Mitigating Hypothetical Bias Evidence on the Effects of Correctives from a Large Field Study

The overestimation of willingness-to-pay (WTP) in hypothetical responses is a wellknown finding in the literature. Various techniques have been proposed to remove or, at least, reduce this bias. Using responses from a panel of about 6,500 German households on their WTP for a variety of power mixes, this article undertakes an analysis that combines two common ex-ante approaches - cheap talk and consequential script - with the ex-post certainty approach to calibrating hypothetical WTP responses. Based on a switching regression model that accounts for the potential endogeneity of respondent certainty, we find that while neither the cheap-talk nor the consequential script corrective bears on the estimates of WTP, there is evidence for a lower WTP among those respondents who classify themselves as definitely certain about their answers.Die Überschätzung von Zahlungsbereitschaften in hypothetischen Befragungssituationen ist ein in der Literatur wohlbekanntes Phänomen. Um diese Verzerrungen zu verhindern oder zumindest zu reduzieren, wurden verschiedene Ansätze vorgeschlagen, darunter die Cheap Talk und Consequential Script genannten Ex-Ante Ansätze sowie ein als Sicherheits-Ansatz bezeichnetes Ex-Post-Korrektiv. Auf Grundlage einer Befragung von etwa 6.500 deutschen Haushalten zu ihrer Zahlungsbereitschaft für verschiedene Strommixe analysiert dieser Artikel die Effektivität dieser Korrektive. Basierend auf einem Switching-Regression-Model, welches die potenzielle Endogenität der Sicherheit der Befragten berücksichtigt, finden wir empirische Evidenz dafür, dass sich weder Cheap Talk noch der Consequential-Script Ansatz auf die geschätzten Zahlungsbereitschaften auswirkt. Es findet sich jedoch eine geringere Zahlungsbereitschaft unter solchen Antwortenden, die sich selbst als ganz sicher in Bezug auf ihre Antworten einstufen

Physiologically based modeling of lisofylline pharmacokinetics following intravenous administration in mice

Lisofylline (LSF), is the R-(−) enantiomer of the metabolite M1 of pentoxifylline, and is currently under development for the treatment of type 1 diabetes. The aim of the study was to develop a physiologically based pharmacokinetic (PBPK) model of LSF in mice and to perform simulations in order to predict LSF concentrations in human serum and tissues following intravenous and oral administration. The concentrations of LSF in serum, brain, liver, kidneys, lungs, muscle, and gut were determined at different time points over 60 min by a chiral HPLC method with UV detection following a single intravenous dose of LSF to male CD-1 mice. A PBPK model was developed to describe serum pharmacokinetics and tissue distribution of LSF using ADAPT II software. All pharmacokinetic profiles were fitted simultaneously to obtain model parameters. The developed model characterized well LSF disposition in mice. The estimated intrinsic hepatic clearance was 5.427 ml/min and hepatic clearance calculated using the well-stirred model was 1.22 ml/min. The renal clearance of LSF was equal to zero. On scaling the model to humans, a good agreement was found between the predicted by the model and presented in literature serum LSF concentration–time profiles following an intravenous dose of 3 mg/kg. The predicted LSF concentrations in human tissues following oral administration were considerably lower despite the twofold higher dose used and may not be sufficient to exert a pharmacological effect. In conclusion, the mouse is a good model to study LSF pharmacokinetics following intravenous administration. The developed PBPK model may be useful to design future preclinical and clinical studies of this compound

Strange hadron collectivity in pPb and PbPb collisions

ARXIV EPRINT: 2205.00080 (https://arxiv.org/abs/2205.00080).Copyright © 2023 CERN, for the benefit of the CMS Collaboration. The collective behavior of $${\textrm{K}}_{\textrm{S}}^0$$ K S 0 and $$\Lambda /\overline{\Lambda}$$ Λ / Λ ¯ strange hadrons is studied by measuring the elliptic azimuthal anisotropy (v2) using the scalar-product and multiparticle correlation methods. Proton-lead (pPb) collisions at a nucleon-nucleon center-of-mass energy $$\sqrt{s_{\textrm{NN}}}$$ s NN = 8.16 TeV and lead-lead (PbPb) collisions at $$\sqrt{s_{\textrm{NN}}}$$ s NN = 5.02 TeV collected by the CMS experiment at the LHC are investigated. Nonflow effects in the pPb collisions are studied by using a subevent cumulant analysis and by excluding events where a jet with transverse momentum greater than 20 GeV is present. The strange hadron v2 values extracted in pPb collisions via the four- and six-particle correlation method are found to be nearly identical, suggesting the collective behavior. Comparisons of the pPb and PbPb results for both strange hadrons and charged particles illustrate how event-by-event flow fluctuations depend on the system size.SCOAP

Enantioselective direct aldol reactions catalyzed by l-prolinamide derivatives

l-Prolinamides 2, prepared from l-proline and simple aliphatic and aromatic amines, have been found to be active catalysts for the direct aldol reaction of 4-nitrobenzaldehyde with neat acetone at room temperature. They give moderate enantioselectivities of up to 46% enantiomeric excess (ee). The enantioselectivity increases as the amide N—H becomes a better hydrogen bond donor. l-Prolinamides 3, derived from the reaction of l-proline with α,β-hydroxyamines such that there is a terminal hydroxyl group, show more efficient catalysis and higher enantioselectivities. In particular, catalyst 3h, prepared from l-proline and (1S,2S)-diphenyl-2-aminoethanol, exhibits high enantioselectivities of up to 93% ee for aromatic aldehydes and up to >99% ee for aliphatic aldehydes under –25°C. Model reactions of benzaldehyde with three enamines derived from the condensation of prolinamides with acetone have been studied by quantum mechanics calculations. The calculations reveal that the amide N—H and the terminal hydroxyl groups form hydrogen bonds with the benzaldehyde substrate. These hydrogen bonds reduce the activation energy and cause high enantioselectivity. Our results suggest a new strategy in the design of new organic catalysts for direct asymmetric aldol reactions and related transformations

Identification of the glomerular podoctye as a target for growth hormone action

GH excess in both the human and transgenic animal models is characterized by significant changes in blood pressure and renal function. The GH/GH receptor (GHR) axis is also implicated in the development of diabetic nephropathy. However, it is not clear whether GH's actions on renal function are due to indirect actions mediated via changes in blood pressure and vascular tone or due to direct action of GH on the kidney. We hypothesized that functional GHRs are expressed on the glomerular podocyte enabling direct actions of GH on glomerular function. Real-time PCR, immunohistochemistry, and Western blot analysis of murine podocyte cells (MPC-5) and kidney glomeruli demonstrated expression of GHR mRNA and protein. Exposure of both murine and human podocytes to GH (50-500 ng/ml) resulted in an increase in abundance of phosphorylated signal transducer and activator of transcription-5, Janus kinase-2, and ERK1/2 proteins. Exposure of podocytes to GH also caused changes in the intracellular distribution of the Janus kinase-2 adapter protein Src homology 2-Bβ, stimulation of focal adhesion kinase, increase in reactive oxygen species, and GH-dependent changes in the actin cytoskeleton. We conclude that glomerular podocytes express functional GHRs and that GH increases levels of reactive oxygen species and induces reorganization of the actin cytoskeleton in these cells. These results provide a novel mechanistic link between GH's actions and glomerular dysfunction in disorders such as acromegaly and diabetic glomerulosclerosis. Copyright © 2007 by The Endocrine Society.link_to_subscribed_fulltex

Cooperation and Competition in Climate Change Policies: Mitigation and Climate Engineering when Countries are Asymmetric

We study a dynamic game of climate policy design in terms of emissions and solar radiation management (SRM) involving two heterogeneous regions or countries. Countries emit greenhouse gasses (GHGs), and can block incoming radiation by unilateral SRM activities, thus reducing global temperature. Heterogeneity is modelled in terms of the social cost of SRM, the environmental damages due to global warming, the productivity of emissions in terms of generating private benefits, the rate of impatience, and the private cost of geoengineering. We determine the impact of asymmetry on mitigation and SRM activities, concentration of GHGs, and global temperature, and we examine whether a trade-off actually emerges between mitigation and SRM. Our results could provide some insights into a currently emerging debate regarding mitigation and SRM methods to control climate change, especially since asymmetries seem to play an important role in affecting incentives for cooperation or unilateral actions