A Cation-π Interaction in the Binding Site of the Glycine Receptor Is Mediated by a Phenylalanine Residue

Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-{pi} interaction with the agonist, whereas in GABAA receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-{pi} interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC50 value and the cation-{pi} binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-{pi} interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-{pi} interaction between Phe and a neurotransmitter

Generalized Phase-Space Techniques to Explore Quantum Phase Transitions in Critical Quantum Spin Systems

We apply the generalized Wigner function formalism to detect and characterize a range of quantum phase transitions in several cyclic, finite-length, spin-$\frac{1}{2}$ one-dimensional spin-chain models, viz., the Ising and anisotropic $XY$ models in a transverse field, and the $XXZ$ anisotropic Heisenberg model. We make use of the finite system size to provide an exhaustive exploration of each system's single-site, bipartite and multi-partite correlation functions. In turn, we are able to demonstrate the utility of phase-space techniques in witnessing and characterizing first-, second- and infinite-order quantum phase transitions, while also enabling an in-depth analysis of the correlations present within critical systems. We also highlight the method's ability to capture other features of spin systems such as ground-state factorization and critical system scaling. Finally, we demonstrate the generalized Wigner function's utility for state verification by determining the state of each system and their constituent sub-systems at points of interest across the quantum phase transitions, enabling interesting features of critical systems to be intuitively analyzed.Comment: 20 pages, 8 figure

Dynamics of levitated nanospheres: towards the strong coupling regime

The use of levitated nanospheres represents a new paradigm for the optomechanical cooling of a small mechanical oscillator, with the prospect of realising quantum oscillators with unprecedentedly high quality factors. We investigate the dynamics of this system, especially in the so-called self-trapping regimes, where one or more optical fields simultaneously trap and cool the mechanical oscillator. The determining characteristic of this regime is that both the mechanical frequency $\omega_M$ and single-photon optomechanical coupling strength parameters $g$ are a function of the optical field intensities, in contrast to usual set-ups where $\omega_M$ and $g$ are constant for the given system. We also measure the characteristic transverse and axial trapping frequencies of different sized silica nanospheres in a simple optical standing wave potential, for spheres of radii $r=20-500$\,nm, illustrating a protocol for loading single nanospheres into a standing wave optical trap that would be formed by an optical cavity. We use this data to confirm the dependence of the effective optomechanical coupling strength on sphere radius for levitated nanospheres in an optical cavity and discuss the prospects for reaching regimes of strong light-matter coupling. Theoretical semiclassical and quantum displacement noise spectra show that for larger nanospheres with $r \gtrsim 100$\,nm a range of interesting and novel dynamical regimes can be accessed. These include simultaneous hybridization of the two optical modes with the mechanical modes and parameter regimes where the system is bistable. We show that here, in contrast to typical single-optical mode optomechanical systems, bistabilities are independent of intracavity intensity and can occur for very weak laser driving amplitudes

Collaborative Musical Expression and Creativity Among Academics: When Intellectualism Meets Twelve Bar Blues

The Professors are a blues, rock, and sometime heavy metal band made up of communication professors from a number of New Jersey schools. Formed in 1995, the band has played in clubs in New York City as well as a number of academic venues, including the annual conference of the International Communication Association in Chicago in 1996 and the annual conference of the National Communication Association in New York City in 1998. The Professors have been featured in both local and national press, including the Chronicle of Higher Education. When we learned of the call for papers for this special issue of the American Communication Journal addressing the creative endeavors of Communication scholars beyond their regular research agendas, we were delighted to have the opportunity to reflect upon the place of musical creativity within our lives as working academics. What follows in this paper are the thoughts of a number of band members, past and present, who trace the relationship of the musical, the creative, and the intellectual in terms of their own personal histories and academic interests

Negotiating professional and social voices in research principles and practice

This paper draws on work conducted for a qualitative interview based study which explores the gendered racialised and professional identifications of health and social care professionals. Participants for the project were drawn from the professional executive committees of recently formed Primary Care Trusts. The paper discusses how the feminist psychosocial methodological approach developed for the project is theoretically, practically and ethically useful in exploring the voices of those in positions of relative power in relation to both health and social care services and the social relations of gender and ethnicity. The approach draws on psychodynamic accounts of (defended) subjectivity and the feminist work of Carol Gilligan on a voice-centred relational methodology. Coupling the feminist with the psychosocial facilitates an emphasis on voice and dialogic communication between participant and researcher not always captured in psychosocial approaches which tend towards favouring the interviewer as ‘good listener’. This emphasis on dialogue is important in research contexts where prior and ongoing relationships with professional participants make it difficult and indeed undesirable for researchers to maintain silence

Brownian Carnot engine

The Carnot cycle imposes a fundamental upper limit to the efficiency of a macroscopic motor operating between two thermal baths. However, this bound needs to be reinterpreted at microscopic scales, where molecular bio-motors and some artificial micro-engines operate. As described by stochastic thermodynamics, energy transfers in microscopic systems are random and thermal fluctuations induce transient decreases of entropy, allowing for possible violations of the Carnot limit. Despite its potential relevance for the development of a thermodynamics of small systems, an experimental study of microscopic Carnot engines is still lacking. Here we report on an experimental realization of a Carnot engine with a single optically trapped Brownian particle as working substance. We present an exhaustive study of the energetics of the engine and analyze the fluctuations of the finite-time efficiency, showing that the Carnot bound can be surpassed for a small number of non-equilibrium cycles. As its macroscopic counterpart, the energetics of our Carnot device exhibits basic properties that one would expect to observe in any microscopic energy transducer operating with baths at different temperatures. Our results characterize the sources of irreversibility in the engine and the statistical properties of the efficiency -an insight that could inspire novel strategies in the design of efficient nano-motors.Comment: 7 pages, 7 figure

Nanoscale temperature measurements using non-equilibrium Brownian dynamics of a levitated nanosphere

Einstein realised that the fluctuations of a Brownian particle can be used to ascertain properties of its environment. A large number of experiments have since exploited the Brownian motion of colloidal particles for studies of dissipative processes, providing insight into soft matter physics, and leading to applications from energy harvesting to medical imaging. Here we use optically levitated nanospheres that are heated to investigate the non-equilibrium properties of the gas surrounding them. Analysing the sphere's Brownian motion allows us to determine the temperature of the centre-of-mass motion of the sphere, its surface temperature and the heated gas temperature in two spatial dimensions. We observe asymmetric heating of the sphere and gas, with temperatures reaching the melting point of the material. This method offers new opportunities for accurate temperature measurements with spatial resolution on the nanoscale, and a new means for testing non-equilibrium thermodynamicsComment: 5 pages, 4 figures, supplementary material available upon reques

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders

Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum

We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders