103 research outputs found

    Students\u27 Perspectives on Their High School Experience

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    This study explored what it is like to be a high school student today. Our purpose was to describe the extent to which the schools in the metropolitan area are meeting the needs of their diverse body of students. Knowing whether disengagement and alienation are widespread is important if we are to determine whether systemic change is needed or a more localized approach that targets particular students. We looked at those internal (school) factors related to instructional time; non-instructional time in school, extracurricular activities and school climate that help or hinder students’ perceived levels of engagement. Obtaining a snapshot of high school students’ opinions about instruction, teachers, friends, and activities can be telling about students’ levels of belonging and engagement in high school. In order to obtain rich, informative data from students, qualitative research techniques were chosen. The purposes of this project were threefold: 1) to review pertinent literature on high school students’ perspectives of the school experience, 2) to present a study of the perspectives of high school students, and 3) to outline implications of the study for school personnel

    Searching for Perfect Fluids: Quantum Viscosity in a Universal Fermi Gas

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    We measure the shear viscosity in a two-component Fermi gas of atoms, tuned to a broad s-wave collisional (Feshbach) resonance. At resonance, the atoms strongly interact and exhibit universal behavior, where the equilibrium thermodynamic properties and the transport coefficients are universal functions of the density nn and temperature TT. We present a new calibration of the temperature as a function of global energy, which is directly measured from the cloud profiles. Using the calibration, the trap-averaged shear viscosity in units of ℏ n\hbar\,n is determined as a function of the reduced temperature at the trap center, from nearly the ground state to the unitary two-body regime. Low temperature data is obtained from the damping rate of the radial breathing mode, while high temperature data is obtained from hydrodynamic expansion measurements. We also show that the best fit to the high temperature expansion data is obtained for a vanishing bulk viscosity. The measured trap-averaged entropy per particle and shear viscosity are used to estimate the ratio of the shear viscosity to the entropy density, which is compared that conjectured for a perfect fluid.Comment: 20 pages, 10 figure

    Deletion of PPAR-Îł in immune cells enhances susceptibility to antiglomerular basement membrane disease

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    Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-γ gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM) mouse model. PPAR-γ+/+ and PPAR-γ−/− mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-γ+/+ and PPAR-γ−/− mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-γ−/− mice were significantly more severe compared with the PPAR-γ+/+ animals. We observed that the PPAR-γ−/− mice had decreased CD4+CD25+ regulatory T cells and an increased CD8+:CD4+ ratio as compared with the PPAR-γ+/+ mice, suggesting that PPAR-γ has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-γ−/− mice at two weeks as compared with the PPAR-γ+/+ animals. Taken together, these studies show that the lack of PPAR-γ expression enhances inflammatory renal disease in the anti-GBM antibody-induced glomerulonephritis mouse model and suggests targeting PPAR-γ may have therapeutic efficacy

    Architecture of the RNA polymerase II–TFIIF complex revealed by cross-linking and mass spectrometry

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    Higher-order multi-protein complexes such as RNA polymerase II (Pol II) complexes with transcription initiation factors are often not amenable to X-ray structure determination. Here, we show that protein cross-linking coupled to mass spectrometry (MS) has now sufficiently advanced as a tool to extend the Pol II structure to a 15-subunit, 670 kDa complex of Pol II with the initiation factor TFIIF at peptide resolution. The N-terminal regions of TFIIF subunits Tfg1 and Tfg2 form a dimerization domain that binds the Pol II lobe on the Rpb2 side of the active centre cleft near downstream DNA. The C-terminal winged helix (WH) domains of Tfg1 and Tfg2 are mobile, but the Tfg2 WH domain can reside at the Pol II protrusion near the predicted path of upstream DNA in the initiation complex. The linkers between the dimerization domain and the WH domains in Tfg1 and Tfg2 are located to the jaws and protrusion, respectively. The results suggest how TFIIF suppresses non-specific DNA binding and how it helps to recruit promoter DNA and to set the transcription start site. This work establishes cross-linking/MS as an integrated structure analysis tool for large multi-protein complexes

    Coumarin anticoagulants and co-trimoxazole: avoid the combination rather than manage the interaction

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    OBJECTIVE: The objective of our study was to examine the management of the interaction between acenocoumarol or phenprocoumon and several antibiotics by anticoagulation clinics and to compare the consequences of this interaction on users of co-trimoxazole with those for users of other antibiotics. METHODS: A follow-up study was conducted at four anticoagulation clinics in The Netherlands. Data on measurements of the International Normalised Ratio (INR), application of a preventive dose reduction (PDR) of the coumarin anticoagulant, fever and time within or outside the therapeutic INR range were collected. RESULTS: The study cohort consisted of 326 subjects. A PDR was given more often to users of co-trimoxazole PDR than to users of other antibiotics. The PDR in co-trimoxazole users resulted in a significantly reduced risk of both moderate overanticoagulation (INR >4.5) and severe overanticoagulation (INR >6.0) compared with no PDR, with odds ratios (ORs) of 0.06 [95% confidence interval (CI): 0.01-0.51] and 0.09 (95% CI: 0.01-0.92), respectively. In co-trimoxazole users without PDR, the risk of overanticoagulation was significantly increased compared with users of other antibiotics. All co-trimoxazole users spent significantly more time under the therapeutic INR range during the first 6 weeks after the course than users of other antibiotics. CONCLUSION: PDR is effective in preventing overanticoagulation in co-trimoxazole users, but results in a significantly prolonged period of underanticoagulation after the course. Avoidance of concomitant use of co-trimoxazole with acenocoumarol or phenprocoumon seems to be a safer approach than management of the interaction between these drugs

    The Pioneer Anomaly

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    Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

    Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair

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    Background: The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription. Methodology/Principal Findings: Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol b-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process. Conclusion/Significance: Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER

    The effect of skewness and kurtosis on the robustness of linear mixed models

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    This study analyzes the robustness of the linear mixed model (LMM) with the Kenward–Roger (KR) procedure to violations of normality and sphericity when used in split-plot designs with small sample sizes. Specifically, it explores the independent effect of skewness and kurtosis on KR robustness for the values of skewness and kurtosis coefficients that are most frequently found in psychological and educational research data. To this end, a Monte Carlo simulation study was designed, considering a split-plot design with three levels of the between-subjects grouping factor and four levels of the within-subjects factor. Robustness is assessed in terms of the probability of type I error. The results showed that (1) the robustness of the KR procedure does not differ as a function of the violation or satisfaction of the sphericity assumption when small samples are used; (2) the LMM with KR can be a good option for analyzing total sample sizes of 45 or larger when their distributions are normal, slightly or moderately skewed, and with different degrees of kurtosis violation; (3) the effect of skewness on the robustness of the LMM with KR is greater than the corresponding effect of kurtosis for common values; and (4) when data are not normal and the total sample size is 30, the procedure is not robust. Alternative analyses should be performed when the total sample size is 30

    Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription

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    Kinases and phosphatases regulate messenger RNA synthesis through post-translational modification of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (ref. 1). In yeast, the phosphatase Cdc14 is required for mitotic exit2,3 and for segregation of repetitive regions4. Cdc14 is also a subunit of the silencing complex RENT (refs 5, 6), but no roles in transcriptional repression have been described. Here we report that inactivation of Cdc14 causes silencing defects at the intergenic spacer sequences of ribosomal genes during interphase and at Yâ€Č repeats in subtelomeric regions during mitosis. We show that the role of Cdc14 in silencing is independent of the RENT deacetylase subunit Sir2. Instead, Cdc14 acts directly on RNA polymerase II by targeting CTD phosphorylation at Ser 2 and Ser 5. We also find that the role of Cdc14 as a CTD phosphatase is conserved in humans. Finally, telomere segregation defects in cdc14 mutants4 correlate with the presence of subtelomeric Yâ€Č elements and can be rescued by transcriptional inhibition of RNA polymerase II

    Biological and trophic consequences of genetic introgression between endemic and invasive Barbus fishes.

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    Genetic introgression with native species is recognized as a detrimental impact resulting from biological invasions involving taxonomically similar invaders. Whilst the underlying genetic mechanisms are increasingly understood, the ecological consequences of introgression are relatively less studied, despite their utility for increasing knowledge on how invasion impacts can manifest. Here, the ecological consequences of genetic introgression from an invasive congener were tested using the endemic barbel populations of central Italy, where the invader was the European barbel Barbus barbus. Four populations of native Barbus species (B. plebejus and B. tyberinus) were studied: two purebred and two completely introgressed with alien B. barbus. Across the four populations, differences in their biological traits (growth, body condition and population demographic structure) and trophic ecology (gut content analysis and stable isotope analysis) were tested. While all populations had similar body condition and were dominated by fish up to 2 years of age, the introgressed fish had substantially greater lengths at the same age, with maximum lengths 410-460 mm in hybrids versus 340-360 mm in native purebred barbel. The population characterized by the highest number of introgressed B. barbus alleles (81 %) had the largest trophic niche and a substantially lower trophic position than the other populations through its exploitation of a wider range of resources (e.g. small fishes and plants). These results attest that the genetic introgression of an invasive congener with native species can result in substantial ecological consequences, including the potential for cascading effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-021-02577-6
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