bluuebunny/crossref_metadata_2025 huggingface dataset:
PKC-θ-Deficient Mice Are Protected from Th1-Dependent Antigen-Induced Arthritis
Authors: Healy Aileen M. , Izmailova Elena , Fitzgerald Michael , Walker Russell , Hattersley Maureen , Silva Matthew , Siebert Elizabeth , Terkelsen Jennifer , Picarella Dominic , Pickard Michael D. , LeClair Brett , Chandra Sudeep , Jaffee Bruce
Published: April 2014

T cell effector functions contribute to the pathogenesis of rheumatoid arthritis. PKC-θ transduces the signal from the TCR through activation of transcription factors NF-κB, AP-1, and NFAT. We examined the effects of PKC-θ deficiency on two Th1-dependent models of Ag-induced arthritis and found that PKC-θ-deficient mice develop disease, but at a significantly diminished severity compared with wild-type mice. In the methylated BSA model, cellular infiltrates and articular cartilage damage were mild in the PKC-θ-deficient mice as compared with wild-type mice. Quantitation of histopathology reveals 63 and 77% reduction in overall joint destruction in two independent experiments. In the type II collagen-induced arthritis model, we observed a significant reduction in clinical scores (p < 0.01) in three independent experiments and diminished joint pathology (p < 0.005) in PKC-θ-deficient compared with wild-type littermates. Microcomputerized tomographic imaging revealed that PKC-θ deficiency also protects from bone destruction. PKC-θ-deficient CD4+ T cells show an impaired proliferative response, decreased intracellular levels of the cytokines IFN-γ, IL-2, and IL-4, and significantly diminished cell surface expression of the activation markers CD25, CD69, and CD134/OX40 on memory T cells. We demonstrate decreased T-bet expression and significantly reduced IgG1 and IgG2a anti-collagen II Ab levels in PKC-θ-deficient mice. Collectively, our results demonstrate that PKC-θ deficiency results in an attenuated response to Ag-induced arthritis, which is likely mediated by the reduced T cell proliferation, Th1/Th2 cell differentiation and T cell activation before and during disease peak.
The Antiapoptotic Effect of Heme Oxygenase-1 in Endothelial Cells Involves the Degradation of p38α MAPK Isoform
Authors: Silva Gabriela , Cunha Andreia , Grégoire Isabel Pombo , Seldon Mark P. , Soares Miguel P.
Published: April 2014

Heme oxygenase-1 (HO-1) protects endothelial cells (EC) from undergoing apoptosis. This effect is mimicked by CO, generated via the catabolism of heme by HO-1. The antiapoptotic effect of CO in EC was abrogated when activation of the p38α and p38β MAPKs was inhibited by the pyridinyl imidazole SB202190. Using small interfering RNA, p38β was found to be cytoprotective in EC, whereas p38α was not. When overexpressed in EC, HO-1 targeted specifically the p38α but not the p38β MAPK isoform for degradation by the 26S proteasome, an effect reversed by the 26S proteasome inhibitors MG-132 or lactacystin. Inhibition of p38α expression was also observed when HO-1 was induced physiologically by iron protoporphyrin IX (hemin). Inhibition of p38α no longer occurred when HO activity was inhibited by tin protoporphyrin IX, suggesting that p38α degradation was mediated by an end product of heme catabolism. Exogenous CO inhibited p38α expression in EC, suggesting that CO is the end product that mediates this effect. The antiapoptotic effect of HO-1 was impaired when p38α expression was restored ectopically or when its degradation by the 26S proteasome was inhibited by MG-132. Furthermore, the antiapoptotic effect of HO-1 was lost when p38β expression was targeted by a specific p38β small interfering RNA. In conclusion, the antiapoptotic effect of HO-1 in EC is dependent on the degradation of p38α by the 26S proteasome and on the expression of p38β.
Alternative Complement Pathway Activation Is Essential for Inflammation and Joint Destruction in the Passive Transfer Model of Collagen-Induced Arthritis
Authors: Banda Nirmal K. , Thurman Joshua M. , Kraus Damian , Wood Allyson , Carroll Michael C. , Arend William P. , Holers V. Michael
Published: April 2014

Activation of each complement initiation pathway (classical, alternative, and lectin) can lead to the generation of bioactive fragments with resulting inflammation in target organs. The objective of the current study was to determine the role of specific complement activation pathways in the pathogenesis of experimental anti-type II collagen mAb-passive transfer arthritis. C57BL/6 mice were used that were genetically deficient in either the alternative pathway protein factor B (Bf−/−) or in the classical pathway component C4 (C4−/−). Clinical disease activity was markedly decreased in Bf−/− compared with wild-type (WT) mice (0.5 ± 0.22 (n = 6) in Bf−/− vs 8.83 ± 0.41 (n = 6) in WT mice (p < 0.0001)). Disease activity scores were not different between C4−/− and WT mice. Analyses of joints showed that C3 deposition, inflammation, pannus, cartilage, and bone damage scores were all significantly less in Bf−/− as compared with WT mice. There were significant decreases in mRNA levels of C3, C4, CR2, CR3, C3aR, and C5aR in the knees of Bf−/− as compared with C4−/− and WT mice with arthritis; mRNA levels for complement regulatory proteins did not differ between the three strains. These results indicate that the alternative pathway is absolutely required for the induction of arthritis following injection of anti-collagen Abs. The mechanisms by which these target organ-specific mAbs bypass the requirements for engagement of the classical pathway remain to be defined but do not appear to involve a lack of alternative pathway regulatory proteins.
MAPKAP Kinase 2-Deficient Mice Are Resistant to Collagen-Induced Arthritis
Authors: Hegen Martin , Gaestel Matthias , Nickerson-Nutter Cheryl L. , Lin Lih-Ling , Telliez Jean-Baptiste
Published: April 2014

TNF-α is a pleiotropic cytokine considered a primary mediator of immune regulation and inflammatory response and has been shown to play a central role in rheumatoid arthritis (RA). MAPKAP kinase 2 (MK2) is a serine/threonine kinase that is regulated through direct phosphorylation by p38 MAPK, and has been shown to be an essential component in the inflammatory response that regulates the biosynthesis of TNF-α at a posttranscriptional level. The murine model of collagen-induced arthritis (CIA) is an established disease model to study pathogenic mechanisms relevant to RA. In this study, we report that deletion of the MK2 gene in DBA/1LacJ mice confers protection against CIA. Interestingly, the MK2 heterozygous mutants display an intermediate level of protection when compared with homozygous mutant and wild-type littermates. We show that MK2−/− and MK2+/− mice exhibit decreased disease incidence and severity in the CIA disease model and reduced TNF-α and IL-6 serum levels following LPS/d-Gal treatment compared with wild-type mice. Additionally, we show that levels of IL-6 mRNA in paws of mice with CIA correlate with the disease status. These findings suggest that an MK2 inhibitor could be of great therapeutic value to treat inflammatory diseases like RA.
TLR2 Stimulation of Intrinsic Renal Cells in the Induction of Immune-Mediated Glomerulonephritis
Authors: Brown Heather J. , Lock Helen R. , Sacks Steven H. , Robson Michael G.
Published: April 2014

Infection may exacerbate organ-specific autoimmune disease such as glomerulonephritis. This may occur in the absence of a measurable effect on the adaptive immune response, and the mechanisms responsible are not fully understood. To investigate this, we have studied the effect of TLR2 ligation by the synthetic ligand Pam3CysSK4 on the development of glomerulonephritis in mice. We demonstrated that glomerular inflammation induced by passive administration of nephrotoxic Ab does not occur in the absence of TLR2 stimulation, with a strong synergy when Ab deposition and TLR2 stimulation occur together. Parameters of glomerular inflammation were neutrophil influx, thrombosis, and albuminuria. To investigate the relative contribution of TLR2 on bone marrow-derived cells and intrinsic renal cells, we constructed bone marrow chimeras. Nephrotoxic Ab and TLR2 ligation caused a neutrophil influx in both types of chimera at a similar level to that seen in sham chimeras totally TLR2 sufficient. Albuminuria was seen in both types of chimera above that seen in sham chimeras that were totally TLR2 deficient. This was greater in chimeras with TLR2 present on bone marrow-derived cells. To find a potential mechanism by which intrinsic renal cells may contribute toward disease exacerbation, mesangial cells were studied and shown to express TLR2 and MyD88. Wild-type but not TLR2-deficient mesangial cells produced CXC chemokines in response to stimulation with Pam3CysSK4. These results demonstrate that TLR2 stimulation on both bone marrow-derived and resident tissue cells plays a role in amplifying the inflammatory effects of Ab deposition in the glomerulus.
Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality
Authors: Osuchowski Marcin F. , Welch Kathy , Siddiqui Javed , Remick Daniel G.
Published: April 2014

Mortality in sepsis remains unacceptably high and attempts to modulate the inflammatory response failed to improve survival. Previous reports postulated that the sepsis-triggered immunological cascade is multimodal: initial systemic inflammatory response syndrome (SIRS; excessive pro-, but no/low anti-inflammatory plasma mediators), intermediate homeostasis with a mixed anti-inflammatory response syndrome (MARS; both pro- and anti-inflammatory mediators) and final compensatory anti-inflammatory response syndrome (CARS; excessive anti-, but no/low proinflammatory mediators). To verify this, we examined the evolution of the inflammatory response during the early phase of murine sepsis by repetitive blood sampling of septic animals. Increased plasma concentrations of proinflammatory (IL-6, TNF, IL-1β, KC, MIP-2, MCP-1, and eotaxin) and anti-inflammatory (TNF soluble receptors, IL-10, IL-1 receptor antagonist) cytokines were observed in early deaths (days 1–5). These elevations occurred simultaneously for both the pro- and anti-inflammatory mediators. Plasma levels of IL-6 (26 ng/ml), TNF-α (12 ng/ml), KC (33 ng/ml), MIP-2 (14 ng/ml), IL-1 receptor antagonist (65 ng/ml), TNF soluble receptor I (3 ng/ml), and TNF soluble receptor II (14 ng/ml) accurately predicted mortality within 24 h. In contrast, these parameters were not elevated in either the late-deaths (day 6–28) or survivors. Surprisingly, either pro- or anti-inflammatory cytokines were also reliable in predicting mortality up to 48 h before outcome. These data demonstrate that the initial inflammatory response directly correlates to early but not late sepsis mortality. This multifaceted response questions the use of a simple proinflammatory cytokine measurement for classifying the inflammatory status during sepsis.
Autoimmune Targeted Disruption of the Pituitary-Ovarian Axis Causes Premature Ovarian Failure
Authors: Altuntas Cengiz Z. , Johnson Justin M. , Tuohy Vincent K.
Published: April 2014

Premature ovarian failure (POF) is characterized by amenorrhea and high serum levels of follicle-stimulating hormone (FSH). POF causes female infertility and represents a substantial women’s health risk affecting 1% of women by age 40. Although ovarian autoimmunity has been associated with POF, the identity of ovarian Ags recognized is unknown. In this study, we show that autoimmune-targeted disruption of the pituitary-ovarian axis leads to POF. Immunization of SWXJ female mice with the p215–234 peptide derived from mouse inhibin-α activates CD4+ T cells and induces experimental autoimmune oophoritis with a unique biphasic phenotype characterized by an early stage of enhanced fertility followed by a delayed stage of POF. Affected mice show high serum levels of inhibin-α-neutralizing Abs that prevent inhibin-mediated down-regulation of activin-induced pituitary FSH release. The loss of activin/FSH down-regulation leads to prolonged metestrus-diestrus, superovulation, increased numbers of mature follicles, increased offspring, accelerated depletion of primordial follicles, and ultimately premature infertility. Thus, inhibin-α-targeted experimental autoimmune oophoritis is initiated by CD4+ Th1 T cells that stimulate B cells to produce inhibin-α-neutralizing Abs directly capable of mediating POF and transferring disease into naive recipients. Our inhibin-α autoimmune model of POF shows how premature infertility may develop in the context of elevated FSH levels thereby closely mimicking the hallmark features of human POF.
The mitochondrial genome of the antarctic springtail Folsomotoma octooculata (Hexapoda; Collembola), and an update on the phylogeny of collembolan lineages based on mitogenomic data
Authors: Carapelli A. , Convey P. , Nardi F. , Frati F.
Published: April 2014

This study provides the description of the complete mitochondrial genome of the Antarctic collembola Folsomotoma octooculata. Since mitogenomic data are extensively used for phylogenetic reconstruction, we also provide a phylogenetic reconstruction of the internal relationships of some collembola taxa using the complete mitochondrial DNA data available at present for this group. The complete mitochondrial genome sequence of F. octooculata has been obtained using standard amplification and sequencing methods for long DNA templates. Sequence data are analyzed using bayesian methods based on the analysis of nucleotide and amino acid sequences. The complete set of available mitochondrial DNA sequences for ten species of the group is also analyzed for the presence of lineage-specific gene order of the 37 encoded genes. The results of the phylogenetic analysis are compared with previous morphological and molecular analyses, showing some intriguing outcomes, such as the paraphyly of Entomobryomorpha, the derived position of Podura aquatica within Poduromorpha, and the sister group relationships between the single Symphypleona species available for comparison and the entomobryid Orchesella villosa. The F. octooculata mitochondrial genome generally conforms with those observed in other basal hexapod species and displays the plesiomorphic gene order observed for Pancrustacea. Mitogenomic data are useful to reconstruct a molecular phylogeny of major collembolan taxa. In spite of the limited number of species for which entire mitochondrial genomes are known, the coverage of many of the major lineages allows some preliminary conclusions concerning the relationships among families and suborders.
Faithfulness of Actions on Riemann-Roch Spaces
Authors: Köck Bernhard , Tait Joseph
Published: April 2014

Given a faithful action of a finite groupGon an algebraic curveXof genusgX≥ 2, we giveexplicit criteria for the induced action ofGon the Riemann–Roch spaceH0(X,OX(D)) to be faithful,whereDis aG-invariant divisor on X of degree at least 2gX− 2. This leads to a concise answer to the question of when the action ofGon the spaceH0(X,Ωx⊗m) of global holomorphic polydifferentials of order m is faithful. IfXis hyperelliptic, we provide an explicit basis of H0(X,Ωx⊗m). Finally, we giveapplications in deformation theory and in coding theory and discuss the analogous problem for theaction ofGon the first homologyH1(X,ℤ/mℤ) ifXis a Riemann surface.
Linking climate and air quality over Europe: effects of meteorology on PM2.5 concentrations
Authors: Megaritis A. G. , Fountoukis C. , Charalampidis P. E. , Denier van der Gon H. A. C. , Pilinis C. , Pandis S. N.
Published: April 2014

Abstract. The effects of various meteorological parameters such as temperature, wind speed, absolute humidity, precipitation and mixing height on PM2.5 concentrations over Europe were examined using a three-dimensional chemical transport model, PMCAMx-2008. Our simulations covered three periods, representative of different seasons (summer, winter, and fall). PM2.5 appears to be more sensitive to temperature changes compared to the other meteorological parameters in all seasons. PM2.5 generally decreases as temperature increases, although the predicted changes vary significantly in space and time, ranging from −700 ng m−3 K−1 (−8% K−1) to 300 ng m−3 K−1 (7% K−1). The predicted decreases of PM2.5 are mainly due to evaporation of ammonium nitrate, while the higher biogenic emissions and the accelerated gas-phase reaction rates increase the production of organic aerosol (OA) and sulfate, having the opposite effect on PM2.5. The predicted responses of PM2.5 to absolute humidity are also quite variable, ranging from −130 ng m−3%−1 (−1.6% %−1) to 160 ng m−3 %−1 (1.6% %−1) dominated mainly by changes in inorganic PM2.5 species. An increase in absolute humidity favors the partitioning of nitrate to the aerosol phase and increases the average PM2.5 during summer and fall. Decreases in sulfate and sea salt levels govern the average PM2.5 response to humidity during winter. A decrease of wind speed (keeping constant the emissions) increases all PM2.5 species (on average 40 ng m−3 %−1) due to changes in dispersion and dry deposition. The wind speed effects on sea salt emissions are significant for PM2.5 concentrations over water and in coastal areas. Increases in precipitation have a negative effect on PM2.5 (decreases up to 110 ng m−3 %−1) in all periods due to increases in wet deposition of PM2.5 species and their gas precursors. Changes in mixing height have the smallest effects (up to 35 ng m−3 %−1) on PM2.5. Regarding the relative importance of each of the meteorological parameters in a changed future climate, the projected changes in precipitation are expected to have the largest impact on PM2.5 levels during all periods (changes up to 2 μg m−3 in the fall). The expected effects in future PM2.5 levels due to wind speed changes are similar in all seasons and quite close to those resulting from future precipitation changes (up to 1.4 μg m−3). The expected increases in absolute humidity in the future can lead to large changes in PM2.5 levels (increases up to 2 μg m−3) mainly in the fall due to changes in particulate nitrate levels. Despite the high sensitivity of PM2.5 levels to temperature, the small expected increases of temperature in the future will lead to modest PM2.5 changes and will not dominate the overall change.
A molecular-level approach for characterizing water-insoluble components of ambient organic aerosol particulates using ultra-high resolution mass spectrometry
Authors: Willoughby A. S. , Wozniak A. S. , Hatcher P. G.
Published: April 2014

Abstract. The chemical composition of organic aerosols in the atmosphere is strongly influenced by human emissions, and the effect these have on the environment, human health, and climate change is determined by the molecular nature of these chemical species. The complexity of organic aerosol samples limits the ability to study the chemical composition, and, therefore, the associated properties and the impacts they have. Many studies address the water-soluble fraction of organic aerosols, and have had much success in identifying specific molecular formulas for thousands of compounds present. However, little attention is given to the water-insoluble portion, which can contain most of the fossil material that is emitted through human activity. Here we compare the organic aerosols present in water extracts and organic solvent extracts (pyridine and acetonitrile) of an ambient aerosol sample collected in a rural location that is impacted by natural and anthropogenic emission sources. A semi-quantitative method was developed using proton nuclear magnetic resonance spectroscopy to determine that the amount of organic matter extracted by pyridine is comparable to that of water. Electrospray ionization Fourier transform ion cyclotron resonance mass spectra show that pyridine extracts a molecularly unique fraction of organic matter compared to water or acetonitrile, which extract chemically similar organic matter components. The molecular formulas unique to pyridine were less polar, more aliphatic, and reveal formulas containing sulfur to be an important component of insoluble aerosol organic matter.
Comparing modelled fire dynamics with charcoal records for the Holocene
Authors: Brücher T. , Brovkin V. , Kloster S. , Marlon J. R. , Power M. J.
Published: April 2014

Abstract. An earth system model of intermediate complexity (CLIMate and BiosphERe – CLIMBER-2) and a land surface model (JSBACH), which dynamically represent vegetation, are used to simulate natural fire dynamics through the last 8000 yr. Output variables of the fire model (burned area and fire carbon emissions) are used to compare model results with sediment-based charcoal reconstructions. Several approaches for processing model output are also tested. Charcoal data are reported in Z-scores with a base period of 8000–200 BP in order to exclude the strong anthropogenic forcing of fire during the last two centuries. The model–data comparison reveals a robust correspondence in fire activity for most regions considered, while for a few regions, such as Europe, simulated and observed fire histories show different trends. The difference between modelled and observed fire activity may be due to the absence of anthropogenic forcing (e.g. human ignitions and suppression) in the model simulations, and also due to limitations inherent to modelling fire dynamics. The use of spatial averaging (or Z-score processing) of model output did not change the directions of the trends. However, Z-score-transformed model output resulted in higher rank correlations with the charcoal Z-scores in most regions. Therefore, while both metrics are useful, processing model output as Z-scores is preferable to areal averaging when comparing model results to transformed charcoal records.
The photolysis module JVAL-13.99gmdd, compatible with the MESSy standard, and the JVal PreProcessor (JVPP)
Authors: Sander R. , Jöckel P. , Kirner O. , Kunert A. T. , Landgraf J. , Pozzer A.
Published: April 2014

Abstract. We present version 13.99gmdd of the photolysis module JVAL. Taking atmospheric conditions as input, JVAL calculates photolysis rate coefficients, i. e., the speed of dissociation of atmospheric molecules in the sunlight. Computational efficiency is obtained through the use of parameters for polynomial curve fitting and lookup tables. JVAL also includes the auxiliary program JVPP (JVal PreProcessor) which pre-calculates these parameters based on the absorption cross sections and quantum yields of the atmospheric molecules. It is possible to either use JVAL as a stand-alone program, or as a module inside the Modular Earth Submodel System (MESSy). JVAL is a community model published under the GNU General Public License.
Panoramic rendering-based polygon extraction from indoor mobile LiDAR data
Authors: Nakagawa M. , Kataoka K. , Yamamoto T. , Shiozaki M. , Ohhashi T.
Published: April 2014

Abstract. In this paper, we propose a method for panoramic point-cloud rendering-based polygon extraction from indoor mobile LiDAR data. Our aim was to improve region-based point-cloud clustering in modeling after point-cloud registration. First, we propose a pointcloud clustering methodology for polygon extraction on a panoramic range image generated with point-based rendering from a massive point cloud. Next, we describe an experiment that was conducted to verify our methodology with an indoor mobile mapping system in an indoor environment. This experiment was wall-surface extraction using a rendered point-cloud from 64 viewpoints over a wide indoor area. Finally, we confirmed that our proposed methodology could achieve polygon extraction through point-cloud clustering from a complex indoor environment.
Modeling extreme wave heights from laboratory experiments with the nonlinear Schrödinger equation
Authors: Zhang H. D. , Guedes Soares C. , Cherneva Z. , Onorato M.
Published: April 2014

Abstract. Spatial variation of nonlinear wave groups with different initial envelope shapes is theoretically studied first, confirming that the simplest nonlinear theoretical model is capable of describing the evolution of propagating wave packets in deep water. Moreover, three groups of laboratory experiments run in the wave basin of CEHIPAR (Canal de Experiencias Hidrodinámicas de El Pardo, known also as El Pardo Model Basin) was founded in 1928 by the Spanish Navy. are systematically compared with the numerical simulations of the nonlinear Schrödinger equation. Although a little overestimation is detected, especially in the set of experiments characterized by higher initial wave steepness, the numerical simulation still displays a high degree of agreement with the laboratory experiments. Therefore, the nonlinear Schrödinger equation catches the essential characteristics of the extreme waves and provides an important physical insight into their generation. The modulation instability, resulting from the quasi-resonant four-wave interaction in a unidirectional sea state, can be indicated by the coefficient of kurtosis, which shows an appreciable correlation with the extreme wave height and hence is used in the modified Edgeworth–Rayleigh distribution. Finally, some statistical properties on the maximum wave heights in different sea states have been related with the initial Benjamin–Feir index.
Meteorological effects in the lower ionosphere as based on VLF/LF signal observations
Authors: Rozhnoi A. , Solovieva M. , Levin B. , Hayakawa M. , Fedun V.
Published: April 2014

Abstract. Very low and low frequency (VLF/LF) data recorded in the Far Eastern stations Petropavlovsk-Kamchatsky (158.92° E, 53.15° N), Yuzhno-Sakhalinsk (142.75° E, 46.95° N) and Yuzhno-Kurilsk (145.861° E, 44.03° N) are investigated to study the meteorological effects in the lower ionosphere. The results demonstrate the sensitivity of the VLF/LF signals to the variations of atmospheric pressure, humidity, wind velocity and temperature, and the VLF/LF record at the station of Yuzhno-Kurilsk is found to be most sensitive to those variations of atmospheric parameters. The region under consideration is characterized by high winter cyclonic activity in midlatitudes and strong summer and autumn typhoon activity in low latitudes. VLF/LF signal variations during 8 tropical cyclones (TCs) with different intensity are considered. Negative nighttime anomalies in the signal amplitude that are most probably caused by TC activity are found for 6 events. Those anomalies are observed during 1–2 days when TCs move inside the sensitivity zones of the subionospheric paths. Perturbations of the VLF signal observed during 2 TCs can be caused by both the TC influence and seismic activity, but no correlation between TC intensity and magnitude of the signal anomalies is found. Spectral analysis of the typhoon-induced disturbed signals revealed the fluctuations with time periods in the range of 7–16 and 15–55 min that corresponds to the range of internal gravity waves periods.
Non-susceptible landslide areas in Italy and in the Mediterranean region
Authors: Marchesini I. , Ardizzone F. , Alvioli M. , Rossi M. , Guzzetti F.
Published: April 2014

Abstract. We used landslide information for 13 study areas in Italy and morphometric information obtained from the 3 arc-second SRTM DEM to determine areas where landslide susceptibility is expected to be null or negligible in Italy, and in the landmasses surrounding the Mediterranean Sea. The morphometric information consisted in the local terrain slope computed in a square 3 × 3 cell moving window, and in the regional relative relief computed in a circular 15 × 15 cell moving window. We tested three different models to determine the non-susceptible landslide areas, including a linear model (LR), a quantile linear model (QLR), and a quantile non-linear model (QNL). We tested the performance of the three models using independent landslide information represented by the Italian Landslide Inventory (Inventario Fenomeni Franosi in Italia – IFFI). Best results were obtained using the QNL model. The corresponding zonation of non-susceptible landslide areas was intersected in a GIS with geographical census data for Italy. The result allowed determining that 57.5% of the population of Italy (in 2001) was located in areas where landslide susceptibility is expected to be null or negligible, and that the remaining 42.5% was located in areas where some landslide susceptibility is expected. We applied the QNL model to the landmasses surrounding the Mediterranean Sea, and we tested the synoptic non-susceptibility zonation using independent landslide information for three study areas in Spain. Results proved that the QNL model was capable of determining where landslide susceptibility is expected to be negligible in the Mediterranean area. We expect our results to be applicable in similar study areas, facilitating the identification of non-susceptible and susceptible landslide areas, at the synoptic scale.
FLIP-MHD-based model sensitivity analysis
Authors: Skandrani C. , Innocenti M. E. , Bettarini L. , Crespon F. , Lamouroux J. , Lapenta G.
Published: April 2014

Abstract. The state of the art in the forecast of the background solar wind speed and of the interplanetary magnetic field at Earth is based on the use as boundary conditions for heliospheric models of the input data provided by solar observations. Magnetogram synoptic maps are used to obtain information on the magnetic field configuration at the solar source surface. Magnetic field inputs at the solar source surface thus constitute one of the main external sources of errors in solar wind models. The assimilation of data into forecasting models used in the terrestrial domain showed the ability to control model state errors. A sensitivity study performed through the analysis of the ensemble variances and the representers technique is used here to assess how process and model state errors propagate in a nonlinear two-dimensional MagnetoHydro Dynamic (MHD) system. The aim is to understand the impact of the source surface input parameters on the evolution of MHD heliospheric models and the potentialities of data assimilation techniques in solar wind forecasting. The representer technique in fact allows one to understand how far from the observation point the improvement granted from the assimilation of a measure propagates.
Fluctuations of a Greenlandic tidewater glacier driven by changes in atmospheric forcing: observations and modelling of Kangiata Nunaata Sermia, 1859–present
Authors: Lea J. M. , Mair D. W. F. , Nick F. M. , Rea B. R. , van As D. , Morlighem M. , Nienow P. W. , Weidick A.
Published: April 2014

Abstract. Many tidewater glaciers in Greenland are known to have undergone significant retreat during the last century following their Little Ice Age maxima. Where it is possible to reconstruct glacier change over this period, they provide excellent records for comparison to climate records, and calibration/validation for numerical models. These records therefore allow tests of numerical models that seek to simulate tidewater glacier behaviour over multi-decadal to centennial timescales. Here we present a detailed record of behaviour from Kangiata Nunaata Sermia (KNS), SW Greenland, between 1859–2012 and compare it against available oceanographic and atmospheric temperature variability between 1871–2012. We also use these records to evaluate the ability of a well-established one-dimensional flow-band model to replicate behaviour for the observation period. The record of terminus change demonstrates that KNS has advanced/retreated in phase with atmosphere and ocean climate anomalies averaged over multi-annual to decadal timescales. Results from an ensemble of model runs demonstrate that observed dynamics can be replicated, with changes in atmospheric forcing not needing to be offset by changes in oceanic forcing sensitivity. Furthermore, successful runs always require a significant atmospheric forcing component, while an oceanic forcing component is not always needed. Although the importance of oceanic forcing cannot be discounted, these results demonstrate that changes in atmospheric forcing are likely to be a primary driver of the terminus fluctuations of KNS from 1859–2012.
Effect of Fetal Sex on Total Levels of Maternal Serum Testosterone
Authors: Nabi Ghulam , Aziz Tariq , Amin Muhammad , Khan Ayaz Ali
Published: April 2014

The aim of this study was to find out the effect of fetal sex on maternal serum total testosterone level and its application for fetal sex determination.Forty healthy pregnant (second trimester) females were recruited in the study from rural areas of district Dir lower, Khyber Pakhtunkhwa, Pakistan, having complete antenatal record. Twenty of them were carrying single male fetuses and twenty female fetuses. The inclusions criteria were age (25 to 30), second trimester, absence of serious diseases, availability of antenatal record, no drug addiction and no exposure to pesticides.  Blood samples at 5 ml size were collected from each woman, serum was obtained and was assayed by Bio-check (USA) kit according to the manufacturer protocol.In male fetus group the mean and SD was 169±27.18 ng/dl and in female fetus group the Mean± SD was 166.6±30.47 ng/dl. There was nosignificant difference (P 0.1062) between the two groups at 95% confidence level.The results suggest that sex of the fetus has no association with maternal serum total testosterone among the study population-and should not be analyzed for sex determination. Further study with bigger sample size of different population groups in different gestational stages is needed to find the fetal effect on maternal serum testosterone because, increased level of testosterone in females can cause aggression, other behavioral changes, acnes and abrupt growth of pubic and axillary hairs.
Are microRNAs key players in epithelial skin cancers? A review focused on basal cell carcinoma and squamous cell carcinoma
Authors: Ruland Rebecca , Florea Ana-Maria
Published: April 2014

The cancer of the skin is an increasing problem for public health worldwide. The fair skin populations that are environmentally or occupationally exposed to solar ultraviolet (UV)-radiation are the most affected. Intensive research investigating the molecular mechanisms of skin cancer is ongoing, however the role of noncoding RNAs in the pathology of cutaneous cell carcinoma is not fully understood. Accumulating evidence show that miRNAs play an important role in physiologic, pathologic and carcinogenic processes but their role in epithelial skin cancers (i.e. basal cell carcinoma and squamous cell carcinoma) was to date not sufficiently highlighted. MiRNAs are single-stranded small RNAs which specifically target mRNAs for translational repression and/or mRNA decay. In this review we focus on the latest findings in this area of research reviewing the newest research trends and perspectives.
Geochemistry of the Um Had Plutonites, Central Eastern Desert, Egypt: Implications for Magma Evolution, and Tectonic Setting
Authors: Qaoud Nedal
Published: April 2014

Geochemistry of gabbroid and granitoid plutonites from the Um Had area indicates island arc subalkaline basic magma with tholeiitic affinity and calc-alkaline, metaluminous and slightly peraluminous magma, respectively. Although different in age both plutonite types were emplaced under compressional regime, where subduction-related environment was dominant. They were formed under relatively low to moderate water-vapour pressure (1–5 k-bars) at moderate depths (20–30 km). Biotite granites were formed at a relatively high temperature range (800–840 °C), while biotite-muscovite granites were formed under relatively moderate temperature conditions (760–800 °C). These two units may represent evolution from island arc to active continental margin. It is suggested that island arc gabbros might have sourced the late subduction-related calc-alkaline granitoids during the waning stages of the pan-African orogeny. The I-type nature of the investigated plutonites in the study area and elsewhere suggests the juvenile character of the basement complex of the Eastern Desert of Egypt.
Recent Trends in Temperature and Relative Humidity in Bawku East, Northern Ghana
Authors: K. Frimpong , J. Oosthuizen , J. Van Etten E.
Published: April 2014

Extensive analyses of trends in mean annual and mean seasonal minimum and maximum temperatures and relative humidity were examined for Bawku East, northern Ghana, for the period 1961 to 2012. Mean monthly maximum and minimum temperatures were used to analyse and establish recent temperature trends on an annual and seasonal basis. The year was divided into rainy and dry seasons for the seasonal trends. Mean monthly relative humidity at 6 am and 3 pm from 1961 to 2012 were considered to show recent trends in humidity since temperature and humidity interact to determine the heat exposure for outdoor workers. Regression analysis was used to illustrate trends and calculate mean yearly and seasonal rate of change. A Durbin-Watson statistical test was employed to verify autocorrelation of the residuals of the trend models and none was detected. Results showed a gradual and statistically significant rise in both mean minimum and mean maximum temperatures at two stations (Manga and Garu). There was an inconsistent pattern of trend observed at the third station (Binduri). Declining trends in relative humidity were observed at 6 am and 3 pm at seasonal and annual levels at Binduri and Garu, while there was a rising trend in relative humidity at Manga. The importance of this study hinges on the linkage between heat exposure (temperature and air humidity) and human health in the wake of climate change on outdoor farmers in developing countries who spend many hours doing manual work in the heat. On the whole, the rising temperature has impacted on ecosystem services in the study area.
Le Prince et le problème de la corruption : réflexions sur une aporie machiavélienne
Authors: Sparling Robert
Published: April 2014

Dans les études sur la corruption politique, on trouve fréquemment des retours au lieu commun que les problèmes d’abus de charge publique en vue d’un intérêt privé ne peuvent être réglés sans la magie du leadership (l’anglicisme malheureux s’impose ici), cette qualité énigmatique de commandement qui saurait mettre en place les dispositifs d’incitatifs, de surveillance et de contrôle nécessaires pour contrer les abus. Mais un tel argument mène à une aporie, car les études qui placent ainsi leur confiance dans cet énigmatique leadership sont également traversées par l’idée, aussi un lieu commun, que toute autorité qui n’est pas sujette à la surveillance et au contrôle aura tendance à être corrompue. Dans cet essai, je propose de lire Le Prince de Machiavel comme une méditation sur le paradoxe suivant : l’autorité du principe est à la fois la source de la purification politique et la cause principale de la corruption. Le Prince, souvent considéré comme un texte fondateur des « leadership ethics », sera mal compris s’il n’est pas lu à la lumière de la préoccupation centrale de Machiavel républicain : la corruption.
The Civic Duty to Report Crime and Corruption
Authors: Delmas Candice
Published: April 2014

Is the civic duty to report crime and corruption a genuine moral duty? After clarifying the nature of the duty, I consider a couple of negative answers to the question, and turn to an attractive and commonly held view, according to which this civic duty is a genuine moral duty. On this view, crime and corruption threaten political stability, and citizens have a moral duty to report crime and corruption to the government in order to help the government’s law enforcement efforts. The resulting duty is triply general in that it applies to everyone, everywhere, and covers all criminal and corrupt activity. In this paper, I challenge the general scope of this argument. I argue that that the civic duty to report crime and corruption to the authorities is much narrower than the government claims and people might think, for it only arises when the state (i) condemns genuine wrongdoing and serious ethical offenses as “crime” and “corruption,” and (ii) constitutes a dependable “disclosure recipient,” showing the will and power to hold wrongdoers accountable. I further defend a robust duty to directly report to the public—one that is weightier and wider than people usually assume. When condition (ii) fails to obtain, I submit, citizens are released of the duty to report crime and corruption to the authorities, but are bound to report to the public, even when the denunciation targets the government and is risky or illegal.
Institutional Corruption and the Rule of Law1
Authors: Gowder Paul
Published: April 2014

The literature contains two concepts of corruption which are often confused with one another: corruption as twisted character (pollution), and corruption as disloyalty. It also contains two sites for corruption: the corruption of individuals, and the corruption of entire institutions such as a state or a legislature.

This paper first draws a clear distinction between the pollution and disloyalty concepts of corruption in the individual context, and then defends a conception of disloyalty corruption according to which the distinguishing feature is an agent who uses powers delegated to her from her principal as her own. Then, the paper shifts gears to the institutional context, arguing that the best account of institutional corruption in the extant literature is of the pollution kind. It then fills the remaining logical space by laying out a conception of institutional corruption as disloyalty and explaining its moral significance for the political legitimacy of a democracy.
Liberal Democratic Institutions and the Damages of Political Corruption1
Authors: Ceva Emanuela , Ferretti Maria Paola
Published: April 2014

This article contributes to the debate concerning the identification of politically relevant cases of corruption in a democracy by sketching the basic traits of an originalliberaltheory of institutional corruption. We define this form of corruption as a deviation with respect to the role entrusted to people occupying certain institutional positions, which are crucial for the implementation of public rules, for private gain. In order to illustrate the damages that corrupt behaviour makes to liberal democratic institutions, we discuss the case of health care professionals’ abuse of their right to conscientious objection to abortion services. We show that the conscience clause can be instrumentally abused to sabotage democratically established public rules and thus exert undue private influence on their implementation. In this sense, from a liberal democratic perspective, institutional corruption is problematic because it is disruptive of such fundamental liberal ideals as the impartiality of public institutions and citizens’ political equality.
La démocratie sans limites : corruption et publicités dans les campagnes électorales américaines
Authors: Roussin Juliette
Published: April 2014

Cet article analyse le risque de corruption que les arrêts Citizens United de 2010 et l’apparition des Super-PACs font peser sur le système électoral états-unien. Lors de la dernière campagne présidentielle, plus de 730 millions de dollars ont été investis dans des publicités électorales par de riches contributeurs et des entreprises privées regroupés en Super-PACs. Nous montrons que cet afflux d’argent consacré à des publicités politiques expose la démocratie américaine à trois formes de « corruption grise », en favorisant la banalisation de pratiques contestables et en troublant la frontière entre ce qui est licite et ce qui ne l’est pas. (1) Déplafonné, le soutien financier aux candidats risque de s’apparenter à de la subornation; (2) certaines des techniques publicitaires employées semblent réduire l’exercice de conviction démocratique à une tentative de corruption de l’électeur; (3) enfin les immenses inégalités d’influence politique que ce système de financement induit participent de la corruption des affaires démocratiques en favorisant leur captation par un petit nombre d’individus fortunés. Nous mettons en évidence que le refus systématique de la Cour Suprême d’envisager ces phénomènes comme des vecteurs de corruption se fonde sur une conception discutable de la démocratie comme système de libre concurrence pour le pouvoir politique. Comprendre la démocratie à partir de son impératif d’égalité permet à l’inverse de rendre visible la corruption à laquelle son système de financement électoral expose la démocratie américaine.
A gene horizontally transferred from bacteria protects arthropods from host plant cyanide poisoning
Authors: Wybouw Nicky , Dermauw Wannes , Tirry Luc , Stevens Christian , Grbić Miodrag , Feyereisen René , Van Leeuwen Thomas
Published: April 2014

Cyanogenic glucosides are among the most widespread defense chemicals of plants. Upon plant tissue disruption, these glucosides are hydrolyzed to a reactive hydroxynitrile that releases toxic hydrogen cyanide (HCN). Yet many mite and lepidopteran species can thrive on plants defended by cyanogenic glucosides. The nature of the enzyme known to detoxify HCN to β-cyanoalanine in arthropods has remained enigmatic. Here we identify this enzyme by transcriptome analysis and functional expression. Phylogenetic analysis showed that the gene is a member of the cysteine synthase family horizontally transferred from bacteria to phytophagous mites and Lepidoptera. The recombinant mite enzyme had both β-cyanoalanine synthase and cysteine synthase activity but enzyme kinetics showed that cyanide detoxification activity was strongly favored. Our results therefore suggest that an ancient horizontal transfer of a gene originally involved in sulfur amino acid biosynthesis in bacteria was co-opted by herbivorous arthropods to detoxify plant produced cyanide.
AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter
Authors: Schulze-Gahmen Ursula , Lu Huasong , Zhou Qiang , Alber Tom
Published: April 2014

Superelongation complexes (SECs) are essential for transcription elongation of many human genes, including the integrated HIV-1 genome. At the HIV-1 promoter, the viral Tat protein binds simultaneously to the nascent TAR RNA and the CycT1 subunit of the P-TEFb kinase in a SEC. To understand the preferential recruitment of SECs by Tat and TAR, we determined the crystal structure of a quaternary complex containing Tat, P-TEFb, and the SEC scaffold, AFF4. Tat and AFF4 fold on the surface of CycT1 and interact directly. Interface mutations in the AFF4 homolog AFF1 reduced Tat–AFF1 affinity in vivo and Tat-dependent transcription from the HIV promoter. AFF4 binding in the presence of Tat partially orders the CycT1 Tat–TAR recognition motif and increases the affinity of Tat-P-TEFb for TAR 30-fold. These studies indicate that AFF4 acts as a two-step filter to increase the selectivity of Tat and TAR for SECs over P-TEFb alone.
The GTPase IFT27 is involved in both anterograde and retrograde intraflagellar transport
Authors: Huet Diego , Blisnick Thierry , Perrot Sylvie , Bastin Philippe
Published: April 2014

The construction of cilia and flagella depends on intraflagellar transport (IFT), the bidirectional movement of two protein complexes (IFT-A and IFT-B) driven by specific kinesin and dynein motors. IFT-B and kinesin are associated to anterograde transport whereas IFT-A and dynein participate to retrograde transport. Surprisingly, the small GTPase IFT27, a member of the IFT-B complex, turns out to be essential for retrograde cargo transport in Trypanosoma brucei. We reveal that this is due to failure to import both the IFT-A complex and the IFT dynein into the flagellar compartment. To get further molecular insight about the role of IFT27, GDP- or GTP-locked versions were expressed in presence or absence of endogenous IFT27. The GDP-locked version is unable to enter the flagellum and to interact with other IFT-B proteins and its sole expression prevents flagellum formation. These findings demonstrate that a GTPase-competent IFT27 is required for association to the IFT complex and that IFT27 plays a role in the cargo loading of the retrograde transport machinery.