641 research outputs found

    Tracking a Lifelong Service Commitment in Alumni of the College of William and Mary

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    In order to better understand the development of a commitment to service, this paper explores the lives of alumni of the College of William and Mary as case studies. It is valuable to students and academic institutions alike to track a student‟s service commitment to see if his or her college experience was able to deepen that commitment. William and Mary is an exemplar in service-learning, which is why its alumni were interviewed and used as case studies. The College of William and Mary has an Office of Civic Engagement (OCE) that has connected students with community partners since 2009 to advance students‟ service-learning achievements. Individual alumnus‟s responses to questions regarding their participation in service and service-learning before, after, and during college provide insight into William and Mary‟s ability to build and inspire a lifelong dedication to community service

    Analysis and Prediction of Constriction Resistance between Coated Surfaces

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    Well-controlled and well-characterized experimental measurements are obtained during the melting of a moderate-Prandtl-number material (n-eicosane) in a cylindrical enclosure heated from the side. The study aims to provide benchmark experimental measurements for validation of numerical codes. Experimental results in terms of measured temperatures and melt front locations are reported in both graphical and tabular forms. The melt front was captured photographically and its location ascertained using digital image processing techniques. To facilitate numerical validation exercises, a complete set of experimental results have been made available on a website for public access. An illustrative numerical comparison exercise was also undertaken using a multiblock finite volume method and the enthalpy method for a range of Stefan numbers. The experimental boundary conditions can be adequately represented with a constant and uniform side wall temperature, a constant and uniform lower surface temperature, and an adiabatic top wall. Very good agreement was obtained between the predictions and the experiment for Stefan numbers of up to 0.1807. The experimental results for a Stefan number of 0.0836 are recommended as being the most suitable for numerical benchmarking, since the boundary conditions are best controlled in this set of experiments

    Accuracy of city postal code coordinates as a proxy for location of residence

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    BACKGROUND: Health studies sometimes rely on postal code location as a proxy for the location of residence. This study compares the postal code location to that of the street address using a database from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH(©)). Cardiac catheterization cases in an urban Canadian City were used for calendar year 1999. We determined location in meters for both the address (using the City of Calgary Street Network File in ArcView 3.2) and postal code location (using Statistic Canada's Postal Code Conversion File). RESULTS: The distance between the two estimates of location for each case were measured and it was found that 87.9% of the postal code locations were within 200 meters of the true address location (straight line distances) and 96.5% were within 500 meters of the address location (straight line distances). CONCLUSIONS: We conclude that postal code locations are a reasonably accurate proxy for address location. However, there may be research questions for which a more accurate description of location is required

    s7a 4 reduction of systemic lupus flares by atacicept in a randomised placebo controlled phase iib study address ii and its extension study

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    Purpose Atacicept targets the B-cell stimulating factors, BLyS and APRIL, and has shown evidence of clinical response in patients with SLE. The 24 week Phase II ADDRESS II (NCT01972568) Study and its long-term extension (LTE; NCT02070978) provided data on disease activity with up to 48 weeks of atacicept treatment. Methods In ADDRESS II, patients were randomised (1:1:1) to receive weekly atacicept (75 or 150 mg SC injection) or placebo (PBO) for 24 weeks. Those who completed treatment were eligible to enter the LTE, to either continue on the same atacicept dose (atacicept groups), or switch from PBO to atacicept 150 mg (PBO/150 mg). The SLE flare analysis from both studies are reported here. Results The ITT population of ADDRESS II included 306 patients; 158 of whom met the predefined high disease activity (HDA) criterion (SLEDAI-2K≥10 at Screening). Of the 262 patients who completed the ADDRESS II, 253 entered the LTE. At 24 weeks in the PBO-controlled trial, cumulative incidence of severe flare was significantly reduced with atacicept 75 mg vs PBO by BILAG A (HR 0.24; p=0.0186), and with atacicept 150 mg vs PBO by SFI (HR 0.18; p=0.002). There was no difference in moderate-to-severe flare by BILAG A/2B. In the HDA subpopulation, incidence of severe flare at 24 weeks was significantly reduced with both atacicept doses vs PBO by BILAG A (75 mg HR 0.08, p=0.002; 150 mg HR 0.32, p=0.038) and SFI (75 mg HR 0.33, p=0.029; 150 mg HR 0.19, p=0.004). Incidence of moderate-to-severe flare by BILAG A/2B was significantly reduced with atacicept 150 mg vs PBO (HR 0.34, p=0.032). At 48 weeks, risk of severe flare by SFI was significantly lower with atacicept 150 mg vs the PBO/150 mg in both the ITT and HDA populations (figure 1); significant flare reductions were seen with atacicept 75 mg by BILAG A, and with both atacicept doses by BILAG A/2B vs PBO/150 mg, in the HDA subpopulation. Conclusions In this 24 week, double-blind, PBO-controlled trial, atacicept treatment was associated with significant flare reductions compared with PBO. Rates of flare continued to be low in atacicept-treated patients between weeks 24–48. Most flares occurred in HDA patients in the PBO group

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    Serious games may improve understanding, involvement, engagement, reasoning and inquiry, and have been successfully used in schools. Recent studies show that serious games are sometimes misused, and not always easy to integrate in an instructional environment. It is often unclear how a game contributes to student learning, or how it should be used in a course. This paper proposes a method to support the analysis, design, development, and use of serious games in education. The method combines the widely used design model ADDIE with the instructional design method ‘10 steps to complex learning’. The method is applied in the development of the Moth game, which supports learning optics at the level of high school physics

    A human MAP kinase interactome.

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    Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

    s7a 5 sri response attainment of low disease activity and safety in patients with systemic lupus treated with atacicept in a phase iib study address ii

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    Purpose Atacicept targets B-cell stimulating factors, BLyS and APRIL. ADDRESS II (NCT01972568) investigates the efficacy and safety of atacicept in SLE. Methods In this Phase IIb multicenter study, patients with active (SLEDAI-2K≥6), autoantibody-positive SLE on standard of care therapy received weekly SC injections of atacicept (75 or 150 mg) or placebo (PBO) for 24 weeks. The primary endpoint was proportion of patients achieving SLE responder index (SRI)−4 response at week 24. Other endpoints included SRI-5 through SRI-8 response and low disease activity (LDA) attainment, defined as LDA-1 (SLEDAI-2K≤2), LDA-2 (SLEDAI-2K≤2 and prednisone-equivalent ≤7.5 mg/day), or LLDAS (SLEDAI–2K≤4 without major organ activity, no new disease activity vs previous visit, Physician's Global Assessment≤1, prednisone-equivalent ≤7.5 mg/day, and stable maintenance doses of immunosuppressants). A pre-defined subset of patients was also evaluated, with high disease activity (HDA: SLEDAI-2K≥10 at Screening). Differences in clinical response between patients treated with atacicept and PBO at Week 24 were analysed using odds ratio estimated from logistic regression. Results The ITT population included 306 patients, and 158 had HDA. There was a trend towards improved SRI-4 response with atacicept vs PBO at Week 24 (p=ns in primary analysis; screening visit as baseline, BL). In a pre-specified sensitivity analysis using study day 1 as BL, a significantly larger proportion of patients on atacicept achieved SRI-4 response at week 24. In the HDA subpopulation, there were significant improvements in SRI-4,–5, −6,–7 and −8 response rates and attainment of LDA with atacicept 150 mg vs PBO (table 1). Atacicept was associated with increased serum C3 and C4, and decreased IgG, IgA, IgM and anti-dsDNA antibodies over time. Rates of treatment emergent adverse event (TEAE) and serious TEAEs were similar among groups. The most frequent serious TEAEs were infections but the incidence was not increased in the atacicept groups vs PBO. Conclusions Atacicept showed evidence of efficacy in SLE with a dose-dependent reduction of SLE disease activity in patients with HDA. Atacicept was associated with an acceptable safety profile. These results also suggest that more discriminatory endpoints will be useful for future SLE clinical trials

    Silver staining of proteins in polyacrylamide gels

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    Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels. It combines excellent sensitivity (in the low nanogram range) with the use of very simple and cheap equipment and chemicals. It is compatible with downstream processing, such as mass spectrometry analysis after protein digestion. The sequential phases of silver staining are protein fixation, then sensitization, then silver impregnation and finally image development. Several variants of silver staining are described here, which can be completed in a time range from 2 h to 1 d after the end of the electrophoretic separation. Once completed, the stain is stable for several weeks

    FGF8 isoform b expression in human prostate cancer.

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    Overexpression of fibroblast growth factor 8 (FGF8) mRNA has been previously described in prostate cancer. Of its four isoforms, FGF8b is thought to be the most important in carcinogenesis. We hypothesised that immunodetection of FGF8b in archival prostate cancer specimens is of potential prognostic value. Using a selected cohort of prostate tumours from transurethral (n=30) and radical prostatectomies (n=59), an optimised protocol for FGF8b immunoreactivity was used to corroborate expression with clinical parameters. No expression was observed in benign prostates (n=10). In prostate cancer, immunoreactivity was localised to the malignant epithelium with weak signals in the adjacent stroma. Expression of FGF8b in stage T1 and T2 cancers were 40 and 67%, respectively. In contrast, FGF8b expression was present in 94% of T3 and 100% of T4 cancers. By histological grade, FGF8b was found in 41% of low-grade cancers (Gleason score 4-6), 60% of intermediate-grade cancers (Gleason score 7 and 92% of high-grade cancers (Gleason score 8-10). The intensity of expression was significantly associated with stage (P=0.0004) and grade (P<0.0001) of disease. We further hypothesised that FGF8b overexpression resulted from enhanced transcription and translation rather than from abnormalities involving the FGF8 gene locus. This was tested by means of fluorescent in situ hybridisation in 20 cancer specimens to map the FGF8 gene locus. FGF8 gene copy number in benign and malignant nuclei was found to be similar (2.33+/-0.57 and 2.0+/-0.81, respectively P=0.51). Based on these findings, we propose a multicentre study on cohorts of patients to further evaluate FGF8b as a potential prognostic marker in prostate cancer
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