Une carte multi-échelle est un ensemble de cartes à différentes échelles, dans lequel l’utilisateur peut naviguer via un géoportail. Chacune de ces cartes est préalablement construite par généralisation cartographique, processus qui adapte la représentation cartographique à une échelle donnée. Les changements de représentations qu’implique la généralisation entre deux cartes à différentes échelles sont susceptibles de perturber l’utilisateur, rendant sa navigation plus difficile. Nous proposons dans cette thèse d’ajouter des représentations intermédiaires dans une carte multi-échelle existante, pour créer une évolution plus fluide du contenu cartographique au fil des échelles. Alors que de solides connaissances théoriques existent pour la conception cartographique traditionnelle, on ne sait pas encore comment concevoir une carte multi-échelle efficace. Pour formaliser des connaissances à ce sujet, nous avons étudié un panel de seize cartes multi-échelles existantes. Nous avons analysé les systèmes de zoom utilisés ainsi que l’évolution des représentations cartographiques au fil des échelles, en particulier les changements de niveaux d’abstraction pour les objets bâtis et routiers. Nous avons aussi évalué la variation de complexité visuelle du contenu cartographique au fil des échelles, en utilisant des mesures de clutter visuel. Nous avons ainsi identifié les tendances générales en termes de représentations multi-échelles (comme l’application du standard WMTS), certains facteurs que nous considérons comme ayant une influence négative sur la navigation de l’utilisateur (comme l’utilisation d’une même carte à différentes échelles), ainsi que des pratiques intéressantes visant à la faciliter (comme les représentations mixtes). A partir de ces constats, nous avons formulé des hypothèses sur l’influence des variables de construction des représentations intermédiaires sur la fluidité de navigation. Nous avons construit un matériel de test à partir d’un extrait de la carte multi-échelle Scan Express de l’IGN, entre les cartes existant au 1 : 25k et au 1 : 100k. Nous avons ainsi produit quatre versions différentes de représentations intermédiaires entre ces deux cartes, implémentant nos différentes hypothèses. Cet exercice nous a permis de mieux cerner les verrous techniques que soulève la production de représentations intermédiaires. Nous avons enfin conduit un test utilisateurs contrôlé, en demandant à 15 participants de réaliser une tâche cartographique sur ces différentes cartes multi-échelles, pour évaluer la pertinence de nos hypothèses / A multi-scale map is a set of maps at different scales, displayed on mapping applications, in which users may navigate by zooming in or out. Each of these maps is produced beforehand by cartographic generalization, which aims to adapt the cartographic representation for a target scale. Due to generalization, the representation changes between maps at different scales may disturb the user during its navigation. We assume that adding intermediate representations in an existing multi-scale map may enable a smooth evolution of cartographic content across scales. While theoretical knowledge exists for traditional cartography, we still do not know how to design efficient multi-scale maps. To formalize knowledge on that subject, we studied sixteen existing multi-scale maps. We focused on the used zooming system (zoom levels and display scales) and on the evolution of cartographic representations across scales, in particular for building and road entities. We also analyzed the variation of visual complexity of the map content across scales, using visual clutter measures. We thus identified general trends in terms of multi-scale representation (i.e. use of WMTS standard), some potential disturbing factors (i.e. use of a same map at different scales), but also good practices which may ease the user navigation (i.e. mixed representations). Based on these findings, we made assumptions on the influence of intermediate representations design on user navigation. We built test material from an extract of the Scan Express multi-scale map of the French IGN, between the existing maps at 1:25k and 1:100k scales. We thus produced four different versions of intermediate representations between these two maps, implementing our different hypotheses. This way, we highlighted the technical issues that we faced when producing intermediate representations. Finally, we conducted a controlled user study, asking 15 participants to perform a cartographic task on these different multi-scale maps, to evaluate our hypotheses

Myofibroblast expansion is a critical event in the pathogenesis of liver fibrosis. The activation of hepatic stellate cells (HSC) to myofibroblast (MFB) results in the enhanced production of extracellular matrix (ECM). We have studied the effect of fibroblast growth factor 1 (FGF-1) on liver MFB. In the second part we investigated effect of transforming growth factor β1 (TGF-β1) and FGF-1 on cell line HSC-T6. Cells were cultured on plastic dishes and in 3D collagen gel mimicking fibrotic tissue. MFB were isolated by repeated passaging of nonparenchymal liver cell fraction. The transfer of MFB from plastic dishes to collagen gel resulted in the change in their shape and phenotype. The expression of cytokine TGF-β1 and of MFB markers, α-smooth muscle actin (α-SMA) and cellular fibronectin (EDA-FN) on protein level was significantly decreased in collagen gel. The experiments with SB 431542, the inhibitor of TGF-β receptor type I, showed that EDA-FN and α-SMA are differently regulated. EDA-FN expression is dependent on TGF-β1, while the expression of α-SMA is primarily determined by the environment and modified by TGF-β1. EDA-FN is more sensitive to the U0126, the inhibitor of protein kinases MEK 1 and 2. Collagen gel does not change the expression of metalloproteinase MMP-2 but activates the proenzyme....

The thesis research was designed to study the characteristics of two important physiological processes in smooth muscle: Ca2+ transport mediated by the plasmalemmal Ca2+-ATPase and muscarinic receptor-G protein interactions. In resting smooth muscle, several Ca2+ extrusion or sequestration processes offset the passive inward leak of Ca2+. Although biochemical evidence suggests that the plasmalemmal Ca2+ pump plays a key role in this process, the precise role of this enzyme could not be proven until a reliable estimate of the inward Ca2+ leak was measured. Recent studies using dispersed smooth muscle cells from the toad stomach provided an estimate of the basal transmembrane Ca2+ flux rate; thus, we examined the transport capacity of the plasmalemmal Ca2+pump in this tissue. Gastric smooth muscle tissue was disrupted by homogenization and nitrogen cavitation. Membranes enriched 20 fold for plasma membrane markers were obtained using differential centrifugation and purification by flotation on discontinuous sucrose gradients. The membrane vesicles exhibited an ATP-dependent 45Ca uptake that was insensitive to azide or oxalate but sensitive to stimulation by calmodulin or inhibition by orthovanadate and the calmodulin antagonists trifluoperazine (TFP) or calmidazolium (CMZ). 45Ca accumulated in the presence of ATP was rapidly released by Ca2+ ionophore but not by agents that stimulate Ca2+ release from the sarcoplasmic rettculum (caffeine, inositol trisphosphate, GTP). However, both CMZ and TFP evoked a Ca2+ release that was comparable to that observed in the presence of Ca2+ ionophore, suggesting that these compounds have profound effects on membrane Ca2+permeability. 45Ca transport exhibited a high affinity for Ca2+ (KD 0.2 μM) and a high transport capacity, producing a > 12,000-fold gradient for Ca2+and a transmembrane flux rate at least 3-fold greater than that observed in resting smooth muscle cells. As a first step toward understanding the biochemical basis for the diversity of muscarinic cholinergic actions on smooth muscle, we examined the distribution of muscarinic receptor subtypes and coupling to guantne nucleotide-binding (G) proteins in airway and gastric smooth muscle. Receptor subtypes were classified in membranes prepared from bovine trachea and toad stomach based on the relative abilities of the selective antagonists pirenzepine (M1), AF-DX 116 (M2) and 4-DAMP (M3) to displace the binding of nonselective antagonist [3H]QNB (quinuclidinyl benzilate). Based on the binding profiles for these antagonists, it was concluded that both smooth muscle types contain a mixture of M2 and M3 subtypes. In trachea the majority of receptors (86%) were M2, whereas in stomach the majority of receptors (88%) were M3. The displacement of [3H]QNB binding by the agonist oxotremorine indicated a mixed population of high affinity (KD = 4 nM) and low affinity (KD = 2-4 μM) binding sites. The addition of GTPγS abolished all high affinity agonist binding, suggesting that coupling of the receptors to G proteins may confer high affinity. Reaction of membranes with pertussis toxin in the presence of [32P]NAD caused the [32P]-labelling of a ~ 41 kD protein in both gastric and tracheal smooth musc1e. Pretreatment of the membranes with pertussis toxin and NAD completely abolished high affinity agonist binding in gastric smooth muscle, but produced little if any decrease in high affinity agonist binding in trachea. We conclude that, although muscarinic receptor activation leads to the elevation of intracellular Ca2+ and to contraction of both airway and gastric smooth muscle, the dissimilar distributions of receptor subtypes and distinct patterns of coupling to G proteins may indicate that each smooth muscle type uses different receptor-G protein interactions to regulate intracellular signalling pathways.

No description available.

Solanum asterophorum is a shrub popularly known as "jurubeba-de-fogo . In Brazil, is distributed in the states of Paraíba and Bahia and its roots are popularly used in the treatment of liver diseases. Several species of Solanum are used in folk medicine to treat diarrhea. Oliveira et al. (2006a) showed that the methanol extract from the leaves of S. asterophorum (Sast-MeOHF) has antispasmodic effect in guinea-pig ileum. Therefore, the objective of this study was to investigate and to compare a possible toxic effect and antispasmodic in guinea-pig ileum of the methanol extract obtained from roots of this species (Sast-MeOHR) in guinea-pig ileum, beyond to evaluate the antidiarrhoeal activity of both extracts in mice. Sast- MeOHR (500 mg/mL) induced low hemolytic activity (Emax = 5.2 ± 1.2%). In guineapig ileum, Sast-MeOHR antagonized the phasic contractions induced by 10-6 M carbachol (IC50 = 48.1 ± 8.7 mg/mL) and histamine (IC50 = 105.0 ± 16.2 mg/mL) in a significant and concentration-dependent manner, being Sast-MeOHR 2 times more potent against the carbachol. Sast-MeOHR also presented concentrationdependent spasmogenic effect (EC50 = 137.1 ± 2.8 mg/mL) when applied on the basal tone, which was inhibited in the presence of atropine, a nonselective muscarinic antagonist. Sast-MeOHR inhibited the cumulative curves to carbachol (CCh) and these were shifted to the right of a non-parallel with a reduction in Emax, suggesting a non-competitive antagonism, and relax in a significant and concentration-dependent manner the guinea-pig ileum pre-contracted with 40 mM KCl (EC50 = 52.9 ± 11.5 mg/mL) and with 10-6 M carbachol (EC50 = 20.1 ± 8.6 mg/mL) or histamine (EC50 = 79, 0 ± 15.0 mg/mL), suggestive of the blockade Ca2+ influx through the Cav. Sast-MeOHR antagonized the CaCl2-induced contractions in depolarizing medium nominally without Ca2+ only at concentrations of 500 and 750 mg/mL, suggesting a blockage of the indirect Cav. The fact that the relaxation curve of Sast-MeOHR in guinea-pig ileum pre-contracted with carbachol (EC50 = 20.1 ± 8.6 mg/mL) have been displaced in the presence of 5 mM CsCl, a potassium channels non-selective blocker (EC50 = 92.8 ± 46.1 mg/mL), suggests activation of these channels. In vivo experiments demonstrated a lack of acute toxicity to the dose of 2 g/kg vo and 5 g/kg for i.p to Sast-MeOHR. Besides Sast-MeOHR present an inhibition on both frequency of defecation (ED50 = 309.6 ± 28.5 mg/kg) as liquid stools (ED50 = 152.1 ± 32.5 mg/kg) in a significant and dose-dependent manner. In contrast, Sast-MeOHF presents significant inhibitory effect on the frequency of defecation only in doses of 500 and 750 mg/kg (48.7 ± 7.4 and 42.3 ± 9.8%, respectively). In relation to liquid stools, the Sast-MeOHF showed significant (ED50 = 268.4 ± 35.2 mg/kg) and dose-dependent inhibition, being Sast-MeOHR 2 times more potent to inhibit diarrhea. Both extracts (until 500 mg/kg) did not inhibit intestinal transit. In contrast, both inhibited in a significant and dose-dependent manner, the contents of intestinal fluid induced by castor oil, being Sast-MeOHR (ED50 = 38.3 ± 10.4 mg/kg) 2 times more potent than Sast-MeOHF (ED50 = 78.6 ± 6.4 mg/kg). Suggest that the antidiarrhoeal effect of Sast-MeOHR and Sast-MeOHF involves changes in intestinal secretion, however other studies must be carried out to elucidate the mechanisms involved in these activity. Thus, the extract obtained from the roots was more potent both in vitro experiments and in vivo, suggesting that the active principles with antispasmodic and antidiarrheal action may be more concentrated in roots. / Fundação de Amparo a Pesquisa do Estado de Alagoas / Solanum asterophorum é uma espécie arbustiva, conhecida popularmente por jurubeba-de-fogo . No Brasil, encontra-se distribuída nos estados da Paraíba e Bahia, e suas raízes são utilizadas para problemas hepáticos. Várias espécies de Solanum são utilizadas na medicina popular para tratar diarréia. Oliveira et al. (2006a) demonstrou que o extrato metanólico obtido das folhas de S. asterophorum (Sast-MeOHF) apresenta efeito antiespasmódico em íleo de cobaia. Com isso, o objetivo desse estudo foi investigar e comparar um possível efeito tóxico e antiespasmódico do extrato metanólico obtido das raízes desta espécie (Sast-MeOHR) em íleo de cobaia, além de avaliar a atividade antidiarréica de ambos os extratos em camundongos. Sast-MeOHR (500 Vg/mL) induziu uma baixa atividade hemolítica (Emax = 5,2 ± 1,2%). Em íleo de cobaia, Sast-MeOHR antagonizou as contrações fásicas induzidas por 10-6 M de CCh (CI50 = 48,1 ± 8,7 Vg/mL) e de histamina (CI50 = 105,0 ± 16,2 Vg/mL) de maneira significante e dependente de concentração, sendo o Sast-MeOHR 2 vezes mais potente frente ao carbacol. Sast-MeOHR também apresentou efeito espasmogênico dependente de concentração (CE50 = 137,1 ± 2,8 Vg/mL) quando aplicado sobre o tônus basal, que foi inibido na presença de atropina, um antagonista muscarínico não-seletivo. Sast-MeOHR inibiu as curvas cumulativas ao CCh e estas foram desviadas para a direita de forma não paralela com redução do Emax, sugerindo um antagonismo não competitivo, além de relaxar de maneira significante e dependente de concentração o íleo de cobaia pré-contraído com 40 mM de KCl (CE50 = 52,9 ± 11,5 Vg/mL) e com 10-6 M de carbacol (CE50 = 20,1 ± 8,6 Vg/mL) ou de histamina (CE50 = 79,0 ± 15,0 Vg/mL), sugestivo do bloqueio do influxo de Ca2+ através dos canais de cálcio operados por voltagem (CaV). Sast-MeOHR antagonizou as contrações induzidas por CaCl2 em meio despolarizante nominalmente sem Ca2+ apenas nas concentrações de 500 e 750 Vg/mL, sugerindo um bloqueio indireto dos Cav. O fato da curva de relaxamento do Sast-MeOHR em íleo de cobaia pré-contraído com carbacol ter sido deslocada por 5 mM de CsCl, um bloqueador não seletivo dos canais de potássio (CE50 = 92,8 ± 46,1 Vg/mL), sugere ativação destes canais. Nos experimentos in vivo, foi demonstrada ausência de toxicidade aguda até a dose de 2 g/kg v.o. e 5 g/kg i.p para Sast-MeOHR. Além do Sast-MeOHR apresentar uma inibição tanto em relação à frequência de defecação (DE50 = 309,6 ± 28,5 mg/kg) como em relação as fezes líquidas (DE50 = 152,1 ± 32,5 mg/kg) de forma significante e dependente de dose. Diferentemente, Sast-MeOHF apresentou efeito inibitório significante sobre a frequência de defecação apenas nas doses de 500 e 750 mg/kg (48,7 ± 7,4 e 42,3 ± 9,8%, respectivamente). Já em relação a fezes líquidas, Sast-MeOHF apresentou inibição significante (DE50 = 268,4 ± 35,2 mg/kg) e dependente de dose. Sendo o Sast-MeOHR duas vezes mais potente que Sast-MeOHF em inibir a diarréia. Ambos os extratos (até 500 mg/kg) não inibiram o trânsito intestinal. Diferentemente, ambos extratos inibiram de maneira significante e dependente da dose o conteúdo de fluido intestinal induzido por óleo de rícino, sendo o Sast-MeOHR (DE50 = 38,3 ± 10,4 mg/kg) duas vezes mais potente que Sast-MeOHF (DE50 = 78,6 ± 6,4 mg/kg). Sugestivo de que o efeito antidiarréico do Sast-MeOHR e do Sast-MeOHF envolve alterações na secreção intestinal, entretanto outros estudos são necessários para elucidar o mecanismo de ação envolvido nesta atividade. Com isso, o extrato obtido das raízes se mostrou mais potente tanto nos experimentos in vitro como in vivo, sugerindo que os princípios ativos com ação antidiarréica e antiespasmódica podem estar mais concentrados nas raízes.

O objetivo do presente trabalho é avaliar através de métodos quantitativos e qualitativos, as alterações nos corpos cavernosos de indivíduos com priapismo isquêmico. Foram estudados fragmentos de corpos cavernosos obtidos por biópsia de sete pacientes com, pelo menos, 48 horas de priapismo isquêmico, com idade entre 27 e 44 anos (média de 38 anos). Os pacientes foram submetidos a tratamento cirúrgico pela técnica de Al-ghorab. O material foi submetido a técnicas histoquímicas e imunohistoquímicas para a caracterização e quantificação do músculo liso e dos elementos fibrosos do tecido conjuntivo. A análise do corpo cavernoso dos pacientes com priapismo e do grupo controle, mostrou os seguintes resultados: Colágeno: controle = 34.76 4.64, priapismo = 39.64 2.91 (p = 0.0019); sistema elástico: controle 28.10 2.85, priapismo 36.10 3.06 (p = 0.0012) fibras musculares: controle = 43.37 4.96, priapismo = 26.48 5.00 (p < 0.0001). Ficou caracterizado aumento estatisticamente significativo dos elementos fibrosos do tecido conjuntivo e diminuição significativa nas fibras musculares lisas do corpo cavernoso dos pacientes com priapismo isquêmico. O presente estudo mostrou que o priapismo isquêmico está associado a alterações significativas nos componentes da matriz extracelular e na musculatura lisa do corpo cavernoso. Esses resultados poderiam explicar a disfunção erétil que acompanha os pacientes com priapismo isquêmico. / The purpose of the present study was to evaluate through quantitative and qualitative methods, the changes in the corpora cavernosa of patients with ischemic priapism. We obtained samples of corpora cavernosa from 7 patients with ischemic priapism, aged between 28 and 44 years (mean = 38), who underwent a cavernosal-glandular shunt. The control tissues were fragments of corpora cavernosa obtained from autopsies of 7 age-matched men who died of causes not related to the urogenital tract. Histochemical and immunohistochemical techniques were used to assess and quantify the extra-cellular matrix and smooth muscle fibers. The volumetric density of smooth muscle, elastic fibers and collagen were determined in corpora cavernosa. The stereological analysis showed the following values of volumetric density in the structures studied. Collagen: controls = 34.76 4.64, priapism = 39.64 2.91 (p = 0.0019); elastic system fibers: controls 28.10 2.85, priapism 36.10 3.06 (p = 0.0012), smooth muscle fibers: controls = 43.37 4.96, priapism = 26.48 5.00 (p < 0.0001). Our results demonstrated a significant increase in the fibrous elements of the connective tissue and a significant decrease of smooth muscle fibers in the corpora cavernosa of patients with ischemic priapism, when compared to controls. As conclusion, this study showed that ischemic priapism is associated with early significant changes in the components of the extra cellular matrix and smooth muscle fibers of corpora cavernosa. This could explain the frequent occurrence of erectile dysfunction found in patients with ischemic priapism.

Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease remain unresolved. In particular, it is not known if all VSMCs proliferate and display plasticity, or whether individual cells can switch to multiple phenotypes. To assess whether proliferation and plasticity in disease is a general characteristic of VSMCs or a feature of a subset of cells, multi-colour lineage labelling is used to demonstrate that VSMCs in injury-induced neointimal lesions and in atherosclerotic plaques are oligo-clonal, derived from few expanding cells, within mice. Lineage tracing also revealed that the progeny of individual VSMCs contribute to both alpha Smooth muscle actin (aSma)-positive fibrous cap and Mac-3-expressing macrophage-like plaque core cells. Co-staining for phenotypic markers further identified a double-positive aSma+ Mac3+ cell population, which is specific to VSMC-derived plaque cells. In contrast, VSMC-derived cells generating the neointima after vascular injury generally retained expression of VSMC markers and upregulation of Mac3 was less pronounced. Monochromatic regions in atherosclerotic plaques and injury-induced neointima did not contain VSMC-derived cells expressing a different fluorescent reporter protein, suggesting that proliferation-independent VSMC migration does not make a major contribution to VSMC accumulation in vascular disease. Similarly, VSMC proliferation was examined in an Angiotensin II perfusion model of aortic aneurysm in mice, oligo-clonal proliferation was observed in remodelling regions of the vasculature, however phenotypic changes were observed in a large proportion of VSMCs, suggesting that the majority of VSMCs have some potential to modulate their phenotype. To understand the mechanisms behind the inherent VSMC heterogeneity and observed functionality, the single cell transcriptomic techniques Smart-seq2 and the Chromium 10X system were optimized for use on VSMCs. The work within this thesis suggests that extensive proliferation of a low proportion of highly plastic VSMCs results in the observed VSMC accumulation after injury, and the atherosclerotic and aortic aneurysm models of cardiovascular disease.

Existe uma grande e crescente literatura sobre especificação e estimação de fronteiras de produção e, portanto, de eficiência de unidades produtivas. Nesta tese, o foco esta sobre modelos de fronteiras determinísticas, os quais são baseados na hipótese de que os dados observados pertencem ao conjunto tecnológico. Dentre os modelos estatísticos e estimadores para fronteiras determinísticas existentes, uma abordagem promissora e a adotada por Martins-Filho e Yao (2007). Esses autores propõem um procedimento de estimação composto por três estágios. Esse estimador e de fácil implementação, visto que envolve procedimentos não-paramétricos bem conhecidos. Além disso, o estimador possui características desejáveis vis-à-vis estimadores para fronteiras determinísticas tradicionais como DEA e FDH. Nesta tese, três artigos, que melhoram o modelo proposto por Martins-Filho e Yao (2007), sao propostos. No primeiro artigo, o procedimento de estimação desses autores e melhorado a partir de uma variação do estimador exponencial local, proposto por Ziegelmann (2002). Demonstra-se que estimador proposto a consistente e assintoticamente normal. Além disso, devido ao estimador exponencial local, estimativas potencialmente negativas para a função de variância condicional, que poderiam prejudicar a aplicabilidade do estimador proposto por Martins-Filho e Yao, são evitadas. No segundo artigo, e proposto um método original para estimação de fronteiras de produção em apenas dois estágios. E mostrado que se pode eliminar o segundo estágio proposto por Martins-Filho e Yao, assim como, eliminar o segundo estagio proposto no primeiro artigo desta tese. Em ambos os casos, a estimação do mesmo modelo de fronteira de produção requer três estágios, sendo versões diferentes para o segundo estagio. As propriedades assintóticas do estimador proposto são analisadas, mostrando-se consistência e normalidade assintótica sob hipóteses razoáveis. No terceiro artigo, a proposta uma variação semi-paramétrica do modelo estudado no segundo artigo. Reescreve-se aquele modelo de modo que se possa estimar a fronteira de produção e a eficiência de unidades produtivas no contexto de múltiplos insumos, sem incorrer no curse of dimensionality. A abordagem adotada coloca o modelo na estrutura de modelos aditivos, a partir de hipóteses sobre como os insumos se combinam no processo produtivo. Em particular, considera-se aqui os casos de insumos aditivos e insumos multiplicativos, os quais são amplamente considerados em teoria econômica e aplicações. Estudos de Monte Carlo são apresentados em todos os artigos, afim de elucidar as propriedades dos estimadores propostos em amostras finitas. Além disso, estudos com dados reais são apresentados em todos os artigos, nos quais são estimador rankings de eficiência para uma amostra de departamentos policiais dos EUA, a partir de dados sobre criminalidade daquele país. / There exists a large and growing literature on the specification and estimation of production frontiers and therefore efficiency of production units. In this thesis we focus on deterministic production frontier models, which are based on the assumption that all observed data lie in the technological set. Among the existing statistical models and estimators for deterministic frontiers, a promising approach is that of Martins-Filho and Yao (2007). They propose an estimation procedure that consists of three stages. Their estimator is fairly easy to implement as it involves standard nonparametric procedures. In addition, it has a number of desirable characteristics vis-a-vis traditional deterministic frontier estimators as DEA and FDH. In this thesis we propose three papers that improve the model proposed in Martins-Filho and Yao (2007). In the first paper we improve their estimation procedure by adopting a variant of the local exponential smoothing proposed in Ziegelmann (2002). Our estimator is shown to be consistent and asymptotically normal. In addition, due to local exponential smoothing, potential negativity of conditional variance functions that may hinder the use of Martins-Filho and Yao's estimator is avoided. In the second paper we propose a novel method for estimating production frontiers in only two stages. (Continue). There we show that we can eliminate the second stage of Martins-Filho and Yao as well as of our first paper, where estimation of the same frontier model requires three stages under different versions for the second stage. We study asymptotic properties showing consistency andNirtnin, asymptotic normality of our proposed estimator under standard assumptions. In the third paper we propose a semiparametric variation of the frontier model studied in the second paper. We rewrite that model allowing for estimating the production frontier and efficiency of production units in a multiple input context without suffering the curse of dimensionality. Our approach places that model within the framework of additive models based on assumptions regarding the way inputs combine in production. In particular, we consider the cases of additive and multiplicative inputs, which are widely considered in economic theory and applications. Monte Carlo studies are performed in all papers to shed light on the finite sample properties of the proposed estimators. Furthermore a real data study is carried out in all papers, from which we rank efficiency within a sample of USA Law Enforcement agencies using USA crime data.

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Existe uma grande e crescente literatura sobre especificação e estimação de fronteiras de produção e, portanto, de eficiência de unidades produtivas. Nesta tese, o foco esta sobre modelos de fronteiras determinísticas, os quais são baseados na hipótese de que os dados observados pertencem ao conjunto tecnológico. Dentre os modelos estatísticos e estimadores para fronteiras determinísticas existentes, uma abordagem promissora e a adotada por Martins-Filho e Yao (2007). Esses autores propõem um procedimento de estimação composto por três estágios. Esse estimador e de fácil implementação, visto que envolve procedimentos não-paramétricos bem conhecidos. Além disso, o estimador possui características desejáveis vis-à-vis estimadores para fronteiras determinísticas tradicionais como DEA e FDH. Nesta tese, três artigos, que melhoram o modelo proposto por Martins-Filho e Yao (2007), sao propostos. No primeiro artigo, o procedimento de estimação desses autores e melhorado a partir de uma variação do estimador exponencial local, proposto por Ziegelmann (2002). Demonstra-se que estimador proposto a consistente e assintoticamente normal. Além disso, devido ao estimador exponencial local, estimativas potencialmente negativas para a função de variância condicional, que poderiam prejudicar a aplicabilidade do estimador proposto por Martins-Filho e Yao, são evitadas. No segundo artigo, e proposto um método original para estimação de fronteiras de produção em apenas dois estágios. E mostrado que se pode eliminar o segundo estágio proposto por Martins-Filho e Yao, assim como, eliminar o segundo estagio proposto no primeiro artigo desta tese. Em ambos os casos, a estimação do mesmo modelo de fronteira de produção requer três estágios, sendo versões diferentes para o segundo estagio. As propriedades assintóticas do estimador proposto são analisadas, mostrando-se consistência e normalidade assintótica sob hipóteses razoáveis. No terceiro artigo, a proposta uma variação semi-paramétrica do modelo estudado no segundo artigo. Reescreve-se aquele modelo de modo que se possa estimar a fronteira de produção e a eficiência de unidades produtivas no contexto de múltiplos insumos, sem incorrer no curse of dimensionality. A abordagem adotada coloca o modelo na estrutura de modelos aditivos, a partir de hipóteses sobre como os insumos se combinam no processo produtivo. Em particular, considera-se aqui os casos de insumos aditivos e insumos multiplicativos, os quais são amplamente considerados em teoria econômica e aplicações. Estudos de Monte Carlo são apresentados em todos os artigos, afim de elucidar as propriedades dos estimadores propostos em amostras finitas. Além disso, estudos com dados reais são apresentados em todos os artigos, nos quais são estimador rankings de eficiência para uma amostra de departamentos policiais dos EUA, a partir de dados sobre criminalidade daquele país. / There exists a large and growing literature on the specification and estimation of production frontiers and therefore efficiency of production units. In this thesis we focus on deterministic production frontier models, which are based on the assumption that all observed data lie in the technological set. Among the existing statistical models and estimators for deterministic frontiers, a promising approach is that of Martins-Filho and Yao (2007). They propose an estimation procedure that consists of three stages. Their estimator is fairly easy to implement as it involves standard nonparametric procedures. In addition, it has a number of desirable characteristics vis-a-vis traditional deterministic frontier estimators as DEA and FDH. In this thesis we propose three papers that improve the model proposed in Martins-Filho and Yao (2007). In the first paper we improve their estimation procedure by adopting a variant of the local exponential smoothing proposed in Ziegelmann (2002). Our estimator is shown to be consistent and asymptotically normal. In addition, due to local exponential smoothing, potential negativity of conditional variance functions that may hinder the use of Martins-Filho and Yao's estimator is avoided. In the second paper we propose a novel method for estimating production frontiers in only two stages. (Continue). There we show that we can eliminate the second stage of Martins-Filho and Yao as well as of our first paper, where estimation of the same frontier model requires three stages under different versions for the second stage. We study asymptotic properties showing consistency andNirtnin, asymptotic normality of our proposed estimator under standard assumptions. In the third paper we propose a semiparametric variation of the frontier model studied in the second paper. We rewrite that model allowing for estimating the production frontier and efficiency of production units in a multiple input context without suffering the curse of dimensionality. Our approach places that model within the framework of additive models based on assumptions regarding the way inputs combine in production. In particular, we consider the cases of additive and multiplicative inputs, which are widely considered in economic theory and applications. Monte Carlo studies are performed in all papers to shed light on the finite sample properties of the proposed estimators. Furthermore a real data study is carried out in all papers, from which we rank efficiency within a sample of USA Law Enforcement agencies using USA crime data.