2,877 research outputs found
The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
Get PDFReproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity
Study of dynamic simulators with ADAMS and Matlab/Simulink for control systems
No full textADAMS-MATLAB co-simulation is widely used in complex system development to control models of closed-loop mechanisms. An advantage of ADAMS is to facilitate the configuration of parameters such as friction. However, its mathematical friction model is unknown. There are alternatives such as Simscape Multibody that facilitate the configuration of any friction model. This paper presents a case study of dynamic simulation using the mathematical model of a mechanism in order to compare it with ADAMS and Simscape Multibody. The state-space model uses the parameters b and fc – viscous and Coulomb friction coefficients. However, ADAMS uses only one dynamic friction parameter µ. Since both friction parameters do not appear in ADAMS, a parametric identification procedure was used to determine the equivalency between the friction coefficients b and fc compared to µ. To identify the friction model of ADAMS, open-loop and closed-loop simulations were proposed. To compare the simulation results numerically, the L2 norm was used. The reference was the model solved with the ODE45 function
Le Corbeau et le Renard: 99 versions réinventées: Style d'exercices
No full textThis book represents a fascinating effort. At first I thought it was going to be a collection of various parodies of La Fontaine's FC. It is not that, but rather a creative presentation of some 97 different versions of La Fontaine created by the author. The first two versions are a French translation of the Greek prose of the most original FC text in the Aesopic manuscripts and then La Fontaine's verse. Thereafter the fun begins! The imagination and the execution of this project are both remarkable. Let me offer a sample of five approaches: (1) an acrostic, so that the opening letters of each verse spell "M Jean La Fontaine"; (2) a prose version after the manner of Balzac; (3) a scientific version needing more than a full page; (4) a tourist guide version; and (5) a rhyming version in English. T of C at the end. 136 pages. 5¼" x 8". Printed upon demand.Language note: FrenchNicolas Mille
The structure of human CD23 and its interactions with IgE and CD21
No full textThe low-affinity immunoglobulin E ( IgE) receptor, CD23 ( Fc epsilon RII), binds both IgE and CD21 and, through these interactions, regulates the synthesis of IgE, the antibody isotype that mediates the allergic response. We have determined the three-dimensional structure of the C-type lectin domain of CD23 in solution by nuclear magnetic resonance spectroscopy. An analysis of concentration-dependent chemical shift perturbations have allowed us to identify the residues engaged in self-association to the trimeric state, whereas ligand-induced changes have defined the binding sites for IgE and CD21. The results further reveal that CD23 can bind both ligands simultaneously. Despite the C-type lectin domain structure, none of the interactions require calcium. We also find that IgE and CD23 can interact to form high molecular mass multimeric complexes. The interactions that we have described provide a solution to the paradox that CD23 is involved in both up- and down-regulation of IgE and provide a structural basis for the development of inhibitors of allergic diseas
Copy number, linkage disequilibrium and disease association in the FCGR locus
Get PDFThe response of a leukocyte to immune complexes (ICs) is modulated by receptors for the Fc region of IgG (FcgammaRs), and alterations in their affinity or function have been associated with risk of autoimmune diseases, including systemic lupus erythematosus (SLE). The low-affinity FcgammaR genomic locus is complex, containing regions of copy number variation (CNV) which can alter receptor expression and leukocyte responses to IgG. Combined paralogue ratio tests (PRTs) were used to distinguish three intervals within the FCGR locus which undergo CNV, and to determine FCGR gene copy number (CN). There were significant differences in FCGR3B and FCGR3A CNV profiles between Caucasian, East Asian and Kenyan populations. A previously noted association of low FCGR3B CN with SLE in Caucasians was supported [OR = 1.57 (1.08-2.27), P = 0.018], and replicated in Chinese [OR = 1.65 (1.25-2.18), P = 4 x 10(-4)]. There was no association of FCGR3B CNV with vasculitis, nor with malarial or bacterial infection. Linkage disequilibrium (LD) between multi-allelic FCGR3B CNV and SLE-associated SNPs in the FCGR locus was defined for the first time. Despite LD between FCGR3B CNV and a variant in FcgammaRIIB (I232T) which abolishes inhibitory function, both reduced CN of FCGR3B and homozygosity of the FcgammaRIIB-232T allele were individually strongly associated with SLE risk. Thus CN of FCGR3B, which controls IC responses and uptake by neutrophils, and variations in FCGR2B, which controls factors such as antibody production and macrophage activation, are important in SLE pathogenesis. Further interpretations of contributions to pathogenesis by FcgammaRs must be made in the context of LD involving CNV regions
The effect of manipulating apoptotic cell uptake on their immunogenicity
Get PDFFailure of the immune system to differentiate between apoptotic tumour cells and cells rendered apoptotic as part of homeostasis prevents a successful response being mounted against tumours. Apoptotic cells are cleared rapidly by professional phagocytes thus preventing the release of potentially inflammatory or immunogenic material into the surrounding environment. In addition, macrophages release immuno-suppressive cytokines such as tumour growth factor ? (TGF-?) and interleukin-10 (IL-10) that dampen the initiation of cytotoxic T cell (CTL) immunity and render T cells tolerant. It was hypothesised that manipulation of this clearance pathway, which is normally employed to prevent autoimmunity, may alleviate immuno-suppression of apoptotic tumour cells and promote the expansion of a tumour antigen-specific T cell response.Milk fat globule – epidermal growth factor 8 (MFG-E8) is a glycoprotein secreted by activated macrophages and immature dendritic cells. It facilitates the uptake of apoptotic cells by acting as a bridging molecule between integrins on the phagocyte and phosphatidylserine (PS) on the apoptotic cell surface. Here, two recombinant dominant-negative MFG-E8 proteins were generated: one which is shown to inhibit PS-dependent apoptotic cell uptake by macrophages by over 40% (DN-MFG-E8), and a second which re-directed apoptotic cells through Fc? receptors and conferred enhanced phagocytosis by both macrophages and immature dendritic cells (DN-MFG-E8-Fc) in a dose-dependent manner.Cross-presentation of cell-associated antigen by bone marrow-derived dendritic cells (BMDCs) was determined by CD8+ T cell proliferation assays in vitro and in vivo. Loading BMDCs with apoptotic cells via a PS-independent pathway or through Fc? receptors (Fc?Rs) reduced their ability to induce CD8+ T cell proliferation in vivo, suggesting the blockade of a mechanism which is intrinsic for DC maturation or migration. Similarly, the balance between activating and inhibitory Fc?Rs proved essential for effective DC maturation. Apoptotic cells treated with DN-MFG-E8-Fc protein resulted in upregulation of costimulatory molecules, CD86 and CD70, when BMDCs were deficient for the inhibitory Fc?R, Fc?RIIb.Additionally, the immunosuppressive effect of apoptotic cells on antibody production proved dependent on the exposure of PS; whereby both DN-MFG-E8 and DN-MFG-E8-Fc proteins were shown to alleviate this suppression
FC Omniworld
No full textHet maken van een stedenbouwkundig plan voor de locatie Almere Poort in Almere. Hierbij is het programma van de Gemeente, zoals gespecificeerd voor de locatie, overgenomen. De kern van het nieuwe plan is een centrale (groene) as waaraan alle centrumfuncties voor deze wijk worden gerealiseerd. Deze nieuwe as zorgt, door de combinatie van functies met verschillende gebruikstijden, voor een continue drukte op deze centrale as. Aan een van de eindes van de as ligt een verhoogd maaiveld. Dit maaiveld gaat over het spoortalud zodat men het spoor over kan steken zonder tunnel of spoorwegovergang. In dit talud worden diverse functies gehuisvest welke normaal dichte dozen zijn (zoals parkeren, expo ruimten en sportzalen). Deze functies met voornaleijk dichte gevels worden omkleed met kleinschalige functies om continue activiteit bij het verhoogde maaiveld te genereren en om interessante gevelbeelden te hebben (i.p.v. dichte wanden van grootschalige functies). In het verhoogde maaiveld ligt verdiept het nieuwe stadion voor FC Omniworld. Dit stadion wordt zo opgenomen in een natuurlijke en groene omgeving. De dakconstructie bestaat uit houten spanten en een semi-transparant doek om zo goed mogelijk aan te sluiten op het park bovenop het nieuwe maaiveld. Bezoekers komen ook via het park binnen. Op dit niveau kan men rondlopen om versnaperingen te kopen en vervolgens af te dalen naar de tribunes. Het stadion is in de toekomst uit te breiden door nieuwe tribunes te positioneren boven de promenade van het stadion en onder het dak. Hiervoor zijn geen aanpassingen vereist. Tevens is het stadion multifuntioneel te gebruiken door verplaatsbare tribunedelen.Architectur
Plant expression of cocaine hydrolase-Fc fusion protein for treatment of cocaine abuse
Get PDFBACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.
RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to the mammalian-cell expressed CocH3-Fc protein, pCocH3-Fc had a shorter biological half-life, probably due to the lack of protein sialylation in plant. Nevertheless, the in vivo half-life was significantly extended upon the PEGylation of pCocH3-Fc. The Fc fusion did not prolong the biological half-life of the plant-expressed enzyme pCocH3-Fc, but increased the yield of the enzyme expression in the plant under the same experimental conditions.
CONCLUSIONS: It is feasible to express pCocH3-Fc in plants. Further studies on the pCocH3-Fc production in plants should focus on the development of vectors with additional genes/promoters for the complete protein sialylation and for a better yield
Membrane changes in murine macrophages after in-vivo stimulation and activation
No full textThe expression of various receptors and other surface determinants on resident, glycogen-and Corynebacterium parvum- elicited mouse peritoneal macrophages has been described. Macrophage Fc (IgG2b) receptors and I-A antigens were slightly increased after stimulation and a more marked increase was shown after activation with C. parvum. Complement receptor expression was enhanced after stimulation but was markedly reduced after activation. C. parvum-elicited macrophages, and to a lesser extent glycogen-elicited macrophages, showed a reduction in lectin-like receptors which recognize bacterial cell-wall sugars. Surface mannosyl determinants of the macrophage membrane were apparently increased after activation. The environment thus can be seen to influence the expression of macrophage surface receptors and antigens. These alterations are likely to influence the role of the macrophage in the immune response
Stable Foliage Cluster (FC), a Basic Unit of the Crown Structure of Tree Species and Its Application to Modeling of Tree and Forest Structure: Configuration of the FC Model
Get PDFThe "foliage cluster (FC) model" shows that the size (the amount of leaves, number of yearly shoots and total twig length), turnover time, and branching (i.e., forking) structure of a twig becomes stable in the top of the crown in an oak species by forming a "stable FC" [1]. A stable FC can be treated as a basic component of the crown structure and as an alternative to individual leaf or current-year shoot. The FC model is composed of several equations approximating the branching structure of twigs. Differences in size and branching morphology among twigs are represented by differences in values of the parameters of the equations. We described details of our analyses of data taken from real twigs and applied to the equations implemented in the FC model
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