bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Immunoglobulin Treatment in Humans Suppresses Dendritic Cell Function via Stimulation of IL-4 and IL-13 Production
Authors: Tjon Angela S. W. , van Gent Rogier , Jaadar Haziz , Martin van Hagen P. , Mancham Shanta , van der Laan Luc J. W. , te Boekhorst Peter A. W. , Metselaar Herold J. , Kwekkeboom Jaap
Published: May 2014

High-dose i.v. Ig (IVIg) is a prominent immunomodulatory therapy for various autoimmune and inflammatory diseases. Recent mice studies suggest that IVIg inhibits myeloid cell function by inducing a cascade of IL-33–Th2 cytokine production causing upregulation of the inhibitory FcγRIIb, as well as by modulating IFN-γ signaling. The purpose of our study was to explore whether and how these mechanisms are operational in IVIg-treated patients. We show that IVIg in patients results in increases in plasma levels of IL-33, IL-4, and IL-13 and that increments in IL-33 levels correlate with rises in plasma IL-4 and IL-13 levels. Strikingly, no upregulation of FcγRIIb expression was found, but instead a decreased expression of the activating FcγRIIa on circulating myeloid dendritic cells (mDCs) after high-dose, but not after low-dose, IVIg treatment. In addition, expression of the signaling IFN-γR2 subunit of the IFN-γR on mDCs was downregulated upon high-dose IVIg therapy. In vitro experiments suggest that the modulation of FcγRs and IFN-γR2 on mDCs is mediated by IL-4 and IL-13, which functionally suppress the responsiveness of mDCs to immune complexes or IFN-γ. Human lymph nodes and macrophages were identified as potential sources of IL-33 during IVIg treatment. Interestingly, stimulation of IL-33 production in human macrophages by IVIg was not mediated by dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN). In conclusion, high-dose IVIg treatment inhibits inflammatory responsiveness of mDCs in humans by Th2 cytokine-mediated downregulation of FcγRIIa and IFN-γR2 and not by upregulation of FcγRIIb. Our results suggest that this cascade is initiated by stimulation of IL-33 production that seems DC-SIGN independent.
Deletion of CD24 Impairs Development of Heat Shock Protein gp96–Driven Autoimmune Disease through Expansion of Myeloid-Derived Suppressor Cells
Authors: Thaxton Jessica E. , Liu Bei , Zheng Pan , Liu Yang , Li Zihai
Published: May 2014

CD24 binds to and suppresses inflammation triggered by danger-associated molecular patterns such as heat shock proteins (HSPs) and high-mobility group box 1. Paradoxically, CD24 has been shown to enhance autoimmune disease. In this study, we attempt to reconcile this paradox by deletion of CD24 (24KO) in a lupus-like disease model driven by forced expression of HSP gp96 at the cell surface (transgenic mice [tm]). As expected, tm24KO mice showed increased CD11c+ dendritic cell activation coupled to a significant increase in dendritic cell–specific IL-12 production compared with tm mice. However, tm24KO mice showed less CD4 T cell activation and peripheral inflammatory cytokine production in comparison with tm mice. We characterized an enhanced immune suppressive milieu in tm24KO mice distinguished by increased TGF-β and greater regulatory T cell–suppressive capacity. We found greater absolute numbers of myeloid-derived suppressor cells (MDSCs) in tm24KO mice and showed that the Ly6C+ MDSC subset had greater suppressive capacity from tm24KO mice. Deletion of CD24 in tm mice led to diminished lupus-like pathology as evidenced by anti-nuclear Ab deposition and glomerulonephritis. Finally, we show that expanded MDSC populations were mediated by increased free high-mobility group box 1 in tm24KO mice. Thus, the deletion of CD24 in an HSP-driven model of autoimmunity led to the unexpected development of regulatory T cell and MDSC populations that augmented immune tolerance. Further study of these populations as possible negative regulators of inflammation in the context of autoimmunity is warranted.
Carbonic Anhydrase IV Is Expressed on IL-5–Activated Murine Eosinophils
Authors: Wen Ting , Mingler Melissa K. , Wahl Benjamin , Khorki M. Eyad , Pabst Oliver , Zimmermann Nives , Rothenberg Marc E.
Published: May 2014

Eosinophilia and its cellular activation are hallmark features of asthma, as well as other allergic/Th2 disorders, yet there are few, if any, reliable surface markers of eosinophil activation. We have used a FACS-based genome-wide screening system to identify transcriptional alterations in murine lung eosinophils recruited and activated by pulmonary allergen exposure. Using a relatively stringent screen with false-positive correction, we identified 82 candidate genes that could serve as eosinophil activation markers and/or pathogenic effector markers in asthma. Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, which was validated by quantitative PCR, immunohistochemistry, and flow cytometry. Eosinophil CAR4 expression was kinetically regulated by IL-5, but not IL-13. IL-5 was both necessary and sufficient for induction of eosinophil CAR4. Although CAR4-deficient mice did not have a defect in eosinophil recruitment to the lung, nor a change in eosinophil pH-buffering capacity, allergen-challenged chimeric mice that contained Car4−/− hematopoietic cells aberrantly expressed a series of genes enriched in biological processes involved in epithelial differentiation, keratinization, and anion exchange. In conclusion, we have determined that eosinophils express CAR4 following IL-5 or allergen exposure, and that CAR4 is involved in regulating the lung transcriptome associated with allergic airway inflammation; therefore, CAR4 has potential value for diagnosing and monitoring eosinophilic responses.
Dectin-1 Pathway Activates Robust Autophagy-Dependent Unconventional Protein Secretion in Human Macrophages
Authors: Öhman Tiina , Teirilä Laura , Lahesmaa-Korpinen Anna-Maria , Cypryk Wojciech , Veckman Ville , Saijo Shinobu , Wolff Henrik , Hautaniemi Sampsa , Nyman Tuula A. , Matikainen Sampsa
Published: May 2014

Dectin-1 is a membrane-bound pattern recognition receptor for β-glucans, which are the main constituents of fungal cell walls. Detection of β-glucans by dectin-1 triggers an effective innate immune response. In this study, we have used a systems biology approach to provide the first comprehensive characterization of the secretome and associated intracellular signaling pathways involved in activation of dectin-1/Syk in human macrophages. Transcriptome and secretome analysis revealed that the dectin-1 pathway induced significant gene expression changes and robust protein secretion in macrophages. The enhanced protein secretion correlated only partly with increased gene expression. Bioinformatics combined with functional studies revealed that the dectin-1/Syk pathway activates both conventional and unconventional, vesicle-mediated, protein secretion. The unconventional protein secretion triggered by the dectin-1 pathway is dependent on inflammasome activity and an active autophagic process. In conclusion, our results reveal that unconventional protein secretion has an important role in the innate immune response against fungal infections.
Regulatory T Cells and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment Undergo Fas-Dependent Cell Death during IL-2/αCD40 Therapy
Authors: Weiss Jonathan M. , Subleski Jeff J. , Back Tim , Chen Xin , Watkins Stephanie K. , Yagita Hideo , Sayers Thomas J. , Murphy William J. , Wiltrout Robert H.
Published: May 2014

Fas ligand expression in certain tumors has been proposed to contribute to immunosuppression and poor prognosis. However, immunotherapeutic approaches may elicit the Fas-mediated elimination of immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) within tumors that represent major obstacles for cancer immunotherapy. Previously, we showed that IL-2 and agonistic CD40 Ab (αCD40) elicited synergistic antitumor responses coincident with the efficient removal of Tregs and MDSCs. We demonstrate in this study in two murine tumor models that Treg and MDSC loss within the tumor microenvironment after IL-2/αCD40 occurs through a Fas-dependent cell death pathway. Among tumor-infiltrating leukocytes, CD8+ T cells, neutrophils, and immature myeloid cells expressed Fas ligand after treatment. Fas was expressed by tumor-associated Tregs and immature myeloid cells, including MDSCs. Tregs and MDSCs in the tumor microenvironment expressed active caspases after IL-2/αCD40 therapy and, in contrast with effector T cells, Tregs significantly downregulated Bcl-2 expression. In contrast, Tregs and MDSCs proliferated and expanded in the spleen after treatment. Adoptive transfer of Fas-deficient Tregs or MDSCs into wild-type, Treg-, or MDSC-depleted hosts resulted in the persistence of Tregs or MDSCs and the loss of antitumor efficacy in response to IL-2/αCD40. These results demonstrate the importance of Fas-mediated Treg/MDSC removal for successful antitumor immunotherapy. Our results suggest that immunotherapeutic strategies that include exploiting Treg and MDSC susceptibility to Fas-mediated apoptosis hold promise for treatment of cancer.
Formal definition of the Neoproterozoic Mackenzie Mountains Supergroup (Northwest Territories), and formal stratigraphic nomenclature for terrigenous clastic units of the Katherine Group
Authors: Long D G F , Turner E C
Published: May 2014

The Mackenzie Mountains Supergroup in NWT is formalised in this and in a companion paper. The supergroup includes carbonate rocks of the Tabasco Formation, mudstones, sandstones and minor carbonate rocks of the Tsezotene Formation, sandstones, mudstones and
carbonate rocks of the Katherine Group (formalised), and carbonate rocks, evaporite rocks and mudstones of the Little Dal Group. Descriptions and type sections are provided for seven new formations in the Katherine Group (Eduni, Tawu, Grafe River, Etagochile, Shattered Range, McClure, and Abraham
Plains formations).
Regional surface rock geochemistry, Athabasca Basin, Saskatchewan
Authors: Wright D M , Potter E G
Published: May 2014

Regional examination and integration of geochemical data with other components of the uranium exploration model can influence
mineral exploration. This approach was applied to regional geochemical data for the Athabasca Basin, northern Saskatchewan, Canada,
which is host to some of the world's most significant high grade unconformity-associated uranium deposits. Four distinct geochemical
signatures are described, each reflecting portions of processes responsible for uranium mineralization, associated alteration, and
background geology. These signatures are significant in that they 1) are present in the exposed and near-surface rocks of the Athabasca
Basin; 2) correspond with lineament traces, and highlight lineament intersections that are loci for uranium mineralization, and 3)
partially define a distinct but locally stratabound hydrothermal signature that is possibly temporally and genetically related to focused
uranium deposition elsewhere in the Athabasca Basin, but is also expressed in the Wolverine Point Formation.
Die groep vroue by die kruis van Jesus (Johannes 19:25): 'n Narratologiese perspektief
Authors: Tolmie D. Francois
Published: May 2014

The group of women at the cross of Jesus (John 19:25): A narratological perspective. The women portrayed at the cross of Jesus in the Fourth Gospel (John 19:25) are often discussed in commentaries and studies on this part of the Gospel. However, as far as can be determined, they have not yet been studied from a narratological perspective. This matter is therefore addressed in the current study. In narratological terms, the women function as a group character, and they are introduced into the narrative world of the Gospel in 19:25 as standing at the cross of Jesus. After a brief overview of the issues that are normally addressed by Johannine scholars when these women are discussed (the number of women, how the list of women mentioned in the Fourth Gospel should be related to the lists in the Synoptic Gospels and the function fulfilled by the women), they are analysed from a narratological perspective. Amongst the issues that are investigated are the composition of the group character, the layers of contrast that may be detected by the reader between the group character and the four soldiers and the defamiliarising effect that ambiguity concerning the number of women may have on the reading process.
A Framework for Building Research Partnerships with First Nations Communities
Authors: Bharadwaj Lalita
Published: May 2014

Solutions to complex health and environmental issues experienced by First Nations communities in Canada require the adoption of collaborative modes of research. The traditional “helicopter” approach to research applied in communities has led to disenchantment on the part of First Nations people and has impeded their willingness to participate in research. University researchers have tended to develop projects without community input and to adopt short term approaches to the entire process, perhaps a reflection of granting and publication cycles and other realities of academia. Researchers often enter communities, collect data without respect for local culture, and then exit, having had little or no community interaction or consideration of how results generated could benefit communities or lead to sustainable solutions. Community-based participatory research (CBPR) has emerged as an alternative to the helicopter approach and is promoted here as a method to research that will meet the objectives of both First Nations and research communities. CBPR is a collaborative approach that equitably involves all partners in the research process. Although the benefits of CBPR have been recognized by segments of the University research community, there exists a need for comprehensive changes in approaches to First Nations centered research, and additional guidance to researchers on how to establish respectful and productive partnerships with First Nations communities beyond a single funded research project. This article provides a brief overview of ethical guidelines developed for researchers planning studies involving Aboriginal people as well as the historical context and principles of CBPR. A framework for building research partnerships with First Nations communities that incorporates and builds upon the guidelines and principles of CBPR is then presented. The framework was based on 10 years’ experience working with First Nations communities in Saskatchewan. The framework for research partnership is composed of five phases. They are categorized as the pre-research, community consultation, community entry, research and research dissemination phases. These phases are cyclical, non-linear and interconnected. Elements of, and opportunities for, exploration, discussion, engagement, consultation, relationship building, partnership development, community involvement, and information sharing are key components of the five phases within the framework. The phases and elements within this proposed framework have been utilized to build and implement sustainable collaborative environmental health research projects with Saskatchewan First Nations communities.
Regulation of Human Neutrophil Apoptosis and Lifespan in Health and Disease
Authors: McCracken Jenna M. , Allen Lee-Ann H.
Published: May 2014

Neutrophils (also called polymorphonuclear leukocytes, PMNs) are the most abundant white blood cells in humans and play a central role in innate host defense. Another distinguishing feature of PMNs is their short lifespan. Specifically, these cells survive for less than 24 hours in the bloodstream and are inherently pre-programed to die by constitutive apoptosis. Recent data indicate that this process is regulated by intracellular signaling and changes in gene expression that define an “apoptosis differentiation program.” Infection typically accelerates neutrophil turnover, and as such, phagocytosis induced cell death (PICD) and subsequent clearance of the corpses by macrophages are essential for control of infection and resolution of the inflammatory response. Herein we reprise recent advances in our understanding of the molecular mechanisms of neutrophil apoptosis with a focus on regulatory factors and pathway intermediates that are specific to this cell type. In addition, we summarize mechanisms whereby perturbation of PMN death contributes directly to the pathogenesis of many infectious and inflammatory disease states.
Corporate Social Responsibility or Payoff Asymmetry? A Study of an Endogenous Timing Game
Authors: Matsumura Toshihiro , Ogawa Akira
Published: May 2014

We revisit an endogenous timing game by introducing corporate social responsibility into firms' payoffs. Previous research investigates an endogenous timing game in a mixed oligopoly, wherein one welfare‐maximizing public firm competes against profit‐maximizing private firms. It shows that the outcome is completely different from that of private oligopoly. In contrast to its result, we find that this change in payoff does not matter as long as the payoffs are symmetric. Our result indicates that asymmetry, and not welfare‐concerning objectives, yields specific results in the literature on mixed oligopoly.
Inverse modeling of CH4 emissions for 2010–2011 using different satellite retrieval products from GOSAT and SCIAMACHY
Authors: Alexe M. , Bergamaschi P. , Segers A. , Detmers R. , Butz A. , Hasekamp O. , Guerlet S. , Parker R. , Boesch H. , Frankenberg C. , Scheepmaker R. A. , Dlugokencky E. , Sweeney C. , Wofsy S. C. , Kort E. A.
Published: May 2014

Abstract. Beginning in 2009 new space-borne observations of dry-air column-averaged mole fractions of atmospheric methane (XCH4) became available from the Thermal And Near infrared Sensor for carbon Observations–Fourier Transform Spectrometer (TANSO-FTS) instrument onboard the Greenhouse Gases Observing SATellite (GOSAT). Until April 2012 concurrent CH4 measurements were provided by the SCanning Imaging Absorption spectroMeter for Atmospheric CartograpHY (SCIAMACHY) instrument onboard ENVISAT. The GOSAT and SCIAMACHY XCH4 retrievals can be compared during their circa 32 month period of overlap. We estimate monthly average CH4 emissions between January 2010 and December 2011, using the TM5-4DVAR inverse modeling system. Additionally, high-accuracy measurements from the National Oceanic and Atmospheric Administration Earth System Research Laboratory (NOAA ESRL) global air sampling network are used, providing strong constraints of the remote surface atmosphere. We discuss five inversion scenarios that make use of different GOSAT and SCIAMACHY XCH4 retrieval products, including two sets of GOSAT proxy retrievals processed independently by the Netherlands Institute for Space Research (SRON)/Karlsruhe Institute of Technology (KIT), and the University of Leicester (UL), and the RemoTeC "Full-Physics" (FP) XCH4 retrievals available from SRON/KIT. 2 year average emission maps show a~good overall agreement among all GOSAT-based inversions, and compared to the SCIAMACHY-based inversion, with consistent flux adjustment patterns, particularly across Equatorial Africa and North America. The inversions are validated against independent shipboard and aircraft observations, and XCH4 measurements available from the Total Carbon Column Observing Network (TCCON). All GOSAT and SCIAMACHY inversions show very similar validation performance.
The effects of nitrate on the heterogeneous uptake of sulfur dioxide on hematite
Authors: Kong L. D. , Zhao X. , Sun Z. Y. , Yang Y. W. , Fu H. B. , Yang X. , Zhang S. C. , Chen J. M. , Wang L. , Cheng T. T.
Published: May 2014

Abstract. Nitrate is often found to be associated with atmospheric particles. Surface nitrate can change the hygroscopicity of these particles, and thus impact their chemical reactivity. However, the influence of nitrate on the heterogeneous reactions of atmospheric trace gases is poorly understood. In this work, the effects of nitrate on heterogeneous conversion of SO2 with hematite at 298 K were investigated using an in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and a White cell coupled with Fourier transform infrared spectroscopy (White cell-FTIR). It is found that nitrate participates in the heterogeneous reactions of SO2, accelerates the formation rate of sulfate, and leads to the formation of surface-adsorbed HNO3 and gas-phase N2O and HONO, revealing that nitrate has a significant impact on the heterogeneous conversion of SO2 to sulfate. The results indicate that small amounts of nitrate significantly enhance the reactivity of hematite-nitrate mixtures and favor the enhancement in SO2 uptake and an increase in the amount of sulfate on hematite. For mixtures, the sample containing 24% nitrate exhibits the highest sulfate formation rate, and its corresponding average sulfate formation rate is about 5 times higher than that of hematite alone. No uptake of SO2 and formation of sulfate are observed on the pure nitrate. Evidence presented herein implies a significant contribution of the unreleased HNO3 and HONO in the particles for the conversion of SO2 and the enhanced formation of sulfate in the atmosphere. A possible mechanism for the influence of nitrate on the heterogeneous conversion of SO2 on hematite is proposed, and atmospheric implications based on these results are discussed.
Quantification of uncertainty in aerosol optical thickness retrieval arising from aerosol microphysical model and other sources, applied to Ozone Monitoring Instrument (OMI) measurements
Authors: Määttä A. , Laine M. , Tamminen J. , Veefkind J. P.
Published: May 2014

Abstract. Satellite instruments are nowadays successfully utilised for measuring atmospheric aerosol in many applications as well as in research. Therefore, there is a growing need for rigorous error characterisation of the measurements. Here, we introduce a methodology for quantifying the uncertainty in the retrieval of aerosol optical thickness (AOT). In particular, we concentrate on two aspects: uncertainty due to aerosol microphysical model selection and uncertainty due to imperfect forward modelling. We apply the introduced methodology for aerosol optical thickness retrieval of the Ozone Monitoring Instrument (OMI) on board NASA's Earth Observing System (EOS) Aura satellite, launched in 2004. We apply statistical methodologies that improve the uncertainty estimates of the aerosol optical thickness retrieval by propagating aerosol microphysical model selection and forward model error more realistically. For the microphysical model selection problem, we utilise Bayesian model selection and model averaging methods. Gaussian processes are utilised to characterise the smooth systematic discrepancies between the measured and modelled reflectances (i.e. residuals). The spectral correlation is composed empirically by exploring a set of residuals. The operational OMI multi-wavelength aerosol retrieval algorithm OMAERO is used for cloud-free, over-land pixels of the OMI instrument with the additional Bayesian model selection and model discrepancy techniques introduced here. The method and improved uncertainty characterisation is demonstrated by several examples with different aerosol properties: weakly absorbing aerosols, forest fires over Greece and Russia, and Sahara desert dust. The statistical methodology presented is general; it is not restricted to this particular satellite retrieval application.
Evaluation of wind profiles from the NERC MST Radar, Aberystwyth, UK
Authors: Lee C. F. , Vaughan G. , Hooper D. A.
Published: May 2014

Abstract. This study quantifies the uncertainties in winds measured by the Aberystwyth Mesosphere-Stratosphere-Troposphere (MST) radar (52.4° N, 4.0° W), before and after its renovation in March 2011. 127 radiosondes provide an independent measure of winds. Differences between radiosonde and radar-measured horizontal winds are correlated with long-term averages of vertical velocities, suggesting an influence from local mountain waves. These local influences are an important consideration when using radar winds as a measure of regional conditions, particularly for numerical weather prediction. In those applications, local effects represent a source of sampling error additional to the inherent uncertainties in the measurements themselves. The radar renovation improved the SNR of measurements, with correspondingly improved altitude coverage. It also corrected an under-estimate of horizontal wind speeds attributed to beam formation problems, due to component failure pre-renovation. The standard error in radar-measured winds averaged over half-an-hour increases with wind speed and altitude, and is 0.6–2.5 m s−1 (5–20% of wind speed) for post-renovation horizontal winds. Pre-renovation values are typically 0.4 m s−1 (0.03 m s−1) larger. The standard error in radial velocities is < 0.04 m s−1. Eight weeks of special radar operation are used to investigate the effects of echo power aspect sensitivity. Corrections for echo power aspect sensitivity remove an underestimate of horizontal wind speeds, however aspect sensitivity is azimuthally anisotropic at the scale of routine observations (≈ 1 h). This anisotropy introduces additional random error into wind profiles. For winds averaged over half-an-hour, the random error is around 3.5% above 8 km, but as large as 4.5% in the mid-troposphere.
HAMP – the microwave package on the High Altitude and LOng range research aircraft HALO
Authors: Mech M. , Orlandi E. , Crewell S. , Ament F. , Hirsch L. , Hagen M. , Peters G. , Stevens B.
Published: May 2014

Abstract. An advanced package of microwave remote sensing instrumentation has been developed for the operation on the new German High Altitude LOng range research aircraft (HALO). The HALO Microwave Package, HAMP, consists of two nadir looking instruments: a cloud radar at 36 GHz and a suite of passive microwave radiometers with 26 frequencies in different bands between 22.24 and 183.31 ± 12.5 GHz. We present a description of HAMP's instrumentation together with an illustration of its potential. To demonstrate this potential synthetic measurements for the implemented passive microwave frequencies and the cloud radar based on cloud resolving and radiative transfer model calculations were performed. These illustrate the advantage of HAMP's chosen frequency coverage, which allows for improved detection of hydrometeors both via the emission and scattering of radiation. Regression algorithms compare HAMP retrieval with standard satellite instruments from polar orbiters and show its advantages particularly for the lower atmosphere with a reduced root mean square error by 5 and 15% for temperature and humidity, respectively. HAMP's main advantage is the high spatial resolution of about 1 km which is illustrated by first measurements from test flights. Together these qualities make it an exciting tool for gaining better understanding of cloud processes, testing retrieval algorithms, defining future satellite instrument specifications, and validating platforms after they have been placed in orbit.
Long-term evolution and seasonal modulation of methanol above Jungfraujoch (46.5° N, 8.0° E): optimisation of the retrieval strategy, comparison with model simulations and independent observations
Authors: Bader W. , Stavrakou T. , Muller J.-F. , Reimann S. , Boone C. D. , Harrison J. J. , Flock O. , Bovy B. , Franco B. , Lejeune B. , Servais C. , Mahieu E.
Published: May 2014

Abstract. Methanol (CH3OH) is the second most abundant organic compound in the Earth's atmosphere after methane. In this work, we present the first long-term time series of methanol total, lower tropospheric and upper tropospheric-lower stratospheric partial columns derived from the analysis of high resolution Fourier transform infrared solar spectra recorded at the Jungfraujoch station (46.5° N, 3580 m a.s.l.). The retrieval of methanol is very challenging due to strong absorptions of ozone in the region of the selected υ8 band of CH3OH. Two wide spectral intervals have been defined and adjusted in order to maximize the information content. Methanol does not exhibit a significant trend over the 1995–2012 time period, but a strong seasonal modulation characterized by maximum values and variability in June–July, minimum columns in winter and a peak-to-peak amplitude of 130%. In situ measurements performed at the Jungfraujoch and ACE-FTS occultations give similar results for the methanol seasonal variation. The total and lower tropospheric columns are also compared with IMAGESv2 model simulations. There is no systematic bias between the observations and IMAGESv2 but the model underestimates the peak-to-peak amplitude of the seasonal modulations.
Partial coupling and differential regulation of biologically and photo-chemically labile dissolved organic carbon across boreal aquatic networks
Authors: Lapierre J.-F. , del Giorgio P. A.
Published: May 2014

Abstract. Despite the rapidly increasing volume of research on the biological and photochemical degradation of DOC in aquatic environments, little is known on the large-scale patterns in biologically and photo-chemically degradable DOC (Bd-DOC and Pd-DOC, respectively) in continental watersheds, and on the links that exist between these two key properties that greatly influence the flow of carbon from continents to oceans. Here we explore the patterns of Bd- and Pd-DOC across hundreds of boreal lakes, rivers and wetlands spanning a large range of system trophy and terrestrial influence, and compared the drivers of these two reactive pools of DOC at the landscape level. Using standardized incubations of natural waters, we found that the concentrations of Bd- and Pd-DOC co-varied across all systems studied but were nevertheless related to different pools of dissolved organic matter (DOM, identified by fluorescence analyses) in ambient waters. A combination of nutrients and protein-like DOM explained nearly half of the variation in Bd-DOC, whereas Pd-DOC was exclusively predicted by DOM optical properties, consistent with the photochemical degradability of specific fluorescent DOM (FDOM) pools that we experimentally determined. The concentrations of colored DOM (CDOM), a proxy of terrestrial influence, almost entirely accounted for the observed relationship between FDOM and the concentrations of both Bd- and Pd-DOC. The concentrations of CDOM and of the putative bio-labile fluorescence component shifted from complete decoupling in clear-water environments to strong coupling in browner streams and wetlands. This suggests a baseline autochthonous Bd-DOC pool fuelled by internal production that is gradually overwhelmed by land-derived Bd-DOC as terrestrial influence increases across landscape gradients. The importance of land as a major source of both biologically and photo-chemically degradable DOC for continental watersheds resulted in a partial coupling of those carbon pools in natural freshwaters, despite fundamental contrasts in terms of their composition and regulation.
Bayesian networks for environmental flow decision-making and an application in the Yellow River estuary, China
Authors: Pang A. P. , Sun T.
Published: May 2014

Abstract. We proposed an approach for environmental flow decision-making based on Bayesian networks considering seasonal water use conflicts between agriculture and ecosystems. Three steps were included in the approach: water shortage assessment after environmental flow allocation using a production-loss model considering temporal variations of river flows; trade-off analysis of water use outcomes by Bayesian networks; and environmental flow decision-making based on a risk assessment under different management strategies. An agricultural water shortage model and a production-loss model were integrated after satisfying environmental flows with temporal variability. The case study in the Yellow River estuary indicated that the average difference of acceptable economic loss for winter wheat irrigation stakeholders was 10% between water saving measures and water diversion projects. The combination of water diversion projects and water-saving measures would allow 4.1% more river inflow to be allocated to ecological needs in normal years without further economic losses in agriculture.
China's water sustainability in the 21st century: a climate-informed water risk assessment covering multi-sector water demands
Authors: Chen X. , Naresh D. , Upmanu L. , Hao Z. , Dong L. , Ju Q. , Wang J. , Wang S.
Published: May 2014

Abstract. China is facing a water resources crisis with growing concerns as to the reliable supply of water for agricultural, industrial and domestic needs. High inter-annual rainfall variability and increasing consumptive use across the country exacerbates the situation further and is a constraint on future development. For water sustainability, it is necessary to examine the differences in water demand and supply and their spatio-temporal distribution in order to quantify the dimensions of the water risk. Here, a detailed quantitative assessment of water risk as measured by the spatial distribution of cumulated deficits for China is presented. Considering daily precipitation and temperature variability over fifty years and the current water demands, risk measures are developed to inform county level water deficits that account for both within-year and across-year variations in climate. We choose political rather than watershed boundaries since economic activity and water use are organized by county and the political process is best informed through that unit. As expected, the risk measures highlight North China Plain counties as highly water stressed. Regions with high water stress have high inter-annual variability in rainfall and now have depleted groundwater aquifers. The stress components due to agricultural, industrial and domestic water demands are illustrated separately to assess the vulnerability of particular sectors within the country to provide a basis for targeted policy analysis for reducing water stress.
Intensively exploited Mediterranean aquifers: resilience to seawater intrusion and proximity to critical thresholds
Authors: Mazi K. , Koussis A. D. , Destouni G.
Published: May 2014

Abstract. We investigate seawater intrusion in three prominent Mediterranean aquifers that are subject to intensive exploitation and modified hydrologic regimes by human activities: the Nile Delta, Israel Coastal and Cyprus Akrotiri aquifers. Using a generalized analytical sharp interface model, we review the salinization history and current status of these aquifers, and quantify their resilience/vulnerability to current and future seawater intrusion forcings. We identify two different critical limits of seawater intrusion under groundwater exploitation and/or climatic stress: a limit of well intrusion, at which intruded seawater reaches key locations of groundwater pumping, and a tipping point of complete seawater intrusion up to the prevailing groundwater divide of a coastal aquifer. Either limit can be reached, and ultimately crossed, under intensive aquifer exploitation and/or climate-driven change. We show that seawater intrusion vulnerability for different aquifer cases can be directly compared in terms of normalized intrusion performance curves. The site-specific assessments show that (a) the intruding seawater currently seriously threatens the Nile Delta aquifer, (b) in the Israel Coastal aquifer the sharp interface toe approaches the well location and (c) the Cyprus Akrotiri aquifer is currently somewhat less threatened by increased seawater intrusion.
Evaluation of forest fire models on a large observation database
Authors: Filippi J.-B. , Mallet V. , Nader B.
Published: May 2014

Abstract. This paper presents the evaluation of several fire propagation models using a large set of observed fires. The observation base is composed of 80 Mediterranean fire cases of different sizes, which come with the limited information available in an operational context (burned surface and approximative ignition point). Simulations for all cases are carried out with 4 different front velocity models. The results are compared with several error scoring methods applied to each of the 320 simulations. All tasks are performed in a fully automated manner, with simulations ran as first guesses with no tuning for any of the models or cases. This approach leads a wide range of simulation performance, including some of the bad simulation results to be expected in an operational context. Regardless the quality of the input data, it is found that the models can be ranked based on their performance and that the most complex models outperform the more empirical ones. Data and source code used for this paper are freely available to the community.
Inferred basal friction and surface mass balance of North-East Greenland Ice Stream using data assimilation of ICESat-1 surface altimetry and ISSM
Authors: Larour E. , Utke J. , Csatho B. , Schenk A. , Seroussi H. , Morlighem M. , Rignot E. , Schlegel N. , Khazendar A.
Published: May 2014

Abstract. We present a new data assimilation method within the ISSM framework that is capable of assimilating surface altimetry data from missions such as ICESat-1 into reconstructions of transient ice flow. The new method relies on algorithmic differentiation to compute gradients of diagnostics with respect to model forcings. It is applied to the North East Greenland Ice Stream where surface mass balance and basal friction forcings are temporally inverted, resulting in significantly improved modeled surface heights that match existing altimetry. This new approach allows for a better quantification of basal and surface processes, and a better understanding of the physical processes currently missing in transient ice flow models to better capture the important intra and inter-annual variability in surface altimetry. It also demonstrates that large spatial and temporal variability is required in model forcings such as surface mass balance and basal friction, variability that can only be explained by including more complex processes such as snowpack compaction at the surface and basal hydrology at the bottom of the ice sheet. This approach is indeed a first step towards assimilating the wealth of high spatial resolution altimetry data available from EnviSat, ICESat-1, Operation IceBridge and CryoSat-2, and that will be available in the near future with the launch of ICESat-2.
Changes in Imja Tsho in the Mt. Everest region of Nepal
Authors: Somos-Valenzuela M. A. , McKinney D. C. , Rounce D. R. , Byers A. C.
Published: May 2014

Abstract. Imja Tsho, located in the Sagarmatha (Everest) National Park of Nepal, is one of the most studied and rapidly growing lakes in the Himalayan range. Compared with previous studies, the results of our sonar bathymetric survey conducted in September 2012 suggest that the maximum depth has increased from 98 m to 116 ± 0.25 m since 2002, and that its estimated volume has grown from 35.8 ± 0.7 million m3 to 61.6 ± 1.8 million m3. Most of the expansion of the lake in recent years has taken place in the glacier terminus–lake interface on the eastern end of the lake, with the glacier receding at about 52.6 ± 0.3 m yr−1 and the lake expanding in area by 0.039 ± 0.0195 km2 yr−1. A ground penetrating radar survey of the Imja-Lhotse Shar glacier just behind the glacier terminus shows that the ice is over 217 ± 12.71 m thick in the center of the glacier. The volume of water that could be released from the lake in the event of a breach in the damming moraine on the western end of the lake has increased from 21 million m3 in 2002 to 34.8 ± 0.54 million m3 in 2012.
Successful Use of Fondaparinux in a Patient with Heparin-induced Thrombocytopenia while on Extracorporeal Membrane Oxygenation after Mitral Valve Redo Surgery
Authors: Parlar Ali Ihsan , Sayar Ufuk , Cevirme Deniz , Yuruk Mehmet Ali , Mataraci Ilker
Published: May 2014

In patients with respiratory failure and impairment of the left ventricle, arteriovenous extracorporeal membrane oxygenation (ECMO) offers further therapeutic options. Systemic anticoagulation is mandatory and heparin is routinely administrated. However, repeated exposure to heparin may cause heparin-induced thrombocytopenia (HIT) and carries a risk of thrombotic mortality and morbidity. We present a patient who developed HIT during ECMO support and was treated successfully and safely by fondaparinux. Fondaparinux can be used for thromboembolic treatment or prophylaxis in a patient with HIT.
First Impressions of Cardiovascular Calcification Treatment in Hemodialysis Patients with a New Dialysis Fluid Containing Sodium Thiosulphate (STS)
Authors: Yonova Diana H. , Vazelov Evgueniy S. , Trendafilov Ivan I. , Stoinova Veselka V. , Nedevska Mariya T. , Antonov Simeon A.
Published: May 2014

Background

Cardiovascular calcification (CVC) in hemodialysis patients (HDP) causes cardiovascular pathology. Up until now very few drugs and therapeutic interventions have been able to reduce cardiovascular calcium deposits in hemodialysis patients and the process requires more than a year. Our idea in this study was to test 2 calcium binders – sodium thiosulfate (STS) and dinatrium ethylene diamine tetraacetic acid (DNEDTA) – for prevention and treatment of cardiovascular calcification of hemodialysis patients, using both substances not as an intravenous infusion but by adding them to the liquid bicarbonate part of the dialysis fluid.

Material and Methods

6 HDPs were treated with sodium thiosulphate (STS), 6 with dinatrium ethylene diamine tetraacetic acid (DNEDTA), and 6 patients served as controls. Electrolytes, liver function, markers of inflammation, oxidative stress, bone metabolism, spiral computed tomography (SCT) of coronary CVC and bone densitometry were performed twice (start and end of the study).

Results

Starting blood parameters were similar to the end (STS group). No toxic or side effects from STS were observed. Initially in the DNEDTA group all the patients had vomiting so we excluded DNEDTA from the study. SCT found a significant reduction of calcification in 4 patients (STS group) and retardation in 2 patients comparatively to controls.

Conclusions

The first results are hopeful, but the number of the patients was small, so we are enlarging the enrollment in the expectation of corroborating our results soon.
The Dialysis Staff Workload and the Blood Volume Tracking System during the Hemodialysis Sessions of Hypotension-prone Patients
Authors: Doria Maria , Genovesi Simonetta , Biagi Fabio , Steckiph Denis , Mancini Elena , Stella Andrea , Santoro Antonio
Published: May 2014

Purpose

Intradialytic hypotension (IDH) represents a common hemodialysis (HD) complication. Blood volume tracking (BVT) is a tool regulating the relative blood volume changes and potentially reducing the occurrence of IDH. The aim of this study was to evaluate the ability of BVT to reduce the staff workload associated to IDH.

Methods

Ten hypotension-prone HD patients were treated each with 39 conventional HD (HD) sessions and then switched to 39 HD sessions with BVT (HD-BVT). The staff interventions related to IDH were monitored by a trained staff.

Results

Dialysis sessions complicated by IDH and staff interventions were affected by BVT (HD: 102 and 127 vs. HD-BVT: 57 and 59, respectively, for both p<0.001). The time consumed by staff in IDH management was decreased by HD-BVT (1416 vs. 578 min, p<0.001).

Conclusions

The effectiveness of BVT to reduce the frequency of IDH leads to a reduction of the dialysis staff workload with fewer staff interventions, allowing for major work-time saving.
Superior in vivo Compatibility of Hydrophilic Polymer Coated Prosthetic Vascular Grafts
Authors: Strang Aart C. , Knetsch Menno L.W. , Idu Mirza M. , Bisoendial Radjesh J. , Kramer Gertjan , Speijer Dave , Koole Leo H. , Stroes Erik S.G. , Rotmans Joris I.
Published: May 2014

Purpose

Protein adsorption, cell adhesion and graft patency was compared in hydrophilic versus hydrophobic polymer-coated prosthetic vascular grafts. We hypothesize that in vivocompatibility of hydrophilic polymer-coated prosthetic vascular grafts is superior to in vivo compatibility of hydrophobic grafts.

Methods

A pairwise side-to-side common carotid artery interposition graft was placed eight female landrace goats (mean weight 55 kg). Protein adsorption was assessed using Western Blot in two hydrophilic and two hydrophobic grafts harvested after three days. Graft patency was monitored for 28 days in six goats with continuous wave Doppler ultrasonography. Adherence of endothelial cells, leukocytes and platelets was determined with ELISA and compared between the two graft types after 28 days.

Results

After three days, more ApoA-l, albumin and VEGF and less fibrin adsorbed to hydrophilic grafts. After 28 days, compared to hydrophobic grafts, higher numbers of endothelial cells were present on hydrophilic grafts (P=0.016), and less thrombocytes and leukocytes (P=0.012 and 0.024, respectively). Two out of eight hydrophobic grafts lost patency, while none of the hydrophilic grafts failed (P=0.157).

Conclusions

Hydrophilic polymer-coated vascular grafts have superior in vivo compatibility when compared to hydrophobic grafts as characterized by reduced platelet and leukocyte adherence as well as higher endothelialization.
Evaluation of Post-Puncture Bleeding Time of Arteriovenous Fistulas with IRIS® Bandage
Authors: Boulanger Henri , Ahriz-Saksi Salima , Flamant Martin , Vigeral Philippe
Published: May 2014

Purpose

Our aim was to evaluate the safety and effectiveness of the IRIS® bandage (Nephrokit®) on post-puncture bleeding compared to conventional manual compression.

Methods

Sixty-four patients, hemodialyzed with an arteriovenous fistula, were enrolled in a 3-week prospective study. Conventional manual compression was used during the first week, the IRIS® bandage during the second week and conventional manual compression again during the third week. The outcomes analyzed were the persistence or absence of bleeding 3 minutes post-puncture with IRIS® device compared to conventional manual compression. The safety of the IRIS® bandage was also evaluated.

Results

Rates of persistent bleeding 3 minutes post-puncture at arterial sites were 53±6% and 56±5%, respectively, during the first and third weeks (conventional compression) versus 18±5% during the second week (IRIS® bandage). Similarly, rates of persistent bleeding 3 minutes post-puncture at venous sites were 45±6% and 45±6%, respectively, with conventional compression versus 23±5% with the IRIS® bandage. The difference between the IRIS® device and conventional compression therefore proved highly statistically significant (p<0.05) for both arterial and venous puncture sites. No particular adverse events were observed with the IRIS® device.

Conclusions

Post-puncture bleeding time at arteriovenous fistula sites is significantly shortened by the IRIS® bandage in comparison with conventional manual compression.