Esta tesis analiza temas de distribución de la renta y desarrollo económico en economías caracterizadas por imperfecciones en el mercado de capitales.El primer capitulo estudia temas de distribución de la renta. La mayoría de la literatura en ese campo a sido desarrollada bajo el supuesto que IMC (esto es imperfecciones en el mercado de capitales) son exógenas. La teoría convencional es que es muy poco probable que los individuos mas pobres puedan invertir porque tomar dinero a préstamo es muy caro en presencia de asimetrías informativas. Consecuentemente, los individuos más pobres no invertirán y sus futuras generaciones permanecerán pobres. Basado en esta línea de pensamiento esta literatura concluye que IMC exógenas producen mayor desigualdad y menor movilidad intergeneracional. Contrariamente as estos análisis este artículo argumenta que cuando las IMC se endogenizan la movilidad intergeneracional aumentará entre los pobres e inteligentes individuos. En mi modelo existe un problema de selección adversa entre el prestamista y el prestatario, pues los bancos no saben la habilidad del prestatario. En este contexto los bancos ofrecen un menú de contratos que satisface la condición de auto-selección. En equilibrio bancos diferencian entre agentes forzando a los más inteligentes a invertir en educación más de lo óptimo. De esta forma el agente menos inteligente no se hace pasar por el agente más inteligente. Estos últimos obtienen más educación de la que ellos desean, aumentando movilidad intergeneracional y la acumulación de capital humano, que son mayores que en el mundo con información perfecta.Los resultados más importantes de este paper son los siguientes: cuando se endogenizan las imperfecciones del mercado de capitales obtenemos que IMC aumentan movilidad intergeneracional y aumenta el número de gente educados en el estado estacionario. Al estudiar desigualdad en renta, yo encuentro que los resultados son ambiguos. Por un lado el número de gente con rentas muy bajas ha disminuido. Por otro lado la clase media de prestatarios inteligentes tienen una renta menor.Una de las cuestiones más importantes que se hacen los economistas es porqué países pobres usan sus recursos de forma ineficiente. En el segundo capítulo nosotros (Andrés Erosa y yo) proponemos una teoría donde IMC son el origen de las diferencias en TFP entre países. En nuestra teoría los empresarios tienen información privada sobre la productividad de su tecnología. Nosotros estudiamos cómo el contrato, descrito como la habilidad de hacer respetar el contrato, afecta la provisión de incentivos, y por tanto, y de repartir los recursos entre los empresarios. Nosotros estudiamos un modelo de crecimiento donde los empresarios están dotados de una tecnología para producir un bien intermedio que es el input de la producción final de bienes. Los empresarios necesitan financiación externa para producir. Esta financiación externa está limitada por dos problemas: Primero, la productividad no es observable para los prestamistas. Segundo, los empresarios pueden pagar, como máximo, una fracción de la producción. Asumimos que los países difieren en su capacidad de hacer respetar los contratos. Demostramos que, en la presencia de asimetrías de información, países con baja capacidad de hacer respetar los contratos utilizan tecnologías ineficientes en equilibrio y es caracterizada por diferencias en productividad entre países. Nuestra teoría sugiere que los empresarios tienen intereses en mantener en status quo con baja capacidad de hacer cumplir los contratos y esto hace posible que los empresarios extraigan rentas de los servicios que contratan. Nuestra teoría tiene implicaciones sobre la distribución de los recursos entre sectores. En fin nuestra teoría implica que la tasa de impuestos sobre la renta puede ser mala para la actividad económica sobre todo cuando los mercados de capitales son imperfectos. / This dissertation analyzes income distribution and economic development issues in macroeconomies with financial frictions. Chapter 1 focuses on income distribution issues. Most of the existing literature in this area has been developed under the assumption that CMI are exogenous. Their conventional view is that since becoming borrower is expensive under high imperfections in the capital markets, poor agents are less likely to make investment decisions. As a consequence their future generations will remain poor. Based on this thought these branch of the literature conclude that exogenous CMI lead to higher inequality and lower mobility. In contrast to these analyses this paper argues that when we endogenize CMI, intergenerational mobility may be promoted among poor and talented agents. In my model there is an adverse selection problem between borrowers and banks, since banks cannot identify borrowers' ability. In this context banks offer a menu of contracts that satisfy the self-selection mechanism. In equilibrium banks differentiate between agents by forcing talented borrowers to make an investment in human capital larger than they would in the first best world. In this way low ability individuals do not pose as high ability ones. Talented children from poor families get educated even more than they wish, so that both income mobility and human capital accumulation are larger than in the first best world. The major results of this paper might be summarized as follows: when we endogenize imperfections in the capital market we obtain that CMI promotes intergenerational mobility and increases the number of educated people in the steady state. When we study inequality of wealth, we find that there are opposite effects making inequality unambiguos. On the one hand there is a small number of people in the lower bound of the wealth distribution. On the other hand the middle class of clever borrowers have a lower wealth. One of the most important research questions faced by economist is why poor countries use productive resources inefficiently. In the second chapter of the thesis we propose a theory where capital market imperfections are at the origin of cross-country TFP differences. In our theory entrepreneurs have private information about the multifactor productivity of their technology. We study how the contracting environment, as described by the ability to enforce contracts, affects the provision of incentives and, thus, resource allocation to and across entrepreneurs. We develop a growth model where entrepreneurs are endowed with a technology to produce an intermediate good that is an input in the production of final goods. Entrepreneurs need external funds in order to operate their technology. External financing is complicated by two problems: First, the productivity of the entrepreneurial technology can not be observed by lenders. Second, entrepreneurs can commit to pay, at most, a fraction of the output. We assume that countries differ in the ability to enforce loans contracts. We show that, in the presence of asymmetric information, countries with low enforcement use inefficient technologies in equilibrium and are characterized by differences in productivity across industries. Our theory also suggests that entrepreneurs have a vested interest in maintaining a status quo with low enforcement since it allows them to extract rents from the factor services they hire. Our theory has implications for the allocation of resources across industries that differ in their needs of external funds and provide some insights into why poor countries face large differences in productivity across sectors. Our theory also implies that income taxation can be more detrimental for economic activity when capital markets are imperfect.

El objetivo principal de la investigación emprendida en la presente tesis doctoral es elaborar una técnica de construcción de un indicador económico compuesto o un conjunto de dichos indicadores que, correspondiendo al concepto teorético del ciclo económico (comercial), permitirán detectar y predecir los puntos de giro del ciclo económico.Como el punto de partida hemos escogido la definición del ciclo económico propuesta por Burns y Mitchell (1946). Según nuestra opinión, el analisis dinámico factorial es el método idóneo para captar los puntos de giro del ciclo económico en el sentido de Burns y Mitchell. Por un lado, tiene en cuenta los movimientos comunes de varias series macroeconómicas que bajan y suben simultaneamente durante las fases de recesiones y expansiones, respectivamente. Por otro lado, refleja las asimetrías que existen entre las dos fases cíclicas, como, por ejemplo, las tasas de crecimiento y la volatilidad distintas durante las recesiones y expansiones. Ambos rasgos estan subrayados por Burns y Mitchell como características definitivas del ciclo económico.El análisis dinámico factorial en su estado actual exige sin duda ciertas modificaciones y algunas extensiones para obtener las estimaciones insesgadas y consistentes de los indicadores económicos compuestos y para utilizar la información disponible de la mejor manera posible.Nuestra investigación está dirigida, en primer lugar, hacia los economistas prácticos que han optado por utilizar el análisis dinámico factorial para la construcción del indicador del ciclo económico tanto a nivél regional como nacional.La tesis esta compuesta por cinco capítulos donde el primer y el último capítulos son, respectivamente, la introducción y la conclusión. En ellos se exponen los objetivos del estudio y los resultados alcanzados en el curso de la investigación.En el capítulo dos describimos varios metodos de análisis de las fluctuaciones económicas que han sido propuestos durante los últimos 20 años. Por un lado, consideramos los modelos con la dinámica nolineal, concretamente el cambio de regímenes o el Markov switching. Por otro lado, examinamos los modelos lineales del análisis dinámico factorial. Al final del capítulo analizamos el modelo del factor común latente con la dinámica nolineal (con cambios de regímenes) que está construido como una combinación de estos dos metodos principales.En el capítulo tres introducimos un modelo general dinámico multifactorial con la dinámica lineal y nolineal. Este modelo permite captar la dimensión intertemporal (indicador avanzado versus indicador coincidente) de los factores comunes inobservables. Se examinan dos modelos dinámicos alternativos con un factor común inobservable avanzado y un factor común inobservable coincidente. En el primer modelo el factor común coincidente esta influido por el factor común avanzado a través del mecanismo de causalidad de Granger. Mientras que en el segundo modelo los dos factores estan relacionados via la matríz de las probabilidades de transición. Debido a que el factor avanzado contiene información sobre los cambios futuros de las fases cíclicas, ambos modelos permiten hacer predicciones de los puntos de giro del ciclo económico.En el capítulo cuatro elaboramos las técnicas sumplementarias necesarias para resolver algunos problemas de datos que son bastante frecuentes en la actividad de un economista empírico. Los dos problemas más importantes son los cambios estructurales y la falta de observaciones, particularmente cuando los datos que estan disponibles con distintas frecuencias (por ejemplo: los datos mensuales y trimestrales). Estos problemas quiebran la continuidad de la serie temporal y reducen el número de observaciones válidas para el análisis estadístico. Se demuestra que estos problemas se resuelven modificando el modelo de análisis dinámico factorial, con lo que se obtienen estimaciones más eficientes de los parametros del modelo. / The main objective of our research undertaken in this thesis is to elaborate a technique of constructing a composite economic indicator or a set of such indicators which would correspond to the theoretical concept of business cycle and reflect a phenomenon which may be interpreted as the cyclical dynamics of the economy.As a point of departure we have chosen the definition of business cycle proposed by Burns and Mitchell (1946). We believe that the most appropriate method to capture the Burns and Mitchell's cycle would be the dynamic factor analysis.The dynamic factor analysis in its current state requires undoubtedly some refinements and extensions to obtain unbiased and consistent estimates of the composite economic indicators and to use the available information in the best possible way.Our research is mostly oriented towards the practitioners who have opted for using the dynamic factor approach in the construction of the business cycle indicator both at the regional and national levels.The thesis is comprised of five chapters where the first and the last chapters are the introduction and conclusion delineating the objectives of the study and summarizing the results achieved during research.Chapter two describes various approaches to the analysis of economic fluctuations proposed during the last 20 years. On the one hand, it concentrates on models with nonlinear, namely Markov-switching, dynamics, on the other hand, it is concerned with dynamic factor models. Finally, it shows the combined techniques which unify these two principal approaches, thus, modeling common latent factor with regime-switching dynamics.In chapter three we introduce a general multifactor dynamic model with linear and regime-switching dynamics. This model allows capturing the intertemporal (leading versus coincident) dimension of the latent common factors. Two alternative multifactor dynamic models with a leading and a coincident unobserved common factors are examined: a model where the common coincident factor is Granger-caused by the common leading factor and a model where the leading relationship is translated into a set of specific restrictions imposed on the transition probabilities matrix.Chapter four concentrates on the supplementary devices which allow to overcome some data problems which are very frequent in the practitioner's life. Among the most prominent are the structural breaks and missing observations. It is shown that some of these troubles can be coped with by modifying the dynamic common factors models, which leads to more efficient estimates of the parameters of the models.

En este trabajo de tesis hemos identificado la presencia de marcadores polimórficos dentro del gen F8 que han permitido identificar el alelo portador de la mutación en el 91% de las mujeres portadoras de hemofilia A en estudio en nuestro laboratorio. Además, hemos descrito 31 mutaciones nuevas responsables de la HA, de las cuales, 20 fueron mutaciones missense. El análisis estructural de dichas mutaciones proporciona un mejor entendimiento de la enfermedad, además ha permitido predecir el impacto que dichos cambios ocasionan en la estructura de la proteína, así como las consecuencias funcionales de las mutaciones en dicho gen, sugiriendo nuevas áreas del FVIIIa involucradas en la unión a otras macromoléculas, tales como el FIXa y el sustrato del complejo Xasa, el FXa. Por otro lado, demostramos que el uso de nuevas técnicas de cuantificación de dosis génica como la PCR a tiempo real y el MLPA junto con el estudio indirecto por marcadores son una buena herramienta para la detección de mutaciones como las deleciones y duplicaciones de uno o más exones del gen F8, en varones y mujeres portadoras de HA que con la PCR cualitativa no era posible detectar. Y por último, proponemos un algoritmo de trabajo práctico de análisis para optimizar el diagnóstico molecular de pacientes con HA y las portadoras de su familia.

In response to growing concerns about the negative impact of GHG emissions, several countries such as the European Union have adopted a cap-and-trade policy to limit the overall emissions levels. Alternatively, other countries including Argentina, Canada, the United Kingdom, and United States have proposed an intensity-based cap-and-trade system that targets emission intensities, measured in emissions per dollars or unit of output. Arguably,intensity regulations can accommodate future economic growth, reduce cost uncertainty, engage developing countries in international efforts to mitigate climate change, and provide incentives to improve energy efficiency and to use less carbon-intensive fuels. This work models and studies a carbon tax scheme where policy makers set a target emission factor, which is used as an intensity measure, for a specific industry and tax firms if they exceed that limit. The policy aims to promote energy efficiency, alleviate the impact on low emitters, and allow high emitters some flexibility to comply. We examine the effectiveness of the policy in reducing the emission factor due to manufacturing and transportation. The major objective of this research is to provide policy makers with a decision support tool that can aid in investigating the impact of an intensity-based carbon tax on regulated sectors and in finding the tax rate that achieves a target reduction. Therefore, we first propose a social-welfare maximizing model that can serve as a tool to evaluate the economic and environmental impacts of the policy. We compare the outcomes of the intensity-based tax and other existing environmental policies; namely, carbon tax imposed on overall emissions, cap-and-trade systems, and mandatory caps using case studies that are built within the context of the cement industry. The effectiveness of the policy is measured by achieving a balance between the target emission factor and the social welfare. To find the optimal tax rate that achieves a target reduction, we propose a bilevel programming model where at the upper level, the government sets a target emission factor for the industry and taxes firms if they exceed that target, and at the lower level, the industry sets output levels that maximize social welfare. In the design of the policy, the government takes into account the decisions of the producers regarding fuel types and production quantities as well as the decisions of the market regarding demand. To evaluate the effectiveness of the policy, we build case studies in the context of cement industry. The policy is found to be effective in reducing the CO2 emissions by opting for a less carbon-intensive fuel with a little impact on social welfare. To examine the effectiveness of the intensity-based carbon tax on reducing CO2 emissions from transportation, which is a major supply chain activity, we finally propose a bilevel program where at the upper level the government decides on the tax rate and at the lower level firms decide on the design of their supply chain and truck types. The policy is found to be effective in inducing firms to reduce their emission factors and consequently reducing the overall emissions.

Tissue engineering strategies have traditionally focused on the use of synthetic polymers as support scaffolds for cell growth. Recently, strategies have shifted towards a natural biologically derived scaffold, with the main focus on decellularized organs. Here, we report the development and engineering of a scaffold naturally secreted by human preadipocytes during differentiation. During this differentiation process, the preadipocytes remodel the extracellular matrix by releasing new extracellular proteins. Finally, we investigated the viability of the new basement membrane as a scaffold for tissue engineering using human pancreatic islets, and as a scaffold for soft tissue repair. After identifying the original scaffold material, we sought to improve the yield of material, treating the cell as a bioreactor, through various nutritional and cytokine stimuli. The results suggest that adipocytes can be used as bioreactors to produce a designer-specified engineered human extracellular matrix scaffold for specific tissue engineering applications.

In over twenty years of operations the Canadian Innovation Centre has evaluated, through its Inventor's Assistance Program (IAP), the commercial potential of over 12,000 early stage inventions. Prior to 1989, the Canadian Innovation Centre (CIC) used a version of the Preliminary Innovation Evaluation System (PIES), developed by Gerald Udell at the Oregon Innovation Center in 1974, to evaluate the commercial potential of early stage inventions. Since 1989, the CIC has used a modified version of PIES in their evaluation process. I first estimate the ability of this program's analysts to forecast the probability that an invention will become commercialized. I also estimate a model to predict the probability that an invention will become commercialized based on the IAP's evaluation of several underlying early stage characteristics of the invention. I find that such a statistical model is based on a limited set of variables and predicts future commercial success almost as well as the IAP's forecast of success. I then use factor analysis to determine if the ratings provided by the CIC evaluation service are representative of the underlying theoretical variable structure of PIES or their modified version. Factor analysis is applied to two distinct periods that are separated by a distinct alteration of the theoretical variable structure in 1989. While I find that the factor analysis provides evidence that the post 1989 theoretical structure does provide interpretation of some of the dimensions in the ranking variables, when a combination of the post 1989 and the pre 1989 structure are examined interpretability of the extracted factors is significantly improved. Finally, I compare the model estimated on the underlying early stage characteristics with a model estimated on the extracted factors. When the predictive accuracy of the two models is compared, I find that both procedures produce models that predict almost equally well. The models and the IAP perform better than R&D managers' predictions of their own R&D projects' successes. The thesis provides recommendations for the assessment and maintenance of evaluation models for inventions, innovations and R&D projects.

In 1975, Elongation Factor P (EF-P) protein was first discovered in the bacterium Escherichia coli. EF-P is believed to facilitate the translation of proteins by stimulating peptide bond synthesis for a number of different aminoacyl-tRNA molecules in conjunction with the 70S ribosome peptidyl transferase. Known eukaryotic homologs, eukaryotic translation initiation factor 5A (eIF-5A) of EF-P exist but with very low sequence conservation. Nevertheless, because of the high sequence similarities seen between bacterial EF-Ps and its low sequence similarity with eIF-5A, there is interest in the pharmaceutical industry of developing a novel antibacterial drug that inhibits EF-P. Of 322 completely sequenced bacterial genomes stored in GenBank, only one organism lacked an EF-P protein. Interestingly, sixty-six genomes were discovered to carry a duplicate copy of efp. The EF-P sequences were then used to construct a protein phylogenetic tree, which provided evidence of horizontal and vertical gene transfer as well as gene duplication. To lend support to these findings, EF-P GC content, codon usage, and nucleotide and amino acid sequences were analyzed with positive and negative controls. The adjacent 10 kb upstream and downstream regions of efp were also retrieved to determine if gene order is conserved in distantly related species. While gene order was not preserved in all species, two interesting trends were seen in some of the distantly related species. The EF-P gene was conserved beside Acetyl-CoA carboxylase genes, accB and accC in certain organisms. In addition, some efp sequences were flanked by two insertion sequence elements. Evidence of gene duplication and horizontal transfers of regions were also observed in the upstream and downstream regions of efp. In combination, phylogenetic, sequence analyses, and gene order conservation confirmed evidence of the complex history of the efp genes, which showed incongruencies relative to the universal phylogenetic tree. To determine how efp is regulated, the upstream regions of efp were used to try to predict motifs in silico. While statistically significant motifs were discovered in the upstream regions of the orthologous efp genes, no conclusive similarities to known binding sites such as the sigma factor binding sites or regulatory protein binding sites were observed. This work may facilitate and enhance the understanding of the regulation, conservation, and role of EF-P in protein translation.

Alzheimer’s disease is neurodegenerative with amyloid plaque and neurofibrillary tangles as pathological hallmarks. The most abundant component in the amyloid plaque is the amyloid-β (Aβ) peptide, with presence of both isoform Aβ40 and Aβ42. In immunological methods studying the Aβ peptide a specific monoclonal antibody, 6E10, is routinly being used. In this master thesis work unspecific binding of 6E10 antibody to the blood coagulating protein factor X has been investigated. Factor X is a protein in the blood coagulation cascade where it forms protein complex that activates thrombin. Non-hemostatic functions with connections to nerves and Aβ peptide are also known. Studies with Western blot show clear binding of 6E10 to denatured factor X. Interaction studies with ELISA gives uncertain results, where binding is found but no clear binding curve is obtained. Studies with native factor X in real time measurements with SPR gave no binding at all. These results suggest binding to denatured factor X. Immunohistochemistry studies of colocalisation of factor X and Aβ peptide gave clear evidence that factor X and Aβ are found near each other in mouse brain tissue. Factor X is located outside the blood vessels and Aβ is located at the inside.

Sjukskrivningar har blivit ett växande problem och företag måste värna om sin personal för att hålla den frisk. Många företag har insett vikten av att satsa på förebyggande åtgärder för att undkomma långtidssjukskrivningar. Vårt huvudsyfte med denna undersökning är att ta fram de friskfaktorer som påverkar välmående. För att göra detta har vi valt ett företag med låg sjukfrånvaro, SBAB i Karlstad. Tidigare forskning visar på lönsamheten av förebyggande åtgärder framför rehabilitering. För att kartlägga vart insatserna bör göras är det angeläget för företag att vara medvetna om vad som håller personalen frisk. Enligt forskning har många faktorer påverkan på välmående, sociala relationer och motion är två av dessa. Resultatet grundar sig på en kvalitativ studie där sex intervjuer bland personalen på SBAB genomförts. De faktorer som enligt undersökningen har visat sig ha störst betydelse för personalens välmående är organisationskultur, socialt stöd, arbetsvillkor, fysisk aktivitet och återhämtning. I resultatet framkom även att individens personlighet och inställning påverkar hur de olika friskfaktorerna upplevs.

In over twenty years of operations the Canadian Innovation Centre has evaluated, through its Inventor's Assistance Program (IAP), the commercial potential of over 12,000 early stage inventions. Prior to 1989, the Canadian Innovation Centre (CIC) used a version of the Preliminary Innovation Evaluation System (PIES), developed by Gerald Udell at the Oregon Innovation Center in 1974, to evaluate the commercial potential of early stage inventions. Since 1989, the CIC has used a modified version of PIES in their evaluation process. I first estimate the ability of this program's analysts to forecast the probability that an invention will become commercialized. I also estimate a model to predict the probability that an invention will become commercialized based on the IAP's evaluation of several underlying early stage characteristics of the invention. I find that such a statistical model is based on a limited set of variables and predicts future commercial success almost as well as the IAP's forecast of success. I then use factor analysis to determine if the ratings provided by the CIC evaluation service are representative of the underlying theoretical variable structure of PIES or their modified version. Factor analysis is applied to two distinct periods that are separated by a distinct alteration of the theoretical variable structure in 1989. While I find that the factor analysis provides evidence that the post 1989 theoretical structure does provide interpretation of some of the dimensions in the ranking variables, when a combination of the post 1989 and the pre 1989 structure are examined interpretability of the extracted factors is significantly improved. Finally, I compare the model estimated on the underlying early stage characteristics with a model estimated on the extracted factors. When the predictive accuracy of the two models is compared, I find that both procedures produce models that predict almost equally well. The models and the IAP perform better than R&D managers' predictions of their own R&D projects' successes. The thesis provides recommendations for the assessment and maintenance of evaluation models for inventions, innovations and R&D projects.