The role of the c-myc gene in pigment cell development and homeostasis

Résumé La dérégulation de c-Myc est un événement fréquent de la transformation cellulaire. Une régulation positive de cette oncoprotéine a été démontrée dans divers mélanomes cutanés primaires et métastatiques et est associée à un pronostic défavorable (Grover et al., 1996; Zhuang et al., 2008). c-Myc est considéré comme une molécule centrale impliquée dans plusieurs processus de l'homéostasie cellulaire. En raison de sa contribution importante dans la progression tumorale, la fonction de c-Myc a été étudiée intensément. Cependant nous connaissons peu le rôle de ce facteur de transcription dans l'embryogenèse et dans la spécification tissulaire. Un déficit total de c-Myc pendant l'embryogenèse conduit à la mort embryonnaire avant 10.5 jours de gestation. Cette mort est causée par de multiples imperfections du développement touchant la taille de l'embryon, le coeur, le péricarde, le tube neural et les cellules sanguines (Davis et al., 1993; Trumpp et al., 2001). Récemment, il a été montré que la plupart de ces anomalies sont secondaires et résultent d'une insuffisance du placenta dans les embryons c-myc-/- (Dubois et al., 2008). Sachant que c-Myc est important dans la maintenance des lignées de la crête neurale (Wei et al., 2007), nous nous sommes intéressés au rôle de c-Myc dans le développement des cellules pigmentaires et à leur homéostasie après la naissance. Un allèle floxé de c-myc (Trumpp et al., 2001) a été utilisé pour supprimer ce gène spécifiquement dans la lignée mélanocytaire à l'aide d'une souris transgénique Tyr::Cre (Delmas et al., 2003). L'ablation des deux allèles de c-myc dans les mélanocytes des souris c-myccKO conduit au phénotype de grisonnement des poils, observé directement après la naissance et associé à une diminution du nombre de mélanocytes dans le bulbe des follicules pileux. Les cellules pigmentaires restantes expriment les marqueurs mélanogéniques (Tyr, TRP-1, Dct and MITF) et semblent être fonctionnelles puisqu'elles peuvent produire et transférer la mélanine. De plus, la capacité de prolifération des mélanocytes déficients en c-Myc dans le bulbe des follicules pileux ne semble pas être affectée chez les nouveaux-nés. Les cellules souches mélanocytaires sont présentes, mais en nombre réduit, dans le bulge des follicules pileux à la fin de la morphogenèse chez les souris c-myccKO âgées de huit jours. Ces cellules sont maintenues sans changement durant le premier cycle pileux (vérifié à l'âge de trente jours), ce qui sous-entend que la fonction de c-Myc n'est pas nécessaire pour ce processus. Ceci explique pourquoi, en supposant que des cellules souches mélanocytaires fonctionnelles sont présentes dans la peau, nous n'observons pas de dilution de couleur de la robe liée à l'âge. Cependant, la présence de ces cellules souches mélanocytaires dans la peau c-myccKO ne suffit pas à assurer une quantité normale de mélanocytes différenciés dans le bulbe des follicules pileux. Cette population de cellules pigmentaires matures est sévèrement affectée par la suppression de c-Myc, ce qui contribue amplement au phénotype de grisonnement des poils. De plus, c-Myc paraît être important pour le développement des mélanocytes. Ainsi, le nombre de mélanoblastes diminue dans les embryons c-myccKO à partir du douzième jour de gestation. A treize jours de gestation, au stade où les mélanoblastes pénètrent dans l'épiderme et prolifèrent, les mélanoblastes déficients en c-Myc ne s'adaptent pas aux signaux de prolifération et se retrouvent en nombre réduit dans l'épiderme. Finalement, nous nous sommes intéressés, au rôle de N-Myc, un homologue proche de c-Myc, dans la lignée mélanocytaire. Nos expériences ont montré que. N-Myc était superflu pour le développement et l'homéostasie des mélanocytes, une seule copie du gène c-myc étant suffisante pour maintenir une pigmentation normale de la robe des souris c-mycc-myccKO/+~N_ myccKO/KO. Cependant, le rôle essentiel de N-Myc dans la maintenance des cellules mélanocytaires précurseurs apparaît lorsque c-Myc est absent, puisque la suppression simultanée des deux Myc résulte en une perte complète de la coloration de la robe. Ceci implique la présence d'un mécanisme compensatoire entre c- et N-Myc dans la lignée mélanocytaire, avec un rôle prédominant de c-Myc. Summary Deregulation of c-Myc is known to be a common event in cellular transformation. Upregulation of this oncoprotein was shown in a variety of primary and metastatic cutaneous melanomas and has been associated with a poor prognosis (Grover et al., 1996; Zhuang et al., 2008). c-myc is seen as a central molecule involved in many aspects of cellular homeostasis. c-Myc function has been intensively studied mostly because of its significant contribution to tumour progression. However little is known on the role of this transcription factor in embryogenesis and tissue specification. Complete loss of c-Myc during embryogenesis results in embryonic death before E10.5 due to multiple developmental defects including embryonic size, heart, pericardium, neural tube and blood cells (Davis et al., 1993; Trumpp et al., 2001). Recently it was discovered that most of these abnormalities are secondary and results of placental insufficiency in c-Myc-/- embryos (Dubois et al., 2008). Here, we focused on the role of c-Myc in pigment cell development and homeostasis after birth, knowing that c-Myc is important in the maintenance of neural crest lineages (Wei et al., 2007). A floxed allele of c-Myc (Trumpp et al., 2001) was used to specifically delete this gene in the melanocyte lineage using Tyr::Cre transgenic mice (Delmas et al., 2003). Removal of both c-Myc alleles in melanocytes of c-MyccKO mouse led to the grey hair phenotype which is seen directly after birth and was associated with a decrease in the melanocyte number in the bulb of the hair follicle. The remaining population of pigment cells express melanogenic markers (Tyr, TRP-1, Dct and MITF) and seem functionally normal since they can produce and transfer melanin. Furthermore proliferation capacity of c-Myc deficient melanocytes in the bulb of hair follicle seems not to be affected in newborn animals. Melanocyte stem cells (MSCs) are present but reduced in numbers in the bulge of the hair follicle at the end of morphogenesis in 8 days old c-MyccKO mice. These cells are maintained through the first hair cycle (as verified at P30) without any further changes, suggesting that c-Myc function is not required for this process. This explains why we did not detect any agerelated coat color dilution, assuming a presence of functional MSCs in the skin. Importantly, presence of MSCs in c-MyccKO skin was not sufficient for assuring a normal number of differentiated melanocytes in the bulb of the hair follicle. This population of mature pigmented cells is severely affected upon c-myc deletion thus largely contributing to the grey hair phenotype. Moreover, c-Myc appears to be important for melanocyte development. Thus, melanoblast number is affected in c-MyccKO embryos day 12 of gestation onwards. At E13.5, when melanoblasts enter the epidermis and proliferate, c-myc deficient melanoblasts failed to adapt to proliferation signals and are therefore reduced in number in the epidermis. Finally, we addressed the role of N-Myc, a closest homologue of c-Myc, in the melanocyte lineage. In these experiments, N-Myc was dispensable for melanocyte development and homeostasis, and even one copy of the c-myc gene was sufficient to maintain normal coat color pigmentation in c-mycc-mycCKO/+ ,N-myccKO/KO mice. However the crucial role of N-Myc in maintenance of melanocyte precursor cells became apparent when c-myc is eliminated since simultaneous deletion of both Myc results in complete loss of coat color pigmentation. This suggests compensatory mechanisms between c- and N-Myc with a predominant role of c-Myc in melanocyte lineage.

Demonstration and Field Evaluation of Alternative Portland Cement Concrete Pavement Reinforcement Materials, HR-1069, 2003

Transverse joints are placed in portland cement concrete pavements to control the development of random cracking due to stresses induced by moisture and thermal gradients and restrained slab movement. These joints are strengthened through the use of load transfer devices, typically dowel bars, designed to transfer load across the joint from one pavement slab to the next. Epoxy coated steel bars are the materials of choice at the present time, but have experienced some difficulties with resistance to corrosion from deicing salts. The research project investigated the use of alternative materials, dowel size and spacing to determine the benefits and limitations of each material. In this project two types of fiber composite materials, stainless steel solid dowels and epoxy coated dowels were tested for five years in side by side installation in a portion of U.S. 65 near Des Moines, Iowa, between 1997 and 2002. The work was directed at analyzing the load transfer characteristics of 8-in. vs. 12-in. spacing of the dowels and the alternative dowel materials, fiber composite (1.5- and 1.88-in. diameter) and stainless steel (1.5-in. diameter), compared to typical 1.5-in. diameter epoxy-coated steel dowels placed on 12-in. spacing. Data were collected biannually within each series of joints and variables in terms of load transfer in each lane (outer wheel path), visual distress, joint openings, and faulting in each wheel path. After five years of performance the following observations were made from the data collected. Each of the dowel materials is performing equally in terms of load transfer, joint movement and faulting. Stainless steel dowels are providing load transfer performance equal to or greater than epoxy-coated steel dowels at the end of five years. Fiber reinforced polymer (FRP) dowels of the sizes and materials tested should be spaced no greater than 8 in. apart to achieve comparable performance to epoxy coated dowels. No evidence of deterioration due to road salts was identified on any of the products tested. The relatively high cost of stainless steel solid and FRP dowels was a limitation at the time of this study conclusion. Work is continuing with the subject materials in laboratory studies to determine the proper shape, spacing, chemical composition and testing specification to make the FRP and stainless (clad or solid) dowels a viable alternative joint load transfer material for long lasting portland cement concrete pavements.

Evaluation of Lightweight Profilers for Construction Smoothness Evaluation, MLR-02-02, 2004

High-speed non-contact laser profilers have become the standard testing equipment for pavement management ride quality testing. The same technology used in the high-speed profilers is now being used in lightweight profilers for construction smoothness testing. The lightweight profilers have many advantages over the California 25-ft profilograph. Despite the many advantages of the lightweight profilers, there is resistance from the contracting industry toward eliminating the 25-ft profilograph for construction ride testing. One way to reduce or overcome the resistance is to evaluate and demonstrate the advantages/disadvantages of the lightweight profiler in actual field use in Iowa. The objective of the study was to purchase a lightweight profiler and to evaluate its suitability for construction smoothness quality verification and quality acceptance on Iowa projects. A lightweight profiler, an Ames Engineering, Inc. LISA single laser unit, was received in February 2003 for the study. Based on the work done during the 2003 construction season, the following conclusions can be made: (1) For hot mix asphalt surfaces, the LISA correlated well with the contractors' profilographs; (2) LISA results are significantly affected by longitudinal tining on portland cement concrete pavements, requiring a laser system upgrade to give accurate results; (3) A significant timesaving was realized by using the LISA; (4) Increasing visibility and reducing time in the construction zone improved safety; (5) One person with limited lifting capabilities could set up and operate the LISA; and (6) With the current Iowa Department of Transportation specification, the LISA cannot totally replace the profilograph, since bridges and short segments with no adjoining pavement would still require a profilograph.

Investigation of High Performance Concrete Pavement, MLR-05-01, 2006

The Iowa DOT has been using blended cements in ternary mixes since 1999. Use of these supplementary cementitious materials gives concrete with higher strengths and much lower permeability. Use of these materials has been incorporated for use in High Performance Concrete (HPC) decks to achieve lower permeability and thus long term performance. Since we have been using these materials in paving, it would be informative to determine what concrete pavement properties are enhanced as related to high performance concrete. The air void system was excellent at a spacing factor of 0.0047 in (0.120 mm). AVA spacing factor results are much higher than the hardened air void analysis. Although only 3 samples were tested between the image analysis air content and the RapidAir457, there is pretty good agreement between those test methods. Air void analysis indicates that excessive vibration was not required to place the concrete. Vibration was well within the specification limits with an average of 6683 vpm’s with a standard deviation of 461. Overall ride of the project was very good. The average smoothness for the project was 2.1 in/mile (33.8 mm/km). The International Roughness Index (IRI) was 81 in/mi (1.29 m/km). The compressive strength was 6260 psi (43.2 MPa) at 28 days and 6830 (47.1 MPa) at 56 days. The modulus of rupture by third point loading (MOR-TPL) tested at 28 days was 660 psi (4.55 MPa). The AASHTO T277 rapid chloride permeability results at 28 days using the Virginia cure method correlate fairly well with the 56 and 90 day results with standard curing. The Virginia cure method 28 day results were 2475 coulombs and the standard cure 56 and 90 day test results were 2180 and 2118, respectively.

A Study of Fine Sand from Nine Mile Island at Dubuque, MLR-88-08, 1988

The specifications for concrete sand in Iowa have been used for many years with very good results. In several locations of the state, it is becoming more difficult to produce concrete sand consistently at a reasonable cost. Both ASTM and AASHTO have specifications for concrete sands that allow a finer, poorer graded sand than the Iowa specification. The ASTM and AASHTO specifications are based on the use of trial mix testing prior to construction. Iowa does not currently use the trial mix procedure.

Instrumentation of Paver Vibrators, MLR-95-10, 1999

Premature deterioration of Portland Cement Concrete (PCC) pavements led to investigations for causes of the concrete failures. Evidence of parallel longitudinal cracks in deteriorating pavements, with crack spacings similar to paver vibrator spacings, made it clear that the vibrators were related to the cause for deterioration. After a number of field trips observing paving operations and measuring vibrator frequencies, it soon became clear that the paver vibrators were, in many cases, not running in compliance with the Iowa DOT specification. The specified frequency was from 5000 to 8000 revolutions per minute (rpm). The pavers visited did not have a monitoring system to give a continuous frequency readout for any of it's vibrators. Occasionally, during a paving operation, frequency readings were taken on some vibrators with a hand held tachometer. However, that degree of monitoring was found to be far from providing the quality of information and control necessary to maintain compliance to the Iowa DOT specification. A paver vibrator monitoring system, which would operate continuously while paving and cover all vibrators, was determined to be essential. The output must be visible to the paver operator and inspector at all times.

Demonstration Project using Railroad Flatcars for Low-Volume Road Bridges, TR-444, 2003

The use of Railroad Flatcars (RRFCs) as the superstructure on low-volume county bridges has been investigated in a research project conducted by the Bridge Engineering Center at Iowa State University. These bridges enable county engineers to replace old, inadequate county bridge superstructures for less than half the cost and in a shorter construction time than required for a conventional bridge. To illustrate their constructability, adequacy, and economy, two RRFC demonstration bridges were designed, constructed, and tested: one in Buchanan County and the other in Winnebago County. The Buchanan County Bridge was constructed as a single span with 56-ft-long flatcars supported at their ends by new, concrete abutments. The use of concrete in the substructure allowed for an integral abutment at one end of the bridge with an expansion joint at the other end. Reinforced concrete beams (serving as longitudinal connections between the three adjacent flatcars) were installed to distribute live loads among the RRFCs. Guardrails and an asphalt milling driving surface completed the bridge. The Winnebago County Bridge was constructed using 89-ft-long flatcars. Preliminary calculations determined that they were not adequate to span 89 ft as a simple span. Therefore, the flatcars were supported by new, steel-capped piers and abutments at the RRFCs' bolsters and ends, resulting in a 66-ft main span and two 10-ft end spans. Due to the RRFC geometry, the longitudinal connections between adjacent RRFCs were inadequate to support significant loads; therefore, transverse, recycled timber planks were utilized to effectively distribute live loads to all three RRFCs. A gravel driving surface was placed on top of the timber planks, and a guardrail system was installed to complete the bridge. Bridge behavior predicted by grillage models for each bridge was validated by strain and deflection data from field tests; it was found that the engineered RRFC bridges have live load stresses significantly below the AASHTO Bridge Design Specification limits. To assist in future RRFC bridge projects, RRFC selection criteria were established for visual inspection and selection of structurally adequate RRFCs. In addition, design recommendations have been developed to simplify live load distribution calculations for the design of the bridges. Based on the results of this research, it has been determined that through proper RRFC selection, construction, and engineering, RRFC bridges are a viable, economic replacement system for low-volume road bridges.

Evaluation of Deicing Materials and Corrosion Reducing Treatments for Deicing Salts, TR-471, 2007

Effective winter maintenance makes use of freezing-point-depressant chemicals (also known as ice-control products) to prevent the formation of the bond between snow and ice and the highway pavement. In performing such winter maintenance, the selection of appropriate ice-control products for the bond prevention task involves consideration of a number of factors, as indicated in Nixon and Williams (2001). The factors are in essence performance measurements of the ice-control products, and as such can be easily incorporated into a specification document to allow for selection of the best ice-control products for a given agency to use in its winter maintenance activities. Once performance measures for de-icing or anti-icing chemicals have been specified, this allows the creation of a quality control program for the acceptance of those chemicals. This study presents a series of performance measurement tests for ice-control products, and discusses the role that they can play in such a quality control program. Some tests are simple and rapid enough that they can be performed on every load of icecontrol products received, while for others, a sampling technique must be used. An appropriate sampling technique is presented. Further, each test is categorized as to whether it should be applied to every load of ice-control products or on a sampling basis. The study includes a detailed literature review that considers the performance of ice-control products in three areas: temperature related performance, product consistency, and negative side effects. The negative side effects are further broken down into three areas, namely operational side effects (such as chemical slipperiness), environmental side effects, and infrastructural side effects (such as corrosion of vehicles and damage to concrete). The review indicated that in the area of side effects the field performance of ice-control products is currently so difficult to model in the laboratory that no particular specification tests can be recommended at this time. A study of the impact of ice-control products on concrete was performed by Professor Wang of Iowa State University as a sub-contract to this study, and has been presented to the Iowa Highway Research Board prior to this report.

Development of Object-Oriented Design and Specifications for Iowa DOT and Urban Standards: Phase I, TR-487, 2004

Currently, individuals including designers, contractors, and owners learn about the project requirements by studying a combination of paper and electronic copies of the construction documents including the drawings, specifications (standard and supplemental), road and bridge standard drawings, design criteria, contracts, addenda, and change orders. This can be a tedious process since one needs to go back and forth between the various documents (paper or electronic) to obtain information about the entire project. Object-oriented computer-aided design (OO-CAD) is an innovative technology that can bring a change to this process by graphical portrayal of information. OO-CAD allows users to point and click on portions of an object-oriented drawing that are then linked to relevant databases of information (e.g., specifications, procurement status, and shop drawings). The vision of this study is to turn paper-based design standards and construction specifications into an object-oriented design and specification (OODAS) system or a visual electronic reference library (ERL). Individuals can use the system through a handheld wireless book-size laptop that includes all of the necessary software for operating in a 3D environment. All parties involved in transportation projects can access all of the standards and requirements simultaneously using a 3D graphical interface. By using this system, users will have all of the design elements and all of the specifications readily available without concerns of omissions. A prototype object-oriented model was created and demonstrated to potential users representing counties, cities, and the state. Findings suggest that a system like this could improve productivity to find information by as much as 75% and provide a greater sense of confidence that all relevant information had been identified. It was also apparent that this system would be used by more people in construction than in design. There was also concern related to the cost to develop and maintain the complete system. The future direction should focus on a project-based system that can help the contractors and DOT inspectors find information (e.g., road standards, specifications, instructional memorandums) more rapidly as it pertains to a specific project.

Review of Inconsistencies Between SUDAS and Iowa DOT Specifications Phase II: Implementation of Recommendations into SUDAS Specifications, TR-565, 2008

The current version of the SUDAS Specifications will be revised to accommodate the DOT’s utilization of SUDAS. The revisions to the SUDAS Specifications will be based upon the recommendations from Phase 1. In some instances, the recommendations will require reorganization of portions of the SUDAS Specifications. Upon incorporation of the Phase 1 recommendations, each applicable Division of the SUDAS Specifications will be updated into the active-imperative style, utilizing the 3- part specification format currently utilized by SUDAS.

Review of Inconsistencies Between SUDAS and Iowa DOT Specifications Phase II: Implementation of Recommendations into SUDAS Specifications, TR-565, Synopsis, 2008

The current version of the SUDAS Specifications will be revised to accommodate the DOT’s utilization of SUDAS. The revisions to the SUDAS Specifications will be based upon the recommendations from Phase 1. In some instances, the recommendations will require reorganization of portions of the SUDAS Specifications. Upon incorporation of the Phase 1 recommendations, each applicable Division of the SUDAS Specifications will be updated into the active-imperative style, utilizing the 3- part specification format currently utilized by SUDAS.

Wind Loads on Dynamic Message Cabinets and Behavior of Supporting Trusses, TR-612, 2013

Large Dynamic Message Signs (DMSs) have been increasingly used on freeways, expressways and major arterials to better manage the traffic flow by providing accurate and timely information to drivers. Overhead truss structures are typically employed to support those DMSs allowing them to provide wider display to more lanes. In recent years, there is increasing evidence that the truss structures supporting these large and heavy signs are subjected to much more complex loadings than are typically accounted for in the codified design procedures. Consequently, some of these structures have required frequent inspections, retrofitting, and even premature replacement. Two manufacturing processes are primarily utilized on truss structures - welding and bolting. Recently, cracks at welding toes were reported for the structures employed in some states. Extremely large loads (e.g., due to high winds) could cause brittle fractures, and cyclic vibration (e.g., due to diurnal variation in temperature or due to oscillations in the wind force induced by vortex shedding behind the DMS) may lead to fatigue damage, as these are two major failures for the metallic material. Wind and strain resulting from temperature changes are the main loads that affect the structures during their lifetime. The American Association of State Highway and Transportation Officials (AASHTO) Specification defines the limit loads in dead load, wind load, ice load, and fatigue design for natural wind gust and truck-induced gust. The objectives of this study are to investigate wind and thermal effects in the bridge type overhead DMS truss structures and improve the current design specifications (e.g., for thermal design). In order to accomplish the objective, it is necessary to study structural behavior and detailed strain-stress of the truss structures caused by wind load on the DMS cabinet and thermal load on the truss supporting the DMS cabinet. The study is divided into two parts. The Computational Fluid Dynamics (CFD) component and part of the structural analysis component of the study were conducted at the University of Iowa while the field study and related structural analysis computations were conducted at the Iowa State University. The CFD simulations were used to determine the air-induced forces (wind loads) on the DMS cabinets and the finite element analysis was used to determine the response of the supporting trusses to these pressure forces. The field observation portion consisted of short-term monitoring of several DMS Cabinet/Trusses and long-term monitoring of one DMS Cabinet/Truss. The short-term monitoring was a single (or two) day event in which several message sign panel/trusses were tested. The long-term monitoring field study extended over several months. Analysis of the data focused on trying to identify important behaviors under both ambient and truck induced winds and the effect of daily temperature changes. Results of the CFD investigation, field experiments and structural analysis of the wind induced forces on the DMS cabinets and their effect on the supporting trusses showed that the passage of trucks cannot be responsible for the problems observed to develop at trusses supporting DMS cabinets. Rather the data pointed toward the important effect of the thermal load induced by cyclic (diurnal) variations of the temperature. Thermal influence is not discussed in the specification, either in limit load or fatigue design. Although the frequency of the thermal load is low, results showed that when temperature range is large the restress range would be significant to the structure, especially near welding areas where stress concentrations may occur. Moreover stress amplitude and range are the primary parameters for brittle fracture and fatigue life estimation. Long-term field monitoring of one of the overhead truss structures in Iowa was used as the research baseline to estimate the effects of diurnal temperature changes to fatigue damage. The evaluation of the collected data is an important approach for understanding the structural behavior and for the advancement of future code provisions. Finite element modeling was developed to estimate the strain and stress magnitudes, which were compared with the field monitoring data. Fatigue life of the truss structures was also estimated based on AASHTO specifications and the numerical modeling. The main conclusion of the study is that thermal induced fatigue damage of the truss structures supporting DMS cabinets is likely a significant contributing cause for the cracks observed to develop at such structures. Other probable causes for fatigue damage not investigated in this study are the cyclic oscillations of the total wind load associated with the vortex shedding behind the DMS cabinet at high wind conditions and fabrication tolerances and induced stresses due to fitting of tube to tube connections.

Review of Inconsistencies Between SUDAS and Iowa DOT Specifications Phase III: Continued Implementation of Recommendations into SUDAS Specifications, TR-607, 2010

The objective of the Phase 3 project was to re-write the identified sections of the SUDAS specifications into the imperative mood, consistent with the format utilized during the Phase 2 project and other work completed by SUDAS staff. Figures for the identified sections were updated to match the new SUDAS format, similar to the Iowa DOT Standard Road Plans. While the Iowa DOT does not intend to incorporate all of the following sections into their specification book, consistency with the Iowa DOT specifications was strived for wherever possible. Maintaining consistency between the specifications simplifies design, bidding, and construction.

Gestió d'incidències

La memòria mostra el procés de desenvolupament d'una aplicació sota el paradigma de J2EE. Per una banda descriu els passos realitzats en matèria d'especificació, anàlisis i disseny utilitzant UML com a eina fonamental de modelatge, per altra pretén mostrar que la utilització de frameworks i l'aplicació de patrons de disseny facilita substancialment el procés de desenvolupament.

Structural macro factors and the affine term structure of interest rates

This work consists of three essays investigating the ability of structural macroeconomic models to price zero coupon U.S. government bonds. 1. A small scale 3 factor DSGE model implying constant term premium is able to provide reasonable a fit for the term structure only at the expense of the persistence parameters of the structural shocks. The test of the structural model against one that has constant but unrestricted prices of risk parameters shows that the exogenous prices of risk-model is only weakly preferred. We provide an MLE based variance-covariance matrix of the Metropolis Proposal Density that improves convergence speeds in MCMC chains. 2. Affine in observable macro-variables, prices of risk specification is excessively flexible and provides term-structure fit without significantly altering the structural parameters. The exogenous component of the SDF is separating the macro part of the model from the term structure and the good term structure fit has as a driving force an extremely volatile SDF and an implied average short rate that is inexplicable. We conclude that the no arbitrage restrictions do not suffice to temper the SDF, thus there is need for more restrictions. We introduce a penalty-function methodology that proves useful in showing that affine prices of risk specifications are able to reconcile stable macro-dynamics with good term structure fit and a plausible SDF. 3. The level factor is reproduced most importantly by the preference shock to which it is strongly and positively related but technology and monetary shocks, with negative loadings, are also contributing to its replication. The slope factor is only related to the monetary policy shocks and it is poorly explained. We find that there are gains in in- and out-of-sample forecast of consumption and inflation if term structure information is used in a time varying hybrid prices of risk setting. In-sample yield forecast are better in models with non-stationary shocks for the period 1982-1988. After this period, time varying market price of risk models provide better in-sample forecasts. For the period 2005-2008, out of sample forecast of consumption and inflation are better if term structure information is incorporated in the DSGE model but yields are better forecasted by a pure macro DSGE model.