Vanishing of phase coherence in underdoped Bi_2Sr_2CaCu_2O_8+d

Coherent time-domain spectroscopy is used to measure the screening and dissipation of high-frequency electromagnetic fields in a set of underdoped Bi_2Sr_2CaCu_2O_8+d thin films. The measurements provide direct evidence for a phase-fluctuation driven transition from the superconductor to normal state, with dynamics described well by the Berezinskii-Kosterlitz-Thouless theory of vortex-pair unbinding.Comment: Nature, Vol. 398, 18 March 1999, pg. 221 4 pages with 4 included figure

Predictions from Lattice QCD

In the past year, we calculated with lattice QCD three quantities that were unknown or poorly known. They are the $q^2$ dependence of the form factor in semileptonic $D\to Kl\nu$ decay, the decay constant of the $D$ meson, and the mass of the $B_c$ meson. In this talk, we summarize these calculations, with emphasis on their (subsequent) confirmation by experiments.Comment: v1: talk given at the International Conference on QCD and Hadronic Physics, Beijing, June 16-20, 2005; v2: poster presented at the XXIIIrd International Symposium on Lattice Field Theory, Dublin, July 25-3

Development of paediatric non-stage prognosticator guidelines for population-based cancer registries and updates to the 2014 Toronto Paediatric Cancer Stage Guidelines

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs

F-Actin-Dependent Regulation of NESH Dynamics in Rat Hippocampal Neurons

Synaptic plasticity is an important feature of neurons essential for learning and memory. Postsynaptic organization and composition are dynamically remodeled in response to diverse synaptic inputs during synaptic plasticity. During this process, the dynamics and localization of postsynaptic proteins are also precisely regulated. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family. Overexpression of NESH is associated with reduced cell motility and tumor metastasis. Strong evidence of a close relationship between NESH and the actin cytoskeleton has been documented. Although earlier studies have shown that NESH is prominently expressed in the brain, its function and characteristics are yet to be established. Data from the present investigation suggest that synaptic localization of NESH in hippocampal neurons is regulated in an F-actin-dependent manner. The dynamic fraction of NESH in the dendritic spine was analyzed using FRAP (fluorescence recovery after photobleaching). Interestingly, F-actin stabilization and disruption significantly affected the mobile fraction of NESH, possibly through altered interactions of NESH with the F-actin. In addition, NESH was synaptically targeted from the dendritic shaft to spine after induction of chemical LTP (long-term potentiation) and the translocation was dependent on F-actin. Our data collectively support the significance of the F-actin cytoskeleton in synaptic targeting of NESH as well as its dynamics

A future without forgiveness: beyond reconciliation in transitional justice

This article questions the promotion of reconciliation in transitional justice contexts. The article puts forward a critique of reconciliation in practice and questions mainstream definitions of reconciliation. The principle that these forms of reconciliation are desirable is also questioned. It is argued that examples of genuine reconciliation are difficult to find, that the promotion of reconciliation is frequently emphasised at the expense of substantive societal change, that emphasis on reconciliation (narrowly defined) risks taking agency away from those affected by conflict and that emphasis on reconciliation may obscure injustice and may promote acceptance of the status quo. The article suggests that reconciliation is not a necessary condition of, and should be de-emphasised in, transitional justice and, if it is promoted at all, that a different, less prescriptive notion of reconciliation is necessary

Behavioral Sequence Analysis Reveals a Novel Role for ß2* Nicotinic Receptors in Exploration

Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the central nervous system and modulate neuronal function in most mammalian brain structures. The contribution of defined nAChR subunits to a specific behavior is thus difficult to assess. Mice deleted for ß2-containing nAChRs (ß2−/−) have been shown to be hyperactive in an open-field paradigm, without determining the origin of this hyperactivity. We here develop a quantitative description of mouse behavior in the open field based upon first order Markov and variable length Markov chain analysis focusing on the time-organized sequence that behaviors are composed of. This description reveals that this hyperactivity is the consequence of the absence of specific inactive states or “stops”. These stops are associated with a scanning of the environment in wild-type mice (WT), and they affect the way that animals organize their sequence of behaviors when compared with stops without scanning. They characterize a specific “decision moment” that is reduced in ß2−/− mutant mice, suggesting an important role of ß2-nAChRs in the strategy used by animals to explore an environment and collect information in order to organize their behavior. This integrated analysis of the displacement of an animal in a simple environment offers new insights, specifically into the contribution of nAChRs to higher brain functions and more generally into the principles that organize sequences of behaviors in animals

The influence of a virtual companion on amusement when watching funny films

We investigated the role of a virtual companion and trait cheerfulness on the elicitation of amusement. Ninety participants watched funny films in four conditions: either alone, with a virtual companion laughing or verbally expressing amusement at fixed time points (pre-scripted), or additionally joining the participant’s laughter (responsive companion). Amusement was assessed facially and vocally by coding Duchenne Displays and laughter vocalizations. Participants’ cheerful mood pre and post the film watching and positive experience were assessed. Results showed that high trait cheerful individuals generally experienced and expressed more amusement than low trait cheerful individuals. The presence of a virtual companion (compared to being alone) led to more laughter for individuals low in trait cheerfulness. Unexpectedly, the responsive companion did not elicit more amusement than the pre-scripted companion. The general disliking of virtual companions and gelotophobia related negatively to amusement. Amusement expressing virtual companions may be used in interventions aiming at eliciting positive responses, especially for individuals with higher thresholds for amusement.European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 27078

Optimization of Cell Morphology Measurement via Single-Molecule Tracking PALM

In neurons, the shape of dendritic spines relates to synapse function, which is rapidly altered during experience-dependent neural plasticity. The small size of spines makes detailed measurement of their morphology in living cells best suited to super-resolution imaging techniques. The distribution of molecular positions mapped via live-cell Photoactivated Localization Microscopy (PALM) is a powerful approach, but molecular motion complicates this analysis and can degrade overall resolution of the morphological reconstruction. Nevertheless, the motion is of additional interest because tracking single molecules provides diffusion coefficients, bound fraction, and other key functional parameters. We used Monte Carlo simulations to examine features of single-molecule tracking of practical utility for the simultaneous determination of cell morphology. We find that the accuracy of determining both distance and angle of motion depend heavily on the precision with which molecules are localized. Strikingly, diffusion within a bounded region resulted in an inward bias of localizations away from the edges, inaccurately reflecting the region structure. This inward bias additionally resulted in a counterintuitive reduction of measured diffusion coefficient for fast-moving molecules; this effect was accentuated by the long camera exposures typically used in single-molecule tracking. Thus, accurate determination of cell morphology from rapidly moving molecules requires the use of short integration times within each image to minimize artifacts caused by motion during image acquisition. Sequential imaging of neuronal processes using excitation pulses of either 2 ms or 10 ms within imaging frames confirmed this: processes appeared erroneously thinner when imaged using the longer excitation pulse. Using this pulsed excitation approach, we show that PALM can be used to image spine and spine neck morphology in living neurons. These results clarify a number of issues involved in interpretation of single-molecule data in living cells and provide a method to minimize artifacts in single-molecule experiments

Synapse Pathology in Psychiatric and Neurologic Disease

Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function—smaller spines have smaller synapses and support reduced synaptic transmission. The relationship between synaptic signaling, spine shape, and brain function is never more apparent than when the brain becomes dysfunctional. Many psychiatric and neurologic disorders, ranging from mental retardation and autism to Alzheimer’s disease and addiction, are accompanied by alterations in spine morphology and synapse number. In this review, we highlight the structure and molecular organization of synapses and discuss functional effects of synapse pathology in brain disease