909 research outputs found

    Detecting Large Concept Extensions for Conceptual Analysis

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    When performing a conceptual analysis of a concept, philosophers are interested in all forms of expression of a concept in a text---be it direct or indirect, explicit or implicit. In this paper, we experiment with topic-based methods of automating the detection of concept expressions in order to facilitate philosophical conceptual analysis. We propose six methods based on LDA, and evaluate them on a new corpus of court decision that we had annotated by experts and non-experts. Our results indicate that these methods can yield important improvements over the keyword heuristic, which is often used as a concept detection heuristic in many contexts. While more work remains to be done, this indicates that detecting concepts through topics can serve as a general-purpose method for at least some forms of concept expression that are not captured using naive keyword approaches

    Banks as potentially crooked secret keepers

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    http://kotlikoff.net/articlesAccepted manuscrip

    Combined Diffusion-Relaxometry MRI to Identify Dysfunction in the Human Placenta

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    Purpose: A combined diffusion-relaxometry MR acquisition and analysis pipeline for in-vivo human placenta, which allows for exploration of coupling between T2* and apparent diffusion coefficient (ADC) measurements in a sub 10 minute scan time. Methods: We present a novel acquisition combining a diffusion prepared spin-echo with subsequent gradient echoes. The placentas of 17 pregnant women were scanned in-vivo, including both healthy controls and participants with various pregnancy complications. We estimate the joint T2*-ADC spectra using an inverse Laplace transform. Results: T2*-ADC spectra demonstrate clear quantitative separation between normal and dysfunctional placentas. Conclusions: Combined T2*-diffusivity MRI is promising for assessing fetal and maternal health during pregnancy. The T2*-ADC spectrum potentially provides additional information on tissue microstructure, compared to measuring these two contrasts separately. The presented method is immediately applicable to the study of other organs

    MAPping the Chiral Inversion and Structural Transformation of a Metal-Tripeptide Complex having Ni-SOD Activity

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright Ā© American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic102295s.The metal abstraction peptide (MAP) tag is a tripeptide sequence capable of abstracting a metal ion from a chelator and binding it with extremely high affinity at neutral pH. Initial studies on the nickel-bound form of the complex demonstrate that the tripeptide asparagine-cysteine-cysteine (NCC) binds metal with 2N:2S, square planar geometry and behaves as both a structural and functional mimic of Ni superoxide dismutase (Ni-SOD). Electronic absorption, circular dichroism (CD), and magnetic CD (MCD) data collected for Ni-NCC are consistent with a diamagnetic NiII center. It is apparent from the CD signal of Ni-NCC that the optical activity of the complex changes over time. Mass spectrometry data show that the mass of the complex is unchanged. Combined with the CD data, this suggests that chiral rearrangement of the complex occurs. Following incubation of the nickel-containing peptide in D2O and back-exchange into H2O, incorporation of deuterium into non-exchangeable positions is observed, indicating chiral inversion occurs at two of the alpha carbon atoms in the peptide. Control peptides were used to further characterize the chirality of the final nickel-peptide complex, and DFT calculations were performed to validate the hypothesized position of the chiral inversions. In total, these data indicate Ni-SOD activity is increased proportionally to the degree of structural change in the complex over time, as cross-correlation between the change in CD signal and change in SOD activity reveals a linear relationship

    Controlling the Chiral Inversion Reaction of the Metallopeptide Ni-Asparagine-Cysteine-Cysteine with Dioxygen

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright Ā© American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic301717q.Synthetically generated metallopeptides have the potential to serve a variety of roles in biotechnology applications, but the use of such systems is often hampered by the inability to control secondary reactions. We have previously reported that the NiII complex of the tripeptide LLL-asparagine-cysteine-cysteine, LLL-NiII-NCC, undergoes metal-facilitated chiral inversion to DLD-NiII-NCC, which increases the observed superoxide scavenging activity. However, the mechanism for this process remained unexplored. Electronic absorption and circular dichroism studies of the chiral inversion reaction of NiII-NCC reveal a unique dependence on dioxygen. Specifically, in the absence of dioxygen, the chiral inversion is not observed, even at elevated pH, whereas the addition of O2 initiates this reactivity and concomitantly generates superoxide. Scavenging experiments using acetaldehyde are indicative of the formation of carbanion intermediates, demonstrating that inversion takes place by deprotonation of the alpha carbons of Asn1 and Cys3. Together, these data are consistent with the chiral inversion being dependent on the formation of a NiIII-NCC intermediate from NiII-NCC and O2. The data further suggest that the anionic thiolate and amide ligands in NiII-NCC inhibit CĪ±ā€“H deprotonation for the NiII oxidation state, leading to a stable complex in the absence of O2. Together, these results offer insights into the factors controlling reactivity in synthetic metallopeptides

    Fragmentation and thresholds in hydrological flowā€based ecosystem services

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    Loss and fragmentation of natural land cover due to expansion of agricultural areas is a global issue. These changes alter the configuration and composition of the landscape, particularly affecting those ecosystem services (benefits people receive from ecosystems) that depend on interactions between landscape components. Hydrological mitigation describes the bundle of ecosystem services provided by landscape features such as woodland that interrupt the flow of runoff to rivers. These services include sediment retention, nutrient retention and mitigation of overland water flow. The position of woodland in the landscape and the landscape topography are both important for hydrological mitigation. Therefore, it is crucial to consider landscape configuration and flow pathways in a spatially explicit manner when examining the impacts of fragmentation. Here we test the effects of landscape configuration using a large number (>7,000) of virtual landscape configurations. We created virtual landscapes of woodland patches within grassland, superimposed onto real topography and stream networks. Woodland patches were generated with userā€defined combinations of patch number and total woodland area, placed randomly in the landscape. The Ecosystem Service model used hydrological routing to map the ā€œmitigated areaā€ upslope of each woodland patch. We found that more fragmented woodland mitigated a greater proportion of the catchment. Larger woodland area also increased mitigation, however, this increase was nonlinear, with a threshold at 50% coverage, above which there was a decline in service provision. This nonlinearity suggests that the benefit of any additional woodland depends on two factors: the level of fragmentation and the existing area of woodland. Edge density (total edge of patches divided by area of catchment) was the best single metric in predicting mitigated area. Distance from woodland to stream was not a significant predictor of mitigation, suggesting that agriā€environment schemes planting riparian woodland should consider additional controls such as the amount of fragmentation in the landscape. These findings highlight the potential benefits of fragmentation to hydrological mitigation services. However, benefits for hydrological services must be balanced against any negative effects of fragmentation or habitat loss on biodiversity and other services

    A novel tripeptide model of nickel superoxide dismutase

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright Ā© American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic901828m.Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of superoxide to molecular oxygen and hydrogen peroxide, but the overall reaction mechanism has yet to be determined. Peptide-based models of the 2N:2S nickel coordination sphere of Ni-SOD have provided some insight into the mechanism of this enzyme. Here we show that the coordination sphere of Ni-SOD can be mimicked using the tripeptide asparagine-cysteine-cysteine (NCC). NCC binds nickel with extremely high affinity at physiological pH with 2N:2S geometry, as demonstrated by electronic absorption and circular dichroism (CD) data. Like Ni-SOD, Ni-NCC has mixed amine/amide ligation that favors metal-based oxidation over ligand-based oxidation. Electronic absorption, CD, and magnetic CD data (MCD) collected for Ni-NCC are consistent with a diamagnetic Ni(II) center bound in square planar geometry. Ni-NCC is quasi-reversibly oxidized with a midpoint potential of 0.72(2) V (versus Ag/AgCl) and breaks down superoxide in an enzyme-based assay, supporting its potential use as a model for Ni-SOD chemistry
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