610 resultados para Carlander-Reutenfelt, Torsten


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The transcription factor PU.1 is a master regulator of myeloid differentiation and function. On the other hand, only scarce information is available on PU.1-regulated genes involved in cell survival. We now identified the glycolytic enzyme hexokinase 3 (HK3), a gene with cytoprotective functions, as transcriptional target of PU.1. Interestingly, HK3 expression is highly associated with the myeloid lineage and was significantly decreased in acute myeloid leukemia patients compared with normal granulocytes. Moreover, HK3 expression was significantly lower in acute promyelocytic leukemia (APL) compared with non-APL patient samples. In line with the observations in primary APL patient samples, we observed significantly higher HK3 expression during neutrophil differentiation of APL cell lines. Moreover, knocking down PU.1 impaired HK3 induction during neutrophil differentiation. In vivo binding of PU.1 and PML-RARA to the HK3 promoter was found, and PML-RARA attenuated PU.1 activation of the HK3 promoter. Next, inhibiting HK3 in APL cell lines resulted in significantly reduced neutrophil differentiation and viability compared with control cells. Our findings strongly suggest that HK3 is: (1) directly activated by PU.1, (2) repressed by PML-RARA, and (3) functionally involved in neutrophil differentiation and cell viability of APL cells.

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Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 (V(1393)I, K(1584)E) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6(V(1393)I) and TRPM6(K(1584)E), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T(1391)) and TRPM6(S(1583)). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6(V(1393)I) and TRPM6(K(1584)E) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6(V(1393)I) and TRPM6(K(1584)E) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6.

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Until a few years ago an interruption of breast-feeding for 12 or even 24 hours was recommended for breast-feeding mothers after anaesthesia, this is no longer valid. If it is the mother's wish, if she is sufficiently awake and physically able, there is no reason not to start breast-feeding a mature and healthy baby immediately after recovery from a general or regional anaesthesia. Even breast-feeding after a Caesarean delivery with administration of the common anaesthetics in the usual (single) doses is no longer considered to be a problem since the amount of the substance taken up from colostrum is vanishingly small in comparison to the amount that is transferred by transplacental routes. Neither the pharmacological properties of the drugs used in association with anaesthesia nor clinical experience justify an interruption of breast-feeding.

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This paper examines the accuracy of software-based on-line energy estimation techniques. It evaluates today’s most widespread energy estimation model in order to investigate whether the current methodology of pure software-based energy estimation running on a sensor node itself can indeed reliably and accurately determine its energy consumption - independent of the particular node instance, the traffic load the node is exposed to, or the MAC protocol the node is running. The paper enhances today’s widely used energy estimation model by integrating radio transceiver switches into the model, and proposes a methodology to find the optimal estimation model parameters. It proves by statistical validation with experimental data that the proposed model enhancement and parameter calibration methodology significantly increases the estimation accuracy.

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Our society uses a large diversity of co-existing wired and wireless networks in order to satisfy its communication needs. A cooper- ation between these networks can benefit performance, service availabil- ity and deployment ease, and leads to the emergence of hybrid networks. This position paper focuses on a hybrid mobile-sensor network identify- ing potential advantages and challenges of its use and defining feasible applications. The main value of the paper, however, is in the proposed analysis approach to evaluate the performance at the mobile network side given the mixed mobile-sensor traffic. The approach combines packet- level analysis with modelling of flow-level behaviour and can be applied for the study of various application scenarios. In this paper we consider two applications with distinct traffic models namely multimedia traffic and best-effort traffic.

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With research on Wireless Sensor Networks (WSNs) becoming more and more mature in the past five years, researchers from universities all over the world have set up testbeds of wireless sensor networks, in most cases to test and evaluate the real-world behavior of developed WSN protocol mechanisms. Although these testbeds differ heavily in the employed sensor node types and the general architectural set up, they all have similar requirements with respect to management and scheduling functionalities: as every shared resource, a testbed requires a notion of users, resource reservation features, support for reprogramming and reconfiguration of the nodes, provisions to debug and remotely reset sensor nodes in case of node failures, as well as a solution for collecting and storing experimental data. The TARWIS management architecture presented in this paper targets at providing these functionalities independent from node type and node operating system. TARWIS has been designed as a re-usable management solution for research and/or educational oriented research testbeds of wireless sensor networks, relieving researchers intending to deploy a testbed from the burden to implement their own scheduling and testbed management solutions from scratch.

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Costly on-site node repairs in wireless mesh networks (WMNs) can be required due to misconfiguration, corrupt software updates, or unavailability during updates. We propose ADAM as a novel management framework that guarantees accessibility of individual nodes in these situations. ADAM uses a decentralised distribution mechanism and self-healing mechanisms for safe configuration and software updates. In order to implement the ADAM management and self-healing mechanisms, an easy-to-learn and extendable build system for a small footprint embedded Linux distribution for WMNs has been developed. The paper presents the ADAM concept, the build system for the Linux distribution and the management architecture.

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The evolution of the Next Generation Networks, especially the wireless broadband access technologies such as Long Term Evolution (LTE) and Worldwide Interoperability for Microwave Access (WiMAX), have increased the number of "all-IP" networks across the world. The enhanced capabilities of these access networks has spearheaded the cloud computing paradigm, where the end-users aim at having the services accessible anytime and anywhere. The services availability is also related with the end-user device, where one of the major constraints is the battery lifetime. Therefore, it is necessary to assess and minimize the energy consumed by the end-user devices, given its significance for the user perceived quality of the cloud computing services. In this paper, an empirical methodology to measure network interfaces energy consumption is proposed. By employing this methodology, an experimental evaluation of energy consumption in three different cloud computing access scenarios (including WiMAX) were performed. The empirical results obtained show the impact of accurate network interface states management and application network level design in the energy consumption. Additionally, the achieved outcomes can be used in further software-based models to optimized energy consumption, and increase the Quality of Experience (QoE) perceived by the end-users.

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Content-centric networking is a novel paradigm for the Future Internet that treats content as a first class citizen. This paper argues that content-centric networking should be generalized towards a service-centric networking scheme. We propose a service-centric networking design based on an object-oriented approach, in which content and services are considered objects. We show implementation architectures for example services and how these can benefit from service-oriented networking.