Outward potassium current oscillations in macrophage polykaryons: extracellular calcium entry and calcium-induced calcium release

Outward current oscillations associated with transient membrane hyperpolarizations were induced in murine macrophage polykaryons by membrane depolarization in the absence of external Na+. Oscillations corresponded to a cyclic activation of Ca2+-dependent K+ currents (IKCa) probably correlated with variations in intracellular Ca2+ concentration. Addition of external Na+ (8 mM) immediately abolished the outward current oscillations, suggesting that the absence of the cation is necessary not only for their induction but also for their maintenance. Oscillations were completely blocked by nisoldipine. Ruthenium red and ryanodine reduced the number of outward current cycles in each episode, whereas quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low molecular weight heparin nor the absence of a Na+ gradient across the membrane had any influence on oscillations. The evidence suggests that Ca2+ entry through a pathway sensitive to Ca2+ channel blockers is elicited by membrane depolarization in Na+-free medium and is essential to initiate oscillations, which are also dependent on the cyclic release of Ca2+ from intracellular Ca2+-sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing slow deactivation of IKCa. Evidence is presented that neither a Na+/Ca2+ antiporter nor Ca2+ release from IP3-sensitive Ca2+ stores participate directly in the mechanism of oscillation

UK commercial property lease structures: Landlord and tenant mismatch

UK commercial property lease structures have come under considerable scrutiny during the past decade since the property crash of the early 1990s. In particular, tenants complained that the system was unfair and that it has blocked business change. Government is committed, through its 2001 election manifesto, to promote flexibility and choice in the commercial property lettings market and a new voluntary Commercial Leases Code of Practice was launched in April 2002. This paper investigates whether occupiers are being offered the leases they require or whether there is a mismatch between occupier requirements and actual leases in the market. It draws together the substantial data now available on the actual terms of leases in the UK and surveys of corporate occupiers' attitude to their occupation requirements. Although the data indicated that UK leases have become shorter and more diverse since 1990, this is still not sufficient to meet the current requirements of many corporate occupiers. It is clear that the inability to manage entry and exit strategies is a major concern to occupiers. Lease length is the primary concern of tenants and a number of respondents comment on the mismatch between lease length in the UK and business planning horizons. The right to break and other problems with alienation clauses also pose serious difficulties for occupiers, thus reinforcing the mismatch. Other issues include repairing and insuring clauses and the type of review clause. There are differences in opinion between types of occupier. In particular, international corporate occupiers are significantly more concerned about the length of lease and the incidence of break clauses than national occupiers and private-sector tenants are significantly more concerned about leasing in general than public-sector occupiers. Proposed solutions by tenants are predictable and include shorter leases, more frequent breaks and relaxation of restrictions concerning alienation and other clauses. A significant number specify that they would pay more for shorter leases and other improved terms. Short leases would make many of the other terms more acceptable and this is why they are the main concern of corporate occupiers. Overall, the evidence suggests that there continues to be a gap between occupiers' lease requirements and those currently offered by the market. There are underlying structural factors that act as an inertial force on landlords and inhibit the changes which occupiers appear to want. Nevertheless, the findings raise future research questions concerning whether UK lease structures are a constraining factor on UK competitiveness.

Forkhead (FOX) transcription factors and the cell cycle: measurement of DNA binding by FoxO and FoxM transcription factors

Certain forkhead (FOX) transcription factors have been shown to play an intrinsic role in controlling cell cycle progression. In particular, the FoxO subclass has been shown to regulate cell cycle entry and exit, whereas the expression and activity of FoxM1 is important for the correct coupling of DNA synthesis to mitosis. In this chapter, I describe a method for measuring FoxO and FoxM1 transcription factor DNA binding in nuclear extracts from mammalian cells.

Video activity extraction and reporting with incremental unsupervised learning

The present work presents a new method for activity extraction and reporting from video based on the aggregation of fuzzy relations. Trajectory clustering is first employed mainly to discover the points of entry and exit of mobiles appearing in the scene. In a second step, proximity relations between resulting clusters of detected mobiles and contextual elements from the scene are modeled employing fuzzy relations. These can then be aggregated employing typical soft-computing algebra. A clustering algorithm based on the transitive closure calculation of the fuzzy relations allows building the structure of the scene and characterises the ongoing different activities of the scene. Discovered activity zones can be reported as activity maps with different granularities thanks to the analysis of the transitive closure matrix. Taking advantage of the soft relation properties, activity zones and related activities can be labeled in a more human-like language. We present results obtained on real videos corresponding to apron monitoring in the Toulouse airport in France.

Organic certification, export market access and the impacts of policy: Bayesian estimation of avocado smallholder “times-to-organic certification” in Michoacán Mexico

This study analyzes organic adoption decisions using a rich set of time-to-organic durations collected from avocado small-holders in Michoacán Mexico. We derive robust, intrasample predictions about the profiles of entry and exit within the conventional-versus-organic complex and we explore the sensitivity of these predictions to choice of functional form. The dynamic nature of the sample allows us to make retrospective predictions and we establish, precisely, the profile of organic entry had the respondents been availed optimal amounts of adoption-restraining resources. A fundamental problem in the dynamic adoption literature, hitherto unrecognized, is discussed and consequent extensions are suggested.

Understanding complexities in international accounting standard setting: agenda entry and the case of IFRS for SMEs

Earlier accounting works have shown that an understanding of agenda entry is critical to better understanding the accounting standards setting process. Consider Walker and Robinson (1993; 1994) and Ryan (1998); and more generally agenda entrance as theorized in Kingdon (2011). In 2003, the IASB placed on its agenda a project to promulgate a standard for small and medium-sized entities (SMEs). This provides our focus. It seemed to be a departure from the IASB’s constitutional focus on capital market participants. Kingdon’s three-streams model of agenda entry helps to identify some of the complexities related to politics and decision making messiness that resulted in a standard setting project for simplified IFRS, misleadingly titled IFRS for SMEs. Complexities relate to the broader international regulatory context, including the boundaries of the IASB’s standard-setting jurisdiction, the role of board members in changing those boundaries, and such sensitivities over the language that the IASB could not agree on a suitably descriptive title. The paper shows similarities with earlier agenda entrance studies by Walker and Robinson (1994) and Ryan (1998). By drawing on interviewees’ recollections and other material it especially reinforces the part played by the nuanced complexities that influence what emerges as an international accounting standard.

Incumbency Reconsidered: Prospects, Strategic Entry, and Incumbent Quality in U.S. House Elections

Efforts to estimate the magnitude of the incumbency effect in U.S. House elections and assess its political meaning have been complicated by two omitted-variables problems. First, in the absence of an adequate measure of incumbent prospects, estimates of the magnitude of the incumbency effect fail to control for selection effects associated with the decision incumbents make about whether to run for reelection. Strategic incumbents enter races they think they can win and withdraw when they expect to lose. The consequence is an upward bias in estimates of incumbents’ electoral advantages. Second, the normative implications of high reelection rates cannot be assessed without measuring incumbent quality, since a possible explanation for their electoral success is that incumbents are of high quality and doing a good job. We propose a strategy for measuring incumbent prospects and quality, demonstrate the strategic nature of incumbent and challenger entry, re-estimate the incumbency effect, and show that incumbent quality has an impact on electoral outcomes. Our conclusion is that incumbents’ advantages in House elections have been over estimated while the positive basis of incumbent safety is typically under appreciated.

The drivers for entry and expansion modes of U.S.- based MNES in Brazil

The drivers for entry and expansion modes of multinational enterprises (MNEs) have been studied by several authors over the last decades but empirical results have been historically mixed. More recently, Hennart (2009) argued that the reason for the inconsistent results to date resided in the fact that prior theories assumed that local markets could be freely accessed based on a unilateral decision by the MNEs, and then proposes an alternative framework in which the entry and expansion modes of MNEs in foreign countries are a solution based on the relative efficiency of both markets. In this study, the proposed framework is tested against the prior theories based on investments made by U.S.-based MNEs in Brazil from 2005 to 2010. The results suggest that the local market characteristics, more specifically the concentration ratio at the firm and asset levels, are indeed important to influence the entry and expansion mode of U.S.-based MNEs in Brazil, reinforcing the argument against MNEs-centric theories. However, differently from Hennart’s proposition, we were not able to confirm the hypotheses that the MNEs skills are relevant to influence the final solution. We have also tested whether the difference in growth rate between the two countries could be a driver for MNEs to favor acquisition over greenfield given the opportunity cost of postponing the investments. The test result, based on our sample, was not able to confirm this hypothesis.

Entry and externality : hydroelectric generators in Brazil

This work analyzes the entry problem in the hydroelectric generation industry. The operation of a generator upstream regularizes the river flow for generators located downstream on the same river, increasing the production capacity of the latter. This positive externality increases the attractiveness of the locations downstream whenever a generator decides to enter upstream. Therefore, the entry decision of a generator in a given location may affect all entry decisions in potential locations for plants downstream. I first model the problem of generators located in cascade on the same river to show the positive effect of the externality. Next, I develop a method to estimate an entry model specific to the hydro generation industry which takes into account the externality of the entry decisions. Finally, I use a data set on investment decisions of Brazilian hydro-generators to estimate the model. The results show a positive incentive to locate downstream from existing plants and from locations where entry is likely to occur. An interesting by-product of the analysis is that the year effects’ estimates show an increase one year before the energy crisis of 2001, providing evidence that the market anticipated the crisis. It contradicts the governmental version that the crisis was due to an unexpected drought.

Barriers to entry and development

This paper analyzes the effect of an accountability system in the Brazilian college market. For each discipline, colleges were assigned a grade that depended on the scores of their students on the ENC, an annual mandatory exam. Those grades were then disclosed to the public, giving applicants information about college quality. The system also established rewards and penalties based on the colleges’ grades. I find that the ENC had a substantial effect on different measures of college quality, such as faculty education and the proportion of full-time faculty. The detailed information from this unique dataset and the fact that the ENC started being required for different disciplines in different years allow me to control for time-specific effects, thus minimizing the bias caused by policy endogeneity. Indeed, I find strong evidence on the importance of controlling for time-specific effects: estimates of the impact of the ENC on college quality more than double when I do not take those effects into account. The ENC also affects positively the ratio between applicants and vacancies, and it decreases the faculty and the entering class sizes. The results suggest that its introduction fostered competition and favored colleges entering the market.

Structural reforms, technological gaps and economic development: a Latin American perspective

Includes bibliography

Essays on Industrial Organization and Environmental Economics

This dissertation studies environmental regulation issues in the hog production industry as well as forces behind the reorganization of the industry during the past two decades. Federal and State-level environmental regulations imposed on U.S. hog production during the year 2003 are examined in Chapter 1. Based on the number of regulations passed by the Federal government and states, the 2003 regulatory index is constructed. The regulatory stringency index suggests that state-level regulations vary across states and have increased over the years. In addition, state-level regulations are more stringent than federal regulations. Chapter 2 develops an empirically implementable theoretical model which allows us to investigate the long-run effects of environmental regulations on the U.S. hog industry. Hog feeding operations (HFOs) are divided into large feeding operations (LHFOs) and small feeding operations (SHFOs). The impact of the presence of a large number of LHFOs on the entry and exit of CHFOs is also examined. Results of this study suggest that: Increased state-level regulation stringency significantly lowers the output of SHFOs; increased state-level regulation stringency significantly lowers the output of LHFOs; increased state-level regulation stringency significantly lowers the number of SHFOs; SHFO output rises significantly in states that have a greater number of LHFOs; LHFO output rises significantly in states that have a greater number of LHFOs; the number of SHFOs significantly increases in states that have a greater numbers of LHFOs; regulation increases the average SHFO size; and regulation decreases the average LHFO size. Chapter 3 examines the importance of input availability, market attractiveness, agglomeration economies and environmental regulations on the reorganization of U.S. hog production for a panel of 22 U.S. hog producing states which include, Northern states, Southern states and Midwest states for the period 1994-2006. Results from this study suggest that: Hog production in a state is positively affected by hog production in a nearby state, confirming the presence of agglomeration economies; Environmental regulations and high corn price have negative effects on state-level U.S. hog production; High hog prices, and favorable labor cost, and land values attract hog production; and transportation cost has no effect on hog production. Advisors: Azzeddine Azzam and Karina Schoengold

Drug delivery, entry and intracellular trafficking of polymeric nanoparticles

Polymere Nanopartikel sind kleine Teilchen, die vielseitige Einsatzmöglichkeiten für den Transport von Wirkstoffen bieten. Da Nanomaterialien in diesen biomedizinischen Anwendungen oft mit biologischen Systemen in Berührung kommen, erfordert das eine genaue Untersuchung ihrer gegenseitigen Wechselwirkungen. In diesem speziellen Forschungsgebiet, welches sich auf die Interaktionen von Nanomaterialien mit biologischen Komponenten konzentriert, wurde bereits eine Vielzahl verschiedener Nanopartikel-Zell-Interaktionen (z. B. Nanotoxizität, Wirkstofftransport-mechanismen) analysiert. Bezüglich der Untersuchungen zu nanopartikulären Wirkstofftransport-mechanismen ist es im Allgemeinen akzeptiert, dass ein erfolgreicher zellulärer Transport hauptsächlich von der Aufnahme des Nanotransporters abhängt. Deshalb analysieren wir in dieser Arbeit (1) den Wirkstofftransportmechanismus für biologisch-abbaubare eisenhaltige Poly-L-Milchsäure Nanopartikel (PLLA-Fe-PMI) sowie (2) die Aufnahmemechanismen und die intrazellulären Transportwege von nicht-abbaubaren superparamagnetischen Polystyrolnanopartikeln (SPIOPSN). rnIn dieser Arbeit identifizieren wir einen bisher unbekannten und nicht-invasiven Wirkstoff-transportmechanismus. Dabei zeigt diese Studie, dass der subzelluläre Transport der nanopartikulärer Fracht nicht unbedingt von einer Aufnahme der Nanotransporter abhängt. Der identifizierte Arzneimitteltransportmechanismus basiert auf einem einfachen physikochemischen Kontakt des hydrophoben Poly-L-Milchsäure-Nanopartikels mit einer hydrophoben Oberfläche, wodurch die Freisetzung der nanopartikulären Fracht ausgelöst wird. In Zellexperimenten führt die membranvermittelte Freisetzung der nanopartikulären Fracht zu ihrem sofortigen Transport in TIP47+- und ADRP+- Lipidtröpfchen. Der Freisetzungsmechanismus („kiss-and-run") kann durch die kovalente Einbindung des Frachtmoleküls in das Polymer des Nanopartikels blockiert werden.rnWeiterhin wird in Langzeitversuchen gezeigt, dass die Aufnahme der untersuchten polymeren Nanopartikel von einem Makropinozytose-ähnlichen Mechanismus gesteuert wird. Im Laufe dieser Arbeit werden mehrere Faktoren identifiziert, die in diesem Aufnahmemechanismus eine Rolle spielen. Darunter fallen unter anderem die kleinen GTPasen Rac1 und ARF1, die die Aufnahme von SPIOPSN beeinflussen. Darauffolgend werden die intrazellulären Transportwege der Nanopartikel untersucht. Mit Hilfe eines neuartigen Massenspektrometrieansatzes wird der intrazelluläre Transport von nanopartikelhaltigen endozytotischen Vesikeln rekonstruiert. Intensive Untersuchungen identifizieren Marker von frühen Endosomen, späten Endosomen/ multivesikulären Körpern, Rab11+- Endosomen, Flotillin-Vesikeln, Lysosomen und COP-Vesikeln. Schließlich wird der Einfluss des lysosomalen Milieus auf die Proteinhülle der Nanopartikel untersucht. Hier wird gezeigt, dass die adsorbierte Proteinhülle auf den Nanopartikeln in die Zelle transportiert wird und anschließend im Lysosom abgebaut wird. rnInsgesamt verdeutlicht diese Arbeit, dass die klassische Strategie des nanopartikulären und invasiven Wirkstofftransportmechanismuses überdacht werden muss. Weiterhin lässt sich aus den Daten schlussfolgern, dass polymere Nanopartikel einem atypischen Makropinozytose-ähnlichen Aufnahmemechanismus unterliegen. Dies resultiert in einem intrazellulären Transport der Nanopartikel von Makropinosomen über multivesikuläre Körperchen zu Lysosomen.rn