Proteomics reveals acute pro-inflammatory and protective responses in rat Kupffer cells and hepatocytes after chemical initiation of liver cancer and after LPS and IL-6

Inflammation is a key event in the development of liver cancer. We studied early inflammatory responses of Kupffer cells (KCs) and hepatocyte (HC) after cancer initiation. The chemical carcinogen N-nitrosomorpholine (NNM) was used in a rat model. We applied a comprehensive analytical strategy including metabolic labeling, 2-D PAGE, LC-MS/MS-based spot identification and shotgun proteomics and thus determined the rates of synthesis of individual proteins, compared whole tissue with isolated constituent cells and performed in vivo to in vitro comparisons of NNM effects. NNM increased synthesis of overall and 138 individual proteins identified in HC and/or KC, indicating reprogramming of metabolism favoring protection, repair and replacement of cell constituents in HC and KC. Secretome analysis by 2-D PAGE and shotgun proteomics of HC revealed the induction of acute phase proteins, in case of KC of proteases, cytokines and chemokines, indicating inflammatory effects. All responses were induced rapidly, independently of signals from other cells, and closely mimicked the pro-inflammatory and protective effects of inflammation modulators LPS in KC and IL-6 in HC. In conclusion, the carcinogen NNM exerts pro-inflammatory effects in the liver, partially by direct activation of KC. The acute inflammation and its protective component will enhance formation, survival and proliferation of initiated cells and may therefore act synergistically with the genotoxic action of the carcinogen.     

A self-stabilizing autonomic recoverer for eventual Byzantine software

We suggest modeling software package flaws (bugs) by assuming eventual Byzantine behavior of the package. We assume that if a program is started in a predefined initial state, it will exhibit legal behavior for a period of time but will eventually become Byzantine. We assume that this behavior pattern can be attributed to the fact that the manufacturer had performed sufficient package tests for limited time scenarios. Restarts are useful for recovering such systems. We suggest a general, yet practical, framework and paradigm for the monitoring and restarting of systems where the framework and paradigm are based on a theoretical foundation. An autonomic recoverer that monitors and initiates system recovery is proposed. It is designed to handle a task, given specific task requirements in the form of predicates and actions. A directed acyclic graph subsystem hierarchical structure is used by a consistency monitoring procedure for achieving a gracious recovery. The existence and correct functionality of the autonomic recovery is guaranteed by the use of a self-stabilizing kernel resident (anchor) process. The autonomic recoverer uses a new scheme for liveness assurance via on-line monitoring that complements known schemes for on-line safety assurance.     

A multifactor approach to student model evaluation

Creating student models for Intelligent Tutoring Systems (ITS) in novel domains is often a difficult task. In this study, we outline a multifactor approach to evaluating models that we developed in order to select an appropriate student model for our medical ITS. The combination of areas under the receiver-operator and precision-recall curves, with residual analysis, proved to be a useful and valid method for model selection. We improved on Bayesian Knowledge Tracing with models that treat help differently from mistakes, model all attempts, differentiate skill classes, and model forgetting. We discuss both the methodology we used and the insights we derived regarding student modeling in this novel domain.

Calibration of a TDR probe for low soil water content measurements

Time domain reflectometry (TDR) probes are increasingly used for field and laboratory estimation of soil water content. Usual calibration of TDR probes for the determination of soil water content uses two media: air for low and water for high values of dielectric permittivity, although the measured range of dielectric permittivity in soil is much smaller as compared to the range implied by the calibration media. The use of air for calibration of short TDR probes gives calibration errors due to overlapping incident and reflected pulses in the reflectogram, which result in their relative shift in time. This phenomenon, named the convolution effect, can be avoided by the application of selected calibration media. The presented approach minimizes of dielectric permittivity measurement errors by choosing the calibration media with dielectric permittivity values close to the limits of the measurement range and the possibility to use TDR probes of various lengths. The comparison of errors of TDR apparent dielectric permittivity measurement in three sandy soils, based on the probe calibrations in various media, is also presented.     

Approaching location-based services from a place-based perspective: from data to services?

Despite the seemingly obvious importance of a link between notions of place and the provision of context in location-based services (LBS), truly place-based LBS remain rare. Place is attractive as a concept for designing services as it focuses on ways in which people, rather than machines, represent and talk about places. We review papers which have extracted place-relevant information from a variety of sources, examining their rationales, the data sources used, the characteristics of the data under study and the ways in which place is represented. Although the data sources used are subject to a wide range of biases, we find that existing methods and data sources are capable of extracting a wide range of place-related information. We suggest categories of LBS which could profit from such information, for example, by using place-related natural language (e.g. vernacular placenames) in tracking and routing services and moving the focus from geometry to place semantics in location-based retrieval. A key future challenge will be to integrate data derived from multiple sources if we are to advance from individual case studies focusing on a single aspect of place to services which can deal with multiple aspects of place.     

Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell‐labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative ¹⁹F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core–shell perfluorocarbon‐based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small‐angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with ¹⁹F MRI and fluorescence imaging, demonstrating their potential for long‐term in vivo multimodal imaging.     

Reduced nitrate concentrations in shallow ground water under a non-fertilised grass buffer strip

In this paper the suitability of a buffer strip to reduce nitrate concentrations in the upper groundwater was tested for a sandy arable soil in The Netherlands during two consecutive leaching seasons. The bufferstrip was a 3.5 m wide unfertilised grass strip adjacent to a ditch on an arable field. In total 24 groundwater wells were installed in 4 transects perpendicular to the ditch to determine Cl, NO₃ and δ¹⁵N concentrations. Piezometers were installed to assess the groundwater flow, which was in the direction of the ditch with small downward leakage across a peat layer at about 3 m depth. Nitrogen was dominantly present as nitrate (NO₃). The NO₃-N concentrations under the bufferstrip were significantly lower than under the adjacent arable field. The lower concentrations were due to dilution, uptake by grass and denitrification. Nitrate was actively removed in the bufferstrip, since the Cl/NO₃ ratios were higher in the bufferstrip than in the remainder of the field. Furthermore, δ¹⁵N data indicated that denitrification occurred in the groundwater and increased with decreasing distance to the ditch. NO₃-N loads to the ditch were estimated at 8.5 kg ha⁻¹yr⁻¹, which is relatively low for this area. We can, however, not determine whether these relatively low NO₃-N loads were causally related to the reduced NO₃-N concentrations in the bufferstrip. Nevertheless, the results of the present study are promising and justify additional research on the efficiency of bufferstrips to reduce NO₃ concentrations in shallow groundwater, and subsequently reduce NO₃ loading of surface water, under Dutch conditions.     

Divergent pattern of polyisoprenoid alcohols in the tissues of <Emphasis Type="Italic">Coluria geoides</Emphasis>: A new electrospray lonization MS approach

Polyisoprenoid alcohols of the plant Coluria geoides were isolated and analyzed by HPLC with UV detection to determine the nature of the polyprenol and dolichol mixture in the organs studied. In roots, a family of dolichols (Dol-15 to Dol-23, with Dol-16 dominating, where Dol-n is dolichol composed of n isoprene units) was accompanied by traces of polyprenols of similar chain lengths, whereas in hairy roots grown in vitro, identical patterns with a slightly broader chain-length range were found. Conversely, in leaves and seeds polyprenols were the dominant form, and their pattern was shifted toward longer chains (maximal content of Pren-19, where Pren-n is polyprenol composed of n isoprene units). Interestingly, the pattern of dolichols in seeds and leaves (in which Dol-17 dominated) was similar to that found in roots. Structures of the dolichols and polyprenols isolated were confirmed by the application of a new HPLC/electrospray ionization-MS method, which also offers a much higher sensitivity in detection of these compounds compared to a UV detector. The highest sensitivity was obtained when the [M+Na]⁺ ions of polyprenols and dolichols were recorded in the selected ion monitoring mode and a small amount of sodium acetate solution was added post-column to enhance the formation of these ions in an electrospray ion source.