education and learning, Final Proceedings of the Conference on Entrepreneurship Education in OsloEurostat (2014) Informes sobre el empleo en la Unión Europea. Available in: http://europa.eu/publications/statistics/index_es.htmFuentes F, Saco F, Rodríguez P (2013) Estudio sobre el perfil emprendedor en el alumnado universitario de Córdoba. UCO Consejo Social de la Universidad de Córdoba, III Edición, Córdoba, pp 1–180Fuentes García FJ (2007) Análisis del Perfil Emprendedor del alumnado universitario y preuniversitario de Córdoba. Consejo Social Universidad de Córdoba, pp 1–105Genesca Garrigosa E, Veciana Verges JM (1984) Actitudes hacia la creación de empresas. Información Comercial Española 611:147–155Gerba DT (2012) Impact of entrepreneurship education on entrepreneurial intentions of business and engineering students in Ethiopia. Afr J Econ Manag Stud 3(2):258–277Gorman G, Hanlon D, King W (1997) Some research perspectives on entrepreneurship education and education for small business management: a ten-year literature review. Int Small Bus J 15(3):56–77Guerrero M, Rialp J, Urbano D (2008) The impact of desirability and feasibility on entrepreneurial intentions: a structural equation model. Int Entrep Manag J 4(1):35–50Haynie JM, Shepherd DA, McMullen JS (2009) An opportunity for me? The role of resources in opportunity evaluation decisions. J Manage Stud 46(3):337–361Hernangomez J, Martín N, Rodriguez AI, Saboia F (2005) El emprendedor nace o se hace? Un análisis de los determinantes del espíritu emprendedor. XVI Spanish-Portuguese Meeting of Scientic Management. Sevilla:33–44Hmieleski KM, Corbett AC (2006) Proclivity for improvisation as a predictor of entrepreneurial intentions. J Small Bus Manage 44(1):45–63Honjo Y (2004) Growth of new start-up firms: evidence from the Japanese manufacturing industry. Appl Econ Lett 11(1):21–32Hyde GC (1989) The relationship between policy and research. In Rosa, P.; Birley, S. Cannon, T. and O´Neill, K. The Role and Contribution of Small Business Research, Chap. 3:55–77, Institute ReportKolvereid L (1996) Prediction of employment status choice intentions. Entrep Theory Pract 21(1):47–57Kourilsky ML, Walstad WB (1998) Entrepreneurship and female youth: knowledge, attitude, gender differences, and educational practices. J Bus Ventur 13(1):77–88Krueger N, Brazeal D (1994) Entrepreneurial Potencial and Potencial Entrepreneurs. Entrep Theory Pract 18(3):91–104Krueger NF, Carsrud AL (1993) Entrepreneurial intentions: applying the theory of planned behaviour. Entrep Reg Dev 5(4):315–330Lanero A, Vázquez JL, Gutiérrez P, García MP (2011) The impact of entrepreneurship education in European universities: an intention-based approach analyzed in the Spanish area. Int Rev Public Nonprofit Marketin 8(2):111–130Miller BK, Bell JD, Palmer M, González A (2009) Predictors of entrepreneurial intentions: a quasi-experiment comparing students enrolled in introductory management and entrepreneurship classes. J Bus Entrep 21(2):39–62Neck HM, Zacharakis AL, Bygrave WD, Reynolds PD (2003) Global entrepreneurship monitor: 2002 executive report. Babson College, Babson, MANorth DC (1990) Institutions, Institutional Change and Economic Performance. Cambridge University Press, Cambridge (UK)North D (1993) Instituciones, cambio institucional y desempeño económico. Fondo de Cultura Económica, MéxicoNorth DC (2005) Understanding the Process of Economic Change. Academic Foundation. University Press, PrincentonGEM Portugal (2012) Estudo sobre o Empreendedorismo. Global Entrepreneruship Monitor (GEM). Instituto Universitário de Lisboa (ISCTEIUL) http://web.spi.pt/GEMportugal2012/files/GEM_PORTUGAL_2012.pdfRaposo M, do Paço A, Ferreira J (2008a) Entrepreneur’s profile: a taxonomy of attribu tes and motivations of university students. J Small Bus Enterp Dev 15(2):405–420Raposo MLB, Ferreira JJM, do Paço AMF, Rodrigues RJG (2008b) Propensity to firm creation: empirical research using structural equations. Int Entrep Manag J 4(4):485–504Robinson PB, Stimpson DV, Huefner JC, Hunt HK (1991) An attitude approach to the prediction of entrepreneurship. Entrep Theory Pract 15(4):13–31Samad Aghayi J (2008) Entrepreneurship organization. Public Administration Training Center Publications, TehranScherer RF, Adams JS, Carley S, Wiebe FA (1989) Role model performance effects on development of entrepreneurial career preference. Entrep Theory and Pract, spring:53–71Scherer RF, Brodzinski JD, Wiebe F (1991) Examining the relationship between personality and entrepreneurial career preference. Entrep Reg Dev 3(2):195–206Shane S (2003) A General Theory of Enttrepreneurship- The Individual Oportunity Nexus. Edward Elgar EditoresShapero A (1982) Social dimensions of entrepreneurship. In: Kent CA et al (eds) The encyclopedia of entrepreneurship. Prentice-Hall, Englewood Cliffs, pp 72–89Shapero A, Sokol L (1982) The social dimensions of entrepreneurship.Encyclopedia of Entrepreneurship:72–90Storey DJ (1994) Employment. In Storey, D.J. Understanding the small business sector. Capítulo 6, pp. 160–203. London: RoutledgeToledano N, Urbano D (2008) Promoting entrepreneurial mindsets at universities: a case study in the South of Spain. Eur J Int Manag 2(4):382–399Trequattrini R, Lombardi R, Lardo A, Cuozzo B (2015). The Impact of Entrepreneurial Universities on Regional Growth: a Local Intellectual Capital Perspective. Journal of the Knowledge Economy, 1–13Urbano D (2006) La creación de empresas en Catalunya. Organismos de apoyo y actitudes hacia la actividad emprendedora, Ed. 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Center for Entrepreneurial Studies Babson College. Wellesley, MA.: 621–635Yari A, Toulabi Z, Pourashraf Y (2013) Designing propensity to entrepreneurship paradigm in Ilam universities (structural equation model approach). J Novel Appl Sci 2:872–88

Entrepreneurs’ age, institutions, and social value creation goals: a multi-country study

This study explores the relationship between an entrepreneur's age and his/her social value creation goals. Building on the lifespan developmental psychology literature and institutional theory, we hypothesize a U-shaped relationship between entrepreneurs’ age and their choice to create social value through their ventures, such that younger and older entrepreneurs create more social value with their businesses while middle age entrepreneurs are relatively more economically and less socially oriented with their ventures. We further hypothesize that the quality of a country’s formal institutions in terms of economic, social, and political freedom steepen the U-shaped relationship between entrepreneurs’ age and their choice to pursue social value creation as supportive institutional environments allow entrepreneurs to follow their age-based preferences. We confirm our predictions using multilevel mixed-effects linear regressions on a sample of over 15,000 entrepreneurs (aged between 18 and 64 years) in 45 countries from Global Entrepreneurship Monitor data. The findings are robust to several alternative specifications. Based on our findings, we discuss implications for theory and practice, and we propose future research directions

Accurate masses and radii of normal stars: modern results and applications

This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl

An analysis of sickness absence in chronically ill patients receiving Complementary and Alternative Medicine: A longterm prospective intermittent study

BACKGROUND: The popularity of complementary and alternative medicine (CAM) has led to a growing amount of research in this area. All the same little is known about the effects of these special treatments in every-day practice of primary care, delivered by general practitioners within the health insurance system. From 1994 to 2000 more than 20 German Company health insurances initiated the first model project on CAM according to the German social law. Aim of this contribution is to investigate the effectiveness of multi-modal CAM on chronic diseases within primary health care. METHODS: A long-term prospective intermittent study was conducted including 44 CAM practitioners and 1221 self-selected chronically ill patients (64% women) of whom 441 were employed. Main outcome measure is sick-leave, controlled for secular trends and regression-to-the mean and self-perceived health status. RESULTS: Sick-leave per year of 441 patients at work increased from 22 (SD ± 45.2) to 31 (± 61.0) days within three years prior to intervention, and decreased to 24 (± 55.6) in the second year of treatment, sustaining at this level in the following two years. Detailed statistical analysis show that this development exceeds secular trends and the regression-toward-the-mean effect. Sick-leave reduction was corroborated by data on self-reported improvement of patients' health status. CONCLUSION: Results of this longterm observational study show a reduction of sick leave in chronically ill patients after a complex multimodal CAM intervention. However, as this is an uncontrolled observational study efficacy of any specific CAM treatment can not be proven. The results might indicate an general effectiveness of CAM in primary care, worthwhile further investigations. Future studies should identify the most suitable patients for CAM practices, the most appropriate and safe treatments, provide information on the magnitude of the effects to facilitate subsequent definitive randomised controlled studies that will help to position complementary and alternative medicine in health care

The Relationship between Regular Sports Participation and Vigilance in Male and Female Adolescents

The present study investigated the relationship between regular sport participation (soccer) and vigilance performance. Two groups of male and female adolescents differentiated in terms of their sport participation (athletes, n = 39, and non-athletes, n = 36) took part in the study. In one session, participants performed the Leger Multi-stage fitness test to estimate their aerobic fitness level. In the other session, participants completed the Psychomotor Vigilance Task (PVT) to evaluate their vigilance performance. Perceived arousal prior to the task and motivation toward the task were also measured in the PVT session. The results revealed that athletes had better cardiovascular fitness and showed better performance in the PVT. However, correlation analyses did not show any significant relationship between cardiovascular fitness and performance in the PVT. Athletes showed larger scores in motivation and perceived arousal measures with respect to non-athletes, although, once again, these variables were not correlated with PVT performance. Gender differences were observed only in the Leger test, with males showing greater fitness level than females. The major outcome of this research points to a positive relationship between regular sport participation and vigilance during adolescence. This relationship did not seem to be influenced by gender, perceived arousal, motivation toward the task or cardiovascular fitness. We discuss our results in terms of the different hypotheses put forward in the literature to explain the relationship between physical activity and cognitive functioning.This research was supported by a Spanish Ministerio de Educación y Cultura (https://sede. educacion.gob.es) predoctoral grant (FPU13-05605) to the first author, and project research grants: Junta de Andalucia Proyecto de Excelencia SEJ-6414 (http://www.juntadeandalucia.es) and Ministerio de Economía y Competitividad PSI2013-46385 (http://www.mineco.gob.es) to DS and FH

現地観測に基づく河川流の乱流特性に関する研究

博士（工学）神戸大

Exploring synergies and trade-offs among the sustainable development goals: collective action and adaptive capacity in marginal mountainous areas of India

Global environmental change (GEC) threatens to undermine the sustainable development goals (SDGs). Smallholders in marginal mountainous areas (MMA) are particularly vulnerable due to precarious livelihoods in challenging environments. Acting collectively can enable and constrain the ability of smallholders to adapt to GEC. The objectives of this paper are: (i) identify collective actions in four MMA of the central Indian Himalaya Region, each with differing institutional contexts; (ii) assess the adaptive capacity of each village by measuring livelihood capital assets, diversity, and sustainable land management practices. Engaging with adaptive capacity and collective action literatures, we identify three broad approaches to adaptive capacity relating to the SDGs: natural hazard mitigation (SDG 13), social vulnerability (SDG 1, 2 and 5), and social–ecological resilience (SDG 15). We then develop a conceptual framework to understand the institutional context and identify SDG synergies and trade-offs. Adopting a mixed method approach, we analyse the relationships between collective action and the adaptive capacity of each village, the sites where apparent trade-offs and synergies among SDGs occur. Results illustrate each village has unique socio-environmental characteristics, implying distinct development challenges, vulnerabilities and adaptive capacities exist. Subsequently, specific SDG synergies and trade-offs occur even within MMA, and it is therefore crucial that institutions facilitate locally appropriate collective actions in order to achieve the SDGs. We suggest that co-production in the identification, prioritisation and potential solutions to the distinct challenges facing MMA can increase understandings of the specific dynamics and feedbacks necessary to achieve the SDGs in the context of GEC

Identification of Genes Contributing to the Virulence of Francisella tularensis SCHU S4 in a Mouse Intradermal Infection Model

Background: Francisella tularensis is a highly virulent human pathogen. The most virulent strains belong to subspecies tularensis and these strains cause a sometimes fatal disease. Despite an intense recent research effort, there is very limited information available that explains the unique features of subspecies tularensis strains that distinguish them from other F. tularensis strains and that explain their high virulence. Here we report the use of targeted mutagenesis to investigate the roles of various genes or pathways for the virulence of strain SCHU S4, the type strain of subspecies tularensis. Methodology/Principal Findings: The virulence of SCHU S4 mutants was assessed by following the outcome of infection after intradermal administration of graded doses of bacteria. By this route, the LD\u2085\u2080 of the SCHU S4 strain is one CFU. The virulence of 20 in-frame deletion mutants and 37 transposon mutants was assessed. A majority of the mutants did not show increased prolonged time to death, among them notably \u394pyrB and \u394recA. Of the remaining, mutations in six unique targets, tolC, rep, FTT0609, FTT1149c, ahpC, and hfq resulted in significantly prolonged time to death and mutations in nine targets, rplA, wbtI, iglB, iglD, purL, purF, ggt, kdtA, and glpX, led to marked attenuation with an LD\u2085\u2080 of >10\ub3 CFU. In fact, the latter seven mutants showed very marked attenuation with an LD\u2085\u2080 of 6510\u2077 CFU. Conclusions/Significance: The results demonstrate that the characterization of targeted mutants yielded important information about essential virulence determinants that will help to identify the so far little understood extreme virulence of F. tularensis subspecies tularensis.Peer reviewed: YesNRC publication: Ye