2,072 research outputs found
The Effect of Teacher Professional Development on Implementing Engineering in Elementary Schools
Increased attention on the implementation of engineering education into elementary school classrooms aims to start preparing students early for potential engineering careers. In order to efficiently and effectively add engineering concepts to the curriculum, appropriate development and facilitation of engineering design challenges are required. Therefore, professional development programs are necessary to educate teachers about engineering and how to adequately teach it. This paper explores the effects of an engineering professional development program for practicing teachers. The program included training elementary teachers about how to implement units from Engineering is Elementary (EiE) by the Science Museum of Boston into their classes. Semi-structured focus group interviews were conducted, both prior to and following the implementation of the EiE units over an academic year. The interviews were transcribed and coded using open-coding, resulting in the development of a codebook. The codes were further analyzed until salient themes emerged that can be used to improve the training and better understand how teachers integrate engineering into their classrooms. The results show that many teachers need training to learn about engineering practices, as well as pedagogical guidance on how to incorporate engineering concepts into their lessons. However, not surprisingly, limited resources such as time, money, materials, and knowledge restrict efficient curricula implementation. We believe these findings reemphasize the need for science, technology, engineering, and mathematics professional development programs to educate K–12 teachers about engineering and will be useful to others interested in integrating engineering into K–12 curricula
The effect of duration of stress relief heat treatments on microstructural evolution and mechanical properties in grade 91 and 92 power plant steels
A detailed examination has been carried out of the microstructural evolution and mechanical properties of samples of T91 and T92 steels which have been subjected to both a 'normal' pre-service heat treatment and an extended stress relief heat treatment at 765°C for up to 16 hours. The samples have subsequently been creep tested to failure at different stresses ranging from 66 to 112 MPa. In each case, a reduction in rupture time was observed of 20-30% in the samples which had experienced the additional stress relief heat treatment compared to those which had not. It is shown that these data, when compared with the mean values expected from European Creep Collaborative Committee (ECCC) Datasheets, result in a reduction in stress of approximately 10% of the mean value predicted from the ECCC data, which is within the allowable scatter band. In order to investigate the reasons behind this reduction in life, extensive analyses have been carried out using a range of advanced electron microscopy techniques. In particular, imaging using both ion and electron beams in combination with image analysis methods have been used to provide a rapid and accurate technique for quantifying the particle size distributions of the M C carbides and also the Laves phase, which was found only in the T92 samples. Electron backscatter diffraction techniques have also been used to quantify the changes occurring in the martensitic matrix with respect to the nature and length of the grain boundaries and the grain size distribution. The effect of the additional heat treatment on microstructural evolution is to coarsen the secondary phase particle distribution and enhance matrix recovery before the steel enters service, to the detriment of the hardness and creep fracture life. It is also demonstrated that there is a significant effect of applied stress on the particle size distributions and matrix recovery during creep testing. Copyright © 2011 Electric Power Research Institute Distributed by ASM International®. All rights reserved
Elevated Integrin α6β4 Expression is Associated with Venous Invasion and Decreased Overall Survival in Non-Small Cell Lung Cancer
Lung cancer carries a poor prognosis and is the most common cause of cancer-related death worldwide. The integrin α6β4, a laminin receptor, promotes carcinoma progression in part by cooperating with various growth factor receptors to facilitate invasion and metastasis. In carcinoma cells with mutant TP53, the integrin α6β4 promotes cell survival. TP53 mutations and integrin α6β4 overexpression co-occur in many aggressive malignancies. Because of the high frequency of TP53 mutations in lung squamous cell carcinoma (SCC), we sought to investigate the association of integrin β4 expression with clinicopathologic features and survival in non–small cell lung cancer (NSCLC). We constructed a lung cancer tissue microarray and stained sections for integrin β4 subunit expression using immunohistochemistry. We found that integrin β4 expression is elevated in SCC compared with adenocarcinoma (P \u3c .0001), which was confirmed in external gene expression data sets (P \u3c .0001). We also determined that integrin β4 overexpression associates with the presence of venous invasion (P = .0048) and with reduced overall patient survival (hazard ratio, 1.46; 95% confidence interval, 1.01-2.09; P = .0422). Elevated integrin β4 expression was also shown to associate with reduced overall survival in lung cancer gene expression data sets (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P \u3c .0001). Using cBioPortal, we generated a network map demonstrating the 50 most highly altered genes neighboring ITGB4 in SCC, which included laminins, collagens, CD151, genes in the EGFR and PI3K pathways, and other known signaling partners. In conclusion, we demonstrate that integrin β4 is overexpressed in NSCLC where it is an adverse prognostic marker
S100A4 Drives Non-Small Cell Lung Cancer Invasion, Associates with Poor Prognosis, and is Effectively Targeted by the FDA-Approved Anti-Helminthic Agent Niclosamide
S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular invasion and decreased overall survival. In addition, depletion of S100A4 by shRNA inhibits NF-κB activity and decreases TNFα-induced MMP9 expression. Furthermore, inhibition of the NF-κB/MMP9 axis decreases lung carcinoma invasive potential. Niclosamide, a reported inhibitor of S100A4, blocks expression and function of S100A4 with a reduction in proliferation, invasion and NF-κB-mediated MMP9 expression. Collectively, this study highlights the importance of the S100A4/NF-κB/MMP9 axis in lung cancer invasion and provides a rationale for targeting S100A4 to combat lung cancer
Dynamics of Trophoblast Differentiation in Peri-Implantation–Stage Human Embryos
Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, while mature STB was at its zenith at D10. A form of MTB with a mixed MTB/CTB phenotype arose around D10. By D12, STB generation was in decline, CTB had entered a new phase of proliferation, and mature MTB cells had begun to move from the main body of the conceptus. Notably, the MTB transcriptome at D12 indicated enrichment of transcripts associated with IFN signaling, migration, and invasion and upregulation of HLA-C, HLA-E, and HLA-G. The STB, which is distinct from the STB of later villous STB, had a phenotype consistent with intense protein export and placental hormone production, as well as migration and invasion. The studies show that TB associated with human embryos is in rapid developmental flux during periimplantation period when it must invade, signal robustly to the mother to ensure that the pregnancy continues, and make first contact with the maternal immune system
The thermal emission of the exoplanets WASP-1b and WASP-2b
We present a comparative study of the thermal emission of the transiting
exoplanets WASP-1b and WASP-2b using the Spitzer Space Telescope. The two
planets have very similar masses but suffer different levels of irradiation and
are predicted to fall either side of a sharp transition between planets with
and without hot stratospheres. WASP-1b is one of the most highly irradiated
planets studied to date. We measure planet/star contrast ratios in all four of
the IRAC bands for both planets (3.6-8.0um), and our results indicate the
presence of a strong temperature inversion in the atmosphere of WASP-1b,
particularly apparent at 8um, and no inversion in WASP-2b. In both cases the
measured eclipse depths favor models in which incident energy is not
redistributed efficiently from the day side to the night side of the planet. We
fit the Spitzer light curves simultaneously with the best available radial
velocity curves and transit photometry in order to provide updated measurements
of system parameters. We do not find significant eccentricity in the orbit of
either planet, suggesting that the inflated radius of WASP-1b is unlikely to be
the result of tidal heating. Finally, by plotting ratios of secondary eclipse
depths at 8um and 4.5um against irradiation for all available planets, we find
evidence for a sharp transition in the emission spectra of hot Jupiters at an
irradiation level of 2 x 10^9 erg/s/cm^2. We suggest this transition may be due
to the presence of TiO in the upper atmospheres of the most strongly irradiated
hot Jupiters.Comment: 10 pages, submitted to Ap
Qatar-2: A K dwarf orbited by a transiting hot Jupiter and a more massive companion in an outer orbit
We report the discovery and initial characterization of Qatar-2b, a hot
Jupiter transiting a V = 13.3 mag K dwarf in a circular orbit with a short
period, P_ b = 1.34 days. The mass and radius of Qatar-2b are M_p = 2.49 M_j
and R_p = 1.14 R_j, respectively. Radial-velocity monitoring of Qatar-2 over a
span of 153 days revealed the presence of a second companion in an outer orbit.
The Systemic Console yielded plausible orbits for the outer companion, with
periods on the order of a year and a companion mass of at least several M_j.
Thus Qatar-2 joins the short but growing list of systems with a transiting hot
Jupiter and an outer companion with a much longer period. This system
architecture is in sharp contrast to that found by Kepler for multi-transiting
systems, which are dominated by objects smaller than Neptune, usually with
tightly spaced orbits that must be nearly coplanar
Domainâ specific impairment in cognitive control among remitted youth with a history of major depression
AimImpairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, setâ shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD.MethodsYouth aged 18â 23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and setâ shifting, processing speed with interference resolution, and cognitive control.ResultsrMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and setâ shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants.ConclusionMDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138407/1/eip12253_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138407/2/eip12253.pd
Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study
Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients
Comparison of plasma and CSF biomarkers in predicting cognitive decline
OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer\u27s disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.
METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over a maximum of 6 years as predicted by the fluid biomarkers.
RESULTS: Analyses included 371 cognitively normal participants, aged 72.7 ± 5.2 years (mean ± standard deviation) with an average length of follow-up of 3.9 ± 1.6 years. Standardized concentrations of biomarkers were associated with annualized cognitive change: plasma Aβ42/Aβ40, 0.014 standard deviations (95% confidence intervals 0.002 to 0.026); CSF Aβ42/Aβ40, 0.020 (0.008 to 0.032); plasma Nfl, -0.018 (-0.030 to -0.005); and CSF NfL, -0.024 (-0.036 to -0.012). Power analyses estimated that 266 individuals in each treatment arm would be needed to detect a 50% slowing of decline if identified by abnormal plasma measures versus 229 for CSF measures.
INTERPRETATION: Both plasma and CSF measures of Aβ42/Aβ40 and NfL predicted cognitive decline. A clinical trial that enrolled individuals based on abnormal plasma Aβ42/Aβ40 and NfL levels would require only a marginally larger cohort than if CSF measures were used
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