5,095 research outputs found

    Effective process for lipid reduction using high speed centrifugation compared with ultracentrifugation

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    Introduction: Reducing laboratory errors and improving patient safety is receiving a lot of attention. Lipaemic samples are cause of analytical errors and present challenges for laboratories, particularly for those without ultracentrifuges. Lipaemia can originate from physiological (postprandial metabo-lism), para-physiological causes (e.g. IV administration of lipids) as well as metabolic disturbances (e.g. hypertriglyceridaemia). Materials and methods: We have evaluated a procedure with 10 native lipaemic sample pools (triglyceride concentration range 11.6-42.7 mmol/L) for the ability to reduce lipid concentration using a high speed micro-centrifuge (double centrifuged at 21.885 x g for 15 min) compared with an ultracen-trifuge, and provide accurate results. Results of sodium, creatinine, urate, total protein, lactate dehydrogenase (LD), magnesium and, cholesterol and triglyceride analysis on a Beckman DxC800 analyser are presented. Results: Data from our tertiary level hospital showed ~0.7% of the samples received for lipid studies have triglyceride levels > 10 mmol/L which can potentially cause analytical interference. The mean differences from the neat aliquot to the ultracentrifuged and high speed centrifuged sample pools were: cholesterol 4.9 mmol/L and 3.1 mmol/L; and triglycerides 17.4 mmol/L and 15.0 mmol/L respectively. The data confirms high speed centrifugation is almost as effective as ultracentrifugation in lipid reduction. Conclusion: The procedure utilized in this study using a high speed micro-centrifuge showed it is effective in reducing lipid levels and provides a suitable alternative to ultracentrifuged samples to pro-vide accurate results

    Alterations of immune response of non-small lung cancer with azacytidine

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    Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

    Developmental plasticity shapes social traits and selection in a facultatively eusocial bee

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    Developmental plasticity generates phenotypic variation, but how it contributes to evolutionary change is unclear. Phenotypes of individuals in caste-based (eusocial) societies are particularly sensitive to developmental processes, and the evolutionary origins of eusociality may be rooted in developmental plasticity of ancestral forms. We used an integrative genomics approach to evaluate the relationships among developmental plasticity, molecular evolution, and social behavior in a bee species (Megalopta genalis) that expresses flexible sociality, and thus provides a window into the factors that may have been important at the evolutionary origins of eusociality. We find that differences in social behavior are derived from genes that also regulate sex differentiation and metamorphosis. Positive selection on social traits is influenced by the function of these genes in development. We further identify evidence that social polyphenisms may become encoded in the genome via genetic changes in regulatory regions, specifically in transcription factor binding sites. Taken together, our results provide evidence that developmental plasticity provides the substrate for evolutionary novelty and shapes the selective landscape for molecular evolution in a major evolutionary innovation: Eusociality

    In situ epitaxial MgB2 thin films for superconducting electronics

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    A thin film technology compatible with multilayer device fabrication is critical for exploring the potential of the 39-K superconductor magnesium diboride for superconducting electronics. Using a Hybrid Physical-Chemical Vapor Deposition (HPCVD) process, it is shown that the high Mg vapor pressure necessary to keep the MgB2_2 phase thermodynamically stable can be achieved for the {\it in situ} growth of MgB2_2 thin films. The films grow epitaxially on (0001) sapphire and (0001) 4H-SiC substrates and show a bulk-like TcT_c of 39 K, a JcJ_c(4.2K) of 1.2×1071.2 \times 10^7 A/cm2^2 in zero field, and a Hc2(0)H_{c2}(0) of 29.2 T in parallel magnetic field. The surface is smooth with a root-mean-square roughness of 2.5 nm for MgB2_2 films on SiC. This deposition method opens tremendous opportunities for superconducting electronics using MgB2_2

    A Study of the Semileptonic Charm Decays D^0 --> pi^- e^+ nu_e, D^+ --> pi^0 e^+ nu_e, D^0 --> K^- e^+ nu_e, and D^+ --> barK^0 e^+ nu_e

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    Using a sample of 1.8 million DDbar meson pairs collected at the psi(3770) with the CLEO-c detector, we study the semileptonic decays D^0 -> pi^- e^+ nu_e, D^+ -> pi^0 e^+ \nu_e, D^0 -> K^- e^+ \nu_e, and D^+ -> Kbar^0 e^+ nu_e. For the total branching fractions we find B(D^0 -> pi^- e^+ \nu_e) = 0.299(11)(9)%, B(D^+ -> pi^0 e^+ \nu_e) = 0.373(22)(13)%, B(D^0 -> K^- e^+ nu_e) = 3.56(3)(9)%, and B(D^+ -> Kbar^0 e^+ nu_e) = 8.53(13)(23)%, where the first error is statistical and the second systematic. In addition, form factors are studied through fits to the partial branching fractions obtained in five q^2 ranges. By combining our results with recent unquenched lattice calculations, we obtain |Vcd| = 0.217(9)(4)(23) and |Vcs| = 1.015(10)(11)(106), where the final error is theoretical.Comment: 18 pages, postscript also available through http://www.lns.cornell.edu/public/CLNS/2006/, submitted to PR

    A Study of the Decays D^0 --> pi^- e^+ nu_e, D^0 --> K^- e^+ nu_e, D^+ --> pi^0 e^+ nu_e, and D^+ --> barK^0 e^+ nu_e

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    Using 1.8 million DDbar pairs and a neutrino reconstruction technique, we have studied the decays D^0 -> K^- e^+ nu_e, D^0 -> pi^- e^+ nu_e, D^+ -> Kbar^0 e^+ nu_e, and D^+ -> pi^0 e^+ nu_e. We find B(D^0 -> pi^- e^+ nu_e) = 0.299(11)(9)%, B(D^+ -> pi^0 e^+ nu_e) = 0.373(22)(13)%, B(D^0 -> K^- e^+ nu_e) = 3.56(3)(9)%, and B(D^+ -> Kbar^0 e^+ nu_e) = 8.53(13)(23)%. In addition, form factors are studied through fits to the partial branching fractions obtained in five q^2 ranges. By combining our results with recent unquenched lattice calculations, we obtain |Vcd| = 0.217(9)(4)(23) and |Vcs| = 1.015(10)(11)(106).Comment: 9 pages, postscript also available through http://www.lns.cornell.edu/public/CLNS/2006/, submitted to PR

    Search for Radiative Decays of Upsilon(1S) into eta and eta'

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    We report on a search for the radiative decay of Upsilon(1S) to the pseudoscalar mesons eta and etaprime in 21.2 +/- 0.2 times 10^6 Upsilon(1S) decays collected with the CLEO III detector at the Cornell Electron Storage Ring (CESR). The eta meson was reconstructed in the three modes eta to gamma-gamma, eta to pi+pi-pi0 and eta to 3pi0. The etaprime meson was reconstructed in the mode etaprime to pi+ pi- eta with eta decaying through any of the above three modes, and also etaprime to gamma rho, where rho decays to pi^+ pi^-. Five out of the seven sub-modes are found to be virtually background-free. In four of them we find no signal candidates and in one Upsilon(1S) to gamma-etaprime, etaprime to pi+ pi- eta, eta to pi+pi-pi0 there are two good signal candidates, which is insufficient evidence to claim a signal. The other two sub-modes eta to gamma-gamma and etaprime to gamma rho are background limited, and show no excess of events in their signal regions. We combine the results from different channels and obtain upper limits at the 90% C.L. which are B(Upsilon(1S) to gamma eta) < 1.0 times 10^-6 and B(Upsilon(1S) to gamma etaprime) < 1.9 times 10^-6. Our limits are an order of magnitude tighter than the previous ones and below the predictions made by some theoretical models.Comment: 14 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2007/, Submitted to PR
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