Theoretical Foundations and Empirical Evaluations of Partisan Fairness in District-Based Democracies

We clarify the theoretical foundations of partisan fairness standards for district-based democratic electoral systems, including essential assumptions and definitions not previously recognized, formalized, or in some cases even discussed. We also offer extensive empirical evidence for assumptions with observable implications. We cover partisan symmetry, the most commonly accepted fairness standard, and other perspectives. Throughout, we follow a fundamental principle of statistical inference too often ignored in this literature—defining the quantity of interest separately so its measures can be proven wrong, evaluated, and improved. This enables us to prove which of the many newly proposed fairness measures are statistically appropriate and which are biased, limited, or not measures of the theoretical quantity they seek to estimate at all. Because real-world redistricting and gerrymandering involve complicated politics with numerous participants and conflicting goals, measures biased for partisan fairness sometimes still provide useful descriptions of other aspects of electoral systems

Estimating three-demensional energy transfer in isotropic turbulence

To obtain an estimate of the spectral transfer function that indicates the rate of decay of energy, an x-wire probe was set at a fixed position, and two single wire probes were set at a number of locations in the same plane perpendicular to the mean flow in the wind tunnel. The locations of the single wire probes are determined by pseudo-random numbers (Monte Carlo). Second order spectra and cross spectra are estimated. The assumption of isotropy relative to second order spectra is examined. Third order spectra are also estimated corresponding to the positions specified. A Monte Carlo Fourier transformation of the downstream bispectra corresponding to integration across the plane perpendicular to the flow is carried out assuming isotropy. Further integration is carried out over spherical energy shells

Painted Faces & Printed Music: Women and Music in the Paintings of Bartolomeo Veneto and Sebastiano Florigerio

The cultural views surrounding musical performances by women rapidly changed during the sixteenth century. The ideal of the preceding century advised ladies of the court to avoid displaying the frivolous and sinful ways of music-making, but the new notion of the female courtier praised women for performing music, for it could only serve to enhance their beauty and virtue. These two opposing concepts can be seen simultaneously in treatises, correspondences, and artwork of this era. Artists’ depictions of courtesans included music to convey what was considered sensual and immoral; yet other works displayed music instruments as representations of women’s nobility and grace. Through an analysis of iconography within Bartolomeo Veneto’s Lady Playing a Lute and Sebastiano Florigerio’s Music Lesson, this research explores the representation of gender through music in Italian paintings of the sixteenth century

Pharmacological Therapy in the Heart as an Alternative to Cellular Therapy: A Place for the Brain Natriuretic Peptide?

The discovery that stem cells isolated from different organs have the ability to differentiate into mature beating cardiomyocytes has fostered considerable interest in developing cellular regenerative therapies to treat cardiac diseases associated with the loss of viable myocardium. Clinical studies evaluating the potential of stem cells (from heart, blood, bone marrow, skeletal muscle, and fat) to regenerate the myocardium and improve its functional status indicated that although the method appeared generally safe, its overall efficacy has remained modest. Several issues raised by these studies were notably related to the nature and number of injected cells, as well as the route and timing of their administration, to cite only a few. Besides the direct administration of cardiac precursor cells, a distinct approach to cardiac regeneration could be based upon the stimulation of the heart's natural ability to regenerate, using pharmacological approaches. Indeed, differentiation and/or proliferation of cardiac precursor cells is controlled by various endogenous mediators, such as growth factors and cytokines, which could thus be used as pharmacological agents to promote regeneration. To illustrate such approach, we present recent results showing that the exogenous administration of the natriuretic peptide BNP triggers "endogenous" cardiac regeneration, following experimental myocardial infarction

Theoretical Foundations and Empirical Evaluations of Partisan Fairness in District-Based Democracies

We clarify the theoretical foundations of partisan fairness standards for district-based democratic electoral systems, including essential assumptions and definitions not previously recognized, formalized, or in some cases even discussed. We also offer extensive empirical evidence for assumptions with observable implications. We cover partisan symmetry, the most commonly accepted fairness standard, and other perspectives. Throughout, we follow a fundamental principle of statistical inference too often ignored in this literature—defining the quantity of interest separately so its measures can be proven wrong, evaluated, and improved. This enables us to prove which of the many newly proposed fairness measures are statistically appropriate and which are biased, limited, or not measures of the theoretical quantity they seek to estimate at all. Because real-world redistricting and gerrymandering involve complicated politics with numerous participants and conflicting goals, measures biased for partisan fairness sometimes still provide useful descriptions of other aspects of electoral systems

Multidimensional Binning Techniques for a Two Parameter Trilinear Gauge Coupling Estimation at LEP II

This paper describes two generalization schemes of the Optimal Variables technique in estimating simultaneously two Trilinear Gauge Couplings. The first is an iterative procedure to perform a 2-dimensional fit using the linear terms of the expansion of the probability density function with respect to the corresponding couplings, whilst the second is a clustering method of probability distribution representation in five dimensions. The pair production of W's at 183 GeV center of mass energy, where one W decays leptonically and the other hadronically, was used to demonstrate the optimal properties of the proposed estimation techniques.Comment: (25 pages, 11 figures

The role of endogenous and exogenous RasGAP-derived fragment N in protecting cardiomyocytes from peroxynitrite-induced apoptosis.

Peroxynitrite (PN) is a potent nitrating and oxidizing agent generated during various pathological situations affecting the heart. The negative effects of PN result, at least in part, from its ability to activate caspases and apoptosis. RasGAP is a ubiquitously expressed protein that is cleaved sequentially by caspase-3. At low caspase-3 activity, RasGAP is cleaved into an N-terminal fragment, called fragment N, that protects cells by activating the Ras/PI3K/Akt pathway. At high caspase-3 activity, fragment N is further cleaved and this abrogates its capacity to stimulate the antiapoptotic Akt kinase. Fragment N formation is crucial for the survival of cells exposed to a variety of stresses. Here we investigate the pattern of RasGAP cleavage upon PN stimulation and the capacity of fragment N to protect cardiomyocytes. PN did not lead to sequential cleavage of RasGAP. Indeed, PN did not allow accumulation of fragment N because it induced its rapid cleavage into smaller fragments. No situations were found in cells treated with PN in which the presence of fragment N was associated with survival. However, expression of a caspase-resistant form of fragment N in cardiomyocytes protected them from PN-induced apoptosis. Our results indicate that the antiapoptotic pathway activated by fragment N is effective at inhibiting PN-induced apoptosis (as seen when cardiomyocytes express a capase-3-resistant form of fragment N) but because fragment N is too transiently generated in response to PN, no survival response is effectively produced. This may explain the marked deleterious consequences of PN generation in various organs, including the heart

Computer modeling of large asteroid impacts into continental and oceanic sites: Atmospheric, cratering, and ejecta dynamics

Numerous impact cratering events have occurred on the Earth during the last several billion years that have seriously affected our planet and its atmosphere. The largest cratering events, which were caused by asteroids and comets with kinetic energies equivalent to tens of millions of megatons of TNT, have distributed substantial quantities of terrestrial and extraterrestrial material over much or all of the Earth. In order to study a large-scale impact event in detail, computer simulations were completed that model the passage of a 10 km-diameter asteroid through the Earth's atmosphere and the subsequent cratering and ejecta dynamics associated with impact of the asteroid into two different targets, i.e., an oceanic site and a continental site. The calcuations were designed to broadly represent giant impact events that have occurred on the Earth since its formation and specifically represent an impact cratering event proposed to have occurred at the end of Cretaceous time. Calculation of the passage of the asteroid through a U.S. Standard Atmosphere showed development of a strong bow shock that expanded radially outward. Behind the shock front was a region of highly shock compressed and intensely heated air. Behind the asteroid, rapid expansion of this shocked air created a large region of very low density that also expanded away from the impact area. Calculations of the cratering events in both the continental and oceanic targets were carried to 120 s. Despite geologic differences, impacts in both targets developed comparable dynamic flow fields, and by approx. 29 s similar-sized transient craters approx. 39 km deep and approx. 62 km across had formed. For all practical purposes, the atmosphere was nearly completely removed from the impact area for tens of seconds, i.e., air pressures were less than fractions of a bar out to ranges of over 50 km. Consequently, much of the asteroid and target materials were ejected upward into a near vacuum. Effects of secondary volcanism and return of the ocean over hot oceanic crater floor could also be expected to add substantial solid and vaporized material to the atmosphere, but these conditions were not studied

P619Role of Toll-like receptor 5 in the development of post-myocardial infarction inflammation

Background: Inflammatory processes play a key role in the pathophysiology of myocardial infarction (MI). Genetic deletion of toll-like recpetors (TLRs), especially TLR2 and TLR4 have shown protective role in murine models of MI. The role of other TLRs remains unknown. We have previously shown that cardiomyocytes express TLR5 and that the ligand of TLR5, flagellin, activates the NF-kappaB and MAPK pathways in cardiomyocytes. We also have shown that injection of flagellin induces acute systolic dysfunction in vivo in mice. Aim: Determine the role of TLR5 in the development of post-MI inflammation. Methods: A murine model of myocardial infarction was done by a 30 minutes ligation of the left anterior descending coronary artery followed by 2 hours of reperfusion. Infarct size was measured by standard Evans blue/TTC staining. Plasma creatine kinase (CK) was quantified as a read out of myocardial necrosis. Tissue and plasma cytokines (MIP-2, MCP-1, IL-6) were quantified by ELISA. To determine the extent of tissue lipid peroxidation we used malondialdehyde and 4-hydroxynonenal-HIS adduct assays. Tissue protein oxidation was tested by protein carbonyl ELISA kit. Phosphorylation of MAPK was analyzed by western blot. Results: Genetic suppression of TLR5 induced a significant increase of myocardial infarct size and plasma CK, of biochemical markers of myocardial oxidative stress, and cytokine levels in the heart and the plasma after MI. These effects were associated with a marked enhancement of p38 phosphorylation in the heart from TLR5 KO mice. Conclusion: TLR5 protects from acute myocardial injury and reduces local and systemic inflammation during myocardial infarction. The mechanisms may involve reduced p38 signaling, decreased oxidative stress and attenuated cytokine expression. Research supported by the Swiss National Science Foundation, Grant n° 310030_135394/

P90Necrotic cardiomyocytes release soluble pro-inflammatory molecule(s) inducing il1r/myd88-dependent inflammatory responses in cardiac fibroblasts

Background: Inflammation comes out to be a critical biological process in the pathophysiology of myocardial infarction (MI). We hypothesize that this inflammation is triggered by necrotic cardiomyocytes (Cmc) that release a set of endogenous molecules (DAMPs: danger-associated molecular patterns) activating inflammatory responses in cardiac fibroblasts. Aim: Analyze in vitro the immune activation of cardiac fibroblasts exposed to necrotic Cmc conditioned media. Methods: Primary neonatal murine cardiac fibroblasts and Cmc were obtained by digestion of neonatal hearts and differential plating technique allowing a selection for cardiomyocytes and cardiac fibroblasts. Cmc were killed by necrotic stimuli including oxidants (hydrogen peroxide) and mechanic stresses (freeze-thaw). Necrosis was assessed using Hoechst/PI stainings. Fibroblasts were exposed to necrotic Cmc conditioned media and mRNA expression of inflammatory genes was measured by real-time PCR and ELISA. Activation of signaling pathways was analyzed by western blot. We used cardiac cells from Myd88-/-, Trif-/- and Nlrp3-/- animals to evaluate the contribution of TLRs/IL1-R and NLRP3 inflammasome in the sensing of necrotic DAMPs. Results: mRNA expression of chemokines such as MCP-1, MIP-2 and IP-10 were induced in fibroblasts exposed to necrotic Cmc conditioned media. Alternatively, fibroblasts exposed to necrotic fibroblasts conditioned media showed a lower increase in mRNA expression of these chemokines. In addition, in fibroblasts from Myd88-/- mice, response to Cmc conditioned media was fully abrogated whereas no difference was observed in Trif-/- and Nlrp3-/- fibroblasts. Conclusion: Cardiac fibroblasts are able to produce a rapid and specific inflammatory response to necrotic Cmc conditioned media involving the expression of neutrophil and monocyte chemoattractants. The dependence on MyD88 adaptor protein strongly suggests that this response relies on TLR/IL-1R signaling. These results engage cardiac fibroblasts as key players in post-MI inflammatory responses as they are able to sense DAMPs from necrotic Cmc and possibly recruit inflammatory cells. Research supported by the Swiss National Science Foundation, Grant n° 310030_135394/