997 research outputs found
Efficient Proactive Caching for Supporting Seamless Mobility
We present a distributed proactive caching approach that exploits user
mobility information to decide where to proactively cache data to support
seamless mobility, while efficiently utilizing cache storage using a congestion
pricing scheme. The proposed approach is applicable to the case where objects
have different sizes and to a two-level cache hierarchy, for both of which the
proactive caching problem is hard. Additionally, our modeling framework
considers the case where the delay is independent of the requested data object
size and the case where the delay is a function of the object size. Our
evaluation results show how various system parameters influence the delay gains
of the proposed approach, which achieves robust and good performance relative
to an oracle and an optimal scheme for a flat cache structure.Comment: 10 pages, 9 figure
An experimental study of the hydrodynamic behavior of a TLP platform for a 5MW wind turbine with OWC devices
An experimental study of the hydrodynamic behavior of a Tension-Leg Platform
(TLP) for a 5MW Wind Turbine, featuring Wave Energy Converter (WEC) devices of the
Oscillating Water Column type is presented. The examined triangular platform includes three
vertical cylinders at the corners, providing the required buoyancy, each of them surrounded by a
thin skirt, open at its lower end, forming the OWC chamber. A central vertical cylinder is included
for the wind turbine installation. All cylinders are structurally connected with
cylindrical bracing. The hydrodynamic response of the platform in the surge direction
is experimentally verified, together with the resulting pressures and air fluxes inside the OWC
chamber and the dynamic tensions in the lines of the mooring system
The interplay between lipoproteins, immunity and tryptophan metabolism in atherosclerosis
Atherosclerotic cardiovascular disease (CVD) is the leading cause of mortality worldwide. Atherosclerosis is initiated by the infiltration and accumulation of low-density lipoprotein (LDL) cholesterol in the vascular wall, which activates the innate and adaptive arm of immunity, thereby causing chronic vascular inflammation. The LDL particle is immunogenic, as it not only activates lesional macrophages but is also recognized by T cells, and it elicits B cell-mediated antibody responses. Animal immunization studies suggest that anti-LDL antibodies inhibit atherosclerosis, but concerns exist about the potential proinflammatory role of lesional LDL-reactive T cells. In addition to lipoproteins, amino acids and their metabolites can shape immune cell responses, which has been the subject of intense research in the emerging field of immunometabolism. Current clinical practice guidelines on the prevention of CVD focus on controlling traditional risk factors, such as hypercholesterolemia, which indirectly influence inflammation in the vascular wall. Despite optimal management, however, residual inflammatory risk persists and underscores the need for novel therapeutics that directly target vascular inflammation.
In Paper I, we generated mouse strains bearing T cell receptor (TCR) transgenic T cells that react to human LDL. Adoptive transfer of these autoreactive T cells or the intercross of TCR transgenic mice with animals expressing human apolipoprotein B-100 (apoB100) on the LDL receptor−/− (LDLR−/−) background led to reduced vascular inflammation and atherosclerosis. Interestingly, a significant proportion of LDL-reactive T cells differentiated into T follicular helper cells, which helped B cells produce anti-LDL antibodies that formed immune complexes with circulating LDL, thereby reducing plasma cholesterol.
In Paper II, we employed dendritic cell (DC) based immunotherapy in an attempt to induce apoB100-specific regulatory T (Treg) cells that can exert anti-inflammatory functions in developing plaques. The vaccine was prepared using bone marrow-derived DCs, which were loaded with apoB100 in the presence of the anti-inflammatory cytokine transforming growth factor beta 2 (TGF-β2). Immunotherapy with these DCs promoted an immune response to apoB100 that favoured the accumulation of Treg cells in atherosclerotic plaques, increased vascular expression of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1), and ameliorated atherosclerosis. In vitro experiments suggested that the Treg molecule cytotoxic T- lymphocyte–associated antigen-4 (CTLA-4) regulates IDO1 expression in macrophages and vascular cells.
In Paper III, we studied the role of IDO1-mediated tryptophan metabolism in atherosclerosis using an inhibitor of IDO1 enzyme, 1-methyl-tryptophan. In vivo and in vitro data indicated that IDO1 regulates vascular inflammation, particularly in smooth muscle cells, and inhibits atherosclerosis possibly via the generation of the metabolite 3-hydroxyanthranilic acid (3- HAA).
In Paper IV, we investigated the effects of increased endogenous 3-HAA levels on plasma lipids and atherosclerosis using an inhibitor of the enzyme 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO). Our data suggested that 3-HAA can lower plasma lipids via inhibition of the sterol regulatory element binding protein-2 (SREBP-2) pathway in hepatocytes and suppress inflammation via inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in macrophages.
The studies included in the present thesis illustrate the intricate interplay between metabolism and immunity in atherosclerosis. It is my belief that our findings will contribute to the development of effective immunomodulatory strategies directly targeting vascular inflammation and addressing the residual inflammatory cardiovascular risk
The potentially dual-faceted nature of fetuin-A in Helicobacter pylori infection and insulin resistance
Nonalcoholic fatty liver disease: Updates on associations with the metabolic syndrome and lipid profile and effects of treatment with PPAR-γ agonists
The potentially dual-faceted nature of fetuin-A in Helicobacter pylori infection and insulin resistance
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