441 research outputs found

    Inventory and monitoring of seabirds in National Park of American Samoa

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    Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.This first island-wide inventory and preliminary monitoring of American Samoa seabird populations has produced several significant results. The beginning of a seabird colony catalog has been established in a digital format. The protocol for surveying seabirds around Tutuila Island by boat is described, and future efforts can be compared to baseline results reported here. A detailed survey of the National Park lands around Tutuila is mapped and photographed and seabird distributions found in the 2000 round-island survey and 2003 partial-island survey are discussed. Our results support anecdotal evidence that the inaccessible north shore of Tutuila supports the majority of that island’s resident seabirds. Greater than 90% of Red-footed Boobies and Great Frigatebird observations during the Tutuila round-island survey were made in NPSA areas. The north shore areas are important for coastal cliff nesters such as Brown, Black Noddies and Blue Noddies, a species of international significance. Bridled Terns are extending their pan tropical range to include Tutuila, including Park areas. White Terns and White-tailed Tropicbirds are more evenly distributed across forests in Tutuila within as well as outside NPSA areas.National Park Service Contract No. 8036 2 900

    Use of top-down and bottom-up fourier transform ion cyclotron resonance mass spectrometry for mapping calmodulin sites modified by platinum anticancer drugs

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    Calmodulin (CaM) is a highly conserved, ubiquitous, calcium-binding protein; it binds to and regulates many different protein targets, thereby functioning as a calcium sensor and signal transducer. CaM contains 9 methionine (Met), 1 histidine (His), 17 aspartic acid (Asp), and 23 glutamine acid (Glu) residues, all of which can potentially react with platinum compounds; thus, one-third of the CaM sequence is a possible binding target of platinum anticancer drugs, which represents a major challenge for identification of specific platinum modification sites. Here, top-down electron capture dissociation (ECD) was used to elucidate the transition metal–platinum(II) modification sites. By using a combination of top-down and bottom-up mass spectrometric (MS) approaches, 10 specific binding sites for mononuclear complexes, cisplatin and [Pt(dien)Cl]Cl, and dinuclear complex [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] on CaM were identified. High resolution MS of cisplatin-modified CaM revealed that cisplatin mainly targets Met residues in solution at low molar ratios of cisplatin–CaM (2:1), by cross-linking Met residues. At a high molar ratio of cisplatin:CaM (8:1), up to 10 platinum(II) bind to Met, Asp, and Glu residues. [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] forms mononuclear adducts with CaM. The alkanediamine linker between the two platinum centers dissociates due to a trans-labilization effect. [Pt(dien)Cl]Cl forms {Pt(dien)}2+ adducts with CaM, and the preferential binding sites were identified as Met51, Met71, Met72, His107, Met109, Met124, Met144, Met145, Glu45 or Glu47, and Asp122 or Glu123. The binding of these complexes to CaM, particularly when binding involves loss of all four original ligands, is largely irreversible which could result in their failure to reach the target DNA or be responsible for unwanted side-effects during chemotherapy. Additionally, the cross-linking of cisplatin to CaM might lead to the loss of the biological function of CaM or CaM–Ca2+ due to limiting the flexibility of the CaM or CaM–Ca2+ complex to recognize target proteins or blocking the binding region of target proteins to CaM

    2D FT-ICR MS of Calmodulin : a top-down and bottom-up approach

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    Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows data-independent fragmentation of all ions in a sample and correlation of fragment ions to their precursors through the modulation of precursor ion cyclotron radii prior to fragmentation. Previous results show that implementation of 2D FT-ICR MS with infrared multi-photon dissociation (IRMPD) and electron capture dissociation (ECD) has turned this method into a useful analytical tool. In this work, IRMPD tandem mass spectrometry of calmodulin (CaM) has been performed both in one-dimensional and two-dimensional FT-ICR MS using a top-down and bottom-up approach. 2D IRMPD FT-ICR MS is used to achieve extensive inter-residue bond cleavage and assignment for CaM, using its unique features for fragment identification in a less time- and sample-consuming experiment than doing the same thing using sequential MS/MS experiments

    A stochastic evolutionary model for capturing human dynamics

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    The recent interest in human dynamics has led researchers to investigate the stochastic processes that explain human behaviour in various contexts. Here we propose a generative model to capture the dynamics of survival analysis, traditionally employed in clinical trials and reliability analysis in engineering. We derive a general solution for the model in the form of a product, and then a continuous approximation to the solution via the renewal equation describing age-structured population dynamics. This enables us to model a wide range of survival distributions, according to the choice of the mortality distribution. We provide empirical evidence for the validity of the model from a longitudinal data set of popular search engine queries over 114 months, showing that the survival function of these queries is closely matched by the solution for our model with power-law mortality

    Assessing behavioural changes in ALS: cross-validation of ALS-specific measures

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    Objective: The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Methods: 60 ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity and overall accuracy of the BBI, when compared to the ALS-FTD-Q, were obtained. Results: The mean score of the whole sample on the BBI was 11.45±13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6±14.64, 9.62±11.38; p<.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed (r=.807, p<.0001), and no significant correlations between the BBI and other clinical/demographic characteristics, indicating good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Discussion: Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition

    Sampling molecular conformations and dynamics in a multiuser virtual reality framework

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    Copyright © 2018 The Authors, some rights reserved. We describe a framework for interactive molecular dynamics in a multiuser virtual reality (VR) environment, combining rigorous cloud-mounted atomistic physics simulations with commodity VR hardware, which we have made accessible to readers (see isci.itch.io/nsb-imd). It allows users to visualize and sample, with atomic-level precision, the structures and dynamics of complex molecular structures “on the fly” and to interact with other users in the same virtual environment. A series of controlled studies, in which participants were tasked with a range of molecular manipulation goals (threading methane through a nanotube, changing helical screw sense, and tying a protein knot), quantitatively demonstrate that users within the interactive VR environment can complete sophisticated molecular modeling tasks more quickly than they can using conventional interfaces, especially for molecular pathways and structural transitions whose conformational choreographies are intrinsically three-dimensional. This framework should accelerate progress in nanoscale molecular engineering areas including conformational mapping, drug development, synthetic biology, and catalyst design. More broadly, our findings highlight the potential of VR in scientific domains where three-dimensional dynamics matter, spanning research and education

    The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase

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    RbpA is a small non-DNA-binding transcription factor that associates with RNA polymerase holoenzyme and stimulates transcription in actinobacteria, including Streptomyces coelicolor and Mycobacterium tuberculosis. RbpA seems to show specificity for the vegetative form of RNA polymerase as opposed to alternative forms of the enzyme. Here, we explain the basis of this specificity by showing that RbpA binds directly to the principal σ subunit in these organisms, but not to more diverged alternative σ factors. Nuclear magnetic resonance spectroscopy revealed that, although differing in their requirement for structural zinc, the RbpA orthologues from S. coelicolor and M. tuberculosis share a common structural core domain, with extensive, apparently disordered, N- and C-terminal regions. The RbpA-σ interaction is mediated by the C-terminal region of RbpA and σ domain 2, and S. coelicolor RbpA mutants that are defective in binding σ are unable to stimulate transcription in vitro and are inactive in vivo. Given that RbpA is essential in M. tuberculosis and critical for growth in S. coelicolor, these data support a model in which RbpA plays a key role in the σ cycle in actinobacteria

    A pilot single-blind multicentre randomized controlled trial to evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on the arm function of children with spastic cerebral palsy

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    OBJECTIVE: To evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on arm function of children with spastic cerebral palsy. DESIGN: A single-blind randomized controlled trial design. Power calculations indicated that 58 children would be required to demonstrate a clinically important difference. SETTING: Intervention was home-based; recruitment took place in regional spasticity clinics. PARTICIPANTS: A total of 15 children with cerebral palsy aged five to 12 years were recruited; eight to the device group. INTERVENTIONS: Both study groups received 'usual follow-up treatment' following spasticity treatment with botulinum toxin; the intervention group also received a rehabilitation gaming device. MAIN MEASURES: ABILHAND-kids and Canadian Occupational Performance Measure were performed by blinded assessors at baseline, six and 12 weeks. RESULTS: An analysis of covariance showed no group differences in mean ABILHAND-kids scores between time points. A non-parametric analysis of variance on Canadian Occupational Performance Measure scores showed a statistically significant improvement across time points (χ(2) (2,15) = 6.778, p = 0.031), but this improvement did not reach minimal clinically important difference. Mean daily device use was seven minutes. Recruitment did not reach target owing to unanticipated staff shortages in clinical services. Feedback from children and their families indicated that the games were not sufficiently engaging to promote sufficient use that was likely to result in functional benefits. CONCLUSION: This study suggests that computer-assisted arm rehabilitation gaming does not benefit arm function, but a Type II error cannot be ruled out

    The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study

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    Objectives To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A1C) achieved during therapy

    Relationship Between Galectin-3 Levels and Mineralocorticoid Receptor Antagonist Use in Heart Failure: Analysis From HF-ACTION

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    Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRA) modulate cardiac fibrosis in HF patients, and have been shown to improve long term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in the HF-ACTION study
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