Comparison of metal ion-induced conformational changes in parvalbumin and oncomodulin as probed by the intrinsic fluorescence of tryptophan 102.

The calcium-induced conformational changes of the 108-amino acid residue proteins, cod III parvalbumin and oncomodulin, were compared using tryptophan as a sensitive spectroscopic probe. As native oncomodulin is devoid of tryptophan, site-specific mutagenesis was performed to create a mutant protein in which tryptophan was placed in the identical position (residue 102) as the single tryptophan residue in cod III parvalbumin. The results showed that in the region probed by tryptophan-102, cod III parvalbumin experienced significantly greater changes in conformation upon decalcification compared to the oncomodulin mutant, F102W. Addition of 1 eq of Ca2+ produced greater than 90% of the total fluorescence response in F102W, while in cod III parvalbumin, only 74% of the total was observed. Cod III parvalbumin displayed a negligible response upon Mg2+ addition. In contrast, F102W did respond to Mg2+, but the response was considerably less when compared to Ca2+ addition. Time-resolved fluorescence showed that the tryptophan in both proteins existed in at least two conformational states in the presence of Ca2+ and at least three conformational states in its absence. Comparison with quantum yield measurements indicated that the local electronic environment of the tryptophan was significantly different in the two proteins. Collectively, these results demonstrate that both cod III parvalbumin and oncomodulin undergo Ca2(+)-specific conformational changes. However, oncomodulin is distinct from cod III parvalbumin in terms of the electronic environment of the hydrophobic core, the magnitude of the Ca2(+)-induced conformational changes, and the number of calcium ions required to modulate the major conformational changes

Site-specific Mutants of Oncomodulin: 1H NMR and optical stopped-flow studies of the effect on the metal binding properties of an Asp59 → Glu59 substitution in the calcium-specific site

Abstract High resolution 1H nuclear magnetic resonance spectroscopy and optical stopped-flow techniques have been used to study the metal binding properties of a site-specific mutant of bacterial recombinant oncomodulin in which glutamate has replaced a liganding aspartate at position 59 in the CD calcium-binding site. In particular we have followed the replacement of calcium by lutetium in bacterial recombinant oncomodulin and D59E oncomodulin to provide a measure of the protein's preferences for metal ions of different ionic radii. The result of the Asp----Glu substitution is to make the mutant oncomodulin more similar to rat parvalbumin in terms of its relative CD- and EF-domain affinities for lutetium(III), that is to increase its affinity for metal ions with smaller ionic radii. This finding supports the original hypothesis that the presence of Asp at sequence position 59 is an important factor in the reduced preference of the CD site of oncomodulin for smaller metals such as magnesium (Williams, T. C., Corson, D. C., Sykes, B. D., and MacManus, J. P. (1987) J. Biol. Chem. 262, 6248-6256). However, our studies show that both the CD and the EF sites are affected by this single residue substitution suggesting that many factors play a role in the metal binding affinity and interaction between the two sites

Navigation Patterns in Ederly During Multitasking in Virtual Environnment

Cognitive assessment and screening can be realized with virtual environments (VE). These VE reproduce ecological situation and give an overview of participants difficulties through scoring systems. The most variables used to qualify participants performance are number of errors and time completion. These variables are link to cognition and navigation skill in VEs. We assessed navigation of adult and elderly in a multitasking VE. Navigation patterns were elaborate with diagram to visually detect differences between the two age groups. Elderly have poorer performance than adults

Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

On biases in precise point positioning with multi-constellation and multi-frequency GNSS data

© 2016 IOP Publishing Ltd. Various types of biases in Global Navigation Satellite System (GNSS) data preclude integer ambiguity fixing and degrade solution accuracy when not being corrected during precise point positioning (PPP). In this contribution, these biases are first reviewed, including satellite and receiver hardware biases, differential code biases, differential phase biases, initial fractional phase biases, inter-system receiver time biases, and system time scale offset. PPP models that take account of these biases are presented for two cases using ionosphere-free observations. The first case is when using primary signals that are used to generate precise orbits and clock corrections. The second case applies when using additional signals to the primary ones. In both cases, measurements from single and multiple constellations are addressed. It is suggested that the satellite-related code biases be handled as calibrated quantities that are obtained from multi-GNSS experiment products and the fractional phase cycle biases obtained from a network to allow for integer ambiguity fixing. Some receiver-related biases are removed using between-satellite single differencing, whereas other receiver biases such as inter-system biases are lumped with differential code and phase biases and need to be estimated. The testing results show that the treatment of biases significantly improves solution convergence in the float ambiguity PPP mode, and leads to ambiguity-fixed PPP within a few minutes with a small improvement in solution precision

Review of code and phase biases in multi-GNSS positioning

A review of the research conducted until present on the subject of Global Navigation Satellite System (GNSS) hardware-induced phase and code biases is here provided. Biases in GNSS positioning occur because of imperfections and/or physical limitations in the GNSS hardware. The biases are a result of small delays between events that ideally should be simultaneous in the transmission of the signal from a satellite or in the reception of the signal in a GNSS receiver. Consequently, these biases will also be present in the GNSS code and phase measurements and may there affect the accuracy of positions and other quantities derived from the observations. For instance, biases affect the ability to resolve the integer ambiguities in Precise Point Positioning (PPP), and in relative carrier phase positioning when measurements from multiple GNSSs are used. In addition, code biases affect ionospheric modeling when the Total Electron Content is estimated from GNSS measurements. The paper illustrates how satellite phase biases inhibit the resolution of the phase ambiguity to an integer in PPP, while receiver phase biases affect multi-GNSS positioning. It is also discussed how biases in the receiver channels affect relative GLONASS positioning with baselines of mixed receiver types. In addition, the importance of code biases between signals modulated onto different carriers as is required for modeling the ionosphere from GNSS measurements is discussed. The origin of biases is discussed along with their effect on GNSS positioning, and descriptions of how biases can be estimated or in other ways handled in the positioning process are provided.QC 20170922</p

Evaluation of ‘The Exercise Effect’: A pilot project integrating an exercise practitioner into outpatient mental health services in Ireland

In April 2019, a submission for funding was made to the Sláintecare Integration Fund (2019) to establish the ‘Exercise Effect’ project, including an independent evaluation of the project. The Exercise Effect builds on a longstanding collaborative partnership between key stakeholders, Health Service Executive (HSE) South East Wexford Mental Health Services, Sports Active Wexford (SAW) (a Local Sports Partnership) and Waterford Institute of Technology (WIT). Exercise is well recognised as a therapeutic tool that can benefit a range of mental health symptoms and cognitive function among trans-diagnostic mental health populations. Exercise interventions are also a valuable resource for improving the disproportionately poor physical health states of people with mental disorders. This report presents a detailed account of the Exercise Effect project and the findings from the research evaluation undertaken

Study on cycle-slip detection and repair methods for a single dual-frequency global positioning system (GPS) receiver

In this work, we assessed the performance of the cycle-slip detection methods: Turbo Edit (TE), Melbourne-Wübbena wide-lane ambiguity (MWWL) and forward and backward moving window averaging (FBMWA). The TE and MWWL methods were combined with ionospheric total electron content rate (TECR), and the FBMWA with second-order time-difference phase ionosphere residual (STPIR) and TECR. Under different scenarios, 10 Global Positioning System (GPS) datasets were used to assess the performance of the methods for cycle-slip detection. The MWWL-TECR delivered the best performance in detecting cycle-slips for 1 s data. The relative comparisons show that the FBMWA-TECR method performed slightly better than its original version, FBMWA-STPIR, detecting 100% and 73%, respectively. For data with a sample rate of 5 s, the FBMWA-TECR performed better than MWWL-TECR. However, the FBMWA is suitable only for post-processing, which refers to applications where the data are processed after the fact

Automated annotation of chemical names in the literature with tunable accuracy

<p>Abstract</p> <p>Background</p> <p>A significant portion of the biomedical and chemical literature refers to small molecules. The accurate identification and annotation of compound name that are relevant to the topic of the given literature can establish links between scientific publications and various chemical and life science databases. Manual annotation is the preferred method for these works because well-trained indexers can understand the paper topics as well as recognize key terms. However, considering the hundreds of thousands of new papers published annually, an automatic annotation system with high precision and relevance can be a useful complement to manual annotation.</p> <p>Results</p> <p>An automated chemical name annotation system, MeSH Automated Annotations (MAA), was developed to annotate small molecule names in scientific abstracts with tunable accuracy. This system aims to reproduce the MeSH term annotations on biomedical and chemical literature that would be created by indexers. When comparing automated free text matching to those indexed manually of 26 thousand MEDLINE abstracts, more than 40% of the annotations were false-positive (FP) cases. To reduce the FP rate, MAA incorporated several filters to remove "incorrect" annotations caused by nonspecific, partial, and low relevance chemical names. In part, relevance was measured by the position of the chemical name in the text. Tunable accuracy was obtained by adding or restricting the sections of the text scanned for chemical names. The best precision obtained was 96% with a 28% recall rate. The best performance of MAA, as measured with the F statistic was 66%, which favorably compares to other chemical name annotation systems.</p> <p>Conclusions</p> <p>Accurate chemical name annotation can help researchers not only identify important chemical names in abstracts, but also match unindexed and unstructured abstracts to chemical records. The current work is tested against MEDLINE, but the algorithm is not specific to this corpus and it is possible that the algorithm can be applied to papers from chemical physics, material, polymer and environmental science, as well as patents, biological assay descriptions and other textual data.</p

S-system theory applied to array-based GNSS ionospheric sensing

The GPS carrier-phase and code data have proven to be valuable sources of measuring the Earth’s ionospheric total electron content (TEC). With the development of new GNSSs with multi frequency data, many more ionosphere-sensing combinations of different precision can be formed as input of ionospheric modelling. We present the general way of interpreting such combinations through an application of S-system theory and address how their precision propagates into that of the unbiased TEC solution. Presenting the data relevant to TEC determination, we propose the usage of an array of GNSS antennas to improve the TEC precision and to expedite the rather long observational time-span required for high-precision TEC determination