Luminescence quenching of the triplet excimer state by air traces in gaseous argon

While developing a liquid argon detector for dark matter searches we investigate the influence of air contamination on the VUV scintillation yield in gaseous argon at atmospheric pressure. We determine with a radioactive alpha-source the photon yield for various partial air pressures and different reflectors and wavelength shifters. We find for the fast scintillation component a time constant tau1= 11.3 +- 2.8 ns, independent of gas purity. However, the decay time of the slow component depends on gas purity and is a good indicator for the total VUV light yield. This dependence is attributed to impurities destroying the long-lived argon excimer states. The population ratio between the slowly and the fast decaying excimer states is determined for alpha-particles to be 5.5 +-0.6 in argon gas at 1100 mbar and room temperature. The measured mean life of the slow component is tau2 = 3.140 +- 0.067 microsec at a partial air pressure of 2 x 10-6 mbar.Comment: 7 pages submitted to NIM

Power-Law Distributions in a Two-sided Market and Net Neutrality

"Net neutrality" often refers to the policy dictating that an Internet service provider (ISP) cannot charge content providers (CPs) for delivering their content to consumers. Many past quantitative models designed to determine whether net neutrality is a good idea have been rather equivocal in their conclusions. Here we propose a very simple two-sided market model, in which the types of the consumers and the CPs are {\em power-law distributed} --- a kind of distribution known to often arise precisely in connection with Internet-related phenomena. We derive mostly analytical, closed-form results for several regimes: (a) Net neutrality, (b) social optimum, (c) maximum revenue by the ISP, or (d) maximum ISP revenue under quality differentiation. One unexpected conclusion is that (a) and (b) will differ significantly, unless average CP productivity is very high

Study of nuclear recoils in liquid argon with monoenergetic neutrons

For the development of liquid argon dark matter detectors we assembled a setup in the laboratory to scatter neutrons on a small liquid argon target. The neutrons are produced mono-energetically (E_kin=2.45 MeV) by nuclear fusion in a deuterium plasma and are collimated onto a 3" liquid argon cell operating in single-phase mode (zero electric field). Organic liquid scintillators are used to tag scattered neutrons and to provide a time-of-flight measurement. The setup is designed to study light pulse shapes and scintillation yields from nuclear and electronic recoils as well as from {\alpha}-particles at working points relevant to dark matter searches. Liquid argon offers the possibility to scrutinise scintillation yields in noble liquids with respect to the populations of the two fundamental excimer states. Here we present experimental methods and first results from recent data towards such studies.Comment: 9 pages, 8 figures, proceedings of TAUP 2011, to be published in Journal of Physics: Conference Series (JCPS

Effect of spermidine on misfolding and interactions of alpha-synuclein.

Alpha-synuclein (α-Syn) is a 140 aa presynaptic protein which belongs to a group of natively unfolded proteins that are unstructured in aqueous solutions. The aggregation rate of α-Syn is accelerated in the presence of physiological levels of cellular polyamines. Here we applied single molecule AFM force spectroscopy to characterize the effect of spermidine on the very first stages of α-Syn aggregation--misfolding and assembly into dimers. Two α-Syn variants, the wild-type (WT) protein and A30P, were studied. The two protein molecules were covalently immobilized at the C-terminus, one at the AFM tip and the other on the substrate, and intermolecular interactions between the two molecules were measured by multiple approach-retraction cycles. At conditions close to physiological ones at which α-Syn misfolding is a rare event, the addition of spermidine leads to a dramatic increase in the propensity of the WT and mutant proteins to misfold. Importantly, misfolding is characterized by a set of conformations, and A30P changes the misfolding pattern as well as the strength of the intermolecular interactions. Together with the fact that spermidine facilitates late stages of α-Syn aggregation, our data demonstrate that spermidine promotes the very early stages of protein aggregation including α-Syn misfolding and dimerization. This finding suggests that increased levels of spermidine and potentially other polyamines can initiate the disease-related process of α-Syn

Direct Detection of α-Synuclein Dimerization Dynamics: Single-Molecule Fluorescence Analysis

AbstractThe aggregation of α-synuclein (α-Syn) is linked to Parkinson’s disease. The mechanism of early aggregation steps and the effect of pathogenic single-point mutations remain elusive. We report here a single-molecule fluorescence study of α-Syn dimerization and the effect of mutations. Specific interactions between tethered fluorophore-free α-Syn monomers on a substrate and fluorophore-labeled monomers diffusing freely in solution were observed using total internal reflection fluorescence microscopy. The results showed that wild-type (WT) α-Syn dimers adopt two types of dimers. The lifetimes of type 1 and type 2 dimers were determined to be 197 ± 3 ms and 3334 ± 145 ms, respectively. All three of the mutations used, A30P, E46K, and A53T, increased the lifetime of type 1 dimer and enhanced the relative population of type 2 dimer, with type 1 dimer constituting the major fraction. The kinetic stability of type 1 dimers (expressed in terms of lifetime) followed the order A30P (693 ± 14 ms) > E46K (292 ± 5 ms) > A53T (226 ± 6 ms) > WT (197 ± 3 ms). Type 2 dimers, which are more stable, had lifetimes in the range of several seconds. The strongest effect, observed for the A30P mutant, resulted in a lifetime 3.5 times higher than observed for the WT type 1 dimer. This mutation also doubled the relative fraction of type 2 dimer. These data show that single-point mutations promote dimerization, and they suggest that the structural heterogeneity of α-Syn dimers could lead to different aggregation pathways

A novel thiol-labile cysteine protecting group for peptide synthesis based on a pyridazinedione (PD) scaffold

Herein we report a thiol-labile cysteine protecting group based on an unsaturated pyridazinedione (PD) scaffold. We establish compatibility of the PD in conventional solid phase peptide synthesis (SPPS), showcasing this in the on-resin synthesis of biologically relevant oxytocin. Furthermore, we establish the applicability of the PD protecting group towards both microwave-assisted SPPS and native chemical ligation (NCL) in a model system