bluuebunny/crossref_metadata_2025_split huggingface dataset:
Batf2/Irf1 Induces Inflammatory Responses in Classically Activated Macrophages, Lipopolysaccharides, and Mycobacterial Infection
Authors: Roy Sugata , Guler Reto , Parihar Suraj P. , Schmeier Sebastian , Kaczkowski Bogumil , Nishimura Hajime , Shin Jay W. , Negishi Yutaka , Ozturk Mumin , Hurdayal Ramona , Kubosaki Atsutaka , Kimura Yasumasa , de Hoon Michiel J. L. , Hayashizaki Yoshihide , Brombacher Frank , Suzuki Harukazu 
Published: May 2015

AbstractBasic leucine zipper transcription factor Batf2 is poorly described, whereas Batf and Batf3 have been shown to play essential roles in dendritic cell, T cell, and B cell development and regulation. Batf2 was drastically induced in IFN-γ–activated classical macrophages (M1) compared with unstimulated or IL-4–activated alternative macrophages (M2). Batf2 knockdown experiments from IFN-γ–activated macrophages and subsequent expression profiling demonstrated important roles for regulation of immune responses, inducing inflammatory and host-protective genes Tnf, Ccl5, and Nos2. Mycobacterium tuberculosis (Beijing strain HN878)–infected macrophages further induced Batf2 and augmented host-protective Batf2-dependent genes, particularly in M1, whose mechanism was suggested to be mediated through both TLR2 and TLR4 by LPS and heat-killed HN878 (HKTB) stimulation experiments. Irf1 binding motif was enriched in the promoters of Batf2-regulated genes. Coimmunoprecipitation study demonstrated Batf2 association with Irf1. Furthermore, Irf1 knockdown showed downregulation of IFN-γ– or LPS/HKTB-activated host-protective genes Tnf, Ccl5, Il12b, and Nos2. Conclusively, Batf2 is an activation marker gene for M1 involved in gene regulation of IFN-γ–activated classical macrophages, as well as LPS/HKTB-induced macrophage stimulation, possibly by Batf2/Irf1 gene induction. Taken together, these results underline the role of Batf2/Irf1 in inducing inflammatory responses in M. tuberculosis infection.
Thymic Involution Perturbs Negative Selection Leading to Autoreactive T Cells That Induce Chronic Inflammation
Authors: Coder Brandon D. , Wang Hongjun , Ruan Linhui , Su Dong-Ming 
Published: May 2015

Abstract
Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non–lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).
Genetic Variation in SP-A2 Leads to Differential Binding to Mycoplasma pneumoniae Membranes and Regulation of Host Responses
Authors: Ledford Julie G. , Voelker Dennis R. , Addison Kenneth J. , Wang Ying , Nikam Vinayak S. , Degan Simone , Kandasamy Pitachaimani , Tanyaratsrisakul Sasipa , Fischer Bernard M. , Kraft Monica , Hollingsworth John W. 
Published: May 2015

Abstract
Mycoplasma pneumoniae is an extracellular pathogen that colonizes mucosal surfaces of the respiratory tract and is associated with asthma exacerbations. Previous reports demonstrate that surfactant protein-A (SP-A) binds live M. pneumoniae and mycoplasma membrane fractions (MMF) with high affinity. Humans express a repertoire of single–amino acid genetic variants of SP-A that may be associated with lung disease, and our findings demonstrate that allelic differences in SP-A2 (Gln223Lys) affect the binding to MMF. We show that SP-A−/− mice are more susceptible to MMF exposure and have significant increases in mucin production and neutrophil recruitment. Novel humanized SP-A2–transgenic mice harboring the hSP-A2 223K allele exhibit reduced neutrophil influx and mucin production in the lungs when challenged with MMF compared with SP-A−/− mice. Conversely, mice expressing hSP-A2 223Q have increased neutrophil influx and mucin production that are similar to SP-A−/− mice. Using tracheal epithelial cell cultures, we show that enhanced mucin production to MMF occurs in the absence of SP-A and is not dependent upon neutrophil recruitment. Increased phosphorylation of the epidermal growth factor receptor (EGFR) was evident in the lungs of MMF-challenged mice when SP-A was absent. Pharmacologic inhibition of EGFR prior to MMF challenge dramatically reduced mucin production in SP-A−/− mice. These findings suggest a protective role for SP-A in limiting MMF-stimulated mucin production that occurs through interference with EGFR-mediated signaling. SP-A interaction with the EGFR signaling pathway appears to occur in an allele-specific manner that may have important implications for SP-A polymorphisms in human diseases.
Cutting Edge: T Follicular Helper Cell Differentiation Is Defective in the Absence of Bcl6 BTB Repressor Domain Function
Authors: Nance J. Philip , Bélanger Simon , Johnston Robert J. , Takemori Toshitada , Crotty Shane 
Published: May 2015

Abstract
T follicular helper (Tfh) cells are essential for germinal centers (GCs) and most long-term humoral immunity. Differentiation of Tfh cells depends on the transcriptional repressor B cell CLL/lymphoma 6 (Bcl6). Bcl6 mediates gene repression via the recruitment of corepressors. Currently, it is unknown how Bcl6 recruits corepressors to regulate gene expression of Tfh cells. In this article, we demonstrate, using a mutant form of Bcl6 with two BTB (bric-a-brac, tramtrack, broad-complex) mutations that abrogate corepressor binding, that the Bcl6 BTB domain is required for proper differentiation of Tfh and GC-Tfh cells in vivo. Importantly, we also observe a significant defect in GC B cell development. These results are consistent in multiple contexts, including a novel lymphocytic choriomeningitis virus nucleoprotein-specific TCR-transgenic mouse model. Taken together, these data suggest that the Bcl6 BTB domain is a key mediator of the differentiation of Tfh cells.
Quantitative Profiling of Immune Repertoires for Minor Lymphocyte Counts Using Unique Molecular Identifiers
Authors: Egorov Evgeny S. , Merzlyak Ekaterina M. , Shelenkov Andrew A. , Britanova Olga V. , Sharonov George V. , Staroverov Dmitriy B. , Bolotin Dmitriy A. , Davydov Alexey N. , Barsova Ekaterina , Lebedev Yuriy B. , Shugay Mikhail , Chudakov Dmitriy M. 
Published: May 2015

Abstract
Emerging high-throughput sequencing methods for the analyses of complex structure of TCR and BCR repertoires give a powerful impulse to adaptive immunity studies. However, there are still essential technical obstacles for performing a truly quantitative analysis. Specifically, it remains challenging to obtain comprehensive information on the clonal composition of small lymphocyte populations, such as Ag-specific, functional, or tissue-resident cell subsets isolated by sorting, microdissection, or fine needle aspirates. In this study, we report a robust approach based on unique molecular identifiers that allows profiling Ag receptors for several hundred to thousand lymphocytes while preserving qualitative and quantitative information on clonal composition of the sample. We also describe several general features regarding the data analysis with unique molecular identifiers that are critical for accurate counting of starting molecules in high-throughput sequencing applications.
Neonatal Exposure to Pneumococcal Phosphorylcholine Modulates the Development of House Dust Mite Allergy during Adult Life
Authors: Patel Preeyam S. , Kearney John F. 
Published: May 2015

Abstract
Currently, ∼20% of the global population suffers from an allergic disorder. Allergies and asthma occur at higher rates in developed and industrialized countries. It is clear that many human atopic diseases are initiated neonatally and herald more severe IgE-mediated disorders, including allergic asthma, which is driven by the priming of Th2 effector T cells. The hygiene hypothesis attempts to link the increased excessively sanitary conditions early in life to a default Th2 response and increasing allergic phenomena. Despite the substantial involvement of IgE Abs in such conditions, little attention has been paid to the effects of early microbial exposure on the B cell repertoire prior to the initiation of these diseases. In this study, we use Ab-binding assays to demonstrate that Streptococcus pneumoniae and house dust mite (HDM) bear similar phosphorylcholine (PC) epitopes. Neonatal C57BL/6 mice immunized with a PC-bearing pneumococcal vaccine expressed increased frequencies of PC-specific B cells in the lungs following sensitizing exposure to HDM as adults. Anti-PC IgM Abs in the lung decreased the interaction of HDM with pulmonary APCs and were affiliated with lowered allergy-associated cell infiltration into the lung, IgE production, development of airway hyperresponsiveness, and Th2 T cell priming. Thus, exposure of neonatal mice to PC-bearing pneumococci significantly reduced the development of HDM-induced allergic disease during adult life. Our findings demonstrate that B cells generated against conserved epitopes expressed by bacteria, encountered early in life, are also protective against the development of allergic disease during adult life.
Van Allen Probes investigation of the large‐scale duskward electric field and its role in ring current formation and plasmasphere erosion in the 1 June 2013 storm
Authors: Thaller S. A. , Wygant J. R. , Dai L. , Breneman A. W. , Kersten K. , Cattell C. A. , Bonnell J. W. , Fennell J. F. , Gkioulidou Matina , Kletzing C. A. , De Pascuale S. , Hospodarsky G. B. , Bounds S. R. 
Published: May 2015

AbstractUsing the Van Allen Probes, we investigate the enhancement in the large‐scale duskward convection electric field during the geomagnetic storm (Dst ~ −120 nT) on 1 June 2013 and its role in ring current ion transport and energization and plasmasphere erosion. During this storm, enhancements of ~1–2 mV/m in the duskward electric field in the corotating frame are observed down to L shells as low as ~2.3. A simple model consisting of a dipole magnetic field and constant, azimuthally westward, electric field is used to calculate the earthward and westward drift of 90° pitch angle ions. This model is applied to determine how far earthward ions can drift while remaining on Earth's nightside, given the strength and duration of the convection electric field. The calculation based on this simple model indicates that the enhanced duskward electric field is of sufficient intensity and duration to transport ions from a range of initial locations and initial energies characteristic of (though not observed by the Van Allen Probes) the earthward edge of the plasma sheet during active times (L ~ 6–10 and ~1–20 keV) to the observed location of the 58–267 keV ion population, chosen as representative of the ring current (L ~ 3.5–5.8). According to the model calculation, this transportation should be concurrent with an energization to the range observed, ~58–267 keV. Clear coincidence between the electric field enhancement and both plasmasphere erosion and ring current ion (58–267 keV) pressure enhancements are presented. We show for the first time nearly simultaneous enhancements in the duskward convection electric field, plasmasphere erosion, and increased pressure of 58–267 keV ring current ions. These 58–267 keV ions have energies that are consistent with what they are expected to pick up by gradient B drifting across the electric field. These observations strongly suggest that we are observing the electric field that energizes the ions and produces the erosion of the plasmasphere.
Real‐time imaging of density ducts between the plasmasphere and ionosphere
Authors: Loi Shyeh Tjing , Murphy Tara , Cairns Iver H. , Menk Frederick W. , Waters Colin L. , Erickson Philip J. , Trott Cathryn M. , Hurley‐Walker Natasha , Morgan John , Lenc Emil , Offringa André R. , Bell Martin E. , Ekers Ronald D. , Gaensler B. M. , Lonsdale Colin J. , Feng Lu , Hancock Paul J. , Kaplan David L. , Bernardi G. , Bowman J. D. , Briggs F. , Cappallo R. J. , Deshpande A. A. , Greenhill L. J. , Hazelton B. J. , Johnston‐Hollitt M. , McWhirter S. R. , Mitchell D. A. , Morales M. F. , Morgan E. , Oberoi D. , Ord S. M. , Prabu T. , Shankar N. Udaya , Srivani K. S. , Subrahmanyan R. , Tingay S. J. , Wayth R. B. , Webster R. L. , Williams A. , Williams C. L. 
Published: May 2015

AbstractIonization of the Earth's atmosphere by sunlight forms a complex, multilayered plasma environment within the Earth's magnetosphere, the innermost layers being the ionosphere and plasmasphere. The plasmasphere is believed to be embedded with cylindrical density structures (ducts) aligned along the Earth's magnetic field, but direct evidence for these remains scarce. Here we report the first direct wide‐angle observation of an extensive array of field‐aligned ducts bridging the upper ionosphere and inner plasmasphere, using a novel ground‐based imaging technique. We establish their heights and motions by feature tracking and parallax analysis. The structures are strikingly organized, appearing as regularly spaced, alternating tubes of overdensities and underdensities strongly aligned with the Earth's magnetic field. These findings represent the first direct visual evidence for the existence of such structures.
New observations of displacement steps associated with volcano seismic long‐period events, constrained by step table experiments
Authors: Thun Johannes , Lokmer Ivan , Bean Christopher J. 
Published: May 2015

AbstractLong‐period (LP) volcano seismic events often precede volcanic eruptions and are viewed with considerable interest in hazard assessment. They are usually thought to be associated with resonating fluid‐filled conduits although alternative models involving material failure have recently been proposed. Through recent field experiments, we uncovered a step‐like displacement component associated with some LP events, outside the spectral range of the typically narrow‐band analysis for this kind of event. Bespoke laboratory experiments with step tables show that steps of the order of a few micrometers can be extracted from seismograms, where long‐period noise is estimated and removed with moving median filters. Using these constraints, we observe step‐like ground deformation in LP recordings near the summits of Turrialba and Etna Volcanoes. This represents a previously unobserved static component in the source time history of LP events, with implications for the underlying source process.
Imbalanced land surface water budgets in a numerical weather prediction system
Authors: Kauffeldt Anna , Halldin Sven , Pappenberger Florian , Wetterhall Fredrik , Xu Chong‐Yu , Cloke Hannah L. 
Published: May 2015

AbstractThere has been a significant increase in the skill and resolution of numerical weather prediction models (NWPs) in recent decades, extending the time scales of useful weather predictions. The land surface models (LSMs) of NWPs are often employed in hydrological applications, which raises the question of how hydrologically representative LSMs really are. In this paper, precipitation (P), evaporation (E), and runoff (R) from the European Centre for Medium‐Range Weather Forecasts global models were evaluated against observational products. The forecasts differ substantially from observed data for key hydrological variables. In addition, imbalanced surface water budgets, mostly caused by data assimilation, were found on both global (P‐E) and basin scales (P‐E‐R), with the latter being more important. Modeled surface fluxes should be used with care in hydrological applications, and further improvement in LSMs in terms of process descriptions, resolution, and estimation of uncertainties is needed to accurately describe the land surface water budgets.
Azimuthal flow bursts in the inner plasma sheet and possible connection with SAPS and plasma sheet earthward flow bursts
Authors: Lyons L. R. , Nishimura Y. , Gallardo‐Lacourt B. , Nicolls M. J. , Chen S. , Hampton D. L. , Bristow W. A. , Ruohoniemi J. M. , Nishitani N. , Donovan E. F. , Angelopoulos V. 
Published: May 2015

AbstractWe have combined radar observations and auroral images obtained during the Poker Flat Incoherent Scatter Radar Ion Neutral Observations in the Thermosphere campaign to show the common occurrence of westward moving, localized auroral brightenings near the auroral equatorward boundary and to show their association with azimuthally moving flow bursts near or within the subauroral polarization stream (SAPS) region. These results indicate that the SAPS region, rather than consisting of relatively stable proton precipitation and westward flows, can have rapidly varying flows, with speeds varying from ~100 m/s to ~1 km/s in just a few minutes. The auroral brightenings are associated with bursts of weak electron precipitation that move westward with the westward flow bursts and extend into the SAPS region. Additionally, our observations show evidence that the azimuthally moving flow bursts often connect to earthward (equatorward in the ionosphere) plasma sheet flow bursts. This indicates that rather than stopping or bouncing, some flow bursts turn azimuthally after reaching the inner plasma sheet and lead to the bursts of strong azimuthal flow. Evidence is also seen for a general guiding of the flow bursts by the large‐scale convection pattern, flow bursts within the duskside convection being azimuthally turned to the west, and those within the dawn cell being turned toward the east. The possibility that the SAPS region flow structures considered here may be connected to localized flow enhancements from the polar cap that cross the nightside auroral poleward boundary and lead to flow bursts within the plasma sheet warrants further consideration.
The effect of different solar wind parameters upon significant relativistic electron flux dropouts in the magnetosphere
Authors: Gao Xinliang , Li Wen , Bortnik Jacob , Thorne Richard M. , Lu Quanming , Ma Qianli , Tao Xin , Wang Shui 
Published: May 2015

AbstractSuperposed epoch analyses were performed on 193 significant relativistic electron flux dropout events, in order to study the roles of different solar wind parameters in driving the depletion of relativistic electrons, using ~16 years of data from the POES and GOES missions, and the OMNIWEB solar wind database. We find that the solar wind dynamic pressure and interplanetary magnetic field (IMF) Bz play key roles in causing the relativistic electron flux dropouts, but also that either large solar wind dynamic pressure or strong southward IMF Bz by itself is capable of producing the significant depletion of relativistic electrons. The relativistic electron flux dropouts occur not only when the magnetopause is compressed closer to the Earth but also when the magnetopause is located very far (> ~10 RE). Importantly, our results show that in addition to the large solar wind dynamic pressure, which pushes the magnetopause inward strongly and causes the electrons to escape from the magnetosphere, relativistic electrons can also be scattered into the loss cone and precipitate into the Earth's atmosphere during periods of strong southward IMF Bz, which preferentially provides a source of free energy for electromagnetic ion cyclotron (EMIC) wave excitation. This is supported by the fact that the strongest electron precipitation into the atmosphere is found in the dusk sector, where EMIC waves are typically observed in the high‐density plasmasphere or plume and cause efficient electron precipitation down to ~1 MeV.
A data assimilation technique to account for the nonlinear dependence of scattering microwave observations of precipitation
Authors: Haddad Z. S. , Steward J. L. , Tseng H.‐C. , Vukicevic T. , Chen S.‐H. , Hristova‐Veleva S. 
Published: May 2015

AbstractSatellite microwave observations of rain, whether from radar or passive radiometers, depend in a very crucial way on the vertical distribution of the condensed water mass and on the types and sizes of the hydrometeors in the volume resolved by the instrument. This crucial dependence is nonlinear, with different types and orders of nonlinearity that are due to differences in the absorption/emission and scattering signatures at the different instrument frequencies. Because it is not monotone as a function of the underlying condensed water mass, the nonlinearity requires great care in its representation in the observation operator, as the inevitable uncertainties in the numerous precipitation variables are not directly convertible into an additive white uncertainty in the forward calculated observations. In particular, when attempting to assimilate such data into a cloud‐permitting model, special care needs to be applied to describe and quantify the expected uncertainty in the observations operator in order not to turn the implicit white additive uncertainty on the input values into complicated biases in the calculated radiances. One approach would be to calculate the means and covariances of the nonlinearly calculated radiances given an a priori joint distribution for the input variables. This would be a very resource‐intensive proposal if performed in real time. We propose a representation of the observation operator based on performing this moment calculation off line, with a dimensionality reduction step to allow for the effective calculation of the observation operator and the associated covariance in real time during the assimilation. The approach is applicable to other remotely sensed observations that depend nonlinearly on model variables, including wind vector fields. The approach has been successfully applied to the case of tropical cyclones, where the organization of the system helps in identifying the dimensionality‐reducing variables.
Metallic Fuels
Authors: Hofman Gerard L. 
Published: May 2015

The article contains sections titled:IntroductionIrradiation BehaviorSwelling and Gas ReleaseUraniumUranium–PlutoniumThorium–Uranium (Plutonium)Alloys with Nonfissile and Nonfertile ConstituentsAlloys Containing Minor ActinidesU–Pu–ZrAlloy Fuels for Fast ReactorsFuel–Cladding InteractionFuel–Cladding Mechanical InteractionFission‐Induced CreepFuel–Cladding Chemical InteractionTransient TestingOperation of Fuel Elements with Breached Cladding