New Estimates of Regional GDP in Spain, 1860-1930

This paper presents a new regional database on GDP in Spain for the years 1860, 1900, 1914 and 1930. Following Geary and Stark (2002), country level GDP estimates are allocated across Spanish provinces. The results are then compared with previous estimates. Further, this new evidence is used to analyze the evolution of regional inequality and convergence in the long run. According to the distribution dynamics approach suggested by Quah (1993, 1996) persistence appears as a main feature in the regional distribution of output. Therefore, in the long run no evidence of regional convergence in the Spanish economy is found.

Una nova estimació retrospectiva del VAB regional industrial. Espanya, 1860-1930

[cat] En aquest treball, es realitza una nova estimació del VAB industrial espanyol a un nivell de desagregació territorial corresponent a les províncies (NUTSIII) i les Comunitats Autònomes (NUTS II). Per assolir aquest objectiu es planteja una nova metodologia d’estimació de les xifres històriques de VAB industrial regional. Front a les aproximacions tradicionals, basades en la utilització de fonts fiscals com a forma d’aproximar la capacitat productiva industrial, en aquest treball s’ofereix una estimació que també es basa en les rendes generades per la producció industrial de les regions. Amb aquest objectiu, es fa servir la metodologia proposada per Geary i Stark (2002) i les millores proposades per Crafts (2005). La utilització d’aquesta metodologia permet elaborar una nova estimació retrospectiva del VAB industrial de les regions espanyoles a diversos talls temporals corresponents al període 1860-1930.

[The World's Columbian Exposition. Portfolio of views issued by the Department of photography, C.D. Arnold, chief. Chicago and St. Louis, National Chemigraph Company, 1893, 36 phot., don du marquis Davidsard en 1930]

Donateur : Davidsard (18..-18.. ; marquis)

Wien, Cambridge, Königsberg: filosofisia tapahtumia 1929-1930

Kirjoittaja on Oulun yliopiston aatehistorian professori. Kirjoittajalta on aiemmin julkaistu Tieteessä tapahtuu -lehdessä Wienin piiriä sivuavat artikkelit "Eino Kaila ja tie Wienin piiriin" (TT 2/ 2002), "Kaila ja kahden tunnistamistavan ero" (TT 4/2002), "Realisti Wienin piirin väittelyissä" (TT 7/2002) ja "Positivismin kriitikosta positivistiksi"(TT 8/2002).

Targeting Cancer Stem-like Cells as an Approach to Defeating Cellular Heterogeneity in Ewing Sarcoma.

Plasticity in cancer stem-like cells (CSC) may provide a key basis for cancer heterogeneity and therapeutic response. In this study, we assessed the effect of combining a drug that abrogates CSC properties with standard-of-care therapy in a Ewing sarcoma family tumor (ESFT). Emergence of CSC in this setting has been shown to arise from a defect in TARBP2-dependent microRNA maturation, which can be corrected by exposure to the fluoroquinolone enoxacin. In the present work, primary ESFT from four patients containing CD133(+) CSC subpopulations ranging from 3% to 17% of total tumor cells were subjected to treatment with enoxacin, doxorubicin, or both drugs. Primary ESFT CSC and bulk tumor cells displayed divergent responses to standard-of-care chemotherapy and enoxacin. Doxorubicin, which targets the tumor bulk, displayed toxicity toward primary adherent ESFT cells in culture but not to CSC-enriched ESFT spheres. Conversely, enoxacin, which enhances miRNA maturation by stimulating TARBP2 function, induced apoptosis but only in ESFT spheres. In combination, the two drugs markedly depleted CSCs and strongly reduced primary ESFTs in xenograft assays. Our results identify a potentially attractive therapeutic strategy for ESFT that combines mechanism-based targeting of CSC using a low-toxicity antibiotic with a standard-of-care cytotoxic drug, offering immediate applications for clinical evaluation.

EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells

Introduction: Cancer stem cells (CSC) display plasticity and self renewal properties reminiscent of normal tissue stem cells but the events responsible for their emergence remain obscure. We have recently identified CSC in Ewing sarcoma family tumors (ESFT) and shown that they arise from mesenchymal stem cells from the bone marrow. Objective of the study: To analyze the mechanisms underlying cancer stem cell development in ESFT. Methods: Primary human mesenchymal stem cells (MSC) isolation from adult and pediatric bone marrow. Retroviral delivery of fusion protein (EWS-FLI1) to primary MSC, and transcriptional and phenotypical analysis. Results: We show that the EWS-FLI-1 fusion gene, associated wit 85-90% of ESFT and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2 and NANOG in human pediatric MSC (hpMSC) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSC expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWSFLI- 1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Conclusion: Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a cancer stem cell phenotype.