Structural and energetic characterisation of interactions at the nucleotide-binding site of Hsp90

Heat Shock Protein 90 (Hsp90) is a ubiquitous molecular chaperone linked to the maturation and activation of a wide range of 'client proteins'. These include steroid hormone receptors, receptor tyrosine kinases and p53. Hsp90 activates ‘clients’ through a series of conformational changes driven by the binding and hydrolysis of ATP in the N-terminal domain. These changes are thought to facilitate the formation of client protein binding sites and aid achieving their functional state. The aims of this thesis are to investigate the thermodynamics of nucleotide-based ligand binding to the N-terminal domain of Hsp90 and to study the mechanism by which conformational changes are induced by ligand binding. Thermodynamic characterization of ligand binding using isothermal titration calorimetry was carried out in order to investigate the contribution of the different groups of the nucleotide to the binding affinity and determined the importance of the charge state of the ligand to binding. Measurements of the change in constant pressure heat capacity induced by ligand binding were also performed in order to further investigate previously reported unusual heat capacity changes in this system that may correspond to differences in the conformational changes induced by ADP vs. an ATP analogue (AMPPNP) . Structural studies by NMR of the N-terminal domain reveal a high degree of flexibility and specific conformational changes in response to the binding of different ligands to the N-terminal domain of Hsp90. The thermodynamics of ligand binding to the full length protein and to the isolated N551 (the first 551 amino acids) were also investigated and found to have a significant influence over both the thermodynamics and the heat capacity measurements compared to the isolated N-terminal domain

Castaing Instability and Precessing Domains in Confined Alkali Gases

We explore analogy between two-component quantum alkali gases and spin-polarized helium systems. Recent experiments in trapped gases are put into the frame of the existing theory for Castaing instability in transverse channel and formation of homogeneous precessing domains in spin-polarized systems. Analogous effects have already been observed in spin-polarized $$ and $^{3}He- ^{4}He$ mixtures systems. The threshold effect of the confining potential on the instability is analyzed. New experimental possibilities for observation of transverse instability in a trap are discussed.Comment: 6 RevTex pages, no figure

Vortex states in binary mixture of Bose-Einstein condensates

The vortex configurations in the Bose-Einstein condensate of the mixture of two different spin states |F=1,m_f=-1> and |2,1> of ^{87}Rb atoms corresponding to the recent experiments by Matthews et. al. (Phys. Rev. Lett. 83, 2498 (1999)) are considered in the framework of the Thomas-Fermi approximation as functions of N_2/N_1, where N_1 is the number of atoms in the state |1,-1> and N_2 - in the state |2,1>. It is shown that for nonrotating condensates the configuration with the |1,-1> fluid forming the shell about the |2,1> fluid (configuration "a") has lower energy than the opposite configuration (configuration "b") for all values of N_2/N_1. When the |1,-1> fluid has net angular momentum and forms an equatorial ring around the resting central condensate |2,1>, the total energy of the system is higher than the ground energy, but the configuration "a" has lower energy than the configuration "b" for all N_2/N_1. On the other hand, when the |2> fluid has the net angular momentum, for the lowest value of the angular momentum \hbar l (l=1) there is the range of the ratio N_2/N_1 where the configuration "b" has lower energy than the configuration "a". For higher values of the angular momentum the configuration "b" is stable for all values of N_2/N_1.Comment: minor changes, references adde

Value-in-acquisition : an institutional view

PURPOSE : By combining consumer culture theory and service dominant logic, this study proposes that value might be understood as value-in-acquisition, such that value outcomes result from the acquisition process in which broader social forces shape the exchange process. DESIGN/METHODOLOGY/APPROACH : This study addresses low-income consumers, for whom societal arrangements strongly determine service interactions. Qualitative interviews reveal service value processes and outcomes for low-income consumers during acquisition processes. FINDINGS : For low-income consumers, inclusion, status, resource access and emotional relief represent key value outcomes. Important value processes shape those value outcomes, reflecting broader societal arrangements at macro, meso and micro levels. Marketing constitutes an institutional arrangement that establishes an empowered “consumer” role. Value processes are hindered if consumers sense that their agency in this role is diminished, because marketing interactions give precedence to other social roles. RESEARCH LIMITATIONS/IMPLICATIONS : Marketing should be studied as an institutional arrangement that shapes value creation processes during acquisition. Micro-level value processes have important implications for service quality and service value. Value outcomes thus might be designed in the acquisition process, not just for the offering. PRACTICAL IMPLICATIONS : The acquisition process for any good or service should be designed with its own value proposition, separate to the core product or service. Careful design of value processes during acquisition could mitigate conflict between social roles and those of consumption. ORIGINALITY/VALUE : There is value in the acquisition process, independent of the value embedded in the goods and services.https://www.emerald.com/insight/publication/issn/0309-0566hj2019Gordon Institute of Business Science (GIBS

Macroscopic Quantum Fluctuations in the Josephson Dynamics of Two Weakly Linked Bose-Einstein Condensates

We study the quantum corrections to the Gross-Pitaevskii equation for two weakly linked Bose-Einstein condensates. The goals are: 1) to investigate dynamical regimes at the borderline between the classical and quantum behaviour of the bosonic field; 2) to search for new macroscopic quantum coherence phenomena not observable with other superfluid/superconducting systems. Quantum fluctuations renormalize the classical Josephson oscillation frequencies. Large amplitude phase oscillations are modulated, exhibiting collapses and revivals. We describe a new inter-well oscillation mode, with a vanishing (ensemble averaged) mean value of the observables, but with oscillating mean square fluctuations. Increasing the number of condensate atoms, we recover the classical Gross-Pitaevskii (Josephson) dynamics, without invoking the symmetry-breaking of the Gauge invariance.Comment: Submitte

Quantum Correlated Interstitials and the Hall Resistivity of the Magnetically Induced Wigner Crystal

We study a trial wavefunction for an interstitial in a Wigner crystal. We find that the electron correlations, ignored in a conventional Hartree-Fock treatment, dramatically lower the interstitial energy, especially at fillings close to an incompressible liquid state. The correlation between the interstitial electron and the lattice electrons at $\nu <1/m$ is introduced by constructing a trial wave- function which bears a Jastrow factor of a Laughlin state at $\nu=1/m$. For fillings close to but just below $\nu=1/m$, we find that a perfect Wigner crystal becomes unstable against formation of such interstitials. It is argued that conduction due to correlated interstitials in the presence of weak disorder leads to the {\it classical} Hall resistivity, as seen experimentally.Comment: 10 pages, RevTe

The socialist blues? Citizenship, class and civil society

This article seeks to explore the relationship between the British labour movement, the Left and the Labour party. It does so through the intellectual prism of debates around citizenship and civil society. In this respect, I seek to recover a critical politics around questions of class from the New Left who were always critical of more mainstream ideas of citizenship. However, I also point to the limitations of those who have argued that meaningful forms of citizenship can no longer be connected to political parties and only occurs outside of state organizations. Political parties continue to need intellectual narratives to legitimate their role in society and to connect with the broader civil order.The Labour Party in this respect has seemingly broken with ‘New Labour’ and is searching for a new narrative. The rise of an intellectual grouping around ‘Blue Labour’ has made considerable headway recently and I seek to take a critical view of some of their ideas and ethical frameworks. Here I argue that changing class formations and a more pluralistic society potentially ask difficult questions of those who seek to revive the labour movement in troubled times

Collective dynamics of internal states in a Bose gas

Theory for the Rabi and internal Josephson effects in an interacting Bose gas in the cold collision regime is presented. By using microscopic transport equation for the density matrix the problem is mapped onto a problem of precession of two coupled classical spins. In the absence of an external excitation field our results agree with the theory for the density induced frequency shifts in atomic clocks. In the presence of the external field, the internal Josephson effect takes place in a condensed Bose gas as well as in a non-condensed gas. The crossover from Rabi oscillations to the Josephson oscillations as a function of interaction strength is studied in detail.Comment: 18 pages, 2 figure

Vortex nucleation in Bose-Einstein condensates in time-dependent traps

Vortex nucleation in a Bose-Einstein condensate subject to a stirring potential is studied numerically using the zero-temperature, two-dimensional Gross-Pitaevskii equation. It is found that this theory is able to describe the creation of vortices, but not the crystallization of a vortex lattice. In the case of a rotating, slightly anisotropic harmonic potential, the numerical results reproduce experimental findings, thereby showing that finite temperatures are not necessary for vortex excitation below the quadrupole frequency. In the case of a condensate subject to stirring by a narrow rotating potential, the process of vortex excitation is described by a classical model that treats the multitude of vortices created by the stirrer as a continuously distributed vorticity at the center of the cloud, but retains a potential flow pattern at large distances from the center.Comment: 22 pages, 7 figures. Changes after referee report: one new figure, new refs. No conclusions altere