1,142 research outputs found

    Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of G oα

    Full text link
    We examined the hypothesis that decreased inhibitory G protein function in diabetic neuropathy is associated with increased protein kinase C (PKC)-dependent phosphorylation of the G oα subunit. Streptozotocin-induced diabetic rats were studied between 4 and 8 weeks after onset of diabetes and compared with aged-matched healthy animals as controls. Opioid-mediated inhibition of forskolin-stimulated cyclic AMP was significantly less in dorsal root ganglia (DRGs) from diabetic rats compared with controls. Activation of PKC in DRGs from control rats was associated with a significant decrease in opioid-mediated inhibition of forskolin-stimulated cyclic AMP that was similar to the decrease in inhibition observed in DRGs from diabetic rats. Both basal and PKC-mediated labeling of G oα with 32 P i was significantly less in DRGs from diabetic rats, supporting increased endogenous PKC-dependent phosphorylation of G oα . Probing of immunoprecipitated G oα with an anti-phospho-serine/threonine specific antibody revealed a significant increase in baseline phosphorylation in diabetic DRGs. Activation of PKC produced a significant increase in phosphorylation in control DRGs but no significant increase in G oα in diabetic DRGs. Phosphorylation of PKC-α was increased, PKC-β II was unchanged and PKC-δ decreased in diabetic DRGs. These results suggest that diminished inhibitory G protein function observed in DRGs neurons from diabetic rats involves an isoform-specific PKC-dependent pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66385/1/j.1471-4159.2003.01912.x.pd

    Conversion of Legal Agreements into Smart Legal Contracts using NLP

    Get PDF
    A Smart Legal Contract (SLC) is a specialized digital agreement comprising natural language and computable components. The Accord Project provides an open-source SLC framework containing three main modules: Cicero, Concerto, and Ergo. Currently, we need lawyers, programmers, and clients to work together with great effort to create a usable SLC using the Accord Project. This paper proposes a pipeline to automate the SLC creation process with several Natural Language Processing (NLP) models to convert law contracts to the Accord Project's Concerto model. After evaluating the proposed pipeline, we discovered that our NER pipeline accurately detects CiceroMark from Accord Project template text with an accuracy of 0.8. Additionally, our Question Answering method can extract one-third of the Concerto variables from the template text. We also delve into some limitations and possible future research for the proposed pipeline. Finally, we describe a web interface enabling users to build SLCs. This interface leverages the proposed pipeline to convert text documents to Smart Legal Contracts by using NLP models

    Variability of temperature and ozone in the upper troposphere and lower stratosphere from multi-satellite observations and reanalysis data

    Get PDF
    Temperature and ozone changes in the upper troposphere and lower stratosphere (UTLS) are important components of climate change. In this paper, variability and trends of temperature and ozone in the UTLS are investigated for the period 2002–2017 using high-quality, high vertical resolution Global Navigation Satellite System radio occultation (GNSS RO) data and improved merged satellite data sets. As part of the Stratosphere-troposphere Processes And their Role in Climate (SPARC) Reanalysis Intercomparison Project (S-RIP), three reanalysis data sets, including the ERA-I, MERRA2 and the recently released ERA5, are evaluated for their representation of temperature and ozone in the UTLS. The recent temperature and ozone trends are updated with a multiple linear regression (MLR) method and related to sea surface temperature (SST) changes based on model simulations made with NCAR's Whole Atmosphere Community Climate Model (WACCM). All reanalysis temperatures show good agreement with the GNSS RO measurements in both absolute value and annual cycle. Interannual variations in temperature related to Quasi-Biennial Oscillation (QBO) and the El Niño–Southern Oscillation (ENSO) processes are well represented by all reanalyses. However, evident biases can be seen in reanalyses for the linear trends of temperature since they are affected by discontinuities in assimilated observations and methods. Such biases can be corrected and the estimated trends can be significantly improved. ERA5 is significantly improved compared to ERA-I and shows the best agreement with the GNSS RO temperature. The MLR results indicate a significant warming of 0.2–0.3&thinsp;K per decade in most areas of the troposphere, with a stronger increase of 0.4–0.5&thinsp;K per decade at midlatitudes of both hemispheres. In contrast, the stratospheric temperature decreases at a rate of 0.1–0.3&thinsp;K per decade, which is most significant in the Southern Hemisphere (SH). Positive temperature trends of 0.1–0.3&thinsp;K per decade are seen in the tropical lower stratosphere (100–50&thinsp;hPa). Negative trends of ozone are found in the Northern Hemisphere (NH) at 150–50&thinsp;hPa, while positive trends are evident in the tropical lower stratosphere. Asymmetric trends of ozone can be found in the midlatitudes of two hemispheres in the middle stratosphere, with significant ozone decrease in the NH and increase in ozone in the SH. Large biases exist in reanalyses, and it is still challenging to do trend analysis based on reanalysis ozone data. According to single-factor-controlled model simulations with WACCM, the temperature increase in the troposphere and the ozone decrease in the NH stratosphere are mainly connected to the increase in SST and subsequent changes of atmospheric circulations. Both the increase in SSTs and the decrease in ozone in the NH contribute to the temperature decrease in the NH stratosphere. The increase in temperature in the lower stratospheric tropics may be related to an increase in ozone in that region, while warming SSTs contribute to a cooling in that area.</p

    Transport through a quantum wire with a side quantum-dot array

    Get PDF
    A noninteracting quantum-dot array side-coupled to a quantum wire is studied. Transport through the quantum wire is investigated by using a noninteracting Anderson tunneling Hamiltonian. The conductance at zero temperature develops an oscillating band with resonances and antiresonances due to constructive and destructive interference in the ballistic channel, respectively. Moreover, we have found an odd-even parity in the system, whose conductance vanishes for an odd number of quantum dots while becomes 2e2/h2e^2/h for an even number. We established an explicit relation between this odd-even parity, and the positions of the resonances and antiresonances of the conductivity with the spectrum of the isolated QD arrayComment: 5 pages, 4 figures, submitted to PR

    Transcatheter Intraarterial Perfusion MRI Approaches to Differentiate Reversibly Electroporated Penumbra From Irreversibly Electroporated Zones in Rabbit Liver

    Get PDF
    RATIONALE AND OBJECTIVES: To investigate whether transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) can differentiate reversible electroporation (RE) zones from irreversible electroporation (IRE) zones immediately after IRE procedure in the rabbit liver. MATERIALS AND METHODS: All studies were approved by the institutional animal care and use committee and performed in accordance with institutional guidelines. A total of 13 healthy New Zealand White rabbits were used. After selective catheterization of the hepatic artery under X-ray fluoroscopy, we acquired TRIP-MRI at 20 minutes post-IRE using 3 mL of 5% intraarterial gadopentetate dimeglumine. Semi-quantitative (peak enhancement, PE; time to peak, TTP; wash-in slope, WIS; areas under the time-intensity curve, AUT, over 30, 60, 90, 120, 150, and 180 seconds after the initiation of enhancement) and quantitative (Ktrans, ve, and vp) TRIP-MRI parameters were calculated. The relationships between TRIP-MRI parameters and histological measurements and the differential ability of TRIP-MRI parameters was assessed. RESULTS: PE, AUT60, AUT90, AUT120, AUT150, AUT180, Ktrans, and ve were significantly higher in RE zones than in IRE zones (all P < 0.05), and AUC for these parameters ranged from 0.91(95% CI, 0.80, 1.00) to 0.99 (95% CI, 0.98, 1.00). There was no significant difference in AUC between any two parameters (Z, 0-1.47; P, 0.14-1.00). Hepatocyte apoptosis strongly correlated with PE, AUT60, AUT90, AUT120, AUT150, AUT180, Ktrans, and vp (the absolute value r, 0.6-0.7, all P < 0.0001). CONCLUSION: AUT150 or AUT180 could be a potential imaging biomarker to differentiate RE from IRE zones, and TRIP-MRI permits to differentiate RE from IRE zones immediately after IRE procedure in the rabbit liver

    A Global Community of Courts? Modelling the Use of Persuasive Authority as a Complex Network

    Get PDF
    There is a growing discussion in the legal literature of an emerging global community of courts composed of a network of increasing judicial dialogue across national borders. We investigate the use of foreign persuasive authority in common law countries by analyzing the network of citations to case law in a corpus of over 1.5 million judgments given by the senior courts of twenty-six common law countries. Our corpus of judgments is derived from data available in the vLex Justis database. In this paper we aim to quantify the flow of jurisprudence across the countries in our corpus and to explore the factors that may influence a judge’s selection of foreign jurisprudence. Utilization of foreign case law varies across the countries in our data, with the courts of some countries presenting higher engagement with foreign jurisprudence than others. Our analysis shows that there has been an upward trend in the use of foreign case law over time, with a marked increase in citations across national borders from the 1990s onward, potentially indicating that increased digital access to foreign judgments has served to facilitate and promote comparative analysis. Not only has the use of foreign case law generally increased over time, the factors that may influence the selection of case law have also evolved, with judges gradually casting their research beyond the most influential and well-known foreign authorities. Notwithstanding that judgments emanating from the United Kingdom (chiefly from the courts of England and Wales) constitute the most frequently consulted body of jurisprudence, we find evidence that domestic courts favor citing the case law of countries that are geographically proximal
    corecore