bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated inversion of TEM and seismic data facilitated by high penetration depths of a segmented receiver setup
Authors: Nyboe Nicklas S. , Jørgensen Flemming , Sørensen Kurt
Published: January 2011

Research aimed at improving and developing methods for noise reduction in the transient electromagnetic method (TEM) has resulted in an alternative strategy for performing TEM measurements called the segmented receiver coil setup. The measurement strategy involves the simultaneous use of two receiver coils and the resulting TEM data sets have demonstrated signal‐to‐noise ratio improvements of up to a factor of 25 when compared to the traditional setup. This significant improvement has opened up new opportunities for deeper penetration and hence an enhanced integrated inversion with seismic data sets. A case study is presented in which the segmented receiver coil setup is employed in the western part of Denmark. Previous geophysical investigations performed in the same area include multi‐channel reflection seismic measurements and SkyTEM measurements performed with an early version of the SkyTEM instrument having a limited depth of investigation. Deep structures recognized in the seismic data therefore remained unresolved in the SkyTEM data. Notably the elevation of the highly conductive Palaeogene clay, expected to be encountered at approximately 300 m depth in the area, has not been determined by the use of SkyTEM data. With the increased signal‐to‐noise ratio of the segmented receiver coil setup it is possible to resolve resistivity changes to greater depth and thus to achieve an enhanced integrated inversion together with the seismic data. The geological setting between depths of 200–300 m, which is effectively only mapped two‐dimensionally along seismic lines, can be mapped three‐dimensionally using the segmented receiver coil setup. In order to obtain the most reliable geological information, from the TEM data individual soundings are inverted in 1D utilizing the seismic data as a priori information thereby optimizing every single inversion model setup to the local sedimentary stratification. Ultimately, the larger penetration depth is the key to an improved geological understanding of the study area, because the integrated interpretation of seismic and TEM data sets yields valuable lithological and structural information that cannot be resolved by either data type alone.
Estimation of inelastic seismic material properties of a surficial sea‐bed from multi‐component marine seismic data
Authors: Eggenberger Kurt , Muijs Remco , Robertsson Johan , van Manen Dirk‐Jan , Holliger Klaus
Published: January 2011

To date, state‐of‐the‐art seismic material parameter estimates from multi‐component sea‐bed seismic data are based on the assumption that the sea‐bed consists of a fully elastic half‐space. In reality, however, the shallow sea‐bed generally consists of soft, unconsolidated sediments that are characterized by strong to very strong seismic attenuation. To explore the potential implications, we apply a state‐of‐the‐art elastic decomposition algorithm to synthetic data for a range of canonical sea‐bed models consisting of a viscoelastic half‐space of varying attenuation. We find that in the presence of strong seismic attenuation, as quantified by ‐values of 10 or less, significant errors arise in the conventional elastic estimation of seismic properties. Tests on synthetic data indicate that these errors can be largely avoided by accounting for the inherent attenuation of the seafloor when estimating the seismic parameters. This can be achieved by replacing the real‐valued expressions for the elastic moduli in the governing equations in the parameter estimation by their complex‐valued viscoelastic equivalents. The practical application of our parameter procedure yields realistic estimates of the elastic seismic material properties of the shallow sea‐bed, while the corresponding ‐estimates seem to be biased towards too low values, particularly for S‐waves. Given that the estimation of inelastic material parameters is notoriously difficult, particularly in the immediate vicinity of the sea‐bed, this is expected to be of interest and importance for civil and ocean engineering purposes.
Automation of the SLUTH method: a novel approach to airborne magnetic data interpretation
Authors: Ulla Joshua , Smith Richard , Samson Claire , Vallée Marc
Published: January 2011

A useful property of the anomalous magnetic field associated with some simple geological bodies is that the field is homogeneous with respect to horizontal distance and height. Its horizontal and vertical derivatives are also homogeneous fields so the angle ratio of the lateral gradient over the vertical gradient is constant along rays emanating outward from a single point that represents the body location. Hence drawing these raypaths, which connect the same values at different upward continued heights along a profile, can be used to identify the location and depth of the source. This is the basis for the source location using the total‐field homogeneity (SLUTH) method. A six‐step procedure is proposed to automate the SLUTH method, allowing large amounts of data to be interpreted quickly and easily. Furthermore, the rate of decay of the field along these raypaths provides a means to estimate the type of body that is the cause of the anomaly. Once the type of body is known, a quantity related to the susceptibility can be estimated.

An analysis of the results in the case when there is interaction between two proximal magnetic sheets shows a distortion when the bodies are within 600 m of each other. A similar distortion is seen when analysing field data from Timmins, Ontario, Canada, which consists of many other magnetic body models such as contacts and thin sheets. Adding noise to synthetic data shows that the estimates we obtain for the source parameters are robust for the typical noise levels seen in survey data.

Because a lot of information about the characteristics of the causative geologic body can be determined using the method, it is a challenge to summarize the results on a single map. Our approach is to use different shaped symbols for each type of body, with the size of the symbol being proportional to the susceptibility‐thickness and the shade indicative of the error in estimating the position. Data from Chibougamau, Quebec, Canada are used to illustrate these display techniques.
Self‐potential signatures associated with an injection experiment at an in situ biological permeable reactive barrier
Authors: Davis Caroline A. , Slater Lee D. , Kulessa Bernd , Ferguson Andrew S. , Atekwana Estella A. , Doherty Rory , Kalin Robert
Published: January 2011

Strategies available to evaluate the performance of in situ permeable reactive barriers are currently not well developed and often rely on fluid and media sampling directly from the permeable reactive barrier (PRB). Here, we investigate the utility of the self‐potential method as a technique to monitor in situ PRB performance. Our field study was conducted at in situ biological PRB in Portadown, Northern Ireland, UK, which was emplaced to assist in the remediation of groundwater contamination (e.g., hydrocarbons, ammonia) that resulted from the operations and waste disposal practices of a former gasworks. Borehole measurements were collected during the injection of contaminant groundwater slugs in an attempt to monitor/detect the response of the microbial activity associated with the breakdown of the added contaminants into the PRB. In addition, an uncontaminated groundwater slug was injected into a different portion of the PRB as a ‘control’ and measurements were collected for comparison to the response of the contaminant slugs. The results of the SP signals due to the contaminant injections show that the magnitude of the response was relatively small (<10 mV) yet showed a consistent decrease during both contaminant injections. The net decrease in recorded during the contaminant injections slowly rebounded to near background values through ~44 hours post‐injection. The response during the uncontaminated injection showed a slight, albeit negligible (within the margin of error), 1 mV increase in the measured signals, in contrast to the contaminant injections. The results of the signals recorded from the uncontaminated groundwater injection also persisted through a period of ~47 hours after injection but show a net increase in relative to pre‐injection values. Based on the difference in response between the contaminated and uncontaminated injections, we suggest that the responses are likely to be the result of differences in the chemistry of the injection types (contaminated versus uncontaminated) and in situ groundwater. We argue that the signals associated with the contaminated injections are dominated by diffusion (electrochemical) potential, possibly enhanced by a microbial effect. While the results of our investigation show a consistent response associated with the contaminant injections that is dominated by diffusional effects, further studies are required in order to better understand the effect of microbial activity on signals and the potential utility for the method to detect/monitor changes that may be indicative of biological PRB performance.
Geophysical characterization of riverbed hydrostratigraphy using electrical resistance tomography
Authors: Clifford Jeremy , Binley Andrew
Published: January 2011

The subsurface structure of a riverbed can play an important role in groundwater‐surface water interactions. Knowledge of this structure provides a basis for characterizing the physical and geochemical processes in this region, for example, how hydrostratigraphy relates to groundwater seeps or controls the transport of nutrients across this critical interface. However, characterization of riverbed sediments using conventional hydrological techniques is difficult and particularly challenging for assessing contiguous units of variable geometry. Also, the destructive nature of conventional drilling in a riverbed is often problematic in some systems because of the disturbance to the ecosystem it supports. Geophysical techniques may provide significant advantages over conventional characterization techniques, provided i) there exists a distinct contrast in the geophysical properties of hydrological units and ii) sufficient resolution and sensitivity to these contrasts can be achieved. We show, through modelling and field application, how electrical resistivity tomography can be used to provide useful knowledge about shallow hydrostratigraphy of riverbed environments. Through synthetic modelling, we show that the main factor affecting sensitivity below the surface water/subsurface interface is the ratio of electrical conductivities of surface water and sub‐strata. The modelling reveals that as this ratio increases, the sensitivity shifts upward across the interface, reducing the information yielded from below the riverbed. We also show that this, coupled with the variability in the riverbed topography and composition, has the effect of rendering conventional data coverage from short arrays unusable. With suitable selection of electrode configuration and measurement scheme, informative results are, however, achievable. We report on a field trial applied to the River Leith, a small groundwater‐fed stream in the Eden Valley of Cumbria, UK. The effect of the depth of the water column is shown and although the depth of investigation is relatively shallow, enough structure is revealed to show the boundary between the sandstone aquifer and overlying alluvial sediments. Our findings from model and field studies suggest that electrical geophysical methods could have a valuable role complementing conventional measurements in shallow hydrogeological characterization studies.
Quantifying field‐scale surface soil water content from proximal GPR signal inversion in the time domain
Authors: Jadoon Khan Zaib , Lambot Sébastien , Scharnagl Benedikt , van der Kruk Jan , Slob Evert , Vereecken Harry
Published: January 2011

We applied inverse modelling of zero‐offset, air‐raised ground‐penetrating radar (GPR) data to measure soil surface water contents over a bare agricultural field. The GPR system consisted of a vector network analyser combined with a low‐frequency 0.2–2.0 GHz off‐ground monostatic horn antenna, thereby setting up an ultra‐wideband stepped‐frequency continuous‐wave radar. A fully automated platform was created by mounting the radar system on a truck for real‐time data acquisition. An antenna calibration experiment was performed by lifting the whole setup to different heights above a perfect electrical conductor. This calibration procedure allowed the flittering out of the antenna effects and antenna‐soil interactions from the raw radar data in the frequency domain. To avoid surface roughness effects, only the lower frequency range of 0.2–0.8 GHz was used for signal processing. Inversions of the radar data using the Green’s functions were performed in the time domain, focusing on a time window containing the surface reflection. GPR measurements were conducted every 4 m along a transect of 100 m. In addition, five time‐domain reflectometry measurements were randomly recorded within the footprint of the GPR antenna. A good agreement was observed between the GPR and time‐domain reflectometry soil water content estimates, as compared to the previous study performed at the same test site using a higher frequency 0.8–1.6 GHz horn antenna. To monitor the dynamics of soil water content, a pair of time‐domain reflectometry probes was installed at 8 cm depth near the footprint of the GPR antenna and both time‐domain reflectometry and GPR measurements were carried out for a period of 20 days. A good agreement of the trend was observed between the time‐domain reflectometry and GPR time‐lapse data with respect to several precipitation events. The proposed method and truck‐mounted setup appear to be promising for the real‐time mapping and monitoring of surface soil moisture contents at the field scale.
Weathering variations in a granitic massif and related geotechnical properties through seismic and electrical resistivity methods
Authors: Olona Javier , Pulgar Javier A. , Fernández‐Viejo Gabriela , López‐Fernández Carlos , González‐Cortina Juan M.
Published: January 2011

Mapping and distribution with depth of alteration in rocks is critical in engineering planning because it has a fundamental impact on the geotechnical properties of the materials. Lateral heterogeneity on a weathered rock massif makes boreholes inadequate for its complete characterization. Geophysical methods increase spatial sampling along the study area and can be related to geotechnical parameters, so subsoil conditions can be better understood.

In order to determine its geotechnical qualities and variability along two different profiles, we attempt to characterize a granite massif in north‐west Spain by the integration of results from seismic refraction, multichannel analysis of surface waves (MASW) and electrical resistivity tomography methods (ERT). The study area, the so‐called Carlés granite, shows all the weathering grades from sandy soil to fresh rock. A reference borehole where samples were taken and laboratory measurements were made, serves as a direct check for the results of one of the profiles, the other being interpreted without any direct information. This approach has permitted the evaluation of the advantages and limitations of each geophysical method and created an accurate geotechnical model of the massif, correlating physical and geotechnical parameters such as rock quality designation, weathering grade, or standard penetration test.

The field seismic velocities have been compared with the ultrasonic measurements at the laboratory, permitting an evaluation of the field and laboratory elastic constants. The trend in the values of these parameters agrees with the field and laboratory test for the shallow parts of the massif. However, unrealistic elastic constants have been obtained for fresh rock based on the results of the field experiments. This is related to an apparent underestimation of the velocity of seismic S‐waves for the deepest layers. This fact suggests that the methodology followed throughout this work is able to provide a full geotechnical model of an altered rock massif for the first tens of metres, discriminating between different weathered levels. It is also useful and reliable when inferring elastic constants for depths of up to 20 m. However, its validity becomes doubtful with depth, so care must be taken when calculating elastic moduli and trying to extrapolate directly to a rock massif.
Shallow seismic investigation of surface deformation associated with the Kilmichael dome, Montgomery County, Mississippi, USA
Authors: Sloan Steven D. , Harris James B.
Published: January 2011

The Kilmichael dome structure is a circular feature exposed in unconsolidated early Tertiary sediments of north‐central Mississippi, USA. The structural complexity of the area, including zones of intense faulting and uplifted strata, has led to several suggested origins for the formation of the Kilmichael dome, including meteorite impact and regional tectonics; however, the origin remains unknown. As part of an undergraduate student research project, we acquired shallow shear‐wave seismic reflection data over a complex zone of surface faults on the northern flank of the Kilmichael dome, with the goal of imaging the subsurface expression of deformation associated with faulting expressed along an exposed road cut. We also collected multi‐component downhole seismic data in a nearby borehole to analyse the shear‐wave velocity structure of the shallow sediments and observe possible anisotropy. Polarization analysis of the downhole data identified shear‐wave anisotropy consistent with structural alignments in the area. Interpretation of the reflection profile and particle motion plots from the downhole data allowed correlation with shallow structural features of the Kilmichael dome.
Training the next generation of near‐surface geophysicists: team‐based, student‐led, problem‐solving field exercises, Cumbria, UK
Authors: Pringle J.K. , Cassidy N.J. , Styles P. , Stimpson I.G. , Toon S.M.
Published: January 2011

Discussions with employers of graduate applied geophysicists (reinforced by recent literature) indicate a progressive reduction in the numeracy and literacy of graduating students. In particular, there is a perception that problem‐solving and quantitative analysis skills are not being gained during university studies, which could be partly attributed to an emphasis on classroom lectures and timetable constraints rather than research‐informed and active learning in the field.

This paper provides a pedagogic overview of a Masters level, student‐led residential field exercise in the Lake District, Cumbria, UK that has run for eight years. The valley has complex glaciated bedrock buried by recent sediments, which poses a challenge for students to recognize, understand and quantify in three dimensions. Participating student ‘companies’ are set a competitive task to win a contract for a full geophysical valley survey to determine the route of a gas pipeline. Students initially complete a desk study, collating available multi‐disciplinary (geology, remote sensing and geotechnical) data sets. The student‐led field exercise then acts as a geophysical reconnaissance mission, with teams mapping depth to bedrock and estimating extents of any coastal salinity incursions. Full costings are produced to simulate a real work contract and the successful company is awarded the ‘contract’, based on ‘client’ presentations on the final day of the exercise.

Comments on the student learning outcomes are provided, including employability skills in team working, problem‐solving, quantitative data analysis, project and budget management and client presentation skills. Recent student evaluations are discussed with very positive comments from graduate geophysicists who have entered related employment emphasizing how the exercise has prepared them for the workplace.
Mucosal Allergic Sensitization to Cockroach Allergens Is Dependent on Proteinase Activity and Proteinase-Activated Receptor-2 Activation
Authors: Arizmendi Narcy G. , Abel Melanie , Mihara Koichiro , Davidson Courtney , Polley Danny , Nadeem Ahmed , El Mays Tamer , Gilmore Brendan F. , Walker Brian , Gordon John R. , Hollenberg Morley D. , Vliagoftis Harissios
Published: January 2011

We have shown that proteinase-activated receptor-2 (PAR2) activation in the airways leads to allergic sensitization to concomitantly inhaled Ags, thus implicating PAR2 in the pathogenesis of asthma. Many aeroallergens with proteinase activity activate PAR2. To study the role of PAR2 in allergic sensitization to aeroallergens, we developed a murine model of mucosal sensitization to cockroach proteins. We hypothesized that PAR2 activation in the airways by natural allergens with serine proteinase activity plays an important role in allergic sensitization. Cockroach extract (CE) was administered to BALB/c mice intranasally on five consecutive days (sensitization phase) and a week later for four more days (challenge phase). Airway hyperresponsiveness (AHR) and allergic airway inflammation were assessed after the last challenge. To study the role of PAR2, mice were exposed intranasally to a receptor-blocking anti-PAR2 Ab before each administration of CE during the sensitization phase. Mucosal exposure to CE induced eosinophilic airway inflammation, AHR, and cockroach-specific IgG1. Heat-inactivated or soybean trypsin inhibitor-treated CE failed to induce these effects, indicating that proteinase activity plays an important role. The use of an anti-PAR2 blocking Ab during the sensitization phase completely inhibited airway inflammation and also decreased AHR and the production of cockroach-specific IgG1. PAR2 activation by CE acts as an adjuvant for allergic sensitization even in the absence of functional TLR4. We conclude that CE induces PAR2-dependent allergic airway sensitization in a mouse model of allergic airway inflammation. PAR2 activation may be a general mechanism used by aeroallergens to induce allergic sensitization.
Ubiquitylation of an Internalized Killer Cell Ig-Like Receptor by Triad3A Disrupts Sustained NF-κB Signaling
Authors: Miah S. M. Shahjahan , Purdy Amanda K. , Rodin Nicholas B. , MacFarlane Alexander W. , Oshinsky Jennifer , Alvarez-Arias Diana A. , Campbell Kerry S.
Published: January 2011

Killer cell Ig-like receptor (KIR) with two Ig-like domains and a long cytoplasmic domain 4 (2DL4; CD158d) is a unique KIR expressed on human NK cells, which stimulates cytokine production, but mechanisms regulating its expression and function are poorly understood. By yeast two-hybrid screening, we identified the E3 ubiquitin ligase, Triad3A, as an interaction partner for the 2DL4 cytoplasmic domain. The protein interaction was confirmed in vivo, and Triad3A expression induced polyubiquitylation and degradation of 2DL4. Overexpression of Triad3A selectively abrogated the cytokine-producing function of 2DL4, whereas Triad3A short hairpin RNA reversed ubiquitylation and restored cytokine production. Expression of Triad3A in an NK cell line did not affect receptor surface expression, internalization, or early signaling, but significantly reduced receptor turnover and suppressed sustained NF-κB activation. 2DL4 endocytosis was found to be vital to stimulate cytokine production, and Triad3A expression diminished localization of internalized receptor in early endosomes. Our results reveal a critical role for endocytosed 2DL4 receptor to generate sustained NF-κB signaling and drive cytokine production. We conclude that Triad3A is a key negative regulator of sustained 2DL4-mediated NF-κB signaling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes.
TANK-Binding Kinase 1 Attenuates PTAP-Dependent Retroviral Budding through Targeting Endosomal Sorting Complex Required for Transport-I
Authors: Da Qi , Yang Xuanming , Xu Youli , Gao Guangxia , Cheng Genhong , Tang Hong
Published: January 2011

Retroviruses need to bud from producer cells to spread infection. To facilitate its budding, some virus hijacks the multivesicular body (MVB) pathway that is normally used to cargo and degrade ubiquitylated cellular proteins, through interaction between the late domain of Gag polyproteins and the components of MVB machinery. In this study, we demonstrated that TANK-binding kinase 1 (TBK1) directly interacted with VPS37C, a subunit of endosomal sorting complex required for transport-I (ESCRT-I) in the MVB pathway, without affecting the ultrastructure or general function of MVB. Interestingly, overexpression of TBK1 attenuated, whereas short hairpin RNA interference of TBK1 enhanced HIV-1 pseudovirus release from Vero cells in type I IFN (IFN-I)-independent manner. Down-regulation of TBK1 by short hairpin RNA in TZM-bl cells also enhanced live HIV-1 NL4-3 or JR-CSF virus budding without involvement of IFN-I induction. Furthermore, infection of TBK1-deficient mouse embryonic fibroblast cells with a chimeric murine leukemia virus/p6, whose PPPY motif was replaced by PTAP motif of HIV-1, showed that lack of TBK1 significantly enhanced PTAP-dependent, but not PPPY-dependent retrovirus budding. Finally, phosphorylation of VPS37C by TBK1 might regulate the viral budding efficiency, because overexpression of the kinase-inactive mutant of TBK1 (TBK1-K38A) in Vero cells accelerated HIV-1 pseudovirus budding. Therefore, through tethering to VPS37C of the ESCRT-I complex, TBK1 controlled the speed of PTAP-dependent retroviral budding through phosphorylation of VPS37C, which would serve as a novel mechanism of host cell defense independent of IFN-I signaling.
Anaphylaxis and Mortality Induced by Treatment of Mice with Anti–VLA-4 Antibody and Pertussis Toxin
Authors: Ji Niannian , Rao Nagarjun , Guentzel Neal M. , Arulanandam Bernard P. , Forsthuber Thomas G.
Published: January 2011

Ab-mediated blockade of the adhesion molecule VLA-4 has been shown to ameliorate disease in human multiple sclerosis patients and experimental autoimmune encephalomyelitis (EAE) animal models. We wanted to determine whether anti–VLA-4 Ab treatment affected the function and persistence of autoreactive T cells in mice with EAE. Unexpectedly, we observed a high level of mortality in anti–VLA-4 mAb (PS/2)-treated mice with actively induced EAE despite decreased disease severity. Investigation of the underlying mechanism showed that injection of PS/2 mAb in combination with pertussis toxin resulted in anaphylaxis and mortality. Furthermore, the data showed that CD4+ T cells were required for this effect and suggested a role for IL-1β and TNF-α in the underlying pathology. The results reveal a previously not appreciated deleterious effect of anti–VLA-4 Ab treatment in combination with exposure to pertussis toxin.
Basophils Are the Major Producers of IL-4 during Primary Helminth Infection
Authors: van Panhuys Nicholas , Prout Melanie , Forbes Elizabeth , Min Booki , Paul William E. , Le Gros Graham
Published: January 2011

IL-4 production by leukocytes is a key regulatory event that occurs early in the type 2 immune response, which induces allergic reactions and mediates expulsion of parasites. CD4+ T cells and basophils are thought to be the key cell types that produce IL-4 during a type 2 response. In this study, we assessed the relative contribution of both CD4+ T cell- and basophil–IL-4 production during primary and secondary responses to Nippostrongylus brasiliensis using a murine IL-4–enhanced GFP reporter system. During infection, IL-4–producing basophils were detected systemically, and tissue recruitment occurred independent of IL-4/STAT6 signaling. We observed that basophil recruitment to a tissue environment was required for their full activation. Basophil induction in response to secondary infection exhibited accelerated kinetics in comparison with primary infection. However, total basophil numbers were not enhanced, as predicted by previous models of protective immunity. Overall, the induction and migration of IL-4–producing basophils into peripheral tissues was found to be a prominent characteristic of the primary but not memory responses to N. brasiliensis infection, in which CD4+ T cells were identified as the major source of IL-4. Whereas basophils were the major initial producers of IL-4, we determined that normal Th2 differentiation occurs independently of basophils, and depletion of basophils led to an enhancement of inflammatory cell recruitment to the site of infection.
β2 Integrin Induces TCRζ–Syk–Phospholipase C-γ Phosphorylation and Paxillin-Dependent Granule Polarization in Human NK Cells
Authors: March Michael E. , Long Eric O.
Published: January 2011

Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of β2 integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study, we investigated the basis for this difference. IL-2–expanded human NK cells were stimulated by incubation with plate-bound ligands of LFA-1 (ICAM-1) and CD16 (human IgG). Surprisingly, LFA-1 elicited signals similar to those induced by CD16, including tyrosine phosphorylation of the TCR ζ-chain, tyrosine kinase Syk, and phospholipase C-γ. Whereas CD16 activated Ca2+ mobilization and LAT phosphorylation, LFA-1 did not, but induced strong Pyk2 and paxillin phosphorylation. LFA-1–dependent granule polarization was blocked by inhibition of Syk, phospholipase C-γ, and protein kinase C, as well as by paxillin knockdown. Therefore, common signals triggered by CD16 and LFA-1 bifurcate to provide independent control of Ca2+-dependent degranulation and paxillin-dependent granule polarization.
Deletion of Tristetraprolin Caused Spontaneous Reactive Granulopoiesis by a Non–Cell-Autonomous Mechanism Without Disturbing Long-Term Hematopoietic Stem Cell Quiescence
Authors: Kaplan Ian M. , Morisot Sebastien , Heiser Diane , Cheng Wen-Chih , Kim Min Jung , Civin Curt I.
Published: January 2011

Tristetraprolin (TTP, Zfp36, Nup475, Tis11) dramatically reduces the stability of target mRNAs by binding to AU-rich elements in their 3′ untranslated regions. Through this mechanism, TTP functions as a rheostatic, temporal regulator of gene expression. TTP knockout (KO) mice exhibit completely penetrant granulocytic hyperplasia. We have shown that the hematopoietic stem-progenitor cell compartment in TTP KO mice is also altered. Although no change was detected in long-term hematopoietic stem cell (HSC) frequency or function, as assayed by immunophenotypic markers or limiting dilution transplants, we observed increases in the frequencies and numbers of short-term HSCs, multipotent progenitors, and granulocyte–monocyte progenitors. This pattern is consistent with “reactive granulopoiesis,” in which committed myeloid progenitors and more primitive progenitors cycle more actively to increase production of mature granulocytes in response to infection or adjuvant. We created reverse chimeras by transplanting wild-type bone marrow into TTP KO mice and found the “reactive granulopoiesis” phenocopied, indicating a non–hematopoietic stem-progenitor cell–autonomous mechanism. Correspondingly, we found elevated levels of the granulopoietic TTP targets IL-1β, TNF-α, and IL-6 in the plasma of TTP KO mice. Consistent with the non–cell-autonomous nature of the phenotype, we found elevated levels of IL-1β, TNF-α, and IL-6 transcripts in the livers of TTP KO mice and no detectable difference in the bone marrows. These findings demonstrate the importance of TTP in inflammatory homeostasis and highlight the ability of the hematopoietic system to respond to stress without significant numbers of quiescent HSCs entering the cell cycle.
Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells
Authors: MacLeod Megan K. L. , David Alexandria , McKee Amy S. , Crawford Frances , Kappler John W. , Marrack Philippa
Published: January 2011

CD4 T cell help for B cells is critical for effective Ab responses. Although many of the molecules involved in helper functions of naive CD4 T cells have been characterized, much less is known about the helper capabilities of memory CD4 T cells, an important consideration for the design of vaccines that aim to prime protective memory CD4 T cells. In this study, we demonstrate that memory CD4 T cells enable B cells to expand more rapidly and class switch earlier than do primary responding CD4 T cells. This accelerated response does not require large numbers of memory cells, and similar numbers of primary responding cells provide less effective help than do memory cells. However, only memory CD4 T cells that express the B cell follicle homing molecule, CXCR5, are able to accelerate the response, suggesting that the rapidity of the Ab response depends on the ability of CD4 memory T cells to migrate quickly toward B cells.
HLA Class I Allelic Sequence and Conformation Regulate Leukocyte Ig-Like Receptor Binding
Authors: Jones Des C. , Kosmoliaptsis Vasilis , Apps Richard , Lapaque Nicolas , Smith Isobel , Kono Azumi , Chang Chiwen , Boyle Louise H. , Taylor Craig J. , Trowsdale John , Allen Rachel L.
Published: January 2011

Leukocyte Ig-like receptors (LILRs) are a family of innate immune receptors predominantly expressed by myeloid cells that can alter the Ag presentation properties of macrophages and dendritic cells. Several LILRs bind HLA class I. Altered LILR recognition due to HLA allelic variation could be a contributing factor in disease. We comprehensively assessed LILR binding to >90 HLA class I alleles. The inhibitory receptors LILRB1 and LILRB2 varied in their level of binding to different HLA alleles, correlating in some cases with specific amino acid motifs. LILRB2 displayed the weakest binding to HLA-B*2705, an allele genetically associated with several autoimmune conditions and delayed progression of HIV infection. We also assessed the effect of HLA class I conformation on LILR binding. LILRB1 exclusively bound folded β2-microglobulin–associated class I, whereas LILRB2 bound both folded and free H chain forms. In contrast, the activating receptor LILRA1 and the soluble LILRA3 protein displayed a preference for binding to HLA-C free H chain. To our knowledge, this is the first study to identify the ligand of LILRA3. These findings support the hypothesis that LILR-mediated detection of unfolded versus folded MHC modulates immune responses during infection or inflammation.
Genetic Labeling Reveals Altered Turnover and Stability of Innate Lymphocytes in Latent Mouse Cytomegalovirus Infection
Authors: Busche Andreas , Schmitz Susanne , Fleige Henrike , Robbins Scott H. , Walzer Thierry , Stewart Charles A. , Förster Reinhold , Messerle Martin , Prinz Immo
Published: January 2011

Mouse CMV (MCMV) infection rapidly induces the proliferation of NK cells, which correlates with immunological protection. Whether NK cells primed during acute response against MCMV are maintained for the long term is not known. In this study, we used TcrdH2BeGFP mice in which maturing NK cells are genetically labeled with a pulse of very stable histone-2B–eGFP. In this system, we found that the reporter protein was diluted out upon NK cell division during acute MCMV infection. At the same time, mature NK cells in uninfected mice showed only very limited turnover in vivo. Three months after primary infection when MCMV latency was established, the majority of peripheral NK cells still displayed a higher record of proliferation than NK cells in mock-infected controls. This observation included both Ly49H+ and Ly49H– NK cells. Conversely, naive NK cells did not show more proliferation after transfer into latently MCMV-infected mice than that after transfer into mock-infected control mice. This indicated that the observed alterations of the NK cell compartment in MCMV latency were “legacy” (i.e., resulting from prior events during the initial immune response). Together, these results suggest that antiviral immune responses induce sustained alterations of innate lymphocyte populations that extend far beyond the first days of acute infection.
CXCR4 Expression on Activated B Cells Is Downregulated by CD63 and IL-21
Authors: Yoshida Nobuya , Kitayama Daisuke , Arima Masafumi , Sakamoto Akemi , Inamine Ayako , Watanabe-Takano Haruko , Hatano Masahiko , Koike Takao , Tokuhisa Takeshi
Published: January 2011

CXCR4 expression is critical for localization of centroblasts in the dark zone of germinal centers (GCs), and centrocytes downregulate CXCR4 and thus leave the dark zone to reside in the light zone. However, mechanisms governing CXCR4 downregulation on centrocytes are not known. In this study, we show that the amount of intracellular CXCR4 in centroblasts was similar to that in centrocytes, suggesting differential control of CXCR4 protein expression in these GC B cells. Restimulation of activated B cells with IL-21, which is a major cytokine produced by T follicular helper cells, accelerated CXCR4 internalization by inducing endocytosis-related GRK6 expression. Although CXCR4 expression was downregulated on GC B cells by IL-21 stimulation, CXCR4low centrocytes developed in the spleens of IL-21R–deficient mice, suggesting other mechanisms for downregulation. The level of CD63 (which recruits CXCR4 to late endosome in CD4 T cells) in centrocytes was more than that in centroblasts and was strikingly elevated in activated Bcl6-deficient B cells. Bcl6, a transcriptional repressor, was detected on the chromatin of the CD63 gene in resting B cells, therefore CD63 is a molecular target of Bcl6. Downregulation of CD63 mRNA in activated Bcl6-deficient B cells by small interfering RNA upregulated CXCR4 expression on the B cells. Furthermore, addition of Bcl6 inhibitor to activated B cell cultures increased CD63 mRNA expression in (and downregulated CXCR4 expression on) those activated B cells. Thus, CXCR4 can be downregulated on activated B cells by IL-21–induced endocytosis and CD63-mediated endosomal recruitment, and these mechanisms may contribute to downregulation of CXCR4 on centrocytes.
Intrinsic Requirement for the Vitamin D Receptor in the Development of CD8αα-Expressing T Cells
Authors: Bruce Danny , Cantorna Margherita T.
Published: January 2011

Vitamin D and vitamin D receptor (VDR) deficiency results in severe symptoms of experimental inflammatory bowel disease in several different models. The intraepithelial lymphocytes of the small intestine contain large numbers of CD8αα+ T cells that have been shown to suppress the immune response to Ags found there. In this study, we determined the role of the VDR in the development of CD8αα+ T cells. There are fewer total numbers of TCRαβ+ T cells in the gut of VDR knockout (KO) mice, and that reduction was largely in the CD8αα+ TCRαβ+ cells. Conversely TCRγδ+ T cells were normal in the VDR KO mice. The thymic precursors of CD8αα+ TCRαβ+ cells (triple-positive for CD4, CD8αα, and CD8αβ) were reduced and less mature in VDR KO mice. In addition, VDR KO mice had a higher frequency of the CD8αα+ TCRαβ+ precursors (double-negative [DN] TCRαβ+ T cells) in the gut. The proliferation rates of the DN TCRαβ+ gut T cells were less in the VDR KO compared with those in wild type. Low proliferation of DN TCRαβ+ T cells was a result of the very low expression of the IL-15R in this population of cells in the absence of the VDR. Bone marrow transplantation showed that the defect in VDR KO CD8αα+ TCRαβ+ cells was cell intrinsic. Decreased maturation and proliferation of CD8αα+ TCRαβ+ cells in VDR KO mice results in fewer functional CD8αα+ TCRαβ+ T cells, which likely explains the increased inflammation in the gastrointestinal tract of VDR KO and vitamin D-deficient mice.
Nonhematopoietic Cells Are Key Players in Innate Control of Bacterial Airway Infection
Authors: LeibundGut-Landmann Salomé , Weidner Kerstin , Hilbi Hubert , Oxenius Annette
Published: January 2011

Airborne pathogens encounter several hurdles during host invasion, including alveolar macrophages (AMs) and airway epithelial cells (AECs) and their products. Although growing evidence indicates pathogen-sensing capacities of epithelial cells, the relative contribution of hematopoietic versus nonhematopoietic cells in the induction of an inflammatory response and their possible interplay is still poorly defined in vivo in the context of infections with pathogenic microorganisms. In this study, we show that nonhematopoietic cells, including AECs, are critical players in the inflammatory process induced upon airway infection with Legionella pneumophila, and that they are essential for control of bacterial infections. Lung parenchymal cells, including AECs, are not infected themselves by L. pneumophila in vivo but rather act as sensors and amplifiers of inflammatory cues delivered by L. pneumophila-infected AM. We identified AM-derived IL-1β as the critical mediator to induce chemokine production in nonhematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways. These data add a new level of complexity to the coordination of the innate immune response to L. pneumophila and illustrate how the cross talk between leukocytes and nonhematopoietic cells contributes to efficient host protection.
High Prevalence and Low Awareness of Hypertension in a Market Population in Enugu, Nigeria
Authors: Ulasi Ifeoma I. , Ijoma Chinwuba K. , Onwubere Basden J. C. , Arodiwe Ejikeme , Onodugo Obinna , Okafor Christian
Published: January 2011

Background. A community-based study put the prevalence of hypertension in Nigeria at 32.8%. Market workers in Nigeria lead sedentary life style and often depend on salt-laden fast food while at work.Method. An unselected population of market workers were screened for hypertension and its risk factors by a pretested, structured questionnaire, clinical examination, and laboratory investigation. Hypertension was defined as BP ≥ 140 and/or ≥ 90 mmHg or being on drug therapy.Results. Forty-two percent of the screened population were hypertensive. Of this number, 70.6% did not know they were hypertensive before the screening. More males than females () were hypertensive. Prevalence of hypertension increased with age from 5.4% in the age group <20 years to 80% in the age group ≥70 years.Conclusion. The prevalence of hypertension in market workers in this study was 42%, and the majority of them were unaware of their disease.
Automated Cardiac Drug Infusion System Using Adaptive Fuzzy Neural Networks Controller
Authors: Karar Mohamed E. , El-Brawany Mohamed A.
Published: January 2011

This paper presents a fuzzy neural network (FNN) control system to automatically manage the hemodynamic variables of patients with hypertension and congestive heart failure (CHF) via simultaneous infusion of cardiac drugs such as vasodilators and inotropic agents. The developed system includes two FNN sub-controllers for regulating cardiac output (CO) and mean arterial pressure (MAP) by cardiac drugs, considering interactive pharmacological effects. The adaptive FNN controller was tested and evaluated on a cardiovascular model. Six short-term therapy conditions of hypertension and CHF are presented under different sensitivities of a vasodilator drug. The results of the automated system showed that root mean square errors were ≤ 5.56 mmHg and ≤ 0.22 L min-1 for regulating MAP and CO, respectively, providing short settling time responses of MAP (≤ 10.9 min) and CO (≤ 8.22 min) in all therapy conditions. The proposed FNN control scheme can significantly improve the performance of cardiac drug infusion System.
Structure of the Set of Norm-attaining Functionals on Strictly Convex Spaces
Authors: Kurka Ondřej
Published: January 2011

Let X be a separable non-reflexive Banach space. We show that there is no Borel class which contains the set of norm-attaining functionals for every strictly convex renorming of X.
Sur la borne inférieure du rang du 2-groupe de classes de certains corps multiquadratiques
Authors: Mouhib A.
Published: January 2011

Soient p1, p2, p3 et q des nombres premiers distincts tels que p1 ≡ p2 ≡ p3 ≡ –q ≡ 1 (mod 4), et Cl2(k) le 2-groupe de classes de k. A. Fröhlich a démontré que Cl2(k) n’est jamais trivial. Dans cet article, nous donnons une extension de ce résultat, en démontrant que le rang de Cl2(k) est toujours supérieur ou égal à 2. Nous démontrons aussi, que la valeur 2 est optimale pour une famille infinie de corps k.
Sensitivity of Sub-critical Mode-coupling Instabilities in Non-conservative Rotating Continua to Stiffness and Damping Modifications
Authors: Kirillov Oleg N.
Published: January 2011

Mode-coupling instability is a widely accepted mechanism for the onset of friction-induced vibrations in car brakes, wheel sets, paper calendars, to name a few. In the presence of damping, gyroscopic, and non-conservative positional forces the merging of modes is imperfect, that is two modes may come close together in the complex plane without collision and then diverge so that one of the modes becomes unstable. In non-conservative rotating continua that respect axial symmetry this movement of eigenvalues is very sensitive to the variation of parameters of the system. Our study reveals some general rules that govern sub-critical mode-coupling instabilities in non-conservative rotating continua to stiffness and damping modifications and provide useful insight for optimisation of such systems and interpretation of experimental results.
Stability Analysis for a Self-exciting Mechanism with Friction Using Interval Computations
Authors: Berger Sebastien , Sinou Jean Jacques
Published: January 2011

The aim of this paper is to present a new strategy based on the interval analysis for the prediction of stable and unstable regions of mechanical systems subjected to friction-induced instability. For the sake of simplicity, a two-degree-of-freedom minimal model is constructed and analysed to examine the numerical procedure and interval algorithm. The efficiency and robustness of the proposed method is demonstrated through numerical simulations versus the variation of the friction coefficient and the damping factor.
Clinical outcome of Zweymüller total hip arthroplasty for patients with high congenital hip dislocation
Authors: Chen Dongyang , Xu Zhihong , Shi Dongquan , Qiu Xusheng , Dai Jin , Yuan Tao , Weng Wenjie , Jiang Qing
Published: January 2011

Treatment of high congenital dislocation of the hip (CDH) remains controversial. We report the outcome of hip arthroplasty using a cementless threaded cup and a cementless straight stem in patients with high congenital hip dislocation.

Between January 2001 and August 2004, 17 patients with high congenital hip dislocation were treated. During surgery, at least 25% of the cup was anchored in bone. By monitoring somatosensory-evoked potentials (SEPs) of the common peroneal nerve we were able to reduce the femoral head into position in the true acetabulum by releasing soft tissues. A bulk autogenous femoral head bone graft was implanted in 5 patients to achieve at least 75% bony coverage of the acertabular component. Follow-up ranged from 48 months to 91 months with an average of 69.7 months. The mean Harris hip score increased from 43 points preoperatively to 89 points at the time of final follow-up (P<0.001). Radiographic analysis showed bony union of the bone graft in all cases.