Binding of malaria T cell epitopes to DR and DQ molecules in vitro correlates with immunogenicity in vivo: identification of a universal T cell epitope in the Plasmodium falciparum circumsporozoite protein

The efficacy of a malaria peptide vaccine would be enhanced by the inclusion of a parasite-derived universal T cell epitope to ensure that all vaccinees develop parasite-specific cellular and humoral immunity. Two circumsporozoite (CS) protein T cell epitopes, previously identified by CD4+ T cell clones derived from Plasmodium falciparum sporozoite-immunized volunteers, were studied to determine their HLA class II binding potential. One epitope, located in amino acid (aa) 326-345 of the P. falciparum (NF54 strain) CS protein, was "universal" in that it could bind to multiple DR and DQ molecules in vitro. In contrast, the second epitope, T1, which is located in the CS repeat region, was recognized by T cells in the context of DQ6 (DQB1*0603) and did not bind with high affinity to any of the class II molecules tested in the peptide binding assays. The in vitro patterns of peptide/HLA interactions correlated with immunogenicity in vivo. A multiple antigen peptide (MAP) containing the aa 326-345 epitope elicited responses in eight inbred strains (H-2(a,b,d,k,p,q,r,s)), while the T1 MAP was recognized by only a single haplotype, H-2b. The combination of the universal aa 326-345 T cell epitope and the T1 repeat in a di-epitope MAP overcame the genetic restriction to the P. falciparum CS repeat region and elicited antisporozoite Ab responses in all of the MAP-immunized mice. Synthetic peptide malaria vaccines containing the aa 326-345 universal T cell epitope would be expected to elicit parasite-specific immune responses in both sporozoite-primed and naive individuals of diverse genetic backgrounds.     

Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules

Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly with respect to TAP affinities of their ligands. As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.     

Does hepatocyte transplantation in a chemically induced acute hepatic failure make sense?

PURPOSE: The aim of this study was to compare the effects of topically applied transforming growth factor-beta 2 (TGF-beta 2) and interleukin 6 (IL-6), alone and combined with fibronectin, on the rate of corneal wound healing in rabbits. METHODS: Twenty-eight rabbits were used for the experiment. After the right eye of each rabbit was debrided with n-heptyl alcohol, the animals were divided into four treatment groups (six rabbits per group) and one control group (four rabbits). The debrided eyes were treated, beginning immediately after wounding and continuing every 2 hours from 8 a.m. to 8 p.m. for 48 hours. Group 1 received TGF-beta 2; group 2 IL-6; group 3, TFR-beta 2 and purified fibronectin; group 4, IL-6 and fibronectin; control group, balanced salt solution. At set intervals each eye was stained with fluorescein and photographed; epithelial defects were measured with a computer-assisted digitizer. The healing rate was calculated by linear regression analysis. RESULTS: The mean healing rates in groups 1, 2, 3, 4, and controls were respectively 1.65 +/- 0.16, 1.68 +/- 0.11, 1.99 +/- 0.12, 2.23 +/- 0.09, and 0.93 +/- 0.18 mm2/h. Mean epithelial healing rates for all drug-treatment groups were significantly faster than controls. The healing rates of groups 3 and 4 were significantly faster than groups 1 and 2. CONCLUSIONS: We conclude that cytokines, in combination with extracellular matrix proteins, facilitate corneal epithelial wound healing in vivo, possibly by making corneal epithelial cells more sensitive to fibronectin receptors.     

Experimental Investigation and Thermodynamic Calculations of the Bi-Ge-Sb Phase Diagram

A phase diagram of the Bi-Ge-Sb ternary system was investigated experimentally by differential thermal analysis (DTA), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and X-ray powder diffraction (XRD) methods and theoretically by the CALPHAD method. The liquidus projection; invariant equilibria; and three vertical sections, Sb-Bi_0.5Ge_0.5, Ge-Bi_0.5Sb_0.5, and Bi-Ge_0.5Sb_0.5, as well as isothermal sections at 773 K and 373 K (500 °C and 100 °C), were predicted using optimized thermodynamic parameters for constitutive binary systems from the literature. In addition, phase transition temperatures of the selected samples with compositions along calculated isopleths were experimentally determined using DTA. Predicted isothermal sections at 773 K and 373 K (500 °C and 100 °C) were compared with the results of the SEM-EDS and XRD analysis from this work. In both cases, good agreement between the extrapolated phase diagram and experimental results was obtained. Alloys from the three studied vertical sections were additionally analyzed using the Brinell hardness test.     

Evaluating mechanical properties and degradation of YTZP dental implants

Lately new biomedical grade yttria stabilized zirconia (YTZP) dental implants have appeared in the implantology market. This material has better aesthetical properties than conventional titanium used for implants but long term behaviour of these new implants is not yet well known. The aim of this paper is to quantify the mechanical response of YTZP dental implants previously degraded under different time conditions and compare the toughness and fatigue strength with titanium implants. Mechanical response has been studied by means of mechanical testing following the ISO 14801 for Standards for dental implants and by finite element analysis. Accelerated hydrothermal degradation has been achieved by means of water vapour and studied by X-ray diffraction and nanoindentation tests. The results show that the degradation suffered by YTZP dental implants will not have a significant effect on the mechanical behaviour. Otherwise the fracture toughness of YTZP ceramics is still insufficient in certain implantation conditions.     

Electrochemical and corrosion behaviour of work-hardened commercial austenitic stainless steels in acid solutions

This paper describes the results of a study concerning the electrochemical and corrosion behaviour of AISI Types 304L and 316L stainless steels, cold worked under various conditions, in 1M H₂SO₄ and in 0.1M HCl de-aerated solutions. Anisotropic behaviour of specimen surfaces with different orientations to the direction of deformation has been observed. Stress corrosion cracking of the deformed steels can occur at room temperature in the 0.1M HCl solution both in the active and transition regions of the polarization curves.     

Crevice corrosion of titanium. Behaviour of galvanic cell between shielded and unshielded titanium in sulphuric acid

An electrochemical study on the crevice corrosion of titanium in sulfuric acid solutions of different molarity has been carried out.For this purpose a cylindrical crevice model made entirely of glass was used. Using this assembly the potential along the crevice and the cell galvanic current were measured as a function of time. It was thus possible to follow the spontaneous evolution of the unshielded titanium-shielded titanium system. Particularly emphasized was:

1. a—the existence of three distinct operating states of the system;

2. b—the conditions which led to the active-passive cell operating;

3. c—the appearance of periodic oscillatory phenomena.

Finally the role played by the TiO²⁺ cation in the rise of the potential and passivation of unshielded titanium and the temporary presence of pertitanyl anion were made evident.     

老邻新居

坐落于布达佩斯市中心的纽约宫无疑是这个城市最著名的建筑之一。这次的工程主要是扩建这个古老建筑,在这座4层老建筑旁边“逐层”平铺,新建一个7层高的五星酒店,一个独一无二的与古城堡相连的五星酒店。整个设计的重点是会议区域,这是一个总占地面积超过1900m2的大型会议区,具     

Phenols and Volatiles of Istarska Bjelica and Leccino Virgin Olive Oils Produced with Talc,NaCl and KCl as Processing Aids

The effect of processing aids (2.5 % of talc, NaCl or KCl) on oil extractability and the profile of phenolic and volatile compounds of Istarska bjelica and Leccino oils was studied. Talc significantly increased extractability in both cultivars, while salts increased extractability in Leccino cv. In the laboratory extracted oils, phenols were determined by a RP‐HPLC–DAD method, whereas volatiles were determined by SPME/GC–MS. Talc addition significantly decreased hydroxytyrosol and increased ligstroside derivatives in produced oils, but did not affect the total phenol content. Among volatile compounds, only Z‐2‐penten‐1‐ol in Leccino and 1‐pentene‐3‐one in Istarska bjelica oils significantly increased by talc addition. Salts improved transfer of most individual phenols into oil, particularly oleuropein derivatives, and increased C6 aldehydes and C5 volatiles in Leccino oils. NaCl exerted a stronger effect in increasing individual phenols and volatiles than KCl.