A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the <em>Saccharomyces cerevisiae</em> Elongator complex

Elongator is a conserved, multi-protein complex discovered in Saccharomyces cerevisiae, loss of which confers a range of pleiotropic phenotypes. Elongator in higher eukaryotes is required for normal growth and development and a mutation in the largest subunit of human Elongator (Elp1) causes familial dysautonomia, a severe recessive neuropathy. Elongator promotes addition of mcm(5) and ncm(5) modifications to uridine in the tRNA anticodon ‘wobble’ position in both yeast and higher eukaryotes. Since these modifications are required for the tRNAs to function efficiently, a translation defect caused by hypomodified tRNAs may therefore underlie the variety of phenotypes associated with Elongator dysfunction. The Elp1 carboxy-terminal domain contains a highly conserved arginine/lysine-rich region that resembles a nuclear localization sequence (NLS). Using alanine substitution mutagenesis, we show that this region is essential for Elongator's function in tRNA wobble uridine modification. However, rather than acting to determine the nucleo-cytoplasmic distribution of Elongator, we find that the basic region plays a critical role in a novel interaction between tRNA and the Elp1 carboxy-terminal domain. Thus the conserved basic region in Elp1 may be essential for tRNA wobble uridine modification by acting as tRNA binding motif

Examining area-level variation in service organisation and delivery across the breadth of primary healthcare. Usefulness of measures constructed from routine data

Australia has a universal healthcare system, yet organisation and delivery of primary healthcare (PHC) services varies across local areas. Understanding the nature and extent of this variation is essential to improve quality of care and health equity, but this has been hampered by a lack of suitable measures across the breadth of effective PHC systems. Using a suite of measures constructed at the area-level, this study explored their application in assessing area-level variation in PHC organisation and delivery. Routinely collected data from New South Wales, Australia were used to construct 13 small area-level measures of PHC service organisation and delivery that best approximated access (availability, affordability, accommodation) comprehensiveness and coordination. Regression analyses and pairwise Pearson’s correlations were used to examine variation by area, and by remoteness and area disadvantage. PHC service delivery varied geographically at the small-area level–within cities and more remote locations. Areas in major cities were more accessible (all measures), while in remote areas, services were more comprehensive and coordinated. In disadvantaged areas of major cities, there were fewer GPs (most disadvantaged quintile 0.9[SD 0.1] vs least 1.0[SD 0.2]), services were more affordable (97.4%[1.6] bulk-billed vs 75.7[11.3]), a greater proportion were after-hours (10.3%[3.0] vs 6.2[2.9]) and for chronic disease care (28%[3.4] vs 17.6[8.0]) but fewer for preventive care (50.7%[3.8] had cervical screening vs 62.5[4.9]). Patterns were similar in regional locations, other than disadvantaged areas had less after-hours care (1.3%[0.7] vs 6.1%[3.9]). Measures were positively correlated, except GP supply and affordability in major cities (-0.41, p < .01). Application of constructed measures revealed inequity in PHC service delivery amenable to policy intervention. Initiatives should consider the maldistribution of GPs not only by remoteness but also by area disadvantage. Avenues for improvement in disadvantaged areas include preventative care across all regions and after-hours care in regional locations

Beam Test Results of the BTeV Silicon Pixel Detector

The results of the BTeV silicon pixel detector beam test carried out at Fermilab in 1999-2000 are reported. The pixel detector spatial resolution has been studied as a function of track inclination, sensor bias, and readout threshold.Comment: 8 pages of text, 8 figures, Proceedings paper of Pixel 2000: International Workshop on Semiconductor Pixel Detectors for Particles and X-Rays, Genova, June 5-8, 200

Performance of prototype BTeV silicon pixel detectors in a high energy pion beam

The silicon pixel vertex detector is a key element of the BTeV spectrometer. Sensors bump-bonded to prototype front-end devices were tested in a high energy pion beam at Fermilab. The spatial resolution and occupancies as a function of the pion incident angle were measured for various sensor-readout combinations. The data are compared with predictions from our Monte Carlo simulation and very good agreement is found.Comment: 24 pages, 20 figure

Beam Test of BTeV Pixel Detectors

The silicon pixel vertex detector is one of the key elements of the BTeV spectrometer. Detector prototypes were tested in a beam at Fermilab. We report here on the measured spatial resolution as a function of the incident angles for different sensor-readout electronics combinations. We compare the results with predictions from our Monte Carlo simulation.Comment: 7 pages, 5 figures, Invited talk given by J.C. Wang at "Vertex 2000, 9th International Workshop on Vertex Detectors", Michigan, Sept 10-15, 2000. To be published in NIM

Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III

Magnetoresistance and spin-transfer torque in magnetic tunnel junctions

We comment on both recent progress and lingering puzzles related to research on magnetic tunnel junctions (MTJs). MTJs are already being used in applications such as magnetic-field sensors in the read heads of disk drives, and they may also be the first device geometry in which spin-torque effects are applied to manipulate magnetic dynamics, in order to make nonvolatile magnetic random access memory. However, there remain many unanswered questions about such basic properties as the magnetoresistance of MTJs, how their properties change as a function of tunnel-barrier thickness and applied bias, and what are the magnitude and direction of the spin-transfer-torque vector induced by a tunnel current.Comment: 37 pages, 2 figures. Contribution to a collection of "Current Perspectives" articles on spin transfer torque now available in the Journal of Magnetism and Magnetic Material

Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity

Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35 ± 10 nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ∆θ(ƒ), measured at 0.1 Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15 min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900 fg/ml to 900 ng/ml. A detection limit of around 90 fg/ml, which is significantly lower than the basal clinical levels of 5-10 pg/ml, was observed. Our results are significant for the development of point-of-care and early diagnostics where high sensitivity and short time-to-results are essential

Control de cambios / Rastrea los cambios / El camino cambia: Reflexiones sobre un mundo en transformación

“Track changes: Reflecting on a transforming world” was the theme chosen to invite panels, papers, posters and alternative presentations to be part of the 2019 international congress of SIEF that was held in Santiago de Compostela, Galicia (Spain). This introduction includes a description of the content of the congress, the rationale of the choice of plenaries and some reflections about the outcomes of the congress.El lema elegido para presentar paneles, ponencias, posters y presentaciones en formatos alternativos para el congreso internacional 2019 de SIEF -que tuvo lugar en Santiago de Compostela, Galicia (España)- fue&nbsp;“Track changes: Reflecting on a transforming world”.&nbsp;Esta introducción incluye una descripción del contenido del congreso, la idea para la elección de las plenarias y algunas reflexiones sobre los resultados del congreso. &nbsp

Phenological mismatch in Arctic-breeding shorebirds: Impact of snowmelt and unpredictable weather conditions on food availability and chick growth

The ecological consequences of climate change have been recognized in numerous species, with perhaps phenology being the most well-documented change. Phenological changes may have negative consequences when organisms within different trophic levels respond to environmental changes at different rates, potentially leading to phenological mismatches between predators and their prey. This may be especially apparent in the Arctic, which has been affected more by climate change than other regions, resulting in earlier, warmer, and longer summers. During a 7-year study near Utqiaġvik (formerly Barrow), Alaska, we estimated phenological mismatch in relation to food availability and chick growth in a community of Arctic-breeding shorebirds experiencing advancement of environmental conditions (i.e., snowmelt). Our results indicate that Arctic-breeding shorebirds have experienced increased phenological mismatch with earlier snowmelt conditions. However, the degree of phenological mismatch was not a good predictor of food availability, as weather conditions after snowmelt made invertebrate availability highly unpredictable. As a result, the food available to shorebird chicks that were 2–10 days old was highly variable among years (ranging from 6.2 to 28.8 mg trap−1 day−1 among years in eight species), and was often inadequate for average growth (only 20%–54% of Dunlin and Pectoral Sandpiper broods on average had adequate food across a 4-year period). Although weather conditions vary among years, shorebirds that nested earlier in relation to snowmelt generally had more food available during brood rearing, and thus, greater chick growth rates. Despite the strong selective pressure to nest early, advancement of nesting is likely limited by the amount of plasticity in the start and progression of migration. Therefore, long-term climatic changes resulting in earlier snowmelt have the potential to greatly affect shorebird populations, especially if shorebirds are unable to advance nest initiation sufficiently to keep pace with seasonal advancement of their invertebrate prey