Non-equilibrium dynamics of an unstable quantum pendulum

A pendulum prepared perfectly inverted and motionless is a prototype of unstable equilibria and corresponds to an unstable hyperbolic fixed point in the dynamical phase space. Unstable fixed points are central to understanding Hamiltonian chaos in classical systems. In many-body quantum systems, mean-field approximations fail in the vicinity of unstable fixed points and lead to dynamics driven by quantum fluctuations. Here, we measure the non-equilibrium dynamics of a many-body quantum pendulum initialized to a hyperbolic fixed point of the phase space. The experiment uses a spin-1 Bose condensate, which exhibits Josephson dynamics in the spin populations that correspond in the mean-field limit to motion of a non-rigid mechanical pendulum. The condensate is initialized to a minimum uncertainty spin state, and quantum fluctuations lead to non-linear spin evolution along a separatrix and non-Gaussian probability distributions that are measured to be in good agreement with exact quantum calculations up to 0.25 s. At longer times, atomic loss due to the finite lifetime of the condensate leads to larger spin oscillation amplitudes compared to no loss case as orbits depart from the separatrix. This demonstrates how decoherence of a many-body system can result in more apparent coherent behaviour. This experiment provides new avenues for studying macroscopic spin systems in the quantum limit and for investigations of important topics in non-equilibrium quantum dynamics.Comment: Main text 6 pages, 5 figures; Supplement 4 pages, 1 figur

Crowding Alone Cannot Account for Cosolute Effect on Amyloid Aggregation

Amyloid fiber formation is a specific form of protein aggregation, often resulting from the misfolding of native proteins. Aimed at modeling the crowded environment of the cell, recent experiments showed a reduction in fibrillation halftimes for amyloid-forming peptides in the presence of cosolutes that are preferentially excluded from proteins and peptides. The effect of excluded cosolutes has previously been attributed to the large volume excluded by such inert cellular solutes, sometimes termed “macromolecular crowding”. Here, we studied a model peptide that can fold to a stable monomeric β-hairpin conformation, but under certain solution conditions aggregates in the form of amyloid fibrils. Using Circular Dichroism spectroscopy (CD), we found that, in the presence of polyols and polyethylene glycols acting as excluded cosolutes, the monomeric β-hairpin conformation was stabilized with respect to the unfolded state. Stabilization free energy was linear with cosolute concentration, and grew with molecular volume, as would also be predicted by crowding models. After initiating the aggregation process with a pH jump, fibrillation in the presence and absence of cosolutes was followed by ThT fluorescence, transmission electron microscopy, and CD spectroscopy. Polyols (glycerol and sorbitol) increased the lag time for fibril formation and elevated the amount of aggregated peptide at equilibrium, in a cosolute size and concentration dependent manner. However, fibrillation rates remained almost unaffected by a wide range of molecular weights of soluble polyethylene glycols. Our results highlight the importance of other forces beyond the excluded volume interactions responsible for crowding that may contribute to the cosolute effects acting on amyloid formation

Pharmaceutical care and its relationship to prescribing behaviour of general practitioners.

Contains fulltext : 50980.pdf (publisher's version ) (Closed access)OBJECTIVE: To study the correlation between pharmaceutical care and prescribing routines of general practitioners (GPs). METHODS: Cross-sectional study; 201 pharmacies, 408 general practices, The Netherlands, 2000/2001. The variation in prescribing behaviour was characterised using 20 validated prescribing indicators based on general practice guidelines. The general construct 'adherence to guidelines' served as the dependent variable and was formed by summing the scores of the prescribing indicators. Four possible determinants of the variation were determined on the basis of survey questions: the construct 'the pharmacist's attitude towards pharmaceutical care', and three partial constructs derived from the pharmacist's care-providing function: the care for the individual patient, the cooperation with general practitioners and the registration of the care provided. A multiple linear regression analysis was then performed. MAIN OUTCOME MEASURE: The weighted score for the prescribing indicators. RESULTS: The weighted average score for the prescribing indicators was 65% (SD 3.7). The response rate to the survey was 71%. The pharmacist's attitude to pharmaceutical care, as well as the degree to which the pharmacist provided care for the individual patient, the degree to which he cooperated with the general practitioner and the degree to which he registered the care provided were not correlated with the 'adherence to guidelines' by the general practitioner with whom the pharmacist frequently cooperated. CONCLUSION: Variations between general practitioners in the quality of prescribing, as measured by their adherence to guidelines, were not correlated with pharmaceutical care by the pharmacist with whom they cooperated on a day-to-day basis