329 research outputs found

    A large scale system for searching and browsing images from the World Wide Web

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    This paper outlines the technical details of a prototype system for searching and browsing over a million images from the World Wide Web using their visual contents. The system relies on two modalities for accessing images — automated image annotation and NNk image network browsing. The user supplies the initial query in the form of one or more keywords and is then able to locate the desired images more precisely using a browsing interface

    NN<sup>k</sup> networks for Content-Based Image Retrieval

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    This paper describes a novel interaction technique to support content-based image search in large image collections. The idea is to represent each image as a vertex in a directed graph. Given a set of image features, an arc is established between two images if there exists at least one combination of features for which one image is retrieved as the nearest neighbour of the other. Each arc is weighted by the proportion of feature combinations for which the nearest neighbour relationship holds. By thus integrating the retrieval results over all possible feature combinations, the resulting network helps expose the semantic richness of images and thus provides an elegant solution to the problem of feature weighting in content-based image retrieval.We give details of the method used for network generation and describe the ways a user can interact with the structure. We also provide an analysis of the network’s topology and provide quantitative evidence for the usefulness of the technique

    FLT3 mutations in Early T-Cell Precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors

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    Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup

    Differential effects of familial Alzheimer’s disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity

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    The amyloid precursor protein (APP) is a key player in Alzheimer`s disease (AD) and the precursor of the Aβ peptide, which is generated by consecutive cleavages of β- and γ-secretases. Familial Alzheimer’s disease (FAD) describes a hereditary subgroup of AD that represents a low percentage of AD cases with an early onset of the disease. Different APP FAD mutations are thought to have qualitatively different effects on its proteolytic conversion. However, few studies have explored the pathogenic and putative physiological differences in more detail. Here, we compared different FAD mutations, located at the β- (Swedish), α- (Flemish, Arctic, Iowa) or γ-secretase (Iberian) cleavage sites. We examined heterologous expression of APP WT and FAD mutants in non-neuronal cells and their impact on presynaptic differentiation in contacting axons of co-cultured neurons. To decipher the underlying molecular mechanism, we tested the subcellular localization, the endocytosis rate and the proteolytic processing in detail by immunoprecipitation–mass spectrometry. Interestingly, we found that only the Iberian mutation showed altered synaptogenic function. Furthermore, the APP Iowa mutant shows significantly decreased α-secretase processing which is in line with our results that APP carrying the Iowa mutation was significantly increased in early endosomes. However, most interestingly, immunoprecipitation–mass spectrometry analysis revealed that the amino acid substitutions of APP FAD mutants have a decisive impact on their processing reflected in altered Aβ profiles. Importantly, N-terminally truncated Aβ peptides starting at position 5 were detected preferentially for APP Flemish, Arctic, and Iowa mutants containing amino acid substitutions around the α-secretase cleavage site. The strongest change in the ratio of Aβ40/Aβ42 was observed for the Iberian mutation while APP Swedish showed a substantial increase in Aβ1–17 peptides. Together, our data indicate that familial AD mutations located at the α-, β-, and γ-secretase cleavage sites show considerable differences in the underlying pathogenic mechanisms

    Особенности процесса трещинообразования в массиве при управлении его газодинамикой

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    Исследован процесс сдерживания перехода угля из потенциально устойчивого состояния в стадию бурного разрушения. Ей, как правило, предшествует некоторый промежуток времени относительного затишья. Особенно важно улавливать этот момент среди массы различных откликов массива на ведение горных работ. Одним из вариантов управления развитием и релаксацией системы трещин может служить физико-химическая обработка.The inhibition process of coal transition from the potentially stable state in the stage of stormy destruction is investigation. As a rule, to it is preceded some interval of relative time calm. It is especially important to catch this moment among mass of different responses of array on the conduct of mountain works. Physical and chemical treatment can serve as one of control variants the development and relaxation of the cracks system

    Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: A randomized, double-blind, placebo-controlled study

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    AbstractObjectives. This study examined the of metoprolol on left ventricular performance, efficiency, neurohormonal activation and myocardial respiratory quotient in patients with dilated cardiomyopathy.Background.The mechanism by which beta-adrenergie blockade improves ejection fraction in patients with dilated cardiomyopathy remains an enigma. Thus, we undertook an extensive hemodynamic evaluation of this mechanism. In addition, because animal models have shown that catecholamine exposure may increase relative fatty acid utilization, we hypothesized that antagonism of sympathetic stimulation may result in increased carbohydrate utilization.Methods. This was a randomized, double-blind, prospective trial in which 24 men with nonischemic dilated cardiomyopathy underwent cardiac catheterization before and after 3 months of therapy with metoprolol (n = 15) or placebo (n = 9) in addition to standard therapy. Pressure-volume relations were examined using a micromanometer catheter and digital ventriculography.Results. At baseline, the placebo-treated patients had somewhat more advanced left ventricular dysfunction. Ejection fraction and left ventricular performance improved only in the metoprolol-treated patients. Stroke and minute work increased without an increase in myocardial oxgen consumption, suggesting increased myocardial efficiency. Further increases in ejection fraction were seen between 3 and 6 months in the metoprolol group. The placebo group had a significant increase in ejection fraction only after crossover to metoprolol. A significant relation the change in coronary sinus norepinephrine and myocardial respiratory quotient was seen, suggesting a possible effect of adrenergic deactivation on substrate utilization.Conclusions. These data demonstrate that in patients with cardiomyopthy, metoprolol treatment improves myocardial performance and energetics, and favorably alters substrate utilization. Beta-adrenergic blocking agents, such as metoprolol, are hemodynamically and energetically beneficial in the treatment of myocardial failure

    Hamiltonian submanifolds of regular polytopes

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    We investigate polyhedral 2k2k-manifolds as subcomplexes of the boundary complex of a regular polytope. We call such a subcomplex {\it kk-Hamiltonian} if it contains the full kk-skeleton of the polytope. Since the case of the cube is well known and since the case of a simplex was also previously studied (these are so-called {\it super-neighborly triangulations}) we focus on the case of the cross polytope and the sporadic regular 4-polytopes. By our results the existence of 1-Hamiltonian surfaces is now decided for all regular polytopes. Furthermore we investigate 2-Hamiltonian 4-manifolds in the dd-dimensional cross polytope. These are the "regular cases" satisfying equality in Sparla's inequality. In particular, we present a new example with 16 vertices which is highly symmetric with an automorphism group of order 128. Topologically it is homeomorphic to a connected sum of 7 copies of S2×S2S^2 \times S^2. By this example all regular cases of nn vertices with n<20n < 20 or, equivalently, all cases of regular dd-polytopes with d9d\leq 9 are now decided.Comment: 26 pages, 4 figure

    Probing photo-ionization: simulations of positive streamers in varying N2:O2 mixtures

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    Photo-ionization is the accepted mechanism for the propagation of positive streamers in air though the parameters are not very well known; the efficiency of this mechanism largely depends on the presence of both nitrogen and oxygen. But experiments show that streamer propagation is amazingly robust against changes of the gas composition; even for pure nitrogen with impurity levels below 1 ppm streamers propagate essentially with the same velocity as in air, but their minimal diameter is smaller, and they branch more frequently. Additionally, they move more in a zigzag fashion and sometimes exhibit a feathery structure. In our simulations, we test the relative importance of photo-ionization and of the background ionization from pulsed repetitive discharges, in air as well as in nitrogen with 1 ppm O2 . We also test reasonable parameter changes of the photo-ionization model. We find that photo- ionization dominates streamer propagation in air for repetition frequencies of at least 1 kHz, while in nitrogen with 1 ppm O2 the effect of the repetition frequency has to be included above 1 Hz. Finally, we explain the feather-like structures around streamer channels that are observed in experiments in nitrogen with high purity, but not in air.Comment: 12 figure

    Probing photo-ionization: Experiments on positive streamers in pure gasses and mixtures

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    Positive streamers are thought to propagate by photo-ionization whose parameters depend on the nitrogen:oxygen ratio. Therefore we study streamers in nitrogen with 20%, 0.2% and 0.01% oxygen and in pure nitrogen, as well as in pure oxygen and argon. Our new experimental set-up guarantees contamination of the pure gases to be well below 1 ppm. Streamers in oxygen are difficult to measure as they emit considerably less light in the sensitivity range of our fast ICCD camera than the other gasses. Streamers in pure nitrogen and in all nitrogen/oxygen mixtures look generally similar, but become somewhat thinner and branch more with decreasing oxygen content. In pure nitrogen the streamers can branch so much that they resemble feathers. This feature is even more pronounced in pure argon, with approximately 10^2 hair tips/cm^3 in the feathers at 200 mbar; this density could be interpreted as the free electron density creating avalanches towards the streamer stem. It is remarkable that the streamer velocity is essentially the same for similar voltage and pressure in all nitrogen/oxygen mixtures as well as in pure nitrogen, while the oxygen concentration and therefore the photo-ionization lengths vary by more than five orders of magnitude. Streamers in argon have essentially the same velocity as well. The physical similarity of streamers at different pressures is confirmed in all gases; the minimal diameters are smaller than in earlier measurements.Comment: 28 pages, 14 figures. Major differences with v1: - appendix and spectra removed - subsection regarding effects of repetition frequency added - many more smaller change
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