66 research outputs found

    Comparison of a Non-linear Purlin Model with Tests

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    A non-linear elastic analysis has been developed for determining the lateral deflections of, and stresses in, the unconnected flanges of simply-supported and continuous channel and Z-section purlins screw-fastened to sheeting and subject to either wind uplift or gravity loading. The analysis incorporates a model, based on a combination of those developed by Pekoz and Soroushian, and Thomasson, which depicts the unconnected purlin flange as a beam-column. The restraint against lateral deflection is provided primarily by the sheeting, and is represented by a linear extensional spring of stiffness k located at the level of the unconnected purlin flange. To verify the model, lateral deflections and failure stresses obtained from vacuum rig tests can be compared with those determined by the non-linear analysis. In this paper, results from vacuum rig tests on continuous Z-section purlins screw-fastened to sheeting and subject to simulated wind uplift and gravity loading are compared

    Determination of Purlin R-factors Using a Non-linear Analysis

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    In both Australia and the U.S.A., the design procedure for purlins under wind uplift loading is based on the use of reduction factors (R-factors), which allow for the flexural-torsional or nonlinear twisting behaviour of purlins with screw-fastened sheeting. To date, all R-factors have been determined by testing. However, in the future it may be more efficient to obtain R-factors from numerical models to minimise testing. This paper shows how a numerical model of the twisting behaviour of channel and Z-section purlins can be used to generate R-factors. Comparisons between experimentally determined and numerically based R-factors are made

    The Utilization of Sunscreen Prescriptions to Increase Patient Use: Examination of Healthcare Provider Perceptions

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    Background: Despite the known benefits, many patients deny receiving sunscreen counseling. Over the past decade rates and treatment costs for skin cancer has risen. Purpose: This study seeks to investigate provider perceptions of using sunscreen prescriptions as a method to increase patient use. Methods: A descriptive online survey using a convenience sample of dermatology, internal medicine, and family medicine providers was used. Descriptive statistics summarized quantitative variables and thematic analysis examined opened ended questions. Results: Provider (n=38 total) thoughts about sunscreen prescriptions were mixed with many viewing sunscreen prescriptions positively (n =15; 42.9%). Commonly listed barriers included patient lack of motivation/interest (3.53±0.89), lack of standard guidelines about sunscreen counseling and prescriptions (3.34±1.12), and lack of education about prescribing sunscreen (3.26±1.35). Facilitators included insurance coverage (n = 21; 61.8%) and having a standardized protocol (n=8; 23.5%). Conclusion: The majority of providers felt prescribing sunscreen would increase patient use. Study results imply providers would utilize sunscreen prescriptions if a clear, standardized protocol was present. Education may help alleviate concerns related to insurance coverage. In consideration of time constraints, it may be beneficial for sunscreen prescriptions to be added to routine after-visit summaries and educational materials

    Leukocyte Counts, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A as Biomarkers for Cardiovascular Disease: Towards a Multi-Biomarker Approach

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    We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk

    Total Synthesis of Paracaseolide A

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    The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification

    Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by Regulating PPAR gamma-Dependent Monocyte Differentiation and Function

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    Objective-Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD)(+) generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis. Approach and Results-Low-density lipoprotein receptor-deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPT(hi)), on a western type diet, showed attenuated plaque burden with features of lesion stabilization. This anti-atherogenic effect was caused by improved resistance of macrophages to apoptosis by attenuated chemokine (C-C motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage polarization toward an anti-inflammatory M2 phenotype. The iNAMPT(hi) phenotype was almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating that iNAMPT catalytic activity is instrumental in the atheroprotection. Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and eNAMPT had no effect on chemokine (C-C motif) receptor 2 expression and promoted an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least partly involved sirtuin 1-dependent molecular crosstalk of NAMPT and peroxisome proliferator-activated receptor.. Finally, iNAMPT and peroxisome proliferator-activated receptor. showed a strong correlation in human atherosclerotic, but not healthy arteries, hinting to a relevance of iNAMPT/peroxisome proliferator-activated receptor. pathway also in human carotid atherosclerosis. Conclusions-This study highlights the functional dichotomy of intracellular versus extracellular NAMPT, and unveils a critical role for the iNAMPT-peroxisome proliferator-activated receptor. axis in atherosclerosis

    Long-Term Conditioning to Elevated pCO2 and Warming Influences the Fatty and Amino Acid Composition of the Diatom Cylindrotheca fusiformis

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    The unabated rise in anthropogenic CO2 emissions is predicted to strongly influence the ocean's environment, increasing the mean sea-surface temperature by 4°C and causing a pH decline of 0.3 units by the year 2100. These changes are likely to affect the nutritional value of marine food sources since temperature and CO2 can influence the fatty (FA) and amino acid (AA) composition of marine primary producers. Here, essential amino (EA) and polyunsaturated fatty (PUFA) acids are of particular importance due to their nutritional value to higher trophic levels. In order to determine the interactive effects of CO2 and temperature on the nutritional quality of a primary producer, we analyzed the relative PUFA and EA composition of the diatom Cylindrotheca fusiformis cultured under a factorial matrix of 2 temperatures (14 and 19°C) and 3 partial pressures of CO2 (180, 380, 750 μatm) for >250 generations. Our results show a decay of ∼3% and ∼6% in PUFA and EA content in algae kept at a pCO2 of 750 μatm (high) compared to the 380 μatm (intermediate) CO2 treatments at 14°C. Cultures kept at 19°C displayed a ∼3% lower PUFA content under high compared to intermediate pCO2, while EA did not show differences between treatments. Algae grown at a pCO2 of 180 μatm (low) had a lower PUFA and AA content in relation to those at intermediate and high CO2 levels at 14°C, but there were no differences in EA at 19°C for any CO2 treatment. This study is the first to report adverse effects of warming and acidification on the EA of a primary producer, and corroborates previous observations of negative effects of these stressors on PUFA. Considering that only ∼20% of essential biomolecules such as PUFA (and possibly EA) are incorporated into new biomass at the next trophic level, thepotential impacts of adverse effects of ocean warming and acidification at the base of the food web may be amplified towards higher trophic levels, which rely on them as source of essential biomolecules

    Endothelial ADAM10 controls cellular response to oxLDL and its deficiency exacerbates atherosclerosis with intraplaque hemorrhage and neovascularization in mice

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    IntroductionThe transmembrane protease A Disintegrin And Metalloproteinase 10 (ADAM10) displays a “pattern regulatory function,” by cleaving a range of membrane-bound proteins. In endothelium, it regulates barrier function, leukocyte recruitment and angiogenesis. Previously, we showed that ADAM10 is expressed in human atherosclerotic plaques and associated with neovascularization. In this study, we aimed to determine the causal relevance of endothelial ADAM10 in murine atherosclerosis development in vivo.Methods and resultsEndothelial Adam10 deficiency (Adam10ecko) in Western-type diet (WTD) fed mice rendered atherogenic by adeno-associated virus-mediated PCSK9 overexpression showed markedly increased atherosclerotic lesion formation. Additionally, Adam10 deficiency was associated with an increased necrotic core and concomitant reduction in plaque macrophage content. Strikingly, while intraplaque hemorrhage and neovascularization are rarely observed in aortic roots of atherosclerotic mice after 12 weeks of WTD feeding, a majority of plaques in both brachiocephalic artery and aortic root of Adam10ecko mice contained these features, suggestive of major plaque destabilization. In vitro, ADAM10 knockdown in human coronary artery endothelial cells (HCAECs) blunted the shedding of lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1) and increased endothelial inflammatory responses to oxLDL as witnessed by upregulated ICAM-1, VCAM-1, CCL5, and CXCL1 expression (which was diminished when LOX-1 was silenced) as well as activation of pro-inflammatory signaling pathways. LOX-1 shedding appeared also reduced in vivo, as soluble LOX-1 levels in plasma of Adam10ecko mice was significantly reduced compared to wildtypes.DiscussionCollectively, these results demonstrate that endothelial ADAM10 is atheroprotective, most likely by limiting oxLDL-induced inflammation besides its known role in pathological neovascularization. Our findings create novel opportunities to develop therapeutics targeting atherosclerotic plaque progression and stability, but at the same time warrant caution when considering to use ADAM10 inhibitors for therapy in other diseases

    Alternative Methods for Measuring Scapular Muscles Protraction and Retraction Maximal Isometric Forces

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    Presentation given at 2009 American Physical Therapy Association PTA Annual Conference and Exposition
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