bluuebunny/crossref_metadata_2025_split huggingface dataset:
cIAP1/2–TRAF2–SHP-1–Src–MyD88 Complex Regulates Lipopolysaccharide-Induced IL-27 Production through NF-κB Activation in Human Macrophages
Authors: Busca Aurelia , Konarski Yulia , Gajanayaka Niranjala , O’Hara Shifawn , Angel Jonathan , Kozlowski Maya , Kumar Ashok 
Published: January 2018

Abstract
The inhibitors of apoptosis (IAP) proteins, initially described in the context of apoptosis regulation as promoting cell survival, have recently emerged as key regulators of innate immune signaling. As a result, downregulation of IAP via Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate cytokine production in murine models either as a single agent or in response to LPS. However, the role of SMM and the involvement of IAPs in primary human cells and in particular macrophages with respect to cytokine production and innate immune responses remain largely unknown. IL-27, a member of the IL-12 cytokine family produced by APCs such as macrophages, has broad immunoregulatory properties in both innate and adaptive immune responses. Herein, we show that cellular IAPs (cIAPs) positively regulate LPS-induced IL-27 production in both primary human monocytes and macrophages. Investigations for the signaling mechanism of cIAPs involvement in IL-27 production in human macrophages revealed that LPS-induced IL-27 production is regulated by a novel signaling complex comprising cIAP1/2, TNFR-associated factor 2 (TRAF2), SHP-1, Src, and MyD88 leading to p38, c-Jun N-terminal kinases (JNK) and Akt activation and NF-κB signaling. In cancer cells, SMM induce the production of cytokines by activating the noncanonical alternate NF-κB pathway. However, in human macrophages, SMM do not induce the production of TNF-α and other cytokines while inhibiting LPS-induced IL-27 production by inhibiting the classical NF-κB pathway. These signaling pathways may constitute novel therapeutic avenues for immune modulation of IL-27 and provide insight into the modulatory immune effects of SMM.
Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation Mechanisms
Authors: Cruz-Leal Yoelys , Marjoram Danielle , Lazarus Alan H. 
Published: January 2018

Abstract
Anti-D prevents hemolytic disease of the fetus and newborn, and this mechanism has been referred to as Ab-mediated immune suppression (AMIS). Anti-D, as well as other polyclonal AMIS-inducing Abs, most often induce both epitope masking and erythrocyte clearance mechanisms. We have previously observed that some Abs that successfully induce AMIS effects could be split into those that mediate epitope masking versus those that induce erythrocyte clearance, allowing the ability to analyze these mechanisms separately. In addition, AMIS-inducing activity has recently been shown to induce Ag modulation (Ag loss from the erythrocyte surface). To assess these mechanisms, we immunized mice with transgenic murine RBCs expressing a single Ag protein comprising a recombinant Ag composed of hen egg lysozyme, OVA sequences comprising aa 251–349, and the human Duffy transmembrane protein (HOD-Ag) with serial doses of polyclonal anti-OVA IgG as the AMIS-inducing Ab. The anti-OVA Ab induced AMIS in the absence of apparent epitope masking. AMIS occurred only when the erythrocytes appeared saturated with IgG. This Ab was capable of inducing HOD-RBC clearance, as well as loss of the OVA epitope at doses of Ab that caused AMIS effects. HOD-RBCs also lost reactivity with Abs specific for the hen egg lysozyme and Duffy portions of the Ag consistent with the initiation of Ag modulation and/or trogocytosis mechanisms. These data support the concept that an AMIS-inducing Ab that does not cause epitope masking can induce AMIS effects in a manner consistent with RBC clearance and/or Ag modulation.
Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1
Authors: DeLong Jonathan H. , Hall Aisling O’Hara , Konradt Christoph , Coppock Gaia M. , Park Jeongho , Harms Pritchard Gretchen , Hunter Christopher A. 
Published: January 2018

Abstract
Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are differentially expressed by multiple immune populations. Ly6C expression has been used to distinguish short-lived effector CD4+ T cells from memory precursor effector cells, whereas Sca-1 has been used in the identification of CD8+ memory stem cells. This study examines the expression patterns of these molecules and establishes that, in vitro, IL-27, type I IFN, and IFN-γ are potent inducers of Ly6C and Sca-1 in naive mouse CD4+ and CD8+ T cells, whereas TGF-β limits their expression. The induction of Ly6C and Sca-1 by IL-27 and IFN-γ is dependent on STAT1, but not STAT3 or T-bet. In mouse splenocytes, at homeostasis, Ly6C and Sca-1 expression was not restricted to effector cells, but was also found at various levels on naive and memory populations. However, in response to infection with Toxoplasma gondii, pathogen-specific T cells expressed high levels of these molecules and in this context, endogenous IL-27 and IFN-γ were required for the expression of Ly6C but not Sca-1. Together, these findings highlight the TCR-dependent and cytokine-mediated signals that modulate T cell expression of Ly6C and Sca-1 in vitro and in vivo during infection.
The Hypoxia–Adenosine Link during Intestinal Inflammation
Authors: Bowser Jessica L. , Phan Luan H. , Eltzschig Holger K. 
Published: January 2018

Abstract
Intestinal inflammation is a key element in inflammatory bowel disease and is related to a combination of factors, including genetics, mucosal barrier dysfunction, bacteria translocation, deleterious host–microbe interactions, and dysregulated immune responses. Over the past decade, it has been appreciated that these inflammatory lesions are associated with profound tissue hypoxia. Interestingly, an endogenous adaptive response under the control of hypoxia signaling is enhancement in adenosine signaling, which impacts these different endpoints, including promoting barrier function and encouraging anti-inflammatory activity. In this review, we discuss the hypoxia–adenosine link in inflammatory bowel disease, intestinal ischemia/reperfusion injury, and colon cancer. In addition, we provide a summary of clinical implications of hypoxia and adenosine signaling in intestinal inflammation and disease.
Human and Rhesus Macaque KIR Haplotypes Defined by Their Transcriptomes
Authors: Bruijnesteijn Jesse , van der Wiel Marit K. H. , Swelsen Wendy T. N. , Otting Nel , de Vos-Rouweler Annemiek J. M. , Elferink Diënne , Doxiadis Gaby G. , Claas Frans H. J. , Lardy Neubury M. , de Groot Natasja G. , Bontrop Ronald E. 
Published: January 2018

Abstract
The killer-cell Ig-like receptors (KIRs) play a central role in the immune recognition in infection, pregnancy, and transplantation through their interactions with MHC class I molecules. KIR genes display abundant copy number variation as well as high levels of polymorphism. As a result, it is challenging to characterize this structurally dynamic region. KIR haplotypes have been analyzed in different species using conventional characterization methods, such as Sanger sequencing and Roche/454 pyrosequencing. However, these methods are time-consuming and often failed to define complete haplotypes, or do not reach allele-level resolution. In addition, most analyses were performed on genomic DNA, and thus were lacking substantial information about transcription and its corresponding modifications. In this paper, we present a single-molecule real-time sequencing approach, using Pacific Biosciences Sequel platform to characterize the KIR transcriptomes in human and rhesus macaque (Macaca mulatta) families. This high-resolution approach allowed the identification of novel Mamu-KIR alleles, the extension of reported allele sequences, and the determination of human and macaque KIR haplotypes. In addition, multiple recombinant KIR genes were discovered, all located on contracted haplotypes, which were likely the result of chromosomal rearrangements. The relatively high number of contracted haplotypes discovered might be indicative of selection on small KIR repertoires and/or novel fusion gene products. This next-generation method provides an improved high-resolution characterization of the KIR cluster in humans and macaques, which eventually may aid in a better understanding and interpretation of KIR allele–associated diseases, as well as the immune response in transplantation and reproduction.
Groundwater impacts on surface water quality and nutrient loads in lowland polder catchments: monitoring the greater Amsterdam area
Authors: Yu Liang , Rozemeijer Joachim , van Breukelen Boris M. , Ouboter Maarten , van der Vlugt Corné , Broers Hans Peter 
Published: January 2018

Abstract. The Amsterdam area, a highly manipulated delta area formed by polders and reclaimed lakes, struggles with high nutrient levels in its surface water system. The polders receive spatially and temporally variable amounts of water and nutrients via surface runoff, groundwater seepage, sewer leakage, and via water inlets from upstream polders. Diffuse anthropogenic sources, such as manure and fertiliser use and atmospheric deposition, add to the water quality problems in the polders. The major nutrient sources and pathways have not yet been clarified due to the complex hydrological system in lowland catchments with both urban and agricultural areas. In this study, the spatial variability of the groundwater seepage impact was identified by exploiting the dense groundwater and surface water monitoring networks in Amsterdam and its surrounding polders. A total of 25 variables (concentrations of total nitrogen (TN), total phosphorus (TP), NH4, NO3, HCO3, SO4, Ca, and Cl in surface water and groundwater, N and P agricultural inputs, seepage rate, elevation, land-use, and soil type) for 144 polders were analysed statistically and interpreted in relation to sources, transport mechanisms, and pathways. The results imply that groundwater is a large source of nutrients in the greater Amsterdam mixed urban–agricultural catchments. The groundwater nutrient concentrations exceeded the surface water environmental quality standards (EQSs) in 93 % of the polders for TP and in 91 % for TN. Groundwater outflow into the polders thus adds to nutrient levels in the surface water. High correlations (R2 up to 0.88) between solutes in groundwater and surface water, together with the close similarities in their spatial patterns, confirmed the large impact of groundwater on surface water chemistry, especially in the polders that have high seepage rates. Our analysis indicates that the elevated nutrient and bicarbonate concentrations in the groundwater seepage originate from the decomposition of organic matter in subsurface sediments coupled to sulfate reduction and possibly methanogenesis. The large loads of nutrient-rich groundwater seepage into the deepest polders indirectly affect surface water quality in the surrounding area, because excess water from the deep polders is pumped out and used to supply water to the surrounding infiltrating polders in dry periods. The study shows the importance of the connection between groundwater and surface water nutrient chemistry in the greater Amsterdam area. We expect that taking account of groundwater–surface water interaction is also important in other subsiding and urbanising deltas around the world, where water is managed intensively in order to enable agricultural productivity and achieve water-sustainable cities.
La Universidad: una visión desde “fuera” orientada al futuro
Authors: Rodríguez Espinar Sebastián 
Published: January 2018

<p class="Cuerpodetexto">En el primer punto se aportan evidencias sobre hechos como la expansión de los sistemas de educación superior, el aumento de los costes de los estudios, la internacionalización de los sistemas o las condiciones de trabajo del profesorado. El negocio de la educación superior ha cambiado, pero permanece estable el modelo tradicional de acceso a la estabilidad. En la segunda parte se asume que algunos sectores de la educación superior probablemente afrontarán cambios fundamentales. Emergerán nuevos modelos –puros o mixtos– de universidad: de élite (research university), de masas, la especializada, la local, la universidad para la formación permanente, o la ‘flagship university’. La universidad investigadora tienen el poder de la tradición y son competentes en sus funciones. Ahora bien, si las universidades líderes necesitan pensamiento estratégico para mantener su posición, las universidades más modestas (cuyos resultados de investigación también son modestos) tienen que hacerse preguntas importantes. Por otra parte, las fusiones o concentraciones de instituciones aparecen por doquier, y en Europa las fusiones en Francia han sido un éxito. El informe ‘University Mergers in Europe’ Un sector de la educación superior tiene poca probabilidad de ser alterado significativamente, sitúa y analiza el creciente fenómeno de los procesos de fusión y concentración en 20 sistemas de educación superior europeos. Finalmente, se aportan evidencias de algunas de las características del sistema universitario español, así como algunas de las cuestiones que deberá plantearse para afrontar con éxito futuros desafíos. <em></em><strong><em> </em></strong><br /><strong><em></em></strong></p>
Estimation of Systematic Errors in the GFS Using Analysis Increments
Authors: Bhargava Kriti , Kalnay Eugenia , Carton James A. , Yang Fanglin 
Published: January 2018

AbstractWe estimate the effect of model deficiencies in the Global Forecast System that lead to systematic forecast errors, as a first step toward correcting them online (i.e., within the model) as in Danforth & Kalnay (2008a, 2008b). Since the analysis increments represent the corrections that new observations make on the 6 h forecast in the analysis cycle, we estimate the model bias corrections from the time average of the analysis increments divided by 6 h, assuming that initial model errors grow linearly and first ignoring the impact of observation bias. During 2012–2016, seasonal means of the 6 h model bias are generally robust despite changes in model resolution and data assimilation systems, and their broad continental scales explain their insensitivity to model resolution. The daily bias dominates the submonthly analysis increments and consists primarily of diurnal and semidiurnal components, also requiring a low dimensional correction. Analysis increments in 2015 and 2016 are reduced over oceans, which we attribute to improvements in the specification of the sea surface temperatures. These results provide support for future efforts to make online correction of the mean, seasonal, and diurnal and semidiurnal model biases of Global Forecast System to reduce both systematic and random errors, as suggested by Danforth & Kalnay (2008a, 2008b). It also raises the possibility that analysis increments could be used to provide guidance in testing new physical parameterizations.
To What Extent is the Day 1 GPM IMERG Satellite Precipitation Estimate Improved as Compared to TRMM TMPA‐RT?
Authors: Gebregiorgis Abebe S. , Kirstetter Pierre‐Emmanuel , Hong Yang E. , Gourley Jonathan J. , Huffman George J. , Petersen Walter A. , Xue Xianwu , Schwaller Mathew R. 
Published: January 2018

AbstractIntegrated Multi‐Satellite Retrievals for Global Precipitation Measurement (IMERG) is the last generation precipitation data source for a wide array of research, operational, and societal applications. The Global Precipitation Measurement mission provides these global and high‐resolution precipitation estimates through advanced satellite‐based radar and radiometers. The degree of improvement of the new IMERG products needs to be investigated to further advance the algorithm's development and application. This study focuses on systematically and extensively evaluating the uncalibrated Version 3 Late Run IMERG product, which has both backward and forward morphing, and highlights the level of improvement in comparison to its predecessor Version 7 Tropical Rainfall Measurement Mission (TRMM)‐based Multi‐satellite Precipitation Analysis real‐time product. Retrievals from different passive microwave (PMW) and infrared (IR) sensors contributing to IMERG are evaluated over the conterminous United States using ground‐based sensor precipitation estimates derived from the Multi‐Radar Multi‐Sensor system as reference. An error decomposition scheme is implemented to separate the total error into three independent components, hit, miss‐rain, and false‐rain biases, to trace the degree of improvement of the new algorithm. IMERG exhibits definite improvement related to miss‐rain and false‐rain bias reduction and hit rate. The improvement relative to the TRMM ‐IR component is more substantial than relative to the PMW retrieval as a result of the new Kalman smoother and the PMW morphing reducing the use of IR relative to the TRMM‐based Multi‐satellite Precipitation Analysis. Findings of this study confirm the advances of the new generation of multisatellite precipitation relative to its predecessor and highlight areas requiring additional investigation.
Physical Conditions of Fast Glacier Flow: 1. Measurements From Boreholes Drilled to the Bed of Store Glacier, West Greenland
Authors: Doyle S. H. , Hubbard B. , Christoffersen P. , Young T. J. , Hofstede C. , Bougamont M. , Box J. E. , Hubbard A. 
Published: January 2018

Marine‐terminating outlet glaciers of the Greenland Ice Sheet make significant contributions to global sea level rise, yet the conditions that facilitate their fast flow remain poorly constrained owing to a paucity of data. We drilled and instrumented seven boreholes on Store Glacier, Greenland, to monitor subglacial water pressure, temperature, electrical conductivity, and turbidity along with englacial ice temperature and deformation. These observations were supplemented by surface velocity and meteorological measurements to gain insight into the conditions and mechanisms of fast glacier flow. Located 30 km from the calving front, each borehole drained rapidly on attaining ∼600 m depth indicating a direct connection with an active subglacial hydrological system. Persistently high subglacial water pressures indicate low effective pressure (180–280 kPa), with small‐amplitude variations correlated with notable peaks in surface velocity driven by the diurnal melt cycle and longer periods of melt and rainfall. The englacial deformation profile determined from borehole tilt measurements indicates that 63–71% of total ice motion occurred at the bed, with the remaining 29–37% predominantly attributed to enhanced deformation in the lowermost 50–100 m of the ice column. We interpret this lowermost 100 m to be formed of warmer, pre‐Holocene ice overlying a thin (0–8 m) layer of temperate basal ice. Our observations are consistent with a spatially extensive and persistently inefficient subglacial drainage system that we hypothesize comprises drainage both at the ice‐sediment interface and through subglacial sediments. This configuration has similarities to that interpreted beneath dynamically analogous Antarctic ice streams, Alaskan tidewater glaciers, and glaciers in surge.
A Diagnostic PDF Cloud Scheme to Improve Subtropical Low Clouds in NCAR Community Atmosphere Model (CAM5)
Authors: Qin Yi , Lin Yanluan , Xu Shiming , Ma Hsi‐Yen , Xie Shaocheng 
Published: January 2018

AbstractLow clouds strongly impact the radiation budget of the climate system, but their simulation in most GCMs has remained a challenge, especially over the subtropical stratocumulus region. Assuming a Gaussian distribution for the subgrid‐scale total water and liquid water potential temperature, a new statistical cloud scheme is proposed and tested in NCAR Community Atmospheric Model version 5 (CAM5). The subgrid‐scale variance is diagnosed from the turbulent and shallow convective processes in CAM5. The approach is able to maintain the consistency between cloud fraction and cloud condensate and thus alleviates the adjustment needed in the default relative humidity‐based cloud fraction scheme. Short‐term forecast simulations indicate that low cloud fraction and liquid water content, including their diurnal cycle, are improved due to a proper consideration of subgrid‐scale variance over the southeastern Pacific Ocean region. Compared with the default cloud scheme, the new approach produced the mean climate reasonably well with improved shortwave cloud forcing (SWCF) due to more reasonable low cloud fraction and liquid water path over regions with predominant low clouds. Meanwhile, the SWCF bias over the tropical land regions is also alleviated. Furthermore, the simulated marine boundary layer clouds with the new approach extend further offshore and agree better with observations. The new approach is able to obtain the top of atmosphere (TOA) radiation balance with a slightly alleviated double ITCZ problem in preliminary coupled simulations. This study implies that a close coupling of cloud processes with other subgrid‐scale physical processes is a promising approach to improve cloud simulations.
All‐Solution‐Processed Cu2ZnSnS4 Solar Cells with Self‐Depleted Na2S Back Contact Modification Layer
Authors: Gu Youchen , Shen Heping , Ye Chen , Dai Xuezeng , Cui Qian , Li Jianbao , Hao Feng , Hao Xiaojing , Lin Hong 
Published: January 2018

AbstractThe thin‐film photovoltaic material Cu2ZnSnS4 (CZTS) has drawn worldwide attention in recent years due to its earth‐abundant, nontoxic element constitution, and remarkable photovoltaic performance. Although state‐of‐the‐art power conversion efficiency is achieved by hydrazine‐based methods, effort to fabricate such devices in a high throughput, environmental‐friendly way is still highlydesired. Here a hydrazine‐free all‐solution‐processed CZTS solar cell with Na2S self‐depleted back contact modification layer for the first time is demonstrated, using a ball‐milled CZTS as light absorber, low‐temperature solution‐processed ZnO electron‐transport layer as well as silver‐nanowire transparent electrode. The inserting of Na2S self‐depleted layer is proven to effectively stabilize the CZTS/Mo interface by eliminating a detrimental phase segregation reaction between CZTS and Mo‐coated soda lime glass, thus leading to a better crystallinity of CZTS light absorbing layer, enhanced carrier transportation at CZTS/Mo interface as well as a smaller series resistance. Furthermore, the self‐depletion feature of the Na2S modification layer also averts hole‐transportation barrier within the devices. The results show the vital importance of interfacial engineering for these CZST devices and the Na2S interface layer can be extended to other optoelectronic devices using Mo contact.