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

Blockchain-based Data Provenance for the Internet of Things

As more and more applications and services depend on data collected and provided by Internet of Things (IoT) devices, it is of importance that such data can be trusted. Data provenance solutions together with blockchain technology are one way to make data more trustworthy. However, current solutions do not address the heterogeneous nature of IoT applications and their data. In this work, we identify functional and non-functional requirements for a generic IoT data provenance framework, and conceptualise the framework as a layered architecture. Using a proof-of-concept implementation based on Ethereum smart contracts, data provenance can be realised for a wide range of IoT use cases. Benefits of a generic framework include simplified adoption and a more rapid implementation of data provenance for the IoT

Edge-ICN and its application to the Internet of Things

While research on Information-Centric Networking (ICN) flourishes, its adoption seems to be an elusive goal. In this paper we propose Edge-ICN: a novel approach for deploying ICN in a single large network, such as the network of an Internet Service Provider. Although Edge-ICN requires nothing beyond an SDN-based network supporting the OpenFlow protocol, with ICN-aware nodes only at the edges of the network, it still offers the same benefits as a clean-slate ICN architecture but without the deployment hassles. Moreover, by proxying legacy traffic and transparently forwarding it through the Edge-ICN nodes, all existing applications can operate smoothly, while offering significant advantages to applications such as native support for scalable anycast, multicast, and multi-source forwarding. In this context, we show how the proposed functionality at the edge of the network can specifically benefit CoAP-based IoT applications. Our measurements show that Edge-ICN induces on average the same control plane overhead for name resolution as a centralized approach, while also enabling IoT applications to build on anycast, multicast, and multi-source forwarding primitives.Comment: IFIP Networking Workshops, IFIP, 201

Comment on "Effect of biofilm formation by clinical isolates of Helicobacter pylori on the efflux-mediated resistance to commonly used antibiotics".

Attaran et al[1] have recently shown that decreased susceptibility of established Helicobacter pylori (H. pylori) biofilms to specific antibiotics, was associated with the overtly enhanced transcription of two efflux pump genes, hp1165 and hefA, involved in specific resistance to tetracycline and multiple antibiotics, respectively. Apart from antibiotic exposure, secretion of multiple antimicrobial peptides, such as human ?-defensins (h?Ds), by the gastric epithelium upon Hp challenge, may act as early triggering events that positively impact biofilm formation and thus, antibiotic resistance. In this regard, we undertook genomic transcriptional studies using Hp 26695 strain following exposure to sublethal, similar to those present in the gastric niche, concentrations of h?Ds in an attempt to provide preliminary data regarding possible mechanisms of immune evasion and selective sensitivity of Hp. Our preliminary results indicate that h?D exposure ignites a rapid response that is largely due to the activation of several, possibly interconnected transcriptional regulatory networks - origons - that ultimately coordinate cellular processes needed to maintain homeostasis and successful adaptation of the bacterium in the gastric environment. In addition, we have shown that both antibiotic and h?D resistance are mediated by dedicated periplasmic transporters, including the aforementioned efflux pump genes hp1165 and hefA, involved in active export of antibiotics from the cell membrane and/or, as recently suggested, substrate sensing and signalling. Furthermore, it appears that sublethal doses of h?Ds may enhance biofilm formation by the sustained expression of, mainly, quorum sensing-related genes. In conclusion, we provide additional data regarding the role of specific innate immune molecules in antibiotic cross-resistance mechanisms that may deepen our understanding in the context of the development of novel eradication regimens

A new mathematical model for the interpretation of translational research evaluating six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon

Adjuvant therapy of stage IIB/III melanoma with interferon reduces relapse and mortality by up to 33% but is accompanied by toxicity-related complications. Polymorphisms of the CTLA-4 gene associated with autoimmune diseases could help in identifying interferon treatment benefits. We previously genotyped 286 melanoma patients and 288 healthy (unrelated) individuals for six CTLA-4 polymorphisms (SNP). Previous analyses found no significant differences between the distributions of CTLA-4 polymorphisms in the melanoma population vs. controls, no significant difference in relapse free and overall survivals among patients and no correlation between autoimmunity and specific alleles. We report new analysis of these CTLA-4 genetic profiles, using Network Phenotyping Strategy (NPS). It is graph-theory based method, analyzing the SNP patterns. Application of NPS on CTLA-4 polymorphism captures allele relationship pattern for every patient into 6-partite mathematical graph P. Graphs P are combined into weighted 6-partite graph S, which subsequently decomposed into reference relationship profiles (RRP). Finally, every individual CTLA-4 genotype pattern is characterized by the graph distances of P from eight identified RRP's. RRP's are subgraphs of S, collecting equally frequent binary allele co-occurrences in all studied loci. If S topology represents the genetic "dominant model", the RRP's and their characteristic frequencies are identical to expectation-maximization derived haplotypes and maximal likelihood estimates of their frequencies. The graphrepresentation allows showing that patient CTLA-4 haplotypes are uniquely different from the controls by absence of specific SNP combinations. New function-related insight is derived when the 6-partite graph reflects allelic state of CTLA-4. We found that we can use differences between individual P and specific RRPs to identify patient subpopulations with clearly different polymorphic patterns relatively to controls as well as to identify patients with significantly different survival. © 2014 Pancoska et al

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