Página 6 dos resultados de 148 itens digitais encontrados em 0.001 segundos

Chemistry and Biology of Macrolide Antiparasitic Agents

Lee, Younjoo; Choi, Jun Yong; Fu, Hong; Harvey, Colin; Ravindran, Sandeep; Roush, William R.; Boothroyd, John C.; Khosla, Chaitan
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Macrolide antibacterial agents inhibit parasite proliferation by targeting the apicoplast ribosome. Motivated by the long-term goal of identifying antiparasitic macrolides that lack antibacterial activity, we have systematically analyzed the structure-activity relationships among erythromycin analogues and have also investigated the mechanism of action of selected compounds. Two lead compounds, N-benzyl-azithromycin (11) and N-phenylpropyl-azithromycin (30), were identified with significantly higher antiparasitic activity and lower antibacterial activity than erythromycin or azithromycin. Molecular modeling based on the co-crystal structure of azithromycin bound to the bacterial ribosome suggested that a substituent at the N-9 position of desmethyl-azithromycin could improve selectivity due to species-specific interactions with the ribosomal L22 protein. Like other macrolides, these lead compounds display a strong “delayed death phenotype”; however, their early effects on T. gondii replication are more pronounced.

Multistep Resistance Development Studies of Ceftaroline in Gram-Positive and -Negative Bacteria▿

Clark, Catherine; McGhee, Pamela; Appelbaum, Peter C.; Kosowska-Shick, Klaudia
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2011 Português
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Ceftaroline, the active component of the prodrug ceftaroline fosamil, is a novel broad-spectrum cephalosporin with bactericidal activity against Gram-positive and -negative isolates. This study evaluated the potential for ceftaroline and comparator antibiotics to select for clones of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis with elevated MICs. S. pneumoniae and S. pyogenes isolates in the present study were highly susceptible to ceftaroline (MIC range, 0.004 to 0.25 μg/ml). No streptococcal strains yielded ceftaroline clones with increased MICs (defined as an increase in MIC of >4-fold) after 50 daily passages. Ceftaroline MICs for H. influenzae and M. catarrhalis were 0.06 to 2 μg/ml for four strains and 8 μg/ml for a β-lactamase-positive, efflux-positive H. influenzae with a mutation in L22. One H. influenzae clone with an increased ceftaroline MIC (quinolone-resistant, β-lactamase-positive) was recovered after 20 days. The ceftaroline MIC for this isolate increased 16-fold, from 0.06 to 1 μg/ml. MICs for S. aureus ranged from 0.25 to 1 μg/ml. No S. aureus isolates tested with ceftaroline had clones with increased MIC (>4-fold) after 50 passages. Two E. faecalis isolates tested had ceftaroline MICs increased from 1 to 8 μg/ml after 38 days and from 4 to 32 μg/ml after 41 days...

Ribosomal Protein L19 and L22 Modulate TLR3 Signaling

Yang, Eun-Jeong; Seo, Jin-Won; Choi, In-Hong
Fonte: The Korean Association of Immunologists Publicador: The Korean Association of Immunologists
Tipo: Artigo de Revista Científica
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Ribosomal Mutations as the Main Cause of Macrolide Resistance in Campylobacter jejuni and Campylobacter coli ▿

Lehtopolku, Mirva; Kotilainen, Pirkko; Haanperä-Heikkinen, Marjo; Nakari, Ulla-Maija; Hänninen, Marja-Liisa; Huovinen, Pentti; Siitonen, Anja; Eerola, Erkki; Jalava, Jari; Hakanen, Antti J.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2011 Português
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The aim of this study was to examine macrolide resistance mutations in Campylobacter species. In 76 strains studied, point mutation A to G at position 2059 of the 23S rRNA gene was detected in 30 of the 33 erythromycin-resistant strains. An amino acid insertion in the ribosomal protein L22 was found in one resistant strain without a 23S rRNA mutation. The A2059G mutation is the main cause of macrolide resistance in Campylobacter species.

Inactivation of Ribosomal Protein Genes in Bacillus subtilis Reveals Importance of Each Ribosomal Protein for Cell Proliferation and Cell Differentiation

Akanuma, Genki; Nanamiya, Hideaki; Natori, Yousuke; Yano, Koichi; Suzuki, Shota; Omata, Shuya; Ishizuka, Morio; Sekine, Yasuhiko; Kawamura, Fujio
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2012 Português
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Among the 57 genes that encode ribosomal proteins in the genome of Bacillus subtilis, a Gram-positive bacterium, 50 genes were targeted by systematic inactivation. Individual deletion mutants of 16 ribosomal proteins (L1, L9, L15, L22, L23, L28, L29, L32, L33.1, L33.2, L34, L35, L36, S6, S20, and S21) were obtained successfully. In conjunction with previous reports, 22 ribosomal proteins have been shown to be nonessential in B. subtilis, at least for cell proliferation. Although several mutants that harbored a deletion of a ribosomal protein gene did not show any significant differences in any of the phenotypes that were tested, various mutants showed a reduced growth rate and reduced levels of 70S ribosomes compared with the wild type. In addition, severe defects in the sporulation frequency of the ΔrplA (L1) mutant and the motility of the ΔrpsU (S21) mutant were observed. These data provide the first evidence in B. subtilis that L1 and S21 are required for the progression of cellular differentiation.

Streptococcus sanguinis Isolate Displaying a Phenotype with Cross-Resistance to Several rRNA-Targeting Agents

Mendes, Rodrigo E.; Deshpande, Lalitagauri M.; Kim, Jihye; Myers, Debra S.; Ross, James E.; Jones, Ronald N.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2013 Português
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This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and a rare linezolid-resistant Streptococcus sanguinis strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The S. sanguinis strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents.

In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains

Jensen, Jørgen Skov; Fernandes, Prabhavathi; Unemo, Magnus
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2014 Português
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Mycoplasma genitalium has become well established as an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few M. genitalium strains are available to determine the MICs of currently used and new antimicrobial agents. Recent clinical trials have suggested that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, and alternative treatment with moxifloxacin is similarly under pressure from emerging resistance. Thus, there is an urgent need for new antimicrobials. The in vitro activity of the newly developed fluoroketolide solithromycin (CEM-101) was evaluated against a collection of 40 M. genitalium strains, including 15 with high-level macrolide resistance and 5 multidrug-resistant strains with resistance to both macrolides and quinolones. Furthermore, the MIC of solithromycin was correlated with mutations in the 23S rRNA gene and in the genes encoding ribosomal proteins L4 and L22. The in vitro results showed that solithromycin has activity against M. genitalium superior to that of other macrolides, doxycycline, and fluoroquinolones. Accordingly, this new fluoroketolide might be an effective option for treatment of M. genitalium infections. However...

Distal Renal Tubules Are Deficient in Aggresome Formation and Autophagy upon Aldosterone Administration

Cheema, Muhammad Umar; Damkier, Helle Hasager; Nielsen, Jakob; Poulsen, Ebbe Toftgaard; Enghild, Jan J.; Fenton, Robert A.; Praetorius, Jeppe
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 07/07/2014 Português
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Prolonged elevations of plasma aldosterone levels are associated with renal pathogenesis. We hypothesized that renal distress could be imposed by an augmented aldosterone-induced protein turnover challenging cellular protein degradation systems of the renal tubular cells. Cellular accumulation of specific protein aggregates in rat kidneys was assessed after 7 days of aldosterone administration. Aldosterone induced intracellular accumulation of 60 s ribosomal protein L22 in protein aggregates, specifically in the distal convoluted tubules. The mineralocorticoid receptor inhibitor spironolactone abolished aldosterone-induced accumulation of these aggregates. The aldosterone-induced protein aggregates also contained proteasome 20 s subunits. The partial de-ubiquitinase ataxin-3 was not localized to the distal renal tubule protein aggregates, and the aggregates only modestly colocalized with aggresome transfer proteins dynactin p62 and histone deacetylase 6. Intracellular protein aggregation in distal renal tubules did not lead to development of classical juxta-nuclear aggresomes or to autophagosome formation. Finally, aldosterone treatment induced foci in renal cortex of epithelial vimentin expression and a loss of E-cadherin expression...

Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas

ZOU, YANG; HUANG, MEI-ZHEN; LIU, FA-YING; YANG, BI-CHENG; WANG, LI-QUN; WANG, FENG; YU, XIAO-HONG; WAN, LEI; WAN, XI-DI; XU, XIAO-YUN; LI, WEI; HUANG, OU-PING; HE, MING
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
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Cancer is caused by multiple genetic alterations within cells. Recently, large-scale sequencing has identified frequent ribonuclease type III (DICER1), CCCTC-binding factor (CTCF), ribosomal protein L22 (RPL22), DNA (cytosine-5-)-methyltransferase 3α (DNMT3A), transformation/transcription domain-associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 hotspot mutations in diverse types of cancer. However, it remains largely unknown whether these mutations also exist in ovarian carcinomas. In the present study, a collection of 251 patients with distinct subtypes of ovarian carcinomas were recruited and sequenced for the presence of these hotspot mutations. However, no mutations in the seven genes were detected in the samples. These negative results, together with certain recent reports, indicate that the hotspot mutations in the CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 genes may not be actively involved in the carcinogenesis of ovarian carcinoma. Of note, the DICER1 mutation frequency in Sertoli-Leydig cell tumor in the present study was significantly lower compared to prior observation, and therefore, it is speculated that this discrepancy may be mainly due to the small sample size analyzed in the study. In addition, among these samples...

Miz-1 regulates translation of Trp53 via ribosomal protein L22 in cells undergoing V(D)J recombination

Rashkovan, Marissa; Vadnais, Charles; Ross, Julie; Gigoux, Mathieu; Suh, Woong-Kyung; Gu, Wei; Kosan, Christian; Möröy, Tarik
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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V(D)J recombination occurs in lymphoid precursors to enable their maturation, but also induces DNA damage. Thus, it has been proposed that the activity of the tumor suppressor and gatekeeper protein p53 must be controlled during this process to prevent premature induction of apoptosis. In this study, we show that the transcription factor Miz-1 can exert such a function. Miz-1 activates expression of the ribosomal protein Rpl22, which in turn controls the translation of p53 specifically in lymphoid precursors. We propose that this Miz-1–Rpl22–p53 pathway prevents p53 from inducing cell death as a response to V(D)J recombination in lymphoid precursors from both the T-lineage and the B-lineage.

Diversidade metabólica de microrganismos em rizosfera de linhagens e híbridos de milho contrastantes para fósforo - campo.

OLIVEIRA, C.A. de; MARRIEL, I.E.; ALVES, V.M.C.; PARENTONI, S.N.; PEREIRA FILHO, I.A.; SCHAFFERT, R.E.; MUZZI, M.R.S.; SA, N.M.H. de
Fonte: In: REUNIAO BRASILEIRA DE FERTILIDADE DO SOLO E NUTRICAO DE PLANTAS, 25., REUNIAO BRASILEIRA SOBRE MICORRIZAS,9., SIMPOSIO BRASILEIRO DE MICROBIOLOGIA DO SOLO, 7, REUNIAO BRASILEIRA DE BIOLOGIA DO SOLO,4, 2002. Rio de Janeiro. FertBIO 2002 - [resumos expandidos]. Rio de Janeiro: SBM: SBCS, 2002. Publicador: In: REUNIAO BRASILEIRA DE FERTILIDADE DO SOLO E NUTRICAO DE PLANTAS, 25., REUNIAO BRASILEIRA SOBRE MICORRIZAS,9., SIMPOSIO BRASILEIRO DE MICROBIOLOGIA DO SOLO, 7, REUNIAO BRASILEIRA DE BIOLOGIA DO SOLO,4, 2002. Rio de Janeiro. FertBIO 2002 - [resumos expandidos]. Rio de Janeiro: SBM: SBCS, 2002.
Tipo: Artigo em anais de congresso (ALICE) Formato: 1 CD-ROM.
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A avaliacao da diversidade microbiana e um bom indicador da qualidade dos solos e de diferencas existentes entre solos de rizosfera de plantas. O objetivo desse trabalho foi avaliar a diversidade metabolica de microrganismos totais da rizosfera, pelo sistema BIOLOG. O solos rizosferico de genotipos de milho, eficientes (E) e ineficientes (I) para fosforo, em alta e baixo P foram coletados na Embrapa Milho e Sorgo, Sete Lagoas, MG, Os hibridos avaliados foram: HT, HS1, HS2, eficientes e L22, ineficientes. Como amostras testemunhas: cerrado natural (mata), plantio direto e solo nao rizosferico dos hibridos e linhagens. As comunidades microbianas tivera, perfil distinto de utilizacao das fontes de carbono, conforme a analise de agrupamento e PCA. Amostras de rizosfera de hibridos e linhagens eficientes sob estresse de P tenderam a se agrupar, indicando que os microrganismos tiveram utilizacao semelhante de fontes de carbono, principalmente acidos carboxílicos. L3, L228 e HT HS2 foram perfil microbiano totalmente distinto quando sob alta dose de P. A diversidade microbiana em solos nao rizosfericos foi menor principalmente em alto P. O genotipos eficientes apresentaram, alta diversidade microbiana quando comparados com o cerrado natural.; 2002

Induced l₂ filtering of fuzzy stochastic systems with time-varying delays; Induced l(2) filtering of fuzzy stochastic systems with time-varying delays

Su, X.; Shi, P.; Wu, L.; Nguang, S.
Fonte: IEEE Publicador: IEEE
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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Xiaojie Su, Peng Shi, Ligang Wu, and Sing Kiong Nguang

What are the Issues in M&A arising from Electricity Market Restructuring?

NEWBERY, David
Fonte: Instituto Universitário Europeu Publicador: Instituto Universitário Europeu
Tipo: Trabalho em Andamento Formato: 401233 bytes; application/pdf; digital
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The energy merger was precipitated by energy market liberalisation that was often accompanied by restructuring and privatisation putting companies into play and creating new market risks that could be internalised by merging generation and supply. Electricity mergers pose distinctive challenges for competition policy - in market definition and for modelling price impacts in markets with no storage, inelastic short-run demand and transmission constraints. The EU has taken a more relaxed approach to merger assessment than the tighter screens of FERC despite greater market concentration and is poorly placed to deal with domestic mergers that impact external energy flows. Britain in contrast has used to desire for vertical mergers as a lever to reduce horizontal market power, and the EU should take more account of mergers foreclosing options for a future more competitive single energy market, notably for horizontal mergers, where cross-border interactions are important. The paper argues that vertical (convergent) mergers between electricity and gas raise particular concerns, given current EU gas market power, exemplified by the E.On-Ruhrgas merger. The form of the Emissions Trading System amplifies these concerns.

The demand of business services in Spain

Rodríguez Rodríguez, Diego; Merino de Lucas, Fernando
Fonte: SERVILAB (Alcalá de Henares) Publicador: SERVILAB (Alcalá de Henares)
Tipo: Trabalho em Andamento Formato: application/pdf
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The growth in the outsourcing of services has become one of the most relevant features of the changes in manufacturing firms¿ behaviour. This paper provides empirical evidence about the extent and evolution of services outsourcing by Spanish manufacturing firms in 1990-1998. A general increase in outsourcing of services has been detected among firms in this period, although with strong differences across sectors and kind of services. Additionally, this paper studies the decision to outsource, devoting particular attention to the relationship between outsourcing and productivity. The results show the influence of variables such as firm size, ownership and location, among others.

Empresa y empresario en la sociedad : contribución a su desarrollo y sostenibilidad; The business and businessman in society : their contribution to development and sustainability

García Echevarría, Santiago
Fonte: Universidad de Alcala. Instituto de Dirección y Organización de Empresas (IDOE) Publicador: Universidad de Alcala. Instituto de Dirección y Organización de Empresas (IDOE)
Tipo: Trabalho em Andamento Formato: application/pdf
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En una Sociedad abierta la empresa y el empresario constituyen una categoría societaria para el desarrollo de las personas y de la Sociedad. Lo que depende tanto de la adecuada ordenación de los entornos Societarios y económicos como de la adecuada armonía entre Estado y Mercado en búsqueda de una eficiente configuración de los dos criterios básicos: libertad y responsabilidad. Hay que ir más allá del pensamiento neoclásico y contractualista para diseñar,configurar y realizar una eficiente disposición de los recursos escasos y buscar en la cooperación la eficiencia económica de los mercados incidiendo en los comportamientos individuales e institucionales. La categoría societaria de la empresa y del empresario en esta nueva configuración abierta es la respuesta del éxito para asegurar el desarrollo integral de las personas y de las instituciones.; In an open Society businesses and businessmen and women conform a social category that contributes to the development of the individual in that Society. This depends upon the suitability of how social and economic environments are ordered as well as upon a harmony between the State and Market in order to conform efficiently the two basic criteria of liberty and responsibility. We need to go beyond Neoclassical and contractualist thinking in order to design...

Corporate diversification and R&D intensity dynamics

Alonso-Borrego, César; Forcadell, Francisco Javier
Fonte: Universidade Carlos III de Madrid Publicador: Universidade Carlos III de Madrid
Tipo: info:eu-repo/semantics/workingPaper; info:eu-repo/semantics/workingPaper Formato: application/pdf
Publicado em /12/2007 Português
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We study the dynamic bidirectional relationship between firm R&D intensity and corporate diversification, using longitudinal data of Spanish manufacturing companies. Our empirical approach takes into account the censored nature of the dependent variables and the existence of firm-specific unobserved heterogeneity. Whereas we find a positive linear effect of R&D intensity on related diversification, the evidence about the effect of related diversification on R&D intensity takes the form of an inverted U. Hence, the effect of related diversification on R&D intensity is positive but marginally decreasing for moderate levels of related diversification, but such effect can turn out negative for high levels of related diversification. Additionally, the consequences of the dynamic relation are that the effects are substantially larger in the long-run than in the short-run.

Optimal Information Transmission in Organizations: Search and Congestion

Arenas, Àlex; Cabrales, Antonio; Danon, Leon; Díaz-Guilera, Albert; Guimerà, Roger; Vega-Redondo, Fernando
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica Formato: application/pdf
Publicado em /11/2008 Português
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We propose a stylized model of a problem-solving organization whose internal communication structure is given by a fixed network. Problems arrive randomly anywhere in this network and must find their way to their respective specialized solvers by relying on local information alone. The organization handles multiple problems simultaneously. For this reason, the process may be subject to congestion. We provide a characterization of the threshold of collapse of the network and of the stock of floating problems (or average delay) that prevails below that threshold. We build upon this characterization to address a design problem: the determination of what kind of network architecture optimizes performance for any given problem arrival rate. We conclude that, for low arrival rates, the optimal network is very polarized (i.e. star-like or centralized), whereas it is largely homogenous (or decentralized) for high arrival rates. These observations are in line with a common transformation experienced by information-intensive organizations as their work flow has risen in recent years.

The microeconomics of bullionism : arbitrage, smuggling and silver outflows in Spain in the early 18th century

Nogues-Marco, Pilar
Fonte: Universidade Carlos III de Madrid Publicador: Universidade Carlos III de Madrid
Tipo: info:eu-repo/semantics/draft; info:eu-repo/semantics/workingPaper Formato: application/pdf
Publicado em /06/2011 Português
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In the Early Modern period, there was a systematic flow of precious metals from the American colonies to Spain and Portugal and, from there, throughout the world. In this paper, I use newly discovered data on the black market for silver in Cadiz to reconstruct a picture of Castilian smuggling and international silver flows in the Age of Bullionism (1729-1741). The arbitrage equation shows persistent violations of the silver-point that made arbitrage systematically profitable until devaluation pegged the exchange rate to the arbitrated parity. Market structure explains the persistent violations. The Cadiz shadow price was lower than the international market price because bullionist regulations configured an oligopsonistic structure. The price gap was the reason for the Castilian silver outflows to Europe

Electricidad e industria en la España rural: el Irati, 1904-1961

Garrués Irurzun Urrutia, Josean
Fonte: Universidad Carlos III de Madrid. Instituto Laureano Figuerola: Centro de Estudios Políticos y Constitucionales Publicador: Universidad Carlos III de Madrid. Instituto Laureano Figuerola: Centro de Estudios Políticos y Constitucionales
Tipo: info:eu-repo/semantics/publishedVersion; info:eu-repo/semantics/article Formato: application/pdf
Publicado em //2006 Português
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El estudio del Irati pretende mostrar algunos de los comportamientos empresariales que se esconden detrás de las primeras fases del desarrollo eléctrico español y, a su vez, establecer nuevas preguntas sobre los factores y condicionamientos de los procesos regionales de industrialización. De hecho, esta firma representa una de las múltiples posibilidades abiertas por la electricidad en una región española no industrializada a principios del siglo XX. La producción eléctrica generada en sus saltos explica la creación del mayor complejo industrial integrado en España alrededor de la primera transformación de la madera (serrerías y destilación química) y su comercialización (ferrocarril), al tiempo que la venta de sus excedentes energéticos en el mercado más importante de Navarra. El análisis de esta última actividad, además, permite ofrecer un modelo explicativo alternativo y complementario al clásico —realizado desde las mayores firmas—, sobre la progresiva articulación de los mercados eléctricos tradicionales en los mercados integrados de las grandes compañías españolas.; The study of the Irati hydroelectric company aims to show some of the business strategies behind the first stages of the development of electricity in Spain and...

Social interactions and spillovers: incentives, segregation and topology

Cabrales, Antonio; Calvó-Armengol, Antoni; Zenou, Yves
Fonte: Universidade Carlos III de Madrid Publicador: Universidade Carlos III de Madrid
Tipo: Trabalho em Andamento Formato: application/pdf
Publicado em 22/01/2009 Português
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The aim of this paper is to understand the interactions between productive e ort and the creation of synergies that are the sources of technological collaboration agreements, agglomeration, and social interactions. We model this interaction in a way that allows us to characterize how agents devote resources to both activities. This permits a full- edged equilibrium/welfare analysis of network formation with endogenous productive e orts, to derive unambiguous comparative statics results and to analyze community sorting by individual traits. In spite of its parsimony the model retains enough richness to replicate a broad range of empirical regularities displayed by social and economic networks, and to relate them to individual and social welfare. Key words: random network, spillovers, network formation, network topology.