bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Control of Simian Immunodeficiency Virusmac251 Viremia to Undetectable Levels in Half of Infected Female Rhesus Macaques Nasally Vaccinated with Simian Immunodeficiency Virus DNA/Recombinant Modified Vaccinia Virus Ankara
Authors: Manrique Mariana , Kozlowski Pamela A. , Cobo-Molinos Antonio , Wang Shainn-Wei , Wilson Robert L. , Montefiori David C. , Mansfield Keith G. , Carville Angela , Aldovini Anna 
Published: February 2011

AbstractThe efficacy of two SIV DNA plus recombinant modified vaccinia virus Ankara nasal vaccine regimens, one combined with plasmids expressing IL-2 and IL-15, the other with plasmids expressing GM-CSF, IL-12, and TNF-α, which may better stimulate humoral responses, was evaluated in two female rhesus macaque groups. Vaccination stimulated significant SIV-specific mucosal and systemic cell-mediated immunity in both groups, whereas SIV-specific IgA titers were sporadic and IgG titers negative. All vaccinated animals, except one, became infected after intravaginal SIVmac251 low-dose challenge. Half of the vaccinated, infected animals (7/13) promptly controlled virus replication to undetectable viremia for the duration of the trial (130 wk) and displayed virological and immunological phenotypes similar to those of exposed, uninfected individuals. When all vaccinated animals were considered, a 3-log viremia reduction was observed, compared with controls. The excellent viral replication containment achieved in vaccinated animals translated into significant preservation of circulating α4β7high+/CD4+ T cells and of circulating and mucosal CD4+/CM T cells and in reduced immune activation. A more significant long-term survival was also observed in these animals. Median survival was 72 wk for the control group, whereas &gt;50% of the vaccinated animals were still disease free 130 wk postchallenge, when the trial was closed. There was a statistically significant correlation between levels of CD4+/IFN-γ+ and CD8+/IFN-γ+ T cell percentages on the day of challenge and the control of viremia at week 60 postchallenge or survival. Postchallenge immunological correlates of protection were systemic anti-SIV Gag + Env CD4+/IL-2+, CD4+/IFN-γ+, and CD8+/TNF-α+ T cells and vaginal anti-SIV Gag + Env CD8+ T cell total monofunctional responses.
Impaired Wound Healing with Defective Expression of Chemokines and Recruitment of Myeloid Cells in TLR3-Deficient Mice
Authors: Lin Qing , Fang Dan , Fang Jiazhu , Ren Xiangrong , Yang Xiaoping , Wen Feng , Su Shao Bo 
Published: February 2011

Abstract
Skin injury evokes both innate and adaptive immune responses to restore tissue integrity. TLRs play a critical role in host responses to injurious insults. Previous studies demonstrated that RNAs released from damaged tissues served as endogenous ligands for TLR3. In this study, we investigated the involvement of TLR3 in skin restoration after injury. Full excisional wounds were created on the skin of mice with TLR3 deficiency. We found that skin wound closure in TLR3−/− mice was significantly delayed compared with control littermates. Wound healing parameters, including re-epithelialization, granulation formation, and neovascularization, were decreased in TLR3−/− mice. Further studies revealed that the absence of TLR3 led to defective recruitment of neutrophils and macrophages, in association with decreased expression of the chemokines, MIP-2/CXCL2, MIP-1α/CCL3, and MCP-1/CCL2, in the wound. Moreover, in wild type mice, the mRNA level and protein content of TLR3 was significantly upregulated in wounded skins and silencing of TLR3 signal adaptor Toll/IL-1R domain-containing adapter inducing IFN-β with small interfering RNA retarded wound closure. These results indicate an essential role for TLR3 and Toll/IL-1R domain-containing adapter inducing IFN-β in wound healing by regulating chemokine production and recruitment of myeloid cells to wound for tissue repair.
Supplemental and Highly Elevated Tocopherol Doses Differentially Regulate Allergic Inflammation: Reversibility of α-Tocopherol and γ-Tocopherol’s Effects
Authors: McCary Christine A. , Abdala-Valencia Hiam , Berdnikovs Sergejs , Cook-Mills Joan M. 
Published: February 2011

AbstractWe have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with Ag and supplemental tocopherols in a first phase of treatment followed by a 4-wk clearance phase, and then the mice received a second phase of Ag and tocopherol treatments. The proinflammatory effects of supplemental levels of γ-tocopherol in phase 1 were only partially reversed by supplemental α-tocopherol in phase 2, but were completely reversed by raising α-tocopherol levels 10-fold in phase 2. When γ-tocopherol levels were increased 10-fold (highly elevated tocopherol) so that the lung tissue γ-tocopherol levels were equal to the lung tissue levels of supplemental α-tocopherol, γ-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly elevated levels of γ-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of Ag challenge without tocopherols. In summary, the proinflammatory effects of supplemental γ-tocopherol on lung inflammation were partially reversed by supplemental levels of α-tocopherol but were completely reversed by highly elevated levels of α-tocopherol. Also, highly elevated levels of γ-tocopherol were inhibitory and reversible in lung lavage but, importantly, were proinflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature.
Cutting Edge: Intravenous Ig Inhibits Invariant NKT Cell-Mediated Allergic Airway Inflammation through FcγRIIIA-Dependent Mechanisms
Authors: Araujo Luiza M. , Chauvineau Angélique , Zhu Ren , Diem Séverine , Bourgeois Elvire A. , Levescot Anaïs , Huerre Michel , Gombert Jean-Marc , Bayry Jagadeesh , Daëron Marc , Bruhns Pierre , Kaveri Srini V. , Herbelin André 
Published: February 2011

Abstract
Despite their increasing use in autoimmune, inflammatory, and allergic conditions, the mechanism of action of i.v. Igs (IVIg) is poorly understood. On the basis of the critical role of invariant NKT (iNKT) cells in allergic airway inflammation (AAI) and their constitutive expression of the low-affinity IgG receptor FcγRIIIA, we surmised that IVIg targets iNKT cells to exert their anti-inflammatory effect. We found that IVIg treatment significantly inhibited AAI in OVA-sensitized C57BL/6 mice and downregulated α-galactosylceramide–induced iNKT cell activation and cytokine production. Allergic responses were restored in iNKT cell-deficient mice by transferring iNKT cells from PBS- but not from IVIg-treated mice, suggesting that IVIg acts directly on activated iNKT cells that have a critical role in AAI. The inhibitory effects of IVIg on both iNKT cell activation/function and OVA-driven AAI were lost in FcγRIIIA−/− mice. Our data unravel an FcγRIIIA-dependent inhibitory effect of IVIg on activated iNKT cells that confers protection in AAI.
Recombinant Dimeric IgA Antibodies against the Epidermal Growth Factor Receptor Mediate Effective Tumor Cell Killing
Authors: Lohse Stefan , Derer Stefanie , Beyer Thomas , Klausz Katja , Peipp Matthias , Leusen Jeanette H. W. , van de Winkel Jan G. J. , Dechant Michael , Valerius Thomas 
Published: February 2011

AbstractDimeric IgA Abs contribute significantly to the humoral part of the mucosal immune system. However, their potential as immunotherapeutic agent has hardly been explored. In this article, we describe the production, purification, and functional evaluation of recombinant dimeric IgA against the epidermal growth factor receptor. Human joining chain-containing IgA was produced by nonadherent Chinese hamster ovarian (CHO)-K1 cells under serum-free conditions. Purification by anti-human κ and anti–His-tag affinity, as well as size exclusion chromatography, resulted in a homogenous preparation of highly pure IgA dimers. Functional studies demonstrated dimeric IgA to be at least as effective as monomeric IgA in triggering Ab-dependent cellular cytotoxicity by isolated monocytes or polymorphonuclear cell and in human whole-blood assays. Importantly, dimeric IgA was more effective in F(ab)-mediated killing mechanisms, such as inhibition of ligand binding, receptor downmodulation, and growth inhibition. Furthermore, only dimeric but not monomeric IgA or IgG was directionally transported by the polymeric Ig receptor through an epithelial cell monolayer. Together, these studies demonstrate that recombinant dimeric IgA Abs recruit a distinct repertoire of effector functions compared with monomeric IgA or IgG1 Abs.
A Barrier-Type Insulator Forms a Boundary between Active and Inactive Chromatin at the Murine TCRβ Locus
Authors: Carabana Juan , Watanabe Akiko , Hao Bingtao , Krangel Michael S. 
Published: February 2011

AbstractIn CD4−CD8− double-negative thymocytes, the murine Tcrb locus is composed of alternating blocks of active and inactive chromatin containing Tcrb gene segments and trypsinogen genes, respectively. Although chromatin structure is appreciated to be critical for regulated recombination and expression of Tcrb gene segments, the molecular mechanisms that maintain the integrity of these differentially regulated Tcrb locus chromatin domains are not understood. We localized a boundary between active and inactive chromatin by mapping chromatin modifications across the interval extending from Prss2 (the most 3′ trypsinogen gene) to Dβ1. This boundary, located 6 kb upstream of Dβ1, is characterized by a transition from repressive (histone H3 lysine 9 dimethylation [H3K9me2]) to active (histone H3 acetylation [H3ac]) chromatin and is marked by a peak of histone H3 lysine 4 dimethylation (H3K4me2) that colocalizes with a retroviral long terminal repeat (LTR). Histone H3 lysine 4 dimethylation is retained and histone H3 lysine 9 dimethylation fails to spread past the LTR even on alleles lacking the Tcrb enhancer (Eβ) suggesting that these features may be determined by the local DNA sequence. Notably, we found that LTR-containing DNA functions as a barrier-type insulator that can protect a transgene from negative chromosomal position effects. We propose that, in vivo, the LTR blocks the spread of heterochromatin, and thereby helps to maintain the integrity of the Eβ-regulated chromatin domain. We also identified low-abundance, Eβ-dependent transcripts that initiate at the border of the LTR and an adjacent long interspersed element. We speculate that this transcription, which extends across Dβ, Jβ and Cβ gene segments, may play an additional role promoting initial opening of the Eβ-regulated chromatin domain.
Highly Activated Cytotoxic CD8 T Cells Express Protective IL-10 at the Peak of Coronavirus-Induced Encephalitis
Authors: Trandem Kathryn , Zhao Jingxian , Fleming Erica , Perlman Stanley 
Published: February 2011

AbstractAcute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10+CD8 and IL-10−CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10+CD8 T cells were more highly activated and cytolytic than IL-10−CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.
Multiscale Computational Modeling Reveals a Critical Role for TNF-α Receptor 1 Dynamics in Tuberculosis Granuloma Formation
Authors: Fallahi-Sichani Mohammad , El-Kebir Mohammed , Marino Simeone , Kirschner Denise E. , Linderman Jennifer J. 
Published: February 2011

AbstractMultiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-α. TNF-α has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-α within a granuloma has been proposed to play a critical role in immunity to M. tuberculosis. However, in vivo measurement of a TNF-α concentration gradient and activities within a granuloma are not experimentally feasible. Further, processes that control TNF-α concentration and activities in a granuloma remain unknown. We developed a multiscale computational model that includes molecular, cellular, and tissue scale events that occur during granuloma formation and maintenance in lung. We use our model to identify processes that regulate TNF-α concentration and cellular behaviors and thus influence the outcome of infection within a granuloma. Our model predicts that TNF-αR1 internalization kinetics play a critical role in infection control within a granuloma, controlling whether there is clearance of bacteria, excessive inflammation, containment of bacteria within a stable granuloma, or uncontrolled growth of bacteria. Our results suggest that there is an interplay between TNF-α and bacterial levels in a granuloma that is controlled by the combined effects of both molecular and cellular scale processes. Finally, our model elucidates processes involved in immunity to M. tuberculosis that may be new targets for therapy.
Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets
Authors: Michalek Ryan D. , Gerriets Valerie A. , Jacobs Sarah R. , Macintyre Andrew N. , MacIver Nancie J. , Mason Emily F. , Sullivan Sarah A. , Nichols Amanda G. , Rathmell Jeffrey C. 
Published: February 2011

Abstract
Stimulated CD4+ T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation promoting Teff and Treg, respectively, Teff were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation. Importantly, AMP-activated protein kinase stimulation was sufficient to decrease Glut1 and increase Treg generation in an asthma model. These data demonstrate that CD4+ T cell subsets require distinct metabolic programs that can be manipulated in vivo to control Treg and Teff development in inflammatory diseases.
Simian Immunodeficiency Virus-Induced Changes in T Cell Cytokine Responses in Cynomolgus Macaques with Latent Mycobacterium tuberculosis Infection Are Associated with Timing of Reactivation
Authors: Mattila Joshua T. , Diedrich Collin R. , Lin Philana Ling , Phuah Jiayao , Flynn JoAnne L. 
Published: February 2011

Abstract
Understanding the early immunologic events accompanying reactivated tuberculosis (TB) in HIV-infected individuals may yield insight into causes of reactivation and improve treatment modalities. We used the cynomolgus macaque (Macaca fascicularis) model of HIV–Mycobacterium tuberculosis coinfection to investigate the dynamics of multifunctional T cell responses and granuloma T cell phenotypes in reactivated TB. CD4+ and CD8+ T cells expressing Th1 cytokines (IFN-γ, IL-2, TNF) and Th2 cytokines (IL-4 and IL-10) were followed from latent M. tuberculosis infection to reactivation after coinfection with a pathogenic SIV. Coinfected animals experienced increased Th1 cytokine responses to M. tuberculosis Ags above the latent-response baseline 3–5 wk post-SIV infection that corresponded with peak plasma viremia. Th2 cytokine expression was not Ag specific, but strong, transient IL-4 expression was noted 4–7 wk post-SIV infection. Animals reactivating &lt;17 wk post-SIV infection had significantly more multifunctional CD4+ T cells 3–5 wk post-SIV infection and more Th2-polarized and fewer Th0-, Th1-polarized CD8+ T cells during weeks 1–10 post-SIV infection than animals reactivating &gt;26 wk post-SIV infection. Granuloma T cells included Th0-, Th1-, and Th2-polarized phenotypes but were particularly rich in cytolytic (CD107+) T cells. When combined with the changes in peripheral blood T cells, these factors indicate that events during acute HIV infection are likely to include distortions in proinflammatory and anti-inflammatory T cell responses within the granuloma that have significant effects on reactivation of latent TB. Moreover, it appears that mycobacteria-specific multifunctional T cells are better correlates of Ag load (i.e., disease status) than of protection.
Studies in the Dispersion of SRF Carbon Black in Butyl Rubber
Authors: Ford F. P. , Mottlau A. Y. 
Published: February 2011

Abstract
A simple method is described for producing different degrees of carbon black dispersion in elastomers under controlled laboratory conditions. Careful selection of milling conditions has made possible the preparation of stocks possessing variations in degree of dispersion, comparable to the wide differences noted in practice. A new technique is described for studying these carbon black dispersions in rubber by means of the electron microscope. Such studies show large differences in degree of agglomeration of carbon black in compounds made under simple variations of conditions. Representative electron micrographs are shown. Good correlation is obtained between these micrographs and light transmission measurements of dilute solutions of the compounds. Such photometric analysis provides a simple method for the measurement of carbon black dispersion in research or control work. The observed differences in degree of dispersion have an effect on the physical properties of the unvulcanized compounds. This effect was observed by means of the parallel-plate plastometer. The viscosity values obtained with this instrument show a direct correlation with electron micrographic observations. Some of the practical and theoretical implications of this study are discussed with reference to recent work in this field by other investigators.
Copolymerization Theory of the Vulcanization of Rubber. VI. Hydrogen Sulfide Effects and Some Self-Limiting Features
Authors: Craig David , Juve A. E. , Davidson W. L. , Semon W. L. , Hay D. C. 
Published: February 2011

Abstract
Vulcanization with sulfur is ascribed to the formation of sulfur radicals, which are believed to copolymerize with the double bonds of the rubber molecule. Hydrogen sulfide is proposed as necessary for chain initiation, but, when formed in sufficient amounts, it serves as a chain terminator. This is believed to lead to numerous self-limiting features, including ceiling temperatures, postvulcanization, and delayed-action effects. Initiation may result from the oxidation of H2S to sulfur radicals, and termination to the formation of HS radicals.
Cold Mastication of Rubber
Authors: Watson W. F. 
Published: February 2011

Abstract
The processes underlying the plasticizing of rubber by cold and hot mastication are of different chemical types. In hot mastication, plasticizing is caused by oxidative reactions. In cold mastication, plasticizing is due to a primary rupture of the long chain rubber molecules by the applied deformation forces, and a secondary consummation of this rupture by oxygen or other compounds reactive towards the ruptured chains. Alternative to consummation of rupture, certain compounds thereby initiate cross-linking. Experimental results are quoted in support of this interpretation of cold mastication processes and some practical conclusions are drawn.
Structure of Alkali Metal-Catalyzed Butadiene Polymers
Authors: Meyer A. W. , Hampton R. R. , Davison J. A. 
Published: February 2011

Abstract
The structures of various sodium and potassium-catalyzed butadiene polymers were determined from infrared absorption measurements. All of the polymers had a higher proportion of butadiene in the 1,2-configuration (45–80 per cent) than emulsion polybutadiene (18–23 per cent). Polybutadienes catalyzed by potassium had 15–20 per cent less butadiene in the 1,2-configuration than those in which sodium was the catalyst. When a mixture of sodium and potassium was used, the results were nearly the same as with the potassium catalyst alone. Polybutadienes made at 5° had 10 to 15 per cent more butadiene in the 1,2-configuration than those made at 45°. Diluent type had little or no effect on the structure of the polybutadienes. The butadiene portions of butadiene-styrene copolymers were found to have the same relative proportions of 1,2-, cis-1,4- and trans-1,4-configurations as the butadiene homopolymers. The second order transition temperature of sodium-catalyzed polybutadiene polymerized at 30° was −45°, whereas the 75° polybutadiene had a value of −64°.
Studies on the Yellow Fraction of Latex
Authors: van Gils G. E. 
Published: February 2011

Abstract
The investigations described in this paper are part of the studies of fresh latex carried out at the INIRO (Indonesian Rubber Research Institute). For readers not acquainted with the special subject, it may be useful to mention that Homans and van Gils have found that fresh Hevea latex is not solely a dispersion of rubber globules in an aqueous medium, the serum, but that there are also present large colloidal jellylike units or agglomerations of them, constituting a separate phase in the rubber dispersion. These bodies were called lutoids by the discoverers, because they contained the yellow coloring substances of the rubber. Under a microscope, however, these lutoids look like transparent islands against a darker background of rubber particles. After centrifugation, the lutoids are separated at the bottom of the tube and look like a viscous yellowish jellylike mass, containing a low percentage of rubber. It is also possible to separate this mass by other means. As a whole, these agglomerations of lutoids are called the yellow fraction. The remaining latex is called the white fraction. Investigations carried out at the Rubber Research Institutes in Indonesia and Malaya have shown that the lutoids are responsible for many phenomena occurring in fresh latex. Recent studies of Ruinen seem to indicate that the lutoids are also involved in the rubber formation in the tree.