Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics.

Microtubule dynamics and polarity stem from the polymerization of αβ-tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate α- and β-tubulin assembly into heterodimers and maintain the soluble tubulin pool in the cytoplasm, but their physical mechanisms are unknown. Here, we reconstitute a core tubulin chaperone consisting of tubulin cofactors TBCD, TBCE, and Arl2, and reveal a cage-like structure for regulating αβ-tubulin. Biochemical assays and electron microscopy structures of multiple intermediates show the sequential binding of αβ-tubulin dimer followed by tubulin cofactor TBCC onto this chaperone, forming a ternary complex in which Arl2 GTP hydrolysis is activated to alter αβ-tubulin conformation. A GTP-state locked Arl2 mutant inhibits ternary complex dissociation in vitro and causes severe defects in microtubule dynamics in vivo. Our studies suggest a revised paradigm for tubulin cofactors and Arl2 functions as a catalytic chaperone that regulates soluble αβ-tubulin assembly and maintenance to support microtubule dynamics

Simulations and cosmological inference: A statistical model for power spectra means and covariances

We describe an approximate statistical model for the sample variance distribution of the non-linear matter power spectrum that can be calibrated from limited numbers of simulations. Our model retains the common assumption of a multivariate Normal distribution for the power spectrum band powers, but takes full account of the (parameter dependent) power spectrum covariance. The model is calibrated using an extension of the framework in Habib et al. (2007) to train Gaussian processes for the power spectrum mean and covariance given a set of simulation runs over a hypercube in parameter space. We demonstrate the performance of this machinery by estimating the parameters of a power-law model for the power spectrum. Within this framework, our calibrated sample variance distribution is robust to errors in the estimated covariance and shows rapid convergence of the posterior parameter constraints with the number of training simulations.Comment: 14 pages, 3 figures, matches final version published in PR

Ensayo de ladrillos a tracción

Not availableEn 1969 se comenzó en la Universidad de Salford un programa de investigación para el ensayo de elementos estructurales de fábrica de ladrillo, bajo los auspicios de la Brick Development Association. El trabajo iba dirigido a determinar la resistencia de los ladrillos bajo las tensiones a que ellos están sometidos en la práctica, que son predominantemente de tracción. Este artículo compara y contrasta los diferentes ensayos de tracción que se investigaron, mientras que un tercer miembro del equipo de investigación describe, en el artículo que continúa, la aplicación de las técnicas de fotoelasticidad a este trabajo

Differentiation of 3-O-Sulfated Heparin Disaccharide Isomers: Identification of Structural Aspects of the Heparin CCL2 Binding Motif

The presence of 3-O-sulfated glucosamine residues in heparin or heparan sulfate plays a role in binding to antithrombin III and HSV infection. In this study, tandem mass spectrometry was used to differentiate between two heparin disaccharide isomers containing variable sulfate at C6 in a common disaccharide and C3 in a more rare one. The dissociation patterns shown by MS2 and MS3 were clearly distinguishable between the isomers, allowing their differentiation and quantitation. Using this technique, we show that an octasaccharide with 11 sulfate groups with high affinity for inflammatory chemokine CCL2 does not contain 3-O-sulfated disaccharides

Unbiased Global Optimization of Lennard-Jones Clusters for N <= 201 by Conformational Space Annealing Method

We apply the conformational space annealing (CSA) method to the Lennard-Jones clusters and find all known lowest energy configurations up to 201 atoms, without using extra information of the problem such as the structures of the known global energy minima. In addition, the robustness of the algorithm with respect to the randomness of initial conditions of the problem is demonstrated by ten successful independent runs up to 183 atoms. Our results indicate that the CSA method is a general and yet efficient global optimization algorithm applicable to many systems.Comment: revtex, 4 pages, 2 figures. Physical Review Letters, in pres

New Tetrahedral Global Minimum for the 98-atom Lennard-Jones Cluster

A new atomic cluster structure corresponding to the global minimum of the 98-atom Lennard-Jones cluster has been found using a variant of the basin-hopping global optimization algorithm. The new structure has an unusual tetrahedral symmetry with an energy of -543.665361, which is 0.022404 lower than the previous putative global minimum. The new LJ_98 structure is of particular interest because its tetrahedral symmetry establishes it as one of only three types of exceptions to the general pattern of icosahedral structural motifs for optimal LJ microclusters. Similar to the other exceptions the global minimum is difficult to find because it is at the bottom of a narrow funnel which only becomes thermodynamically most stable at low temperature.Comment: 3 pages, 2 figures, revte

Superconducting Rebalance Accelerometer

A multi-axis accelerometer which utilizes a magnetically-suspended, high-TC proof mass is under development. The design and performance of a single axis device which is stabilized actively in the axial direction but which utilizes ring magnets for passive radial stabilization is discussed. The design of a full six degree-of-freedom device version is also described

Multiple Sclerosis Patient Sequence Variation In Epstein-Barr Virus Nuclear Antigen 1

No abstract availabl

Harnessing ward-level administrative data and expert knowledge to improve staffing decisions: A multi-method case study

© 2019 John Wiley & Sons Ltd Aim: The aim of this study was to investigate the impact of changes to bed configuration and patient mix on nurses’ workload in a single ward. Design: Multi-method case study. Method: The study was undertaken in an acute 28-bed ward in a tertiary referral public hospital in Queensland, Australia. Ward-level administrative data were obtained for a 2-year period, 12 months before bed configuration changes in October 2015 and 12 months after. These data included patient activity (bed occupancy, transfers, length of stay and casemix) and nurse staffing (budgeted and actual staffing levels, employment status and skillmix). Semi-structured interviews were conducted with ward nurses (N = 17) to explore the impact of the bed configuration changes on their workload. Results: Administrative data showed that the bed configuration changes resulted in more complex and dependent patients, increased patient transfers and greater variability in casemix. The interview data found these changes to patient complexity and activity intensified workloads, which were further increased by staffing decisions that resulted in greater reliance on temporary staff. Conclusion: Hospitals already possess the data and expert knowledge needed to improve staffing and bed management decisions without the need for additional, costly workload systems. Impact: Determining appropriate nurse staffing in light of the complexities and variation of patient needs at the ward level remains a challenge. This study identified increases in patient complexity, dependency, variability and churn that increased workload. Staffing grew but hidden factors associated with temporary staffing and skillmix further intensified nurses’ workload. Harnessing existing data and the expertise and experience of nursing unit managers (NUMs) would help staff wards more efficiently and effectively, providing reasonable workloads and appropriate skillmix that can enhance the safety and quality of patient care. To facilitate this, NUMs need access to accurate, timely, data and authority in staffing and bed management decisions