3,626 research outputs found

    Informing Recommended Makerspace Outcomes Through Linguistic Analytics

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    An after-school maker club collected student reflections on makerspace projects in different formats over two years: private written reflections captured in the 3D GameLab gamification platform and video-recorded reflections posted in the more social FlipGrid platform. Club mentors selected these documentation platforms on the basis of their motivational affordances thought to encourage club members to document their work. Transcribed documentation was analyzed using Linguistic Inquiry Word Count (LIWC) software to generate linguistic profiles for comparison. Differences between written and video-recorded documentation suggest: private, written documentation is more likely to capture evidence of cognitive processing and achievement- or risk-oriented drives, but may be more negative in tone; semi-public, video documentation is more likely to capture evidence of social affiliation-oriented drives and may be more positive in tone. Future research should investigate linguistic impacts given merged approaches of reflective writing for social spaces, or reflective writing in social groups

    A Work in Progress: The Lived Experiences of Black Male Undergraduates at One Predominantly White University

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    This exploratory study examines the lived academic and social experiences of current black male undergraduate students, including their perceived barriers and their strategies for persistence and achieving success. Study participants included black male undergraduate students at one predominantly white, four-year, public research university. Data collection methods included two focus group interviews with a purposeful sample of 12 undergraduate, black male students. Students reported that explicit and implicit messages of racial hatred have contributed to a general campus atmosphere of discomfort for black male students. The students described an environment where they continually encounter racial micro aggressions and prejudice. Students reported that persisting at Mid-South has been challenging for them. Nevertheless, they have persisted. Among their lessons learned is that networking is powerful; both inter- and intra-racial networking

    Informing Makerspace Outcomes Through a Linguistic Analysis of Written and Video-Recorded Project Assessments

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    A growing body of research focuses on what outcomes to assess in makerspaces, and appropriate formats for capturing those outcomes (e.g. reflections, surveys, and port-folios). Linguistic analysis as a data mining technique holds promise for revealing different dimensions of learning exhibited by students in makerspaces. In this study, student reflections on makerspace projects were gathered in 2 formats over 2 years: private written assessments captured in the 3D GameLab gamification platform, and semi-public video-recorded assessments posted in the more social FlipGrid platform. Transcripts of student assessments were analyzed using Linguistic Inquiry Word Count (LIWC) to generate 4 summary variables thought to inform makerspace outcomes of interest (i.e. analytical thinking, authenticity, clout, and emotional tone). Comparative findings indicate that written assessments may elicit more analytical thinking about maker projects compared with less analytical conversation in videos, while video assessments may elicit somewhat higher clout scores as evidence of social scaffolding along with a much more positive emotional tone. Recommendations are provided for layering assessment approaches to maximize the potential benefits of each format, including reflective writing for social spaces, in social groups, and about design processes and procedures

    AKT regulates NPM dependent ARF localization and p53mut stability in tumors

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    Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2 activity in response to oncogenic stress, though the precise mechanism has remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers antagonizes MDM2 association with the inhibitory complex, leading to activation of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21 expression and senescence. We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status

    Recruitment, growth and mortality of an Antarctic hexactinellid sponge, Anoxycalyx joubini.

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    Polar ecosystems are sensitive to climate forcing, and we often lack baselines to evaluate changes. Here we report a nearly 50-year study in which a sudden shift in the population dynamics of an ecologically important, structure-forming hexactinellid sponge, Anoxycalyx joubini was observed. This is the largest Antarctic sponge, with individuals growing over two meters tall. In order to investigate life history characteristics of Antarctic marine invertebrates, artificial substrata were deployed at a number of sites in the southern portion of the Ross Sea between 1967 and 1975. Over a 22-year period, no growth or settlement was recorded for A. joubini on these substrata; however, in 2004 and 2010, A. joubini was observed to have settled and grown to large sizes on some but not all artificial substrata. This single settlement and growth event correlates with a region-wide shift in phytoplankton productivity driven by the calving of a massive iceberg. We also report almost complete mortality of large sponges followed over 40 years. Given our warming global climate, similar system-wide changes are expected in the future

    Incidence of acute lower respiratory tract disease hospitalisations, including pneumonia, among adults in Bristol, UK, 2019, estimated using both a prospective and retrospective methodology

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    OBJECTIVES: To determine the disease burden of acute lower respiratory tract disease (aLRTD) and its subsets (pneumonia, lower respiratory tract infection (LRTI) and heart failure) in hospitalised adults in Bristol, UK. SETTING: Single-centre, secondary care hospital, Bristol, UK. DESIGN: We estimated aLRTD hospitalisations incidence in adults (≥18 years) in Bristol, UK, using two approaches. First, retrospective International Classification of Diseases 10th revision (ICD-10) code analysis (first five positions/hospitalisation) identified aLRTD events over a 12-month period (March 2018 to February 2019). Second, during a 21-day prospective review (19 August 2019 to 9 September 2019), aLRTD admissions were identified, categorised by diagnosis and subsequently annualised. Hospital catchment denominators were calculated using linked general practice and hospitalisation data, with each practice’s denominator contribution calculated based on practice population and per cent of the practices’ hospitalisations admitted to the study hospital. PARTICIPANTS: Prospective review: 1322 adults screened; 410 identified with aLRTD. Retrospective review: 7727 adult admissions. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence of aLRTD and its subsets in the adult population of Southmead Hospital, Bristol UK. RESULTS: Based on ICD-10 code analysis, annual incidences per 100 000 population were: aLRTD, 1901; pneumonia, 591; LRTI, 739; heart failure, 402. aLRTD incidence was highest among those ≥65 years: 65–74 (3684 per 100 000 adults), 75–84 (6962 per 100 000 adults) and ≥85 (11 430 per 100 000 adults). During the prospective review, 410/1322 (31%) hospitalised adults had aLRTD signs/symptoms and annualised incidences closely replicated retrospective analysis results. CONCLUSIONS: The aLRTD disease burden was high, increasing sharply with age. The aLRTD incidence is probably higher than estimated previously due to criteria specifying respiratory-specific symptoms or radiological change, usage of only the first diagnosis code and mismatch between case count sources and population denominators. This may have significant consequences for healthcare planning, including usage of current and future vaccinations against respiratory infection

    SUMO targeting of a stress-tolerant Ulp1 SUMO protease

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    SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1. We find that the catalytic UD domains of both ScUlp1 and KmUlp1 show a high degree of sequence conservation, complement a ulp1 Delta mutant in vivo, and process a SUMO precursor in vitro. Next, to compare the SUMO-trapping features of both SUMO proteases we produced catalytically inactive recombinant fragments of the UD domains of ScUlp1 and KmUlp1, termed ScUTAG and KmUTAG respectively. Both ScUTAG and KmUTAG were able to efficiently bind a variety of purified SUMO isoforms and bound immobilized SUMO1 with nanomolar affinity. However, KmUTAG showed a greatly enhanced ability to bind SUMO and SUMO-modified proteins in the presence of oxidative, temperature and other stressors that induce protein misfolding. We also investigated whether a SUMO-interacting motif (SIM) in the UD domain of KmULP1 that is not conserved in ScUlp1 may contribute to the SUMO-binding properties of KmUTAG. In summary, our data reveal important details about how SUMO proteases target and bind their sumoylated substrates, especially under stress conditions. We also show that the robust pan-SUMO binding features of KmUTAG can be exploited to detect and study SUMO-modified proteins in cell culture systems

    Portable prehospital methods to treat near-hypothermic shivering cold casualties

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    Objectives To compare the effectiveness of a single-layered polyethylene survival bag (P), a single-layered polyethylene survival bag with a hot drink (P+HD), a multi-layered metalized plastic sheeting survival bag (MPS: Blizzard Survival), and a multi-layered MPS survival bag with four large chemical-heat pads (MPS+HP: Blizzard Heat) to treat cold casualties. Methods Portable cold casualty treatment methods were compared by examining core and skin temperature, metabolic heat production and thermal comfort during a 3-h, 0°C cold-air exposure in seven shivering, near-hypothermic men (35.4°C). The hot drink (70°C, ~400ml, ~28kJ) was consumed at 0, 1 and 2 h during the cold-air exposure. Results During the cold-air exposure, core-rewarming and thermal comfort were similar on all trials (P = 0.45 and P = 0.36, respectively). However, skin temperature was higher (10-13%, P 2.7) and metabolic heat production lower (15-39%, P 0.9) on MPS and MPS+HP than P and P+HD. The addition of heat pads further lowered metabolic heat production by 15% (MPS+HP vs. MPS, P = 0.05, large effect size d = 0.9). The addition of the hot drink to polyethylene survival bag did not increase skin temperature or lower metabolic heat production. Conclusions Near-hypothermic cold casualties are rewarmed with less peripheral cold stress and shivering thermogenesis using a multi-layered MPS survival bag compared with a polyethylene survival bag. Prehospital rewarming is further aided by large chemical heat pads but not by hot drinks
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