| 1. |
- Mani, Katrin, et al.
(författare)
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HIV-Tat protein transduction domain specifically attenuates growth of polyamine deprived tumor cells.
- 2007
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Ingår i: Molecular Cancer Therapeutics. - 1538-8514. ; 6:2, s. 782-788
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Tidskriftsartikel (refereegranskat)abstract
- Polyamines are essential for tumor cell growth, and the polyamine pathway represents an attractive target for cancer treatment. Several polyamine transport proteins have been cloned and characterized in bacteria and yeast cells; however, the mechanism of polyamine entry into mammalian cells remains poorly defined, although a role for proteoglycans has been suggested. Here, we show that the HIV-Tat transduction peptide, which is known to enter cells via a proteoglycan-dependent pathway, efficiently inhibits polyamine uptake. Polyamine uptake–deficient mutant cells with intact proteoglycan biosynthesis (CHO MGBG) displayed unperturbed HIV-Tat uptake activity compared with wild-type cells, supporting the notion that HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter. HIV-Tat specifically inhibited growth of human carcinoma cells made dependent on extracellular polyamines by treatment with the polyamine biosynthesis inhibitor {alpha}-difluoromethylornithine; accordingly, the Tat peptide prevented intracellular accumulation of exogenous polyamines. Moreover, combined treatment with {alpha}-difluoromethylornithine and HIV-Tat efficiently blocked tumor growth in an experimental mouse model. We conclude that HIV-Tat transduction domain and polyamines enter cells through a common pathway, which can be used to target polyamine-dependent tumor growth in the treatment of cancer.
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| 2. |
- Svensson, Katrin, et al.
(författare)
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Exosome uptake depends on ERK1/2-heat shock protein 27 signalling and lipid raft-mediated endocytosis negatively regulated by caveolin-1.
- 2013
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 288:24, s. 17713-17724
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Tidskriftsartikel (refereegranskat)abstract
- The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signalling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signalling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signalling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signalling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.
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| 3. |
- Awad, Wael, et al.
(författare)
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Improvements in the order, isotropy and electron density of glypican-1 crystals by controlled dehydration.
- 2013
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; 69:Pt 12, s. 2524-2533
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Tidskriftsartikel (refereegranskat)abstract
- The use of controlled dehydration for improvement of protein crystal diffraction quality is increasing in popularity, although there are still relatively few documented examples of success. A study has been carried out to establish whether controlled dehydration could be used to improve the anisotropy of crystals of the core protein of the human proteoglycan glypican-1. Crystals were subjected to controlled dehydration using the HC1 device. The optimal protocol for dehydration was developed by careful investigation of the following parameters: dehydration rate, final relative humidity and total incubation time Tinc. Of these, the most important was shown to be Tinc. After dehydration using the optimal protocol the crystals showed significantly reduced anisotropy and improved electron density, allowing the building of previously disordered parts of the structure.
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| 4. |
- Awad, Wael, et al.
(författare)
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Structural and Biophysical Characterization of Human EXTL3 : Domain Organization, Glycosylation, and Solution Structure
- 2018
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 57:7, s. 1166-1177
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate proteoglycans are proteins substituted with one or more heparan sulfate (HS) polysaccharides, found in abundance at cell surfaces. HS chains influence the activity of many biologically important molecules involved in cellular communication and signaling. The exostosin (EXT) proteins are glycosyltransferases in the Golgi apparatus that assemble HS chains on HSPGs. The EXTL3 enzyme mainly works as an initiator in HS biosynthesis. In this work, human lumenal N-glycosylated EXTL3 (EXTL3ΔN) was cloned, expressed in human embryonic kidney cells, and purified. Various biophysical and biochemical approaches were then employed to elucidate the N-glycosylation sites and the function of their attached N-glycans. Furthermore, the stability and conformation of the purified EXTL3ΔN protein in solution have been analyzed. Our data show that EXTL3ΔN has N-glycans at least at two positions, Asn290 and Asn592, which seem to be critical for proper protein folding and/or release. EXTL3ΔN is quite stable, as high temperature (∼59 °C) was required for denaturation. Deconvolution of the EXTL3ΔN far-UV CD spectrum revealed a substantial fraction of β sheets (25%) with a minor proportion of α-helices (14%) in the secondary structure. Solution small-angle X-ray scattering and dynamic light scattering revealed an extended structure suggestive of a dimeric arrangement and consisting of two distinct regions, narrow and broad, respectively. This is consistent with bioinformatics analyses suggesting a 3-domain structure with two glycosyltransferase domains and a coiled-coil domain.
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| 5. |
- Bergnell, Anneli
(författare)
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Med kroppen som illustration : Hur förskolebarn prat-skapar naturvetenskap med hjälp av multimodala och kroppsförankrade förklaringar
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to combine three research areas, namely preschool, science and illustrations, in order to examine (a) how modes are combined when references to the body are made or the body as such are used to explain scientific concepts and phenomena in preschool science education, and (b) how do the children handle, explore, discuss and talk science when approaching multimodally illustrated scientific contents in the studied activities. Four studies were conducted, all of which were built on empirically generated questions and were theoretically grounded in cultural-historical and multimodal perspectives. Participants were preschool students, aged 4-6 years, from three preschool groups, as well as their teachers and two science centre guides. Specific focus was directed toward activities where adults and children use their bodies or refer to their bodies to illustrate scientific concepts, for example, “the water circle” in a board-and-dice-game (study I); “water has the power to lift,” in experiments relating to a life-jacket (study II); stability in a drama-play and related experiments (study III); and evaporation in embodied illustrations and hands-on activities (study IV). The empirical material consisted mainly of video recordings. A multimodal approach was adopted for the analyses.The results indicate that multimodal illustrations may be complicated for this target group. Difficulties were found to intensify, rather than decrease, by the fact that different modes and elements were often intricately combined in the same illustration, presumably with the intention of providing instruction as well as entertainment. From the four studies, it became evident that, even if the current natural science offered in preschool education often is conducted as “discovery learning”, the assumption that children can learn complex content without support cannot be left unquestioned. This thesis illustrates the crucial role played by a guiding teacher when it comes to concretizing abstract scientific phenomena for young children. A conscious introduction of bodily-based elements in multimodal illustrations may be useful on such occasions. However, even with such seemingly transparent components included, we cannot take adequate meaning-making for granted.
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| 6. |
- Bilstrup, Urban, et al.
(författare)
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A fault tolerance test enabling QoS in a Bluetooth piconet
- 2004
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Konferensbidrag (populärvet., debatt m.m.)abstract
- An important trend, in personal area networks, is that time critical application becomes more common, e.g., voice over IP, video phone calls, network games. This segment of applications demands for quality of service (QoS) guarantees, to provide the correct functionality. The Bluetooth standard provides an optional interface to support QoS guarantees, but the standard does not suggest any actual implementation. A wireless communication channel is stochastic by nature, providing QoS guarantees with this precondition make traditional deterministic real-time theory obsolete. In this paper a probabilistic fault tolerance test enabling quality of service guarantees in a Bluetooth piconet is given. The basic Bluetooth network architecture is based on a master-slave configuration, i.e., a point to point connection. More advanced network architectures are possible where up to eight Bluetooth equipped units can be active members of one network (piconet). Furthermore, several piconets can interconnect and form a so called scatternet.
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| 7. |
- Bilstrup, Urban, et al.
(författare)
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Capacity limitations in wireless sensor networks
- 2003
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Ingår i: ETFA 2003. - Piscataway, N.J. : IEEE. - 0780379373 ; , s. 529-536
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Konferensbidrag (refereegranskat)abstract
- It is expected that wireless sensor network will be used in home automation and industrial manufacturing in the future. The main driving forces for wireless sensor networks are fault tolerance, energy gain and spatial capacity gain. Unfortunately, an often forgotten issue is the capacity limits that the network topology of a wireless sensor network represents. In this paper we identify gains, losses and limitations in a wireless sensor network, using a simplified theoretical network model. Especially, we want to point out the stringent capacity limitations that this simplified network model provide. Where a comparison between the locality of the performed information exchange and the average capacity available for each node is the main contribution.
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| 8. |
- Bilstrup, Urban, et al.
(författare)
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The use of clustered wireless multihop networks in industrial settings
- 2007
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Ingår i: ETFA 2007. - Piscataway, NJ : IEEE Press. - 9781424408252 ; , s. 211-218
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Konferensbidrag (refereegranskat)abstract
- This paper suggests a cluster collision avoidance mechanism and a dual transceiver architecture to be used in a clustered wireless multihop network. These two contributions make the clustered wireless multihop network the preferred architecture for future industrial wireless networks. The wireless multihop cluster consists of one master and several slaves, where some of the slaves will act as gateways between different clusters. Frequency hopping spread spectrum is used on a cluster level and to avoid frequency collisions between clusters a "neighbor cluster collision avoidance mechanism" is proposed and evaluated through simulations. To break up the dependence between the clusters, introduced by the gateway nodes, each node is equipped with two transceivers. The paper is concluded with a suggestion to use a clustered wireless multihop network with orthogonal hopping sequences for an industrial setting.
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| 9. |
- Bilstrup, Urban, et al.
(författare)
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Using Dual-Radio Nodes to Enable Quality of Service in a Clustered Wireless Mesh Network
- 2006
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Ingår i: IEEE Conference on Emerging Technologies and Factory Automation, 2006. ETFA '06. - Piscataway, N.J. : IEEE Press. - 0780397584 ; , s. 54-61
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Konferensbidrag (refereegranskat)abstract
- In this paper some well established wireless technologies are merged into a new concept solution for a future industrial wireless mesh network. The suggested clustered wireless mesh network can handle probabilistic quality of service guarantees and is based on a dual-radio node architecture using synchronized frequency hopping spread spectrum Bluetooth radios. The proposed architecture gives a heuristic solution to the inter-cluster scheduling problem of gateway nodes in clustered architectures and breaks up the dependence between the local medium access schedules of adjacent clusters. The dual-radio feature also enables higher network connectivity, implying, for example, that a higher link redundancy can be achieved.
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| 10. |
- Chaib, Mohamed, et al.
(författare)
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Teacher’s Responsiveness Towards IT-based Learning
- 1997
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper discusses some basic aspects of computer-based education in Sweden. Reporting the results of three ongoing studies conducted at the University of Jšnkšping, the central roles played by the teachers in computer-based education is thoroughly analysed. The studies reported in this paper were all conducted at the comprehensive school level. In the first one, studentsÕ communicative interactions in front of the computer were compared to the interaction occurring in other forms of activities. The second study is concerned with the analysis of how students communicate between themselves when working with different types of software. Finally the third study is related to the analysis of teachersÕ Social representations of information technology in educational settings. In all three studies, we found evidence for the central roles teachers are playing in the process of monitoring communicative interactions in front of the computer. Our discussion will particularly address this aspect of IT-based learning. We furthermore find evidence for teachers ambivalence and confused representations of the computer as a technological teaching device. From these empirical evidence we discuss, in this paper, some possible outcomes for computer based learning in the future. We will particularly pay attention to the necessity of a better understanding and enhancing of teachersÕ preparedness for the roles they are expected to play in this important educational issue.
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