847 resultados para variable aggregation
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A social Semantic Web empowers its users to have access to collective Web knowledge in a simple manner, and for that reason, controlling online privacy and reputation becomes increasingly important, and must be taken seriously. This chapter presents Fuzzy Cognitive Maps (FCM) as a vehicle for Web knowledge aggregation, representation, and reasoning. With this in mind, a conceptual framework for Web knowledge aggregation, representation, and reasoning is introduced along with a use case, in which the importance of investigative searching for online privacy and reputation is highlighted. Thereby it is demonstrated how a user can establish a positive online presence.
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[1] In the event of a termination of the Gravity Recovery and Climate Experiment (GRACE) mission before the launch of GRACE Follow-On (due for launch in 2017), high-low satellite-to-satellite tracking (hl-SST) will be the only dedicated observing system with global coverage available to measure the time-variable gravity field (TVG) on a monthly or even shorter time scale. Until recently, hl-SST TVG observations were of poor quality and hardly improved the performance of Satellite Laser Ranging observations. To date, they have been of only very limited usefulness to geophysical or environmental investigations. In this paper, we apply a thorough reprocessing strategy and a dedicated Kalman filter to Challenging Minisatellite Payload (CHAMP) data to demonstrate that it is possible to derive the very long-wavelength TVG features down to spatial scales of approximately 2000 km at the annual frequency and for multi-year trends. The results are validated against GRACE data and surface height changes from long-term GPS ground stations in Greenland. We find that the quality of the CHAMP solutions is sufficient to derive long-term trends and annual amplitudes of mass change over Greenland. We conclude that hl-SST is a viable source of information for TVG and can serve to some extent to bridge a possible gap between the end-of-life of GRACE and the availability of GRACE Follow-On.
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Alzheimer's disease (AD) is characterized by the cerebral accumulation of misfolded and aggregated amyloid-beta protein (Abeta). Disease symptoms can be alleviated, in vitro and in vivo, by 'beta-sheet breaker' pentapeptides that reduce plaque load. However the peptide nature of these compounds, made them biologically unstable and unable to penetrate membranes with high efficiency. The main goal of this study was to use computational methods to identify small molecule mimetics with better drug-like properties. For this purpose, the docked conformations of the active peptides were used to identify compounds with similar activities. A series of related beta-sheet breaker peptides were docked to solid state NMR structures of a fibrillar form of Abeta. The lowest energy conformations of the active peptides were used to design three dimensional (3D)-pharmacophores, suitable for screening the NCI database with Unity. Small molecular weight compounds with physicochemical features and a conformation similar to the active peptides were selected, ranked by docking and biochemical parameters. Of 16 diverse compounds selected for experimental screening, 2 prevented and reversed Abeta aggregation at 2-3microM concentration, as measured by Thioflavin T (ThT) fluorescence and ELISA assays. They also prevented the toxic effects of aggregated Abeta on neuroblastoma cells. Their low molecular weight and aqueous solubility makes them promising lead compounds for treating AD.
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The Lyme disease agent Borrelia burgdorferi can persistently infect humans and other animals despite host active immune responses. This is facilitated, in part, by the vls locus, a complex system consisting of the vlsE expression site and an adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes recombine with the vlsE region during infection of mammalian hosts, resulting in combinatorial antigenic variation of the VlsE outer surface protein. We now demonstrate that synthesis of VlsE is regulated during the natural mammal-tick infectious cycle, being activated in mammals but repressed during tick colonization. Examination of cultured B. burgdorferi cells indicated that the spirochete controls vlsE transcription levels in response to environmental cues. Analysis of PvlsE::gfp fusions in B. burgdorferi indicated that VlsE production is controlled at the level of transcriptional initiation, and regions of 5' DNA involved in the regulation were identified. Electrophoretic mobility shift assays detected qualitative and quantitative changes in patterns of protein-DNA complexes formed between the vlsE promoter and cytoplasmic proteins, suggesting the involvement of DNA-binding proteins in the regulation of vlsE, with at least one protein acting as a transcriptional activator.
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An exact knowledge of the kinetic nature of the interaction between the stimulatory G protein (G$\sb{\rm s}$) and the adenylyl cyclase catalytic unit (C) is essential for interpreting the effects of Gs mutations and expression levels on cellular response to a wide variety of hormones, drugs, and neurotransmitters. In particular, insight as to the association of these proteins could lead to progress in tumor biology where single spontaneous mutations in G proteins have been associated with the formation of tumors (118). The question this work attempts to answer is whether the adenylyl cyclase activation by epinephrine stimulated $\beta\sb2$-adrenergic receptors occurs via G$\sb{\rm s}$ proteins by a G$\sb{\rm s}$ to C shuttle or G$\sb{\rm s}$-C precoupled mechanism. The two forms of activation are distinguishable by the effect of G$\sb{\rm s}$ levels on epinephrine stimulated EC50 values for cyclase activation.^ We have made stable transfectants of S49 cyc$\sp-$ cells with the gene for the $\alpha$ protein of G$\sb{\rm s}$ $(\alpha\sb{\rm s})$ which is under the control of the mouse mammary tumor virus LTR promoter (110). Expression of G$\sb{\rm s}\alpha$ was then controlled by incubation of the cells for various times with 5 $\mu$M dexamethasone. Expression of G$\sb{\rm s}\alpha$ led to the appearance of GTP shifts in the competitive binding of epinephrine with $\sp{125}$ICYP to the $\beta$-adrenergic receptors and to agonist dependent adenylyl cyclase activity. High expression of G$\sb{\rm s}\alpha$ resulted in lower EC50's for the adenylyl cyclase activity in response to epinephrine than did low expression. By kinetic modelling, this result is consistent with the existence of a shuttle mechanism for adenylyl cyclase activation by hormones.^ One item of concern that remains to be addressed is the extent to which activation of adenylyl cyclase occurs by a "pure" shuttle mechanism. Kinetic and biochemical experiments by other investigators have revealed that adenylyl cyclase activation, by hormones, may occur via a Gs-C precoupled mechanism (80, 94, 97). Activation of adenylyl cyclase, therefore, probably does not occur by either a pure "'Shuttle" or "Gs-C Precoupled" mechanism, but rather by a "Hybrid" mechanism. The extent to which either the shuttle or precoupled mechanism contributes to hormone stimulated adenylyl cyclase activity is the subject of on-going research. ^
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Prostate cancer (PC) is a significant economic and health burden in the U.S. and Europe but its causes are largely unknown. The most significant risk factors (after gender) are age and family history of the disease. A gene with high penetrance but low frequency on chromosome 1q, HPC 1, has been suggested to cause a proportion of the familial aggregation of PC but other more common genes, conferring less risk, are also thought to contribute to disease predisposition. We have pursued a strategy to study both types of genetic risk in PC. To identify high penetrance genes, affected men from thirteen families have been genotyped for genetic linkage analysis at six microsatellite markers spanning 45 cM of 1q24-25. Both LOD score and non-parametric statistics provide no significant support for HPC1 in this genomic region, although 3 of the families did combine to produce a LOD score of 0.9. These families will be included in a genome wide search for other PC predisposition genes as part of a multinational collaboration.^ For study of common genetic factors in PC development, leukocyte DNA samples from an unselected series of 55 patients and 67 controls have been examined for genetic differences in two other candidate genes, the androgen receptor gene, hAR, at Xq11-12, and the vitamin D receptor gene, hVDR, at 12q12-14. hAR was typed for two trinucleotide repeat length polymorphisms, (CAG)$\rm\sb{n}$ and (GGC)$\rm\sb{n},$ encoding polyglutamine and polyglycine tracts, respectively, which have been implicated in PC susceptibility. These data, combined with similarly processed patients and controls from the U.K. show no consistent association of allele length with PC risk. A novel finding, however, has been a significant association between the number of GGC repeats and the length of time between diagnosis and relapse in stage T1-T4 Caucasian patients irrespective of therapy and age of the patient. Of 49 patients who relapsed out of 108 entering the study, those with 16 or fewer GGC repeats had an average relapse-free-period of 101 (+/$-$7.7) months while for those with more than 16 repeats the period averaged 48 (+/$-$2.9) months, a difference of 2.1 fold or 4.4 years.^ The second gene, hVDR, was genotyped at two polymorphisms, a synonymous C/T substitution in exon 9 identified by differential TaqI enzymatic digestion and a variable length polyA tract in the 3$\sp\prime$ UTR. Although these polymorphisms are in strong linkage disequilibrium only the polyA region showed a possible association with PC risk. Men homozygous for alleles with fewer than 18 A's had an increased risk (OR = 3.0, p = 0.0578) compared to controls. This result is opposite to the findings of others and may either indicate off-setting random errors which together balance out to no significant overall effect or reflect more complex genetic and/or environmental associations.^ Overall, this research suggests that single gene familial predisposition may be less prominent in PC than in other cancers and that the characteristics of PC pathology may be useful in identifying the effects of common genetic factors. ^
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Evidence suggests a strong relation between superior motor performance and the duration of the last fixation before movement initiation (called Quiet Eye, QE). Although this phenomenon proves to be quite robust, to date, only little is known about its functional role. Therefore, in two experiments, a novel paradigm is introduced, testing the QE as independent variable by experimentally manipulating the duration of the last fixation in a throwing task. In addition, this paradigm allowed for the manipulation of the predictability of the target position. Results of the first study revealed an increase in throwing accuracy as function of experimentally prolonged QE durations. Thus, the assumption that the QE does not surface as a mere by-product of superior performance could be confirmed. In the second study, this dependency was found only under high task-demand conditions in which the target position was not predictable. This finding confirms the hypothesis that it is the optimization of information processing which serves as the crucial mechanisms behind QE effects.
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Calving has been studied for glaciers ranging from slow polar glaciers that calve on dry land, such as on Deception Island (63.0-degrees-S, 60.6-degrees-W) in Antarctica, through temperate Alaskan tide-water glaciers, to fast outlet glaciers that float in fiords and calve in deep water, such as Jakobshavns Isbrae (69.2-degrees-N, 49.9-degrees-W) in Greenland. Calving from grounded ice walls and floating ice shelves is the main ablation mechanism for the Antarctic and Greenland ice sheets, as it was along marine and lacustrine margins of former Pleistocene ice sheets, and is for tide-water and polar glaciers. Yet, the theory of ice calving is underdeveloped because of inherent dangers in obtaining field data to test and constrain calving models. An attempt is made to develop a calving theory for ice walls grounded in water of variable depth, and to relate slab calving from ice walls to tabular calving from ice shelves. A calving law is derived in which calving rates from ice walls are controled by bending creep behind the ice wall, and depend on wall height h, forward bending angle-theta, crevasse distance c behind the ice wall and depth d of water in front of the ice wall. Reasonable agreement with calving rates reported by Brown and others (1982) for Alaskan tide-water glaciers is obtained when c depends on wall height, wall height above water and water depth. More data are needed to determine which of these dependencies is correct. A calving ratio c/h is introduced to understand the transition from slab calving to tabular calving as water deepens and the calving glacier becomes afloat.
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The widespread deployment of wireless mobile communications enables an almost permanent usage of portable devices, which imposes high demands on the battery of these devices. Indeed, battery lifetime is becoming one the most critical factors on the end-users satisfaction when using wireless communications. In this work, the optimized power save algorithm for continuous media applications (OPAMA) is proposed, aiming at enhancing the energy efficiency on end-users devices. By combining the application specific requirements with data aggregation techniques, {OPAMA} improves the standard {IEEE} 802.11 legacy Power Save Mode (PSM) performance. The algorithm uses the feedback on the end-user expected quality to establish a proper tradeoff between energy consumption and application performance. {OPAMA} was assessed in the OMNeT++ simulator, using real traces of variable bitrate video streaming applications, and in a real testbed employing a novel methodology intended to perform an accurate evaluation concerning video Quality of Experience (QoE) perceived by the end-users. The results revealed the {OPAMA} capability to enhance energy efficiency without degrading the end-user observed QoE, achieving savings up to 44 when compared with the {IEEE} 802.11 legacy PSM.
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Thigmomorphogenesis, the characteristic phenotypic changes by which plants react to mechanical stress, is a widespread and probably adaptive type of phenotypic plasticity. However, little is known about its genetic basis and population variation. Here, we examine genetic variation for thigmomorphogenesis within and among natural populations of the model system Arabidopsis thaliana. Offspring from 17 field-collected European populations was subjected to three levels of mechanical stress exerted by wind. Overall, plants were remarkably tolerant to mechanical stress. Even high wind speed did not significantly alter the correlation structure among phenotypic traits. However, wind significantly affected plant growth and phenology, and there was genetic variation for some aspects of plasticity to wind among A. thaliana populations. Our most interesting finding was that phenotypic traits were organized into three distinct and to a large degree statistically independent covariance modules associated with plant size, phenology, and growth form, respectively. These phenotypic modules differed in their responsiveness to wind, in the degree of genetic variability for plasticity, and in the extent to which plasticity affected fitness. It is likely, therefore, that thigmomorphogenesis in this species evolves quasi-independently in different phenotypic modules.
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Both theoretically and empirically there is a continuous interest in understanding the specific relation between cognitive and motor development in childhood. In the present longitudinal study including three measurement points, this relation was targeted. At the beginning of the study, the participating children were 5-6-year-olds. By assessing participants' fine motor skills, their executive functioning, and their non-verbal intelligence, their cross-sectional and cross-lagged interrelations were examined. Additionally, performance in these three areas was used to predict early school achievement (in terms of mathematics, reading, and spelling) at the end of participants' first grade. Correlational analyses and structural equation modeling revealed that fine motor skills, non-verbal intelligence and executive functioning were significantly interrelated. Both fine motor skills and intelligence had significant links to later school achievement. However, when executive functioning was additionally included into the prediction of early academic achievement, fine motor skills and non-verbal intelligence were no longer significantly associated with later school performance suggesting that executive functioning plays an important role for the motor-cognitive performance link.
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Two factors that have been suggested as key in explaining individual differences in fluid intelligence are working memory and sensory discrimination ability. A latent variable approach was used to explore the relative contributions of these two variables to individual differences in fluid intelligence in middle to late childhood. A sample of 263 children aged 7–12 years was examined. Correlational analyses showed that general discrimination ability (GDA)and working memory (WM) were related to each other and to fluid intelligence. Structural equation modeling showed that within both younger and older age groups and the sample as a whole, the relation between GDA and fluid intelligence could be accounted for by WM. While WM was able to predict variance in fluid intelligence above and beyond GDA, GDA was not able to explain significant amounts of variance in fluid intelligence, either in the whole sample or within the younger or older age group. We concluded that compared to GDA, WM should be considered the better predictor of individual differences in fluid intelligence in childhood. WM and fluid intelligence, while not being separable in middle childhood, develop at different rates, becoming more separable with age.
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von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways.