1,206 research outputs found

    How people know their risk preference

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    People differ in their willingness to take risks. Recent work found that revealed preference tasks (e.g., laboratory lotteries)—a dominant class of measures—are outperformed by survey-based stated preferences, which are more stable and predict real-world risk taking across different domains. How can stated preferences, often criticised as inconsequential “cheap talk,” be more valid and predictive than controlled, incentivized lotteries? In our multimethod study, over 3,000 respondents from population samples answered a single widely used and predictive risk-preference question. Respondents then explained the reasoning behind their answer. They tended to recount diagnostic behaviours and experiences, focusing on voluntary, consequential acts and experiences from which they seemed to infer their risk preference. We found that third-party readers of respondents’ brief memories and explanations reached similar inferences about respondents’ preferences, indicating the intersubjective validity of this information. Our results help unpack the self perception behind stated risk preferences that permits people to draw upon their own understanding of what constitutes diagnostic behaviours and experiences, as revealed in high-stakes situations in the real world

    Point-Contact Conductances from Density Correlations

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    We formulate and prove an exact relation which expresses the moments of the two-point conductance for an open disordered electron system in terms of certain density correlators of the corresponding closed system. As an application of the relation, we demonstrate that the typical two-point conductance for the Chalker-Coddington model at criticality transforms like a two-point function in conformal field theory.Comment: 4 pages, 2 figure

    Acid-Labile Traceless Click Linker for Protein Transduction

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    Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive ß-galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system

    Proteasome assembly from 15S precursors involves major conformational changes and recycling of the Pba1-Pba2 chaperone

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    The chaperones Ump1 and Pba1-Pba2 promote efficient biogenesis of 20S proteasome core particles from its subunits via 15S intermediates containing alpha and beta subunits, except beta7. Here we elucidate the structural role of these chaperones in late steps of core particle biogenesis using biochemical, electron microscopy, cross-linking and mass spectrometry analyses. In 15S precursor complexes, Ump1 is largely unstructured, lining the inner cavity of the complex along the interface between alpha and beta subunits. The alpha and beta subunits form loosely packed rings with a wider alpha ring opening than in the 20S core particle, allowing for the Pba1-Pba2 heterodimer to be partially embedded in the central alpha ring cavity. During biogenesis, the heterodimer is expelled from the alpha ring by a restructuring event that organizes the beta ring and leads to tightening of the alpha ring opening. In this way, the Pba1-Pba2 chaperone is recycled for a new round of proteasome assembly

    Localization in non-chiral network models for two-dimensional disordered wave mechanical systems

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    Scattering theoretical network models for general coherent wave mechanical systems with quenched disorder are investigated. We focus on universality classes for two dimensional systems with no preferred orientation: Systems of spinless waves undergoing scattering events with broken or unbroken time reversal symmetry and systems of spin 1/2 waves with time reversal symmetric scattering. The phase diagram in the parameter space of scattering strengths is determined. The model breaking time reversal symmetry contains the critical point of quantum Hall systems but, like the model with unbroken time reversal symmetry, only one attractive fixed point, namely that of strong localization. Multifractal exponents and quasi-one-dimensional localization lengths are calculated numerically and found to be related by conformal invariance. Furthermore, they agree quantitatively with theoretical predictions. For non-vanishing spin scattering strength the spin 1/2 systems show localization-delocalization transitions.Comment: 4 pages, REVTeX, 4 figures (postscript

    Disordered Electrons in a Strong Magnetic Field: Transfer Matrix Approaches to the Statistics of the Local Density of States

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    We present two novel approaches to establish the local density of states as an order parameter field for the Anderson transition problem. We first demonstrate for 2D quantum Hall systems the validity of conformal scaling relations which are characteristic of order parameter fields. Second we show the equivalence between the critical statistics of eigenvectors of the Hamiltonian and of the transfer matrix, respectively. Based on this equivalence we obtain the order parameter exponent α03.4\alpha_0\approx 3.4 for 3D quantum Hall systems.Comment: 4 pages, 3 Postscript figures, corrected scale in Fig.

    Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

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    Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes

    Li–Na interdiffusion and diffusion-driven lithium isotope fractionation in pegmatitic melts

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    In this study, we investigate the diffusion of Li and its stable isotopes (6Li and 7Li) in flux-rich (1.8 % Li2O, 2.6 % B2O3, 2.3 % P2O5 and 3 % F) pegmatitic melts in order to contribute to the understanding of Li enrichment in such systems. Two glasses were synthesized with a model pegmatitic composition, one of which is highly enriched in Li (&gt; 1 wt %, PEG2-blue) and the other one essentially Li-free (PEG2-Li-free). Diffusion couple experiments were performed to determine the chemical diffusivity of Li in dry pegmatitic melts. Experiments were conducted using rapid-heat and rapid-quench cold-seal pressure vessels in a temperature range of 650–940 ∘C at 100 MPa with Ar as the pressure medium. We observed rapidly formed diffusion profiles, driven by an interdiffusive exchange of the monovalent alkalis Li and Na, while the other elements are immobile on the timescale of experiments (1–30 min). From these experiments, activation energies for Li–Na interdiffusion were determined as 99 ± 7 kJ mol−1 with a pre-exponential factor of log D0 = −5.05 ± 0.33 (D0 in m2 s−1). Li and Na partitioning between the stronger depolymerized PEG2-blue and the less depolymerized PEG2-Li-free leads to a concentration jump at the interface; i.e. Na is enriched in the more depolymerized PEG2-blue. Li–Na interdiffusion coefficients in the studied melt composition are in a similar range as Li and Na tracer diffusivities in other dry aluminosilicate melts, confirming little to no effect of aluminosilicate melt composition on Li diffusivity. Thus, added fluxes do not enhance the Li diffusivity in the same way as observed for H2O (Holycross et al., 2018; Spallanzani et al., 2022). Using melt viscosity as a proxy for the polymerization of the melt shows that water has a stronger potential to depolymerize a melt compared to other fluxing elements. Faster diffusion of 6Li compared to 7Li leads to a strong Li isotope fractionation along the diffusion profile, resulting in δ7Li as low as −80 ‰ relative to the diffusion-unaffected regions. This diffusive isotope fractionation can be quantified with an empirical isotope fractionation factor (β) of 0.20 ± 0.04, similar to previously observed β values for Li diffusion in melts. This suggests in accordance with previously published data that a β value of ca. 0.2 seems to be universally applicable to diffusive Li isotope fractionation in aluminosilicate melts.</p

    Levosimendan may improve survival in patients requiring mechanical assist devices for post-cardiotomy heart failure

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    INTRODUCTION: Most case series suggest that less than half of the patients receiving a mechanical cardiac assist device as a bridge to recovery due to severe post-cardiotomy heart failure survive to hospital discharge. Levosimendan is the only inotropic substance known to improve medium term survival in patients suffering from severe heart failure. METHODS: This retrospective analysis covers our single centre experience. Between July 2000 and December 2004, 41 consecutive patients were treated for this complication. Of these, 38 patients are included in this retrospective analysis as 3 patients died in the operating room. Levosimendan was added to the treatment protocol for the last nine patients. RESULTS: Of 29 patients treated without levosimendan, 20 could be weaned off the device, 9 survived to intensive care unit discharge, 7 left hospital alive and 3 survived 180 days. All 9 patients treated with levosimendan could be weaned, 8 were discharged alive from ICU and hospital, and 7 lived 180 days after surgery (p < 0.002 for 180 day survival). Plasma lactate after explantation of the device was significantly lower (p = 0.002), as were epinephrine doses. Time spent on renal replacement therapy was significantly shorter (p = 0.023). CONCLUSION: Levosimendan seems to improve medium term survival in patients failing to wean off cardiopulmonary bypass and requiring cardiac assist devices as a bridge to recovery. This retrospective analysis justifies prospective randomised investigations of levosimendan in this group of patients
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