bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Crucial Role of GATA-1 in CCR3 Gene Transcription: Modulated Balance by Multiple GATA Elements in the CCR3 Regulatory Region
Authors: Kim Byung Soo , Uhm Tae Gi , Lee Seol Kyoung , Lee Sin-Hwa , Kang Jin Hyun , Park Choon-Sik , Chung Il Yup 
Published: November 2010

Abstract
GATA-1, a zinc finger-containing transcription factor, regulates not only the differentiation of eosinophils but also the expression of many eosinophil-specific genes. In the current study, we dissected CCR3 gene expression at the molecular level using several cell types that express varying levels of GATA-1 and CCR3. Chromatin immunoprecipitation analysis revealed that GATA-1 preferentially bound to sequences in both exon 1 and its proximal intron 1. A reporter plasmid assay showed that constructs harboring exon 1 and/or intron 1 sequences retained transactivation activity, which was essentially proportional to cellular levels of endogenous GATA-1. Introduction of a dominant-negative GATA-1 or small interfering RNA of GATA-1 resulted in a decrease in transcription activity of the CCR3 reporter. Both point mutation and EMSA analyses demonstrated that although GATA-1 bound to virtually all seven putative GATA elements present in exon 1–intron 1, the first GATA site in exon 1 exhibited the highest binding affinity for GATA-1 and was solely responsible for GATA-1–mediated transactivation. The fourth and fifth GATA sites in exon 1, which were postulated previously to be a canonical double-GATA site for GATA-1–mediated transcription of eosinophil-specific genes, appeared to play an inhibitory role in transactivation, albeit with a high affinity for GATA-1. Furthermore, mutation of the seventh GATA site (present in intron 1) increased transcription, suggesting an inhibitory role. These data suggest that GATA-1 controls CCR3 transcription by interacting dynamically with the multiple GATA sites in the regulatory region of the CCR3 gene.
A Critical Role for Mast Cells and Mast Cell-Derived IL-6 in TLR2-Mediated Inhibition of Tumor Growth
Authors: Oldford Sharon A. , Haidl Ian D. , Howatt Mackenzie A. , Leiva Carlos A. , Johnston Brent , Marshall Jean S. 
Published: November 2010

Abstract
Several TLR agonists are effective in tumor immunotherapy, but their early innate mechanisms of action, particularly those of TLR2 agonists, are unclear. Mast cells are abundant surrounding solid tumors where they are often protumorigenic and enhance tumor angiogenesis. However, antitumor roles for mast cells have also been documented. The impact of mast cells may be dependent on their activation status and mediator release in different tumors. Using an orthotopic melanoma model in wild-type C57BL/6 and mast cell-deficient KitW-sh/W-sh mice and a complementary Matrigel–tumor model in C57BL/6 mice, mast cells were shown to be crucial for TLR2 agonist (Pam3CSK4)-induced tumor inhibition. Activation of TLR2 on mast cells reversed their well-documented protumorigenic role. Tumor growth inhibition after peritumoral administration of Pam3CSK4 was restored in KitW-sh/W-sh mice by local reconstitution with wild-type, but not TLR2-deficient, mast cells. Mast cells secrete multiple mediators after Pam3CSK4 activation, and in vivo mast cell reconstitution studies also revealed that tumor growth inhibition required mast cell-derived IL-6, but not TNF. Mast cell-mediated anticancer properties were multifaceted. Direct antitumor effects in vitro and decreased angiogenesis and recruitment of NK and T cells in vivo were observed. TLR2-activated mast cells also inhibited the growth of lung cancer cells in vivo. Unlike other immune cells, mast cells are relatively radioresistant making them attractive candidates for combined treatment modalities. This study has important implications for the design of immunotherapeutic strategies and reveals, to our knowledge, a novel mechanism of action for TLR2 agonists in vivo.
IL-22RA2 Associates with Multiple Sclerosis and Macrophage Effector Mechanisms in Experimental Neuroinflammation
Authors: Beyeen Amennai D. , Adzemovic Milena Z. , Öckinger Johan , Stridh Pernilla , Becanovic Kristina , Laaksonen Hannes , Lassmann Hans , Harris Robert A. , Hillert Jan , Alfredsson Lars , Celius Elisabeth G. , Harbo Hanne F. , Kockum Ingrid , Jagodic Maja , Olsson Tomas 
Published: November 2010

Abstract
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS. Recent advances in whole-genome screening tools have enabled discovery of several MS risk genes, the majority of which have known immune-related functions. However, disease heterogeneity and low tissue accessibility hinder functional studies of established MS risk genes. For this reason, the MS model experimental autoimmune encephalomyelitis (EAE) is often used to study neuroinflammatory disease mechanisms. In this study, we performed high-resolution linkage analysis in a rat advanced intercross line to identify an EAE-regulating quantitative trait locus, Eae29, on rat chromosome 1. Eae29 alleles from the resistant strain both conferred milder EAE and lower production of proinflammatory molecules in macrophages, as demonstrated by the congenic line, DA.PVG-Eae29 (Dc1P). The soluble IL-22R α2 gene (Il-22ra2) lies within the Eae29 locus, and its expression was reduced in Dc1P, both in activated macrophages and splenocytes from immunized rats. Moreover, a single nucleotide polymorphism located at the end of IL-22RA2 associated with MS risk in a combined Swedish and Norwegian cohort comprising 5019 subjects, displaying an odds ratio of 1.26 (p = 8.0 × 10−4). IL-22 and its receptors have been implicated in chronic inflammation, suggesting that IL-22RA2 regulates a central immune pathway. Through a combined approach including genetic and immunological investigation in an animal model and large-scale association studies of MS patients, we establish IL-22RA2 as an MS risk gene.
Influenza Epitope-Specific CD8+ T Cell Avidity, but Not Cytokine Polyfunctionality, Can Be Determined by TCRβ Clonotype
Authors: Moffat Jessica M. , Handel Andreas , Doherty Peter C. , Turner Stephen J. , Thomas Paul G. , La Gruta Nicole L. 
Published: November 2010

Abstract
Cytokine polyfunctionality has recently emerged as a correlate of effective CTL immunity to viruses and tumors. Although the determinants of polyfunctionality remain unclear, there are published instances of a link between the production of multiple effector molecules and the peptide plus MHC class I molecule avidity of T cell populations. Influenza A virus infection of C57BL/6J mice induces CTL populations specific for multiple viral epitopes, each with varying proportions of monofunctional (IFN-γ+ only) or polyfunctional (IFN-γ+TNF-α+IL-2+) CTLs. In this study, we probe the link between TCR avidity and polyfunctionality for two dominant influenza epitopes (DbNP366 and DbPA224) by sequencing the TCR CDR3β regions of influenza-specific IFN-γ+ versus IFN-γ+IL-2+ cells, or total tetramer+ versus high-avidity CTLs (as defined by the peptide plus MHC class I molecule-TCR dissociation rate). Preferential selection for particular clonotypes was evident for the high-avidity DbPA224-specific set but not for any of the other subsets examined. These data suggest that factors other than TCRβ sequence influence cytokine profiles and demonstrate no link between differential avidity and polyfunctionality.
Lipopolysaccharide-Mediated IL-10 Transcriptional Regulation Requires Sequential Induction of Type I IFNs and IL-27 in Macrophages
Authors: Iyer Shankar Subramanian , Ghaffari Amir Ali , Cheng Genhong 
Published: November 2010

Abstract
IL-10 is a potent anti-inflammatory molecule that regulates excessive production of inflammatory cytokines during an infection or tissue damage. Dysregulation of IL-10 is associated with a number of autoimmune diseases, and so, understanding the mechanisms by which IL-10 gene expression is regulated remains an important area of study. Macrophages represent a major source of IL-10, which is generated in response to TLR signaling as a feedback mechanism to curtail inflammatory response. In this study, we identify a signaling pathway in murine bone marrow-derived macrophages in which activation of TLR4 by LPS induces the expression of IL-10 through the sequential induction of type I IFNs followed by induction and signaling through IL-27. We demonstrate that IL-27 signaling is required for robust IL-10 induction by LPS and type I IFNs. IL-27 leads directly to transcription of IL-10 through the activation of two required transcription factors, STAT1 and STAT3, which are recruited to the IL-10 promoter. Finally, through systematic functional promoter-reporter analysis, we identify three cis elements within the proximal IL-10 promoter that play an important role in regulating transcription of IL-10 in response to IL-27.
Early Enhanced Local Neutrophil Recruitment in Peritonitis-Induced Sepsis Improves Bacterial Clearance and Survival
Authors: Craciun Florin L. , Schuller Elizabeth R. , Remick Daniel G. 
Published: November 2010

Abstract
Neutrophils are critical for the rapid eradication of bacterial pathogens, but they also contribute to the development of multiple organ failure in sepsis. We hypothesized that increasing early recruitment of neutrophils to the focus of infection will increase bacterial clearance and improve survival. Sepsis was induced in mice, using cecal ligation and puncture (CLP); blood samples were collected at 6 and 24 h; and survival was followed for 28 d. In separate experiments, peritoneal bacteria and inflammatory cells were measured. Septic mice predicted to die based on IL-6 levels (Die-P) had higher concentrations of CXCL1 and CXCL2 in the peritoneum and plasma compared with those predicted to live (Live-P). At 6 h, Live-P and Die-P had equivalent numbers of peritoneal neutrophils and bacteria. In Die-P mice the number of peritoneal bacteria increased between 6 and 24 h post-CLP, whereas in Live-P it decreased. The i.p. injection of CXCL1 and CXCL2 in naive mice resulted in local neutrophil recruitment. When given immediately after CLP, CXC chemokines increased peritoneal neutrophil recruitment at 6 h after CLP. This early increase in neutrophils induced by exogenous chemokines resulted in significantly fewer peritoneal bacteria by 24 h [CFU (log) = 6.04 versus 4.99 for vehicle versus chemokine treatment; p &lt; 0.05]. Chemokine treatment significantly improved survival at both 5 d (40 versus 72%) and 28 d (27 versus 52%; p &lt; 0.02 vehicle versus chemokines). These data demonstrate that early, local treatment with CXC chemokines enhances neutrophil recruitment and clearance of bacteria as well as improves survival in the CLP model of sepsis.
Robust Vaccine-Elicited Cellular Immune Responses in Breast Milk following Systemic Simian Immunodeficiency Virus DNA Prime and Live Virus Vector Boost Vaccination of Lactating Rhesus Monkeys
Authors: Wilks Andrew B. , Christian Elizabeth C. , Seaman Michael S. , Sircar Piya , Carville Angela , Gomez Carmen E. , Esteban Mariano , Pantaleo Giuseppe , Barouch Dan H. , Letvin Norman L. , Permar Sallie R. 
Published: November 2010

Abstract
Breast milk transmission of HIV remains an important mode of infant HIV acquisition. Enhancement of mucosal HIV-specific immune responses in milk of HIV-infected mothers through vaccination may reduce milk virus load or protect against virus transmission in the infant gastrointestinal tract. However, the ability of HIV/SIV strategies to induce virus-specific immune responses in milk has not been studied. In this study, five uninfected, hormone-induced lactating, Mamu A*01+ female rhesus monkey were systemically primed and boosted with rDNA and the attenuated poxvirus vector, NYVAC, containing the SIVmac239 gag-pol and envelope genes. The monkeys were boosted a second time with a recombinant Adenovirus serotype 5 vector containing matching immunogens. The vaccine-elicited immunodominant epitope-specific CD8+ T lymphocyte response in milk was of similar or greater magnitude than that in blood and the vaginal tract but higher than that in the colon. Furthermore, the vaccine-elicited SIV Gag-specific CD4+ and CD8+ T lymphocyte polyfunctional cytokine responses were more robust in milk than in blood after each virus vector boost. Finally, SIV envelope-specific IgG responses were detected in milk of all monkeys after vaccination, whereas an SIV envelope-specific IgA response was only detected in one vaccinated monkey. Importantly, only limited and transient increases in the proportion of activated or CCR5-expressing CD4+ T lymphocytes in milk occurred after vaccination. Therefore, systemic DNA prime and virus vector boost of lactating rhesus monkeys elicits potent virus-specific cellular and humoral immune responses in milk and may warrant further investigation as a strategy to impede breast milk transmission of HIV.
Effect of Element Distortion on the Numerical Dispersion of Spectral Element Methods
Authors: Oliveira S.P. , Seriani G. 
Published: November 2010

AbstractSpectral element methods are well established in the field of wave propagation, in particular because they inherit the flexibility of finite element methods and have low numerical dispersion error. The latter is experimentally acknowledged, but has been theoretically shown only in limited cases, such as Cartesian meshes. It is well known that a finite element mesh can contain distorted elements that generate numerical errors for very large distortions. In the present work, we study the effect of element distortion on the numerical dispersion error and determine the distortion range in which an accurate solution is obtained for a given error tolerance. We also discuss a double-grid calculation of the spectral element matrices that preserves accuracy in deformed geometries.
Numerical Simulations of Hydrodynamics of Nematic Liquid Crystals: Effects of Kinematic Transports
Authors: Zhang Shupeng , Liu Chun , Zhang Hui 
Published: November 2010

AbstractIn this paper, we investigate the effects of kinematic transports on the nematic liquid crystal system numerically and theoretically. The model we used is a “1+2” elastic continuum model simplified from the Ericksen-Leslie system. The numerical experiments are carried out by using a Legendre-Galerkin spectral method which can preserve the energy law in the discrete form. Based on this highly accurate numerical approach we find some interesting and important relationships between the kinematic transports and the characteristics of the flow. We make some analysis to explain these results. Several significant scaling properties are also verified by our simulations.
A Lattice Boltzmann-Direct Forcing/Fictitious Domain Model for Brownian Particles in Fluctuating Fluids
Authors: Nie Deming , Lin Jianzhong 
Published: November 2010

AbstractThe previously developed LB-DF/FD method derived from the lattice Boltzmann method and Direct Forcing/Fictitious Domain method is extended to deal with 3D particle’s Brownian motion. In the model the thermal fluctuations are introduced as random forces and torques acting on the Brownian particle. The hydrodynamic interaction is introduced by directly resolving the fluid motions. A sphere fluctuating in a cubic box with the periodic boundary is considered to validate the present model. By examining the velocity autocorrelation function (VCF) and rotational velocity autocorrelation function (RVCF), it has been found that in addition to the two relaxation times, the mass density ratio should be taken into consideration to check the accuracy and effectiveness of the present model. Furthermore, the fluctuation-dissipation theorem and equipartition theorem have been investigated for a single spherical particle. Finally, a Brownian particle trapped in a harmonic potential has been simulated to further demonstrate the ability of the LB-DF/FD model.
TEM Orientation Imaging in Characterization of Texture Changes in FCC Metals
Authors: Paul Henryk 
Published: November 2010

AbstractAspects of crystal subdivision and nucleation of recrystallization in fcc‐lattice metals are studied by TEM‐based orientation mapping. This method is suitable to study fine‐grained materials because of the good spatial resolution and a direct comparison of the orientation distribution with the dislocation structure is possible. Orientation measurements of subcells in the deformed state shows that and the unstable behavior leads strain inhomogeneities and therefore to specific texture components. The first‐formed nuclei develop within the as‐deformed dislocation structures; successive stages of recrystallization are observed in annealed samples.
Lattice dynamics of ZnAl2O4 and ZnGa2O4 under high pressure
Authors: López‐Moreno S. , Rodríguez‐Hernández P. , Muñoz A. , Romero A.H. , Manjón F.J. , Errandonea D. , Rusu E. , Ursaki V.V. 
Published: November 2010

AbstractIn this work we present a first‐principles density functional study of the vibrational properties of ZnAl2O4 and ZnGa2O4 as function of hydrostatic pressure. Based on our previous structural characterization of these two compounds under pressure, herewith, we report the pressure dependence on both systems of the vibrational modes for the cubic spinel structure, for the CaFe2O4‐type structure (Pnma) in ZnAl2O4 and for marokite (Pbcm) ZnGa2O4. Additionally we report a second order phase transition in ZnGa2O4 from the marokite towards the CaTi2O4‐type structure (Cmcm), for which we also calculate the pressure dependence of the vibrational modes at the Γ point. Our calculations are complemented with Raman scattering measurements up to 12 GPa that show a good overall agreement between our calculated and measured mode frequencies.
Hairy cell leukaemia: biological and clinical overview from immunogenetic insights
Authors: Forconi Francesco 
Published: November 2010

AbstractHairy cell Leukaemia (HCL) is a rare neoplasm of peripheral B cells which represents a paradox in oncology. Despite its largely unknown origin and behaviour, HCL is one of the few example of dramatic success in the treatment of a malignancy. The recent steps forward to understanding the biology of HCL from immunogenetic and genomic studies have recently provided new insight into diagnosis and prognosis. Several data from immunoglobulin gene (IG) analysis have provided hints regarding the cell of origin and the ongoing selective interactions of the tumour BCR with environmental stimuli. It has also recently emerged that an unmutated status of the HCL IG can be associated with failure to respond to cladribine, genetic abnormalities indicative of poor outcome and aggressive disease. These observations suggest a central role of the tumour B‐cell receptor in defining the outcome of HCL and that that IG gene analysis may have biological and prognostic relevance. Hopefully, IG analysis will help tailor treatment strategies for the most aggressive cases. Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis of [15N3]melamine and [13C3]cyanuric acid
Authors: Luo Yong , Zhang Liya , Yang Weicheng , Liu Weixia , Lu Weijing , Li Meihua 
Published: November 2010

AbstractThis report presents an efficient syntheses of two labelled internal standards [15N3]melamine and [13C3]cyanuric acid with the common substrates [15N]NH4Cl and [13C]urea, respectively. Both standards with excellent isotopic and chemical purities were prepared in good yields and could be used as internal standards without further purification. Copyright © 2010 John Wiley & Sons, Ltd.
Thermodynamics of Phosphorus and Sulphur Removal during Basic Oxygen Steelmaking
Authors: Basu S. , Seetharaman S. , Lahiri A. K. 
Published: November 2010

AbstractRemoval of impurity elements from hot metal is essential in basic oxygen steelmaking. Oxidation of phosphorus from hot metal has been studied by several authors since the early days of steelmaking. Influence of different parameters on the distribution of phosphorus, seen during the recent work of the authors, differs somewhat from that reported earlier. On the other hand, removal of sulphur during steelmaking has drawn much less attention. This may be due to the magnitude of desulphurisation in oxygen steelmaking being relatively low and desulphurisation during hot metal pre‐treatment or in the ladle furnace offering better commercial viability. Further, it is normally accepted that sulphur is removed to steelmaking slag in the form of sulphide only. However, recent investigations have indicated that a significant amount of sulphur removed during basic oxygen steelmaking can exist in the form of sulphate in the slag under oxidising conditions. The distribution of sulphur during steelmaking becomes more important in the event of carry‐over of sulphur‐rich blast‐furnace slag, which increases sulphur load in the BOF. The chemical nature of sulphur in this slag undergoes a gradual transition from sulphide to sulphate as the oxidative refining progresses.
Oxygen Penetration in the Protection Shroud in Steel Casting
Authors: Ragnarsson L. , Song W. , Ma Y. , Sichen D. 
Published: November 2010

AbstractPhysical modelling of argon shroud used in ingot casting was carried out using a 2D 1:1 scaled model in order to determine the oxygen distribution around the steel stream. The oxygen concentrations were measured by an oxygen sensor. Complementary PIV measurements were also carried out for a gas inlet configuration using dual (horizontal and vertical) gas inlet. The main findings were: (1) The oxygen concentrations were considerably high in the ordinary operation conditions. The oxygen contents were the highest in the case of vertical gas injection (higher than 11% in all cases). (2) A minimized distance between the ladle and the collar on the top of the vertical runner would reduce the oxygen entrainment by convection and diffusion, in the case of horizontal gas injection and a dual gas inlet configuration. (3) A modest flow rate of argon gas should be used. Further increase of the gas flow would not improve the protection. (4) A dual gas inlet configuration would be more effective than a single inlet, especially in the case of larger distances between the ladle and the runner.
Proximate Composition and Fatty Acid Profile of Pongamia pinnata, a Potential Biodiesel Crop
Authors: Bala Manju , Nag T. N. , Kumar Sandeep , Vyas Manmohan , Kumar Arun , Bhogal N. S. 
Published: November 2010

AbstractThe chemical characteristics of Pongamia pinnata seeds, focussing on proximate composition and the fatty acid profile of its oil, are presented. The proximate composition of P. pinnata seeds was: 3.8% ash, 9.7% sugar, 7.07% protein, 24% oil, 10.7% free amino acids, and 0.24% free fatty acids. The oil was extracted from seeds by use of different solvents and the highest yield (29%) was obtained by use of n‐hexane. Monounsaturated and polyunsaturated fatty acids accounted for 63.3 and 22.9%, respectively, of the seed oil. Oleic acid was the major fatty acid but a substantial amount of erucic acid was also detected; this was not reported in previous studies. The level of erucic acid and the presence of toxic flavonoids, for example karanjin, pongapin, and pongaglabrin, render the oil inedible according to WHO recommendations. However, low levels of saturated and polyunsaturated fatty acids with desirable cetane number and iodine value suggest potential for application as a biodiesel fuel.
Evidence for Using Chlorhexidine Gluconate Preoperative Cleansing to Reduce the Risk of Surgical Site Infection
Authors: Edmiston Charles E. , Okoli Obi , Graham Mary Beth , Sinski Sharon , Seabrook Gary R. 
Published: October 2010

AbstractSurgical site infections are associated with significant patient morbidity and mortality and are the third most frequently reported health care‐associated infection. A suggested risk reduction strategy has been the preadmission shower or skin cleansing with chlorhexidine gluconate (CHG). Although older clinical trials question the clinical efficacy of cleansing with CHG, recent evidence‐based scientific and clinical studies support two types of CHG application (ie, a 2% CHG‐coated cloth or 4% CHG soap) using a standardized, timed process before hospital admission as an effective strategy for reducing the risk of postoperative surgical site infection.