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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.
Many processes in living cells involve interaction and cooperation of multiple proteins to fulfill a specific function. To understand biological processes in their full complexity, it is not sufficient to only identify the molecules being involved but also to understand the kinetic aspects of a reaction. Mass spectrometry (MS) is a very powerful tool which allows to precisely identify the molecules of a reaction. Usually this is done with tandem-MS experiments for purpose of de-novo peptide sequencing. However, since this involves protein digestion, a statement of the in-vivo constitution of non-covalently bound protein complexes is not possible. In order to detect an intact protein complex it is necessary to analyze the biological system softly and in a near-native environment with native MS. Native MS allows the non-destructive analysis of these non-covalent protein complexes as well as to detect their components. However, up to now native MS does not offer a possibility to resolve the timing of the constitution of protein complexes on a fast time-scale. Therefore, the progress of reactions on fast time-scales is invisible. However, a method which delivers both types of information - identification of the components of a protein complex, as well as time-resolving their interaction - would be of high interest.
A suitable ionization technique for native MS is laser-induced liquid-bead ion desorption (LILBID). LILBID employs well-defined droplets which are irradiated by IR laser pulses to generate gas phase ions. The not-continuous, repetitive nature of ion generation offers itself to the development of a time-resolved (TR) native MS system which is able to investigate protein complexes on a fast time scale. The LILBID-droplets can serve as reaction vessels if they are levitated in an electrodynamic Paul-trap. This new setup would allow sample manipulation and MS analysis on precise and fast reaction time-scales. The first part of this dissertation presents the construction and characterization of a setup for TR-LILBID-MS.
An example for a complex biological system is the self-assembly of beta-amyloid (Aβ). This small peptide is the major component in plaques related to Alzheimer’s disease. Clinically relevant is especially the 42 amino acid peptide Aβ42 which aggregates from monomers to oligomers through to fibrils. The oligomers are the neurotoxic species in this process and thus of high interest. Nevertheless, standard analytical techniques are unable to detect those oligomers which makes MS an optimal tool to study the oligomerization process of Aβ with the focus on disease relevant oligomers. TR-LILBID-MS allows to follow the oligomerization of Aβ enabling to study molecules which influence this kinetic. Combining MS with ion-mobility spectrometry adds an additional dimension - the collision cross section - to the mass-to-charge ratio obtained from MS. Therewith structural alterations induced by ligands can be correlated to differences in the aggregation kinetic. This allows to draw a picture of the aggregation process of Aβ for the development of disease-relevant small oligomers on a molecular level.
Die in der vorliegenden Arbeit gewonnenen Erkenntnisse zur Reaktivität zweifach reduzierter 9,10-Dihydro-9,10-diboraanthracene [A]2– erweitern das Einsatzspektrum von Hauptgruppenverbindungen im Hinblick auf die Aktivierung kleiner Moleküle. Komplementär zu Übergangsmetallkomplexen und FLPs ermöglichen die Salze M2[A] (M+ = Li+, Na+, K+) die Entwicklung neuartiger Synthesestrategien. Als besondere Herausforderung gilt die Aktivierung des stabilen H2-Moleküls, dessen Bindung die Dianionen [A]2– homolytisch in einer konzertierten Reaktion spalten.
Untersuchungen zur Kinetik der H2-Addition an M2[A] stellten die Abhängigkeit dieses Reaktionsschritts vom borgebundenen Substituenten und vom Kation heraus. Eine geringe sterische Abschirmung der Boratome durch kleine borgebundene Substituenten (C≡CtBu, Me, H) begünstigt die H2-Aufnahme gegenüber großen Substituenten (pTol, Xyl, Et). Die maximale Ausbeute an M2[A-H2] wird für M+ = Li+ erst nach mehreren Tagen bei 100 °C erhalten, während einige Stunden bei nur 50 °C für die quantitative Bildung von K2[A-H2] ausreichen.
Unter den Salzen M2[A] eignet sich Li2[68] mit borgebundenen Me-Substituenten besonders gut für den Einsatz als Hydrierungskatalysator. Mit Li2[68] konnten das Imin Ph(H)C=NtBu, das terminale Alken Ph2C=CH2 und Anthracen erfolgreich im NMR-Maßstab hydriert werden (Katalysatorladung 37 mol%, THF-d8, 1 atm H2-Initialdruck, 100 °C, 16 h). Im Reaktionsautoklaven war für die Hydrierung von Ph(H)C=NtBu eine Verringerung der Katalysatorladung auf 10 mol% Li2[68] möglich (THF, 7 atm H2-Initialdruck, 100 °C, 18 h). Konkurrenzreaktionen begründen Einschränkungen in Bezug auf die Substratpalette, da M2[68] (M+ = Li+, Na+) mit elektronenarmen ungesättigten Verbindungen, die C=C-, C≡C-, C=O- oder C=N-Bindungen enthalten, [4+2]-Cycloadditionsprodukte bilden können. Die Reversibilität dieser Reaktion entscheidet, ob Li2[68] als Katalysator fungiert oder irreversibel in den Strukturen gebunden bleibt.
Vielseitiger sind die H2-Aktivierungsprodukte M2[A-H2] als H–-Donoren geeignet: Na2[68-H2] ersetzt Halogenid- durch H–-Substituenten in Bromethan, sowie in Chlorsilanen und PCl3; CO2 wird in Natriumformiat überführt. Unabhängig von der Anzahl der Chlorliganden werden die Produkte immer vollständig hydriert. Eine erneute Reduktion von 68 kann wieder Na2[68] bereitstellen, das H2 aufnimmt und Na2[68-H2] regeneriert, welches für neue H–-Abgaben zur Verfügung steht. Bei der experimentellen Umsetzung des Kreislaufs ist es wichtig, die beschriebenen Reaktionsschritte nacheinander auszuführen und jeweils nur stöchiometrische Mengen des Elektrophils zuzugeben. Bei Abweichungen vom schrittweisen Syntheseprotokoll finden formale nukleophile Substitutionen mit M2[68] statt und monoanionische Spezies entstehen, z. B. wenn Et3SiBr als Elektrophil anwesend ist.
Gegenüber CO2 zeigt Li2[68] eine hohe Reaktivität, durch die selektiv CO und [CO3]2– gebildet werden. Wie zuvor bei den H–-Transferreaktionen ermöglicht die Reduktion der Neutralverbindung 68 die Regeneration von Li2[68].
Die Dianionen [A]2– stechen unter anderen cyclischen Borverbindungen in niedrigen Oxidationsstufen heraus, da mit [A]2– nicht nur die Aktivierung von H2 oder CO2 gelang, sondern erstmalig über die Einbindung der Additionsprodukte in zum Teil katalytische Folgereaktionen berichtet werden konnte.
Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.
Purpose: Bacterial biofilms are a major problem in the treatment of infected dental and orthopedic implants. The purpose of this study is to investigate the cleaning effect of an electrolytic approach (EC) compared to a powder-spray system (PSS) on titanium surfaces. Materials and Methods: The tested implants (different surfaces and alloys) were collated into six groups and treated ether with EC or PSS. After a mature biofilm was established, the implants were treated, immersed in a nutritional solution, and streaked on Columbia agar. Colony-forming units (CFUs) were counted after breeding and testing (EC), and control (PSS) groups were compared using a paired sample t-test. Results: No bacterial growth was observed in the EC groups. After thinning to 1:1,000,000, 258.1 ± 19.9 (group 2), 264.4 ± 36.5 (group 4), and 245.3 ± 40.7 (group 6) CFUs could be counted in the PSS groups. The difference between the electrolytic approach (test groups 1, 3, and 5) and PSS (control groups 2, 4, and 6) was statistically extremely significant (p-value < 2.2 × 10−16). Conclusion: Only EC inactivated the bacterial biofilm, and PSS left reproducible bacteria behind. Within the limits of this in vitro test, clinical relevance could be demonstrated.
Formation of the anteroposterior and dorsoventral body axis in Caenorhabditis elegans depends on cortical flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization after formation of cell-cell contacts is not fully understood. Here, we demonstrate that planar asymmetries are established during left-right symmetry breaking: Centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) from contacts to the medial cortex, resulting in their unmixing from apical myosin. Contact localization and advection of PAR-6 requires balanced CDC-42 activation, while asymmetric retention and advection of PAR-3 can occur independently of PAR-6. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1 and opposing retention of antagonistic CDC-42 and Wnt pathway components leads to planar asymmetries. The most obvious mark of planar asymmetry, retention of PAR-3 at a single cell-cell contact, is required for proper cytokinetic cell intercalation. Hence, our data uncover how planar polarity is established in a system without the canonical planar cell polarity pathway through planar asymmetric retention of aPARs.
Die Dissertation (Universität Eichstätt-Ingolstadt) beginnt mit dem Satz "Am Ende stritt man um Akten" und endet auf Seite 483 mit eben dem gleichen Satz. Zwischen Anfang und Ende dieser akribisch gearbeiteten Publikation, die Denzler bescheiden eine "Studie" nennt, werden die massenweise in den Archiven vorhandenen Akten, die während der letzten Visitation des Reichskammergerichts von 1767–1776 produziert wurden, nach ihrer Entstehung und Funktion untersucht. Als Leitbild der Untersuchung dient der "Reformhorizont" der Aufklärung, vor dessen Hintergrund das Visitationsgeschehen in Gestalt seiner Hand- und Druckschriften analysiert wird. "Reform"-zeiten, -räume, -akteure, -verfahren sowie -inhalte geben dem engagiert geschriebenen Buch eine klare Gliederung für die Untersuchung aller Schriftgattungen von den Protokollen, Schreiben, Diktaten, Abschriften, Diarien, Korrespondenzen, Instruktionen, Berichten bis zu Gutachten und Notizen, die alle das Visitationsgeschehen in und als "Akten" repräsentieren: 562 Aktenbündel; von 1056 Sitzungen sind 13 Bände Beratungsprotokolle überliefert, die 15732 Folioseiten umfassen; 50 Visitationsbeschlüsse liegen vor; die schriftlichen Befragungen von 92 Gerichtsmitgliedern ergaben 25000 Antworten (355, 478); hinzu kommen noch die Produktion aus der visitationseigenen Druckerei sowie 200 Einzelpublikationen zur Visitation und eine visitationseigene Zeitschrift als schriftliches Untersuchungsmaterial. Daraus entsteht ein höchst umfassendes und anschauliches Bild über Medientechnik, Schriftkultur, Justizkontrolle und Dienstaufsicht im Rahmen der Visitation. Aus dem quantitativen Befund in diesem "tintenklecksenden Saeculum", wie es Schiller genannt hat, leitet Denzler die These ab, dass die Visitation von 1767 eine enorme Vermehrung und Aufwertung von Schriftlichkeit schlechthin dokumentiert (16). Vor diesem Hintergrund soll die alltägliche Bedeutung der Schriftlichkeit für die Visitation analysiert und der "Entstehungs- und Überlieferungskontext" möglichst genau im "Schriftalltag" rekonstruiert werden. Dieser "Schriftalltag" reflektiert auch den Justizalltag in seiner rechtshistorischen Bedeutung. Diesen zu beschreiben ist zwar nicht Denzlers vorrangiges Ziel, aber die Kulturgeschichte des Geschriebenen beleuchtet und ergänzt die Geschichte der Rechtspraxis am Beispiel der Visitation von 1767 in vielfältiger Weise. Das belegen auch das reiche Quellen- und Literaturverzeichnis (489–562) und die Statistiken über Personalia, Visitationskosten, Examina, Gesandtschaftsquartiere, Verfahren usw. (565–604). ...
A twentieth century-long coupled atmosphere-ocean regional climate simulation with COSMO-CLM (Consortium for Small-Scale Modeling, Climate Limited-area Model) and NEMO (Nucleus for European Modelling of the Ocean) is studied here to evaluate the added value of coupled marginal seas over continental regions. The interactive coupling of the marginal seas, namely the Mediterranean, the North and the Baltic Seas, to the atmosphere in the European region gives a comprehensive modelling system. It is expected to be able to describe the climatological features of this geographically complex area even more precisely than an atmosphere-only climate model. The investigated variables are precipitation and 2 m temperature. Sensitivity studies are used to assess the impact of SST (sea surface temperature) changes over land areas. The different SST values affect the continental precipitation more than the 2 m temperature. The simulated variables are compared to the CRU (Climatic Research Unit) observational data, and also to the HOAPS/GPCC (Hamburg Ocean Atmosphere Parameters and Fluxes from Satellite Data, Global Precipitation Climatology Centre) data. In the coupled simulation, added skill is found primarily during winter over the eastern part of Europe. Our analysis shows that, over this region, the coupled system is dryer than the uncoupled system, both in terms of precipitation and soil moisture, which means a decrease in the bias of the system. Thus, the coupling improves the simulation of precipitation over the eastern part of Europe, due to cooler SST values and in consequence, drier soil.
Libra – a global virtual currency project initiated by Facebook – has been the subject of many controversial discussions since its announcement in June 2019. This paper provides a differentiated view on Libra, recognising that different development scenarios of Libra are conceivable.
Libra could serve purely as an alternative payment system in combination with a dedicated payment token, the Libra coin. Alternatively, the Libra project could develop into a broader financial infrastructure for advanced financial services such as savings and loan products operating on the Libra blockchain. Based on a comparison of the Libra architecture with other cryptocurrencies, the opportunities and challenges for the development of the respective Libra ecosystems are investigated form a commercial, regulatory and monetary policy perspective.
Wir lassen die überwältigende Fülle an Werken im Arsenale hinter uns. Das Ziel sind die Giardini, der ursprüngliche und neben dem Arsenale zweite große Ausstellungsort der Kunstschau. Dort befindet sich einer der Hauptanziehungspunkte der Biennale: Im Zentralpavillon steht die in den Medien bereits oft erwähnte und gezeigte sogenannte "Blutmaschine". Ein riesiger Roboterarm mit überdimensionaler Wischschaufel, wirkt sie in ihrer Motorik dennoch ausgesprochen menschlich. Die 32 Bewegungen, die das chinesische Künstlerduo Sun Yuan und Peng Yu dem Industrieroboter "in den Leib" programmiert haben, erinnern an Winken, Tanzen, Po-Wackeln, Innehalten und Überlegen. ...
Local crowding out in China
(2019)
In China, between 2006 and 2013, local public debt crowded out the investment of private firms by tightening their funding constraints, while leaving state-owned firms’ investment unaffected. We establish this result using a purpose-built dataset for Chinese local public debt. Private firms invest less in cities with more public debt, the reduction in investment being larger for firms located farther from banks in other cities or more dependent on external funding. Moreover, in cities where public debt is high, private firms’ investment is more sensitive to internal cash flow, also when cash-flow sensitivity is estimated jointly with the probability of being credit-constrained.