Hay competencia en el mercado europeo de transporte aéreo?: el caso español

La liberalización del transporte aéreo que se llevó a término en la Unión Europea a principios de los años noventa ha tenido efectos positivos sobre el bienestar del viajero. No obstante, existe un consenso en la literatura académica que estos efectos dependen de la existencia de una competencia efectiva en el nivel de la ruta. En este sentido, se plantea el problema que puede llegar a suponer las ventajas de escalera de las compañías dominantes en cada mercado interior. Además, se pretende capturar la diferenciación de productos como característica esencial de la industria del transporte aéreo. El análisis de estas cuestiones se realiza de la forma siguiente. En primer lugar, se hace referencia a los principales aspectos económicos que condicionan la competencia en el transporte aéreo. Y en segundo lugar, se implementa un modelo empírico basado en un sistema de tres ecuaciones, que se estima mediante la técnica de las variables instrumentales. La muestra utilizada hace referencia al año 2001 para la mayoría de las rutas del mercado interior español de vuelos regulares en dónde hay competencia. Los resultados de la estimación muestran la existencia de unas condiciones de competencia diferentes según el segmento del mercado al cual se dirigen las compañías aéreas. Efectivamente, la competencia en precios (calidad) parece ser predominante en el segmento de viajeros por motivos personales (negocios). Adicionalmente, el dominio que la compañía dominante tiene sobre la mayoría de las rutas parece descansar en las ventajas competitivas, tanto en términos de costes como en términos de demanda, que le proporciona el control de la red aeroportuaria nacional. De todo esto se puede inferir que el mantenimiento y/o aumento de los beneficios de la liberalización de los servicios de transporte aéreo exige extender la liberalización al uso del aeropuertos así como descentralizar su gestión.

2012-2016 Iowa Transportation Improvement Program

The Iowa Transportation Improvement Program (Program) is published to inform Iowans of planned investments in our state’s transportation system. The Iowa Transportation Commission (Commission) and Iowa Department of Transportation (Iowa DOT) are committed to programming those investments in a fiscally responsible manner. This document reflects Iowa’s multimodal transportation system by the inclusion of investments in aviation, transit, railroads, trails, and highways. A major component of this program is the highway section that documents programmed investments on the primary highway system for the next five years. A large part of funding available for highway programming comes from the federal government. Accurately estimating future federal funding levels is dependent on having a current enacted multi-year federal transportation authorization. The most recent authorization, Safe, Accountable, Flexible, Efficient Transportation Equity Act: A Legacy for Users (SAFETEA-LU), expired September 30, 2009, and to date it has been extended seven times because a new authorization has not yet been enacted. The current extension will expire September 30, 2011. This leads to significant uncertainty in federal funding; however, it is becoming evident that, in Federal Fiscal Year 2012 and beyond, federal funding revenue will likely be reduced by 25 percent from current levels in order to match revenue that flows into the Highway Trust Fund. This Program reflects this anticipated reduction in federal funding. While Iowa law does not require the adoption of a Program when federal transportation funding is being reauthorized, the Commission believes it is important to adopt a Program in order to continue on-going planning and project development efforts so that Iowa will be well positioned when a new authorization is adopted. However, it is important to recognize that, absent a federal authorization bill, there is significant uncertainty in the forecast of federal revenues. The Commission and the Iowa DOT will continue to monitor federal revenues and will adjust future investments as needed to maintain a fiscally responsible Program. For 2012-2016, approximately $2.3 billion is forecast to be available for highway right of way and construction. In developing the highway section of the Program, the Commission’s primary investment objective remains stewardship (i.e. safety, maintenance and preservation) of Iowa’s existing highway system. Over $1.3 billion is programmed in FY2012 through FY2016 for preservation of Iowa’s existing highway system and for enhanced highway safety features. The highway section also includes significant interstate investments on I-29 in Sioux City, I-29/80/480 in Council Bluffs, and I-74 in Bettendorf/Davenport. The FY2016 programming for construction on I-74 in Bettendorf/Davenport is the first of several years of significant investments that will be monitored for available funding. Approximately $200 million of the investments on these three major urban interstate projects address preservation needs. In total, approximately $1.5 billion is programmed for highway preservation activities for 2012- 2016. Another highway programming objective is maintaining the scheduled completion of capacity and economic development projects. Projects that were previously scheduled to be completed within the previous Program continue on their current schedule. However, due to the reduction of projected federal revenues, the Commission has delayed by one year the initiation of construction of all multi-year non-Interstate capacity and economic development projects that cannot be completed within this Program. These projects are U.S. 20 in Woodbury County, U.S. 30 in Benton County, U.S. 61 in Louisa County, and Iowa 100 in Linn County. The Iowa DOT and Commission appreciate the public’s involvement in the state’s transportation planning process. Comments received personally, by letter or through participation in the Commission’s regular meetings or public input meetings held around the state each year, are invaluable in providing guidance for the future of Iowa’s transportation system. It should be noted that this document is a planning guide. It does not represent a binding commitment or obligation of the Commission or Iowa DOT, and is subject to change.

Cell therapies for tendons: old cell choice for modern innovation.

Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950's for vaccine production, and these "old" cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair.

2011 Road Use Tax Fund (RUTF) Study A report to the Iowa Legislature, per 2011 Iowa Code Section 307.31

The transportation system is in demand 24/7 and 365 days a year irrespective of neither the weather nor the conditions. Iowa’s transportation system is an integral and essential part of society serving commerce and daily functions of all Iowans across the state. A high quality transportation system serves as the artery for economic activity and, the condition of the infrastructure is a key element for our future growth opportunities. A key component of Iowa’s transportation system is the public roadway system owned and maintained by the state, cities and counties. In order to regularly re-evaluate the conditions of Iowa’s public roadway infrastructure and assess the ability of existing revenues to meet the needs of the system, the Iowa Department of Transportation’s 2006 Road Use Tax Fund (RUTF) report to the legislature included a recommendation that a study be conducted every five years. That recommendation was included in legislation adopted in 2007 and signed into law. The law specifically requires the following (2011 Iowa Code Section 307.31): •“The department shall periodically review the current revenue levels of the road use tax fund and the sufficiency of those revenues for the projected construction and maintenance needs of city, county, and state governments in the future. The department shall submit a written report to the general assembly regarding its findings by December 31 every five years, beginning in 2011. The report may include recommendations concerning funding levels needed to support the future mobility and accessibility for users of Iowa's public road system.” •“The department shall evaluate alternative funding sources for road maintenance and construction and report to the general assembly at least every five years on the advantages and disadvantages and the viability of alternative funding mechanisms.” Consistent with this requirement, the Iowa Department of Transportation (DOT) has prepared this study. Recognizing the importance of actively engaging with the public and transportation stakeholders in any discussion of public roadway conditions and needs, Governor Terry E. Branstad announced on March 8, 2011, the creation of, and appointments to, the Governor’s Transportation 2020 Citizen Advisory Commission (CAC). The CAC was tasked with assisting the Iowa DOT as they assess the condition of Iowa’s roadway system and evaluate current and future funding available to best address system needs. In particular the CAC was directed to gather input from the public and stakeholders regarding the condition of Iowa’s public roadway system, the impact of that system, whether additional funding is needed to maintain/improve the system, and, if so, what funding mechanisms ought to be considered. With this input, the CAC prepared a report and recommendations that were presented to Governor Branstad and the Iowa DOT in November 2011 for use in the development of this study. The CAC’s report is available at www.iowadot.gov/transportation2020/pdfs/CAC%20REPORT%20FINAL%20110211.pdf. The CAC’s report was developed utilizing analysis and information from the Iowa DOT. Therefore, the report forms the basis for this study and the two documents are very similar. Iowa is fortunate to have an extensive public roadway system that provides access to all areas of the state and facilitates the efficient movement of goods and people. However, it is also a tremendous challenge for the state, cities and counties to maintain and improve this system given flattening revenue, lost buying power, changing demands on the system, severe weather, and an aging system. This challenge didn’t appear overnight and for the last decade many studies have been completed to look into the situation and the legislature has taken significant action to begin addressing the situation. In addition, the Iowa DOT and Iowa’s cities and counties have worked jointly and independently to increase efficiency and streamline operations. All of these actions have been successful and resulted in significant changes; however, it is apparent much more needs to be done. A well-maintained, high-quality transportation system reduces transportation costs and provides consistent and reliable service. These are all factors that are critical in the evaluation companies undertake when deciding where to expand or locate new developments. The CAC and Iowa DOT heard from many Iowans that additional investment in Iowa’s roadway system is vital to support existing jobs and continued job creation in the state of Iowa. Beginning June 2011, the CAC met regularly to review material and discuss potential recommendations to address Iowa’s roadway funding challenges. This effort included extensive public outreach with meetings held in seven locations across Iowa and through a Transportation 2020 website hosted by the Iowa DOT (www.iowadot.gov/transportation2020). Over 500 people attended the public meetings held through the months of August and September, with 198 providing verbal or written comment at the meetings or through the website. Comments were received from a wide array of individuals. The public comments demonstrated overwhelming support for increased funding for Iowa’s roads. Through the public input process, several guiding principles were established to guide the development of recommendations. Those guiding principles are: • Additional revenues are restricted for road and bridge improvements only, like 95 percent of the current state road revenue is currently. This includes the fuel tax and registration fees. • State and local governments continue to streamline and become more efficient, both individually and by looking for ways to do things collectively. • User fee concept is preserved, where those who use the roads pay for them, including non¬residents. • Revenue-generating methods equitable across users. • Increase revenue generating mechanisms that are viable now but begin to implement and set the stage for longer-term solutions that bring equity and stability to road funding. • Continue Iowa’s long standing tradition of state roadway financing coming from pay-as-you-go financing. Iowa must not fall into the situation that other states are currently facing where the majority of their new program dollars are utilized to pay the debt service of past bonding. Based on the analysis of Iowa’s public roadway needs and revenue and the extensive work of the Governor’s Transportation 2020 Citizen Advisory Commission, the Iowa DOT has identified specific recommendations. The recommendations follow very closely the recommendations of the CAC (CAC recommendations from their report are repeated in Appendix B). Following is a summary of the recommendations which are fully documented beginning on page 21. 1. Through a combination of efficiency savings and increased revenue, a minimum of $215 million of revenue per year should be generated to meet Iowa’s critical roadway needs. 2. The Code of Iowa should be changed to require the study of the sufficiency of the state’s road funds to meet the road system’s needs every two years instead of every five years to coincide with the biennial legislative budget appropriation schedule. 3.Modify the current registration fee for electric vehicles to be based on weight and value using the same formula that applies to most passenger vehicles. 4.Consistent with existing Code of Iowa requirements, new funding should go to the TIME-21 Fund up to the cap ($225 million) and remaining new funding should be distributed consistent with the Road Use Tax Fund distribution formula. 5.The CAC recommended the Iowa DOT at least annually convene meetings with cities and counties to review the operation, maintenance and improvement of Iowa’s public roadway system to identify ways to jointly increase efficiency. In direct response to this recommendation, Governor Branstad directed the Iowa DOT to begin this effort immediately with a target of identifying $50 million of efficiency savings that can be captured from the over $1 billion of state revenue already provided to the Iowa DOT and Iowa’s cities and counties to administer, maintain and improve Iowa’s public roadway system. This would build upon past joint and individual actions that have reduced administrative costs and resulted in increased funding for improvement of Iowa’s public roadway system. Efficiency actions should be quantified, measured and reported to the public on a regular basis. 6.By June 30, 2012, Iowa DOT should complete a study of vehicles and equipment that use Iowa’s public roadway system but pay no user fees or substantially lower user fees than other vehicles and equipment.

Development of Updated Specifications for Roadway Rehabilitation Techniques, May 2011

As our nation’s highway system continues to age, asphalt maintenance and rehabilitation techniques have become increasingly important. The deterioration of pavement over time is inevitable. Preventive maintenance is a strategy to extend the serviceable life of a pavement by applying cost-effective treatments that slow the deterioration of pavement and extend its usable life. Thin maintenance surfaces (TMSs) are preventive maintenance techniques that can effectively prolong the life of pavement when applied at an opportune time. Common TMSs include bituminous fog seal, bituminous seal coat, slurry seal, cold in-place recycling (CIR), and micro-surfacing. This research project investigated ways to improve Iowa Statewide Urban Design and Specifications (SUDAS) and Iowa Department of Transportation (DOT) documents regarding asphalt roadway maintenance and rehabilitation. Researchers led an effort to review and help ensure that the documents supporting proper selection, design, and construction for asphalt maintenance and rehabilitation techniques reflect the latest research findings on these processes: seal coating, slurry sealing, micro-surfacing, and fog sealing. Full results of this investigation are included in this report and its appendices. This report also presents a summary of the recommendations based on the study results.

Guide to Cement-Based Integrated Pavement Solutions, August 2011

This guide provides a clear, concise, and cohesive presentation of cement-bound materials options for 10 specific engineering pavement applications: new concrete pavements, concrete overlays, previous concrete, precast pavements, roller-compacted concrete, cement-treated base, full-depth reclamation with cement, cement-modified soils, recycled concrete aggregates, and repair and restoration. Each application is presented as a method for meeting specific design and construction objectives that today’s pavement practitioners must accomplish. The benefits, considerations, brief description, and summary of materials, design, and construction requirements, as well as a list of sustainable attributes, are provided for every solution. This guide is intended to be short, simple, and easy to understand. It was designed so that the most up-to-date and relevant information is easily extractable. It is not intended to be used as a design guide for any of the applications identified herein. Recommendations for additional information that can provide such details are given at the end of each solution discussion. The intended audience is practitioners, including engineers and managers who face decisions regarding what materials to specify in the pavement systems they design or manage. The audience also includes city and county engineers, along with the A/E firms that often represent them, and state DOT engineers at all levels who are seeking alternatives in this era of changing markets.

Road Use Tax Fund Efficiency Report, January 2012

In the November 2011 report issued by the Governor’s Transportation 2020 Citizen Advisory Commission (CAC), the commission recommended the Iowa Department of Transportation (DOT), at least annually, convene meetings with the cities and counties to review the operation, maintenance and improvement of Iowa’s public roadway system to identify ways to jointly increase efficiency. In response to this recommendation, Gov. Branstad directed the Iowa DOT to begin this effort immediately with a target of identifying $50 million of efficiency savings that can be captured from the $1.2 billion of Road Use Tax Funds (RUTF) provided to the Iowa DOT, cities and counties to administer, maintain and improve the public roadway system. This would build upon past joint and individual actions that have reduced administrative costs and resulted in increased funding for system improvements. Efficiency actions should be quantified, measured and reported to the public on a regular basis. Beyond the discussion of identifying funding solutions to our road and bridge needs, it is critical that all jurisdictions that own, maintain and improve the nation’s road and bridge systems demonstrate to the public these funds are utilized in the most efficient and effective manner. This requires continual innovation in all aspects of transportation planning, design, construction and maintenance - done in a transparent manner to clearly demonstrate to the public how their funds are being utilized. The Iowa DOT has identified 13 efficiency measures separated into two distinct categories – Program Efficiencies and Partnership Efficiencies. The total value of the efficiency measures is $50 million. Many of the efficiency items will need input, refinement and partnership from cities, counties, other local jurisdictions, and stakeholder interest groups. The Iowa DOT has begun meetings with many of these groups to help identify potential efficiency measures and strategies for moving forward. These partnerships and discussions will continue through implementation of the efficiency measures. Dependent on the measures identified, additional action may be required by the legislature, Iowa Transportation Commission, and/or other bodies to implement the action. In addition, a formal process will be developed to quantify, measure and report the results of actions taken on a regular basis.

Role of notch signalling in mammary gland

ÁBSTRACT : Mammary gland is composed of two main epithelial cell types, myoepithelial and luminal. The mechanisms involved in determination and maintenance of them remain poorly understood. Notch signaling is known to regulate cell fate determination in other tissues like skin and nervous system. It was also shown that it can act as tumor suppressor or oncogene depending on the tissue type. The mouse models overexpressing active Notch receptors indicated that Notch signaling is oncogenic in the mammary gland. This observation was followed by some descriptive and functional studies in human breast cancer and it was reported that Notch signaling activity or expression of its components are increased in some of the breast tumor samples compared to normal tissue. However, the physiological role of the Notch signaling and its downstream mechanisms in mammary gland is poorly defined. p63, a member of p53 family, has been implicated in the cell fate determination of keratinocytes. Knockout mouse models revealed that p63 is required for the formation of the mammary anlagen in embryo and its ΔN isoform is expressed exclusively in the myoepithelial layer of the adult breast. In order to understand its function in normal breast epithelial cells, I activated Notch signaling by expression of Notch1 intracellular domain (NICD) in normal primary human breast epithelial cells (HBECs). In this context, NICD reduced growth of HBECs and led to downmodulation of extracellular matrix-receptor interaction network (ECM) components as well as ΔNp63. Expression of ΔNp63 together with NICD partially rescued Notch induced growth reduction, which was correlated with an increase in ECM components. Moreover, silencing ΔNp63 in myoepithelial HBECs reduced growth similar to Notch activation and it led to downregulation of myoepithelial and upregulation of luminal markers. Complementing this observation, forced expression of ONp63 in luminal HBECs induced myoepithelial phenotype and decreased luminal markers. In vivo, by the analysis of a Notch reporter mouse strain, I showed that Notch is activated during puberty specifically at the sites of ductal morphogenesis, terminal end buds. FAGS analysis revealed that it can be detected in two different populations based on CD24 expression (low (lo) or high (high)): at lower levels in CD24lo, which includes stem/progenitor and myoepithelial cells and higher levels in CD24hi, which contains luminal cells. In parallel with in vitro results, the CD24lo mouse mammary epithelial cells displaying Notch activity have lower levels of p63 expression. Furthermore, deletion of RBPjk, the main mediator of Notch signaling, or the overexpression of ΔNp63 inhibited luminal cell lineage in vivo. Another important point revealed by Notch reporter mouse strain is the simultaneous activation of Notch with estrogen signaling during pubertal development. The expression of FOXA1, the mediator of estrogen receptor (ER) transcriptional activity, is correlated with Notch activation in vivo that it is lower in CD24lo than in CD24hi cells. Moreover, FOXA1 is regulated by NICD in vitro supporting the presence of a link between Notch and ER signaling. Taken together, I report that Notch signaling is involved in luminal cell fate determination and its effects are partially mediated through inhibition of ONp63. Besides, ΔNp63 is required for the maintenance and sufficient for the induction of myoepithelial phenotype in HBECs in vitro and is not compatible with luminal lineage in vivo. Based on these results, I propose a model for epithelial cell hierarchy in mammary gland, whereby there are two different types of luminal progenitors, early and late, displaying different levels of Notch activity. Notch signaling contributes to the determination of luminal cell lineage in these two progenitor steps: In "Early Luminal Progenitor" stage, it inhibits myoepithelial fate by decreasing p63 expression, and in "Late Luminal Progenitor" stage, Notch signaling is involved in induction of luminal lineage by acting on ER-FOXA1 axis. It has to be investigated further whether Notch signaling might behave as an oncogene or tumor suppressor depending on which cell type in the epithelial hierarchy it is modulated and which one is more likely to occur in different human breast cancer types. RÉSUMÉ : La glande mammaire est composée de deux types principaux de cellules: les cellules luminales, qui bordent le lumen et les cellules myoépithéliales, qui se trouvent entre la lame basale et les cellules luminales. Les mécanismes intervenant dans leur différenciation et leur maintenance demeurent encore mal compris. La protéine transmembranaire Notch est connue pour déterminer le destin des cellules dans plusieurs types de tissus comme la peau ou le système nerveux. Selon le type de tissu dans lequel se trouve Notch, il agira soit comme un suppresseur de tumeur soit comme un oncogène. A l'aide de modèles de souris surexprimant les récepteurs actifs de Notch, il a été démontré que la voie de signalisation de Notch est oncogénique au niveau de la glande mammaire. Des études descriptives et fonctionnelles dans le cadre du cancer du sein ont permis de mettre en évidence une augmentation de l'activité de Notch ou de l'expression de ces composants dans certains tissus cancéreux. Toutefois, le rôle physiologique de Notch et des mécanismes qu'il active restent méconnus. P63, une protéine membre de la famille p53, est impliquée dans la différenciation des kératinocytes. Le modèle issu de l'étude des souris p63 knockout a révélé que cette protéine est requise pour la formation des primordia mammaires chez l'embryon et que son isoforme ΔNp63 est exclusivement exprimée dans la couche myoépithéliale de la glande mammaire adulte. Dans le but de comprendre les fonctions physiologiques de Notch, je l'ai activé en exprimant le domaine intracellulaire de Notch 1 (NICD) dans des cellules épithéliales primaires de glande mammaire humaine (HBECs). Le NICD a alors réduit la croissance des HBECs et conduit à la régulation négative non seulement de p63 mais également des composants du réseau d'interaction des récepteurs de la matrice extracellulaire (ECM). En exprimant conjointement ΔNp63 et NICD, il est apparu que la réduction de croissance induite par Notch était partiellement compensée, et qu'il y avait également une augmentation des composants ECM. De plus, lorsque ΔNp63 a été inactivé dans les cellules HBECs myoépithéliales, une réduction de croissance cellulaire identique à celle provoquée par l'activation de Notch a pu être mise en évidence, de même qu'une régulation négative des marqueurs myoépithéliaux ainsi qu'une augmentation des marqueurs luminaux. Afin de compléter ces informations, l'expression de ΔNp63 a été forcée dans les HBECs luminales, ce qui a induit un phénotype myoépithélial et une diminution des marqueurs lumineux. In vivo, par l'analyse de souris ayant un gène rapporteur de l'activité de Notch, j'ai démontré que Notch est activé pendant la puberté au niveau des sites de la morphogenèse canalaire, à savoir les bourgeons terminaux. Les analyses par FACS (Fluorescence-activated cell sorting) basées sur l'expression de l'antigène CD24 ont révélé qu'il peut tre détecté dans deux populations différentes : une population qui l'exprime faiblement, qui regroupe les cellules souches/progéniteurs et les cellules myoépithéliales, et une population qui l'exprime fortement qui est composé des cellules luminales. Parallèlement aux résultats in vitro, j'ai mis en évidence un faible niveau d'expression de p63 dans les cellules épithéliales de la glande mammaire de souris, exprimant faiblement l'antigène CD24 et présentant une activité de Notch. De plus, la délétion de RBPjr~, médiateur principal de la signalisation de Notch, ainsi que la surexpression de ΔNp63 in vivo ont inhibé la lignée des cellules luminales. Un autre point important révélé par les souris rapporteur de l'activité de Notch a été l'activation simultanée de Notch et de la signalisation de l'oestrogène pendant le développement pubertaire. L'expression de FOXA1, médiateur de l'activité transcriptionnelle des récepteurs aux oestrogènes (ER), est en corrélation avec l'activation de Notch in vivo, plus basse dans les cellules avec une faible expression de l'antigène CD24 que dans celles avec une forte expression. De plus, FOXA1 est régulé par NICD in vitro confirmant la présence d'un lien entre Notch et la signalisation des ER. En résumé, la signalisation de Notch est impliquée dans la détermination du destin cellulaire des cellules luminales et ses effets sont partiellement modifiés par l'inhibition de ΔNp63. ΔNp63 est requis pour la maintenance et est suffisant pour l'induction du phénotype myoépithéliale dans les HBECs in vitro et ne peut donc pas se trouver dans les cellules luminales in vivo. Basé sur ces résultats, je propose un modèle de hiérarchisation des cellules épithéliales de la glande mammaire, dans lequel sont présents deux types de progéniteurs des cellules luminales exprimant des niveaux différents d'activité de Notch, les progéniteurs lumineux précoces et tardifs. La signalisation de Notch contribue à la différenciation de la lignée cellulaire luminale au niveau de ces deux progéniteurs : dans la forme précoce, il inhibe la différenciation des cellules myoépithéliales en réduisant l'expression de p63 et dans la forme tardive, Notch est impliqué dans l'induction de la lignée luminale en agissant sur l'axe ER-FOXA1. Il serait nécessaire d'investiguer plus loin si le fait que Notch agisse comme oncogène ou suppresseur de tumeur dépend du stade de différenciation de la cellule dans laquelle il est modulé et laquelle de ces deux fonctions il est le plus probable de rencontrer dans les différents types de cancer du sein.

Signing on Very Low Volume Rurd Roads Iowa DOT Project HR-262, July, 1984

Research was undertaken to define an appropriate level of use of traffic control devices on rural secondary roads that carry very low traffic volumes. The goal of this research was to improve the safety and efficiency of travel on the rural secondary road system. This goal was to be accomplished by providing County Engineers with guidance concerning the cost-effective use of traffic control devices on very low volume rural roads. A further objective was to define the range of traffic volumes on the roads for which the recommendations would be appropriate. Little previous research has been directed toward roads that carry very low traffic volumes. Consequently, the factual input for this research was developed by conducting an inventory of the signs and markings actually in use on 2,069 miles of rural road in Iowa. Most of these roads carried 15 or fewer vehicles per day. Additional input was provided by a survey of the opinions of County Engineers and Supervisors in Iowa. Data from both the inventory and the opinion survey indicated a considerable lack of uniformity in the application of signs on very low volume rural roads. The number of warning signs installed varied from 0.24 per mile to 3.85 per mile in the 21 counties in which the inventory was carried out. The use of specific signs not only varied quite widely among counties but also indicated a lack of uniform application within counties. County officials generally favored varying the elaborateness of signing depending upon the type of surface and the volume of traffic on different roads. Less elaborate signing would be installed on an unpaved road than on a paved road. A concensus opinion was that roads carrying fewer than 25 vehicles per day should have fewer signs than roads carrying higher volumes. Although roads carrying 0 to 24 vehicles per day constituted over 24% of the total rural secondary system, they carried less than 3% of the total travel on that system. Virtually all of these roads are classified as area service roads and would thus be expected to carry only short trips primarily by local motorists. Consequently, it was concluded that the need for warning signs rarely can be demonstrated on unpaved rural roads with traffic volumes of fewer than 25 vehicles per day. It is recommended that each county designate a portion of its roads as an Area Service Level B system. All road segments with very low traffic volumes should be considered for inclusion in this system. Roads included in this system may receive a lesser level of maintenance and a reduced level of signing. The county is also afforded protection from liability arising from accidents occurring on roads designated as part of an Area Service Level B system. A uniform absence of warning signs on roads of this nature is not expected to have any discernible effect on the safety or quality of service on these very low volume roads. The resources conserved may be expended more effectively to upgrade maintenance and traffic control on roads carrying higher volumes where the beneficial effect on highway safety and service will be much more consequential.

The oxygen concentrator : an appropriate technology for treating hypoxaemic children in developing countries

RÉSUMÉ L'Organisation Mondiale de la Santé (OMS) recommande d'administrer l'oxygène par concentrateurs dans les pays en voie de développement (PVD), les cylindres posant des problèmes logistiques et financiers trop importants. Cette technologie a été proposée aux enfants d'un hôpital sénégalais (Ndioum) qui présentaient les critères d'oxygénation de l'OMS. Les bénéfices cliniques et financiers ont été majeurs. En revanche, les connaissances des soignants sur les diverses techniques d'administration d'oxygène ainsi que les prestations du service de maintenance étaient insuffisantes. L'implantation de concentrateurs doit être encouragée dans les PVD, mais doit respecter une stratégie englobant enseignement, maintenance et suivi de l'opération. Diverses actions correctrices ont été entreprises à Ndioum où plusieurs concentrateurs fonctionnent désormais régulièrement. Summary: The World Health Organisation (WHO) recommends supplying oxygen in developing countries by concentra¬tors because cylinders pose considerable logistic and financial problems. This technology was employed to treat children in a hospital in Ndioum, Senegal, who met the WHO oxygenation criteria. There were clear clinical and financial benefits, but neither the nurses' knowledge of the various techniques of oxygen supply nor the maintenance service were satisfactory. The use of concentra¬tors should be encouraged in developing countries. A strategy including technical training, maintenance and monitoring should be adopted. Corrective actions were undertaken in Ndioum, and several concentrators are now being used on a regular basis.

Hay competencia en el mercado europeo de transporte aéreo?: el caso español

La liberalización del transporte aéreo que se llevó a término en la Unión Europea a principios de los años noventa ha tenido efectos positivos sobre el bienestar del viajero. No obstante, existe un consenso en la literatura académica que estos efectos dependen de la existencia de una competencia efectiva en el nivel de la ruta. En este sentido, se plantea el problema que puede llegar a suponer las ventajas de escalera de las compañías dominantes en cada mercado interior. Además, se pretende capturar la diferenciación de productos como característica esencial de la industria del transporte aéreo. El análisis de estas cuestiones se realiza de la forma siguiente. En primer lugar, se hace referencia a los principales aspectos económicos que condicionan la competencia en el transporte aéreo. Y en segundo lugar, se implementa un modelo empírico basado en un sistema de tres ecuaciones, que se estima mediante la técnica de las variables instrumentales. La muestra utilizada hace referencia al año 2001 para la mayoría de las rutas del mercado interior español de vuelos regulares en dónde hay competencia. Los resultados de la estimación muestran la existencia de unas condiciones de competencia diferentes según el segmento del mercado al cual se dirigen las compañías aéreas. Efectivamente, la competencia en precios (calidad) parece ser predominante en el segmento de viajeros por motivos personales (negocios). Adicionalmente, el dominio que la compañía dominante tiene sobre la mayoría de las rutas parece descansar en las ventajas competitivas, tanto en términos de costes como en términos de demanda, que le proporciona el control de la red aeroportuaria nacional. De todo esto se puede inferir que el mantenimiento y/o aumento de los beneficios de la liberalización de los servicios de transporte aéreo exige extender la liberalización al uso del aeropuertos así como descentralizar su gestión.

The membrane-associated transient receptor potential vanilloid channel is the central heat shock receptor controlling the cellular heat shock response in epithelial cells.

The heat shock response (HSR) is a highly conserved molecular response to various types of stresses, including heat shock, during which heat-shock proteins (Hsps) are produced to prevent and repair damages in labile proteins and membranes. In cells, protein unfolding in the cytoplasm is thought to directly enable the activation of the heat shock factor 1 (HSF-1), however, recent work supports the activation of the HSR via an increase in the fluidity of specific membrane domains, leading to activation of heat-shock genes. Our findings support the existence of a plasma membrane-dependent mechanism of HSF-1 activation in animal cells, which is initiated by a membrane-associated transient receptor potential vanilloid receptor (TRPV). We found in various non-cancerous and cancerous mammalian epithelial cells that the TRPV1 agonists, capsaicin and resiniferatoxin (RTX), upregulated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70 and Hsp90 respectively, while the TRPV1 antagonists, capsazepine and AMG-9810, attenuated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70, Hsp90, respectively. Capsaicin was also shown to activate HSF-1. These findings suggest that heat-sensing and signaling in mammalian cells is dependent on TRPV channels in the plasma membrane. Thus, TRPV channels may be important drug targets to inhibit or restore the cellular stress response in diseases with defective cellular proteins, such as cancer, inflammation and aging.

Feasibility of Cooperative Development of Wetland Mitigation Projects, TR-526, 2006

The Iowa Department of Transportation (Iowa DOT) currently performs wetland mitigation on a project-by-project basis. At the same time, other agencies like the Iowa Department of Natural Resources and Natural Resource Conservation Service are performing wetland restoration projects, and counties and cities may be mitigating wetland losses as well. This project examined the feasibility of developing cooperative wetland mitigation projects in order to utilize state and local resources more efficiently to benefit both Iowa and local communities. The project accomplished the following objectives: (1) Identified and characterized cooperative wetland mitigation programs nationwide; (2) Developed a needs assessment through a survey of state, county, and large city agencies in Iowa to describe wetland mitigation programs and determine challenges with mitigation and program improvements, including long-term risks associated with maintenance and monitoring programs; (3) Surveyed state, county, and city agencies and organizations to identify resources available for developing cooperative mitigation projects and procedures; (4) Developed a conceptual framework for cooperative wetland mitigation.

Longevity differs among sexes but is not affected by repeated immune activation in voles (Microtus arvalis)

Investment of resources in immune defences, despite obvious short-term benefits, may be detrimental to long-term maintenance and thus decrease longevity in absence of parasites. In addition, females and males may differ in immune investment and intrinsic longevity because they are subjected to different degrees of sexual competition and extrinsic mortality. In order to test if sex-specific investment in mounting an immune response reduced longevity, we compared the longevity of captive male and female common voles Microtus arvalis regularly challenged with keyhole limpet haemocyanin, an antigen which elicits the production of antibodies, to the longevity of voles injected with the corresponding antigen-free buffer (phosphate-buffered saline). Injections were repeated every 28 days to mimic a chronic infection. The magnitude of immune response did not vary between males and females and did not affect longevity. Overall, females lived longer than males, independently of the immune challenge. Thus, the long-term costs of immunity seem small in voles. The longevity pattern is consistent with the prediction that male-biased predation or parasitism in the wild causes reduced intrinsic lifespan, but this reduction is not mediated by a decrease in male immunity

This is YOUR Highway Commission,1968

Before the Iowa Department of Transportation (DOT) was established by legislation in July 1974, there were several state agencies that handled the tasks that are now the responsibility of an integrated, multimodal Iowa DOT. Among those agencies was the Iowa State Highway Commission (IHC). You are invited to read a brief history of the Iowa DOT here:http://www.iowadot.gov/about/organizationalhistory.htm The IHC operated as an independent state agency between 1913 and 1974. In 1968, the IHC created and released This is YOUR Highway Commission, a 24 ½- minute film that showcased the responsibilities and functions of the IHC. The narrator describes the activities of various offices and employees, and explains how those activities benefited Iowa’s citizens and motorists. The film journeys through all areas of IHC responsibility to Iowa’s roadways, including administration, planning, design, bidding, right of way, materials, construction, maintenance and facilities. As part of the Iowa DOT’s effort to preserve and archive its historical resources, the original 16mm film was professionally cleaned, restored and digitized so that it could be made available via this website. The Iowa DOT is currently researching and compiling information necessary to prepare detailed biographies of the IHC employees identified in the film. Included in each biography will be still frames taken from the film, as well as other images from the Iowa DOT’s archives. This more comprehensive description of the film will be available in the future. In the meantime, below is a list of the IHC employees who have been identified. The list is arranged in the order in which each employee first appears in the film. There remain numerous unidentified employees in the film, and the Iowa DOT would greatly appreciate any assistance in identifying them. If you recognize an IHC employee in the film who is not on this list, please contactbeth.collins@dot.iowa.gov with any information you feel would be useful. Identified employees: Joseph Coupal, Jr.—Director of Highways Harry Bradley—Commissioner Derby Thompson—Commissioner John Hansen—Commissioner Koert Voorhees—Commissioner Harold Shiel—Engineer Howard Gunnerson—Chief engineer Martha Groth—Commission Secretary Robert Barry—Commissioner Nancy Groomes—Director’s Secretary Russell Moreland—Planning C.B. Anderson—Planning Gus Anderson—Engineer Carl Schach—Deputy chief engineer Raymond Kassel—Hearings engineer (later director of Transportation) Bob Given—Deputy chief engineer Don McLean—Director of Engineering Howard Thielen—Surveying (using rod) John Huss—Surveying (using leveling transit) John “Harley” McCoy—Surveying (taking notes) Jim Smith—Right of Way Keith Davis—Contracts Sherrill P. Freed—Sign Shop Olav Smedal—Director of Public Information