Showing papers by "University of Mainz published in 2002"
TL;DR: DEC-205 provides an efficient receptor-based mechanism for dendritic cells to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
Abstract: To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
1,379 citations
TL;DR: The results suggest that apolipoproteins B and E are involved in the mediation of the transport of drugs bound to poly(butyl cyanoacrylate) nanoparticles across the BBB.
Abstract: Recent studies have shown that drugs that are normally unable to cross the blood-brain barrier (BBB) following intravenous injection can be transported across this barrier by binding to poly(butyl cyanoacrylate) nanoparticles and coating with polysorbate 80 However, the mechanism of this transport so far was not known In the present paper, the possible involvement of apolipoproteins in the transport of nanoparticle-bound drugs into the brain is investigated Poly(butyl cyanoacrylate) nanoparticles loaded with the hexapeptide dalargin were coated with the apolipoproteins AII, B, CII, E, or J without or after precoating with polysorbate 80 In addition, loperamide-loaded nanoparticles were coated with apolipoprotein E alone or again after precoating with polysorbate 80 After intravenous injection to ICR mice the antinociceptive threshold was measured by the tail flick test Furthermore, the antinociceptive threshold of polysorbate 80-coated dalargin-loaded nanoparticles was determined in ApoEtm1Unc and C57BL/6J mice The results show that only dalargin or loperamide-loaded nanoparticles coated with polysorbate 80 and/or with apolipoprotein B or E were able to achieve an antinociceptive effect This effect was significantly higher after polysorbate-precoating and apolipoprotein B or E-overcoating With the apolipoprotein E-deficient ApoEtm1Unc mice the antinociceptive effect was considerably reduced in comparison to the C57BL/6J mice These results suggest that apolipoproteins B and E are involved in the mediation of the transport of drugs bound to poly(butyl cyanoacrylate) nanoparticles across the BBB Polysorbate 80-coated nanoparticles adsorb these apolipoproteins from the blood after injection and thus seem to mimic lipoprotein particles that could be taken up by the brain capillary endothelial cells via receptor-mediated endocytosis Bound drugs then may be further transported into the brain by diffusion following release within the endothelial cells or, alternatively, by transcytosis
761 citations
TL;DR: It is demonstrated that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+, and explains previously published conflicting data on the role of T GF-β in CD25- Treg cell–induced immunosuppression.
Abstract: Regulatory CD4 � CD25 � T cells (Treg) are mandatory for maintaining immunologic selftolerance. We demonstrate that the cell-cell contact‐mediated suppression of conventional CD4 � T cells by human CD25 � Treg cells is fixation resistant, independent from membrane-bound TGF- � but requires activation and protein synthesis of CD25 � Treg cells. Coactivation of CD25 � Treg cells with Treg cell‐depleted CD4 � T cells results in anergized CD4 � T cells that in turn inhibit the activation of conventional, freshly isolated CD4 � T helper (Th) cells. This infectious suppressive activity, transferred from CD25 � Treg cells via cell contact, is cell contact‐independent and partially mediated by soluble transforming growth factor (TGF)- � . The induction of suppressive properties in conventional CD4 � Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF- � in CD25 � Treg cell‐ induced immunosuppression.
638 citations
TL;DR: T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.
Abstract: Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.
636 citations
TL;DR: In concert with other effects, the stimulation of eNOS expression and activity may contribute to the cardiovascular protective effects attributed to resveratrol.
Abstract: Background— Estrogens can upregulate endothelial nitric oxide synthase (eNOS) in human endothelial cells by increasing eNOS promoter activity and enhancing the binding activity of the transcription factor Sp1. Resveratrol, a polyphenolic phytoalexin found in grapes and wine, has been reported to act as an agonist at the estrogen receptor. Therefore, we tested the effect of this putative phytoestrogen on eNOS expression in human endothelial cells. Methods and Results— Incubation of human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 cells with resveratrol for 24 to 72 hours upregulated eNOS mRNA expression in a time- and concentration-dependent manner (up to 2.8-fold). eNOS protein expression and eNOS-derived NO production were also increased after long-term incubation with resveratrol. Resveratrol increased the activity of the eNOS promoter (3.5-kb fragment) in a concentration-dependent fashion, with the essential trans-stimulated sequence being located in the proximal 263 bp of the...
627 citations
TL;DR: A critical role is described for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease and specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.
Abstract: The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-γ/interleukin (IL)-4 and transforming growth factor (TGF)-β activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L+ CD4+ T cells exacerbated colitis in reconstituted SCID mice, T-bet–deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet–deficient CD62L− CD4+ T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-β signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-γ/IL-4 and TGF-β responses and the development of chronic intestinal inflammation in T cell–mediated colitis. Furthermore, TGF-β was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-β and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell–mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.
590 citations
TL;DR: There was substantial variation in the growth factor content of platelet-rich plasma, and the factors influencing this are still worthy of further investigation.
Abstract: Introduction: Platelet-rich plasma contains autologous thrombocyte growth factors and might be promising for acceleration of dentoalveolar bone regeneration. In this study, it was analysed for platelet counts and growth factor concentrations. Material and method: Platelet-rich plasma was isolated by discontinuous cell separation from 158 healthy men and 55 women aged 17–62 years. One hundred and fifteen specimens (stratified for age and gender of the donor) were analysed for growth factor concentrations and platelet count. Results: The platelet count in platelet-rich plasma (1,407,640±320,100/μl) was 5 times higher than in donor blood (266,040±60,530/μl). Platelet-derived growth factor AB (117±63 ng/ml), transforming growth factor (TGF) β -1 (169±84 ng/ml), and insulin-like growth factor (IGF) I (84±23 ng/ml) were found in large amounts, while platelet-derived growth factor (PDGF) BB (10±8 ng/ml) and transforming growth factor β -2 (0.4±0.3 ng/ml) were found in small amounts only. The growth factor content was not well correlated with the platelet count in whole blood nor with the platelet-rich plasma ( r p =0.35). No influence of gender or age on platelet count or growth factor concentrations was discovered (except IGF-I). Conclusions: While there was substantial variation in the growth factor content of platelet-rich plasma, the factors influencing this are still worthy of further investigation. Furthermore, a technique whereby the growth factor content could be rapidly assessed in platelet-rich plasma may be of therapeutic benefit. Copyright 2002 European Association for Cranio-Maxillofacial Surgery. Published by Elsevier Science Ltd. All rights reserved.
579 citations
TL;DR: Soluble adhesion molecules sVCAM- 1, sICAM-1, and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD and added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death.
Abstract: Background —Vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability. In a prospective study, we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease (CAD). Methods and Results —We obtained baseline samples from a prospective cohort of 1246 patients with CAD. Besides various markers of inflammation, soluble VCAM-1 (sVCAM-1), sICAM-1, and sE-selectin were determined. Follow-up information on cardiovascular events was obtained (mean, 2.7; maximum, 4.1 years). Independently higher levels of sVCAM-1 (1932 versus 1128 ng/mL; P<0.0001), sICAM-1 (353 versus 287 ng/mL; P=0.015), and sE-selectin (81 versus 63 ng/mL; P=0.003) were observed in patients with future death from cardiovascular causes. In a multivariate model, fatal risk was...
570 citations
TL;DR: ER stress-induced programmed cell death defines a novel, mitochondrial and Apaf-1-independent, intrinsic apoptotic pathway, and the molecular requirements for this Apf-1 and cytochrome c-independent apoptosis pathway are defined.
553 citations
TL;DR: The polarization of T helper cells plays a key role in maintaining or disrupting the balance between antigen responsiveness and tolerance in the human immune system as discussed by the authors, and the polarization of helper cells is a key mechanism in maintaining the equilibrium.
Abstract: Mucosal immunity relies on the delicate balance between antigen responsiveness and tolerance. The polarization of T helper cells plays a key role in maintaining or disrupting this equilibrium.
552 citations
TL;DR: Serum IL-18 level was identified as a strong independent predictor of death from cardiovascular causes in patients with coronary artery disease regardless of the clinical status at admission, and this result strongly supports recent experimental evidence ofIL-18–mediated inflammation leading to acceleration and vulnerability of atherosclerotic plaques.
Abstract: Background— Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking. Methods and Results— In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P<0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend <0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory var...
TL;DR: In this article, the exact renormalization group equation for pure quantum gravity is used to derive the nonperturbative \ensuremath{\beta}-functions for the dimensionless Newton constant and cosmological constant on the theory space spanned by the Einstein-Hilbert truncation.
Abstract: The exact renormalization group equation for pure quantum gravity is used to derive the nonperturbative \ensuremath{\beta}-functions for the dimensionless Newton constant and cosmological constant on the theory space spanned by the Einstein-Hilbert truncation. The resulting coupled differential equations are evaluated for a sharp cutoff function. The features of these flow equations are compared to those found when using a smooth cutoff. The system of equations with a sharp cutoff is then solved numerically, deriving the complete renormalization group flow of the Einstein-Hilbert truncation in $d=4.$ The resulting renormalization group trajectories are classified and their physical relevance is discussed. The nontrivial fixed point which, if present in the exact theory, might render quantum Einstein gravity nonperturbatively renormalizable is investigated for various spacetime dimensionalities.
TL;DR: The identification of a fourth and novel type of globin in mouse, man, and zebrafish has been reported, which indicates that the vertebrate myoglobins are in fact a specialized intracellular globin that evolved in adaptation to the special needs of muscle cells.
Abstract: Vertebrates possess multiple respiratory globins that differ in terms of structure, function, and tissue distribution. Three types of globins have been described so far: hemoglobin facilitates the transport of oxygen in the blood, myoglobin serves oxygen transport and storage in the muscle, and neuroglobin has a yet unidentified function in nerve cells. Here we report the identification of a fourth and novel type of globin in mouse, man, and zebrafish. It is expressed in apparently all types of human tissue and therefore has been called cytoglobin (CYGB). Mouse and human CYGBs comprise 190 amino acids; the zebrafish CYGB, 174 amino acids. The human CYGB gene is located on chromosome 17q25. The mammalian genes display a unique exon-intron pattern with an additional exon resulting in a C-terminal extension of the protein, which is absent in the fish CYGB. Phylogenetic analyses suggest that the CYGBs had a common ancestor with vertebrate myoglobins. This indicates that the vertebrate myoglobins are in fact a specialized intracellular globin that evolved in adaptation to the special needs of muscle cells.
TL;DR: The data indicate that the present ligands are only partly satisfactory tools and further ligands with subtype-selective properties are needed for imaging purposes and for confirming the behavioral and functional results of the studies presently carried out in gene-targeted mice with other species, including man.
TL;DR: Experiments demonstrate that anergic T cells induced by IL-10-treated DCs are able to suppress activation and function of T cells in an antigen-specific manner.
TL;DR: GiNaC as mentioned in this paper is a special-purpose system for loop calculations in theoretical quantum field theory that is written in C++ and the user can interact with it directly in that language.
TL;DR: It is shown that the fluorescence decay time is fluctuating during the investigation leading to a multiexponential decay even for a single nanocrystal, consistent with a model of fluctuating nonradiative decay channels leading to variable dynamic quenching processes of the excited state.
Abstract: We present fluorescence decay measurements of single ZnS covered CdSe nanocrystals. It is shown that the fluorescence decay time is fluctuating during the investigation leading to a multiexponential decay even for a single nanocrystal. In combination with measurements of the fluorescence blinking behavior we find that a high fluorescence intensity is correlated with a long fluorescence decay time. This is consistent with a model of fluctuating nonradiative decay channels leading to variable dynamic quenching processes of the excited state.
TL;DR: It is proposed that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia.
Abstract: Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia.
TL;DR: This chapter discusses Hydrocarbyl Complexes with Rare-EarthMetal to Chlorine, Oxygen, and NitrogenBonds, and links Pnicogenido CyclopentadienylComplexes1966, which are connected to Hydrido Complexes 1966, which were previously discussed.
Abstract: I. Introduction 1953II. Overview of Synthesis, Structure, and Properties 1954A. Synthetic Methods 1954B. Ligands and Structures 1955III. Halo Complexes 1956A. General 1956B. Divalent Halo Complexes 1956C. Trivalent Halo Complexes 1957IV. Chalcogenido Complexes 1958A. General 1958B. Divalent Chalcogenido Complexes 1958C. Trivalent Chalcogenido Complexes 1959V. Pnicogenido Complexes 1960A. General 1960B. Divalent Amido and Phosphido Complexes 1960C. Trivalent Pnicogenido Complexes 19611. Bis(amido) Complexes 19612. Mixed Halo and Chalcogenido Complexes 1962VI. Hydrocarbyl and Silyl Complexes 1963A. General 1963B. Divalent Complexes 19631. Metallacarbaboranes 19632. Bimetallic Naphthalene Complexes 19643. Silyl Complexes 1964C. Bis(Hydrocarbyls) 19641. Bis(alkyl), Bis(aryl), and Anionic Tris(alkyl)Complexes19642. Allyl and Anionic Tris(allyl) Complexes 19653. Metallacyclopentenes 19654. Metallacarbaboranes 19655. Fullerides 1966D. Hydrocarbyl Complexes with Rare-EarthMetal to Chlorine, Oxygen, and NitrogenBonds19661. Aryloxo, Silylamido, and AmidinatoComplexes19662. Linked Pnicogenido CyclopentadienylComplexes1966VII. Hydrido Complexes 1968A. General 1968B. Complexes with a [Ln(
TL;DR: This review summarizes the current knowledge about the immunoregulatory role of immature DC that might act as guardians for the induction and maintenance of T cell tolerance in the periphery.
Abstract: The induction of antigen-specific T cell tolerance and its maintenance in the periphery is critical for the prevention of autoimmunity. Recent evidence shows that dendritic cells (DC) not only initiate T cell responses, but are also involved in silencing of T cell immune responses. The functional activities of DC are mainly dependent on their state of activation and differentiation, that is, terminally differentiated mature DC can efficiently induce the development of T effector cells, whereas immature DC are involved in maintenance of peripheral tolerance. The means by which immature DC maintain peripheral tolerance are not entirely clear, however, their functions include the induction of anergic T cells, T cells with regulatory properties as well as the generation of T cells that secrete immunomodulatory cytokines. This review summarizes the current knowledge about the immunoregulatory role of immature DC that might act as guardians for the induction and maintenance of T cell tolerance in the periphery.
TL;DR: It is suggested that Huh-7 cells lack host cell factors that are important for virus particle assembly and/or release, and selectable full-length HCV genomes that amplify to high levels in the human hepatoma cell line Huh- 7 are generated.
Abstract: The recently developed subgenomic hepatitis C virus (HCV) replicons were limited by the fact that the sequence encoding the structural proteins was missing. Therefore, important information about a possible influence of these proteins on replication and pathogenesis and about the mechanism of virus formation could not be obtained. Taking advantage of three cell culture-adaptive mutations that enhance RNA replication synergistically, we generated selectable full-length HCV genomes that amplify to high levels in the human hepatoma cell line Huh-7 and can be stably propagated for more than 6 months. The structural proteins are efficiently expressed, with the viral glycoproteins E1 and E2 forming heterodimers which are stable under nondenaturing conditions. No disulfide-linked glycoprotein aggregates were observed, suggesting that the envelope proteins fold productively. Electron microscopy studies indicate that cell lines harboring these full-length HCV RNAs contain lipid droplets. The majority of the core protein was found on the surfaces of these structures, whereas the glycoproteins appear to localize to the endoplasmic reticulum and cis-Golgi compartments. In agreement with this distribution, no endoglycosidase H-resistant forms of these proteins were detectable. In a search for the production of viral particles, we noticed that these cells release substantial amounts of nuclease-resistant HCV RNA-containing structures with a buoyant density of 1.04 to 1.1 g/ml in iodixanol gradients. The same observation was made in transient-replication assays using an authentic highly adapted full-length HCV genome that lacks heterologous sequences. However, the fact that comparable amounts of such RNA-containing structures were found in the supernatant of cells carrying subgenomic replicons demonstrates a nonspecific release independent of the presence of the structural proteins. These results suggest that Huh-7 cells lack host cell factors that are important for virus particle assembly and/or release.
TL;DR: The physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases are outlined.
Abstract: The nuclear spin polarization of the noble gas isotopes (3)He and (129)Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments.
TL;DR: Evaluated EVLT of the incompetent greater saphenous vein with a 940-nm diode laser is effective in inducing thrombotic vessel occlusion and is associated with only minor adverse effects.
TL;DR: The Dunzhugur ophiolite of Eastern Sayan provides evidence for the early opening of the palaeo-Asian ocean not later than 1000 Ma ago as mentioned in this paper, which is the oldest ophiola so far dated from the Central Asian fold belt.
TL;DR: In this paper, the exact renormalization group equation of QEG is evaluated in a truncation of theory space which generalizes the Einstein-Hilbert truncation by the inclusion of a higher-derivative term.
Abstract: Motivated by recent evidence indicating that quantum Einstein gravity (QEG) might be nonperturbatively renormalizable, the exact renormalization group equation of QEG is evaluated in a truncation of theory space which generalizes the Einstein-Hilbert truncation by the inclusion of a higher-derivative term ${(R}^{2})$ The beta functions describing the renormalization group flow of the cosmological constant, Newton's constant, and the ${R}^{2}$ coupling are computed explicitly The fixed point properties of the 3-dimensional flow are investigated, and they are confronted with those of the 2-dimensional Einstein-Hilbert flow The non-Gaussian fixed point predicted by the latter is found to generalize to a fixed point on the enlarged theory space In order to test the reliability of the ${R}^{2}$ truncation near this fixed point we analyze the residual scheme dependence of various universal quantities; it turns out to be very weak The two truncations are compared in detail, and their numerical predictions are found to agree with a surprisingly high precision Because of the consistency of the results it appears increasingly unlikely that the non-Gaussian fixed point is an artifact of the truncation If it is present in the exact theory QEG is probably nonperturbatively renormalizable and ``asymptotically safe'' We discuss how the conformal factor problem of Euclidean gravity manifests itself in the exact renormalization group approach and show that, in the ${R}^{2}$ truncation, the investigation of the fixed point is not afflicted with this problem Also the Gaussian fixed point of the Einstein-Hilbert truncation is analyzed; it turns out that it does not generalize to a corresponding fixed point on the enlarged theory space
TL;DR: The data show that Rho proteins are overexpressed in breast tumours (2) overexpression is not regulated on the mRNA level (3) the expression level of RhoA-like proteins correlates with malignancy and (4) Rhoprotein expression was neither related to p53 nor to HER-2/neu oncogene status and are not altered by mutation in Breast tumours.
Abstract: In the present study, we addressed the question of a putative relevance of Rho proteins in tumour progression by analysing their expression on protein and mRNA level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42 protein is largely enhanced in all tumour samples analysed (n=15) as compared to normal tissues originating from the same individual. The same is true for (32)P-ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall (32)P-GTP binding activity was tumour-specific elevated, yet to a lower extent than Rho proteins. Although the amount of Rho proteins was enhanced in tumours, most of them did not show changes in rho mRNA expression as compared to the corresponding normal tissue. Thus, elevated gene expression seems not to be the underlying mechanism of tumour-specific overexpression of Rho proteins. Sequence analysis of RhoA, RhoB, RhoC and Rac1 failed to detect any mutations in both the GTP-binding site and effector binding region. By analysing >50 tumour samples, the amount of RhoA-like proteins (i.e. RhoA, B, C), but not of Rac1, was found to significantly increase with histological grade and proliferation index. Rho protein expression was neither related to p53 nor to HER-2/neu oncogene status. Expression of rho mRNAs did not show a significant increase with histological grade. Overall the data show that (1) Rho proteins are overexpressed in breast tumours (2) overexpression is not regulated on the mRNA level (3) the expression level of RhoA-like proteins correlates with malignancy and (4) Rho proteins are not altered by mutation in breast tumours.
TL;DR: In this article, a causative role of infections in the pathogenesis of atherosclerosis was suggested. But, they did not consider the role of infectious agents in the development of the disease.
Abstract: Background— Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atheroscl...
TL;DR: In this paper, the cosmological evolution equations are renormalization group improved by including the scale dependence of Newton's constant and of the Cosmological constant as it is given by the flow equation of the effective average action for gravity, and it is argued that the Planck regime can be treated reliably in this framework because gravity is found to become asymptotically free at short distances.
Abstract: Homogeneous and isotropic cosmologies of the Planck era before the classical Einstein equations become valid are studied taking quantum gravitational effects into account. The cosmological evolution equations are renormalization group improved by including the scale dependence of Newton's constant and of the cosmological constant as it is given by the flow equation of the effective average action for gravity. It is argued that the Planck regime can be treated reliably in this framework because gravity is found to become asymptotically free at short distances. The epoch immediately after the initial singularity of the Universe is described by an attractor solution of the improved equations which is a direct manifestation of an ultraviolet attractive renormalization group fixed point. It is shown that quantum gravity effects in the very early Universe might provide a resolution to the horizon and flatness problems of standard cosmology, and could generate a scale-free spectrum of primordial density fluctuations.
TL;DR: The data suggest that laccase/mediator systems are effective biocatalysts for the treatment of effluents from textile, dye or printing industries.
Abstract: Laccases from the lignin-degrading basidiomycetes Trametes versicolor, Polyporus pinisitus and the ascomycete Myceliophthora thermophila were found to decolorize synthetic dyes to different extents. Differences were attributed to the specific catalytic properties of the individual enzymes and to the structure of the dyes. Due to their higher oxidative capacities, the laccases from the two basidiomycetes decolorized dyes more efficiently than that of the ascomycete. The azo dye Direct Red 28, the indigoid Acid Blue 74 and anthraquinonic dyes were directly enzymatically decolorized within 16 h. The addition of 2 mM of the redox-mediator 1-hydroxybenzotriazole further improved and facilitated the decolorization of all nine dyes investigated. Laccases decolorized dyes both individually and in complex mixtures in the presence of bentonite or immobilized in alginate beads. Our data suggest that laccase/mediator systems are effective biocatalysts for the treatment of effluents from textile, dye or printing industries.
TL;DR: It is shown that introducing short-ranged attraction to a colloid suspension of nearly hard spheres by addition of a free polymer produces new glass-transition phenomena that is in qualitative agreement with recent theoretical predictions.
Abstract: Performing light scattering experiments we show that introducing short-ranged attraction to a colloid suspension of nearly hard spheres by addition of a free polymer produces new glass-transition phenomena. We observe a dramatic acceleration of the density fluctuations amounting to the melting of a colloidal glass. Upon increasing the strength of the attractions the system freezes into another nonergodic state sharing some qualitative features with gel states occurring at lower colloid packing fractions. This re-entrant glass transition is in qualitative agreement with recent theoretical predictions.