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The potential therapeutic use of peptides to activate or anergize specific T cells is seriously limited by their susceptibility to proteolytic degradation. Classically, peptides are stabilized by incorporation of non-natural modifications including main chain modifications. In the case of MHC II-restricted peptides, the peptide backbone actively participates to the interaction with the MHC molecule and hence may preclude the peptidomimetic approach. We thus investigated whether a single amide bond modification influenced the peptide capacity to bind to a MHC II molecule and to stimulate specific T cells. Twenty pseudopeptide analogs of the I-Ed binder 24-36 peptide, whose sequence was derived from a snake neurotoxin, were obtained by replacing each amide bond of the peptide central part, by either a reduced psi[CH2-NH] or N-methylated psi[CO-NMe] peptide bond. In agreement with the major interacting role played by the peptide backbone, several peptides displayed a low, if any, capacity to bind to the MHC II molecule and did not lead to T cell stimulation. However, one-third of the peptides were almost as active as the 24-36 peptide in I-Ed binding assays and one-fifth in T cell stimulation assays. Among them, two pseudopeptides displayed native-like activity. Good binders were not necessarily good at stimulating T cells, demonstrating that main chain modification also affected T cell recognition. We thus showed that a peptidomimetic approach could create a new type of MHC II ligand to control T cell responses.     

Catalytic efficiencies of allelic variants of human glutathione S-transferase P1-1 toward carcinogenic anti-diol epoxides of benzo[c]phenanthrene and benzo[g]chrysene

Four allelic variants of glutathione (GSH) S-transferase P1-1 (hGSTP1-1) that differ in their structures at amino acid(s) in position(s) 104 and/or 113 are known to exist in human populations. However, the physiological significance of hGSTP1-1 polymorphism is not fully understood. In this communication, we report that the I104,A113 allele of hGSTP1-1, which is most frequent in human populations, is also most efficient in the GSH conjugation of carcinogenic anti-diol epoxides of benzo[g]chrysene and benzo[c]phenanthrene (anti-BGCDE and anti-BCPDE, respectively). The catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BGCDE, 0.36 mM(-1) x s(-1), was approximately 1.7-fold higher (P < 0.05) compared with hGSTP1-1(V104,V113). Interestingly, the frequency of codon 104-valine alleles is significantly higher in certain cancers compared with codon 104-isoleucine alleles. Like anti-BGCDE, the catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BCPDE was higher by about 1.4- to 2.2-fold (P < 0.05) than those of other hGSTP1-1 variants. These observations are interesting because we have shown previously (Hu, X. et al., Biochem. Biophys. Res. Commun., 238: 397-402, 1997) that the V104,V113 variant, not the I104,A113 isoform, is most efficient in the GSH conjugation of bay-region anti-diol epoxide of benzo(a)pyrene (anti-BPDE), which, unlike anti-BGCDE or anti-BCPDE, is a planar molecule. In conclusion, our results suggest that hGSTP1-1 polymorphism may be an important factor in differential susceptibility of humans to cancers where polycyclic aromatic hydrocarbons are etiological factors and that I104,A113 variant may play a major role in the detoxification of nonplanar, sterically hindered fjord-region diol epoxides (e.g., anti-BGCDE).     

A prospective study of bipolar disorder in children and adolescents from India

In the light of new opportunities for structural arrangements in Germany calling for higher co-operation between physicians in private practice, determinants for diagnostic and therapeutic co-operation need to be examined. In the present study, 130 general practitioners were asked in regard to four typical primary care indication groups whether they prefer to diagnose and treat the patients on their own or in co-operation with colleagues. This self-assessment was validated using the data from 2,069 physician-patient contacts: physicians preferring therapy in co-operation actually referred patients three times more often. Concerning both gastro-intestinal and rheumatic disorders, physicians' preferences for diagnostic and therapeutic co-operation are highly correlated (phi = 0.491 and 0.528 respectively); preferences for diagnostic and therapeutic co-operation across indications are not as strongly correlated (phi = 0.334 and 0.397 respectively). However, there is no general indication-independent attitude towards co-operation for individual physicians: Indication and type of services are two factors which--probably in addition to others--affect co-operation independently. We confirm earlier conclusions that the detailed analysis of provider and patient characteristics together with the actual patient management on a case by case basis is a powerful tool for health services research.     

Evolution of microstructure during fabrication of Zr-2.5 Wt pct Nb alloy pressure tubes

Microstructural changes occurring during the fabrication of Zr-2.5 pct Nb alloy pressure tubes by a modified route, involving hot extrusion followed by two pilgering operations with an intermediate annealing step, have been examined in detail. In the conventional fabrication route, the hot extrusion step is followed by a single cold drawing operation in which the cold work to the extent of 25 pct is imparted to the material for achieving the required mechanical properties. Tensile properties obtained at each stage of fabrication have been evaluated and compared between the two processes. The main aim of this work has been to produce a microstructure and texture which are known to yield a lower irradiation growth. Additionally, suitable annealing conditions have been optimized for the intermediate annealing which annihilates the cold work introduced by the first cold pilgering operation without disturbing the two-phase elongated microstructure. This elongated α+ β _I microstructure is required for obtaining the desired level of strength at 310 °C. The final microstructure and the crystallographic texture of the finished pressure tube have been compared with those reported for the conventionally processed material. presently on leave from BARC, is Postdoctoral Fellow, Department of Materials Science and Engineering, University of Cincinnati, Cincinnati, OH-45221.     

Investigation of high temperature superconductivity through microwave absorption method

The field dependence and near zero magnetic field microwave absorption as a function of rf power in YBa₂Cu₃O_7−δ and Bi-Ca-Sr-Cu-O has been studied using a varian ESR spectrometer. A model of microwave absorption built on diamagnetic tensor susceptibility has been proposed which explains the observed results satisfactorily.     

A novel technique for measurement of the mode indexes of channelwaveguides

An accurate technique for measurement of small differences in the mode indexes of channel waveguides is presented and compared with the prism coupler. It has a distinct advantage over the prism coupler method since it allows measurements in buried waveguides as well. The absolute mode index of an individual guide can also be obtained provided a guide near the mode cutoff is available on the same substrate. The technique is expected to be useful with waveguides of high index materials, especially when the prism coupler monitoring the uniformity of optical fibers or measuring the waveguide birefringence     

Silver-doping effects on electrical properties of Ge-Te alloy

Measurements showing that the electrical properties of Ge₁₇ Te₈₃ are drastically changed when it is doped with silver are reported. The pure material acts as a linear element whose a.c. impedance and phase angle were found to be invariant over a wide frequency range 10^–3 to 10⁵ Hz. On doping with silver, the sample displayed considerably higher values of a.c. impedance, capacitance and d.c. resistance than those shown by the pure material. The silver-doped system also showed non-linearI–V characteristics and a voltage-dependent capacitance. The change in electrical properties is explained using the dipolar model proposed. It is also shown that correlated barrier hopping model is applicable to the silver-doped chalcogenide and that the dipolar model is consistent with this model.     

Heating and cooling of a building by double hollow concrete slab

This paper presents the thermal performance, in the heating and cooling of a building, of a double hollow concrete slab, one of whose faces is exposed to solar radiation and ambient air while the other is in contact with room air at constant temperature. A blackwened network of pipes is laid on the top surface and glazed sutiably. the flow rate of water / air through pipes is kept constant. It is seen that there is a time difference of 10-12 h between the maximum/ minimum of the thermal flux extering the room and the solair temperature for any flow rate. the heat flux inside the room is reduced appreciably for higher infiltration when there is no water flow to heat the building. the effect of a water film on the performance of the wall/roof has also been discussed and found to be more effective for the reduction of the heat flux coming into the building.