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Verstanden die europäischen Invasoren und die Angehörigen indigener Völker in Amerika sich eigentlich, wenn sie Verträge schlossen, über Rechte verhandelten, vor Gericht miteinander stritten? Fanden sie einen middle ground oder agierten sie nach dem Prinzip des code switching? Diese Fragen stehen im Mittelpunkt des von den US-amerikanischen Rechtshistorikern Brian P. Owensby und Richard J. Ross herausgegebenen Bandes Justice in a New World. Negotiating Legal Intelligibility in British, Iberian, and Indigenous America. Sieben Fallstudien rekonstruieren Momente der rechtlichen Interaktion zwischen Angehörigen indigener Gemeinschaften und Euro-Amerikanern in Anglo- und Iberoamerika zwischen dem 16. und dem 19. Jahrhundert. Sie werden gerahmt von einleitenden Überlegungen der beiden Herausgeber zur Möglichkeit des Vergleichs zwischen britischen und iberischen Rechtsräumen sowie zwei zusammenfassenden Beobachtungen. ...
Purpose: The design of biorelevant conditions for in vitro evaluation of orally administered drug products is contingent on obtaining accurate values for physiologically relevant parameters such as pH, buffer capacity and bile salt concentrations in upper gastrointestinal fluids.
Methods: The impact of sample handling on the measurement of pH and buffer capacity of aspirates from the upper gastrointestinal tract was evaluated, with a focus on centrifugation and freeze-thaw cycling as factors that can influence results. Since bicarbonate is a key buffer system in the fasted state and is used to represent conditions in the upper intestine in vitro, variations on sample handling were also investigated for bicarbonate-based buffers prepared in the laboratory.
Results: Centrifugation and freezing significantly increase pH and decrease buffer capacity in samples obtained by aspiration from the upper gastrointestinal tract in the fasted state and in bicarbonate buffers prepared in vitro. Comparison of data suggested that the buffer system in the small intestine does not derive exclusively from bicarbonates.
Conclusions: Measurement of both pH and buffer capacity immediately after aspiration are strongly recommended as “best practice” and should be adopted as the standard procedure for measuring pH and buffer capacity in aspirates from the gastrointestinal tract. Only data obtained in this way provide a valid basis for setting the physiological parameters in physiologically based pharmacokinetic models.
In the recent historiography on the canon law of the early modern Spanish Empire, legal historians have been considering many forms of normativity. Nevertheless, law still remains, and there is no reason to think otherwise, as a primary source of legal orders. In the case of canon law, many of the legislations drafted remained largely unknown due to their lack of recognitio by the Holy See and pase regio granted by the Spanish Monarch. Such texts were not printed and only circulated in manuscript form, likely resulting in a very low and uncertain degree of compliance. During the 20thcentury, gradually but fragmentally, many of these texts became known in academic publications. The book reviewed here finally gathers together in a single volume all the legislative texts drafted at church assemblies celebrated in the archdiocese of Santafé (today Bogotá) before 1625. ...
The particle-in-cell (PIC) method was developed to investigate microscopic phenomena, and with the advances in computing power, newly developed codes have been used for several fields, such as astrophysical, magnetospheric, and solar plasmas. PIC applications have grown extensively, with large computing powers available on supercomputers such as Pleiades and Blue Waters in the US. For astrophysical plasma research, PIC methods have been utilized for several topics, such as reconnection, pulsar dynamics, non-relativistic shocks, relativistic shocks, and relativistic jets. PIC simulations of relativistic jets have been reviewed with emphasis placed on the physics involved in the simulations. This review summarizes PIC simulations, starting with the Weibel instability in slab models of jets, and then focuses on global jet evolution in helical magnetic field geometry. In particular, we address kinetic Kelvin-Helmholtz instabilities and mushroom instabilities.
Background: Although mechanistic target of rapamycin (mTOR) inhibitors, such as temsirolimus, show promise in treating bladder cancer, acquired resistance often hampers efficacy. This study evaluates mechanisms leading to resistance. Methods: Cell growth, proliferation, cell cycle phases, and cell cycle regulating proteins were compared in temsirolimus resistant (res) and sensitive (parental—par) RT112 and UMUC3 bladder cancer cells. To evaluate invasive behavior, adhesion to vascular endothelium or to immobilized extracellular matrix proteins and chemotactic activity were examined. Integrin α and β subtypes were analyzed and blocking was done to evaluate physiologic integrin relevance. Results: Growth of RT112res could no longer be restrained by temsirolimus and was even enhanced in UMUC3res, accompanied by accumulation in the S- and G2/M-phase. Proteins of the cdk-cyclin and Akt-mTOR axis increased, whereas p19, p27, p53, and p73 decreased in resistant cells treated with low-dosed temsirolimus. Chemotactic activity of RT112res/UMUC3res was elevated following temsirolimus re-exposure, along with significant integrin α2, α3, and β1 alterations. Blocking revealed a functional switch of the integrins, driving the resistant cells from being adhesive to being highly motile. Conclusion: Temsirolimus resistance is associated with reactivation of bladder cancer growth and invasive behavior. The α2, α3, and β1 integrins could be attractive treatment targets to hinder temsirolimus resistance.
Is it true that speed bumps level the playing field, make financial markets more stable and reduce negative externalities of high-frequency trading (HFT) firms? We examine how the implementation of a particular speed bump – Midpoint Extended Life order (M-ELO) on Nasdaq impacted financial markets stability in terms of occurrences of mini-flash crashes in individual securities. We use high-frequency order book message data around the implementation date and apply difference-in-differences analysis to estimate the average treatment effect of the speed bump on market stability and liquidity provision. The results suggest that the introduction of the M-ELO decreases the average number of crashes on Nasdaq compared to other exchanges by 4.7%. Liquidity provision by HFT firms also improves. These findings imply that technology-based solutions by exchanges are feasible alternatives to regulatory intervention towards safer markets.
We study the accuracy and usefulness of automated (i.e., machine-generated) valuations for illiquid and heterogeneous real assets. We assemble a database of 1.1 million paintings auctioned between 2008 and 2015. We use a popular machine-learning technique—neural networks—to develop a pricing algorithm based on both non-visual and visual artwork characteristics. Our out-of-sample valuations predict auction prices dramatically better than valuations based on a standard hedonic pricing model. Moreover, they help explaining price levels and sale probabilities even after conditioning on auctioneers’ pre-sale estimates. Machine learning is particularly helpful for assets that are associated with high price uncertainty. It can also correct human experts’ systematic biases in expectations formation—and identify ex ante situations in which such biases are likely to arise.
In this study, we investigate the wealth decumulation decision from the perspective of a retiree who is averse to the prospect of fully annuitizing her accumulated savings. We field a large online survey of hypothetical product choices for phased drawdown offerings and annuities. While the demand for annuities remains low in our sample, we find significant demand for phased withdrawal products with equity-based asset allocations and flexible payout structures. Consistent with the product choice, the most important self-reported considerations for the wealth decumulation decision are low default risk in the products they purchase, the size of the withdrawal rates, and flexibility in the timing of their withdrawal. As determinants of the decision of how much wealth individuals are willing to draw down, we identify consumers’ attitudes towards future economic conditions, the extent to which they are protected against longevity risk, and their desire to leave bequests. Policy implications are discussed.