1,399 research outputs found

    Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

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    Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether

    Inducible nitric oxide synthase in human lymphomononuclear cells activated by synthetic peptides derived from extracellular matrix proteins.

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    Synthetic peptides with sequences present in extracellular matrix proteins are capable of causing the expression of the inducible form of nitric oxide synthase (iNOS), detected by immunocytochemistry, and the release of NO by human lymphomononuclear cells incubated in their presence. Active peptides are 15-mers containing a characteristic 2-6-11 motif in which the amino acid residue at position 2 is Leu, Ile, Val, Gly, Ala or Lys; the residue at position 6 is always Pro; and residue 11 is Glu or Asp. The induction of iNOS in human monocytes and macrophages could be involved in the cytotoxicity against tumor cell lines also elicited by these peptides

    Exploring the Expanding Universe and Dark Energy using the Statefinder Diagnostic

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    The coming few years are likely to witness a dramatic increase in high quality Sn data as current surveys add more high redshift supernovae to their inventory and as newer and deeper supernova experiments become operational. Given the current variety in dark energy models and the expected improvement in observational data, an accurate and versatile diagnostic of dark energy is the need of the hour. This paper examines the Statefinder diagnostic in the light of the proposed SNAP satellite which is expected to observe about 2000 supernovae per year. We show that the Statefinder is versatile enough to differentiate between dark energy models as varied as the cosmological constant on the one hand, and quintessence, the Chaplygin gas and braneworld models, on the other. Using SNAP data, the Statefinder can distinguish a cosmological constant (w=−1w=-1) from quintessence models with w≄−0.9w \geq -0.9 and Chaplygin gas models with Îș≀15\kappa \leq 15 at the 3σ3\sigma level if the value of \om is known exactly. The Statefinder gives reasonable results even when the value of \om is known to only ∌20\sim 20% accuracy. In this case, marginalizing over \om and assuming a fiducial LCDM model allows us to rule out quintessence with w≄−0.85w \geq -0.85 and the Chaplygin gas with Îș≀7\kappa \leq 7 (both at 3σ3\sigma). These constraints can be made even tighter if we use the Statefinders in conjunction with the deceleration parameter. The Statefinder is very sensitive to the total pressure exerted by all forms of matter and radiation in the universe. It can therefore differentiate between dark energy models at moderately high redshifts of z \lleq 10.Comment: 21 pages, 17 figures. Minor typos corrected to agree with version published in MNRAS. Results unchange

    Scalar field cosmology in the energy phase-space -- unified description of dynamics

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    In this letter we apply dynamical system methods to study all evolutional paths admissible for all initial conditions of the FRW cosmological model with a non-minimally coupled to gravity scalar field and a barotropic fluid. We choose "energy variables" as phase variables. We reduce dynamics to a 3-dimensional dynamical system for an arbitrary potential of the scalar field in the phase space variables. After postulating the potential parameter Γ\Gamma as a function of λ\lambda (defined as −Vâ€Č/V-V'/V) we reduce whole dynamics to a 3-dimensional dynamical system and study evolutional paths leading to current accelerating expansion. If we restrict the form of the potential then we will obtain a 2-dimensional dynamical system. We use the dynamical system approach to find a new generic quintessence scenario of approaching to the de Sitter attractor which appears only for the case of non-vanishing coupling constant.Comment: revtex4, 16 pages, 3 figs; (v2) refs. added, published versio

    Cutaneous Biology: In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades

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    Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades. OBJECTIVES: To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo. METHODS: We used the passive transfer mouse model. Mice were injected with IgG fractions of sera from a patient with PV, with or without pretreatment with inhibitors of proteins that mediate intracellular signalling cascades. RESULTS: Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo. CONCLUSIONS: These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysi

    An approach to the toxicity and toxicokinetics of aflatoxin B1 and ochratoxin A after simultaneous oral administration to fasted F344 rats

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    Humans are exposed to the hepatotoxic aflatoxin B1 (AFB1) and nephrotoxic ochratoxin A (OTA) through diet. However, kinetic and toxicological data after their co-administration are scarce. In this study, a single oral dose of AFB1 (0.25mg/kg bw)+OTA (0.5mg/kgbw) was administered to fasted F344 rats. Blood, liver and kidney were harvested at different timepoints for mycotoxins quantification, relative weight calculation, clinical biochemistry and histopathology analysis. Toxicity parameters pointed to acute toxicity in liver due to AFB1. No remarkable toxicity was observed in kidneys or immunological organs. Maximum observed concentrations in plasma (C(max)) were at 10min and 2h for AFB1 and OTA, respectively. AFB1 plasma concentration could indicate a rapid absorption/ metabolism of the mycotoxin; and AFB1 liver and kidney concentrations were lower than LOQ and LOD, respectively. For OTA, C(max) was 4326.2ÎŒg/L in plasma. In kidney and liver C(max) was reached at 8h and concentrations were very similar between both organs at all timepoints. Due to the low levels of AFB1, the effect of OTA on AFB1 kinetics could not be assessed. However, AFB1 seems not to affect OTA kinetics, as its profile seems very similar to kinetic studies performed only with OTA in similar conditions

    Size effects in the structural phase transition of VO2 nanoparticles

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    We have observed size effects in the structural phase transition of submicron vanadium dioxide precipitates in silica. The VO2 nanoprecipitates are produced by the stoichiometric coimplantation of vanadium and oxygen and subsequent thermal processing. The observed size dependence in the transition temperature and hysteresis loops of the semiconductor-to-metal phase transition in VO2 is described in terms of heterogeneous nucleation statistics with a phenomenological approach in which the density of nucleating defects is a power function of the driving force

    Enhanced hysteresis in the semiconductor-to-metal phase transition of VO2 precipitates formed in SiO2 by ion implantation

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    A strongly enhanced hysteresis with a width of >34°C has been observed in the semiconductor-to-metal phase transition of submicron-scale VO2 precipitates formed in the near-surface region of amorphous SiO2 by the stoichiometric coimplantation of vanadium and oxygen and subsequent thermal processing. This width is approximately an order of magnitude larger than that reported previously for the phase transition of VO2 particles formed in Al2O3 by a similar technique. The phase transition is accompanied by a significant change in infrared transmission. The anomalously wide hysteresis loop observed here for the VO2/SiO2 system can be exploited in optical data storage and switching applications in the infrared region
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