3,999 research outputs found

    In situ epitaxial MgB2 thin films for superconducting electronics

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    A thin film technology compatible with multilayer device fabrication is critical for exploring the potential of the 39-K superconductor magnesium diboride for superconducting electronics. Using a Hybrid Physical-Chemical Vapor Deposition (HPCVD) process, it is shown that the high Mg vapor pressure necessary to keep the MgB2_2 phase thermodynamically stable can be achieved for the {\it in situ} growth of MgB2_2 thin films. The films grow epitaxially on (0001) sapphire and (0001) 4H-SiC substrates and show a bulk-like TcT_c of 39 K, a JcJ_c(4.2K) of 1.2×1071.2 \times 10^7 A/cm2^2 in zero field, and a Hc2(0)H_{c2}(0) of 29.2 T in parallel magnetic field. The surface is smooth with a root-mean-square roughness of 2.5 nm for MgB2_2 films on SiC. This deposition method opens tremendous opportunities for superconducting electronics using MgB2_2

    Automating unobtrusive personalized services in ambient media environments

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-013-1634-2In the age of ambient media, people are surrounded by lots of physical objects (media objects) for rendering the digital world in the natural environment. These media objects should interact with users in a way that is not disturbing for them. To address this issue, this work presents a design and automation strategy for augmenting the world around us with personalized ambient media services that behave in a considerate manner. That is, ambient services are capable of adjusting its obtrusiveness level (i.e., the extent to which each service intrudes the user¿s mind) by using the appropriate media objects for each user¿s situation.This work has been developed with the support of MICINN, under the project EVERYWARE TIN2010-18011, and the support of the Christian Doppler Forschungsgesellschaft and the BMWFJ, Austria.Serral Asensio, E.; Gil Pascual, M.; Valderas Aranda, PJ.; Pelechano Ferragud, V. (2014). Automating unobtrusive personalized services in ambient media environments. Multimedia Tools and Applications. 71(1):159-178. https://doi.org/10.1007/s11042-013-1634-2S159178711Bencomo N, Grace P, Flores-Cortés CA, Hughes D, Blair GS (2008) Genie: supporting the model driven development of reflective, component-based adaptive systems. In: ICSE, pp 811–814Blumendorf M, Lehmann G, Albayrak S (2010) Bridging models and systems at runtime to build adaptive user interfaces. In: Proc. of EICS 2010. ACM, pp 9–18Brown DM (2010) Communicating design: developing web site documentation for design and planning, 2nd edn. New Riders PressCalinescu R (2011) When the requirements for adaptation and high integrity meet. In: Proceedings of the 8th workshop on assurances for self-adaptive systems, ASAS ’11. ACM, New York, pp 1–4Filieri A, Ghezzi C, Tamburrelli G (2011) Run-time efficient probabilistic model checking. In: Proceedings of the 33rd International Conference on Software Engineering, ICSE ’11. ACM, New York, pp 341–350Gershenfeld N, Krikorian R, Cohen D (2004) The internet of things. Sci Am 291(4):46–51Gibbs WW (2005) Considerate computing. Sci Am 292(1):54–61Gulliksen J, Goransson B, Boivie I, Blomkvist S, Persson J, Cajander A (2003) Key principles for user-centred systems design. Behav Inform Technol 22:397–409Hinckley K, Horvitz E (2001) Toward more sensitive mobile phones. In: Proc. of the UIST ’01, pp 191–192Ho J, Intille SS (2005) Using context-aware computing to reduce the perceived burden of interruptions from mobile devices. In: Proc. of CHI ’05. ACM, pp 909–918Horvitz E, Kadie C, Paek T, Hovel D (2003) Models of attention in computing and communication: from principles to applications. Commun ACM 46:52–59Ju W, Leifer L (2008) The design of implicit interactions: making interactive systems less obnoxious. Des Issues 24(3):72–84Kortuem G, Kawsar F, Fitton D, Sundramoorthy V (2010) Smart objects as building blocks for the internet of things. IEEE Internet Comput 14(1):44–51Lewis JR (1995) Ibm computer usability satisfaction questionnaires: psychometric evaluation and instructions for use. Int J Hum Comput Interact 7(1):57–78Lugmayr A, Risse T, Stockleben B, Laurila K, Kaario J (2009) Semantic ambient media—an introduction. Multimed Tools Appl 43(3):337–359Mattern F (2003) From smart devices to smart everyday objects. In: Proc. Smart Objects Conf. (SOC 03). Springer, pp 15–16Morin B, Barais O, Jezequel JM, Fleurey F, Solberg A (2009) Models run.time to support dynamic adaptation. Comput 42(10):44–51Nelson L, Churchill EF (2005) User experience of physical-digital object systems: implications for representation and infrastructure. Paper presented at smart object systems workshop, in cojunction with ubicomp 2005Paternò F (2002) Concurtasktrees: an engineered approach to model-based design of interactive systems. In: L.E. Associates (ed) The handbook of analysis for human-computer interaction, pp 483–500Paternò F (2003) From model-based to natural development. HCI International, pp 592–596Ramchurn SD, Deitch B, Thompson MK, Roure DCD, Jennings NR, Luck M (2004) Minimising intrusiveness in pervasive computing environments using multi-agent negotiation. MobiQuitous ’04, pp 364–372Runeson P, Höst M (2009) Guidelines for conducting and reporting case study research in software engineering. Empir Softw Eng 14(2):131–164Schmidt A (2000) Implicit human computer interaction through context. Pers Technol 4(2–3):191–199Serral E, Valderas P, Pelechano V (2010) Supporting runtime system evolution to adapt to user behaviour. In: Proc. of CAiSE’10, pp 378–392Serral E, Valderas P, Pelechano V (2010) Towards the model driven development of context-aware pervasive systems. PMC 6(2):254–280Siegemund F (2004) A context-aware communication platform for smart objects. In: Proc of the int conf on pervasive computing. Springer, pp 69–86Streitz NA, Rocker C, Prante T, Alphen Dv, Stenzel R, Magerkurth C (2005) Designing smart artifacts for smart environments. Comput 38(3):41–49. doi: 10.1109/MC.2005.92Thiesse F, Kohler M (2008) An analysis of usage-based pricing policies for smart products. Electron Mark 18(3):232–241. doi: 10.1080/10196780802265751Vastenburg MH, Keyson DV, de Ridder H (2008) Considerate home notification systems: a field study of acceptability of notifications in the home. Pers Ubiquit Comput 12(8):555–56

    Nucleocytoplasmic transport: a thermodynamic mechanism

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    The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

    Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria

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    <p>Abstract</p> <p>Background</p> <p>Two criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes.</p> <p>Methods</p> <p>We searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I<sup>2</sup>) > 50%.</p> <p>Results</p> <p>Data were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I<sup>2 </sup>≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO.</p> <p>Conclusions</p> <p>The WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.</p

    Dinosaur peptides suggest mechanisms of protein survival

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    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival

    The Immune System Strikes Back: Cellular Immune Responses against Indoleamine 2,3-dioxygenase

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    The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses.The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations.IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general

    Evolutionary and pulsational properties of white dwarf stars

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    Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

    Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage

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    SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways

    Human Polycomb 2 Protein Is a SUMO E3 Ligase and Alleviates Substrate-Induced Inhibition of Cystathionine β-Synthase Sumoylation

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    Human cystathionine β-synthase (CBS) catalyzes the first irreversible step in the transsulfuration pathway and commits homocysteine to the synthesis of cysteine. Mutations in CBS are the most common cause of severe hereditary hyperhomocysteinemia. A yeast two-hybrid approach to screen for proteins that interact with CBS had previously identified several components of the sumoylation pathway and resulted in the demonstration that CBS is a substrate for sumoylation. In this study, we demonstrate that sumoylation of CBS is enhanced in the presence of human polycomb group protein 2 (hPc2), an interacting partner that was identified in the initial yeast two-hybrid screen. When the substrates for CBS, homocysteine and serine for cystathionine generation and homocysteine and cysteine for H2S generation, are added to the sumoylation mixture, they inhibit the sumoylation reaction, but only in the absence of hPc2. Similarly, the product of the CBS reaction, cystathionine, inhibits sumoylation in the absence of hPc2. Sumoylation in turn decreases CBS activity by ∼28% in the absence of hPc2 and by 70% in its presence. Based on these results, we conclude that hPc2 serves as a SUMO E3 ligase for CBS, increasing the efficiency of sumoylation. We also demonstrate that γ-cystathionase, the second enzyme in the transsulfuration pathway is a substrate for sumoylation under in vitro conditions. We speculate that the role of this modification may be for nuclear localization of the cysteine-generating pathway under conditions where nuclear glutathione demand is high
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