447 research outputs found
Demonstration of PLOTs from the EuroPLOT project
The EuroPLOT project (2010-2013) has been funded to explore the concept of persuasive design for learning and teaching. It has developed Persuasive Learn-ing Objects and Technologies (PLOTs), manifested in two tools and a set of learning objects that have been tested and evaluated in four different case studies. These PLOTs will be shown in this demonstration, and the participants can try them out and experience for themselves the impact of persuasive technology that is embedded in these PLOTs. This will be one authoring tool (PLOTMaker) and one delivery tool (PLOTLearner). Furthermore, there will be learning objects shown which have been developed for those four different case studies. All of these PLOTs have already been tested and evaluated during case studies with real learners
Meta-Analysis of in vitro-Differentiated Macrophages Identifies Transcriptomic Signatures That Classify Disease Macrophages in vivo
Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage models to perform a meta-analysis. Specifically, we obtained gene expression data from unstimulated macrophages (M0) and macrophages stimulated with lipopolysaccharides (LPS) for 2-4 h (M-LPSearly), LPS for 24 h (M-LPSlate), LPS and interferon-gamma (M-LPS+IFN gamma), IFN gamma (M-IFN gamma), interleukin-4 (M-IL4), interleukin-10 (M-IL10), and dexamethasone (M-dex). Our meta-analysis identified consistently differentially expressed genes that have been implicated in inflammatory and metabolic processes. In addition, we built macIDR, a robust classifier capable of distinguishing macrophage activation states with high accuracy (>0.95). We classified in vivo macrophages with macIDR to define their tissue- and disease-specific characteristics. We demonstrate that alveolar macrophages display high resemblance to IL10 activation, but show a drop in IFN gamma signature in chronic obstructive pulmonary disease patients. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but acquired LPS-activation features in diabetic-obese patients. Rheumatoid arthritis synovial macrophages exhibit characteristics of IL10- or IFN gamma-stimulation. Altogether, we defined consensus transcriptional profiles for the eight in vitro macrophage activation states, built a classification model, and demonstrated the utility of the latter for in vivo macrophages
Numerical solution of gas dynamics equations on the computational meshes with arbitrary number of cell faces using high order spatial accuracy schemes
In the present study methodology and algorithm of numerical solution of gas dynamics equations on the computational meshes with arbitrary number of cell faces using high order spatial accuracy schemes is presented. For realization of calculation algorithm, the system of data storage is offered, the system does not depend on mesh topology, and it allows to use the computational meshes with arbitrary number of cell faces
Breakup of F on Pb near the Coulomb barrier
Angular distributions of oxygen produced in the breakup of F incident
on a Pb target have been measured around the grazing angle at beam
energies of 98 and 120 MeV. The data are dominated by the proton stripping
mechanism and are well reproduced by dynamical calculations. The measured
breakup cross section is approximately a factor of 3 less than that of fusion
at 98 MeV. The influence of breakup on fusion is discussed.Comment: 7 pages, 8 figure
Nonlinear Enhancement of the Multiphonon Coulomb Excitation in Relativistic Heavy Ion Collisions
We propose a soluble model to incorporate the nonlinear effects in the
transition probabilities of the multiphonon Giant Dipole Resonances based on
the SU(1,1) algebra. Analytical expressions for the multi-phonon transition
probabilities are derived. Enhancement of the Double Giant Resonance excitation
probabilities in relativistic ion collisions scales as for
the degree of nonlinearity and is able to reach values
compatible with experimental data. The enhancement factor is found to decrease
with increasing bombarding energy. [KEYWORDS: Relativistic Heavy Ion
Collisions,Double Giant Resonance]Comment: 12 pages, 2 figure
HDAC3 Mediates the Inflammatory Response and LPS Tolerance in Human Monocytes and Macrophages
Histone deacetylases (HDACs) are a group of enzymes that control histone deacetylation and bear potential to direct expression of large gene sets. We determined the effect of HDAC inhibitors (HDACi) on human monocytes and macrophages, with respect to their polarization, activation, and their capabilities of inducing endotoxin tolerance. To address the role for HDACs in macrophage polarization, we treated monocytes with HDAC3i, HDAC6i or pan-HDACi prior to polarization into M1 or M2 macrophages using IFNγ or IL-4 respectively. To study the HDAC inhibition effect on cytokine expression, macrophages were treated with HDACi prior to LPS-stimulation. TNFα, IL-6, and p40 were measured with ELISA, whereas modifications of Histone 3 and STAT1 were assessed using western blot. To address the role for HDAC3 in repeated LPS challenge induction, HDAC3i or HDAC3 siRNA was added to monocytes prior to incubation with IFNγ, which were then repeatedly challenged with LPS and analyzed by means of protein analyses and transcriptional profiling. Pan-HDACi and HDAC3i reduced cytokine secretion in monocytes and M1 macrophages, whereas HDAC6i yielded no such effect. Notably, neither pan-HDACi nor HDAC3i reduced cytokine secretion in M2 macrophages. In contrast to previous reports in mouse macrophages, HDAC3i did not affect macrophage polarization in human cells. Likewise, HDAC3 was not required for IFNγ signaling or IFNβ secretion. Cytokine and gene expression analyses confirmed that IFNγ-treated macrophages consistently develop a cytokine response after LPS repeated challenge, but pretreatment with HDAC3i or HDAC3 siRNA reinstates a state of tolerance reflected by general suppression of tolerizable genes, possibly through decreasing TLRs expression, and particularly TLR4/CD14. The development of endotoxin tolerance in macrophages is important to reduce exacerbated immune response and limit tissue damage. We conclude that HDAC3 is an attractive protein target to mediate macrophage reactivity and tolerance induction in inflammatory macrophages
Theory of Multiphonon Excitation in Heavy-Ion Collisions
We study the effects of channel coupling in the excitation dynamics of giant
resonances in relativistic heavy ions collisions. For this purpose, we use a
semiclassical approximation to the Coupled-Channels problem and separate the
Coulomb and the nuclear parts of the coupling into their main multipole
components. In order to assess the importance of multi-step processes, we
neglect the resonance widths and solve the set of coupled equations exactly.
Finite widths are then considered. In this case, we handle the coupling of the
ground state with the dominant Giant Dipole Resonance exactly and study the
excitation of the remaining resonances within the Coupled-Channels Born
Approximation. A comparison with recent experimental data is made.Comment: 29 pages, 7 Postscript figures available upon reques
Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation
Rationale: Patients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state. Objective: We hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism. Methods and Results: We evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, activates arterial endothelial cells, facilitating increased transendothelial migration of monocytes. Transcriptome analysis of Lp(a)-stimulated human arterial endothelial cells revealed upregulation of inflammatory pathways comprising monocyte adhesion and migration, coinciding with increased 6-phophofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)-3-mediated glycolysis. ICAM (intercellular adhesion molecule)-1 and PFKFB3 were also found to be upregulated in carotid plaques of patients with elevated levels of Lp(a). Inhibition of PFKFB3 abolished the inflammatory signature with concomitant attenuation of transendothelial migration. Conclusions: Collectively, our findings show that Lp(a) activates the endothelium by enhancing PFKFB3-mediated glycolysis, leading to a proadhesive state, which can be reversed by inhibition of glycolysis. These findings pave the way for therapeutic agents targeting metabolism aimed at reducing inflammation in patients with cardiovascular disease
Myeloid IκBα Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques
Activation of the transcription factor NF-κB appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-κB inhibitor IκBα in atherosclerosis. Myeloid-specific deletion of IκBα results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma. We show that IκBα-deleted macrophages display enhanced adhesion to an in vitro endothelial cell layer, coinciding with an increased expression of the chemokine CCL5. Also, in vivo we found that IκBαdel mice had more leukocytes adhering to the luminal side of the endothelial cell layers that cover the atherosclerotic plaques. Moreover, we introduce ER-MP58 in this paper as a new immunohistochemical tool for quantifying newly recruited myeloid cells in the atherosclerotic lesion. This staining confirms that in IκBαdel mice more leukocytes are attracted to the plaques. In conclusion, we show that IκBα deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques
High density lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-kb/stat1-irf1 signaling
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