El impacto de la reforma de la segunda vuelta: Perú en perspectiva comparada

Although no electoral rule is a panacea, the runoff was a successful reform in Peru as well as in Latin America in general. Presidential candidates were enticed towards the political centre and, with majorities of votes, presidents rarely suffered legitimacy deficits. Runoff does, however, lower entry barri- ers and enable a larger number of parties. Although lower entry barriers were helpful in the incorporation of the left into the electoral arena in the post-Cold War period, a large number of parties is problematic. Whilst the challenge of party-building is herculean, various additional electoral-rule reforms are likel.Si bien ninguna regla electoral es una panacea, la introducción de la segunda vuelta fue una reforma exitosa en Perú y en América Latina en general. Las y los candidatos presidenciales fueron atraídos hacia el centro político y, con la mayoría de los votos, las y los presidentes rara vez sufrieron déficits de legitimidad. Sin embargo, la segunda vuelta también reduce las barreras de entrada y permite un mayor número de partidos. Si bien la reducción de las barreras de entrada ayudó a incorporar a la izquierda a la arena electoral en el periodo posterior a la Guerra Fría, un número grande de partidos resulta problemático para el sistema democrático. Aunque el desafío de la construcción de partidos es gigantesco, es probable que varias reformas adicionales a las reglas electorales sean útiles en el esfuerzo por construir partidos políticos receptivos en Perú y en otras partes de América Latina

Distinct encounter complexes of PAI-1 with plasminogen activators and vitronectin revealed by changes in the conformation and dynamics of the reactive center loop

© 2015 The Protein Society Plasminogen activator inhibitor-1 (PAI-1) is a biologically important serine protease inhibitor (serpin) that, when overexpressed, is associated with a high risk for cardiovascular disease and cancer metastasis. Several of its ligands, including vitronectin, tissue-type and urokinase-type plasminogen activator (tPA, uPA), affect the fate of PAI-1. Here, we measured changes in the solvent accessibility and dynamics of an important unresolved functional region, the reactive center loop (RCL), upon binding of these ligands. Binding of the catalytically inactive S195A variant of tPA to the RCL causes an increase in fluorescence, indicating greater solvent protection, at its C-terminus, while mobility along the loop remains relatively unchanged. In contrast, a fluorescence increase and large decrease in mobility at the N-terminal RCL is observed upon binding of S195A-uPA to PAI-1. At a site distant from the RCL, binding of vitronectin results in a modest decrease in fluorescence at its proximal end without restricting overall loop dynamics. These results provide the new evidence for ligand effects on RCL conformation and dynamics and differences in the Michaelis complex with plasminogen activators that can be used for the development of more specific inhibitors to PAI-1. This study is also the first to use electron paramagnetic resonance (EPR) spectroscopy to investigate PAI-1 dynamics. Significance: Balanced blood homeostasis and controlled cell migration requires coordination between serine proteases, serpins, and cofactors. These ligands form noncovalent complexes, which influence the outcome of protease inhibition and associated physiological processes. This study reveals differences in binding via changes in solvent accessibility and dynamics within these complexes that can be exploited to develop more specific drugs in the treatment of diseases associated with unbalanced serpin activity

Copper(II) Ions Increase Plasminogen Activator Inhibitor Type 1 Dynamics in Key Structural Regions That Govern Stability

© 2016 American Chemical Society. Plasminogen activator inhibitor type 1 (PAI-1) regulates the fibrinolysis pathway by inhibiting the protease activity of plasminogen activators. PAI-1 works in concert with vitronectin (VN), an extracellular protein that aids in localization of active PAI-1 to tissues. The Peterson laboratory demonstrated that Cu(II) and other transition metals modulate the stability of PAI-1, exhibiting effects that are dependent on the presence or absence of the somatomedin B (SMB) domain of VN. The study presented here dissects the changes in molecular dynamics underlying the destabilizing effects of Cu(II) on PAI-1. We utilize backbone amide hydrogen/deuterium exchange monitored by mass spectrometry to assess PAI-1 dynamics in the presence and absence of Cu(II) ions with and without the SMB domain of VN. We show that Cu(II) produces an increase in dynamics in regions important for the function and overall stability of PAI-1, while the SMB domain elicits virtually the opposite effect. A mutant form of PAI-1 lacking two N-terminal histidine residues at positions 2 and 3 exhibits similar increases in dynamics upon Cu(II) binding compared to that of active wild-type PAI-1, indicating that the observed structural effects are not a result of coordination of Cu(II) to these histidine residues. Finally, addition of Cu(II) results in an acceleration of the local unfolding kinetics of PAI-1 presumed to be on pathway to the latency conversion. The effect of ligands on the dynamics of PAI-1 adds another intriguing dimension to the mechanisms for regulation of PAI-1 stability and function

Resolving distinct molecular origins for copper effects on PAI-1

© 2017, The Author(s). Components of the fibrinolytic system are subjected to stringent control to maintain proper hemostasis. Central to this regulation is the serpin plasminogen activator inhibitor-1 (PAI-1), which is responsible for specific and rapid inhibition of fibrinolytic proteases. Active PAI-1 is inherently unstable and readily converts to a latent, inactive form. The binding of vitronectin and other ligands influences stability of active PAI-1. Our laboratory recently observed reciprocal effects on the stability of active PAI-1 in the presence of transition metals, such as copper, depending on the whether vitronectin was also present (Thompson et al. Protein Sci 20:353–365, 2011). To better understand the molecular basis for these copper effects on PAI-1, we have developed a gel-based copper sensitivity assay that can be used to assess the copper concentrations that accelerate the conversion of active PAI-1 to a latent form. The copper sensitivity of wild-type PAI-1 was compared with variants lacking N-terminal histidine residues hypothesized to be involved in copper binding. In these PAI-1 variants, we observed significant differences in copper sensitivity, and these data were corroborated by latency conversion kinetics and thermodynamics of copper binding by isothermal titration calorimetry. These studies identified a copper-binding site involving histidines at positions 2 and 3 that confers a remarkable stabilization of PAI-1 beyond what is observed with vitronectin alone. A second site, independent from the two histidines, binds metal and increases the rate of the latency conversion

Cargese Lectures on the Kerr/CFT Correspondence

We give a short introduction, beginning with the Kerr geometry itself, to the basic results, motivation, open problems and future directions of the Kerr/CFT correspondence.Comment: Lectures given by A. Strominger at Cargese 2010. References update

THE INCLINATION OF THE SOFT X-RAY TRANSIENT A0620–00 AND THE MASS OF ITS BLACK HOLE

We analyze photometry of the soft X-ray transient A0620 – 00 spanning nearly 30 years, including previously published and previously unpublished data. Previous attempts to determine the inclination of A0620 using subsets of these data have yielded a wide range of measured values of i. Differences in the measured value of i have been due to changes in the shape of the light curve and uncertainty regarding the contamination from the disk. We give a new technique for estimating the disk fraction and find that disk light is significant in all light curves, even in the infrared. We also find that all changes in the shape and normalization of the light curve originate in a variable disk component. After accounting for this disk component, we find that all the data, including light curves of significantly different shapes, point to a consistent value of i. Combining results from many separate data sets, we find i = 51fdg0 ± 0fdg9, implying M = 6.6 ± 0.25 M ☉. Using our dynamical model and zero-disk stellar VIH magnitudes, we find d = 1.06 ± 0.12 kpc. Understanding the disk origin of nonellipsoidal variability may assist with making reliable determinations of i in other systems, and the fluctuations in disk light may provide a new observational tool for understanding the three-dimensional structure of the accretion disk.National Science Foundation (U.S.) (NSF Graduate Research Fellowship DGE-0202738)National Science Foundation (U.S.) (NSF/AST grant 0407063)National Science Foundation (U.S.) (NSF/AST grant 0707627

The Death and Rebirth of a Party System, Peru 1978-2001

This article evaluates structural, institutional, and actor-centered explanations of the collapse of the Peruvian party system around 1990 and its surprising partial recovery in 2001. It begins by describing the changes in the dependent variable, the emergence, collapse, and partial resurrection of the 1980s Peruvian party system. The next section examines the argument that the large size and rapid growth of the informal sector undermined the party system and led to its collapse. The author shows that the evidence does not support this argument. The article then examines changes in the electoral system. The author demonstrates that, contrary to theoretical expectations, the changes in the electoral system do not correlate with the observed changes in the party system. The final section shows that performance failure by political elites, including corruption in government, was more important than social cleavages or electoral institutions in the collapse and partial recovery of the party system.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

IR Contamination in Galactic X-Ray Novae

The most widely used means of measuring the mass of black holes in Galactic binaries - specifically the X-ray novae - involves both radial velocity measurements of the secondary star, and photometric measurements of its ellipsoidal variability. The latter is important in constraining the inclination and mass ratio, and requires as direct a measure of the flux of the secondary as possible. Up to now, such measurements have been preferentially carried out in the NIR (1 -- 2.5$\mu m$), where the flux from the cooler secondary is expected to dominate over that from the accretion disc. However, here we present evidence of a significant non-stellar contribution to the NIR flux in many of those quiescent X-ray novae that are thought to contain a black hole primary. We discuss origins of this excess and the effect of such contamination on Galactic black hole mass measurements.Comment: 9 pages, 4 figures, 2 tables, accepted for publication in MNRA

Multiwavelength Observations of A0620-00 in Quiescence

[Abridged.] We present multiwavelength observations of the black hole binary system, A0620-00. Using the Cosmic Origins Spectrograph on the Hubble Space Telescope, we have obtained the first FUV spectrum of A0620-00. The observed spectrum is flat in the FUV and very faint (with continuum fluxes \simeq 1e - 17 ergs/cm^2/s/A). We compiled the dereddened, broadband spectral energy distribution of A0620-00 and compared it to previous SEDs as well as theoretical models. The SEDs show that the source varies at all wavelengths for which we have multiple samples. Contrary to previous observations, the optical-UV spectrum does not continue to drop to shorter wavelengths, but instead shows a recovery and an increasingly blue spectrum in the FUV. We created an optical-UV spectrum of A0620-00 with the donor star contribution removed. The non-stellar spectrum peaks at \simeq3000 {\deg}A. The peak can be fit with a T=10,000 K blackbody with a small emitting area, probably originating in the hot spot where the accretion stream impacts the outer disk. However, one or more components in addition to the blackbody are needed to fit the FUV upturn and the red optical fluxes in the optical-UV spectrum. By comparing the mass accretion rate determined from the hot spot luminosity to the mean accretion rate inferred from the outburst history, we find that the latter is an order of magnitude smaller than the former, indicating that \sim90% of the accreted mass must be lost from the system if the predictions of the disk instability model and the estimated interoutburst interval are correct. The mass accretion rate at the hot spot is 10^5 the accretion rate at the black hole inferred from the X-ray luminosity. To reconcile these requires that outflows carry away virtually all of the accreted mass, a very low rate of mass transfer from the outer cold disk into the inner hot region, and/or radiatively inefficient accretion.Comment: ApJ, accepte

"Mother-weights" and lost fathers: parents in South Asian American literature

That parent-child relationships should play a significant role within South Asian American literature is perhaps no surprise, since this is crucial material for any writer. But the particular forms they so often take – a dysfunctional mother-daughter dynamic, leading to the search for maternal surrogates; and the figure of the prematurely deceased father – are more perplexing. Why do families adhere to these patterns in so many South Asian American texts and what does that tell us about this œuvre? More precisely, why are mothers subjected to a harsher critique than fathers and what purpose does this critique serve? How might we interpret the trope of the untimely paternal death? In this article I will seek to answer these questions – arguably key to an understanding of this growing body of writing – by considering works produced between the 1990s and the early twenty-first century by a range of South Asian American writers