997 resultados para Industrial maintenance
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This paper tries to resolve some of the main shortcomings in the empirical literature of location decisions for new plants, i.e. spatial effects and overdispersion. Spatial effects are omnipresent, being a source of overdispersion in the data as well as a factor shaping the functional relationship between the variables that explain a firm’s location decisions. Using Count Data models, empirical researchers have dealt with overdispersion and excess zeros by developments of the Poisson regression model. This study aims to take this a step further, by adopting Bayesian methods and models in order to tackle the excess of zeros, spatial and non-spatial overdispersion and spatial dependence simultaneously. Data for Catalonia is used and location determinants are analysed to that end. The results show that spatial effects are determinant. Additionally, overdispersion is descomposed into an unstructured iid effect and a spatially structured effect. Keywords: Bayesian Analysis, Spatial Models, Firm Location. JEL Classification: C11, C21, R30.
Resumo:
Summary Division of labor between reproducers (queens) and helpers (workers) is the main characteristic of social insect societies and at the root of their ecological success. Kin selection models predict that phenotypic differences between queens and workers should result from environmental rather than from genetic differences. However, genetic effects on queen and worker differentiation were found in two populations-of Pogonomyrmex harvester ants. Each of the two populations is composed of two genetically distinct lineages. Queens (which can be of either lineage) generally mate with males of their own and of the alternate lineage and produce two types of female offspring, those fertilized by males of the queens' lineage which develop into queens and those fertilized by males of the alternate lineage which develop into workers. All four lineages were further suggested to be themselves of hybrid origin between-the species P: barbatus and P. rugosus, in which queens and workers do not differ genetically. In a first set of experiments, we tested if female caste determination (the differentiation into queens and workers) in the lineages was genetically hardwired and if it was associated with costs in terms of the ability to optimally allocate resources to the production of queens and workers. To this end we first mated queens of-two lineages to a single male. Queens mated to a male of the alternate lineage successfully raised worker offspring whereas queens mated to a male of their own lineage almost always failed to produce workers. This reveals that pure-lineage individuals have lost the ability to develop into workers. Second, we analyzed offspring produced by naturally mated queens. During the stage of colony founding when only workers are produced, naturally mated queens laid a high proportion of pure-lineage eggs but the large majority of these eggs failed to develop. As a consequence, the number of offspring produced by incipient colonies decreased linearly with the proportion of pure-lineage eggs laid by queens. Moreover, queens of the lineage most commonly represented in a given population produced more pure-lineage eggs, in line with the view that they mate randomly with the two types of males and indiscriminately use their sperm. Altogether these results predict frequency-dependent founding success for pairs of lineages because queens of the more common lineage will produce more pure-lineage eggs and their colonies be less successful during the stage of colony founding. To describe the distribution of populations characterized with genetic caste determination relative to the populations with environmental caste determination we genotyped queens and workers collected during a large survey of -additional populations. Genetic caste determination associated with pairs of interbreeding lineages was frequent and widespread in the studied range and we identified four additional lineages displaying genetic caste determination. Overall, there were thus eight highly differentiated lineages with genetic caste determination. These lineages always co-occurred in the same complementary lineage pairs. Three of the four lineage pairs appeared to have a common origin, while their relationship with the forth could not be resolved. The genetic survey also revealed that, in addition to being genetically isolated from one another, all eight lineages were genetically distinct from P. rugosus and P. barbatus, even when colonies of interbreeding lineages co-occurred with colonies of either putative parent at the same site. This raised the question of the mechanisms involved in the reproductive isolation between the lineages and the parental species and between the two lineages of a lineage pair. At a site where one lineage pair co-occurred with P. rugosus, we identified two pre-zygotic mechanisms (differences in timing for mating flights between P. rugosus and the lineage pair and assortative mating) and one post-zygotic mechanism (high levels of hybrid unviablility) which in combination may largely account for the reproductive isolation between the lineages and their parental species. The mechanisms accounting for the reproductive isolation between the two lineages of a lineage pair varied across lineage pairs. In one lineage pair, inter-lineage individuals exclusively occurred in the sterile worker caste, raising the possibility that inter-lineage eggs have completely lost the ability to develop into queens in this lineage pair and that there is thus no opportunity for gene flow. In each of the three remaining lineage pairs, inter-lineage queens were produced by a minority of colonies. In these lineage pairs, colonies headed by inter-lineage queens failed to grow sufficiently to produce reproductive individuals which may account for the reproductive isolation between co-occurring lineages in three lineage pairs. In conclusion, the results of this thesis show that genetic caste determination is costly but widespread in Pogonomyrmex harvester ants. Reproductive isolation among the lineages and between the lineages and the parental species as well as frequency-dependent founding success for co-occurring lineages may contribute to the persistence of this extraordinary system. Résumé La division du travail entre individus reproducteurs (les reines) et individus non-reproducteurs (ouvrières) représente la caractéristique principale des sociétés d'insectes et est à la base de leur succès écologique. Des modèles de sélection de parentèle prédisent que les différences phénotypiques entre reines et ouvrières devraient provenir d'effets environnementaux plutôt que de différences génétiques. Malgré ce fait, des effets génétiques sur la différentiation entre reines et ouvrières ont été montrés dans deux populations de fourmis moissonneuses du genre Pogonomyrmex. Chacune des deux populations est composée de deux lignées génétiquement distinctes. Les reines de chaque lignée s'accouplent en général avec des mâles de leur propre lignée ainsi qu'avec des mâles de l'autre lignée et produisent deux types d'oeufs, ceux qui sont fécondés par les mâles de leur propre lignée qui se développent en nouvelles reines et ceux qui sont fécondés par les mâles de l'autre lignée qui se développent en ouvrières. Il a été suggéré que les lignées sont elles-mêmes des hybrides entre les deux espèces P. barbatus et P. rugosus. Dans ces deux espèces, les reines et ouvrières ne sont pas génétiquement distinctes. Dans une première série d'expériences, nous avons testé si la détermination de la caste femelle (le développement en reine ou en ouvrière) est génétiquement rigide et si elle est associée à des coûts en terme de capacité à allouer de façon optimale les ressources pour la production de reines et d'ouvrières. Pour cela nous avons accouplé des reines de deux lignées avec un seul mâle. Les reines accouplées avec un mâle de l'autre lignée ont élevé de nouvelles ouvrières avec succès alors que les reines accouplées avec un mâle de leur propre lignée ont presque toujours échoué à produire des ouvrières. Ceci montre que les individus de lignée pure ont perdu la capacité de se développer en ouvrière. Deuxièmement, nous avons analysé la descendance de reines qui se sont accouplées naturellement. Durant le stade de fondation de la colonie, où seules des ouvrières sont élevées, les reines accouplées naturellement ont pondu une grande proportion d'oeufs de lignée pure mais la majorité de ces derniers ne se sont pas développés. En conséquence, le nombre de descendants produits par des colonies fondatrices diminuait linéairement avec la proportion des oeufs de lignée pure pondus par la reine en accord avec l'hypothèse que les reines s'accouplent au hasard avec les deux types de mâles et utilisent leur sperme aléatoirement. Dans l'ensemble; ces résultats prédisent un succès de fondation fréquence-dépendant pour les deux lignées, car les reines de la lignée la plus fréquente produiront .plus d'oeufs de lignée pure et leurs colonies auront moins de succès lors de la fondation de colonies par rapport aux colonies de la lignée la moins fréquente. Pour décrire la distribution des-populations caractérisées par une détermination génétique des castes par rapport aux populations caractérisées par une détermination environnementale des castes, nous avons génotypé des reines et des ouvrières qui ont été collectées lors d'une analyse de populations supplémentaires. La détermination génétique des castes associée à des croisements entre lignées est fréquente et largement répartie dans l'aire étudiée. Nous avons identifié quatre lignées supplémentaires, ayant une détermination génétique des castes, pour un total de huit lignées. Ces huit lignées forment quatre paires de lignées et on ne trouve jamais deux lignées de paires différentes, dans une population. Trois des quatre paires de lignées s'avèrent avoir une origine commune alors que leur relation avec la quatrième paire de lignées n'a pas pu être résolue. L'analyse génétique de populations supplémentaires a également révélé qu'en plus d'être génétiquement isolées les unes des autres, les huit lignées sont génétiquement distinctes de P. rugosus et P. barbatus même si les colonies d'une paire de lignées se trouvent en sympatrie avec l'une ou l'autre des espèces parentales. Ceci relève la question des mécanismes impliqués dans l'isolation reproductive entre les lignées et les espèces parentales ainsi qu'entre les deux lignées d'une paire. En étudiant un site où une paire de lignées se trouve en sympatrie avec P. rugosus, nous avons identifié deux mécanismes pré-zygotiques (des différences dans le timing du vol nuptial entre P. rugosus et les lignées et des accouplements assortis) ainsi qu'un mécanisme post-zygotique (un niveau élevé de non-viabilité des hybrides). En combinaison, ces mécanismes peuvent largement expliquer l'isolement reproductif entre les lignées et leurs espèces parentales. Les mécanismes contribuant à l'isolement reproductif entre les deux lignées d'une paire variaient entre paires de lignées. Dans une paire, les individus de génotype inter-lignée se trouvent uniquement dans la caste stérile des ouvrières, suggérant qu'il n'y a pas d'opportunité pour avoir du flux de gènes entre les deux lignées ce cette paire. Dans chacune des trois autres paires de lignées des nouvelles reines de génotype inter-lignée sont produites par une minorité de colonies. Par contre, les colonies avec une reine mère de génotype inter-lignée ne se développent pas suffisamment pour produire des individus reproducteurs. Ceci peut donc expliquer pourquoi il n'y a pas de flux de gènes entre les deux lignées de trois paires. En conclusion, les résultats de cette thèse montrent que la détermination génétique de la caste est coûteuse mais très répandue chez les fourmis. moissonneuses du genre Pogonomyrmex. L'isolement reproductif des lignées entre elles et avec les espèces parentales, ainsi qu'un succès de fondation fréquence-dépendant contribuent à la persistance de ce système extraordinaire.
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Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair, and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here, we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep), or its specific downregulation by short hairpin RNA (shRNA), strongly impairs GBM cancer stem cell (CSC) self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM CSCs, we found the expression of c-myc, recently reported to be essential for GBM CSCs, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated downregulation of EZH2 in combination with chromatin immunoprecipitation experiments revealed that c-myc is a direct target of EZH2 in GBM CSCs. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM CSC maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.
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BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10-3 to 0.76×10-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.
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In this study we examined whether the maintenance of Trypanosoma cruzi by long-time in axenic culture produces changes in gene expression and antigenic profiles. The studies were made with a Dm30L-clone from a low-virulent strain and a non-cloned virulent EP-strain of T. cruzi. Both parasites were maintained, for at least seven years, by successive alternate passage triatomine/mouse (triatomine condition), or by serial passage in axenic medium (culture condition). The comparison of the [35S]methionine metabolic labeling products of virulent and non-virulent parasites by 2D-SDS-PAGE, clearly indicates that the expression of metacyclic trypomastigotes (but not of epimastigotes) proteins have been altered by laboratory maintenance conditions. Western blot analysis of EP and Dm30L-epimastigotes using a serum anti-epimastigotes revealed that although most of antigens are conserved, four antigens are characteristics of triatomine condition parasites and three other are characteristics of culture condition parasites. Anti-metacyclics serum revealed significative differences in EP- and Dm30L-metacyclic trypomastigotes from triatomine condition. However, avirulent metacyclic forms were antigenically very similar. These results suggest that besides a possible selection of avirulent subpopulation from T. cruzi strains genetically heterogeneous when maintained by long time in axenic culture, changes in virulence might be due to post-translational modifications of the antigens induced by the absence of the natural alternability (vertebrate-invertebrate) in the life-cycle of T. cruzi
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Accumulating evidence suggests that changes in the metabolic signature of astrocytes underlie their response to neuroinflammation, but how proinflammatory stimuli induce these changes is poorly understood. By monitoring astrocytes following acute cortical injury, we identified a differential and region-specific remodeling of their mitochondrial network: while astrocytes within the penumbra of the lesion undergo mitochondrial elongation, those located in the core-the area invaded by proinflammatory cells-experience transient mitochondrial fragmentation. In brain slices, proinflammatory stimuli reproduced localized changes in mitochondrial dynamics, favoring fission over fusion. This effect was triggered by Drp1 phosphorylation and ultimately resulted in reduced respiratory capacity. Furthermore, maintenance of the mitochondrial architecture critically depended on the induction of autophagy. Deletion of Atg7, required for autophagosome formation, prevented the reestablishment of tubular mitochondria, leading to marked reactive oxygen species accumulation and cell death. Thus, our data reveal autophagy to be essential for regenerating astrocyte mitochondrial networks during inflammation.
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Continuous turnover of epithelia is ensured by the extensive self-renewal capacity of tissue-specific stem cells. Similarly, epithelial tumour maintenance relies on cancer stem cells (CSCs), which co-opt stem cell properties. For most tumours, the cellular origin of these CSCs and regulatory pathways essential for sustaining stemness have not been identified. In murine skin, follicular morphogenesis is driven by bulge stem cells that specifically express CD34. Here we identify a population of cells in early epidermal tumours characterized by phenotypic and functional similarities to normal bulge skin stem cells. This population contains CSCs, which are the only cells with tumour initiation properties. Transplants derived from these CSCs preserve the hierarchical organization of the primary tumour. We describe beta-catenin signalling as being essential in sustaining the CSC phenotype. Ablation of the beta-catenin gene results in the loss of CSCs and complete tumour regression. In addition, we provide evidence for the involvement of increased beta-catenin signalling in malignant human squamous cell carcinomas. Because Wnt/beta-catenin signalling is not essential for normal epidermal homeostasis, such a mechanistic difference may thus be targeted to eliminate CSCs and consequently eradicate squamous cell carcinomas.
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A malaria control pilot project was developed in the Urupá agro-industrial farm that is situated in the State of Rondônia (Western Amazon Region, Brazil). Around 180 inhabitants had been surveyed for the past five years. The control measures were based on (1) training a community agent to perform on the spot microscopical diagnosis of malaria and to treat the uncomplicated cases of malaria; (2) limiting the use of insecticides to a short period before the high transmission season. This resulted in a significant reduction in the time between the onset of clinical symptoms and specific chemotherapy which fell from 3.5 to 1.3 days. In relation to the previous three reference years the total number of malaria cases was reduced to 50% in the first year and to 25% in the second year. The introduction of these measures coincided with pronounced reduction in the frequency of Plasmodium falciparum infections but this was less marked for P. vivax infections. In the second year of the pilot experiment there was no P. falciparum transmission on the farm. During the last decade there was a general decrease in the endemicity of malaria in the State of Rondônia. The linear regression coefficient values indicate that the decline was more pronounced in Urupá than in the general municipality and that the falciparum malaria API in Urupá farm is significantly lower than in the general municipality of Candeias were the farm is situated.
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La contaminación de suelos y aguas subterráneas es uno de los problemas ambientales más extendidos en gran parte de los terrenos industriales de Cataluña. En este proyecto se ha analizado el proceso de gestión de la contaminación: caracterización, remediación y seguimiento de la descontaminación en suelos y aguas subterráneas por un caso de afección por organoclorados (percloroetileno) y otros contaminantes (hidrocarburos, selenio y cromo) en un emplazamiento industrial situado en una zona agroforestal (superficie de 81.462 m2). A partir de la implantación en la empresa del sistema de gestión ISO 14.001 en 1.996, se abrieron diferentes proyectos de gestión para los posibles contaminantes. Por las mismas fechas, también se detectó una afección por selenio en aguas subterráneas, ajena a la empresa de estudio. Por el momento, el único contaminante que ha requerido de un proceso de descontaminación ha sido el percloroetileno. En suelos se emplea el método “soil vapor extraction” y en aguas subterráneas el método “airstripping”. Finalmente, se ha llevado a cabo una comparación de los costes reales derivados del proceso de descontaminación del percloroetileno en contra de los costes que se hubiesen derivado la implantación de medidas de prevención de la contaminación. El resultado de la valoración indica que la descontaminación de éste compuesto requiere de una inversión económica importante, unas 10 veces más elevada que los costes derivados de las medidas de prevención.
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Projecte de recerca elaborat a partir d’una estada a la University of Sussex, Gran Bretanya, entre març i juliol del 2008. L’estada ha estat centrada en obtenir fonts documentals primàries, per avançar en el projecte d’investigació sobre la transferència de tecnologia entre Catalunya i Anglaterra durant la Segona Revolució Industrial. Això ha estat possible gràcies a la consulta de les patents britàniques (Business & Intellectual Property Centre at the British Library). Així mateix, l’obtenció dels recursos documentals especialitzats de diverses biblioteques de referència situades al campus de la University of Sussex (Keith Pavitt Libray (SPRU), Library of Sussex, British Library of Development Studies) i a Ruddignton Framework Knitters’ Library a Nottingham han estat fonamentals, tal i com es pot veure en la relació detallada que es presenta.
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With some 30,000 dependent persons, opiate addiction constitutes a major public health problem in Switzerland. The Swiss Federal Office of Public Health (FOPH) has long played a leading role in the prevention and treatment of opiate addiction and in research on effective means of containing the epidemic of opiate addiction and its consequences. Major milestones on that path have been the successive "Methadone reports" published by that Office and providing guidance on the care of opiate addiction with substitution treatment. In view of updating the recommendations for the appropriateness of substitution treatment for opiate addiction, in particular for the prescription of methadone, the FOPH commissioned a multi-component project involving the following elements. A survey of current attitudes and practices in Switzerland related to opiate substitution treatment Review of Swiss literature on methadone substitution treatment Review of international literature on methadone substitution treatment National Methadone Substitution Conference Multidisciplinary expert panel to evaluate the appropriateness of substitution treatment. The present report documents the process and summarises the results of the latter element above. The RAND appropriateness method (RAM) was used to distil from literature-based evidence and systematically formulated expert opinion, areas where consensus exist on the appropriateness (or inappropriateness) of methadone maintenance treatment (MMT) and areas where disagreement or uncertainty persist and which should be further pursued. The major areas which were addressed by this report are Initial assessment of candidates for MMT Appropriate settings for initiation of MMT (general and special cases) Appropriateness of methadone supportive therapy Co-treatments and accompanying measures Dosage schedules and pharmacokinetic testing Withdrawal from MMT Miscellaneous questions Appropriateness of other (non-methadone) substitution treatment Summary statements for each of the above categories are derived from the panel meeting and presented in the report. In the "first round", agreement was observed for 31% of the 553 theoretical scenarios evaluated. The "second round" rating, following discussion of divergent ratings, resulted in a much higher agreement among panellists, reaching 53% of the 537 scenarios. Frank disagreement was encountered for 7% of all scenarios. Overall 49% of the clinical situations (scenarios) presented were considered appropriate. The areas where at least 50% of the situations were considered appropriate were "initial assessment of candidates for MMT", the "appropriate settings for initiation of MMT", the "appropriate settings for methadone supportive treatment" and "Appropriateness of other (non-methadone) substitution treatment". The area where there was the least consensus on appropriateness concerned "appropriateness of withdrawal from MMT" (6%). The report discusses the implications and limitations of the panel results and provides recommendations for the dissemination, application, and future use of the criteria for the appropriateness of MMT. The RAND Appropriateness Method proved to be an accepted and appreciated method to assess the appropriateness of methadone maintenance treatment for opiate addicts. In the next step, the results of the expert panel process must now be combined with those of the Swiss and international literature reviews and the survey of current attitudes and practices in Switzerland, to be synthesized into formal practice guidelines. Such guidelines should be disseminated to all concerned, promoted, used and rigorously evaluated for compliance and outcome.
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Fascioliasis is a parasitic disease of domestic ruminants that occurs worldwide. The lymnaeid intermediate hosts of Fasciola hepatica include Lymnaea columella, which is widely distributed in Brazil. A colony of L. columella from Belo Horizonte, MG, was reared in our laboratory to be used in studies of the F. hepatica life cycle, the intermediate host-parasite relationship and development of an anti-helminthic vaccine. In the first experiment 1,180 snails were exposed to miracidia of F. hepatica eggs removed from the biliary tracts of cattle from the State of Rio Grande do Sul. In the second and third experiments the snails were exposed to miracidia that had emerged from F. hepatica eggs from Uruguay, maintained in rabbits. The rates of infection in the first, second and third experiments were 0, 42.1 and 0% respectively. Over 15,806 metacercariae were obtained and stored at 4ºC. Four rabbits weighing 1.5 kg each were infected with 32-44 metacercariae and two with 200. Three rabbits begin to eliminate eggs of the parasite in the feces from 84 days after infection onwards. The biological cycle of F. hepatica in L. columella and the rabbit was completed within 124 days.
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We studied profile of patients (n=1782) treated in specialized centers and general practice (GP) enrolled in methadone maintenance treatment (MMT) programs during 2001 in the Swiss Canton of Vaud. We found that GPs treated the majority of patients (76%). Specialized centers treated a higher proportion of patients with uncontrolled intravenous use of cocaine and heroin, and prescribed neuroleptics as concomitant medication three times more frequently than GPs. Patients treated in specialized centers were more likely to undergo screening for HIV, HBV, HCV, and receive complete HBV immunization. In conclusion, specialized centers are more likely to treat severely addicted patients and patients with a poor global assessment (physical, psychiatric, and social).