Using Social Judgment Theory method to examine how experienced occupational therapy driver assessors use information to make fitness-to-drive recommendations

Introduction - As people with a range of disabilities strive to increase their community mobility, occupational therapy driver assessors are increasingly required to make complex recommendations regarding fitness-to-drive. However, very little is known about how therapists use information to make decisions. The aim of this study was to model how experienced occupational therapy driver assessors weight and combine information when making fitness-to-drive recommendations and establish their level of decision agreement. Method - Using Social Judgment Theory method, this study examined how 45 experienced occupational therapy driver assessors from the UK, Australia and New Zealand made fitness-to-drive recommendations for a series of 64 case scenarios. Participants completed the task on a dedicated website, and data were analysed using discriminant function analysis and an intraclass correlation coefficient. Results - Accounting for 87% of the variance, the cues central to the fitness-to-drive recommendations made by assessors are the client’s physical skills, cognitive and perceptual skills, road law craft skills, vehicle handling skills and the number of driving instructor interventions. Agreement (consensus) between fitness-to-drive recommendations was very high: intraclass correlation coefficient = .97, 95% confidence interval .96–.98). Conclusion - Findings can be used by both experienced and novice driver assessors to reflect on and strengthen the fitness-to-drive recommendations made to clients.This work was supported by the UK Occupational Therapy Research Foundation, Research Priority Grant scheme, 2012

AMPA receptor activation promotes non-amyloidogenic amyloid precursor protein processing and suppresses neuronal amyloid-β production

Soluble oligomeric amyloid β peptide (Aβ) generated from processing of the amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's Disease (AD) and through actions at glutamatergic synapses affects excitability and plasticity. The physiological control of APP processing is not fully understood but stimulation of synaptic NMDA receptors (NMDAR) can suppress Aβ levels through an ERK-dependent increase in α-secretase activity. AMPA-type glutamate receptors (AMPAR) couple to ERK phosphorylation independently of NMDAR activation raising the possibility that stimulation of AMPAR might similarly promote non-amyloidogenic APP processing. We have tested this hypothesis by investigating whether AMPAR directly regulate APP processing in cultured mouse cortical neurons, by analyzing APP C-terminal fragments (CTFs), soluble APP (sAPP), Aβ levels, and cleavage of an APP-GAL4 reporter protein. We report that direct stimulation of AMPAR increases non-amyloidogenic α-secretase-mediated APP processing and inhibits Aβ production. Processing was blocked by the matrix metalloproteinase inhibitor TAPI-1 but was only partially dependent on Ca(2+) influx and ERK activity. AMPAR can therefore, be added to the repertoire of receptors that couple to non-amyloidogenic APP processing at glutamatergic synapses and thus pharmacological targeting of AMPAR could potentially influence the development and progression of Aβ pathology in AD

Modeling the Multiwavelength Evolution of the V960 Mon System

We study the evolution of the FU Ori object V960 Mon since its outburst, using available multi-wavelength photometric time series over 8 years, complemented by several epochs of moderate-dispersion spectrophotometry. We find that the source fading can be well-described by a decrease in the temperature of the inner disk, which results from a combination of decreasing accretion rate and increasing inner disk radius. We model the system with a disk atmosphere model that produces the observed variations in multi-band photometry (this paper) and high resolution spectral lines (a companion paper).Comment: 15 pages, 13 figures, 2 tables, Accepted to Ap

Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring

Defining intracellular protein concentration is critical in molecular systems biology. Although strategies for determining relative protein changes are available, defining robust absolute values in copies per cell has proven significantly more challenging. Here we present a reference data set quantifying over 1800 Saccharomyces cerevisiae proteins by direct means using protein-specific stable-isotope labeled internal standards and selected reaction monitoring (SRM) mass spectrometry, far exceeding any previous study. This was achieved by careful design of over 100 QconCAT recombinant proteins as standards, defining 1167 proteins in terms of copies per cell and upper limits on a further 668, with robust CVs routinely less than 20%. The selected reaction monitoring-derived proteome is compared with existing quantitative data sets, highlighting the disparities between methodologies. Coupled with a quantification of the transcriptome by RNA-seq taken from the same cells, these data support revised estimates of several fundamental molecular parameters: a total protein count of ∼100 million molecules-per-cell, a median of ∼1000 proteins-per-transcript, and a linear model of protein translation explaining 70% of the variance in translation rate. This work contributes a “gold-standard” reference yeast proteome (including 532 values based on high quality, dual peptide quantification) that can be widely used in systems models and for other comparative studies. Reliable and accurate quantification of the proteins present in a cell or tissue remains a major challenge for post-genome scientists. Proteins are the primary functional molecules in biological systems and knowledge of their abundance and dynamics is an important prerequisite to a complete understanding of natural physiological processes, or dysfunction in disease. Accordingly, much effort has been spent in the development of reliable, accurate and sensitive techniques to quantify the cellular proteome, the complement of proteins expressed at a given time under defined conditions (1). Moreover, the ability to model a biological system and thus characterize it in kinetic terms, requires that protein concentrations be defined in absolute numbers (2, 3). Given the high demand for accurate quantitative proteome data sets, there has been a continual drive to develop methodology to accomplish this, typically using mass spectrometry (MS) as the analytical platform. Many recent studies have highlighted the capabilities of MS to provide good coverage of the proteome at high sensitivity often using yeast as a demonstrator system (4⇓⇓⇓⇓⇓–10), suggesting that quantitative proteomics has now “come of age” (1). However, given that MS is not inherently quantitative, most of the approaches produce relative quantitation and do not typically measure the absolute concentrations of individual molecular species by direct means. For the yeast proteome, epitope tagging studies using green fluorescent protein or tandem affinity purification tags provides an alternative to MS. Here, collections of modified strains are generated that incorporate a detectable, and therefore quantifiable, tag that supports immunoblotting or fluorescence techniques (11, 12). However, such strategies for copies per cell (cpc) quantification rely on genetic manipulation of the host organism and hence do not quantify endogenous, unmodified protein. Similarly, the tagging can alter protein levels - in some instances hindering protein expression completely (11). Even so, epitope tagging methods have been of value to the community, yielding high coverage quantitative data sets for the majority of the yeast proteome (11, 12). MS-based methods do not rely on such nonendogenous labels, and can reach genome-wide levels of coverage. Accurate estimation of absolute concentrations i.e. protein copy number per cell, also usually necessitates the use of (one or more) external or internal standards from which to derive absolute abundance (4). Examples include a comprehensive quantification of the Leptospira interrogans proteome that used a 19 protein subset quantified using selected reaction monitoring (SRM)1 to calibrate their label-free data (8, 13). It is worth noting that epitope tagging methods, although also absolute, rely on a very limited set of standards for the quantitative western blots and necessitate incorporation of a suitable immunogenic tag (11). Other recent, innovative approaches exploiting total ion signal and internal scaling to estimate protein cellular abundance (10, 14), avoid the use of internal standards, though they do rely on targeted proteomic data to validate their approach. The use of targeted SRM strategies to derive proteomic calibration standards highlights its advantages in comparison to label-free in terms of accuracy, precision, dynamic range and limit of detection and has gained currency for its reliability and sensitivity (3, 15⇓–17). Indeed, SRM is often referred to as the “gold standard proteomic quantification method,” being particularly well-suited when the proteins to be quantified are known, when appropriate surrogate peptides for protein quantification can be selected a priori, and matched with stable isotope-labeled (SIL) standards (18⇓–20). In combination with SIL peptide standards that can be generated through a variety of means (3, 15), SRM can be used to quantify low copy number proteins, reaching down to ∼50 cpc in yeast (5). However, although SRM methodology has been used extensively for S. cerevisiae protein quantification by us and others (19, 21, 22), it has not been used for large protein cohorts because of the requirement to generate the large numbers of attendant SIL peptide standards; the largest published data set is only for a few tens of proteins. It remains a challenge therefore to robustly quantify an entire eukaryotic proteome in absolute terms by direct means using targeted MS and this is the focus of our present study, the Census Of the Proteome of Yeast (CoPY). We present here direct and absolute quantification of nearly 2000 endogenous proteins from S. cerevisiae grown in steady state in a chemostat culture, using the SRM-based QconCAT approach. Although arguably not quantification of the entire proteome, this represents an accurate and rigorous collection of direct yeast protein quantifications, providing a gold-standard data set of endogenous protein levels for future reference and comparative studies. The highly reproducible SIL-SRM MS data, with robust CVs typically less than 20%, is compared with other extant data sets that were obtained via alternative analytical strategies. We also report a matched high quality transcriptome from the same cells using RNA-seq, which supports additional calculations including a refined estimate of the total protein content in yeast cells, and a simple linear model of translation explaining 70% of the variance between RNA and protein levels in yeast chemostat cultures. These analyses confirm the validity of our data and approach, which we believe represents a state-of-the-art absolute quantification compendium of a significant proportion of a model eukaryotic proteome

Field Guide for the Geology of Central Park and New York City

Teachers guide for geology of Central Park. Supplement to: Jaret, S. J., et. al. (2021). Geology of Central Park, Manhattan, New York City, USA: New geochemical insights. Geological Society of America bulletin. https://doi.org/10.1130/2020.0061(02

Stakeholder perceptions of the benefits and barriers of implementing environmental management systems in the Nigerian construction industry

© 2016 Vilnius Gediminas Technical University (VGTU) Press. This study investigates stakeholder opinions of the major benefits and barriers of Environmental Management Systems (EMS) to the Nigerian construction industry, and the perceived issues to EMS adoption among organisations in the industry. The study highlights the environment as an important stakeholder in the industry because it affects and is affected by construction activities on a regular basis. It identifies the importance of ISO 14001 in ensuring adequate consideration for the environment is maintained on construction projects. The research adopts a quantitative approach by analysing responses from an online survey among construction industry professionals in Nigeria. The questions on the survey were drawn from a similar study carried out in Asia and the results were analysed using the Weighted Average and Standard Deviation statistical approach. Results reveal that the major benefits of EMS to the Nigerian construction industry were improved efficiency in waste management and environmental protection, as well as an overall increase in employee motivation due to better opportunities for training and development. Lack of technological support in organisations and the high cost of implementing EMS were viewed as the major barriers towards its uptake in construction companies. The findings also indicate that a feasible EMS implementation strategy must not ignore the unique nature of the Nigerian construction industry, which comprises mostly small and medium enterprises. The study concludes by recommending the use of a waste management plan based on the Reuse-Reduce-Recycle-Recover model and an employee training plan to ensure continuous improvement in the organisation’s environmental management strategy

A MEMS gravimeter with multi-axis gravitational sensitivity

A single-axis Microelectromechanical system gravimeter has recently been developed at the University of Glasgow. The sensitivity and stability of this device was demonstrated by measuring the Earth tides. The success of this device was enabled in part by its extremely low resonant frequency. This low frequency was achieved with a geometric anti-spring design, fabricated using well-established photolithography and dry etch techniques. Analytical models can be used to calculate the results of these non-linear oscillating systems, but the power of finite element analysis has not been fully utilised to explore the parameter space before now. In this article, the results of previous analytical solutions are replicated using finite element models, before applying the same techniques to optimise the design of the gravimeter. These computer models provide the ability to investigate the effect of the fabrication material of the device: anisotropic <100> crystalline silicon. This is a parameter that is difficult to investigate analytically, but finite element modelling is demonstrated here to provide accurate predictions of real gravimeter behaviour by taking anisotropy into account. The finite element models are then used to demonstrate the design of a three-axis gravimeter enabling the gravity tensor to be measured - a significantly more powerful surveying tool than the original single-axis device

Human platelets generate phospholipid-esterified prostaglandins via cyclooxygenase-1 that are inhibited by low dose aspirin supplementation

Oxidized phospholipids (oxPLs) generated nonenzymatically display pleiotropic biological actions in inflammation. Their generation by cellular cyclooxygenases (COXs) is currently unknown. To determine whether platelets generate prostaglandin (PG)-containing oxPLs, then characterize their structures and mechanisms of formation, we applied precursor scanning-tandem mass spectrometry to lipid extracts of agonist-activated human platelets. Thrombin, collagen, or ionophore activation stimulated generation of families of PGs comprising PGE2 and D2 attached to four phosphatidylethanolamine (PE) phospholipids (16:0p/, 18:1p/, 18:0p/, and 18:0a/). They formed within 2 to 5 min of activation in a calcium, phospholipase C, p38 MAP kinases, MEK1, cPLA2, and src tyrosine kinase-dependent manner (28.1 ± 2.3 pg/2 × 108 platelets). Unlike free PGs, they remained cell associated, suggesting an autocrine mode of action. Their generation was inhibited by in vivo aspirin supplementation (75 mg/day) or in vitro COX-1 blockade. Inhibitors of fatty acyl reesterification blocked generation significantly, while purified COX-1 was unable to directly oxidize PE in vitro. This indicates that they form in platelets via rapid esterification of COX-1 derived PGE2/D2 into PE. In summary, COX-1 in human platelets acutely mediates membrane phospholipid oxidation via formation of PG-esterified PLs in response to pathophysiological agonists