The work function of titanium and selected metals in vacuum

The work functions of titanium films have been measured at room temperature with a scanning probe version of the Kelvin-Zisman dynamic capacitor. The values for the clean surfaces of films deposited onto a gold substrate at 2.10-9 torr lay between 4.5 and 6.0 eV. The surface potentials of hydrogen were positive apparently due to penetration of the adsorbed hydrogen atom with a partial negative ionicity below the surface electronic plane. The maximum surface potential increased approximately linearly with the initial work function and varied between 0.26 and 1.30 eV. A surface potential model was proposed which attempted to account for dissociative adsorption of molecular hydrogen and solution of adsorbed atomic hydrogen. The time dependant changes of the surface potential were consistent with the theoretical predictions and the activation energy for solution of atomic hydrogen was derived to be between 0.7 and 1.5 Kcal gr-atom-1. The work function and surface potential of rapidly deposited films at 1.10-7 torr onto a silver substrate behaved similarly to those above and mass spectrometric analysis of the residual gas provided evidence for a predominant adsorption of hydrogen. Slowly deposited films at this pressure onto a silver substrate, however, possessed a low work function between 2.5 and 3.8 eV which broadly encompassed the range of values recently published by others for thin titanium films deposited apparently under similar conditions. The low values apparently arise from impurities. The surface potential of the residual gas adsorbate was negative on contaminated films and the time dependant changes were of a similar form to those of purer films. These results were discussed in relation to the hydrogen surface potential model and the adsorption of other gases. The work function of two polished stainless steel electrodes were 4.65 + 0.10 eV at 1.10-7 torr and 5.60 + 0.10 eV (after baking) at 2.10-9 torr. The work function was reversibly decreased by illumination, prolonged exposure to hydrogen and by applied electrostatic fields; it was reversibly increased by an incident electron current. These effects are interpreted as the result of an oxide layer on the steel surface. Theoretical models are proposed which attempt to account for these as due to changes in the density of surface states at a semiconducting oxide surface. The results are generally consistent with the theoretical predictions with the exception of the field effect. The effect of stray capacitive coupling on contact potential measurements was experimentally investigated. The results were partially consistent with the predictions of a model which is proposed. These effects are shown to be a major source of error if simple precautionary measures are not taken to avoid them

Matching small β\beta functions using centroid jitter and two beam position monitors

Matching to small beta functions is required to preserve emittance in plasma accelerators. The plasma wake provides strong focusing fields, which typically require beta functions on the mm-scale, comparable to those found in the final focusing of a linear collider. Such beams can be time consuming to experimentally produce and diagnose. We present a simple, fast, and noninvasive method to measure Twiss parameters in a linac using two beam position monitors only, relying on the similarity of the beam phase space and the jitter phase space. By benchmarking against conventional quadrupole scans, the viability of this technique was experimentally demonstrated at the FLASHForward plasma-accelerator facility.Comment: 8 pages, 7 figure

Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone.

We report the crystal structure of nuclear import receptor Importin-9 bound to its cargo, the histones H2A-H2B. Importin-9 wraps around the core, globular region of H2A-H2B to form an extensive interface. The nature of this interface coupled with quantitative analysis of deletion mutants of H2A-H2B suggests that the NLS-like sequences in the H2A-H2B tails play a minor role in import. Importin-9•H2A-H2B is reminiscent of interactions between histones and histone chaperones in that it precludes H2A-H2B interactions with DNA and H3-H4 as seen in the nucleosome. Like many histone chaperones, which prevent inappropriate non-nucleosomal interactions, Importin-9 also sequesters H2A-H2B from DNA. Importin-9 appears to act as a storage chaperone for H2A-H2B while escorting it to the nucleus. Surprisingly, RanGTP does not dissociate Importin-9•H2A-H2B but assembles into a RanGTP•Importin-9•H2A-H2B complex. The presence of Ran in the complex, however, modulates Imp9-H2A-H2B interactions to facilitate its dissociation by DNA and assembly into a nucleosome

Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition.

BubR1 is essential for the mitotic checkpoint that prevents aneuploidy in cellular progeny by triggering anaphase delay in response to kinetochores incorrectly/not attached to the mitotic spindle. Here, we define the molecular architecture of the functionally significant N-terminal region of human BubR1 and present the 1.8 A crystal structure of its tetratricopeptide repeat (TPR) domain. The structure reveals divergence from the classical TPR fold and is highly similar to the TPR domain of budding yeast Bub1. Shared distinctive features include a disordered loop insertion, a 3(10)-helix, a tight turn involving glycine positive Phi angles, and noncanonical packing of and between the TPR motifs. We also define the molecular determinants of the interaction between BubR1 and kinetochore protein Blinkin. We identify a shallow groove on the concave surface of the BubR1 TPR domain that forms multiple discrete and potentially cooperative interactions with Blinkin. Finally, we present evidence for a direct interaction between BubR1 and Bub1 mediated by regions C-terminal to their TPR domains. This interaction provides a mechanism for Bub1-dependent kinetochore recruitment of BubR1. We thus present novel molecular insights into the structure of BubR1 and its interactions at the kinetochore-microtubule interface. Our studies pave the way for future structure-directed engineering aimed at dissecting the roles of kinetochore-bound and other pools of BubR1 in vivo

Identifying drivers of spatio-temporal dynamics in Barley Yellow Dwarf Virus epidemiology as a critical factor in disease control

Barley yellow dwarf virus (BYDV) is one of the most important viral diseases of small grains worldwide. An understanding of its epidemiology is crucial to control this disease in a sustainable way. The virus moves through the agricultural landscape via cereal aphids as vectors. Understanding movement of these aphids in space and time is of key importance and in doing so, the spatial and temporal variables that influence BYDV epidemiology can be identified. The presence of summer hosts, crop rotation, crop diversity, agricultural practices and climate variables are crucial. Through digitalization, spatial (e.g. land-use) and temporal (e.g. weather) information is becoming more readily available. Including this information into a prediction model could improve decision support systems that will rationalize the decision-making process towards a more integrated control of the disease

<i>In vitro - in vivo </i>relations for the parenteral liposomal formulation of Amphotericin B:A clinically relevant approach with PBPK modeling

In vitro release testing is a useful tool for the quality control of controlled release parenteral formulations, but in vitro release test conditions that reflect or are able to predict the in vivo performance are advantageous. Therefore, it is important to investigate the factors that could affect drug release from formulations and relate them to in vivo performance. In this study the effect of media composition including albumin presence, type of buffer and hydrodynamics on drug release were evaluated on a liposomal Amphotericin B formulation (Ambisome®). A physiologically based pharmacokinetic (PBPK) model was developed using plasma concentration profiles from healthy subjects, in order to investigate the impact of each variable from the in vitro release tests on the prediction of the in vivo performance. It was found that albumin presence was the most important factor for the release of Amphotericin B from Ambisome®; both hydrodynamics setups, coupled with the PBPK model, had comparable predictive ability for simulating in vivo plasma concentration profiles. The PBPK model was extrapolated to a hypothetical hypoalbuminaemic population and the Amphotericin B plasma concentration and its activity against fungal cells were simulated. Selected in vitro release tests for these controlled release parenteral formulations were able to predict the in vivo AmB exposure, and this PBPK driven approach to release test development could benefit development of such formulations.</p

Investigation of fMRI activation in the internal capsule

<p>Abstract</p> <p>Background</p> <p>Functional magnetic resonance imaging (fMRI) in white matter has long been considered controversial. Recently, this viewpoint has been challenged by an emerging body of evidence demonstrating white matter activation in the corpus callosum. The current study aimed to determine whether white matter activation could be detected outside of the corpus callosum, in the internal capsule. Data were acquired from a 4 T MRI using a specialized asymmetric spin echo spiral sequence. A motor task was selected to elicit activation in the posterior limb of the internal capsule.</p> <p>Results</p> <p>White matter fMRI activation was examined at the individual and group levels. Analyses revealed that activation was present in the posterior limb of the internal capsule in 80% of participants. These results provide further support for white matter fMRI activation.</p> <p>Conclusions</p> <p>The ability to visualize functionally active tracts has strong implications for the basic scientific study of connectivity and the clinical assessment of white matter disease.</p

Does metformin improve vascular health in children with Type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial

Background: Cardiovascular disease is the leading cause of mortality in Type 1 diabetes (T1D). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2D for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1D. Methods/Design: This study is a 12 month, double blind, randomised, placebo controlled trial to determine the effect of metformin on vascular health in children (age 8–18) with T1D. The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group. Vascular health and biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness, using standardised protocols. Discussion: This study will be the first to investigate the effect of metformin on vascular health in children with T1D. It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease.Jemma Anderson, Alexia S Peña, Thomas Sullivan, Roger Gent, Bronwen D’Arcy, Timothy Olds, Brian Coppin and Jennifer Coupe