No evidence for an effect of testosterone administration on delay discounting in male university students

SummaryIntertemporal choices between a smaller sooner and a larger delayed reward are one of the most important types of decisions humans face in their everyday life. The degree to which individuals discount delayed rewards correlates with impulsiveness. Steep delay discounting has been associated with negative outcomes over a wide range of behaviors such as addiction. However, little is known about the biological foundations of delay discounting. Here, we examine a potential causal link between delay discounting and testosterone, a hormone which has been associated with other types of impulsive behavior. In our double-blind placebo-controlled study 91 healthy young men either received a topical gel containing 50mg of testosterone (N=46) or a placebo (N=45) before participating in a delay discounting task with real incentives. Our main finding is that a single dose administration of testosterone did not lead to significant differences in discount rates between the placebo and the testosterone group. Within groups and in the pooled sample, no significant relationship between testosterone and discount rates was observed. At the same time, we do replicate standard findings from the delay discounting literature such as a magnitude-of-rewards effect on discount rates. In sum, our findings suggest that circulating testosterone does not have a significant effect on delay discounting in young men

Acid-Labile Traceless Click Linker for Protein Transduction

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

Point-Contact Conductances from Density Correlations

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

Robust DC and efficient time-domain fast fault simulation

Purpose – Imperfections in manufacturing processes may cause unwanted connections (faults) that are added to the nominal, "golden", design of an electronic circuit. By fault simulation one simulates all situations. Normally this leads to a large list of simulations in which for each defect a steady-state (DC) solution is determined followed by a transient simulation. We improve the robustness and the e¿iciency of these simulations. Design/methodology/approach – Determining the DC solution can be very hard. For this we present an adaptive time domain source stepping procedure that can deal with controlled sources. The method can easily be combined with existing pseudo-transient procedures. The method is robust and e¿cient. In the subsequent transient simulation the solution of a fault is compared to a golden, fault-free, solution. A strategy is developed to e¿ciently simulate the faulty solutions until their moment of detection. Finding – We fully exploit the hierarchical structure the circuit in the simulation process to bypass parts of the circuit that appear to be una¿ected by the fault. Accurate prediction and e¿cient solution procedures lead to fast fault simulation. Originality/value – Our fast fault simulation helps to store a database with detectable deviations for each fault. If such a detectable output "matches" a result of a product that has been returned because of malfunctioning it helps to identify the subcircuit that may contain the real fault. One aims to detect as much as possible candidate faults. Because of the many options the simulations must be very e¿cient

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

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 $\alpha_0\approx 3.4$ for 3D quantum Hall systems.Comment: 4 pages, 3 Postscript figures, corrected scale in Fig.

Robust DC and efficient time-domain fast fault simulation

Purpose – Imperfections in manufacturing processes may cause unwanted connections (faults) that are added to the nominal, "golden", design of an electronic circuit. By fault simulation one simulates all situations. Normally this leads to a large list of simulations in which for each defect a steady-state (DC) solution is determined followed by a transient simulation. We improve the robustness and the e¿iciency of these simulations. Design/methodology/approach – Determining the DC solution can be very hard. For this we present an adaptive time domain source stepping procedure that can deal with controlled sources. The method can easily be combined with existing pseudo-transient procedures. The method is robust and e¿cient. In the subsequent transient simulation the solution of a fault is compared to a golden, fault-free, solution. A strategy is developed to e¿ciently simulate the faulty solutions until their moment of detection. Finding – We fully exploit the hierarchical structure the circuit in the simulation process to bypass parts of the circuit that appear to be una¿ected by the fault. Accurate prediction and e¿cient solution procedures lead to fast fault simulation. Originality/value – Our fast fault simulation helps to store a database with detectable deviations for each fault. If such a detectable output "matches" a result of a product that has been returned because of malfunctioning it helps to identify the subcircuit that may contain the real fault. One aims to detect as much as possible candidate faults. Because of the many options the simulations must be very e¿cient

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

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