646 research outputs found
Measurement of the spatial dependence of temperature and gas and soot concentrations within large open hydrocarbon fuel fires
A series of large-scale JP-4 fuel pool fire tests was conducted to refine existing mathematical models of large fires. Seven tests were conducted to make chemical concentration and temperature measurements in 7.5 and 15 meter-diameter pool fires. Measurements were made at heights of 0.7, 1.4, 2.9, 5.7, 11.4, and 21.3 meters above the fires. Temperatures were measured at up to 50 locations each second during the fires. Chemistry samples were taken at up to 23 locations within the fires and analyzed for combustion chemistry and soot concentration. Temperature and combustion chemistry profiles obtained during two 7.5 meter-diameter and two 15 meter-diameter fires are included
A self-determination perspective of strengths use at work: Examining its determinant and performance implications
We investigate the role of strengths use in the workplace by drawing on self-determination theory (SDT) to propose that strengths use at work can yield performance benefits in terms of task performance and discretionary helping, and that the social context, in the form of leader autonomy support, can promote employees’ strengths use. Further, consistent with an interactional psychology perspective, we contend that the relationship between autonomy support and strengths use will be stronger among individuals with strong independent self-construal. We tested the model using matched data from 194 employees and their supervisors and found evidence for the relevance of strengths use at work, even after accounting for the role of intrinsic motivation. In addition to providing practical implications on developing employee strengths use and how to do so, this study advances theory and research on workplace strength use, SDT, and positive organizational behavior
Microplastics and synthetic particles ingested by deep-sea amphipods in six of the deepest marine ecosystems on Earth
Funding Funding for the laboratory work and analysis was from Newcastle University internal support. This work was supported by the 2007–2010 HADEEP project, funded by the Nippon Foundation (2009765188) and the Natural Environmental Research Council (NE/E007171/1). The 2011–2013 Kermadec Trench sampling was supported by the TOTAL Foundation (France) through the projects ‘Multi-disciplinary investigations of the deepest scavengers on Earth’ (2010–2012) and ‘Trench Connection’ (2013–2015). The Mariana samples were derived from the ‘FISH2017’ expedition (RV Shinyo-Maru SY1615) supported by the Tokyo University for Marine Science and Technology. Acknowledgements We thank the captain, crew and company of the research expeditions who assisted in the collection of the amphipods between 2008 and 2017, namely the Japanese Hakuho-Maru, Tansei Maru and Shinyo-Maru, the German Sonne and the RV Kaharoa in New Zealand. The assistance of David Whitaker and Peter McParlin from The School of Marine Science and Technology at Newcastle University are much appreciated. We are extremely grateful to Bob Keighley and Dan Parnaby at Shimadzu UK Limited for facilitating the FTIR analysis and access to their material database. We also thank Heather Stewart from the British Geological Survey for calculating the distances between trenches.Peer reviewedPublisher PD
The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1
The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro
Donor milk intake and infant growth in a South African neonatal unit: a cohort study
Background
Implications of donor milk feedings on infant growth in resource limited settings remain uncertain. This knowledge gap includes the impact of donor milk availability on infant intake of mother’s own milk. Therefore, this investigation aimed to measure intake and growth in infants receiving donor milk when born to women from resource limited backgrounds with high rates of human immunodeficiency virus (HIV).
Methods
A retrospective cohort study enrolled eligible infants admitted to a South African combined neonatal intensive and secondary high care unit, within a one year admission period during 2015, with signed consent for donor milk feedings. A certified milk bank provided donor milk. Daily nutritional intake during the first month was recorded. Details included proportional intake of donor milk, mother’s own milk and infant formula. The primary outcome of infant growth velocity from day back to birth weight to discharge was calculated when length of stay was ≥14 days. Analyses primarily used T-tests; mixed effects models compared weekly calorie intake.
Results
One hundred five infants with donor milk consent were born at 30.9 ± 3.6 weeks of gestation, weighing 1389 ± 708 g. Forty percent of mothers had HIV. Infant growth velocity did not differ based on percent of feedings as donor milk (≥ 50%: 11.8 ± 4.9 g/kg/d; < 50%: 13.5 ± 5.3 g/kg/d; p = 0.3). Percent of feedings from donor milk was similar based on maternal HIV status (positive: 31 ± 25%; negative: 36 ± 29%; p = 0.4), as was percent of feedings as mother’s milk (positive: 53 ± 35%; negative: 58 ± 30%; p = 0.4). Calorie intake increased markedly during the first two weeks and then plateaued (p < 0.0001).
Conclusions
Donor milk feedings in higher proportions did not further impair growth of infants managed in a South African combined neonatal intensive and secondary high care unit with growth rates already below reference ranges. The provision of donor milk contributed to feedings being composed of primarily human milk during the first month. Increasing early calorie intake may improve infant growth in this center
Characterization of glycan substrates accumulating in GM1 Gangliosidosis
Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the GLB1 gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase. For example, a number of N-linked glycan structures that have galactose at their non-reducing end have been shown to accumulate in GM1 gangliosidosis patient tissues and biological fluids. Objective: In this study, we attempt to fully characterize the broad array of GLB1 substrates that require GLB1 for their lysosomal turnover. Results: Using tandem mass spectrometry and glycan reductive isotope labeling with data-dependent mass spectrometry, we have confirmed the accumulation of glycolipids (GM1 and GA1) and N-linked glycans with terminal beta-linked galactose. We have also discovered a novel set of core 1 and 2 O-linked glycan metabolites, many of which are part of structurally-related isobaric series that accumulate in disease. In the brain of GLB1 null mice, the levels of these glycan metabolites increased along with those of both GM1 and GA1 as a function of age. In addition to brain tissue, we found elevated levels of both N-linked and O-linked glycan metabolites in a number of peripheral tissues and in urine. Both brain and urine samples from human GM1 gangliosidosis patients exhibited large increases in steady state levels for the same glycan metabolites, demonstrating their correlation with this disease in humans as well. Conclusions: Our studies illustrate that GLB1 deficiency is not purely a ganglioside accumulation disorder, but instead a broad oligosaccharidosis that include representatives of many β-linked galactose containing glycans and glycoconjugates including glycolipids, N-linked glycans, and various O-linked glycans. Accounting for all β-galactosidase substrates that accumulate when this enzyme is deficient increases our understanding of this severe disorder by identifying metabolites that may drive certain aspects of the disease and may also serve as informative disease biomarkers to fully evaluate the efficacy of future therapies
Seroprevalence of SARS-CoV-2 among Blood Donors and Changes after Introduction of Public Health and Social Measures, London, UK
We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17–69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15–16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays
HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer
Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC
‘More willing to carry on in the face of adversity’: how beginner teachers facing challenging circumstances experience positive psychology coaching. An interpretative phenomenological analysis
Positive psychology coaching (PPC) is defined as activating positive psychology (PP) in an applied and systematic way through coaching (Passmore, J., & Oades, P. (2014). Positive psychology coaching – A model for coaching practice. The Coaching Psychologist, 10(2), 68–70). Currently studies looking at how PPC is experienced by coachees are limited. While there has been some early success cited in using a PPC approach in professional development in education with adults (Zwart, R. C., Korthagen, F. A. J., & Attema-Noordewier, S. (2014). A strength-based approach to teacher professional development. Professional Development in Education, 41(3), 579–596. https://doi.org/10.1080/19415257.2014.919341) it is not yet known how teachers experience PPC. The purpose of this paper was to gain an understanding of how PPC is experienced by beginner teachers undergoing challenging circumstances. This initial explorative study adopted a qualitative approach using Interpretative Phenomenological Analysis (IPA) (Smith, J., Flowers, P., & Larkin, M. (2009). Interpretative phenomenological analysis: Theory, method and research. Sage). Four superordinate themes emerged: ‘perfectly normal to feel this way’; making sense and ‘joining the dots’; increased positive emotion; and, time to think ‘in an easy-going environment’. Further studies of the application of PPC in educational settings are needed
- …